Objectives Endotracheal intubation is a critical airway intervention in severe acute poisoning, but its indications, timing, and outcomes are inconsistently described, and there are limited prospective data from Indian emergency departments (EDs). The primary objective of this prospective observational study was to determine the incidence of endotracheal intubation in adults (≥18 years) presenting with acute poisoning to the ED of AIIMS Rishikesh, Rishikesh, India. The secondary objectives were to (i) identify the clinical indications prompting intubation, (ii) enumerate indications stratified by poison type, (iii) record the timing and duration of intubation among intubated patients, and (iv) compare mortality between intubated and non-intubated patients.  Methods A prospective observational study was conducted over 15 months (October 2024-December 2025) in the ED of AIIMS Rishikesh. Adult patients (≥18 years) presenting with acute poisoning were enrolled using consecutive sampling. Based on past departmental records, a sample size of 120 patients was estimated. Participants were followed for 28 days through hospital records or telephonic follow-up after discharge. Results This study included predominantly young adults with a slight male predominance (51.7%; 62/120), and the majority of poisoning cases were suicidal in nature. Pesticides, particularly organophosphorus (OP) compounds, were the most common poisoning agents, followed by household corrosives. Endotracheal intubation was required in 15.8% (19/120) of patients, with threatened airway due to a reduced Glasgow Coma Scale being the most common indication, followed by respiratory distress and excessive secretions. OP poisoning frequently required intubation due to multiple indications, while paraquat poisoning often required delayed intubation because of progressive respiratory failure. The overall mortality was 9.2% (11/120), with significantly higher mortality among intubated patients. Most deaths were attributed to OP compounds and paraquat poisoning. Male patients had higher rates of intubation and mortality. Conclusion This study found that 15.8% of adults with acute poisoning presenting to emergency required endotracheal intubation, with significantly higher mortality among intubated patients. OP compounds and paraquat were the leading causes of intubation and death. Most intubations were performed at presentation, emphasizing the importance of early airway assessment in the emergency while maintaining close monitoring for delayed respiratory deterioration, especially in paraquat poisoning.

The COVID-19 pandemic created social disruptions, leading to high levels of mental health problems for adolescents. Interpersonal stressors, such as lack of familial support, peer victimization, and discrimination, may have further exacerbated teen mental health issues. Yet, the psychological impact of interpersonal stressors and their interactive effects with high levels of loneliness remains unknown. In this pre-registered study, conducted in November and December 2020 (approximately eight months into the COVID-19 pandemic), we used a diverse sample of adolescents from across 43 U.S. states with elevated depressive symptoms (n = 2,452, ages 13-16) to examine how familial support, peer victimization, and discrimination are concurrently associated with mental health outcomes. Results indicated that perceived discrimination was the strongest standardized correlate across continuous internalizing outcomes (depressive symptoms, anxiety symptoms, and hopelessness), whereas lack of familial support was the primary correlate of suicidal ideation; if youth reported a lack of familial support, they were over three times as likely to report suicidal ideation. Loneliness significantly moderated the cross-sectional links between lack of familial support and depressive symptoms, as well as perceived discrimination and hopelessness. Simple slope probing demonstrated a distress ceiling effect: interpersonal stressors were most strongly associated with elevated distress among youth reporting low baseline loneliness, whereas youth experiencing high loneliness exhibited consistently elevated distress regardless of stressor exposure. These findings underscore interpersonal stressors and loneliness as high-priority targets for youth prevention and intervention programs, particularly during periods of widespread social disruption.

Precise manipulation of the mycobacterial genome is required to study the effect of specific mutations without confounding influences from the diverse genetic backgrounds in clinical isolates. This is particularly important for interrogating gene function and drug resistance mechanisms, where background mutations may enhance or suppress the effects of a mutation of interest. Here, two targeted site-directed mutagenesis approaches, two-step allelic exchange using a suicide vector and oligonucleotide-mediated recombineering, are described and compared for introducing defined mutations into an isogenic Mycobacterium tuberculosis background. Two-step allelic exchange uses a suicide vector lacking a mycobacterial origin of replication and carrying a mutated DNA fragment, selectable markers such as sacB for sucrose sensitivity, lacZ for blue-white screening, and antibiotic resistance genes (kan or hyg). The process involves generating the mutated fragment via a multi-step polymerase chain reaction (PCR) or synthesis, cloning it into the vector, electroporating it into M. tuberculosis, and selecting single-crossover (SCO) integration events using antibiotic resistance and blue-white colony screening. This is followed by counter-selection with sucrose and X-gal to eliminate bacteria carrying the wild-type sequence. This method ensures stable, unmarked mutations but is time-consuming and labor-intensive. Recombineering uses a recombinase-expressing plasmid, such as pJV75amber expressing Che9c gp61 recombinase under an inducible acetamidase promoter, together with a single-stranded DNA (ssDNA) oligonucleotide to introduce precise mutations. Transformants are selected on appropriate antibiotics and confirmed by PCR and Sanger sequencing. This approach is simpler, faster, and more cost-effective, but may be limited by low transformation efficiency, the need for fresh competent cells, and variable efficiency depending on the genomic region and oligonucleotide design. Together, two-step allelic exchange and recombineering offer complementary strategies for introducing defined mutations into M. tuberculosis. Both methods enable experimental validation of mutations, such as variants associated with gene function and drug resistance.

Background: Antidepressant self-poisoning is a common form of intentional self-harm, and comparisons across antidepressant groups are complicated by differences in ingested dose and coexposures. Methods: This retrospective cross-sectional study reviewed emergency department presentations coded with International Classification of Diseases, 10th Revision (ICD-10) X61/X64 between 01 January 2023 and 15 May 2025. Among 15,160 screened records, 168 patients with documented antidepressant ingestion with self-harm/suicidal intent were included. Antidepressant exposures were classified by group and standardized using defined daily dose (DDD). Clinical presentation, serotonin toxicity based on the Hunter Serotonin Toxicity Criteria, management, and short-term outcomes were evaluated. Multivariable logistic regression was used to adjust for log-transformed DDD. Results: The median age was 27.0 years, and 66.7% of patients were female. Selective serotonin reuptake inhibitors (SSRIs) were the most frequently ingested antidepressants (79.8%). Symptomatic presentation occurred in 33.3% of patients and was more frequent in non-SSRI than in SSRI exposures (55.9% vs 27.6%; adjusted OR, 3.40; 95% CI, 1.55-7.43; P = .002). Serotonin toxicity was identified in 7.7% and was also more frequent in non-SSRI exposures (23.5% vs 3.7%; adjusted OR, 8.17; 95% CI, 2.45-27.26; P = .001). Serotonin toxicity was associated with intensive care unit (ICU) admission (53.8% vs 10.3%; P < .001). Conclusion: Non-SSRI antidepressant exposures were associated with greater short-term clinical severity than SSRI exposures. Because non-SSRI subgroups were small and heterogeneous, class-specific findings should be interpreted as exploratory. The early clinical pattern of toxicity may inform short-term risk assessment.

Incretin receptor agonists (IRAs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual/triple receptor co-agonists, have transformed the treatment of obesity, type 2 diabetes mellitus, and cardiovascular disease. Given the extraordinary burden of cardiometabolic comorbidity and excess premature mortality in persons living with psychiatric disorders, IRAs represent a highly relevant and potentially transformative pharmacologic class for this population. Beyond their established metabolic indications, a triangulation of preclinical, neuroimaging, observational, and emerging controlled trial evidence suggests that IRAs may exert direct central nervous system effects-augmenting neurogenesis, neuroplasticity, and functional brain connectivity-that underpin putative psychiatric benefits. Replicated evidence supports effects on alcohol and substance use disorders, and preliminary data indicate benefits in mood and neurocognitive disorders. However, controlled trial evidence remains limited and mixed, and several clinical considerations specific to psychiatric populations-including suicidality surveillance, sarcopenia, constipation risk, drug-drug interactions, and aspiration risk with ketamine-require careful attention. Whether IRAs ultimately meet the evidentiary threshold to be classified as psychiatric drugs remains to be determined by ongoing phase III trials. In the interim, their use for cardiometabolic indications in psychiatric populations is well-justified and may confer meaningful mortality reduction.