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In this study, the feasibility of the trigeneration system, which is one of the on-site energy production methods, was determined for Kocaeli University Umuttepe Campus, exergy and energy analyses were made for each point of the system and exergy destruction in the lines was found. The key point of the gains, losses, and efficiency analyses in the lines are presented with engineering solutions and thermodynamic proofs. The seasonal mathematical models covering the whole of the feasibility of the trigeneration system were carried out and the energy and equilibrium equations of the entire system were established. In addition, energy and exergy analysis, 2nd law efficiency, coefficient of performance (COP), and thermal efficiency were calculated for all the systems. The seasonal numerical analyses of the system have been prepared so that it can work effectively in two different working disciplines separately for summer and winter seasons. Thanks to these numerical analyses that are mentioned, the seasonal exergic destructions of the system are found, seasonal working methods are shown, and working conditions and operating load values suitable for the current season are determined. In addition, in the light of the technical studies mentioned above, both the hourly energy capacities and hourly consumption values that the university will produce after trigeneration have been compared by performing separate mathematical models for summer and winter modes. Thus, it has been aimed to reduce the energy production costs by selling the excess energy to the mains. It is for this reason that it is aimed to reduce the energy production costs of the country, to reduce foreign dependency to meet energy demand, to present both a ready to apply feasibility report to investors and a ready to use design of a medium-sized power plant that will set an example of trigeneration studies in academic terms. In today’s practical applications, it is known that the system efficiency of trigeneration systems can be between 70 and 80%. In the light of the studies, 66% exergic efficiency in winter, thermal efficiency of 0.87411 with 2.05 MW thermal capacity, 63% exergic efficiency in summer, COP of 0.82 with 1.5 MW cooling capacity, and 2.02 MWe instantaneous electrical power was found in summer and winter. It was decided that the system could be a facility that is technically open to development and worth establishing in the light of the exergic and energetic analyses results obtained in this study and the exergic system efficiency comparisons made in the literature. In this study, attention was drawn to the importance of exergy and energy analyses in deciding the installation of a trigeneration system, and it was shown that exergic and energetic analyses played a key role in the verification of decision mechanisms. In order to give an idea for other studies in the literature, it is aimed to draw attention to the need to perform seasonal exergy and energy analyses of the designed or desired trigeneration systems.

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was −10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test–Revised, −0.9±1.1 in the ketamine group vs. −9.7±1.2 in the ECT group; scores range from −300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. [ABSTRACT FROM AUTHOR]

Importance: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD., Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT., Design, Setting, and Participants: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians., Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks., Main Outcomes and Measures: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses., Results: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment., Conclusions and Relevance: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Purpose: This study aimed to describe patient experiences and attitudes about the role of the mental health professional as it relates to pursuing gender affirmation surgery., Methods: This was a mixed-models study with semi-structured interviews. Participants who presented for gender affirming vaginoplasty and had completed pre-surgical requirements but had not yet had the procedure were invited to participate in the study. Semi-structured phone interviews were conducted from November 2019 and December 2020 until saturation of themes was achieved at a sample size of 14. Interviews were then transcribed verbatim and coded by theme. Qualitative analysis was performed using a grounded theory approach., Results: Almost half of the patients did not identify any barriers to obtaining mental health care, but a majority brought up concerns for less advantaged peers, with less access to resources. Some patients also felt that there was benefit to be obtained from the mental health care required before going through with surgery, while others felt the requirements were discriminatory. Finally, a large proportion of our participants reported concerns with the role of mental health care and the requirements set forth by the World Professional Association for Transgender Health (WPATH), and patients gave suggestions for future improvements including decreasing barriers to care while rethinking how guidelines impact patients., Conclusion: There are many competing goals to balance when it comes to the guidelines for gender affirmation surgery, and patients had differing and complex relationships with mental health care and the pre-surgical process., (© 2023. The Author(s).)

Objectives: Retrospective analysis of cases diagnosed with brain death in our hospital in the last 15 years., Methods: The files and computer records of the cases diagnosed with brain death in the intensive care units of our hospital between January 2008 and January 2023 were evaluated retrospectively. The demographic data of the cases, the primary disease leading to brain death, the complementary tests used in the diagnosis of brain death, the day on which brain death was diagnosed in the intensive care unit, and the donor status were examined., Results: A total of 228 cases diagnosed as brain death were detected. Seven patients with missing data were excluded from the study. 61.99% of the cases were male, 38.01% were female, 14.02% were under 18 years old, 68.34% were between 18 and 65 years old, 17.64% were over 65 years old. Brain death was diagnosed in 69.69% of the patients admitted to the intensive care unit in the first 7 days, 22.17% in 7-14 days, and 8.14% after 14 days. The primary disease causing brain death was found to be 47% hemorrhagic cerebral injury, 21% traumatic hemorrhagic injury, 18% ischemic cerebral injury, and 14% hypoxic cerebral injury. No ancillary testing was used in 38% of the cases. Carotid doppler ultrasound was used in 36%, computed tomography angiography was used in 22%, and transcranialdoppler was used in 4%. Families agreed to be organ transplant donors in 28.95% of the cases. 71.05% family members refused to be organ transplant donors., Conclusion: The number of organ donations and the diagnosis of brain death has decreased rapidly with the covid-19 pandemic. In order to increase organ donation, we think that the necessary education should be given at an early age to increase organ donation awareness and social awareness., Competing Interests: None declared., (© Copyright 2023 by The Medical Bulletin of Sisli Etfal Hospital.)

Objectives: In our study, we aimed to determine the effect of vitamin C on short-term mortality and length of intensive care unit (ICU) stay in patients with coronavirus disease (COVID-19) followed up in the ICU., Methods: The patients who received and those who did not receive the high-dose intravenous vitamin C protocol were assigned to the treatment and control groups, respectively. The primary study findings in both groups were length of ICU stay and short-term mortality, while the secondary findings were vasopressor and invasive mechanical ventilation requirements and change in sequential organ failure assessment score from the 0 to the 96th hour., Results: Thirty-eight patients were included in the treatment group and 40 were included in the control group. The mortality rates were 44% and 60% in the treatment and control groups, respectively; however, the difference between the groups was not statistically significant (p>0.05). The median length of ICU stay in both groups was 10 days (p>0.05). No significant differences in the invasive mechanical ventilation and vasopressor requirements were found between the groups (p>0.05)., Conclusion: Consequently, the high-dose vitamin C therapy in the patients with acute respiratory failure due to COVID-19 pneumonia did not reduce the length of ICU stay, mortality, and invasive mechanical ventilation and vasopressor reqirements., Competing Interests: None declared., (©Copyright 2023 by The Medical Bulletin of Sisli Etfal Hospital.)

Objectives: The aim of this study was to compare intensive care unit (ICU) and overall hospital mortality in patients treated with favipiravir and lopinavir-ritonavir for COVID-19., Methods: Data were collected retrospectively between March 10 and May 10, 2020, from patients' records admitted to ICU due to COVID-19. Laboratory data, clinical characteristics, ICU and hospital mortality, ICU and hospital length of stay were compared in patients treated with favipiravir and lopinavir-ritonavir., Results: A total of 100 patients' data were investigated. Favipiravir was used as the treatment for 85% of patients, with the rest treated with lopinavir-ritonavir. Clinical and laboratory data of both antiviral treatment groups were similar. Length of hospital stay was 16 (9-24) days with favipiravir and 8.5 (5-12.5) days with lopinavir-ritonavir (p=0.002). Length of ICU stay for favipiravir and lopinavir-ritonavir groups were 8 (5-15) days and 4 (3-9) days, respectively (p=0.011). ICU mortality was 65.9% for the favipiravir and 80% for lopinavir-ritonavir (p=0.002). Hospital mortality for favipiravir and lopinavir-ritonavir was 67.1% and 80%, respectively (p=0.001)., Conclusion: The mortality in patients treated with favipiravir was less than patients treated with lopinavir-ritonavir. Favipiravir needs more attention and trials for its effect to be confirmed., Competing Interests: None declared., (© Copyright 2022 by The Medical Bulletin of Sisli Etfal Hospital.)

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Differentiation between Bipolar Disorder Depression (BDD) and Unipolar Major Depressive Disorder (MDD) is critical to clinical practice. This study investigated machine learning classification of BDD and MDD using graph properties of Diffusion-weighted Imaging (DWI)-based structural connectome., Methods: This study included a large number of medication-free (N =229) subjects: 60 BDD, 95 MDD, and 74 Healthy Control (HC) subjects. DWI probabilistic tractography was performed to create Fractional Anisotropy (FA) and Total Streamline (TS)-based structural connectivity matrices. Global and nodal graph properties were computed from these matrices and tested for group differences. Next, using identified graph properties, machine learning classification (MLC) between BDD, MDD, MDD with risk factors for developing BD (MDD+), and MDD without risk factors for developing BD (MDD-) was conducted., Results: Communicability Efficiency of the left superior frontal gyrus (SFG) was significantly higher in BDD vs. MDD. In particular, Communicability Efficiency using TS-based connectivity in the left SFG as well as FA-based connectivity in the right middle anterior cingulate area was higher in the BDD vs. MDD- group. There were no significant differences in graph properties between BDD and MDD+. Direct comparison between MDD+ and MDD- showed differences in Eigenvector Centrality (TS-based connectivity) of the left middle frontal sulcus. Acceptable Area Under Curve (AUC) for classification were seen between the BDD and MDD- groups, and between the MDD+ and MDD- groups, using the differing graph properties., Conclusion: Graph properties of DWI-based connectivity can discriminate between BDD and MDD subjects without risk factors for BD., (Copyright © 2022. Published by Elsevier B.V.)

Background: Major Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects., Methods: Resting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted., Results: LMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency., Limitation: Although participants were medication-free, they were not medication-naïve., Conclusion: Functional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD., (Copyright © 2022. Published by Elsevier B.V.)

Background: We evaluated the effect of early awake prone position administration on oxygenation and intubation requirements and short-term mortality in patients with acute respiratory failure due to coronavirus disease 2019 (COVID-19) pneumonia., Methods: This is an observational-cohort study. Patients receiving mask oxygen therapy in our intensive care units because of acute respiratory failure due to COVID-19 pneumonia were included. The Awake Prone Position (APP) group consisted of patients who were applied awake prone position, whereas non-APP group consisted of patients who were not applied awake prone position. PaCO 2 , PaO 2 , pH, SpO 2 values and PaO 2 /FiO 2 ratios were recorded at the beginning and 24th hour. Demographic data, comorbidities, intubation requirements, ventilator-free days, length of intensive care unit stay and short-term mortality of the patients were recorded., Results: The data of total 225 patients were examined, and 48 patients who met our study criteria were included. At the 24th hour, the median SpO 2 value of the APP group was 95%, the median PaO 2 value was 82 mmHg, whereas the SpO 2 value of the non-APP group was 90% and the PaO 2 value was 66 mmHg. (p = 0.001, p = 0.002). There was no statistically significant difference between the groups in length of intensive care unit stay and ventilator-free days, but short-term mortality and intubation requirements was lower in the APP group (p = 0.020, p = 0.001) CONCLUSION: Awake prone position application in patients receiving non-rebreather mask oxygen therapy for respiratory failure due to COVID-19 pneumonia improves oxygenation and decreases the intubation requirements and mortality., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

About 20-40% of estimated 121 million patients with major depressive disorder (MDD) are not adequately responsive to medication treatment. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive, non-convulsive neuromodulation/neurostimulation method, has gained popularity in treatment of MDD. Because of the high cost involved in rTMS therapy, ability to predict the therapy effectiveness is both clinically and cost wise significant. This study seeks an imaging biomarker to predict efficacy of rTMS treatment using a standard high frequency 10-Hz 4- to 6-week protocol in adult population. Given the significance of excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma aminobutyric acid (GABA) in the pathophysiology of MDD, and the involvement of the site of rTMS application, left dorsolateral prefrontal cortex (lDLPFC), in MDD, we explored lDLPFC Glx (Glu + glutamine) and GABA levels, measured by single voxel magnetic resonance spectroscopy (MRS) with total creatine (tCr; sum of creatine and phosphocreatine) as reference, as possible biomarkers of rTMS response prediction. Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data from 7 patients (40-74 y) were used in the study; 6 of these patients were scanned before and after 6 weeks of rTMS therapy. Findings from this study show inverse correlation between pretreatment lDLPFC Glx/tCr and (i) posttreatment depression score and (ii) change in depression score, suggesting higher Glx/tCr as a predictor of treatment efficacy. In addition association was observed between changes in depression scores and changes in Glx/tCr ratio. The preliminary findings did not show any such association between GABA/tCr and depression score., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bhattacharyya, Anand, Lin and Altinay.)

Tolerance education started at an early age in primary schools for a multicultural life. Video-based educational applications provide that child actively participate and learn. This study aims to explore perceptions of primary school children toward tolerance by technology-enhanced learning in Covid 19 period. Online semi-structured interview form was used and the data were analyzed with content analysis. Children developed the universal values such as equality, empathy, not harming themselves, being fair, helping others, happiness, smiling, hugging, respecting, giving gifts, loving people and all living beings without discrimination against disability by technological materials and online education. Future of education relies on tolerance education by incorporating universal values., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sakalli, Altinay, Altinay and Dagli.)

Background: Many subjects with major depression (MDD) exhibit subthreshold mania symptoms (MDD+). This study investigated, for the first time, using emotional inhibition tasks, whether the neural organization of MDD+ subjects is more similar to bipolar depression (BDD) or to MDD subjects without subthreshold bipolar symptoms (MDD-)., Method: This study included 118 medication-free young adults (15 - 30 yrs.): 20 BDD, 28 MDD+, 41 MDD- and 29 HC subjects. Participants underwent fMRI during emotional and non-emotional Go/No-go tasks during which they responded for Go stimuli and inhibited response for happy, fear, and non-emotional (gender) faces No-go stimuli. Univariate linear mixed-effects (LME) analysis for group effects and multivariate Gaussian Process Classifier (GPC) analyses were conducted., Results: MDD- group compared to both the BDD and MDD+ groups, exhibited significantly lower activation in parietal, temporal and frontal regions (cluster-wise corrected p <0.05) for emotional inhibition conditions vs. non-emotional condition. GPC classification of emotional (happy + fear) vs. non-emotional response-inhibition activation pattern showed good discrimination between BDD and MDD- subjects (AUC: 0.70; balanced accuracy: 70% (corrected p = 0.018)) as well as between MDD+ and MDD- subjects (AUC: 0.72; balanced accuracy: 67% (corrected p = 0.045)) but less efficient discrimination between BDD and MDD+ groups (AUC: 0.68; balanced accuracy: 61% (corrected p = 0.273)). Notably, classification of the MDD- group was weighted for left amygdala activation pattern., Limitations: Results also need to be tested in a different independent dataset., Conclusion: Using an fMRI emotional Go-Nogo task, MDD- subjects can be discriminated from BDD and MDD+ subjects., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: The effects of chronic renin-angiotensin-aldosterone system (RAAS) blockers usage on adverse outcomes and disease severity remain uncertain in COVID-19 patients with hypertension. In this study, we aimed to determine the relationship between chronic use of RAAS inhibitors and in-hospital adverse events among hypertensive patients hospitalized with COVID-19., Methods: In this retrospective single-center study, we enrolled 349 consecutive hypertensive patients diagnosed with COVID-19 infection. All patients were chronically on angiotensin-converting enzyme inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) or other antihypertensive therapies before hospital admission. Adverse clinical events were defined as in-hospital mortality, admission to intensive care unit, need for high-flow oxygen and intubation., Results: Patients were categorized into two groups according to the type of antihypertensive therapy. (ACEI/ARBs users, N=201; ACEI/ARB nonusers, N=148) There was no statistically significant difference between ACEI/ARBs users and ACEI/ARBs nonusers concerning adverse clinical events, such as in-hospital mortality (29 (14.4%) vs. 20 (13.5%), p=0.81), ICU admission (45(22.4%) vs. 27 (18.2%), p=0.34), need for high-flow oxygen (97 (48.3%) vs. 68 (45.9%), p=0.67) and need for intubation (32(15.9%) vs. 23(15.5%), p=0.92), respectively. Also, the severity of infection did not differ among groups. The logistic regression multivariate analysis showed that age, neutrophil-lymphocyte ratio, procalcitonin and ferritin levels were independent predictors of in-hospital mortality., Conclusion: Our results suggest that chronic use of ACEI/ARBs did not increase in-hospital adverse outcomes of hypertensive patients hospitalized with COVID-19. Although the recent data are contradictory, chronic ACEI/ARB therapy is not recommended to be discontinued in hypertensive patients during their hospitalization for COVID-19., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2020 by The Medical Bulletin of Sisli Etfal Hospital.)

Gender identity development is complex and involves several key processes. Transgender people experience incongruence between their biological and identified gender. This incongruence can cause significant impairment in overall functioning and lead to gender dysphoria (GD). The pathophysiology of GD is complex and is poorly understood. A PubMed search based on predetermined eligibility criteria was conducted to review neuropsychiatric articles focused on neurological, biological and neuroimaging aspects of gender development, transgender identity and GD. The information obtained from the literature was then used to formulize a GD model. Distinct gray matter volume and brain activation and connectivity differences were found in individuals with GD compared to controls, suggesting a neurobiological basis of GD; which leads to the concept of brain gender. Individuals with GD encounter a recurrent conflict between their brain gender and the societal feedback; which causes recurrent and ongoing cognitive dissonance, finally leading to GD and functional connectivity and activation changes in the transgender brain. GD has neurobiological basis, but it is closely associated with the individuals' interaction with the external world, their self-perception and the feedback received in return. We propose a novel model where the development of GD includes cognitive dissonance, involving anterior cingulate cortex and ventral striatum as the key brain structures. This model can be used to generate testable hypotheses using behavioral and neuroimaging techniques to understand the neuropsychobiology of GD.

Objectives: Brachial plexus block is the most effective analgesia and anesthesia procedure for the upper extremity surgeries in pediatric patients. In recent years, ultrasound guidance for this procedure has reduced the fail and complications like pneumothorax, intravascular injection and nerve damage. However, the number of studies about brachial plexus block is not enough, particularly in pediatric patients, which remained under-researched. In our study, we aimed to discuss the efficacy and safety of the ultrasound-guided brachial plexus block in pediatric patients by retrospectively examining their data., Methods: We retrospectively reviewed the data of pediatric patients who underwent ultrasound-guided brachial block in our clinic between January 2015-January 2017. Demographic data, diagnosis, procedure and operation times, medications, motor and sensorial block times were recorded., Results: Between January 2015 and January 2017, the number of pediatric patients who underwent ultrasound-guided peripheral nerve block in our clinic was 24. In 15 of these patients, the supraclavicular block was applied in 15, and the infraclavicular block was applied in nine patients. The mean age of the patients was 9.6±3.12, with a male/female ratio 14/10. The mean duration of the procedure was 9.54±2.14 minutes in patients for the supraclavicular block and 12.9 ± 2.8 minutes for the infraclavicular block. The mean surgery time was 64±13.6 minutes. As a local anesthetic, bupivacaine was used in three patients; bupivacaine+lidocaine combination was used in 21 patients and adjuvants were added in eight patients. The block procedure was performed under general anesthesia in 12 patients and under sedation in 12 patients. The mean motor block time was 7.5±2 hours in patients who received supraclavicular block, and 7.4±1.5 hours in patients who received infraclavicular block. The mean sensorial block time was 10.5±1.7 hours in the supraclavicular block, and 10.45±1.15 hours in the infraclavicular block. The mean motor block period with added adjuvants was 7.7±0.5 hours, and the sensorial block period was 11.12±1.1 hours. No complications were seen during the procedure, intraoperative and postoperative follow-up., Conclusion: Ultrasound-guided brachial plexus block in pediatric patients is effective and safe, with longer analgesia duration and lower complication rates. Prospective studies with a larger number of patients are needed in this regard., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2020 by The Medical Bulletin of Sisli Etfal Hospital.)

Background: There are many putative mechanisms by which ketamine has its effect and many unanswered questions about risks and benefits of long-term ketamine therapy. A research imperative is the identification of predictors of response to intravenous ketamine, especially a sustained response to maintenance ketamine. Temperament is an inherited aspect of personality and is a predictive factor for outcome in treatment resistant depressed (TRD) patients., Methods: We analyzed which domains of personality impacted initial and sustained ketamine response. Utilizing the Neuroticism Extraversion Openness Five Factor Inventory (NEO-FFI) on 125 participants with TRD, we tested (1) whether the degree of neuroticism predicted initial and/or sustained response to ketamine; and (2) whether extraversion, agreeableness, openness to experience, and conscientiousness had an impact on response., Results: Our findings confirmed previous literature that elevated neuroticism, low conscientiousness, and low extraversion was the pattern of our TRD population regardless of response. Openness was the only factor to significantly predict sustained treatment outcome., Limitations: Our findings are limited by the lack of placebo control, small sample size, non- standardized infusion intervals, polypharmacy rather than ketamine monotherapy, a select TRD population in that they had all failed ECT, and a primarily Caucasian population., Conclusions: Our registry adds to the literature that factors making up temperament may have predictive value in regard to treatment response, specifically the outcome for TRD patients receiving long-term ketamine infusion therapy. If confirmed, assessing for Openness could reduce inappropriate exposure to ketamine with its attendant unknown long-term risks., (Copyright © 2019. Published by Elsevier B.V.)

We performed a cross-sectional analysis of the prevalence of psychiatric diagnoses among transgender patients in clinical care using an all-payer electronic health record database. Of 10,270 transgender patients identified, 58% ( n =5940) had at least one psychiatric diagnosis compared with 13.6% ( n =7,311,780) in the control patient population ( p <0.0005). Transgender patients had a statistically significant increase in prevalence for all psychiatric diagnoses queried, with major depressive disorder and generalized anxiety disorder being the most common diagnoses (31% and 12%, respectively). Utilizing an all-payer database, although not without limitations, enables assessment of mental health and substance use diagnoses in this otherwise small population., Competing Interests: No competing financial interests exist., (© Jonathon W. Wanta et al. 2019; Published by Mary Ann Liebert, Inc.)

Unique ethical issues arise in the provision of gender-affirming care to transgender and gender diverse people. One of the distinctive trends in transgender health care has been the development of interdisciplinary specialty teams with expertise in gender-affirming care. Clinical ethicists can play an important role on these teams in helping gender variant patients and gender-affirming providers navigate complex ethical issues, creating opportunities for enhancing patient experience, and easing provider moral uncertainty. Many opportunities exist for clinical ethicists to lend their skills to this area of clinical care. It is important for interdisciplinary transgender health care teams and other health care professionals providing transgender-specific care to understand the ethical issues involved in such care, the ways in which ethics expertise can be a resource, and the benefits and drawbacks of integrating a clinical ethicist into their team., Competing Interests: Cecile A. Ferrando, MD, MPH receives royalties for the publication C. Ferrando (Unger) and T.N. Thomas, “Transgender surgery: Male to female,” UptoDate (June 4, 2018), https://www.uptodate.com/contents/transgender-surgery-male-to-female. Aspects of this article were presented by Hilary Mabel, JD on behalf of the authors at the American Society for Bioethics & Humanities conference in Kansas City, MO on October 19, 2017.

Purpose: There is an immediate need for more sustainable, effective therapies for treatment-resistant depression in patients who do not respond to traditional psychopharmacology. The aim of this study was to determine the efficacy and safety of intravenous ketamine infusions on the elderly population by using a case series of 6 geriatric patients with treatment-resistant depression., Methods: Eligible patients aged 65 to 82 were given a subanesthetic ketamine hydrochloride dose of 0.5 mg/kg delivered intravenously over 40 minutes twice weekly for an acute series. If patients reported a 50% decrease in depression symptoms after the acute series of 2 to 4 infusions, they would be moved to a maintenance series of infusions, which would occur every 2 to 6 weeks on an individual basis., Results: Of the 6 patients given ketamine, 1 failed to respond to the acute treatment phase, 4 responded to the acute infusion phase but failed to sustain a response after a range of 8 to 22 maintenance infusions, and 1 responded to the infusions but relapsed into alcohol use; therefore, treatment was discontinued., Conclusions: The relative safety of intravenous ketamine in the elderly was demonstrated by the mild, transient adverse effects seen by this patient group. The geriatric population is unable to maintain an antidepressant response to intravenous ketamine over time, signifying that ketamine has low efficacy for the elderly.

Background: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC)., Methods: One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition., Results: Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p < 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(p = 0.04)., Conclusion: Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD., Trial Registration: NCT01811147., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction and Background: Patients with depression who fail to respond to at least two antidepressants in their current episode are considered to have Treatment Resistant Depression (TRD). ECT is an effective treatment of TRD but cognitive side effects limit its use. Ketamine elicits a rapid antidepressant response in sub-anesthetic repeated doses. ECT and ketamine may be modulating the glutamate system, therefore when administered in an interleaved fashion, they could have a synergistic effect., Methods: 15 TRD patients were recruited and 12 were included in the analysis. Patients were randomly assigned to an ECT + iv. ketamine or ECT + iv. placebo (midazolam). At baseline and before each infusion, depression severity scales were administered. At baseline, halfway through and at the end of the study, cognitive tests were administered., Results: There was no difference between the ketamine and placebo arms, per change in 17-item Hamilton Depression Scores (HAM-D), Young Mania Rating Scores or cognitive tests. Per HAMD scores, 3 ECT +ketamine subjects (42%) showed early remission (HAMD < 8) and maintained euthymia for 3 additional visits. None of the ECT +midazolam subjects (0%) achieved early remission. This difference showed a trend level significance (Chi square P-Value = 0.0910)., Conclusion: The results of the study were limited due to the small sample size. However, a trend level difference in rates of early remission was seen, suggesting that ketamine + ECT may lead to a faster symptom relief. A larger sample size is needed for statistical confirmation.

Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5 weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies., (Copyright © 2018. Published by Elsevier Inc.)

Background: This study, for the first time, investigated lithium monotherapy associated effects on amygdala- ventromedial prefrontal cortex (vMPFC) resting-state functional connectivity and correlation with clinical improvement in bipolar disorder (BP) METHODS: Thirty-six medication-free subjects - 24 BP (12 hypomanic BPM) and 12 depressed (BPD)) and 12 closely matched healthy controls (HC), were included. BP subjects were treated with lithium and scanned at baseline, after 2 weeks and 8 weeks. HC were scanned at same time points but were not treated. The effect of lithium was studied for the BP group as a whole using two way (group, time) ANOVA while regressing out effects of state. Next, correlation between changes in amygdala-vMPFC resting-state connectivity and clinical global impression (CGI) of severity and improvement scale scores for overall BP illness was calculated. An exploratory analysis was also conducted for the BPD and BPM subgroups separately., Results: Group by time interaction revealed that lithium monotherapy in patients was associated with increase in amygdala-medial OFC connectivity after 8 weeks of treatment (p = 0.05 (cluster-wise corrected)) compared to repeat testing in healthy controls. Increased amygdala-vMPFC connectivity correlated with clinical improvement at week 2 and week 8 as measured with the CGI-I scale., Limitations: The results pertain to open-label treatment and do not account for non-treatment related improvement effects. Only functional connectivity was measured which does not give information regarding one regions effect on the other., Conclusions: Lithium monotherapy in BP is associated with modulation of amygdala-vMPFC connectivity which correlates with state-independent global clinical improvement., (Copyright © 2017. Published by Elsevier B.V.)

Background: This study investigated extended release quetiapine (quetiapine XR) associated changes in functional MRI (fMRI) measures of task-induced amygdalar activation and resting state connectivity in anxious unipolar major depressive disorder (AMDD)., Methods: Anxious unipolar major depressive disorder patients (n = 15) (17-item Hamilton Depression Rating Scale (HAM-D) >18 and Hamilton Anxiety Scale (HAM-A) >18) and closely matched healthy control (HC) subjects were compared at baseline for task induced amygdala activation and resting state connectivity on fMRI. Subsequently, AMDD patients were treated for 8 weeks with open-label quetiapine XR. Weekly HAM-D and HAM-A ratings were obtained, and the fMRI scan was repeated at weeks 2 and 8. Changes in fMRI measures were calculated using repeated-measures analysis of variance and correlation with decrease in HAM-D and HAM-A scores was examined., Results: At baseline, AMDD compared with HC exhibited increased task-induced left amygdalar activation (P = 0.05 clusterwise corrected) and decreased resting state amygdala-cortical and amygdala-pons connectivity (P < 0.05 clusterwise corrected). Quetiapine XR treatment was associated with significant decrease in HAM-D (df = 1,28; female [F] = 39; P = 0.001) and HAM-A scores (df = 1,28; F = 55; P = 0.001). The AMDD group showed increased amygdala-cortical connectivity (P < 0.05 [clusterwise corrected]) at week 2, which was maintained at week 8. At week 8, additional areas showed increased connectivity including insula and putamen. At 8 weeks, decrease in HAM-D scores correlated with increase in amygdala-mid cingulate and amygdala-cuneus connectivity (P = 0.05 [clusterwise corrected]). Decrease in HAM-A scores correlated with increase in amygdala-cuneus and parietal cortex connectivity (P = 0.05 [clusterwise corrected])., Limitations: Small sample-size, open-label single-arm design, HC only tested at baseline, focused only on amygdala., Conclusions: Quetiapine XR effects in the treatment of AMDD are associated with modulation of amygdala connectivity.

Research on resting functional brain networks in bipolar disorder (BP) has been unable to differentiate between disturbances related to mania or depression, which is necessary to understand the mechanisms leading to each state. Past research has also been unable to elucidate the impact of BP-related network disturbances on the organizational properties of the brain (eg, communication efficiency). Thus, the present work sought to isolate network disturbances related to BP, fractionate these into components associated with manic and depressive symptoms, and characterize the impact of disturbances on network function. Graph theory was used to analyze resting functional magnetic resonance imaging data from 60 medication-free patients meeting the criteria for BP and either a current hypomanic (n=30) or depressed (n=30) episode and 30 closely age/sex-matched healthy controls. Correction for multiple comparisons was carried out. Compared with controls, BP patients evidenced hyperconnectivity in a network involving right amygdala. Fractionation revealed that (hypo)manic symptoms were associated with hyperconnectivity in an overlapping network and disruptions in the brain's 'small-world' network organization. Depressive symptoms predicted hyperconnectivity in a network involving orbitofrontal cortex along with a less resilient global network organization. Findings provide deeper insight into the differential pathophysiological processes associated with hypomania and depression, along with the particular impact these differential processes have on network function.

Background: Neurostimulation as a treatment option for refractory neuropsychiatric disorders has been increasingly utilized in recent years. For patients with such refractory disorders who have often failed to respond to various medical interventions, deep brain stimulation (DBS) has emerged as a promising treatment modality. DBS is a reversible and adjustable form of brain stimulation (also known as functional neurosurgery) in which desired brain structures (or circuits) are given focal electric stimulation via electrodes that are implanted in the brain tissue during a surgical procedure. It has been utilized among various psychiatric and neurological illnesses, in particular headache disorders. This article reviews the most relevant data regarding DBS for psychiatric and primary headache disorders., Methods: Authors conducted a detailed literature search of Medline/PubMed database and studies that used DBS for the treatment of refractory neuropsychiatric disorders were reviewed. Response, remission, and safety measures of these studies were obtained., Results: Despite the advancement in DBS treatment, the number of randomized controlled studies remains very limited due to ethical and methodological difficulties of setting up invasive procedures of this magnitude. So at present, DBS represents a modality used only in the most refractory patients., Conclusion: Current data support DBS as a promising treatment option for neuropsychiatric disorders that do not respond to conventional treatments; however, it is clear that more research and patient volume is needed to demonstrate its efficacy in treating these conditions. The use of functional imaging to understand the pathophysiology of these disorders has been crucial for the utilization of DBS., (© 2015 American Headache Society.)

Major depressive disorder is a serious medical illness which is responsible for considerable morbidity and disability. Despite decades of research, the neural basis for depression is still incompletely understood. In this review, evidence from neuroimaging, neuropsychiatric and brain stimulations studies are explored to answer the question regarding the localization of depression in the brain. Neuroimaging studies indicate that although many regions of the brain have been repeatedly implicated in the pathophysiology of depression, not many consistent findings have been found until present. In recent times, the focus of neuroimaging has shifted from regional brain abnormalities to circuit level connectivity abnormalities. However, connectivity models are inherently more complicated, and the validity of these models remains to be tested. Neuropsychiatric studies of illnesses such as Parkinson's disease and stroke provide promising clues regarding areas involved in depression, but again consistent findings are rare. Similarly, stimulation of a variety of brain regions and circuits has been reported as being effective in depression. Therefore, the current knowledge indicates that the pathophysiology of depression may be distributed across many brain regions and circuits. In future studies, this distributed nature of depression needs to be further investigated, primary and secondary areas affected need to be identified, and new paradigms to explain complex mental functions need to be explored.

Automatic segmentation using multi-atlas label fusion has been widely applied in medical image analysis. To simplify the label fusion problem, most methods implicitly make a strong assumption that the segmentation errors produced by different atlases are uncorrelated. We show that violating this assumption significantly reduces the efficiency of multi-atlas segmentation. To address this problem, we propose a regression-based approach for label fusion. Our experiments on segmenting the hippocampus in magnetic resonance images (MRI) show significant improvement over previous label fusion techniques.

We propose a simple but generally applicable approach to improving the accuracy of automatic image segmentation algorithms relative to manual segmentations. The approach is based on the hypothesis that a large fraction of the errors produced by automatic segmentation are systematic, i.e., occur consistently from subject to subject, and serves as a wrapper method around a given host segmentation method. The wrapper method attempts to learn the intensity, spatial and contextual patterns associated with systematic segmentation errors produced by the host method on training data for which manual segmentations are available. The method then attempts to correct such errors in segmentations produced by the host method on new images. One practical use of the proposed wrapper method is to adapt existing segmentation tools, without explicit modification, to imaging data and segmentation protocols that are different from those on which the tools were trained and tuned. An open-source implementation of the proposed wrapper method is provided, and can be applied to a wide range of image segmentation problems. The wrapper method is evaluated with four host brain MRI segmentation methods: hippocampus segmentation using FreeSurfer (Fischl et al., 2002); hippocampus segmentation using multi-atlas label fusion (Artaechevarria et al., 2009); brain extraction using BET (Smith, 2002); and brain tissue segmentation using FAST (Zhang et al., 2001). The wrapper method generates 72%, 14%, 29% and 21% fewer erroneously segmented voxels than the respective host segmentation methods. In the hippocampus segmentation experiment with multi-atlas label fusion as the host method, the average Dice overlap between reference segmentations and segmentations produced by the wrapper method is 0.908 for normal controls and 0.893 for patients with mild cognitive impairment. Average Dice overlaps of 0.964, 0.905 and 0.951 are obtained for brain extraction, white matter segmentation and gray matter segmentation, respectively., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Multi-atlas based segmentation has been applied widely in medical image analysis. For label fusion, previous studies show that image similarity-based local weighting techniques produce the most accurate results. However, these methods ignore the correlations between results produced by different atlases. Furthermore, they rely on pre-selected weighting models and ad hoc methods to choose model parameters. We propose a novel label fusion method to address these limitations. Our formulation directly aims at reducing the expectation of the combined error and can be efficiently solved in a closed form. In our hippocampus segmentation experiment, our method significantly outperforms similarity-based local weighting. Using 20 atlases, we produce results with 0.898 +/- 0.019 Dice overlap to manual labelings for controls.

Measurement of brain change due to neurodegenerative disease and treatment is one of the fundamental tasks of neuroimaging. Deformation-based morphometry (DBM) has been long recognized as an effective and sensitive tool for estimating the change in the volume of brain regions over time. This paper demonstrates that a straightforward application of DBM to estimate the change in the volume of the hippocampus can result in substantial bias, i.e., an overestimation of the rate of change in hippocampal volume. In ADNI data, this bias is manifested as a non-zero intercept of the regression line fitted to the 6 and 12 month rates of hippocampal atrophy. The bias is further confirmed by applying DBM to repeat scans of subjects acquired on the same day. This bias appears to be the result of asymmetry in the interpolation of baseline and followup images during longitudinal image registration. Correcting this asymmetry leads to bias-free atrophy estimation., (Copyright 2009 Elsevier Inc. All rights reserved.)

We propose a simple strategy to improve automatic medical image segmentation. The key idea is that without deep understanding of a segmentation method, we can still improve its performance by directly calibrating its results with respect to manual segmentation. We formulate the calibration process as a bias correction problem, which is addressed by machine learning using training data. We apply this methodology on three segmentation problems/methods and show significant improvements for all of them.