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Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck Feb 2026

Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck

Faculty, Staff and Student Publications

Anti-apoptotic B-cell lymphoma 2 (BCL-2) controls inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca²+ signalling. As cells typically express all three IP3R isoforms in variable abundances that assemble in hetero-tetrameric channels, the specific effects of BCL-2 on each isoform remain unclear. Here, we employed a reductionist approach using HEK293 cells triple-IP3R knockout reconstituted with a single IP3R isoform to elucidate the impact of BCL-2 on Ca2+ signalling by homo-tetrameric IP3R channels. Co-immunoprecipitation experiments demonstrated that BCL-2 interacts with each IP3R isoform. Live-cell Ca²+ imaging revealed that BCL-2 overexpression suppresses Ca²+ signals evoked by any of the three IP3R isoforms. Moreover, BCL-2 overexpression impaired …


The Link Between Weight Gain And Hippocampal Atrophy In Bipolar Disorder: A Longitudinal Investigation In 934 Participants, Julia Fraiha-Pegado, Sean R Mcwhinney, Martin Alda, Nina Alexander, Gerard Anmella, Christoph Abé, Luisa Altegoer, Francesco H Benedetti, Michael Berk, Erland Bøen, David J Bond, Brigitte Boye, Beatrice Bravi, Dara M Cannon, Emily L V Corkum, Emma Corley, Lorielle M F Dietze, Udo Dannlowski, Torbjorn Elvsåshagen, Paola Fuentes-Claramonte, Janice M Fullerton, Benjamin I Goldstein, Janik Goltermann, Dominik Grotegerd, Tim Hahn, Diego Hidalgo-Mazzei, Yanghee Im, Melody Kang, Andriana Karuk, Kody G Kennedy, Tilo Kircher, Anna Luisa Klahn, Anna Kraus, Mikael Landén, Elisabeth J Leehr, Rodrigo Machado-Vieira, Bradley J Macintosh, Ulrik F Malt, Elena Mazza, Colm Mcdonald, Susanne Meinert, Elisa Melloni, Phillip B Mitchell, Leila Nabulsi, Robert Nitsch, John O'Connor, Nils Opel, Maria C G Otaduy, Brownyn J Overs, Nadine Parker, Sara Poletti, Edith Pomarol-Clotet, Joaquim Radua, Gloria Roberts, Raymond Salvador, Chao Suo, Peter R Schofield, Maya Selitser, Kang Sim, Benjamin Straube, Lea Teutenberg, Sophia I Thomopoulos, Paula Usemann, Eduard Vieta, Lars T Westlye, Linzhi Wu, Lakshmi N Yatham, Paul M Thompson, Ole A Andreassen, Christopher R K Ching, Tomas Hajek, Enigma Bipolar Disorder And Bmix Working Groups Feb 2026

The Link Between Weight Gain And Hippocampal Atrophy In Bipolar Disorder: A Longitudinal Investigation In 934 Participants, Julia Fraiha-Pegado, Sean R Mcwhinney, Martin Alda, Nina Alexander, Gerard Anmella, Christoph Abé, Luisa Altegoer, Francesco H Benedetti, Michael Berk, Erland Bøen, David J Bond, Brigitte Boye, Beatrice Bravi, Dara M Cannon, Emily L V Corkum, Emma Corley, Lorielle M F Dietze, Udo Dannlowski, Torbjorn Elvsåshagen, Paola Fuentes-Claramonte, Janice M Fullerton, Benjamin I Goldstein, Janik Goltermann, Dominik Grotegerd, Tim Hahn, Diego Hidalgo-Mazzei, Yanghee Im, Melody Kang, Andriana Karuk, Kody G Kennedy, Tilo Kircher, Anna Luisa Klahn, Anna Kraus, Mikael Landén, Elisabeth J Leehr, Rodrigo Machado-Vieira, Bradley J Macintosh, Ulrik F Malt, Elena Mazza, Colm Mcdonald, Susanne Meinert, Elisa Melloni, Phillip B Mitchell, Leila Nabulsi, Robert Nitsch, John O'Connor, Nils Opel, Maria C G Otaduy, Brownyn J Overs, Nadine Parker, Sara Poletti, Edith Pomarol-Clotet, Joaquim Radua, Gloria Roberts, Raymond Salvador, Chao Suo, Peter R Schofield, Maya Selitser, Kang Sim, Benjamin Straube, Lea Teutenberg, Sophia I Thomopoulos, Paula Usemann, Eduard Vieta, Lars T Westlye, Linzhi Wu, Lakshmi N Yatham, Paul M Thompson, Ole A Andreassen, Christopher R K Ching, Tomas Hajek, Enigma Bipolar Disorder And Bmix Working Groups

Faculty, Staff and Student Publications

Background: Obesity, which is common in bipolar disorder (BD), is associated with smaller hippocampal volumes. We do not know the role of weight/weight gain in relation to longitudinal hippocampal changes among individuals with BD.

Methods: In collaboration with the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-BD Working Group, we obtained T1-weighted magnetic resonance imaging and clinical data from 233 participants with BD and 701 healthy control participants (HCs) scanned twice, 2.84 ± 1.63 years apart on average. We estimated subcortical volumes using FreeSurfer longitudinal image processing stream and used linear mixed models to assess the bidirectional relationship between baseline …


Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne Feb 2026

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …


Imaging In Acute Neurovascular Emergencies: Optimizing Outcomes In Large Vessel Occlusion Stroke, Chandu Goli, Rohit Patel, Elliott Beard, Anna Liles, Saeed Saleh, Aleeza Namit, Alissa Ongaco, Kevin Steed Ph.D. Feb 2026

Imaging In Acute Neurovascular Emergencies: Optimizing Outcomes In Large Vessel Occlusion Stroke, Chandu Goli, Rohit Patel, Elliott Beard, Anna Liles, Saeed Saleh, Aleeza Namit, Alissa Ongaco, Kevin Steed Ph.D.

Annual Research Symposium

Purpose:

Large vessel occlusion (LVO) stroke is associated with high rates of morbidity and mortality, and patient outcomes are strongly influenced by rapid identification and timely reperfusion. Advances in acute neurovascular imaging have transformed stroke care by enabling precise patient selection, extending treatment windows, and accelerating clinical workflows. The purpose of this project is to evaluate how modern neurovascular imaging strategies influence treatment selection, workflow efficiency, and clinical outcomes in patients with acute LVO stroke.

Methods:

A narrative review of peer-reviewed literature published within the past decade was conducted. The review focused on CT-based imaging (non-contrast CT, CT angiography, CT …


Epimedin A Prevents Glioblastoma Growth And Invasion, Michael B. Mildner, Erick A. Zecena Feb 2026

Epimedin A Prevents Glioblastoma Growth And Invasion, Michael B. Mildner, Erick A. Zecena

Annual Research Symposium

No abstract provided.


Lymphatic Pumping Failure In The Arm Precedes Dermal Backflow And Breast Cancer-Related Lymphedema, Melissa B Aldrich, Meghan E Mcwain, Simona F Shaitelman, Rian E Kuhns, John C Rasmussen, Wendy A Woodward, Sarah M Desnyder, Wenyaw Chan, Eva M Sevick-Muraca Feb 2026

Lymphatic Pumping Failure In The Arm Precedes Dermal Backflow And Breast Cancer-Related Lymphedema, Melissa B Aldrich, Meghan E Mcwain, Simona F Shaitelman, Rian E Kuhns, John C Rasmussen, Wendy A Woodward, Sarah M Desnyder, Wenyaw Chan, Eva M Sevick-Muraca

The Brown Foundation: Institute of Molecular Medicine

Background

Breast cancer patients who undergo regional nodal irradiation therapy (RNI) following neoadjuvant chemotherapy and mastectomy or lumpectomy with axillary lymph node dissection (ALND) frequently encounter breast cancer-related lymphedema (BCRL). Early detection and treatment can significantly improve outcomes. Previously, near-infrared fluorescence lymphatic imaging (NIRF-LI) detection of dermal backflow, or retrograde lymphatic flow into initial lymphatics, was shown to precede clinical BCRL diagnosis by 8–23 months. Herein, we hypothesize that lymphatic pump failure is responsible for dermal backflow and may be a target to prevent onset of BCRL symptoms.

Methods

Arm lymphatics in 51 patients with locally advanced breast cancer were …


Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang Feb 2026

Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven …


Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao Feb 2026

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …


Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur Feb 2026

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …


When Nutrition Fails: Modeling Protein Malnutrition-Driven Vulnerability In Hepatic Drug Metabolism And Inflammatory Stress, Vijitha D. Kantety, Victor Jiminez Jr. Feb 2026

When Nutrition Fails: Modeling Protein Malnutrition-Driven Vulnerability In Hepatic Drug Metabolism And Inflammatory Stress, Vijitha D. Kantety, Victor Jiminez Jr.

Annual Research Symposium

Background

Protein malnutrition remains a major global health problem and frequently co-occurs with alcohol use, opioid exposure, and infectious disease, particularly in low- and middle-income settings. The liver is central to both metabolism and inflammatory regulation, yet the effects of a malnutrition-like nutrient environment on hepatic responses to combined metabolic and inflammatory insults are not well defined. Cytochrome P450 3A4 (CYP3A4), a key enzyme involved in opioid metabolism, is highly sensitive to inflammatory signaling and may be especially vulnerable under conditions of nutritional deficiency. This project aims to 1) develop an in vitro model of nutritionally competent versus amino acid–restricted …


Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger Feb 2026

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …


Mutant Kras In Brain Endothelial Cells Promotes Vascular Inflammation And Impairs Vascular Integrity In Brain Arteriovenous Malformation, Jung-Eun Park, Bridger H Freeman, Hyejin Park, Sehee Kim, Adrian E Bafor, Ohnmar Myint, Song Gao, Zhen Xu, Jakob Körbelin, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park Feb 2026

Mutant Kras In Brain Endothelial Cells Promotes Vascular Inflammation And Impairs Vascular Integrity In Brain Arteriovenous Malformation, Jung-Eun Park, Bridger H Freeman, Hyejin Park, Sehee Kim, Adrian E Bafor, Ohnmar Myint, Song Gao, Zhen Xu, Jakob Körbelin, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Somatic KRAS (KRASG12V) mutation in endothelial cells (EC) induces brain arteriovenous malformation (bAVM) that could lead to vascular instability and ultimately bleeding. However, the causes of bAVM instability remain unclear. Here we demonstrate that KRASG12V expressing cultured ECs (KRAS-G12V-EC) have increased expression of pro-inflammatory mediators and reduced expression of blood-brain-barrier (BBB) junction constituents. The conditioned medium from KRAS-G12V-EC can activate BV2-microglia (BV2-MG) and conditioned media from this primed BV2-MG can compromise the expression of EC-junction constituents when added to wild-type ECs. In an in vitro BBB model, KRAS-G12V-EC form a dysfunctional EC barrier that is further disrupted, leading to lower …


Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage Feb 2026

Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage

Faculty, Staff and Students Publications

Forensic human identification relies on length-based differences in short tandem repeats (STRs) across autosomal and Y chromosomes, which require separate reactions and provide limited resolution. While next-generation sequencing offers greater discriminatory power, most platforms are expensive and restricted to traditional lab settings. Nanopore sequencing has the potential to change this with the real-time, portable MinION sequencer. However, forensic-specific tools that generate STR profiles compatible with established length-based databases are lacking. To address this, we developed STRspy2.0, which simultaneously profiles autosomal and Y-STRs using nanopore reads. STRspy2.0 produced accurate profiles for 54 multiplexed control libraries and 41 mock casework samples (blood, …


Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, And Treatment, Edward J. Filippone, John L. Farber Feb 2026

Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, And Treatment, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary membranoproliferative glomerulonephritis (MPGN) is an ultrarare disease characterized by immunofluorescence microscopy as either immune-complex mediated (IC-MPGN) or C3 glomerulopathy (C3), the latter subdivided by electron microscopy to C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both IC-MPGN and C3G typically have obvious C3 staining differentiating them from other causes of MPGN histology. Secondary causes must be excluded, including infections, autoimmune disease, and neoplasia. Clinical presentations are variable, including urinary sediment abnormalities, nephrotic syndrome, or a rapidly progressive course. The prognosis is unfavorable with about 50% reaching kidney failure by 10 years. Recurrence following transplantation is frequent, and allograft survival …


Validity Of The Turkish Version Of The Oral Frailty Index-8 And Its Relationship With Frailty, Malnutrition, And Sarcopenia In Older Adults, Süleyman Emre Koçyi̇ği̇t, Bi̇lal Kati̇poğlu, Yilmaz Önal, Kübra Bahar Baykan, İlknur Şeker Kaya, Fatma Sena Dost, Özge Dokuzlar, Esra Ateş Bulut, Ali̇ Ekrem Aydin, Derya Kaya, Ahmet Turan Işik Feb 2026

Validity Of The Turkish Version Of The Oral Frailty Index-8 And Its Relationship With Frailty, Malnutrition, And Sarcopenia In Older Adults, Süleyman Emre Koçyi̇ği̇t, Bi̇lal Kati̇poğlu, Yilmaz Önal, Kübra Bahar Baykan, İlknur Şeker Kaya, Fatma Sena Dost, Özge Dokuzlar, Esra Ateş Bulut, Ali̇ Ekrem Aydin, Derya Kaya, Ahmet Turan Işik

Turkish Journal of Medical Sciences

Background/aim: The Oral Frailty Index-8 (OFI-8) is a reliable screening for oral frailty. In our study, while presenting the Turkish reliability and validity study of the OFI-8, we also aimed to establish a cut-off value for oral frailty in Turkish population.

Materials and methods: Patients who presented to the outpatient clinic between January 2024 and January 2025 were evaluated. The test’s internal consistency and test–retest reliability were assessed. Divergent validity was evaluated using frailty scores, muscle strength, and nutritional status. A receiver operating characteristic (ROC) curve was generated to determine the optimal cut-off values for identifying frailty, malnutrition, and probable …


Mandibular Extension As A Trigger Of The Proprioceptive Trigeminocardiac Reflex, Massimo Conti, Giovanna Traina, Daniele Tonlorenzi Feb 2026

Mandibular Extension As A Trigger Of The Proprioceptive Trigeminocardiac Reflex, Massimo Conti, Giovanna Traina, Daniele Tonlorenzi

Turkish Journal of Medical Sciences

The trigeminocardiac reflex (TCR) is a physiological response characterized by a reduction in heart rate and arterial blood pressure following stimulation of any branch of the fifth cranial nerve. This review presents a novel mechanism of TCR induction through proprioceptive activation of the trigeminal nerve via mandibular extension (ME). Accordingly, it is referred to as the “proprioceptive trigeminocardiac reflex” (pTCR). An overview of the existing literature on ME-evoked TCR in humans and animals is presented, with particular emphasis on evidence of cerebral microcirculatory alterations. The magnitude of cardiovascular responses appears to depend on the duration of ME, with repeated applications …


Canakinumab Treatment In Patients With Colchicine-Resistant Familial Mediterranean Fever: A Multicenter Observational Study, Emrah Koç, Mete Pekdi̇ker, Mete Kara Feb 2026

Canakinumab Treatment In Patients With Colchicine-Resistant Familial Mediterranean Fever: A Multicenter Observational Study, Emrah Koç, Mete Pekdi̇ker, Mete Kara

Turkish Journal of Medical Sciences

Background/aim: Anti-interleukin-1 agents have known beneficial effects in the treatment of colchicine-resistant familial Mediterranean fever (cr-FMF); however, studies to date have tended to have small sample sizes and to be based on pooled data. The present study investigates the efficacy of Canakinumab (CAN) in a homogeneous cohort of cr-FMF cases.

Materials and methods: The study included patients who underwent treatment in three tertiary rheumatology departments, whose electronic medical records were reviewed retrospectively. The inclusion criteria were presence of colchicine resistant disease activity or persistent proteinuria secondary to AA-amyloidosis, and treatment with CAN for at least 6 months. Clinical and laboratory …


Retrospective Evaluation Of Treatment Outcomes Of Gasserian Ganglion Radiofrequency Thermocoagulation In Trigeminal Neuralgia Patients With Multiple Sclerosis, Emel Başar, Nevci̇han Şahutoğlu Bal, Erkan Yavuz Akçaboy Feb 2026

Retrospective Evaluation Of Treatment Outcomes Of Gasserian Ganglion Radiofrequency Thermocoagulation In Trigeminal Neuralgia Patients With Multiple Sclerosis, Emel Başar, Nevci̇han Şahutoğlu Bal, Erkan Yavuz Akçaboy

Turkish Journal of Medical Sciences

Background/aim: Trigeminal neuralgia (TN) secondary to multiple sclerosis (MS) is a rare but debilitating condition. Aside from two case reports, there are limited data on the use of Gasserian ganglion radiofrequency interventions in this patient population. This study aims to evaluate the outcomes of combined radiofrequency thermocoagulation (RFT) and pulsed radiofrequency (PRF) treatment targeting the Gasserian ganglion in patients with MS-related TN.

Materials and methods: We retrospectively analyzed 12 patients with MS-associated TN who underwent combined Gasserian ganglion RFT and PRF treatment between 1 January 2021 and 1 January 2025. Patients were followed for six months. Visual analog scale (VAS) …


Preoperative Inflammatory And Molecular Marker Changes In 125 Supratentorial Glioma Cases, Semi̇h Can Çeti̇ntaş, Burak Tahmazoğlu, Tufan Agah Kartum, Rahşan Kemerdere, Taner Tanriverdi̇ Feb 2026

Preoperative Inflammatory And Molecular Marker Changes In 125 Supratentorial Glioma Cases, Semi̇h Can Çeti̇ntaş, Burak Tahmazoğlu, Tufan Agah Kartum, Rahşan Kemerdere, Taner Tanriverdi̇

Turkish Journal of Medical Sciences

Background/aim: To determine whether there is a possible link between selected preoperative systemic inflammatory markers and molecular pathological indices.Material and methods: For this retrospective study, 125 patients served as subjects. Preoperative systemic inflammatory markers, namely neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), and postoperative pathological indices, namely mitosis, Ki-67 labeling index (LI), isocitrate dehydrogenase-1 (IDH1) mutation, and 1p/19q codeletion, were obtained from the electronic database.

Results: Results showed that NLR positively correlated with PLR (p = 0.00001), mitotic activity (p = 0.001), and Ki-67 LI (p = 0.00001). On the other …


Proximal Fragment Perfusion Following Hip Arthroplasty With Subtrochanteric Shortening Osteotomy In Patients With Severe Developmental Dysplasia Of The Hip, Vedat Bi̇çi̇ci̇, Hi̇lmi̇ Alkan, Enejd Vei̇zi̇, Şahan Güven, Serkan Ünlü, Eli̇f Özdemi̇r, Tural Talibli, Ahmet Firat Feb 2026

Proximal Fragment Perfusion Following Hip Arthroplasty With Subtrochanteric Shortening Osteotomy In Patients With Severe Developmental Dysplasia Of The Hip, Vedat Bi̇çi̇ci̇, Hi̇lmi̇ Alkan, Enejd Vei̇zi̇, Şahan Güven, Serkan Ünlü, Eli̇f Özdemi̇r, Tural Talibli, Ahmet Firat

Turkish Journal of Medical Sciences

Background/aim: The changes in proximal femoral blood flow occurring after reconstructive surgery for Crowe types III– IV developmental dysplasia of the hip (DDH) and their impact on healing remain unclear. In the present study, blood flow around the osteotomy site is evaluated with particular focus on the proximal segment in patients who underwent subtrochanteric shortening osteotomy and hip arthroplasty. To this end, single-photon emission computed tomography (SPECT/CT) scans were conducted to evaluate changes in proximal blood flow and to assess the impact on union rates and potential complications.

Materials and methods: A retrospective analysis was conducted of 26 hips from …


Radial Peripapillary Capillary Changes And Retinal Nerve Fiber Layer Alterations In Diabetic Foot Ulcers With Mild-To-Moderate Nonproliferative Diabetic Retinopathy: An Octa Study, Eyüpcan Şensoy, Hi̇kmet Erhan Güven, Mehmet Çitirik Feb 2026

Radial Peripapillary Capillary Changes And Retinal Nerve Fiber Layer Alterations In Diabetic Foot Ulcers With Mild-To-Moderate Nonproliferative Diabetic Retinopathy: An Octa Study, Eyüpcan Şensoy, Hi̇kmet Erhan Güven, Mehmet Çitirik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to evaluate the impact of diabetic foot ulcers (DFUs) on retinal microvascular changes, specifically the radial peripapillary capillary (RPC) vessel density and retinal nerve fiber layer (RNFL) thickness in patients with mild-to-moderate nonproliferative diabetic retinopathy (NPDR).

Materials and methods: Ninety participants were enrolled and divided into three groups: 30 patients with DFUs and mild-to-moderate NPDR, 30 patients with NPDR but without DFUs, and 30 healthy controls. RPC density and RNFL thickness were evaluated using optical coherence tomography angiography (OCTA), a noninvasive imaging method. Comparisons between groups were made with statistical adjustments, including optic disc area.

Results: …


Evaluation Of Colonization With Multidrug-Resistant Microorganisms And The Incidence Of Attributable Infections In Patients Undergoing Hematopoietic Stem Cell Transplantation, Burcu Çalişkan Demi̇rkiran, Gülşen İskender, İpek Mumcuoğlu, Duygu Mert, Si̇nan Dal, Tuba Dal, Semra Tunçbi̇lek, Mustafa Ertek, Fevzi̇ Altuntaş Feb 2026

Evaluation Of Colonization With Multidrug-Resistant Microorganisms And The Incidence Of Attributable Infections In Patients Undergoing Hematopoietic Stem Cell Transplantation, Burcu Çalişkan Demi̇rkiran, Gülşen İskender, İpek Mumcuoğlu, Duygu Mert, Si̇nan Dal, Tuba Dal, Semra Tunçbi̇lek, Mustafa Ertek, Fevzi̇ Altuntaş

Turkish Journal of Medical Sciences

Background/aim: The global rise in multidrug-resistant organisms (MDROs) has led to an increased incidence of MDRO infections following hematopoietic stem cell transplantation (HSCT), particularly during the preengraftment period. The objective of this study was to evaluate the relationship between pretransplant colonization by MDROs or carbapenem-resistant Enterobacterales (CRE) and the occurrence of infections caused by phenotypically similar microorganisms during the preengraftment period, as well as to assess the clinical outcomes of patients colonized with MDROs prior to transplantation.

Materials and methods: This prospective cohort study included patients diagnosed with hematological malignancies who underwent HSCT at the bone marrow transplant unit of …


Levothyroxine Poisoning In Children: A Multicenter Study From Türkiye, Kübra Şen Küçük, Şule Demi̇r, Reyhan Deveci̇ Sevi̇m, Fatma Akgül, Gülşen Yalçin, Öznur Eser, Alkan Bal, Eli̇f Ergi̇n, Sercan Öztürk, Ahmet Anik Feb 2026

Levothyroxine Poisoning In Children: A Multicenter Study From Türkiye, Kübra Şen Küçük, Şule Demi̇r, Reyhan Deveci̇ Sevi̇m, Fatma Akgül, Gülşen Yalçin, Öznur Eser, Alkan Bal, Eli̇f Ergi̇n, Sercan Öztürk, Ahmet Anik

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the clinical features, laboratory findings, treatment approaches, and follow-up strategies employed in the management of pediatric patients with levothyroxine poisoning.

Materials and methods: This multicenter retrospective study included patients aged ≤18 years who presented with acute, single-episode levothyroxine ingestion to the pediatric emergency departments of six tertiary care centers between 2010 and 2023. Clinical data, laboratory findings, symptom onset and severity, and treatment modalities were extracted from medical records. Thyroid function tests (TFTs) were interpreted according to the age-specific reference ranges of each center. Treatment decisions, including gastric decontamination and pharmacologic therapy, were evaluated …


Effects Of Transversus Abdominis And Erector Spinae Plane Blocks On Postoperative Pain Control And Postpartum Depression After Cesarean Section: A Randomized Prospective Study, Hi̇lal Bi̇radli, Feyza Çalişir, Alev Özer Feb 2026

Effects Of Transversus Abdominis And Erector Spinae Plane Blocks On Postoperative Pain Control And Postpartum Depression After Cesarean Section: A Randomized Prospective Study, Hi̇lal Bi̇radli, Feyza Çalişir, Alev Özer

Turkish Journal of Medical Sciences

Background/aim: Effective postoperative pain management after cesarean section is essential for maternal recovery. Poor pain control can lead to complications, including postpartum depression. This study aimed to compare the postoperative analgesic efficacy of erector spinae plane (ESP) and transversus abdominis plane (TAP) blocks following cesarean section, with a particular focus on their potential impact on postpartum depression.

Materials and methods: Sixty patients were randomly assigned to receive either an ESP block (Group E, n = 30) or a TAP block (Group T, n = 30) after cesarean section. Pain severity was assessed using a visual analog scale (VAS), and the …


Cd20 Molecule Deficiency And Carrier Frequency: A Village-Based Screening Study, Ebru Sümen, Mehmet Ali̇ Karaselek, Serkan Küççüktürk, Tuğçe Duran, Büşra Yüksel, Mustafa Gençeli̇, Ayşe Sümeyra Engi̇n, Muhammed Furkan Erden, Tuğba Esra Pekcandanoğlu, Bi̇lal Bostan, Mahmut Esad Yurtseven, Nazi̇re Nur Onat, Şükrü Nai̇l Güner, Sevgi̇ Keleş, İsmai̇l Rei̇sli̇ Feb 2026

Cd20 Molecule Deficiency And Carrier Frequency: A Village-Based Screening Study, Ebru Sümen, Mehmet Ali̇ Karaselek, Serkan Küççüktürk, Tuğçe Duran, Büşra Yüksel, Mustafa Gençeli̇, Ayşe Sümeyra Engi̇n, Muhammed Furkan Erden, Tuğba Esra Pekcandanoğlu, Bi̇lal Bostan, Mahmut Esad Yurtseven, Nazi̇re Nur Onat, Şükrü Nai̇l Güner, Sevgi̇ Keleş, İsmai̇l Rei̇sli̇

Turkish Journal of Medical Sciences

Background/aim: CD20 deficiency is an autosomal recessive inborn error of immunity (IEI), and the only known affected individual worldwide has been under follow-up in our clinic. Because the consanguineous parents of the index patient are putative carriers, we hypothesized that additional individuals with reduced CD20 expression might exist within their village population. This study aimed to evaluate clinical features associated with IEI and to identify individuals displaying CD20 mean fluorescence intensity (MFI) patterns consistent with putative carrier status, while also providing appropriate genetic counseling.

Materials and methods: This cross-sectional screening study was conducted in December 2024 in Çukurbağ village. Participants …


Association Between Frailty Status And Pain, Balance, And Quality Of Life In Patients With Lumbar Spinal Stenosis, Musa Güneş, Aydin Si̇nan Apaydin Feb 2026

Association Between Frailty Status And Pain, Balance, And Quality Of Life In Patients With Lumbar Spinal Stenosis, Musa Güneş, Aydin Si̇nan Apaydin

Turkish Journal of Medical Sciences

Background/aim: Frailty is a clinical syndrome that affects individuals physically and psychosocially. However, the association between lumbar spinal stenosis (LSS) and frailty remains unclear. This study aimed to compare pain, balance, disability, fear of falling, and quality of life between patients with LSS with and without frailty.

Materials and methods: This cross-sectional study included 43 frail and 48 nonfrail patients with LSS according to the frailty criteria of Fried et al. Pain intensity (numeric rating scale [NRS]), static balance (single leg stance test [SLST]), dynamic balance (Timed Up and Go test [TUG]), disability (Oswestry Disability Index [ODI]), fear of falling …


Oleanolic Acid–Chitosan Compound Inhibits Mitochondrial Autophagy And Malignant Transformation Of Lung Cancer Through The Pten/Akt Pathway, Abuli̇mi̇ti̇ Abulai̇ti̇, Xi̇aohong Sun, Waresijiang Yibulayin, Dan He, Kemi̇ng Xu, Xi̇ayi̇mai̇erdan Yi̇bulayi̇n Feb 2026

Oleanolic Acid–Chitosan Compound Inhibits Mitochondrial Autophagy And Malignant Transformation Of Lung Cancer Through The Pten/Akt Pathway, Abuli̇mi̇ti̇ Abulai̇ti̇, Xi̇aohong Sun, Waresijiang Yibulayin, Dan He, Kemi̇ng Xu, Xi̇ayi̇mai̇erdan Yi̇bulayi̇n

Turkish Journal of Medical Sciences

Background/aim: Oleanolic acid–chitosan compound (OAC) shows potent antinonsmall cell lung cancer (NSCLC) activity, but its mechanisms remain unclear. This study elucidates how OAC modulates autophagy and apoptosis via the Phosphatase and Tensin Homolog/Protein Kinase B (PTEN/AKT) signaling pathway.

Materials and methods: Oleanolic acid was coupled with chitosan to synthesize OAC. A549 and MRC-5 cells were cultured in Dulbecco’s Modified Eagle Medium and Minimum Essential Medium, respectively, supplemented with 10% fetal bovine serum and penicillin–streptomycin. Cells were pretreated with chloroquine before OAC treatment. Cell viability was assessed using the CCK- 8 assay, while 5-bromo-2′-deoxyuridine (BrdU) and colony formation tests were employed …


Neuroendocrine Effects Of Exogenous Adropin Administration On The Hypothalamic Pituitary Testicular Axis In Male Rats, Ersen Eraslan, Ayhan Tanyeli̇, Mustafa Can Güler, Asli Özbek Bi̇lgi̇n, Fazi̇le Nur Eki̇nci̇ Akdemi̇r, Eli̇f Polat, Seli̇m Çomakli, Nezahat Kurt, Tuğba Bal Taştan Feb 2026

Neuroendocrine Effects Of Exogenous Adropin Administration On The Hypothalamic Pituitary Testicular Axis In Male Rats, Ersen Eraslan, Ayhan Tanyeli̇, Mustafa Can Güler, Asli Özbek Bi̇lgi̇n, Fazi̇le Nur Eki̇nci̇ Akdemi̇r, Eli̇f Polat, Seli̇m Çomakli, Nezahat Kurt, Tuğba Bal Taştan

Turkish Journal of Medical Sciences

Background/aim: Obesity impairs male fertility through metabolic dysfunction, oxidative stress, and disruption of the hypothalamic– pituitary–testicular (HPT) axis. Adropin (ADR), a peptide hormone whose circulating levels are reduced in obesity, plays emerging roles in metabolic homeostasis; however, its involvement in reproductive endocrine regulation remains unclear. The present study was conducted in healthy, nonobese male rats and aimed to investigate the neuroendocrine and testicular effects of exogenous ADR administration, focusing on circulating reproductive hormones, hypothalamic regulatory peptides, and testicular antioxidant pathways.

Materials and methods: Thirty-two male Wistar rats were randomized into control, sham, low-dose ADR (4 μg/kg/day), and high-dose ADR (40 …


Fitness Cost And Biofilm Formation In Fosfomycin-Resistant Clinical Escherichia Coli And Klebsiella Pneumoniae Isolates, Mustafa Ökeer, Sabi̇re Şöhret Aydemi̇r, Bayri Eraç Feb 2026

Fitness Cost And Biofilm Formation In Fosfomycin-Resistant Clinical Escherichia Coli And Klebsiella Pneumoniae Isolates, Mustafa Ökeer, Sabi̇re Şöhret Aydemi̇r, Bayri Eraç

Turkish Journal of Medical Sciences

Background/aim: Fosfomycin has regained importance owing to its unique mechanism of action and effectiveness against extended-spectrum β-lactamase-producing Gram-negative bacteria. This study aimed to evaluate the biological fitness cost associated with fosfomycin resistance and its impact on biofilm formation in clinical Enterobacteriaceae isolates.

Materials and methods: A total of 78 Escherichia coli and 34 Klebsiella pneumoniae strains isolated from urine samples at Ege University Hospital were analyzed. Fosfomycin minimum inhibitory concentrations (MICs) were determined using the reference agar dilution method. Resistance was induced by exposing two K. pneumoniae strains with a fosfomycin MIC of 4 μg/mL and two E. coli strains …


Association Of Mir-34a With Metastatic Progression Through The Foxo3a–Sirt1 Regulatory Axis In Breast Cancer, Banu Şahi̇n, İlker Batuhan Bural, Hüseyi̇n Özcan, Sendegül Yildirim, Gamze Tanriöver, Şükran Burçak Yoldaş Feb 2026

Association Of Mir-34a With Metastatic Progression Through The Foxo3a–Sirt1 Regulatory Axis In Breast Cancer, Banu Şahi̇n, İlker Batuhan Bural, Hüseyi̇n Özcan, Sendegül Yildirim, Gamze Tanriöver, Şükran Burçak Yoldaş

Turkish Journal of Medical Sciences

Background/aim: Breast cancer represents the foremost cause of cancer-related mortality among women worldwide and is characterized by a markedly high metastatic potential, contributing substantially to its clinical severity and poor prognosis. This study aimed to evaluate the interrelationship among silent information regulator (SIRT1), Forkhead box O3a (FoxO3a), and microRNA-34a (miR- 34a), the latter of which promotes apoptosis by suppressing the proliferation, migration, and invasion of breast cancer cells. Specifically, we investigated the tumor microenvironment associated with metastatic progression of malignant primary tumors, the influence of nonmetastatic (benign) tumors, and the potential roles of these proteins in both primary tumor development …