Multi-Stage Learning Framework Using Convolutional Neural Network and Decision Tree-Based Classification for Detection of DDoS Pandemic Attacks in SDN-Based SCADA Systems.

Supervisory Control and Data Acquisition (SCADA) systems, which play a critical role in monitoring, managing, and controlling industrial processes, face flexibility, scalability, and management difficulties arising from traditional network structures. Software-defined networking (SDN) offers a new opportunity to overcome the challenges traditional SCADA networks face, based on the concept of separating the control and data plane. Although integrating the SDN architecture into SCADA systems offers many advantages, it cannot address security concerns against cyber-attacks such as a distributed denial of service (DDoS). The fact that SDN has centralized management and programmability features causes attackers to carry out attacks that specifically target the SDN controller and data plane. If DDoS attacks against the SDN-based SCADA network are not detected and precautions are not taken, they can cause chaos and have terrible consequences. By detecting a possible DDoS attack at an early stage, security measures that can reduce the impact of the attack can be taken immediately, and the likelihood of being a direct victim of the attack decreases. This study proposes a multi-stage learning model using a 1-dimensional convolutional neural network (1D-CNN) and decision tree-based classification to detect DDoS attacks in SDN-based SCADA systems effectively. A new dataset containing various attack scenarios on a specific experimental network topology was created to be used in the training and testing phases of this model. According to the experimental results of this study, the proposed model achieved a 97.8% accuracy rate in DDoS-attack detection. The proposed multi-stage learning model shows that high-performance results can be achieved in detecting DDoS attacks against SDN-based SCADA systems.

Role of ultrasonography in upper airway assessment: A comparison with computerized tomography measurements.

INTRODUCTION: This study aimed to compare ultrasonography (US) measurements of the upper airway to computerized tomography (CT) measurements. Our study's primary outcome is to research the accuracy of US measurements in the evaluation of upper airway diameters when CT is taken as the gold standard; the secondary outcome is to determine the time required to obtain US measurements. METHODS: This prospective study included patients ≥18 years old that had undergone thoracic or neck CT due to current clinical necessity. The US measurement for each patient was performed by two researchers with different levels of experience, both of whom were blinded to each other and the CT measurements. Measurements were obtained from the vocal cords and subglottic region. The duration of the US performance was also recorded. RESULTS: The US and CT measurements were obtained from 94 patients. Concordance between US and CT measurements was found in the Bland-Altman analysis, with a mean -0.05 mm difference for vocal cord diameter and -1.2 mm for subglottic diameter. The intra-class correlation coefficients (ICC) between the CT and US measurements were 0.993, and 0.609 for vocal cord and subglottic diameter measurements, respectively. The ICC between US performers was 0.992 for vocal cord diameter and 0.959 for subglottic diameter. The US's mean time for vocal cord diameter measurement was 38 ± 23 s, and the mean time for subglottic diameter measurement was 49 ± 30 s. CONCLUSION: The concordance between US and CT measurements is high and the measurements of different practitioners with different experience levels are compatible with each other.

Comparison of the effects PRICE and POLICE treatment protocols on ankle function in patients with ankle sprain.

BACKGROUND: Ankle sprain is a frequent reason for presentation to the emergency department. Current treatment modalities include Protection, Optimal Loading, Ice, Compression, and Elevation (POLICE) and Protection, Rest, Ice, Compression, and Elevation (PRICE). This study aimed to compare the effects of PRICE and POLICE treatment protocols. METHODS: This randomized controlled study was conducted between October 15, 2020, and October 15, 2021, at Ankara University's Department of Emergency Medicine. Double-blind randomization was used to assign patients to either the POLICE or PRICE treatment groups. RESULTS: In total, 109 patients were included. In the POLICE group, the median difference between the American Orthopedic Foot and Ankle Scores on admission and the 14th day following the injury was 34.5 (IQR: 27.25-41.75), while that of the PRICE group was 24 (IQR: 15.5-35). In the POLICE group, the median value of the difference in the Foot and Ankle Disability Index scores on admission and the 14th day following the injury was 42 (IQR: 35.25-50), while that of the PRICE group was 31 (IQR: 22-41.5). CONCLUSION: The POLICE treatment protocol provided more effective and faster recovery than the PRICE treatment protocol.

Rectus Sheath Hematoma in a Patient with Dual-Antiplatelet Therapy Including Ticagrelor: A Case Report.

Rectus sheath hematoma (RSH) is an uncommon cause of abdominal pain associated with several risk factors including trauma, asthma, chronic obstructive pulmonary disease, pregnancy, and anticoagulation as it can be iatrogenic. Dual-antiplatelet therapy (DAPT), combined usage of a P2Y12 receptor inhibitor and aspirin, is a cornerstone treatment for patients with acute coronary syndromes. Ticagrelor is a P2Y12 receptor inhibitor with several adverse hemorrhagic complications. An 86-year-old male patient was admitted to the emergency department with abdominal pain and a palpable abdominal mass at the left upper quadrant of the abdomen. His medical history revealed coronary artery disease with medications including acetylsalicylic acid and ticagrelor. Contrast-enhanced abdominal computed tomography revealed RSH. The patient was treated conservatively with bed rest and analgesia. DAPT is an essential component of the management of acute coronary syndromes to prevent recurrent cardiac thrombotic events. However, hemorrhagic complications such as RSH may be encountered with DAPT. Emergency medicine physicians and cardiologists should keep in mind RSH in patients presenting with abdominal pain and using DAPT with ticagrelor.

ResMIBCU-Net: an encoder-decoder network with residual blocks, modified inverted residual block, and bi-directional ConvLSTM for impacted tooth segmentation in panoramic X-ray images.

OBJECTIVE: Impacted tooth is a common problem that can occur at any age, causing tooth decay, root resorption, and pain in the later stages. In recent years, major advances have been made in medical imaging segmentation using deep convolutional neural network-based networks. In this study, we report on the development of an artificial intelligence system for the automatic identification of impacted tooth from panoramic dental X-ray images. METHODS: Among existing networks, in medical imaging segmentation, U-Net architectures are widely implemented. In this article, for dental X-ray image segmentation, blocks and convolutional block structures using inverted residual blocks are upgraded by taking advantage of U-Net's network capacity-intensive connections. At the same time, we propose a method for jumping connections in which bi-directional convolution long short-term memory is used instead of a simple connection. Assessment of the proposed artificial intelligence model performance was evaluated with accuracy, F1-score, intersection over union, and recall. RESULTS: In the proposed method, experimental results are obtained with 99.82% accuracy, 91.59% F1-score, 84.48% intersection over union, and 90.71% recall. CONCLUSION: Our findings show that our artificial intelligence system could help with future diagnostic support in clinical practice.

The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5.

Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Other studies using TRPC5 gain-of-function transgenic mice have questioned the pathogenic role of TRPC5 in podocytes. Here, we show that TRPC5 over-expression or inhibition does not ameliorate proteinuria induced by the expression of constitutively active Rac1 in podocytes. Additionally, single-cell patch-clamp studies did not detect functional TRPC5 channels in primary cultures of podocytes. Thus, we conclude that TRPC5 plays a role redundant to that of TRPC6 in podocytes and is unlikely to be a useful therapeutic target for podocytopathies.

Effect of candesartan treatment on echocardiographic indices of cardiac remodeling in post-myocardial infarction patients.

OBJECTIVE: Myocardial infarction has unfavorable effect on structural and functional properties of the myocardium, referred to as cardiac remodeling. Left ventricular mass, left ventricular mass index, and relative wall thickness are important predictors of cardiac remodeling. In this study, we investigated the effect of candesartan treatment in comparison with zofenopril treatment on echocardiographic indices of cardiac remodeling in post myocardial infarction patients. MATERIAL AND METHODS: In this prospective study, patients who underwent successful percutaneous coronary intervention were randomly assigned to a candesartan or zofenopril treatment. After randomization, echocardiographic indices of cardiac remodeling including left ventricular mass, left ventricular mass index, and relative wall thickness were evaluated before the start of treatment along with 1- and 6-month follow-ups. RESULTS: According to our study, candesartan group showed significant reduction of estimated left ventricular mass and left ventricular mass index at 6-month follow-up visit compared to baseline values (199.53±38.51 g vs. 212.69±40.82 g; 99.05 g/m2 (90.00-116.5) vs. 106.0 g/m2 (96.0∼123.00), p<0.05, respectively). This trend was also observed in zofenopril group during the 6-month period (201.22±40.07 g vs. 207.52±41.61 g; 101.0 g/m2 (92.25-111.75.0) vs. 104.50 g/m2 (95.0∼116.75), p<0.05, respectively). Although both classes of drugs had favorable effects on post-myocardial infarction cardiac remodeling, the absolute benefit was more prominent in candesartan group as compared to zofenopril group (p<0.05). CONCLUSION: Our results suggest that candesartan treatment following myocardial infarction may potentially be useful in terms of improving post-myocardial infarction cardiac remodeling.

Effect of candesartan treatment on echocardiographic indices of cardiac remodeling in post-myocardial infarction patients

SUMMARY Objective: Myocardial infarction has unfavorable effect on structural and functional properties of the myocardium, referred to as cardiac remodeling. Left ventricular mass, left ventricular mass index, and relative wall thickness are important predictors of cardiac remodeling. In this study, we investigated the effect of candesartan treatment in comparison with zofenopril treatment on echocardiographic indices of cardiac remodeling in post myocardial infarction patients. Material and Methods: In this prospective study, patients who underwent successful percutaneous coronary intervention were randomly assigned to a candesartan or zofenopril treatment. After randomization, echocardiographic indices of cardiac remodeling including left ventricular mass, left ventricular mass index, and relative wall thickness were evaluated before the start of treatment along with 1- and 6-month follow-ups. Results: According to our study, candesartan group showed significant reduction of estimated left ventricular mass and left ventricular mass index at 6-month follow-up visit compared to baseline values (199.53±38.51 g vs. 212.69±40.82 g; 99.05 g/m2 (90.00-116.5) vs. 106.0 g/m2 (96.0∼123.00), p<0.05, respectively). This trend was also observed in zofenopril group during the 6-month period (201.22±40.07 g vs. 207.52±41.61 g; 101.0 g/m2 (92.25-111.75.0) vs. 104.50 g/m2 (95.0∼116.75), p<0.05, respectively). Although both classes of drugs had favorable effects on post-myocardial infarction cardiac remodeling, the absolute benefit was more prominent in candesartan group as compared to zofenopril group (p<0.05). Conclusion: Our results suggest that candesartan treatment following myocardial infarction may potentially be useful in terms of improving post-myocardial infarction cardiac remodeling.

Evaluation of the Validity and Reliability of ANKUTRIAGE, a New Decision Support System in Pediatric Emergency Triage.

BACKGROUND: The intensity of emergency services is an increasing health problem all over the world, necessitating an effective triage system. The aim of this study was to evaluate the validity and reliability of the "ANKUTRIAGE" in children. METHODS: This prospective, longitudinal study was carried out at a pediatric emergency department. ANKUTRIAGE, a 5-level computer-aided triage decision support system, was developed. Patients younger than 18 years who do not need emergency intervention, who had complete vital sign measurements, who gave consent for the study, and who were admitted to the emergency service during working hours with trained personnel were included. For validity, agreement between the urgency levels determined by ANKUTRIAGE and the reference triage systems: Pediatric Canadian Triage and Acuity Scale and Emergency Severity Index, was evaluated. In addition, the association of urgency levels with clinical outcomes was studied. To assess reliability, patients were evaluated by 2 blinded healthcare professionals using ANKUTRIAGE and a quadratic weighted κ was estimated. RESULTS: A total of 1232 children with a median age of 4.00 years were included. ANKUTRIAGE acuity levels significantly correlated with the number of resources used, the number of patients undergoing life-saving procedures, pediatric intensive care unit, and overall hospitalization rates, respectively ( P < 0.001, P < 0.001, P < 0.001, P < 0.001). The agreement of ANKUTRIAGE with Pediatric Canadian Triage and Acuity Scale was found to be 0.94 (95% confidence interval [CI], 0.93-0.94), with an Emergency Severity Index of 0.75 (95% CI, 0.70-0.80). The interrater agreement between 2 evaluators who used ANKUTRIAGE reflected as excellent consistency 0.92 (95% CI, 0.89-0.95; κ > 0.8). CONCLUSIONS: ANKUTRIAGE demonstrated high agreement with clinical outcomes and with proven triage systems and reflected high reliability between users. ANKUTRIAGE will enable a more standardized and practical triage, especially in crowded pediatric emergency departments and in situations where triage is performed by health professionals with different experience and professions.

Comparison of sweep visual evoked potential of visual acuity and Snellen visual acuity in healthy and amblyopic children / Comparação da acuidade visual por potenciais evocados visuais de varredura e pelo teste de Snellen em crianças saudáveis e ambliópicas

ABSTRACT Purpose: To evaluate the visual acuity of healthy and amblyopic children using sweep visual evoked potential and compare the results with those of Snellen visual acuity testing. Methods: A total of 160 children aged 6-17 years were included in the study. Of these, 104 (65%) were aged 7-17 years old, able to verbally communicate, and did not have any systemic or ocular pathology (Group 1). Group 2 included 56 (35%) children aged 6-17 years, able to verbally communicate, and had strabismus or anisometropic amblyopia whose best corrected visual acuity was between 0.1 and 0.8. All subjects underwent a detailed ophthalmological examination and sweep visual evoked potential measurement. Demographic characteristics, ocular findings, best corrected visual acuity, and sweep visual evoked potential results were recorded. Results: In Group 1, the mean and maximum visual acuity values for sweep visual evoked potential were lower than the Snellen best corrected visual acuity (p<0.001, for both, respectively). Bland-Altman analysis revealed that in Group 1, the distribution of the differences between the Snellen best corrected visual acuity and mean sweep visual evoked potential visual acuity was ±0.11 logMAR, and the distribution of the differences between the Snellen best corrected visual acuity and maximum sweep visual evoked potential visual acuity was ±0.023 logMAR. In Group 2, the mean and maximum sweep visual evoked potential visual acuity were lower than the Snellen best corrected visual acuity (p<0.001 and p=0.009, respectively). Bland-Altman analysis revealed that the distribution of the differences between the Snellen best corrected visual acuity and mean sweep visual evoked potential visual acuity was ±0.16 logMAR, and the distribution of the differences between the Snellen best corrected visual acuity and maximum sweep visual evoked potential visual acuity was ±0.19 logMAR. Conclusions: Sweep visual evoked potential visual acuity measurements have comparable results with Snellen visual acuity measurements. This technique is an objective and reliable method for evaluating visual acuity in children.

RESUMO Objetivo: Avaliar a acuidade visual através de po­tenciais evocados visuais de varredura em crianças saudáveis e ambliópicas, comparando-a com a acuidade visual pelo teste de Snellen. Métodos: Foram incluídas no estudo 160 crianças com idades entre 6 e 17 anos. Desse total, 104 crianças (65%) estavam entre 7 e 17 anos de idade, eram capazes de comunicação verbal e não tinham nenhuma patologia ocular ou sistêmica (Grupo 1). O grupo 2 incluiu 56 crianças verbais (35%) com idades entre 6 e 17 anos e portadoras de estrabismo ou ambliopia anisometrópica, com a melhor acuidade visual corrigida entre 0,1 e 0,8. Todos os pacientes foram submetidos a um exame oftalmológico detalhado e a uma medição do potencial evocado visual por varredura. Registraram-se as características demográficas, os achados oculares, a melhor acuidade visual corrigida e os resultados do potencial evocado visual por varredura. Resultados: No Grupo 1, os valores médios e máximos da acuidade visual pelo potencial evocado visual por varredura mostraram-se menores que a melhor acuidade visual corrigida medida através do teste de Snellen (p<0,001 para ambas as medições). Uma análise de Bland-Altman revelou que no grupo 1, a distribuição das diferenças entre a melhor acuidade visual corrigida pelo teste de Snellen e a média do potencial evocado visual por varredura foi de ± 0,11 logMAR, enquanto a distribuição das diferenças entre a melhor acuidade visual corrigida pelo teste de Snellen e o valor máximo do potencial evocado visual por varredura foi de ± 0,023 logMAR. No Grupo 2, os valores médio e máximo do potencial evocado visual por varredura mostraram-se menores que a melhor acuidade visual corrigida pelo teste de Snellen (respectivamente, p<0,001 e p=0,009). A análise de Bland-Altman revelou que a distribuição das diferenças entre a melhor acuidade visual corrigida pelo teste de Snellen e a média do potencial evocado visual por varredura foi de ± 0,16 logMAR, enquanto a distribuição das diferenças entre a melhor acuidade visual corrigida pelo teste de Snellen e o valor máximo do potencial evocado visual por varredura foi de ± 0,19 logMAR. Conclusões: As medidas da acuidade visual através do potencial evocado visual por varredura mostram resultados comparáveis às medidas da acuidade visual pelo teste de Snellen. Essa técnica é um método objetivo e confiável de se avaliar a acuidade visual em crianças.

Ensemble Learning Framework for DDoS Detection in SDN-Based SCADA Systems.

Supervisory Control and Data Acquisition (SCADA) systems play a crucial role in overseeing and controlling renewable energy sources like solar, wind, hydro, and geothermal resources. Nevertheless, with the expansion of conventional SCADA network infrastructures, there arise significant challenges in managing and scaling due to increased size, complexity, and device diversity. Using Software Defined Networking (SDN) technology in traditional SCADA network infrastructure offers management, scaling and flexibility benefits. However, as the integration of SDN-based SCADA systems with modern technologies such as the Internet of Things, cloud computing, and big data analytics increases, cybersecurity becomes a major concern for these systems. Therefore, cyber-physical energy systems (CPES) should be considered together with all energy systems. One of the most dangerous types of cyber-attacks against SDN-based SCADA systems is Distributed Denial of Service (DDoS) attacks. DDoS attacks disrupt the management of energy resources, causing service interruptions and increasing operational costs. Therefore, the first step to protect against DDoS attacks in SDN-based SCADA systems is to develop an effective intrusion detection system. This paper proposes a Decision Tree-based Ensemble Learning technique to detect DDoS attacks in SDN-based SCADA systems by accurately distinguishing between normal and DDoS attack traffic. For training and testing the ensemble learning models, normal and DDoS attack traffic data are obtained over a specific simulated experimental network topology. Techniques based on feature selection and hyperparameter tuning are used to optimize the performance of the decision tree ensemble models. Experimental results show that feature selection, combination of different decision tree ensemble models, and hyperparameter tuning can lead to a more accurate machine learning model with better performance detecting DDoS attacks against SDN-based SCADA systems.

Pelvic Compression Device (Binder) Application Training in Medical Students: A Manikin Study.

BACKGROUND: Correct application of external pelvic compression devices (binders) is crucial in managing multitrauma patients with suspected pelvic fractures to control hemorrhage. Yet, there is a lack of practical training standards for pelvic compression device application in medical school education. OBJECTIVE: This study aimed to evaluate simulation training of pelvic compression device application by medical students to determine the number of applications required to meet proficiency measured by correct application and timeliness. METHODS: This is an observational cross-sectional measurement study of a convenience sample of 132 volunteer senior medical students who participated in a 30-min theoretical and simulation training session on the application of pelvic compression devices. The study was conducted between January 1, 2020, and March 1, 2020. Two weeks after the training, the students performed 10 consecutive pelvic compression device applications, each followed by a 5-min feedback session break. Application step accuracy and timing were observed and recorded. The percentage of correct applications was compared by χ2 test. RESULTS: The correct application rate for the first application was 42.4%, with an average of 92 s, 95% confidence interval (CI): 91.00-93.72. The highest correct application rate occurred in the eighth application (97%, p < .001), with an average application time of 87 s, 95% CI: 85.62-87.72. CONCLUSION: We found that at least eight pelvic compression device manikin applications were required to achieve proficiency.

Validation of the Turkish version of the second victim experience and Support Tool (T-SVEST).

Objectives: Second victim experience defines the healthcare professionals involved in unexpected adverse patient events. The Second Victim Experience and Support Tool (SVEST) is a tool used to measure the second victim experience and the desired support resources. This study aims to carry out a cross-cultural adaptation of the SVEST and to evaluate the psychometric properties of the Turkish version (T-SVEST). Methods: The T-SVEST was translated and adapted according to World Health Organization guidelines. 221 healthcare professionals including physicians, residents and nurses working at the emergency department, completed the survey. â€‹Cronbach's â€‹α â€‹values were assessed for reliability, and construct validity was assessed through confirmatory factor analysis in order to evaluate model fit. Results: The global Cronbach's α score of the T-SVEST was 0.90. The final version of the TSVEST including 24 items was consistent with values between 0.83 and 0.89. The most consistent dimension was turnover intentions with a Cronbach's value of 0.89, it was followed by institutional support (Cronbach α = 0.88). After applying modifications suggested by â€‹confirmatory factor analysis, a final model including 9 factor-structure (7 dimensions and 2 outcome variables) and 24 items was significantly improved with acceptable â€‹comparative fit index, â€‹Tucker-Lewis index â€‹and â€‹root mean square error of approximation. Conclusion: The Turkish version of the SVEST is a reliable and valid instrument that can be used to identify second victims and help implement support resources.

The acute motor axonal neuropathy variant of Guillain-Barré Syndrome diagnosed after ankle trauma.

A case of Guillain-Barré syndrome (GBS) was diagnosed in a patient admitted to the emergency department (ED) after ankle trauma was presented. GBS is generally defined as immune-mediated peripheral neuropathy that develops after an infection. Our patient presented to ED with ankle trauma that developed after fatigue. Lateral, medial, and posterior malleolar fractures were detected in the ankle. The patient with loss of motor strength in the distal muscles was diagnosed with acute motor axonal neuropathy variant of GBS. After GBS treatment, the patient's loss of muscle strength regressed, and then surgical treatment was performed. We aimed to present this case report, which emphasizes the systematic approach of the emergency physician without having a large differential diagnosis list.

Comparison of sweep visual evoked potential of visual acuity and Snellen visual acuity in healthy and amblyopic children.

PURPOSE: To evaluate the visual acuity of healthy and amblyopic children using sweep visual evoked potential and compare the results with those of Snellen visual acuity testing. METHODS: A total of 160 children aged 6-17 years were included in the study. Of these, 104 (65%) were aged 7-17 years old, able to verbally communicate, and did not have any systemic or ocular pathology (Group 1). Group 2 included 56 (35%) children aged 6-17 years, able to verbally communicate, and had strabismus or anisometropic amblyopia whose best corrected visual acuity was between 0.1 and 0.8. All subjects underwent a detailed ophthalmological examination and sweep visual evoked potential measurement. Demographic characteristics, ocular findings, best corrected visual acuity, and sweep visual evoked potential results were recorded. RESULTS: In Group 1, the mean and maximum visual acuity values for sweep visual evoked potential were lower than the Snellen best corrected visual acuity (p<0.001, for both, respectively). Bland-Altman analysis revealed that in Group 1, the distribution of the differences between the Snellen best corrected visual acuity and mean sweep visual evoked potential visual acuity was ±0.11 logMAR, and the distribution of the differences between the Snellen best corrected visual acuity and maximum sweep visual evoked potential visual acuity was ±0.023 logMAR. In Group 2, the mean and maximum sweep visual evoked potential visual acuity were lower than the Snellen best corrected visual acuity (p<0.001 and p=0.009, respectively). Bland-Altman analysis revealed that the distribution of the differences between the Snellen best corrected visual acuity and mean sweep visual evoked potential visual acuity was ±0.16 logMAR, and the distribution of the differences between the Snellen best corrected visual acuity and maximum sweep visual evoked potential visual acuity was ±0.19 logMAR. CONCLUSIONS: Sweep visual evoked potential visual acuity measurements have comparable results with Snellen visual acuity measurements. This technique is an objective and reliable method for evaluating visual acuity in children.

Reliability and Validity of a New Computer-Based Triage Decision Support Tool: ANKUTRIAGE.

OBJECTIVE: Triage is a tool used to determine patients' severity of illness or injury within minutes of arrival. This study aims to assess the reliability and validity of a new computer-based triage decision support tool, ANKUTRIAGE, prospectively. METHODS: ANKUTRIAGE, a 5-level triage tool was established considering 2 major factors, patient's vital signs and characteristics of the admission complaint. Adult patients admitted to the ED between July and October, 2019 were consecutively and independently double triaged by 2 assessors using ANKUTRIAGE system. To measure inter-rater reliability, quadratic-weighted kappa coefficients (Kw) were calculated. For the validity, associations among urgency levels, resource use, and clinical outcomes were evaluated. RESULTS: The inter-rater reliability between users of ANKUTRIAGE was excellent with an agreement coefficient (Kw) greater than 0.8 in all compared groups. In the validity phase, hospitalization rate, intensive care unit admission and mortality rate decreased from level 1 to 5. Likewise, according to the urgency levels, resource use decreased significantly as the triage level decreased (P < 0.05). CONCLUSIONS: ANKUTRIAGE proved to be a valid and reliable tool in the emergency department. The results showed that displaying the key discriminator for each complaint to assist decision leads to a high inter-rater agreement with good correlation between urgency levels and clinical outcomes, as well as between urgency levels and resource consumptions.

Critical contributions of pre-S1 shoulder and distal TRP box in DAG-activated TRPC6 channel by PIP2 regulation.

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) regulates the activities of numerous membrane proteins, including diacylglycerol(DAG)-activated TRPC3/6/7 channels. Although PIP2 binding is known to support DAG-activated TRP channel activity, its binding site remains unknown. We screened for PIP2 binding sites within TRPC6 channels through extensive mutagenesis. Using voltage-sensitive phosphatase (DrVSP), we found that Arg437 and Lys442, located in the channel's pre-S1 domain/shoulder, are crucial for interaction with PIP2. To gain structural insights, we conducted computer protein-ligand docking simulations with the pre-S1 domain/shoulder of TRPC6 channels. Further, the functional significance of PIP2 binding to the pre-S1 shoulder was assessed for receptor-operated channel functions, cross-reactivity to DAG activation, and the kinetic model simulation. These results revealed that basic residues in the pre-S1 domain/shoulder play a central role in the regulation of PIP2-dependent gating. In addition, neutralizing mutation of K771 in the distal TRP box reversed the effect of PIP2 depletion from inhibiting to potentiating channel activity. A similar effect was seen in TRPV1 channels, which suggests that TRPC6 possesses a common but robust polarity switch mediating the PIP2-dependent effect. Overall, these mutagenesis studies reveal functional and structural insights for how basic residues and channel segments in TRP channels are controlled through phosphoinositides recognition.

Renal cell markers: lighthouses for managing renal diseases.

Kidneys, one of the vital organs in our body, are responsible for maintaining whole body homeostasis. The complexity of renal function (e.g., filtration, reabsorption, fluid and electrolyte regulation, and urine production) demands diversity not only at the level of cell types but also in their overall distribution and structural framework within the kidney. To gain an in depth molecular-level understanding of the renal system, it is imperative to discern the components of kidney and the types of cells residing in each of the subregions. Recent developments in labeling, tracing, and imaging techniques have enabled us to mark, monitor, and identify these cells in vivo with high efficiency in a minimally invasive manner. In this review, we summarize different cell types, specific markers that are uniquely associated with those cell types, and their distribution in the kidney, which altogether make kidneys so special and different. Cellular sorting based on the presence of certain proteins on the cell surface allowed for the assignment of multiple markers for each cell type. However, different studies using different techniques have found contradictions in cell type-specific markers. Thus, the term "cell marker" might be imprecise and suboptimal, leading to uncertainty when interpreting the data. Therefore, we strongly believe that there is an unmet need to define the best cell markers for a cell type. Although the compendium of renal-selective marker proteins presented in this review is a resource that may be useful to researchers, we acknowledge that the list may not be necessarily exhaustive.

Switch to aflibercept in the treatment of neovascular age-related macular degeneration: 30-month results / Mudança de tratamento para o aflibercepte no tratamento da Degeneração Macular neovascular Relacionada à Idade: resultados de 30 meses

ABSTRACT Purpose: This study was conducted to evaluate visual function and changes in the central macular thickness of patients with unresponsive neovascular age-related macular degeneration who were switched from ranibizumab (Lucentis®) to aflibercept (Eylea®) treatment at 30 months. Methods: This retrospective study examined patients with neovascular age-related macular degeneration who were switched to aflibercept after ≥6 previous intravitreal ranibizumab injections at 4- to 8-week intervals. All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections followed by a prore nata dosing regimen and after 30 months of treatment. Best corrected visual acuity, biomicroscopic examination, intraocular pressure, fundus examination, and central macular thickness were recorded at the start of treatment, before the transition to intravitreal aflibercept treatment, and at 6, 12, 18, 24, and 30 months of intravitreal aflibercept treatment. Results: A total of 33 eyes met the inclusion criteria. The median age of the patients was 73.57 ± 7.98 years, and 21 (61.8%) patients were males and 12 (35.3%) were females. Before the transition, the patients received a mean of 16.8 ± 8.8 ranibizumab injections (range 6-38).After the transition to intravitreal aflibercept treatment, the mean number of aflibercept injections was 9.09 ± 3.94. No significant differences were observed in best corrected visual acuity after the aflibercept switch in any of the months. The central macular thickness was significantly decreased at 6, 12, 18, and 30 months (p=0.01, p=0.03, p=0.05, p=0.05, p<0.001, respectively). Conclusion: Patients with neovascular age-related macular degeneration who were switched to intravitreal aflibercept treatment due to unresponsiveness to intravitreal ranibizumab exhibited a significant anatomic improvement in the retina, and although this state persisted, there was no significant functional gain.(AU)

RESUMO Objetivo: Avaliar, depois de 30 meses, a função visual e as alterações na espessura macular central de pacientes com degeneração macular relacionada à idade sem resposta terapêutica ao ranibizumabe (Lucentis®) que mudaram seu tratamento para o aflibercepte (Eylea®). Métodos: Realizou-se um estudo retrospectivo de pacientes com degeneração macular neovascular relacionada à idade que mudaram o tratamento para o aflibercepte após 6 ou mais injeções intravítreas de ranibizumabe a intervalos de 4-8 semanas. Todos os pacientes mudaram para o aflibercepte intravítreo (2,0 mg) e depois de 3 injeções consecutivas, seguidas de um regime de dosagem pro re nata, foram avaliados após 30 meses de tratamento. A melhor acuidade visual corrigida, o exame biomicroscópico, a pressão intraocular, a fundoscopia e a espessura macular central foram registrados no início do tratamento, antes da transição para o tratamento com aflibercepte intravítreo e aos 6, 12, 18, 24 e 30 meses de tratamento com o aflibercepte intravítreo. Resultados: Satisfizeram aos critérios de inclusão 33 olhos. A mediana da idade dos pacientes foi de 73,57 ± 7,98 anos. Dos pacientes, 21 (61,8%) eram homens e 12 (35,3%) eram mulheres. Antes da transição para o tratamento com o aflibercepte intravítreo, os pacientes receberam em média 16,8 ± 8,8 injeções de ranibizumabe (faixa 6-38).Depois da transição, o número médio de injeções de aflibercepte foi de 9,09 ± 3,94. Não houve diferenças significativas na melhor acuidade visual corrigida depois da mudança para o aflibercepte em qualquer das avaliações. Houve diminuição significativa da espessura macular central aos 6, 12, 18 e 30 meses (respectivamente, p=0,01, p=0,03, p=0,05, p=0,05 e p<0,001). Conclusão: Pacientes com degeneração macular neovascular relacionada à idade que mudaram seu tratamento para o aflibercepte intravítreo devido à falta de resposta ao ranibizumabe intravítreo, tiveram melhora anatômica significativa da retina; mas embora esse estado tenha persistido, não foi observado nenhum ganho funcional significativo.(AU)

Switch to aflibercept in the treatment of neovascular age-related macular degeneration: 30-month results.

PURPOSE: This study was conducted to evaluate visual function and changes in the central macular thickness of patients with unresponsive neovascular age-related macular degeneration who were switched from ranibizumab (Lucentis®) to aflibercept (Eylea®) treatment at 30 months. METHODS: This retrospective study examined patients with neovascular age-related macular degeneration who were switched to aflibercept after ≥6 previous intravitreal ranibizumab injections at 4- to 8-week intervals. All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections followed by a prore nata dosing regimen and after 30 months of treatment. Best corrected visual acuity, biomicroscopic examination, intraocular pressure, fundus examination, and central macular thickness were recorded at the start of treatment, before the transition to intravitreal aflibercept treatment, and at 6, 12, 18, 24, and 30 months of intravitreal aflibercept treatment. RESULTS: A total of 33 eyes met the inclusion criteria. The median age of the patients was 73.57 ± 7.98 years, and 21 (61.8%) patients were males and 12 (35.3%) were females. Before the transition, the patients received a mean of 16.8 ± 8.8 ranibizumab injections (range 6-38).After the transition to intravitreal aflibercept treatment, the mean number of aflibercept injections was 9.09 ± 3.94. No significant differences were observed in best corrected visual acuity after the aflibercept switch in any of the months. The central macular thickness was significantly decreased at 6, 12, 18, and 30 months (p=0.01, p=0.03, p=0.05, p=0.05, p<0.001, respectively). CONCLUSION: Patients with neovascular age-related macular degeneration who were switched to intravitreal aflibercept treatment due to unresponsiveness to intravitreal ranibizumab exhibited a significant anatomic improvement in the retina, and although this state persisted, there was no significant functional gain.