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Supplementary Figure from Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS–MAPK Pathway Inhibition in Pancreatic Cancer

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS–MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the selective degradation of the iron storage complex ferritin, in MEKi-treated cells. Ferritinophagy promotes mitochondrial iron–sulfur cluster protein synthesis and enhanced mitochondrial respiration. Accordingly, suppressing iron utilization sensitizes PDA cells to MEKi, highlighting a critical and targetable reliance on lysosome-dependent iron supply during adaptation to KRAS–MAPK inhibition.Significance:Reduced c-MYC levels following MAPK pathway suppression facilitate the upregulation of autophagy and lysosome biogenesis. Increased autophagy–lysosome activity is required for increased ferritinophagy-mediated iron supply, which supports mitochondrial respiration under therapy stress. Disruption of ferritinophagy synergizes with KRAS–MAPK inhibition and blocks PDA growth, thus highlighting a key targetable metabolic dependency.See related commentary by Jain and Amaravadi, p. 2023.See related article by Santana-Codina et al., p. 2180.This article is highlighted in the In This Issue feature, p. 2007

Supplementary Data from Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS–MAPK Pathway Inhibition in Pancreatic Cancer

SUMMARY OBJECTIVE: This study aimed to evaluate the effectiveness of cryotherapy in elderly patients with rib fractures due to blunt thoracic trauma. METHODS: In this prospective randomized controlled study, geriatric patients were assigned to groups to receive either coolant spray (n=51) or placebo spray (n=50). The visual analog scale scores of all patients were recorded before starting spray application (V0), as well as at 10th (V1), 20th (V2), 30th (V3), 60th (V4), 120th (V5), and 360th (V6) minute. The mean decreases in the visual analog scale scores were calculated. RESULTS: The differences between V0 and V1, V0 and V2, V0 and V3, and V0 and V4 mean visual analog scale scores measured in the coolant spray group were found to be significantly higher (p

In our study, it was aimed to create a new drug delivery system by loading the chemotherapeutic drugs into exosome vesicles. This system act as a Trojan horse to targeting GBM cancer. Exosomes were isolated from the T-98G cell line and characterized. Exosomes were encapsulated with Temozolomide. Then, the effectiveness of this new delivery system was evaluated by using MTT, LDH, TAC, TOS, GR. MTT results show a dose-dependent decrease in the TMZ and Exolimer+TMZ groups. But this rate decreased significantly in the Exolimer+TMZ groups. The lowest viability was observed at the Exolimer+TMZ 800 ng/ml concentration. Our results in LDH, GR, TAS and TOS analyzes shows correlation with MTT. Based on this study, we think that targeting the exosome to cancer by combining with special molecules and nanotechnology will bring a new perspective to cancer treatment.

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS–MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the selective degradation of the iron storage complex ferritin, in MEKi-treated cells. Ferritinophagy promotes mitochondrial iron–sulfur cluster protein synthesis and enhanced mitochondrial respiration. Accordingly, suppressing iron utilization sensitizes PDA cells to MEKi, highlighting a critical and targetable reliance on lysosome-dependent iron supply during adaptation to KRAS–MAPK inhibition. Significance: Reduced c-MYC levels following MAPK pathway suppression facilitate the upregulation of autophagy and lysosome biogenesis. Increased autophagy–lysosome activity is required for increased ferritinophagy-mediated iron supply, which supports mitochondrial respiration under therapy stress. Disruption of ferritinophagy synergizes with KRAS–MAPK inhibition and blocks PDA growth, thus highlighting a key targetable metabolic dependency. See related commentary by Jain and Amaravadi, p. 2023. See related article by Santana-Codina et al., p. 2180. This article is highlighted in the In This Issue feature, p. 2007

BACKGROUND: Acute coronary syndrome (ACS) is a common cause of mortality and morbidity. An ACS diagnosis can be made with electrocardiogram (ECG) and cardiac markers. However, despite medical advances, 2–5% of ACS patients are undiagnosed and discharged from emergency departments (EDs) because clinicians often find it difficult not only to diagnose and treat high-risk patients but also to define nonemergency diseases or safely discharge healthy patients. Risk stratification can be prevented, and inappropriate diagnosis and treatment protocols can be identified. The ED Assessment of Chest Pain Score-Accelerated Diagnostic Protocol (EDACS-ADP) scoring system, developed to identify patients with chest pain but at low risk for a major adverse cardiac event (MACE), is the first score based on clinical data from emergency medicine. OBJECTIVES: This study investigates the usability of EDACS-ADP in Turkey. MATERIALS AND METHODS: This is a prospective observational study of 392 patients. The primary outcome was a major adverse cardiovascular event (MACE) within thirty days. RESULTS: A total of 116 MACEs occurred in 65 (16,6%) patients during a one-month follow-up. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+ LR), and negative likelihood ratio (–LR) values of the EDACS-ADP score for the evaluation of 30-day MACE rate in patients who admitted with chest pain for two months were as follows: 96.9%, 64.5%, 35.2%, 99.1%, + LR: 2.73, and –LR: 0.05. CONCLUSION: Most of these patients were classified by the EDACS-ADP as low risk and suitable for discharge. The 30-day MACE rate of development was significantly low (0.9%) and acceptable in patients grouped as low risk.

Aim: The aim of our study is to the evaluation of melatonin (MLT) and Momordica charantia (MC) combination on PC-3 and HT-29 cancer lines and to address the question of where or not MLT increases MC antitumor effect in the PC-3 and HT-29 cancer lines. Material and Method: The PC-3 and HT-29 cell lines were grown in a manufacturer-specified culture medium. Cisplatin, MLT, increasing concentrations of MC, 40 μg/ml MLT + increasing concentrations MC were applied to PC-3 and HT-29 cell lines for 72 hours. 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell viability, Total Antioxidant Capacity (TAC), Total Oxidant Status (TOS), Cellular Migration (Wound Healing test), and Lactate Dehydrogenase (LDH) tests were done 72 hours after drug administration.Results: The combination of MLT 40 μg/ml + MC 100 µg/ml reduced cell viability in both PC-3 and HT-29 cells. Besides, TAC and TOS levels showed a correlation with LDH and MTT assays and were found to be statistically significant (P, Amaç: Çalışmamızın amacı, PC-3 ve HT-29 kanser hatlarında melatonin (MLT) ve Momordica charantia (MC) kombinasyonunun değerlendirilmesi ve MLT'nin PC-3 ve HT-29 kanser hatlarında MC antitümör etkisini nerede artırdığı sorusunu ele almaktır. Gereç ve yöntem: PC-3 ve HT-29 hücre çizgileri, üreticinin belirlediği bir kültür ortamında büyütüldü. Sisplatin, MLT, artan MC konsantrasyonları, MLT 40 μg / ml + artan konsantrasyonlar MC, PC-3 ve HT-29 hücre hatlarına 72 saat süreyle uygulandı. 3- (4,5-Dimetiltiyazol-2-Yl) -2,5-Difeniltetrazolyum Bromür (MTT) hücre canlılığı, Toplam Antioksidan Kapasitesi (TAC), Toplam Oksidan Durumu (TOS), Hücresel Göç (Yara İyileştirme testi) ve Laktat Dehidrojenaz (LDH) testleri, ilaç uygulamasından 72 saat sonra yapıldı.Bulgular: MLT 40 ug / ml + MC 100 ug / ml kombinasyonu, hem PC-3 hem de HT-29 hücrelerinde hücre canlılığını azalttı. Ayrıca TAC ve TOS seviyeleri LDH ve MTT testleri ile korelasyon gösterdi ve istatistiksel olarak anlamlı bulundu (P

Objective The most important problem for emergency physicians in patients presenting with chest pain is deciding whether to discharge the patient or not. Therefore, many scoring systems have been developed to help with this decision making process. We aim to achieve a modified HEART value by combining the VAS value with the HEART score. Materials and methods Data were collected on age, sex, duration of the symptoms, pain severity using a 10-point visual analog scale (VAS), and the presence of a major adverse cardiac event (MACE). The HEART score was calculated and modified (mHEART) by adding 1 point to the total HEART score for a VAS score of ≥7. Results During the study period, 4781 patients were admitted, and 293 participants were analyzed. Of the patients, 34(11.6%) experienced MACE within a month after the encounter. The mean VAS scores were 5.65±1.44. However, 77(26.3%) patients had VAS scores ≥7. Taking 3 as the threshold, 42(14.3%) patients had HEART scores of 4 and above, where 47(16.0%) had mHEART scores ≥4. The mHEART scoring demonstrated better test indicators than the HEART score. According to the HEART score, 6(2.3%) of the 251 patients predicted as negative would develop MACE, but this number decreased to 1(0.4%) in 246 using the mHEART score. Conclusion Although the HEART score performs reasonably well in discriminating patients who are MACE negative, it is possible to further improve the score by adding the VAS item. After validation by other studies, we would suggest modifying the HEART score by including the VAS item.

Objectives The aim of this study was to evaluate the diagnostic capacity of integrated pulmonary index (IPI) in predicting the pulmonary embolism (PE) in patients admitted to emergency departments (ED) with dyspnea. Background The acute dyspnea is one of the most common chief complaints in EDs. PE is a potentially fatal disease and the delay in specific therapy increases the worst outcomes. Methods This study is a prospective methodological study, in which we evaluated the diagnostic performance of the IPI in predicting PE in patients admitted to ED with dyspnea. ROC analysis was used for estimating the accuracy of IPI and OCRS. Results Of the 144 patients included in the study, there were 20 (13.9 %) PE patients. In the ROC analysis, the best cut-off point for IPI was ≤ 2. For this cut-off point, the sensitivity and specificity of IPI were 100.0 % and 96.0 %, respectively. Besides, the accuracy of IPI was 96.5 % with a +LR of 24.8 and a -LR of 0.0. Conclusion IPI was a potential candidate for evaluating the respiratory status, and a limiting tool to prevent unnecessary diagnostic tests and save time in determining the treatment course in dyspneic patients at ED (Tab. 5, Fig. 3, Ref. 34).

This study aimed to compare the analgesic efficacy of topical ibuprofen and topical piroxicam for acute musculoskeletal injuries.In this prospective, randomized, controlled, double-blinded study, geriatric patients were assigned to groups to receive either topical ibuprofen (n = 70) or topical piroxicam (n = 69). The first dose of gel was applied in the emergency department and the remaining doses were self-administered at home by the patients thrice daily for 72 h. For each patient, the initial baseline visual analog scale (VAS) score (V 0) was compared with the VAS scores at the 60 min (V1), 120 min (V2), 24 h (V3) and 72 h (V4) time points. The decreases in VAS scores, clinical effectiveness of the treatments, and incidence of adverse events were evaluated.In the topical ibuprofen group, the VAS scores were significantly lower at each measurement time point compared to baseline (p .001). The results were as follows: V0 -V: 1.08, 95% CI: 0.56-1.61; V0 -V2: 1.09, 95% CI: 0.49-1.69; V0 -V3: 1.44, 95% CI: 0.81-2.07; V0 -V4: 1.59, 95% CI: 0.91-2.26. The mean percentage decrease in the VAS scores in the topical ibuprofen group was significantly higher than that in the topical piroxicam group (p .001). The clinical effect of treatment was found to be significantly higher for the ibuprofen gel group (p .001). There was no substantial difference in treatment-related adverse events between the groups (p .05).Ibuprofen gel, which is a safe treatment option for geriatric patients, is more clinically effective than piroxicam gel. Response to Reviewers.

Introduction Coolant spray application in musculoskeletal injuries is an effective and harmless method to treat pain and reduce functional limitation. This study assessed the clinical value of coolant spray application on patient comfort before and during the radiographic imaging process along with its early analgesic and anti-edema effects. Methods A total of 155 patients, admitted to the emergency department between April 1, 2019, and June 31, 2019, were included in this study. The patients were randomly assigned to either a coolant spray or a saline spray (placebo) group. To the coolant spray group patients, Cryos ®Spray (Phyto Performance, Italy) was applied. To the placebo group patients, a normal saline solution in a bottle covered with white opaque paper and refrigerated at 4 °C was sprayed. Radiographic images of the patients were scored for appropriateness of the standard imaging characteristics. Results The mean scores were 8.13 ± 1.8 and 6.58 ± 2.2 for the coolant spray and normal saline spray groups, respectively; the differences were statistically significant between the two groups (mean difference: -1.56, 95% CI:-2.20 to −0.92; p = .000). Patients with fractures on their radiographs and treated with coolant spray received higher scores than similar patients treated with normal saline spray (mean difference:-1.92, 95% CI:-3.28 to −0.55; p = .009). The proportion of patients requesting analgesic treatment before discharge was statistically lower in the coolant spray group compared to the normal saline group (p = .025). Conclusions The radiographic images taken after coolant spray intervention in patients with acute ankle trauma were more successful in showing the target structures.

Introduction Musculoskeletal pain such as low back pain (LBP) are routinely encountered in the ED and contribute to ED overcrowding. The aim of our study was to compare the efficiency of mesotherapy with systemic therapy in pain control in patients with lumbar disk herniation. Methods We conducted this prospective parallel randomized controlled trial with the patients admitted to the emergency department with low back pain related to herniated lumbar disk. Mesotherapy was performed to one group, while intravenous dexketoprofen was administered to the control group. Changes in pain intensity at 15th minute, 30th minute, 60th minute and 24th hours after treatment using Visual Analogue Scale (VAS), need to use analgesic drug within 24 h after treatment, and adverse effect of the treatment methods were compared between groups. Results The decreases in pain intensity were statistically significantly higher in mesotherapy group for all time intervals. The need to use analgesics was statistically significantly three fold higher in the systemic therapy group. There was no statistically significant difference in having any adverse effect between study groups during one-week follow-up period. Conclusions Changes in medical practices, from the systemic administration of NSAIDs to the minimally invasive techniques such as mesotherapy with potent efficacy and minimal side effects, may enhance the ability of EDs to meet the waiting time targets and improve patient's satisfaction.

Introduction Chronic Obstructive Pulmonary Disease (COPD) related visits to the emergency department have increased substantially during the past decade. An important challenge facing emergency physicians when treating COPD patients is deciding on disposition. The aim of this study was to evaluate Integrated Pulmonary Index scoring to guide the disposition decisions of emergency physicians by comparing its compatibility with Ottawa COPD Risk Score. Methods This is a prospective methodological study, in which we compared the accuracies of the Integrated Pulmonary Index and Ottawa COPD Risk Score in predicting of the short-term serious outcomes in patients admitted to the emergency department with COPD exacerbation. Patients who admitted to our emergency department between 01.01.2019–31.03.2019 were evaluated. The results Among the 208 patients, there were 154 (74.0%) short-term serious outcomes. The AUCs were 0.915 and 0.943 for Integrated Pulmonary Index and Ottawa COPD Risk Score, respectively. The difference between AUCs for two scores was not statistically significant. The best cut-off point for Integrated Pulmonary Index and Ottawa COPD Risk Score were ≤3 and >4, respectively. For these best cut-off points, the sensitivity and specificity of Integrated Pulmonary Index were 92.9 and 87.1, respectively. The sensitivity and specificity of Ottawa COPD Risk Score were 99.3 and 85.2, respectively. Besides, the accuracy of Integrated Pulmonary Index was 91.3, and the accuracy of Ottawa COPD Risk Score was 95.7. Conclusions Integrated Pulmonary Index was a potential candidate for evaluating respiratory status and prediction of short-term severe events in patients with acute COPD exacerbation in emergency departments.

Background: Ischemic stroke is a leading cause of death and functional disability worldwide. Several clinical scores or stroke scales, biological test or markers, clinical signs, and radiological imaging have been performed to predict both worse neurologic outcome and mortality for ischemic stroke. Objectives: The aim of our study was to investigate the association between early Bispectral Index scores and in-hospital mortality in patients with ischemic stroke. Methods: This is a comparative prospective methodological study, in which we evaluated the predictive accuracies of Bispectral Index, Glasgow Coma Scale, and Charlson Comorbidity Index for in-hospital mortality of patients with ischemic stroke. Receiver operating characteristic analysis was used for comparing the accuracy of the scoring systems, areas under receiver operating characteristic curves were calculated, and Youden J index was used for estimating associated cut-off values. Results: Among the 80 ischemic stroke patients, in-hospital mortality rate was 38.8% (n = 31). The areas under receiver operating characteristic curves were 0.984, 0.960, and 0.863 for Bispectral Index, Glasgow Coma Scale, and Charlson Comorbidity Index, respectively. The difference between areas under receiver operating characteristic curves for Bispectral Index and Glasgow Coma Scale was statistically similar. Besides, the difference between areas under receiver operating characteristic curves for Bispectral Index and Charlson Comorbidity Index, and the difference between areas under receiver operating characteristic curves for Glasgow Coma Scale and Charlson Comorbidity Index were statistically significant. The associated cut-off values were ⩽74, ⩽12, and >4 for Bispectral Index, Glasgow Coma Scale, and Charlson Comorbidity Index, respectively. For these cut-off points, sensitivity and specificity of Bispectral Index were 93.6% and 95.9%, sensitivity and specificity of Glasgow Coma Scale were 100.0% and 83.7%, and sensitivity and specificity of Charlson Comorbidity Index were 83.9% and 69.4%, respectively. However, accuracy of Bispectral Index was 95.0%, accuracy of Glasgow Coma Scale was 90.0%, and accuracy of Charlson Comorbidity Index was 75.0. Conclusion: Knowledge of the risk factors for mortality in patients with ischemic stroke can help to identify which patients have a higher risk of fatal outcome. The Bispectral Index score improved discrimination and classified patients with higher mortality better than both Glasgow Coma Scale and Charlson Comorbidity Index.

Introduction. The 2019-novel-coronavirus (2019-nCoV) outbreak has become a common problem for the whole world. Aim. To investigate the impact of the 2019-nCoV pandemic period in our country on emergency room admissions. Materials and methods. The study was designed as a retrospective cohort. The first case of pneumonia infected with nCoV in our country was diagnosed on March 11, 2020. Considering the date of March 11, 2020, emergency room admissions for two periods of 7 days were investigated, pre-COVID-19 and COVID19. Demographic data, admission diagnosis, vital findings, stay times in emergency room, terminations and emergency department mortality examined. A group of ‘geriatric’ patient populations were created to examine the admission characteristics of patients aged-65 and over. Results. The 3466 patients included in the study. The average number of daily admissions was significantly higher in the pre-COVID-19 period (350.4 ± 54.5), compared to the COVID-19 period (144.7 ± 20.2, p=0001). While the proportion of cardiac- caused admissions increased during the COVID period, the proportion of gastrointestinal-induced admissions decreased (p

This study is supported in part by TUBITAK grant 119C028, and in part by Turkcell Technology within the framework of 5G and Beyond Joint Graduate Support Programme coordinated by Information and Communication Technologies Authority. A communication receiver that wants to pull data from a remote sensor by exploiting wireless energy transfer is considered. The receiver has a long-term average energy budget for this operation, and its goal is to keep the time average of a general age penalty function as small as possible. The channel from the source to the receiver is a two-state (ON/OFF) communication link whose state is IID or Markovian, and known instantaneously by the receiver. Modeling the problem as a constrained Markov decision problem, we obtain a randomized threshold-based decision policy that achieves the minimum possible average age penalty. We determine the optimal time average Age of Information and age violation probabilities by exploiting the optimality of the derived policy. IEEE Control Systems Society Information Theory Society Communication Systems Technical Committee (Performance of Communication Systems Working Group) Publisher's Version WOS:000766966900006

INTRODUCTION: It is not the right behaviour to accept every anxiety pathologically. On the contrary, the sense of anxiety is an indicator of the response of individuals to internal or external changes. More importantly, anxiety is a beneficial affective state for individuals who contribute to the development of self and bodily adaptability to the new environment in which they live. MATERIAL AND METHODS: This is a prospective study. The study was conducted on the parents of the patients who applied to the paediatric emergency department and paediatric trauma units of the emergency department at Ataturk University Faculty of Medicine. Beck Anxiety Scale was administered to one of the relatives who brought the patient to the hospital. Beck anxiety test was filled in by using face-to-face interview method. Pre-defined study forms for patients included in the study were completed. RESULTS: The study was completed with 68 family members in both groups. The values of the patients who were admitted to the paediatric emergency and adult emergency departments on the Beck Anxiety Scale were equal. CONCLUSIONS: family members of paediatric patients admitted to hospital were compared; The family members of the paediatric trauma unit and the family members of the paediatric emergency department have the same level of anxiety.

INTRODUCTION: Fasting is one of the five basic obligations of Islam. Muslims fast during the month of Ramadan according to the lunar calendar. Fasting during Ramadan involves abstinence from food and drinks from sunrise to sunset. The present study investigated the effect of fasting during Ramadan in patients who presented to emergency departments. Results of this study may guide healthcare authorities in countries that provide health services to Muslim communities because of increased migration. MATERIAL AND METHODS: This is the first prospective multicentre study to examine emergency department applications for Ramadan. The study was performed between 05.26.2017 and 06.24.2017. Patients were classified according to cardiopulmonary complaints, trauma-associated complaints, neurological complaints, gastrointestinal complaints, headache, renal colic, upper respiratory tract complaints, and malaise. Vital signs, age, gender, presentation type, complaint type, hospital stay duration, requested laboratory examination, radiological examination, treatment outcomes, application time, smoking status, and fasting status of the study patients were recorded by using a questionnaire. RESULTS: Fasting and non-fasting patients showed a significant difference with respect to presentation type, gastrointestinal complaints, upper respiratory tract complaints, hospitalization status, requested radiological and biochemical examinations, hospitalization duration, and application time (p < 0.05). CONCLUSIONS: To the authors’ knowledge, the present study is the first to compare the complaints of fasting and non-fasting patients during Ramadan. The authors feel that this study is superior to several previous studies because it has been performed using a different perspective and provides more accurate and objective data than those reported in previous studies.

Lysosomes must maintain integrity of their limiting membrane to ensure efficient fusion with incoming organelles and degradation of substrates within their lumen. Pancreatic cancer cells upregulate lysosomal biogenesis to enhance nutrient recycling and stress resistance, but whether dedicated programs for maintaining lysosomal membrane integrity facilitate pancreatic cancer growth is unknown. Using proteomic-based organelle profiling, we identify the Ferlin family plasma membrane repair factor, Myoferlin, as selectively and highly enriched on the membrane of pancreatic cancer lysosomes. Mechanistically, lysosome localization of Myoferlin is necessary and sufficient for maintenance of lysosome health and provides an early-acting protective system against membrane damage that is independent from the endosomal sorting complex required for transport (ESCRT)-mediated repair network. Myoferlin is upregulated in human pancreatic cancer, predicts poor survival, and its ablation severely impairs lysosome function and tumour growth in vivo. Thus, retargeting of plasma membrane repair factors enhances pro-oncogenic activities of the lysosome.

INTRODUCTION: The aim of this study is to examine the story, clinical findings, initial computed tomography (CT) findings and reverse transcription-polymerase chain reaction (RT-PCR) results and evaluate the consistency of this data. METHODS: This is a multi-center retrospective study and out of patients aged 18 and over who were evaluated for COVID-19 in the emergency department between 01.04.2020 and 01.05.2020. Data regarding the patients such as age, gender, comorbidity, COVID-19 contact, symptoms, vital findings, laboratory parameters, CT findings, hospitalization status and case fatality rate (CFR) were examined. RESULTS: 62.4% of 687 patients were male, the mean age was 49.7.49.9% of patients had at least one comorbidity. The most common symptoms were fever (61.6%), cough (56.5%), dyspnea (33.2%). 33.9% of patients had RT-PCR positivity, 69.9% had CT positivity, and 72.5% had both RT-PCR and CT positivity. Sensitivity of CT was 72.5, its specificity was 31.5% and its accuracy was 45.5%. Most common CT pattern was pure GGO (47.9%). CFR was 6% and it was significantly higher in both RT-PCR and CT positive patients (p=0.01). According to logistic regression analysis, male gender (p=0.037;OR: 0.385;95% CI, 0.157-0.943), higher age (p=0.000;OR: 1.068;95% CI, 1.031-1.106) and comorbidity presence (p=0.008;OR: 5.374;95% CI, 1.539-7.618) were found to be associated with mortality. DISCUSSION AND CONCLUSION: In our study, we found that using RT-PCR and CT together and supporting them with clinical data was the strongest approach in the diagnosis of COVID-19 cases.

Lysosomes must maintain the integrity of their limiting membrane to ensure efficient fusion with incoming organelles and degradation of substrates within their lumen. Pancreatic cancer cells upregulate lysosomal biogenesis to enhance nutrient recycling and stress resistance, but it is unknown whether dedicated programmes for maintaining the integrity of the lysosome membrane facilitate pancreatic cancer growth. Using proteomic-based organelle profiling, we identify the Ferlin family plasma membrane repair factor Myoferlin as selectively and highly enriched on the membrane of pancreatic cancer lysosomes. Mechanistically, lysosomal localization of Myoferlin is necessary and sufficient for the maintenance of lysosome health and provides an early acting protective system against membrane damage that is independent of the endosomal sorting complex required for transport (ESCRT)-mediated repair network. Myoferlin is upregulated in human pancreatic cancer, predicts poor survival and its ablation severely impairs lysosome function and tumour growth in vivo. Thus, retargeting of plasma membrane repair factors enhances the pro-oncogenic activities of the lysosome.

Paracetamol is the most widely used and prescribed drug word-wide. It is the most common cause of the poisoning and of the fatality due to the toxic administration throughout the world. A 34-year-old female patient applied to our ED with the complaint of swallowing 33 g of paracetamol. After routine toxicity treatment, on the third day of the hospitalization, dyspnea and pain on the right hemithorax and right flank occurred. Chest X-ray showed blunted right sinus. CT revealed bilateral pleural effusion. With thoracentesis, clear, colorless and odor-free fluid of about 500cc was drained. Laboratory examination of the fluid confirmed it as transudate. We believed pleural effusion is related to high-dose paracetamol intake and it occurred due to decrease in pleural permeability and the consequent decrease of the fluid absorption. In conclusion, high-dose intake of paracetamol might cause transudative pleural effusion as a complication.

This study aimed to compare the analgesic efficacy of topical capsaicin and topical piroxicam in acute musculoskeletal injuries.This is a prospective, randomized, controlled, double-blinded study. The data for the 67 patients in the piroxicam group and the 69 in the capsaicin group were examined. The initial visual analog scale (VAS) scores were compared with the 60th and 120th minute as well as the 24th and 72nd hour values. Differences between the VAS scores, clinical effectiveness of the treatment and side effects were evaluated.In the capsaicin group, the mean difference in the delta VAS scores was significantly higher at each measurement time. The mean of the percentage of reduction in the VAS scores of the topical capsaicin group was significantly higher than that in the topical piroxicam group. The highest difference in terms of both outcomes was determined at the 72nd hour VAS change. Mean differences were 1.53 (95% CI: 0.85-2.221) and 19.7 (95% CI: 12.4-27.2) respectively (p 0.001). In the capsaicin group, the clinical effect of the treatment was found significantly higher (p 0.01). The difference between the clinical effectiveness of the groups regarding the treatment outcomes was also statistically significant (p 0.001). There was no significant difference between the patient groups regarding the presence of side effects.Topical capsaicin can be used as an alternative to topical piroxicam initially and at follow-up in patients presenting to the emergency department with acute pain as there were no observable differences in side-effects between the two groups.

Hiccup is a condition caused by involuntary contraction of inspiratory muscles, especially the diaphragm. Although it is generally considered as a physiological. response, if hiccup persists for a long time, it can lead to many undesirable conditions such as depression, weight loss, insomnia, and fatigue. A 35-year-old male patient was admitted to our emergency department with hiccup lasting for 15 h. He had a history of several hiccup attacks. Classical non-pharmacological and pharmacological therapies were used to treat the condition without any response. As an alternative method, an intradermal injection was applied. A mixture of thiocolchicoside and lidocaine was administered intradermally to a depth of 1–3 mm at the epigastric region and adjacent to the sternocleidomastoid muscle. The patient's hiccup ended after the intradermal injection procedure. During 48 h of follow-up the hiccup attack did not develop again. No complications related to the process were detected. This is the first case in the literature demonstrating the use of intradermal injection to terminate hiccups. The intradermal injection approach can be administered in cases of hiccups that do not respond to medical treatment.

Glutamate release and reuptake play a key role in the pathophysiology of depression. glutamatergic nerves in the hippocampus region are modulated by histaminergic afferents. Excessive accumulation of glutamate in the synaptic area causes degeneration of neuron cells. The H4 receptor is defined as the main immune system histamine receptor with a pro-inflammatory role. To understand the role of this receptor, the drug JNJ7777120 was used to reveal the chronic depression-glutamate relationship. We have important findings showing that the H4 antagonist increases the glutamate transporters’ instantaneous activity. In our experiment, it has been shown that blocking the H4 receptor leads to increased neuron cell viability and improvement in behavioral ability due to glutamate. Therefore, JNJ can be used to prevent neurotoxicity, inhibit membrane phospholipase activation and free radical formation, and minimize membrane disruption. In line with our findings, results have been obtained that indicate that JNJ will contribute to the effective prevention and treatment of depression.

Aim: The sixth grade of medical school is a true preparatory stage for the physicians. This places the physician candidates at stress before the emergency medicine (EM) internship and can lead to anxiety and depression. The present study is the first study to investigate depression, anxiety, and stress levels of sixth-grade medical students before and after the EM internship.Materials and Methods: This is a prospective study,which is conducted on sixth-grade medical students. Anxiety, depression, and stress scores were assessed on the first and last day of the EM internship. The Beck depression and Beck anxiety scales and Depression Anxiety Stress Scale-42 (DASS-42) were used. Overall, 131 sixth-grade medical students who met the inclusion criteria were enrolled in the study.Results: The mean Beck depression score was 10.15±6.11 on the first day of internship and 6.37±4.79 on the last day of internship. The difference was statistically significant (p

Introduction: Water pipe is a different form of tobacco consumption. In recent years, water pipe usage has become increasingly widespread. The thought that it is less harmful than cigarettes increases its usage. Long-term exposure to high carbon monoxide levels due to water pipe consumption may cause carbon monoxide poisoning.Case Report: We present four patients aged 18–29 who consulted our emergency department with complaints regarding fainting, blackout, and headache. While three of them consumed water pipe, one who was a non-consumer, was in an environment in which water pipe was consumed. Carboxyhemoglobin values of the patients were between 18.7%-35.5%. Our patients received one session of hyperbaric oxygen treatment. Patients with improved clinical situations after treatment were discharged. Conclusion: Water pipe consumption is the most observed form of tobacco consumption in the Eastern-Mediterranean Region, followed by in the US. Although it is considered that all toxic agents are filtered while water pipe smoke passes through water, water pipe consumption increases levels of carcinogens, carbon monoxide, nicotine, and tar in the blood compared to smoking. It is striking that carboxyhemoglobin values of our cases are as high as, or even higher than, that in stove poisoning cases. It must be kept in mind that non-specific symptoms following water pipe consumption may be symptoms of carbon monoxide poisoning

Burn is the tissue damage on body caused due to various reasons. Although all burns caused by hot liquids are investigated as scalding burns, dense liquid burns (DLB) caused by such as milk and oil are different from other burns. The aim of this study was to report the properties of DLB.Patients admitted to the Emergency Service of Atatürk University Hospital, with DLB from June 2003 to December 2008, were examined retrospectively.During the study, 28 DLB patients were admitted to the emergency service. The most common admission were found in autumn 28.6% (n=8), and in May and June, 17.9% (n=5). The frequency of burns on the right upper extremity was seen in 50% (n=14) of the patients. The burn degree of all patients was determined as 2(nd) degree. Seventy-five percent (n=21) of the patients were discharged, 14.3% (n=4) were hospitalized. None of the patients died.Dense liquid burns is a burn type that is commonly seen in women, absolutely causing 2(nd) degree burns, frequently reported in upper extremity and head/neck regions, and in contrast to other studies, in our region it is completely seen in patients living in city centre.Yanık sıklıkla sıcak suya bağlı (haşlanma) oluşan hayatı tehdit eden bir durumdur. Bununla birlikte, bizim deneyimlerimize göre, sıcak süt ve yağ gibi yoğun sıvılara bağlı yanıklar, klinik seyir ve taburculuk açısından farklılıkları sebebi ile ayrı değerlendirilmelidir. Burada yoğun sıvılara bağlı yanıkların özelliklerini sunduk.Acil servisimize 2003 ile 2008 yılları arasında yoğun sıvılara bağlı yanık sebebi ile başvuran hastaları retrospektif olarak inceledik.Toplam olarak, 28 hasta çalışmaya dahil edildi. Ortalama yaş 26,5 idi ve hastaların %75’i kadındı. Hastaların %89,3’ü acil servisimize direk başvurdu ve %10,7’si başka acil servislerden hastanemize sevk edilmiş idi. Hastaların %75’i acil servisteki tedavilerinin ardından taburcu edildi, %14,3’ü yanık merkezine yatırıldı, %7,1’i başka hastaneye sevk edildi ve %3,6’sı yatışı reddetti. Yanık merkezindeki ortalama yatış süresi 24,5 gündü. Ortalama yanık alanı %3 idi. Vücut bölümlerine göre yanık sıklığı yüzdeleri: Baş ve boyun %39,3, gövde ön yüzü %14,3, gövde arka yüzü %17,9, sağ üst ekstremite %50, sol üst ekstremite %35,7, sağ alt ekstremite %21,4, sol alt ekstremite %89,3. Yanıkların tümü 2. dereceydi.Sıcak süt ve yağa bağlı yoğun sıvı yanıkları sıklıkla kadınlarda görülür. Yanıkların tamamı 2. derecedir.

Background: Acute musculoskeletal pain is one of the common causes of emergency admissions. Topical analgesics are an easily tolerated option in the treatment of these pains. Objective: This study aimed to compare the efficacy of topical capsaicin and topical non-steroidal anti-inflammatory drugs in acute musculoskeletal injuries. Methods: In this prospective, randomized, controlled, double-blinded study, patients were allocated to two groups—the topical non-steroidal anti-inflammatory drug (n = 60) and topical capsaicin (n = 59). For both groups, the first dose treatment was applied as a thin layer in the emergency department to a maximum area of 5 × 5 cm. The remaining doses were administered at home by the patients for 72 h. The initial visual analog scale scores were compared with the 60th and 120th minute as well as the 24th and 72nd hour values. Differences between the visual analog scale scores, clinical response to the treatment, and side effects were evaluated. Results: The proportional reduction in visual analog scale scores for topical capsaicin was significantly higher, especially at 36 and 72 h. These rates were 0.75 (95% confidence interval: 0.77–1.42; p = 0.029) and 9.08 (95% confidence interval: 1.02–17.14; p = 0.028) at 36 h, respectively. At 72 h, they were 1.27 (95% confidence interval: 0.48–2.05; p = 0.002) and 17.07 (95% confidence interval: 8.39–25.76; p Conclusion: Topical capsaicin can be used safely in patients presenting to the emergency department with acute pain with its high analgesic efficacy and absence of systemic side effects.

1 , Bunyami Ozogul 2 , Umit Avsar 3 Abstract Aim: Electrical burns may develop because of the direct effect of electric current on the cell membrane and smooth muscle of blood vessels and because of the transformation into heat energy when passing through body tissues. Electrical burns account for 3%-5% of all cases of burns. Materials and Methods: A total of 213 patients with electrical burns who were admitted to our emergency department (ED) between 2001 and 2011 were retro- spectively analyzed. Results: The mean age of patients was 33.7±10.8 (min: 18, max: 72 years), and 86.9% (n=185) of the patients were male. The majority of patients (63.4%; n=135) were living in city centers, followed by patients in the village (22.5%; n=48) and the countryside (14.1%; n=30) respectively. The most common occurrence times of the burns were 14:00 (5.6%; n=12) and 10:00-11:00 (4.2%; n=9). Of the patients, 39.4% (n=84) were admitted to our ED between 18:00 and 24:00. Third degree burns were seen in 57.9% (n=127) patients, second degree in 39.4% (n=84), and first degree in 0.9% (n=2). Subarachnoid hemorrhage was accompanied in one patient and acute abdomen in another. Mortality was 1% (n=2) in the burn center. Electrical burns were most frequently seen in August (14.1%; n=30), June (11.3%; n=24), and July (10.3%; n=22). However, it was rarely seen during winter months (16%; n=34). The average days of hospitalization were 26.4±24.8 (min: 1, max: 141 days).

The buildings, working personnel, and patients and their relatives may directly or indirectly be affected by the disasters. Here we will discuss evacuation, establishing a field hospital, communication, the role of the media in disasters, and defending against sabotage. The affected individuals should be evacuated and transferred to secure zones safely and rapidly. How the decision for evacuation should be made and how the evacuation triage should be performed are important issues. Field hospitals should be established within the bounds of possibility for continuation of the treatments of evacuated people. The standards for the field hospitals and its sections that may be created according to the needs will be explained. Undoubtedly, since one of the most important subjects in disasters is communication, the types of communication in disasters and their significance will be mentioned. How the relationships with the media should be an aspect of communication and how they can be beneficially used will also be mentioned. As in all organizations and institutions, sabotage attempts may also be present concerning health facilities. For this reason, during the preparation of the hospital disaster plan, defending against sabotage will be discussed, and what should be done at that stage will be mentioned.Afetlerden binalar, çalışan personeller, hasta ve hasta yakınları doğrudan veya dolaylı olarak etkilenebilir. Biz burada tahliye, sahra hastanesinin kurulumu, haberleşme, medyanın afetlerdeki rolü ve sabotajlara karşı koyma konularını tartışacağız. Etkilenen kişiler güvenli bir şekilde ve hızlıca tahliye edilerek güvenli bölgelere nakledilmelidir. Tahliye kararının nasıl verileceği ve tahliye triyajının nasıl yapılacağı önem arz etmektedir. Tahliye edilen kişilerin tedavilerinin devamı için sahra hastanelerinin imkânlar doğrultusunda oluşturulması gerekir. Sahra hastanelerinin standartları ve ihtiyaca göre oluşturulabileceği bölümler açıklanacaktır. Hiç şüphesiz afetlerdeki en önemli konulardan biri de haberleşme olduğu için afetlerdeki haberleşme çeşitlerine ve önemine değinilecektir. Haberleşmenin bir parçası olarak medya ile ilişkilerin nasıl olması gerektiği ve nasıl faydalı olarak kullanılabileceğine de değinilecektir. Tüm kurum ve kuruluşlara karşı sabotaj eylemleri olabildiği gibi sağlık kuruluşlarına yönelikte sabotaj eylemleri de olabilir. Bunun için hastane afet planı hazırlanmasında sabotajlara karşı koymaya da yer verilerek bu aşamada yapılacaklara değinilecektir.

The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by constant retrotranslocation into the cytosol of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wild-type proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death.

Blue code systems (BCS) are communication systems that ensure the most rapid and effective resuscitation when a patient is in respiratory or cardiac arrest. A hospital employee faced with the situation of a cardiopulmonary arrest (CPA) starts the system by dialing 6666 from any phone in the hospital. We created a five-person team that includes a doctor, nurse, anesthesia technician, stretcher officer and security guard. The purpose of this study is to share our experiences in initiating the use of the BCS in our hospital.In our hospital, the records of calls that were made by Callvision BCS were analyzed retrospectively from May 2010 to the end of January 2011.A total of 474 calls were made using the blue code system. Of those calls, 402 (84.5%) were determined to be inappropriate calls. The remaining 72 calls were responded to. Of the 72 patients who were treated, 21 were discharged after they were hospitalized in the service or intensive care unit, 45 cases resulted in exitus, and 5 cases were referred to the Ataturk University faculty of medicine.The BCS has achieved its goal. The discharge rate of 29.5% that we achieved is a successful result.Mavi Kod sistemleri, bir hastanın solunumsal veya kardiyak arresti durumunda, hastaya en hızlı ve verimli resüsitasyonu sağlamaya yönelik çalışan iletişim sistemleridir. Bir kardiyopulmoner arrest durumu ile karşılaşan hastane çalışanı hastanedeki herhangi bir telefondan 6666’yı aradığı zaman sistemi tetiklemiş oluyor. Biz, doktor, hemşire, anestezi teknisyenleri, sedye görevlisi ve güvenlik görevlisinden oluşan beş kişilik bir ekip oluşturduk. Bu çalışmanın amacı hastanemizde başlattığımız mavi kod sistemi ile ilgili deneyimlerimizi paylaşmaktır.Hastanemizde Callvision mavi kod sisteminden elde edilen kayıtlar, Mayıs 2010’dan itibaren Ocak 2011 sonuna kadar retrospektif olarak incelendi.Mavi kod sistemi kullanılarak 474 arama yapıldı. Bu çağrıların, 402’sinin (84,5%), uygunsuz çağrı olduğu tespit edildi. Geri kalan 72 olguya müdahale edildi.Bu 72 vakadan, 21 vaka servis ya da yoğun bakım ünitesinde yatışı sonrası taburcu edildi, 45 olgu exitus ile sonuçlandı ve 5 olgu Atatürk Üniversitesi Tıp Fakültesine sevk edildi.Mavi kod sistemi hedefine ulaşmıştır. Çalışmamızda elde ettiğimiz 29,5%’lik taburculuk oranı başarılı bir sonuçtur.

The pro-apoptotic BCL-2 protein BAX commits human cells to apoptosis by permeabilizing the outer mitochondrial membrane. BAX activation has been suggested to require the separation of helix α5 from α6 and thus the ‘latch’ from the ‘core’ domain among other conformational changes. Here we show that conformational changes in this region impair BAX translocation to the mitochondria and retrotranslocation back into the cytosol and therefore BAX inhibition, but not activation. Redirecting misregulated BAX to the mitochondria revealed an alternative mechanism of BAX inhibition. The E3 ligase Parkin, known to trigger mitochondria-specific autophagy, ubiquitinates BAX K128 and targets the pro-apoptotic BCL-2 protein for proteasomal degradation. Retrotranslocation-deficient BAX is completely degraded in a Parkin-dependent manner. Although only a minor pool of endogenous BAX escapes retrotranslocation into the cytosol, Parkin-dependent targeting of misregulated BAX on the mitochondria provides substantial protection against BAX apoptotic activity.

Background: Despite the developments in medicine in recent years, people in many regions of the world still tend to use alternative, or non-medical, folkloric treatment methods for many different health problems. One of these methods is “rope wrapping to the back,” which is considered to be therapeutic for patients with lumbar disc hernias or low back pain. This method is practiced by local individuals without medical training. Case Report: Over the course of 3 years, 14 patients, 8 women and 6 men, presented to Ataturk University and Erzurum state hospitals in eastern Turkey after undergoing the folk treatment known as “rope wrapping to the back” for low back pain. One of the patients, who had symptoms of systemic infection, later died. Of the other patients, 4 had local infections, 6 had unresolved complaints, and 3 had other complaints. Nine of the patients were treated in the emergency department and 4 required surgery. Two case reports are provided as examples. Conclusion: Improvements are needed to increase the accessibility of health care, improve physician–patient communication, and provide information to people, so as to prevent the use of folk remedies, which can have serious complications, sometimes resulting in death.

Summary What is known and Objective: Imatinib is a specific BCR/ABL inhibitor, commonly used for the treatment of chronic myeloid leukaemia (CML), a hematological malignancy resulting from a chromosomal translocation that generates the BCR/ABL fusion protein. Recent studies showed that the imatinib has cytotoxic and apoptotic effects on many BCR/ABL-negative cancers. Numerous compounds with cytotoxic potential exert their functions by interfering with the DNA topoisomerase. In this study, we examined the effects of imatinib on tumour cell-killing in relation to DNA topoisomerase enzyme inhibition. Methods: We determined the cytotoxicity by cell proliferation assay (XTT; tetrazolium hydroxide), using the human K562 CML cells, and loss of mitochondrial membrane potential by monitoring the changes in caspase-3 enzyme activity. Type I and II topoisomerase activities were measured by supercoiled plasmid relaxation and minicircle DNA decatenation assays respectively. Results and Discussion: Imatinib-induced apoptosis and inhibited cell proliferation in a dose-dependent manner. We also found that the imatinib was effective in both type I and type II topoisomerase reactions to a varying degree between 94% and 7% for the concentration range of 1 mm–0·02 mm in a dose-dependent manner. What is new and Conclusion: Our results suggest that the inhibition of topoisomerases may be a significant factor in imatinib-induced apoptosis in CML.