Real-World Efficacy and Safety of First-Line Nivolumab Plus Chemotherapy in Patients with Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Nationwide Observational Turkish Oncology Group (TOG) Study.

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes.

Comparison of anthracycline-containing and anthracycline-free regimens in neoadjuvant HER-2 positive breast cancer treatment.

While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics.

Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: a retrospective multi-center study by the Turkish Oncology Group (TOG).

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.

Turkish Hematologists' Preferences for Related Donor Selection: Results of a Multicenter Survey

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely utilized treatment for various hematological diseases. While selection criteria for unrelated donors are well established, there is a lack of consistency and standardization in the selection of related donors. This study investigated the current approach of hematologists to the selection of related donors at Turkish HSCT centers. The study employed a cross-sectional survey design, distributing a self-administered questionnaire to 95 adult and pediatric transplantation centers in Türkiye to investigate their approaches to related donor selection for allo-HSCT. The questionnaire collected data on various topics including the center's experience in performing allo-HSCT, patient groups treated, number of allo-HSCT procedures conducted between 2015 and 2021, preferences for related donors, considerations in related donor selection (such as sex and past pregnancies), guidelines utilized for related donor selection, upper age limit for related donors, and the use of specialized advanced analyses for elderly donors. The response rate to the survey was 38.9%. Variability was observed across centers in terms of sex consideration and the impact of past pregnancies on related female donor rejection. Different guidelines were employed for related donor selection, with the European Bone Marrow Transplantation guidelines being the most commonly used. Regarding the upper age limit for related donors, 8.1% of centers accepted an upper age limit of 55 years, 48.7% preferred an upper age limit of 65 years, and 43.2% selected related donors aged 65 and above. The lack of standardized guidelines for related donor selection in HSCT centers leads to variability in criteria and potential risks. Collaboration among centers is essential to establish consensus and develop standardized protocols.

A model proposal development study for adults with intellectual disabilities in Turkey compared to USA.

Intellectual disability (ID) persists from birth through adulthood and aging. Thus, the support provided to individuals with intellectual disabilities (IwID) in adulthood is essential to increase their self-determination and quality of life. This research aimed to determine how IwID may receive support for education, working life, accommodation, and leisure in adulthood in the Turkish context by increasing their and their families' quality of life without socially discriminating against them. Qualitative data were collected in two stages, combining semi-structured interviews and the Delphi study technique. Results prompted the recommendation that a legal basis for transition-to-adulthood planning be established in Turkey for a functional adult service model. Next, a model with specific standards by which multidisciplinary experts analyse education, work, leisure, and housing alternatives for preadulthood and adulthood should be developed and coordinated by the Turkish Ministry of National Education and the Ministry of Family. Implications for the future are further discussed.

Extraction of Lightweight Platanus orientalis L. Fruit's Stem Fiber and Determination of Its Mechanical and Physico-Chemical Properties and Potential of Its Use in Composites.

Natural fibers extracted from plants are preferred as an alternative to synthetic products. The main reasons for this preference are their affordable cost, light weight and good mechanical properties. However, finding new natural raw materials is challenging due to growth limitations in different geographical areas. Platanus orientalis L. (Eastern plane tree) is a tree with abundant fruits that can grow in many regions of the world. The aim of this study was to determine the mechanical (tensile strength, tensile modulus, elongation), physical (density, fiber diameter) and chemical (cellulose, hemicellulose and lignin) properties of Platanus orientalis L. fruit's stem by fiber extraction from the stems of the tree. It was determined that the extracted fiber had good mechanical properties and cellulose content of 42.03%. As a result of thermogravimetric analysis, it was determined that the plane tree fruit's stem fiber had thermal resistance of up to 299 °C. The tensile strength value was 157.76 MPa, the tensile modulus value was 1.39 GPa and the elongation value was 22.01%. It was determined that it is suitable for use in fiber reinforcement in thermoplastic-based composites at temperatures below 299 °C. According to the results obtained by the mechanical, chemical and physical analysis of Platanus orientalis L. fruit's stem fiber (PoLfs), it could be recommended as a suitable alternative as a reinforcing fiber in thermoplastic and thermoset composites.

Comparison of the Efficacy and Safety Profiles of Different P2Y12 Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction in the COVID-19 Era.

BACKGROUND/AIM: Coronavirus Disease 2019 (COVID-19) is characterized by an increased risk of thrombotic and hemorrhagic events resulting from endothelial dysfunction. In patients with ST-elevation myocardial infarction (STEMI), the dual antiplatelet therapy used to reduce mortality may increase the risk of bleeding. The study aimed to compare the efficacy and safety profiles of P2Y12 inhibitors used during the COVID-19 era. MATERIALS AND METHODS: Three hundred and ninety patients who underwent primary percutaneous intervention for STEMI between January 1, 2020, and December 31, 2021, were included in this study, retrospectively. The patients were divided into groups according to their COVID-19 history and all-cause mortality, cardiac mortality, stent thrombosis, and bleeding complications during hospitalization and at one-year follow-up were compared. RESULTS: The mean age of the patients was 64.3 years and the mean follow-up period was 10.2 months; 80% of the patients were male and 44.6% had a history of COVID-19 infection. The in-hospital mortality rate was 11.3%. Cardiac mortality was significantly higher in the clopidogrel group compared to the other groups, regardless of COVID-19 history (21.9% in the clopidogrel group, 1.6% in the prasugrel group, and 6.7% in the ticagrelor group (p<0.001)). There was no significant difference between the groups in terms of bleeding complications and relation to COVID-19. CONCLUSION: In STEMI patients treated with different P2Y12 inhibitors, there was no significant difference in mortality, bleeding, stroke, and thrombotic complications, regardless of the presence or absence of COVID-19 infection.

'I did not even receive even a phone call from any institution!': experiences and recommendations related to disability during COVID-19.

Background: Individuals with disabilities and their families, among the disadvantaged groups in society, have encountered increased hardships accessing support and services in various social contexts, such as education, health, transportation, rehabilitation, and social services. Thus, it is essential to examine parents' experiences as a background catalyzer to improve the currently available services and provide psychological and social support. This study examined the experiences of families of children with disabilities who were in Turkey during the pandemic's early stages, and yielded suggestions based on these experiences. Method: A phenomenological design was used in this study, and semi-structured interviews were conducted with 10 parents of children with disabilities. Findings: Three themes emerged from data analysis: (a) quarantine, (b) education, and (c) children with disabilities. Conclusions: The findings revealed the importance of taking necessary precautions for individuals with disabilities and their families to access social services. Additionally, findings underline the essentiality of providing psychological support to families while providing and extending family education.

Structure of a 10-23 Deoxyribozyme Exhibiting a Homodimer Conformation.

Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.

Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation.

Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA-cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.

"I think they do not know how to lie:" The perceptions of legal support staff about person with intellectual disabilities/autism in Turkish legal system.

BACKGROUND: Increased social integration of individuals with intellectual disabilities or autism could may raise their likelihood of interacting with justice system and legal staff. AIMS: The present article aimed to determine the perceptions of the legal support staff about the individuals with intellectual disabilities or autism. MATERIALS AND METHODS: In the study, conducted with the phenomenological method, the views of 15 legal support staff were obtained. The study reported what participants perceived and examined whether participants had an accurate understanding of the experiences/support needs of people with intellectual disabilities/autism. The data were analysed with content analysis. RESULTS: Three themes were determined: (1) Experience of interview with an individual with intellectual disabilities/autism, (2) attitudes of judges, lawyers and other staff, and (3) abuse/trauma. DISCUSSION: Findings are consistent with literature. Individuals with intellectual disabilities/autism have problems in expressing themselves, also staff do not know them, do not know their features. Studies show that staff often do not know what to do in these interviews. CONCLUSION: Based on the participant perspectives, it was determined that individuals with intellectual disabilities/autism experienced self-expression problems, interviewees did not understand children/individuals with intellectual disabilities or autism and could exhibit negative attitudes, the children could be abused and traumatised during judicial processes, they were more prone to abuse when compared to their peers, they could be involved in certain events more frequently and could be pushed to crime.

Myeloproliferative Neoplasms and Aspirin: Does Increased Platelet Turnover Matter?

Objective: Platelet aggregation tests and the analysis of thromboxane A2 metabolites [serum thromboxane B2 (TXB2) and urine 11-dehydro TXB2] are used to evaluate the efficacy of aspirin. In myeloproliferative neoplasms (MPNs), the immature platelet fraction (IPF) rises due to enhanced platelet turnover, and this has been thought to reduce the efficacy of aspirin. This phenomenon is overcome by the recommendation of aspirin intake in divided doses. We aimed to evaluate aspirin efficacy in patients who were receiving aspirin treatment of 100 mg/day. Materials and Methods: Thirty-eight MPN patients and 30 control patients (non-MPN patients who received a single daily dose of aspirin at 100 mg for nonhematological conditions) were enrolled. IPF, serum TXB2, and urine 11-dehydro TXB2 levels were measured and aggregation tests with arachidonic acid and adenosine diphosphate were performed by light transmission aggregometry (LTA). Results: Mean IPF and TXB2 levels were higher in the MPN group (p=0.008 and p=0.003, respectively). IPF levels were lower in patients on cytoreductive therapy in the MPN group (p=0.001), but these values were similar between patients on hydroxyurea and the non-MPN group (p=0.72). TXB2 levels did not differ according to hydroxyurea treatment status but were higher in the MPN group compared to non-MPN patients (23.63 ng/mL and 19.78 ng/mL, respectively; p=0.04). TXB2 values were higher in patients with essential thrombocythemia and a history of thrombotic events (p=0.031). No difference was observed in LTA between the MPN and non-MPN patient groups (p=0.513). Conclusion: Higher levels of IPF and TXB2 in the MPN patient group indicated platelets that could not be inhibited by aspirin. It was observed that patients under cytoreductive therapy had lower IPF values, but the expected decrease in TXB2 levels was not observed. These findings suggest that a lack of response to aspirin may be due to additional intrinsic factors rather than increased platelet turnover.

The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment.

OBJECTIVE: Alzheimer's disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide. Novel therapeutic agents therefore need to be discovered in addition to traditional medications. Nimodipine appears to possess the potential to reverse cognitive impairment-induced dysfunction in learning and memory through its regulatory effect on the brain-derived neurotrophic factor (BDNF), acetylcholine (Ach), and acetylcholinesterase (AChE) pathway in the hippocampus and prefrontal cortex. METHODS: Twenty-four male Sprague Dawley rats weighing 380 ± 10 g were used for behavioral and biochemical analyses. These were randomly and equally assigned into one of three groups. Group 1 received saline solution alone via the intraperitoneal (i.p) route, and Group 2 received 1 mg/kg/day i.p. scopolamine once a day for three weeks for induction of learning and memory impairments. In Group 3, 10 mg/kg/day nimodipine was prepared in tap water and administered orally every day for three weeks, followed after 30 min by 1 mg/kg/day scopolamine i.p. Behavior was evaluated using the Morris Water Maze test. BDNF, ACh, and AChE levels were determined using the ELISA test in line with the manufacturer's instructions. RESULTS: Nimodipine treatment significantly increased the time spent in the target quadrant and the number of entries into the target quadrant compared to the scopolamine group alone. Additionally, BDNF and ACh levels in the hippocampus and prefrontal cortex decreased following 20-day scopolamine administration, while AChE activation increased. CONCLUSION: Nimodipine exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration in the hippocampus and prefrontal cortex.

Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group.

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.

Management of Spinal Lymphomas: Spinal Instability Assessment Using the Spinal Instability Neoplastic Score and a Proposed Treatment Algorithm.

AIM: To propose a treatment algorithm, and to assess spinal instability in patients diagnosed with spinal lymphoma. MATERIAL AND METHODS: Demographics, symptoms, tumor level and location, and presence of spinal instability were reviewed in 22 patients with spinal lymphomas. Each patient's neurological state was reviewed using the American Spinal Injury Association and modified McCormick scale scores, and spinal instability was assessed using the Spinal Instability Neoplastic Score (SINS). RESULTS: Initially, percutaneous biopsy was performed in 16 patients, and open biopsy was performed in 6 patients. Eight of the patients who underwent percutaneous biopsy were followed up with hematological examination alone, as they had no additional complaints. The SINS was used to evaluate the presence of spinal instability, and the type of surgery to be performed was decided accordingly. In the second surgery, decompression and stabilization were performed in 5 of the remaining 8 patients, and only decompression was performed in 3 of them. Neurological improvement was observed in 6 of 7 patients with acute neurological deficit. CONCLUSION: Percutaneous biopsy for tissue diagnosis is the first step in the management of spinal lymphomas. Patients without neurological deficit should be referred for hematological examination. Those with acute neurological deficit require emergency surgery, and those with chronic symptoms must undergo operation for decompression and/or stabilization. This study confirmed the safety of the SINS in the evaluation of spinal instability in spinal lymphoma cases.

Ecofriendly Usability of Mushroom Cultivation Substrate as a Ruminant Feed: Anaerobic Digestion Using Gas Production Techniques.

The current study was carried out to evaluate the nutritive value of mushroom-uncultivated and -cultivated substrates, and their in vitro gas and methane production. The experiment was conducted in a completely randomized design, and analyzed with GLM using SAS 9.4. Analysis of the structural morphology of mushroom-cultivated substrate was performed using a scanning electron microscope. Mushroom cultivation led to lower ether extract, acid detergent fiber, and crude fiber level of substrate (p < 0.05). Mushroom-cultivated substrate showed higher in vitro cumulative gas production (p < 0.05). Moreover, mushroom cultivation led to a higher sample surface, and improved the microorganisms' access to feed materials, thus stimulating rumen fermentation and increasing methane production (p < 0.05). The organic matter digestibility, metabolizable energy, and net energy lactation values were higher for mushroom-cultivated substrate than uncultivated substrate. The results demonstrate that mushroom-cultivation not only increases the contact surface of cellulose, leading to higher ruminal microorganisms' access to feedstuff, but could also had higher nutritive value; this material might be used in ruminant ration formulation, to reduce environmental pollution and feed costs.

The Two Non-Visual Arrestins Engage ERK2 Differently.

Arrestin binding to active phosphorylated G protein-coupled receptors terminates G protein coupling and initiates another wave of signaling. Among the effectors that bind directly to receptor-associated arrestins are extracellular signal-regulated kinases 1/2 (ERK1/2), which promote cellular proliferation and survival. Arrestins may also engage ERK1/2 in isolation in a pre- or post-signaling complex that is likely in equilibrium with the full signal initiation complex. Molecular details of these binary complexes remain unknown. Here, we investigate the molecular mechanisms whereby arrestin-2 and arrestin-3 (a.k.a. ß-arrestin1 and ß-arrestin2, respectively) engage ERK1/2 in pairwise interactions. We find that purified arrestin-3 binds ERK2 more avidly than arrestin-2. A combination of biophysical techniques and peptide array analysis demonstrates that the molecular basis in this difference of binding strength is that the two non-visual arrestins bind ERK2 via different parts of the molecule. We propose a structural model of the ERK2-arrestin-3 complex in solution using size-exclusion chromatography coupled to small angle X-ray scattering (SEC-SAXS). This binary complex exhibits conformational heterogeneity. We speculate that this drives the equilibrium either toward the full signaling complex with receptor-bound arrestin at the membrane or toward full dissociation in the cytoplasm. As ERK1/2 regulates cell migration, proliferation, and survival, understanding complexes that relate to its activation could be exploited to control cell fate.

Ozone gas applied through nebulization as adjuvant treatment for lung respiratory diseases due to COVID-19 infections: a prospective randomized trial.

The objective of this study was to provide lung disinfection by nebulizing ozone gas with distilled water and olive oil for patients who have clinical symptoms due to coronavirus disease 2019 (COVID-19). The study attempted to reduce the viral load of COVID-19 in the lungs of patients, to provide a faster response to medical treatment. Between August 2020 and September 2020, 30 patients who met the study criteria were prospectively evaluated. There were 2 groups with 15 patients in each group: patients in control group were not treated with ozone and only received standard COVID-19 treatment; patients in ozone group received lung disinfection technique with ozone and standard COVID-19 treatment. A statistically significant difference was found in the length of stay in hospital, change in C-reactive protein, polymerase chain reaction results after 5 days, and computed tomography scores between two groups. There was no statistically significant difference in D-dimer, urea, lactate dehydrogenase, lymphocyte, leukocyte, and platelet between two groups. According to the data, we think that the lung disinfection technique applied with ozone inhalation reduces the rate of pneumonia in COVID-19 patients and makes the patients respond faster to the treatment and become negative according to the polymerase chain reaction tests. The study was approved by the Ethical Committee of the Istanbul Medipol University Clinical Trials (approval No. 0011) on July 2, 2020.

Specificities of Gßγ subunits for the SNARE complex before and after stimulation of α2a-adrenergic receptors.

Ligand binding to G protein­coupled receptors (GPCRs), such as the α2a-adrenergic receptor (α2aAR), results in the activation of heterotrimeric G proteins, which consist of functionally distinct Gα subunits and Gßγ dimers. α2aAR-dependent inhibition of synaptic transmission regulates functions such as spontaneous locomotor activity, anesthetic sparing, and working memory enhancement and requires the soluble NSF attachment protein receptor (SNARE) complex, a Gßγ effector. To understand how the Gßγ-SNARE complex underlies the α2aAR-dependent inhibition of synaptic transmission, we examined the specificity of Gßγ subunits for the SNARE complex in adrenergic neurons, in which auto-α2aARs respond to epinephrine released from these neurons, and nonadrenergic neurons, in which hetero-α2aARs respond to epinephrine released from other neurons. We performed a quantitative, targeted multiple reaction monitoring proteomic analysis of Gß and Gγ subunits bound to the SNARE complex in synaptosomes from mouse brains. In the absence of stimulation of auto-α2aARs, Gß1 and Gγ3 interacted with the SNARE complex. However, Gß1, Gß2, and Gγ3 were found in the complex when auto-α2aARs were activated by epinephrine. Further understanding of the specific usage of distinct Gßγ subunits in vivo may provide insights into the homeostatic regulation of synaptic transmission and the mechanisms of dysfunction that occur in neurological diseases.

Management of thrombotic microangiopathy after hematopoietic cell transplantation: A position statement of ThREG (Turkish Hematology Research and Education Group).

Hematopoietic stem cell transplantation associated-thrombotic microangiopathy (TA-HCT) is one of the early complications of endothelial origin in the course of HCT. Endothelial damage to the microvascular structure and the platelet-rich microthrombi, which are formed as a result of accompanying complement activation, constitute the main pathological conditions resulting TA-TMA. Early diagnosis and management are of utmost importance to prevent multi-organ failure and death. This review summarizes the current understanding of TA-TMA regarding pathogenesis, definition, differential diagnosis, risk factors, surveillance for early diagnosis and management.