BACKGROUND: Diabetes mellitus (DM) significantly impacts global health and economies. Despite various therapies, managing DM remains challenging. Bariatric surgery has shown efficacy in obese patients with type 2 diabetes mellitus (T2DM), but its utilization remains low. Innovative, less invasive endoscopic approaches such as duodenal mucosal resurfacing show potential in treating T2DM. This article presents the results of a First in Human (FIH) study using a duodenal submucosal laser ablation investigational device for T2DM treatment. METHODS: A prospective, single-arm, open-label study evaluated the safety and efficacy of the Digma System Endoscopic procedure for duodenal submucosal laser ablation in consecutive enrolled T2DM patients. RESULTS: The study was conducted from July 2017 to December 2020 and enrolled 31 patients for the Digma System Endoscopic procedure. The Dose Escalation Cohort (DEC) used sub-therapeutic laser doses for training and safety. The Treatment Cohort (TC) of 25 patients received therapeutic doses, resulting in HbA1c reductions of -0.6% at 6 months (p = 0.014) and -0.4% at 12 months (p = 0.062). Fasting glucose dropped 17.3 mg/dL (p = 0.173) at 6 months and 28 mg/dL (p = 0.022) at 12 months. Post-prandial glucose improvements were also observed. HOMA-IR improved at 3 and 6 months. PAGI-SYM and PAGI-QOL showed stable to slightly improved GI symptoms and quality of life. Two severe adverse events were unrelated to the procedure. CONCLUSION: The study demonstrates the safety, feasibility, and potential efficacy of the Digma System Endoscopic procedure. Evidence suggests improvements in HbA1c, fasting and post-prandial glucose, and HOMA-IR levels could be attributed to the Digma System Endoscopic procedure.
- MeSH
- Diabetes Mellitus, Type 2 * surgery blood MeSH
- Adult MeSH
- Duodenum * surgery MeSH
- Glycated Hemoglobin analysis metabolism MeSH
- Blood Glucose analysis metabolism MeSH
- Quality of Life MeSH
- Laser Therapy * methods adverse effects instrumentation MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Aged MeSH
- Intestinal Mucosa surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The temporomandibular joint (TMJ) is one of the most used joints in the body. Defects and wear in the cartilage of the joint, condyle, and fibrocartilage disc lie at the heart of many common TMJ disorders. During postnatal development, the condyle acts as a growth center for the mandible, with cells moving as a conveyor belt away from the top of the condyle as they differentiate. The superficial layers of the condyle have been proposed to contain stem/progenitor populations to allow growth and maintain homeostasis. Here we have focused on the role of fibroblast-specific protein 1 (FSP1; also known as S100a4) as a key fibroblast stem/progenitor marker for the condyle. Lineage tracing with FSP1-Cre;R26RmTmG mice revealed that FSP1-expressing cells were restricted to the superficial fibroblast zone, giving rise to all layers of the condyle over time. The FSP1-expressing cells overlapped with other putative stem cell markers of the condyle, such as Gli1 and scleraxis. BrdU pulse chase experiments highlighted that a subset of FSP1 fibrocartilage was label retaining, suggesting that FSP1 labels a novel stem/progenitor cell population in the condyle. Destruction of FSP1-expressing cells by conditional diphtheria toxin activity in FSP1-Cre;R26RDTA mice resulted in severe TMJ osteoarthritis with loss of the cartilage structure. Lgr5-expressing cells in the superficial layer of the condyle have been shown to create a Wnt inhibitory niche. FSP1 expression postnatally was associated with a reduction in canonical Wnt activity in the condyle. Importantly, constitutive activation of Wnt/β catenin in FSP1-expressing cells led to a downregulation of FSP1 and progressive postnatal loss of TMJ condylar hyaline cartilage due to loss of the superficial stem/progenitor cells. These data demonstrate a novel role for FSP1-expressing cells in the superficial zone in growth and maintenance of the TMJ condylar cartilage and highlight the importance of regulating Wnt activity in this population.
- MeSH
- Fibroblasts metabolism MeSH
- Homeostasis physiology MeSH
- Stem Cells * metabolism physiology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Mandibular Condyle growth & development cytology metabolism MeSH
- Receptors, G-Protein-Coupled MeSH
- S100 Calcium-Binding Protein A4 * metabolism physiology MeSH
- Temporomandibular Joint * growth & development cytology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Laser-induced breakdown spectroscopy (LIBS) is a promising technique for the readout of immunochemical assays utilizing indirect detection of labels (Tag-LIBS), typically based on nanoparticles. We have previously demonstrated that Tag-LIBS immunoassay employing yttrium-based photon-upconversion nanoparticles (UCNPs) can reach sensitivity similar to commonly used enzyme and fluorescence immunoassays. In this study, we report on further increasing the sensitivity of UCNP-based Tag-LIBS immunoassay by employing magnetic microbeads (MBs) as the solid phase in the determination of cancer biomarker prostate-specific antigen. Due to the possibility of analyte preconcentration, MBs enabled achieving a limit of detection (LOD) of 4.0 pg·mL-1, representing two orders of magnitude improvement compared with equivalent microtiter plate-based assay (LOD of 460 pg·mL-1). In addition, utilizing MBs opens up the possibility of an internal standardization of the LIBS readout by employing iron spectral lines, which improves the assay robustness by compensating for LIBS signal fluctuations and bead-bound immunocomplexes lost throughout the washing steps. Finally, the practical applicability of the technique was confirmed by the successful analysis of clinical samples, showing a strong correlation with the standard electrochemiluminescence immunoassay. Overall, MB-based Tag-LIBS was confirmed as a promising immunoassay approach, combining fast readout, multiplexing possibilities, and high sensitivity approaching upconversion luminescence scanning while avoiding the requirement of luminescence properties of labels.
- MeSH
- Immunoassay methods MeSH
- Lasers * MeSH
- Humans MeSH
- Limit of Detection * MeSH
- Microspheres MeSH
- Prostate-Specific Antigen * analysis immunology blood MeSH
- Spectrum Analysis methods MeSH
- Yttrium chemistry radiation effects MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
PURPOSE: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol. METHODS: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. RESULTS: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. CONCLUSION: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Urea * analogs & derivatives therapeutic use pharmacology MeSH
- Morpholines * therapeutic use pharmacology MeSH
- Aged MeSH
- Shock, Septic * drug therapy complications physiopathology MeSH
- Heart Rate * drug effects MeSH
- Tachycardia * drug therapy physiopathology complications MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- Europe MeSH
OBJECTIVE: Prepregnancy optimization of cardiovascular function may reduce the risk of pre-eclampsia. We aimed to assess the feasibility and effect of preconception cardiovascular monitoring, exercise, and beetroot juice on cardiovascular parameters in women planning to conceive. DESIGN AND METHOD: Prospective single-site, open-label, randomized controlled trial. Thirty-two women, aged 18-45 years, were allocated into one of four arms (1 : 1 : 1 : 1): exercise, beetroot juice, exercise plus beetroot juice and no intervention for 12 weeks. Blood pressure (BP) was measured at home daily. Cardiac output ( CO ) and total peripheral resistance (TPR) were assessed via bio-impedance. RESULTS: Twenty-nine out of 32 (91%) participants completed the study. Adherence to daily BP and weight measurements were 81% and 78%, respectively ( n = 29). Eight out of 15 (53%) of participants did not drink all the provided beetroot juice because of forgetfulness and taste. After 12 weeks, exercise was associated with a reduction in standing TPR (-278 ± 0.272 dynes s cm -5 , P < 0.05), and an increase in standing CO (+0.88 ± 0.71 l/min, P < 0.05). Exercise and beetroot juice together was associated with a reduction in standing DBP ( 7 ± 6 mmHg, P < 0.05), and an increase in standing CO (+0.49 ± 0.66 l/min, P < 0.05). The control group showed a reduction in standing TPR ( 313 ± 387 dynes s cm -5 ) and standing DBP ( 8 ± 5mmHg). All groups gained weight. CONCLUSION: Exercise and beetroot juice in combination showed a signal towards improving cardiovascular parameters. The control group showed improvements, indicating that home measurement devices and regular recording of parameters are interventions in themselves. Nevertheless, interventions before pregnancy to improve cardiovascular parameters may alter the occurrence of hypertensive conditions during pregnancy and require further investigation in adequately powered studies.
- MeSH
- Exercise physiology MeSH
- Nitrates * MeSH
- Double-Blind Method MeSH
- Hypertension * MeSH
- Blood Pressure MeSH
- Humans MeSH
- Dietary Supplements MeSH
- Prospective Studies MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
AIMS: Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. METHODS AND RESULTS: The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.
- MeSH
- Atrial Fibrillation * surgery physiopathology diagnosis therapy MeSH
- Catheter Ablation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Recurrence MeSH
- Pulmonary Veins surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Clinical Trial Protocol MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain.
- MeSH
- Antiviral Agents administration & dosage chemistry pharmacology pharmacokinetics MeSH
- Endothelial Cells * drug effects metabolism MeSH
- Blood-Brain Barrier * metabolism MeSH
- Coculture Techniques * MeSH
- Drug Delivery Systems methods MeSH
- Humans MeSH
- Microbubbles * MeSH
- Oligopeptides * chemistry administration & dosage pharmacokinetics MeSH
- Pericytes * metabolism drug effects MeSH
- Polymers chemistry administration & dosage MeSH
- Ribavirin administration & dosage chemistry pharmacokinetics MeSH
- Ultrasonic Waves MeSH
- Inflammation drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Úvod: Cílem této studie je vyhodnocení výkonu nově vyvinutého rytmového modelu určeného pro interpretaci EKG a založeného na umělé inteligenci (AI-ECGRM) v binární klasifikaci mezi sinusovým rytmem a arytmiemi. Metody: Interpretace EKG záznamů generované pomocí AI-ECGRM byly v rámci studie porovnány s diagnostickými závěry zkušeného kardiologa. Metodou použitou ke klasifikaci dat byla matice záměn, přičemž vyhodnocení zahrnuje senzitivitu, specificitu, pozitivní prediktivní hodnotu a negativní prediktivní hodnotu. Výsledky: Testovací datová sada obsahuje 1 491 náhodně vybraných EKG záznamů (průměrný věk 65 ± 21 let; 54 % žen). Pro danou datovou sadu čítala diagnostika kardiologa 1 271 záznamů se závěrem sinusový rytmus a 220 záznamů se závěrem arytmie. Oproti tomu interpretace generovaná pomocí AI-ECGRM čítala 1 169 záznamů se závěrem sinusový rytmus a 322 záznamů se závěrem arytmie. Senzitivita a specificita AI-ECGRM byla 94 % a 91 %. Pozitivní prediktivní hodnota byla 64 %. Negativní prediktivní hodnota dosáhla 99 %, což značí velmi nízkou pravděpodobnost vynechání potenciální patologie. Závěr: Výsledky ukazují na účinnost nově vyvinutého AI-ECGRM pro rozlišení záznamů se sinusovým rytmem a arytmií. Navíc metoda vykazuje vysokou negativní prediktivní hodnotu blížící se 100 %.
Objective: This study aimed to evaluate the performance of a developed novel AI-based ECG rhythm model (AI-ECGRM) in binary classification between sinus rhythm and arrhythmias. Methods: The interpretations generated by the AI-ECGRM were compared to the diagnostic conclusions made by cardiologists. The confusion matrix was used to verify the AI-ECGRM's sensitivity, specificity, positive predictive value, and negative predictive value. Results: The testing dataset included 1,491 randomly selected ECGs (mean age 65±21 years; 54% female). Out of the testing dataset, the highly advanced cardiologists diagnosed 1,271 ECGs as sinus rhythm and 220 as arrhythmia. The AI-ECGRM labelled 1,169 as sinus rhythm and 322 as arrhythmia out of the same ECGs. The sensitivity and specificity of the model were 94% and 91%, respectively. The positive predictive value was 64%. The negative predictive value was 99%, indicating a very low probability of missing any potential pathology. Conclusion: The results demonstrated the efficacy of the developed AI-ECGRM in accurately discriminating between ECGs exhibiting normal sinus rhythm and those indicating cardiac arrhythmias. Moreover, the AI-ECGRM exhibited an exceptional negative predictive value, approaching 100%.
BACKGROUND: Autologous tumor cell-based vaccines (ATVs) aim to prevent and treat tumor metastasis by activating patient-specific tumor antigens to induce immune memory. However, their clinical efficacy is limited. Mannan-BAM (MB), a pathogen-associated molecular pattern (PAMP), can coordinate an innate immune response that recognizes and eliminates mannan-BAM-labeled tumor cells. TLR agonists and anti-CD40 antibodies (TA) can enhance the immune response by activating antigen-presenting cells (APCs) to present tumor antigens to the adaptive immune system. In this study, we investigated the efficacy and mechanism of action of rWTC-MBTA, an autologous whole tumor cell vaccine consisting of irradiated tumor cells (rWTC) pulsed with mannan-BAM, TLR agonists, and anti-CD40 antibody (MBTA), in preventing tumor metastasis in multiple animal models. METHODS: The efficacy of the rWTC-MBTA vaccine was evaluated in mice using breast (4T1) and melanoma (B16-F10) tumor models via subcutaneous and intravenous injection of tumor cells to induce metastasis. The vaccine's effect was also assessed in a postoperative breast tumor model (4T1) and tested in autologous and allogeneic syngeneic breast tumor models (4T1 and EMT6). Mechanistic investigations included immunohistochemistry, immunophenotyping analysis, ELISA, tumor-specific cytotoxicity testing, and T-cell depletion experiments. Biochemistry testing and histopathology of major tissues in vaccinated mice were also evaluated for potential systemic toxicity of the vaccine. RESULTS: The rWTC-MBTA vaccine effectively prevented metastasis and inhibited tumor growth in breast tumor and melanoma metastatic animal models. It also prevented tumor metastasis and prolonged survival in the postoperative breast tumor animal model. Cross-vaccination experiments revealed that the rWTC-MBTA vaccine prevented autologous tumor growth, but not allogeneic tumor growth. Mechanistic data demonstrated that the vaccine increased the percentage of antigen-presenting cells, induced effector and central memory cells, and enhanced CD4+ and CD8+ T-cell responses. T-cells obtained from mice that were vaccinated displayed tumor-specific cytotoxicity, as shown by enhanced tumor cell killing in co-culture experiments, accompanied by increased levels of Granzyme B, TNF-α, IFN-γ, and CD107a in T-cells. T-cell depletion experiments showed that the vaccine's antitumor efficacy depended on T-cells, especially CD4+ T-cells. Biochemistry testing and histopathology of major tissues in vaccinated mice revealed negligible systemic toxicity of the vaccine. CONCLUSION: The rWTC-MBTA vaccine demonstrated efficacy in multiple animal models through T-cell mediated cytotoxicity and has potential as a therapeutic option for preventing and treating tumor metastasis with minimal systemic toxicity.
- MeSH
- CD40 Antigens MeSH
- Antigens, Neoplasm MeSH
- Immunologic Memory MeSH
- Humans MeSH
- Mannans MeSH
- Melanoma * MeSH
- Mice MeSH
- Breast Neoplasms * therapy MeSH
- Cancer Vaccines * therapeutic use MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Článek shrnuje poznatky o efektivitě a bezpečnostním profilu racemického ketaminu přidaného k běžné antidepresivní léčbě u pacientů s rezistentní depresivní poruchou. Racemický ketamin aplikovaný intravenózně v dávkách 0,5–1 mg/kg po dobu 40 minut prokazuje ve srovnání s placebem či midazolamem rychlý (po 24 h) antidepresivní i antisuicidální účinek u pacientů s rezistentní unipolární i bipolární depresí. Čtyři nebo 6 infuzí racemického ketaminu aplikovaných během 2 týdnů v dávkách 0,5 mg/kg po dobu 40 minut měly stejný antidepresivní efekt, který byl významně vyšší ve srovnání s placebem po 15 dnech od zahájení léčby. Opakované infuze racemického ketaminu aplikované během 2 týdnů zdvojnásobily šanci na dosažení odpovědi ve srovnání s jednou aplikací ketaminu. Antidepresivní i antisuicidální účinek racemického ketaminu dosažený po 2 týdnech opakovaných infuzí setrval při následné 4týdenní udržovací léčbě. Mimo intravenózní aplikace jsou studovány aplikace ketaminu intramuskulární, subkutánní, intranazální a perorální. Nežádoucí účinky (NÚ) po aplikaci i.v. racemického ketaminu, jako jsou zvýšení tlaku krve, pulzu, disociace, nevolnost a závratě, jsou přechodné a do 1–2 hodin po aplikaci spontánně mizí, po perorálním podání jsou NÚ minimální. Neexistují placebem kontrolované studie popisující dlouhodobý efekt racemického ketaminu přesahující jeho užívání 6 týdnů. Existují zprávy z klinické praxe o udržovací léčbě a bezpečnosti racemického ketaminu v délce několika měsíců i let. Protože racemický ketamin není registrován pro léčbu rezistentní deprese ani sebevražedných myšlenek, lze ho použít jen v off-label režimu.
The article summarizes the findings on the efficacy and safety profile of racemic ketamine added to conventional antidepressant treatment in patients with resistant depressive disorder (TRD). Racemic ketamine (intravenous doses 0.5–1 mg/kg 40 minute infusion) has higher antidepressant and antisuicidal effect than placebo or midazolam after 24 h in patients with TRD (unipolar or bipolar). Four or six ketamine infusions (i.v. doses 0.5–1 mg/kg 40 minute infusion) per 2 weeks has the same antidepressant effect, that was higher than placebo after 15 days. Four or six ketamine infusions per 2 weeks doubled the chance to reach response than single ketamine infusion. The two week antidepressant and antisuicidal effect of racemic ketamine was sustained after next 4 weeks of ketamine maintence infusions. In addition to intravenous administration, intramuscular, subcutaneous, intranasal and oral applications of ketamine have been studied. Side effects after intravenous ketamine like increase of blood pres- sure, pulse, dissociation, nausea and dizziness are transient and spontaneously dissapeared 1 to 2 hours after the aplication. These side effects are slighter after per os aplication. There are no long-term placebo controlled studies lasting longer than 6 weeks. There are retrospective chart reports from the clinical practice of maintenance treatment and safety of racemic ketamine over months or years. The racemic ketamine is not registered for the treatment of treatment resistant depression or suicidal thought and its aplication is possible only in off-label regime.
- MeSH
- Antidepressive Agents * administration & dosage pharmacology therapeutic use MeSH
- Depressive Disorder, Treatment-Resistant drug therapy MeSH
- Administration, Intravenous MeSH
- Ketamine * administration & dosage pharmacology adverse effects MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Suicidal Ideation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
