Send-out laboratory testing has increased substantially with the expansion of specialized assays, introducing operational complexity and risk of inefficiencies in test ordering and review. While laboratory stewardship programs emphasize appropriate test utilization, practical approaches to standardizing send-out test review at the individual request level remain limited. We implemented a structured, informatics-enabled workflow for send-out test review at an academic medical center. The workflow standardized request submission, reviewer notification, decision documentation, and communication without modifying existing clinical review criteria. This quality improvement initiative was evaluated over 8 months (August 2025 to March 2026). A total of 3055 requests were reviewed. Median monthly volume was 381 (range, 306-446). Documentation completeness was 98%. Median review turnaround time was 1 day (IQR, 0-1), with 83.9% completed within 1 day. Overall, 81.2% were approved, 11.8% were declined or canceled, and 6.9% were replaced. Review outcomes varied across clinical services, and a limited number of tests accounted for a disproportionate share of declined and modified requests. Implementation of a structured workflow for send-out test review enabled standardized documentation, rapid turnaround, and improved visibility into utilization patterns. This approach provides a scalable framework for enhancing laboratory oversight and supporting targeted test utilization interventions.
We developed a web-based application to help patients with cancer write high-quality secure messages to clinicians. Our objective was to test the effectiveness of the application, SEND, to determine if it positively impacted the clarity, directness, ability to express concerns and questions, specificity, and overall quality of messages. Patients with cancer 18 years and older were recruited through an online data collection and testing resource. They reflected on a time during their cancer treatment and wrote a simulated message to a clinician. After viewing SEND, they wrote another simulated message. Three oncology fellows blindly rated messages (pre- or post-intervention) based on five criteria: clarity, directness, expressiveness, specificity, and overall quality. Each criterion was rated on a five-point Likert scale ranging from 1 =poor to 5 =excellent. Data were analyzed using mixed-effects linear models to examine changes in outcomes over time while accounting for the non-independence of repeated measures within participants. Twenty-eight participants viewed SEND and wrote simulated messages. Most (53.6%) were female, and the mean age was 53 years. Raters evaluated a total of 56 messages (28 pre- and 28 post-). The word count of messages decreased from 47 to 43 words post-intervention. We found a significant improvement in the needs domain (β = 0.40, SE = 0.15, t = 2.64, p = .011), while all other domains increased post-intervention, but were not statistically significant. Our intervention was associated with improving the communication of patient needs (i.e. stating the main goal of the message). Improving the quality of secure messages written by patients has the potential to benefit both patients and clinicians. Patients can learn to craft succinct messages focusing on their main concerns, which may reduce clinicians' workload.
This paper examines how Italian teenagers construct meanings, norms and boundaries around sexting within their everyday digital cultures. Drawing on six vignette-based focus groups with 49 participants aged 16-18 years, the study used a media practice approach to analyse how teenagers collectively interpret a hypothetical sexting vignette. Findings show that participants overwhelmingly rely on heteronormative scripts, reproducing the dominant "girl-sends-nude-to-boy" narrative and positioning boys as initiators, while girls bear the potential risks. Sexting was consistently framed through risk discourses-particularly the threat of non-consensual dissemination-leading girls to internalise fear, self-policing, and responsibility for managing potential harm. Peer gossip further reinforced these risk narratives, circulating cautionary tales that blurred the boundaries between consensual and non-consensual practices and sustained moral regulation among peers. In response, teenagers constructed informal boundaries distinguishing "appropriate" from "unsafe" sexting, often limiting acceptable practices to long-term relationships and less explicit content. These findings highlight how risk discourses, peer surveillance and entrenched gender norms constrain teenagers' digital intimacies, particularly in an Italian context marked by limited sexuality education and persistent gender inequalities. The paper argues for research and pedagogical approaches that move beyond risk prevention to support teenagers' rights to agentic digital intimacies.
Objective: This study examined effects of exposure to a campus mental health promotion exhibit (Send Silence Packing®; SSP) on changes in college students' help-seeking intentions. Participants: College students (n = 576) from six campuses completed online surveys (baseline, 1-month, 6-month follow-up) assessing exposure to their campus' SSP exhibit (fall, 2022) and mental health help-seeking intentions, psychological distress, and service utilization. Methods: Fixed effects regression models examined associations between exposure to SSP (any vs. no) and changes in help-seeking intentions. Results: Relative to baseline, SSP exposure was associated with increases in intentions to seek help from informal sources (friend; family) at 1-month (B = 0.22, SE = 0.08, p = 0.006) and 6-month follow-up (B = 0.20, SE = 0.08, p = 0.01) but not from a mental health professional. Conclusions: Peer-informed campus mental health promotion exhibits may increase students' intentions to leverage informal sources of support when experiencing a mental health challenge.
Testing for acetylcholine receptor and muscle-specific kinase antibodies (anti-AChR and anti-MuSK) is of central diagnostic importance in myasthenia gravis (MG), yet practical evaluations of strategies to improve sensitivity using cell-based assays (CBAs) are lacking. We evaluated strategies to improve sensitivity of autoantibody testing for MG using CBAs at our center, including repeat fixed CBA at routine 1:10 dilution, send-out live CBA, and fixed CBA at lower 1:5 dilution. Quality improvement/quality assurance (QI/QA) evaluation of all patients at London Health Sciences Centre/St. Joseph's Health Care London (LHSC/SJHC) who underwent anti-AChR/MuSK fixed CBA testing from January 2023-January 2026. During the 3-year evaluation period, 973 patients underwent anti-AChR/MuSK fixed CBA at routine 1:10 dilution. Of these, 127 (13.1%) exhibited autoantibody positivity, 3 (0.3%) were indeterminable, and 843 (86.6%) were negative. Testing of 78 patients represented repeat testing after initially negative anti-AChR/MuSK fixed CBA, of whom 4 (5%) were positive. Thirteen patients with negative/indeterminable anti-AChR/MuSK fixed CBA underwent send-out live CBA, of whom 4 (31%) were positive. Of all 131 anti-AChR/MuSK-positive patients identified, 123 (94%) had positivity on initial fixed CBA, 4 (3%) on repeat fixed CBA, and 4 (3%) on send-out live CBA. Among 8 samples with negativity by fixed CBA at 1:10 dilution from patients with subsequent autoantibody positivity, 4 (50%) exhibited positivity at 1:5 dilution. Repeat fixed CBA at routine 1:10 dilution, send-out live CBA, and fixed CBA at lower 1:5 dilution are all strategies that may improve sensitivity of autoantibody testing for MG at our center.
Feasible and potentially scalable strategies are needed to address the growing cardiovascular disease (CVD) risk among people living with HIV. Bidirectional automated texting (BAT) programs that remind and encourage adherence to evidence-based CVD-reducing interventions represent a potentially scalable strategy, but data on their feasibility are lacking. The goal of the study was to determine whether participant sociodemographic factors and technological constraints influenced engagement with a BAT CVD prevention program by people living with HIV. We conducted an observational cohort analysis embedded within a stepped-wedge cluster randomized trial. The BAT program was designed to address the "Million Hearts" ABCS (aspirin therapy, blood pressure control, cholesterol management, and smoking cessation) of cardiovascular health. The parent study was a stepped-wedge randomized trial that rolled out in 3 wedges across 8 practice sites that provided care to people living with HIV. Participants received and could engage with the text messages weekly using their own phones during the study period. We used a zero-inflated negative binomial model to identify factors associated with participants sending text messages during the study. Of the 471 participants, 94% owned a smartphone capable of text messaging, and 70% reported monthly incomes less than US $1500. Overall, 60.3% (n=284) engaged with the BAT program at least once. Regarding texting behavior, participants aged ≥65 years were more likely to send a text than those aged <50 years (P=.047), although age did not influence the number of texts sent. White participants showed lower texting intensity than Black participants (incidence rate ratio 0.69; P=.04). Overall, 60.3% (n=284) of the participants in the study engaged with BAT at least once. The BAT intervention for ABCS appears to be a feasible intervention for people living with HIV. Only a few factors were associated with sending a text or with the number of text messages sent.
Discharged Emergency Department (ED) patients should receive instructions about their condition, including self-care and return-to-care guidance, while satisfying medicolegal requirements. Verbal instructions are forgotten or poorly understood. Written instructions are best practice, but usage barriers include multifactorial inefficiencies getting them to the patient and patient challenges finding them later when needed. In this feasibility and uptake study, we sought to address these barriers by developing a website that enables physicians to send condition-specific discharge instructions by text message. We recruited from the approximately 60 physicians working in the Saskatoon, Canada adult EDs, which serve > 140,000 patients/year. The physician visits our website, enters the patient's phone number, selects a condition, and taps "send." The patient receives a text message with a link to condition-specific discharge instructions. We analyzed link access data and surveyed physician feedback. Over a 2-month study period, 115 discharge instructions were texted (< 1% of an estimated maximum 17,000 discharges). 83% were accessed, 43% repeatedly. Links were visited quickly: 57% within one minute, 81% within one hour, and 97% within 24 h. 36 conditions were selected, most commonly concussion (19%), abdominal pain (9%), laceration (7%), and renal colic (7%). Seventeen physicians (28%) responded to our survey. 47% indicated they do not typically provide written (paper-based) discharge instructions. 87% ranked our system ≥ 8/10 in ease of use (0 = very difficult, 10 = very easy), 73% ranked it ≥ 7/10 in efficiency compared to usual practice (0 = maximally inefficient, 10 = maximally efficient). 93% said they would use our system going forward. Our study is limited by low physician uptake. However, positive physician feedback and quick and repeated patient access to instructions together suggest our approach might be a feasible way to improve ED discharge practice. RéSUMé: OBJECTIFS: Les patients des services d’urgence (SU) doivent recevoir des instructions sur leur état, y compris des conseils sur l’autosoins et le retour aux soins, tout en respectant les exigences médico-légales. Les instructions verbales sont oubliées ou mal comprises. Les instructions écrites sont la meilleure pratique, mais les obstacles à l’utilisation incluent des inefficacités multifactorielles pour les acheminer au patient et des difficultés pour le patient à les trouver plus tard lorsque cela est nécessaire. Dans cette étude de faisabilité et d’adoption, nous avons cherché à surmonter ces obstacles en développant un site web qui permet aux médecins d’envoyer des instructions de sortie spécifiques à une condition par message texte. MéTHODES: Nous avons recruté parmi les quelque 60 médecins travaillant dans les services d’urgence pour adultes de Saskatoon, au Canada, qui traitent plus de 140 000 patients par année. Le médecin visite notre site web, saisit le numéro de téléphone du patient, sélectionne une condition et tape « envoyer ». Le patient reçoit un message texte avec un lien vers les instructions de sortie spécifiques à la condition. Nous avons analysé les données d’accès aux liens et sondé les commentaires des médecins. RéSULTATS: Sur une période d’étude de 2 mois, 115 instructions de sortie ont été envoyées par texto (<1 % d’un maximum estimé de 17 000 sorties). 83 % ont été consultés, 43 % à plusieurs reprises. Les liens ont été visités rapidement : 57 % en une minute, 81 % en une heure et 97 % en 24 heures. 36 affections ont été sélectionnées, le plus souvent commotion cérébrale (19 %), douleur abdominale (9 %), lacération (7 %) et colique néphrétique (7 %). Dix-sept médecins (28 %) ont répondu à notre sondage. 47 % ont indiqué qu’ils ne fournissent généralement pas d’instructions de congé écrites (sur papier). 87 % ont classé notre système ≥8/10 en termes de facilité d’utilisation (0 = très difficile, 10 = très facile), 73 % l’ont classé ≥7/10 en efficacité par rapport à la pratique habituelle (0 = au maximum inefficace, 10 = au maximum efficace). 93 % ont dit qu’ils utiliseraient notre système à l’avenir. CONCLUSIONS: Notre étude est limitée par la faible adhésion des médecins. Cependant, les commentaires positifs des médecins et l’accès rapide et répété des patients aux instructions suggèrent que notre approche pourrait être un moyen réalisable d’améliorer la pratique de sortie du service d’urgence.
S-RNase-mediated gametophytic self-incompatibility (GSI) prevents self‑fertilization by inhibiting the growth of self-pollen tubes, yet the contribution of DNA metabolism, particularly radiation sensitive 2 (RAD2) family nucleases, to this process remains largely unknown. In this study, 49 RAD2 family genes were identified across pear and eight other fruit crops and classified into four conserved subfamilies (XPG, FEN-1, EXO1, and SEND). Of these, six RAD2 members were identified in pear, among which only PbrFEN-1 was significantly downregulated in pollen tubes treated with self S-RNases compared to non-self S-RNases, Furthermore, overexpression of PbrFEN-1 was found to alleviate the toxic effect of self S-RNase, indicating its involvement in the GSI response. Notably, antisense oligonucleotide-mediated knockdown of PbrFEN-1 disrupted ROS homeostasis at the pollen tube tip, leading to reduced ROS levels and subsequent inhibition of pollen tube growth. In contrast, pollen magnetofection-mediated overexpression of PbrFEN-1 helped maintain ROS homeostasis at the pollen tube tip, which was associated with faster pollen tube growth. These results suggest that PbrFEN-1 positively regulates ROS levels at the tip of pollen tube to support pollen tube elongation. These findings extend the mechanistic understanding of S-RNase-mediated GSI to the level of DNA metabolism and genome stability, providing new insights into the molecular basis of pollen tube inhibition in Rosaceae species.
Post-traumatic Stress Disorder (PTSD) is a debilitating psychiatric condition caused by severe trauma exposure and characterized by ongoing dysregulation of fear processing, hyperarousal, and amygdala activation, but with limited effective treatments. Recent large-scale genome-wide association studies (GWAS) of PTSD have identified the transcription factor FOXP2 as a highly-significant, top putative risk gene. Both fine-mapping of the PTSD GWAS with amygdala-specific expression quantitative trait loci (eQTL) data, and transcriptome-wide association analyses, show that altered expression of FOXP2 is associated with increased PTSD risk. In vertebrates, FOXP2 mRNA is most densely expressed in the intercalated cells (ITCs) of the amygdala. ITC neurons receive excitatory input from external regulatory and sensory brain regions, as well as the basolateral amygdala, and send inhibitory projections to the central amygdala, which regulates downstream fear responses. While ITCs are critical for conditioned fear acquisition and extinction, the role of the FOXP2 gene in modulating fear-related behaviors remains unknown. Here, we used complementary bioinformatic, molecular, circuit, behavioral, and electrophysiological approaches to characterize the function of mouse (Foxp2) and human (FOXP2) orthologs in amygdala-mediated fear learning. To assess Foxp2 function in vivo, we first used shRNA-mediated knockdown (KD) of Foxp2 in ITC neurons of adult mice. Targeted Foxp2 KD robustly and significantly reduced freezing (threat/fear expression) during and after auditory fear conditioning. Whole-cell recordings from individual ITC neurons revealed that Foxp2 KD increased their intrinsic membrane excitability and action potential frequency, consistent with hypothesized enhanced inhibitory output to the central amygdala and thus reduced fear expression. This hyperexcitability was associated with reduced potassium channel conductance. Bulk RNA sequencing (RNA-seq) of mouse amygdala after ITC Foxp2 KD confirmed decreased potassium channel transcription and revealed broader Foxp2-dependent regulation of multiple genes implicated in fear learning, including Wnt, Crh (which encodes corticotropin-releasing hormone), and neurokinin signaling pathways. Consistent with these findings, bulk RNA-seq of medial amygdala postmortem tissue from humans with PTSD versus neurotypical controls showed decreased potassium channel transcription in samples with low FOXP2 expression. Downstream transcriptional changes following Foxp2 KD in the mouse amygdala also showed marked enrichment of genes identified in PTSD risk loci from the largest PTSD GWAS to date. Specifically, downregulated genes were enriched for mouse orthologs of Tier 1 PTSD GWAS risk genes. This enrichment appears to reflect subcortical Foxp2 signaling within the amygdala, driven predominantly by decreased expression of genes lacking promoter-anchored chromatin loops. This finding suggests that Foxp2 may directly bind regulatory elements of multiple top PTSD risk genes, acting as a key regulatory node for fear-related pathways in the amygdala. Collectively, our findings establish FOXP2 as a central transcriptional regulator of fear-related gene networks in the amygdala and potential regulatory hub for PTSD genetic risk.
Ureteral double-J stents (UDJS) are frequently placed in urologic practice for a range of indications, including ureteral obstruction, strictures, stone disease, peri- and post-ureteroscopy, and following ureteral reconstruction or reimplantation. Recent studies suggest that approximately 13% of inserted stents become overdue or neglected, which can lead to serious, potentially life-threatening complications. We therefore aimed to develop a smartphone application to track patients with UDJS and reduce the incidence of overdue indwelling ureteral stents. For the development of the application, we worked with a specialized team of programmers. To facilitate universal access to the complete patient database, a cloud-based database was implemented. The application was designed to send a Short Message Service (SMS) to the patients and their general practitioner to remind the timing for UDJS extraction. We prospectively enrolled a total of 200 patients who underwent UDJS insertion for any indication by six urologists from June 2023, to March 2024. The patients were divided into two groups: the first group was monitored using the Stentless mobile application, while the second group was monitored using an electronic patient registry. The two groups were compared with respect to stent overdue times and complete loss-to-follow-up rates. In this study, a total of 200 patients were enrolled non-randomly and assigned to one of the study groups. 100 patients assigned to group 1 (mobile application group) and 100 to group 2 (electronic registry group). Among these, 187 patients (93.5%) underwent unilateral ureteral stent placement, while 13 patients (6.5%) required bilateral stent placements. The study also included patients with long-term indwelling stents, with the maximum stent replacement interval extending up to 360 days. The median indwelling time across the cohort was 17 days (range 14-360), reflecting the inclusion of long-term stents. In group 1, no patients missed their scheduled stent removal appointments, corresponding to an LTFU rate of 0% and no overdue removals. In group 2, four patients failed to attend their scheduled appointments (p = 0.121). These patients were identified through the electronic patient registry and subsequently contacted for follow-up. The delay in stent removal among these four patients was (7, 10, 13, and 60 days) beyond the planned appointment date. Notably, one patient from group 2 presented with an encrusted stent requiring two flexible ureteroscopy procedures for removal. Ultimately, all ureteral stents were successfully removed in an office-based setting, ensuring complete management for all participants. By notifying the patient and general practitioner with a mobile phone text message automatically transmitted from the application, there is the potential to increase patient compliance, reduce the rate of those who have a UDJS and fail to return for follow-up, respectively to reduce the rate of patients presenting for complications due to stent encrusting.
Emergency theatre capacity is under increasing strain due to rising demand and workforce pressures, contributing to delays and poor compliance with national targets. By prioritising patient selection for low-complexity cases/day-case discharge, we implemented a novel Golden Patient Protocol in a multi-specialty tertiary centre and assessed the impact on surgical wait times and overall theatre flow. The golden patient was agreed upon between surgical/anaesthetic registrars, taking into consideration the urgency/fitness of patient and anaesthetic/technical difficulties. Eligible patients were identified early and scheduled for a huddle and sent for by 08:30. Data were collected over four cycles: 1 month before and after the Golden Patient Protocol introduction, following a 4-month 'cooling-off' (post-Golden Patient Protocol) period and at 24 months, using the trust theatre management system (TMIS). For each patient we obtained 'send time', 'time-in-anaesthetic-room', and 'start-time' aka knife-to-skin. Across 86 patients (pre-Golden Patient Protocol n = 16; Golden Patient Protocol n = 24; post-Golden Patient Protocol n = 20; 24 months n = 26), median 'time-sent' improved from 08:54 pre-Golden Patient Protocol to 08:28 post-Golden Patient Protocol and remained improved at 08:41 at 24 months (p = 0.013). Median 'time in anaesthetic room' improved from 09:10 to 08:47 and was sustained at 08:58 at 24 months (p = 0.046). Significant pairwise differences persisted between pre-Golden Patient Protocol and both post-Golden Patient Protocol and 24-month cohorts. 'Knife-to-skin' showed a trend towards improvement (09:39 to 09:24; p = 0.244). The Golden Patient Protocol significantly improved early emergency theatre flow for lower-complexity cases while supporting registrar autonomy and reducing delays to first send. Although knife-to-skin improvements were modest, earlier patient preparation and anaesthetic room arrival demonstrated statistically and clinically meaningful gains that were sustained at 24-month follow-up. This low-cost, scalable intervention aligns with Getting It Right First Time priorities and represents a pragmatic strategy to improve emergency theatre efficiency and workflow sustainability.
Two contrasting frameworks have guided research on adolescent sexting. The deviancy perspective regards sexting as a risky behavior. The normalcy perspective acknowledges consensual sexting as a form of sexual expression with potential benefits. Drawing on both perspectives, this study compared adolescents who actively engaged in voluntary sexting (i.e., sent a sext of themselves or others) with those who were only passively (i.e., received, asked, or were asked for a sext, but did not send one) or never involved in sexting. The three groups were compared regarding sexuality-related cognitions, sexual behavior, and depressive symptoms, considering risk- and competence-related variables of sexual development. A sample of 216 adolescents (Mage = 16.93) completed an online questionnaire. Half reported active sexting (AS; active sexters), 16.2% exclusively passive sexting (PS; exclusively passive sexters), and 33.8% no sexting (NS; non-sexters). Supporting the deviancy perspective, AS reported higher levels on all risk-related variables, including risky sexual behavior, risky sexual scripts, acceptance of sexual coercion, perceived realism/utility of pornography, non-violent and violent pornography use, and depressive symptoms, than NS. Several significant differences emerged between AS and PS. Contrary to our hypotheses informed by the normalcy perspective, no significant group differences were found in indicators of sexual competence, namely communication about sexuality, sexual self-esteem, and sexual assertiveness. Results suggest that active sexting is embedded in a broader constellation of risk-related sexual behaviors and cognitions. Potential benefits of sexting may depend on factors not captured in the study, such as relationship context, underscoring the need for future research.
Hospitals desire knowledge of bedside sensors in real time but they do not wish to send everything to the cloud. We propose an Edge-AI framework used in the IoT environment that maintains intelligence as near as possible to the patient, and ensures privacy and a trusted audit trail. A quantized CNN-LSTM is run on-device to detect anomalies and protects data in transit and at rest (TLS plus lightweight homomorphic encryption), logs notable events to a private block chain to give an auditable, tamper-proof history, and improves models off-device using federated learning to ensure that raw patient data never reaches the cloud. Reply The framework was tested against a cloud-only baseline on the MIT-BIH Arrhythmia dataset and a live multi-sensor synthetic stream, beating it across all metrics: accuracy 94.7% versus 83.1% accuracy, median inference latency 118 ms versus 246 ms (a 52% reduction), daily communication overhead 36.2 MB versus 56.3 MB (a savings of 38.1%), and energy usage 1.21 mW/sample (near 22% energy efficiency improvement). Block chain logging endured 75 events/s, which helped medico-legal tractability. Federated rounds provided ~ 1.5-2.3 accuracy points per round across five rounds, whereas INT8 quantization reduced model size by ~ 74% with only a ~ 0.4 accuracy degrade-practical in Jetson-class edge devices. SHAP explanations accompany alerts to enable the establishment of clinical trust in the model by demonstrating why a case was flagged. In general, the framework provides a safe, decipherable, and standard-aligned course to hospital-scale implementation (> 1,000 nodes) with quantifiable gains in responsiveness and bandwidth as well as power.
The duodenum has historically been regarded as a passive digestive conduit for nutrient transit and absorption. However, emerging experimental and clinical evidence supports a revision of this view. In a contemporary model, the proximal small intestine also has roles as a metabolic sensor and endocrine signalling hub that exerts a powerful influence over systemic metabolism. The duodenum contains the highest concentration of enteroendocrine cells in the gastrointestinal tract, secreting a variety of hormones that regulate digestive processes and metabolic networks. In addition, a dense bidirectional vagal network enables rapid communication between duodenal nutrient sensing and central regulation of metabolism. Recent advances have highlighted how the duodenum undergoes a series of maladaptive changes in the setting of obesity and Type 2 diabetes (T2D), including changes in the mucosal layer, accelerated transport of nutrients, chronic low-grade inflammation and impaired barrier integrity. These alterations have raised the hypothesis that duodenal dysfunction may be a major contributor to the pathogenesis of metabolic disease. In support of this, bariatric procedures that exclude the duodenum from nutrient contact, most notably Roux-en-Y gastric bypass, produce rapid and weight-independent improvements in metabolic homeostasis. This mechanistic framework has driven the development of targeted endoscopic and pharmacological strategies, including the duodenal-jejunal bypass liner, duodenal mucosal resurfacing and various pharmacological interventions. A common goal of these interventions is to exploit duodenal biology to restore metabolic homeostasis. This review examines duodenal anatomy and function, the pathological remodelling that takes place in metabolic disease, and provides an overview of the expanding therapeutic landscape that targets this underappreciated organ in the treatment of obesity and T2D. The duodenum—the short segment of intestine just beyond the stomach—has long been viewed as a passive digestive conduit. However, it is now understood to be the most hormonally active region of the gastrointestinal tract, packed with specialised cells that detect nutrients and send signals to the pancreas, liver, brain, and adipose tissue. In people with obesity and type 2 diabetes (T2D), the duodenal lining undergoes damaging changes: it absorbs nutrients more rapidly, produces fewer metabolic hormones, becomes chronically inflamed, and loses its normal barrier function—allowing harmful bacterial products to leak into the circulation. The powerful and rapid metabolic improvements seen after bariatric surgery, which bypasses the duodenum, strongly implicate these changes in the pathogenesis of metabolic disease. This review examines duodenal physiology, its dysfunction in obesity and T2D, and the growing landscape of therapies that target this underappreciated organ. We conducted a narrative review of the literature covering duodenal anatomy, enteroendocrine cell biology, the pathological remodelling that occurs in obesity and T2D, and the mechanisms underlying the metabolic benefits of bariatric surgery. We then reviewed the evidence for interventions that therapeutically target the duodenum, including the duodenal‐jejunal bypass liner (EndoBarrier), duodenal mucosal resurfacing (DMR), and pharmacological agents with duodenal mechanisms of action—metformin, alpha‐glucosidase inhibitors, orlistat, and the investigational drug GLY‐200. Duodenal dysfunction in obesity and T2D encompasses accelerated nutrient absorption, reduced enteroendocrine cell density, chronic mucosal inflammation, and increased gut permeability—changes that collectively impair metabolic regulation and may actively drive disease progression. Interventions that exclude or remodel the duodenal mucosa produce rapid, weight‐independent improvements in glycaemic control, mirroring the effects of gastric bypass surgery. DMR is now approved in Europe for T2D and fatty liver disease, and has received FDA breakthrough device designation. Pharmacological agents including metformin and alpha‐glucosidase inhibitors exert clinically meaningful effects partly through duodenal mechanisms. Across all interventions, shared downstream effects include improved insulin sensitivity, reduced hepatic glucose production, changes in bile acid signalling, and reconfigured postprandial gut hormone secretion. This review provides a unified framework positioning the duodenum as both a site of pathophysiology and a compelling therapeutic target in metabolic disease. By linking the mechanistic lessons of bariatric surgery to emerging endoscopic and pharmacological strategies, it highlights a rapidly expanding therapeutic axis that is largely complementary to existing drug classes. As the pipeline of duodenal‐targeting interventions grows—including devices, ablative procedures, and barrier‐forming drugs—this framework offers clinicians and researchers a coherent basis for understanding and exploiting duodenal biology in the treatment of obesity and T2D.
While the movement of one's eyes to extract information from the visual environment often occurs without conscious reflection, this may not be true when one's eyes are also a signal of information to others, such as in a social interaction. Metacognitive monitoring of one's ability to balance the use of gaze to both receive and send information has not been empirically tested. The present study investigated this issue by eye-tracking participants during a novel hide-and-seek paradigm. Hiders selected boxes on a computer display with the goal of cooperating with or deceiving a future seeker. Displays were either homogeneous or contained a visually conspicuous box. Hiders were either aware or unaware that their gaze would be revealed to future seekers. Hiders reported their confidence in their hiding success after every trial. To assess hider performance, a new group of participants ("seekers") were tasked with identifying the hiders' box selections after seeing an animation of hiders' fixations toward displays. The results indicate that hiders' confidence effectively predicted seeker accuracy, with this metacognitive ability being strongest when hiders both intentionally and cooperatively signaled with their eyes and when a visually conspicuous box aided communication. These findings highlight the capacity to monitor the use of one's gaze for both gathering and signaling information and reveal that this ability varies with both the environmental context and the form of communication. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Brain-computer interfaces (BCIs) can provide naturalistic communication and digital access to people with severe paralysis by decoding neural activity associated with attempted speech and movement. Recent work has demonstrated highly accurate intracortical BCIs for speech and cursor control, but two critical capabilities needed for practical viability were unmet: independent at-home operation without researcher assistance and reliable long-term performance supporting accurate speech and cursor decoding. Here we demonstrate the independent and near-daily use of a multimodal BCI with novel brain-to-text speech and computer cursor decoders by a man with paralysis and severe dysarthria due to amyotrophic lateral sclerosis. Over nearly 2 years, the participant used the BCI for more than 3,800 h at home with no researchers present to maintain rich interpersonal communication with his family and friends, independently control his personal computer and sustain full-time employment-despite being paralyzed. He communicated 183,060 sentences-totaling 1,960,163 words-at an average rate of 56 words per minute. He labeled 92% of sentences as being decoded at least mostly correctly. In formal quantifications of performance where he was asked to say words presented on a screen, attempted speech was consistently decoded with more than 99% word accuracy (125,000 word vocabulary). The participant also used the speech BCI as keyboard input and the cursor BCI as mouse input to control his personal computer, enabling him to send text messages and emails and to browse the internet. These results demonstrate that intracortical BCIs have the potential to support independent use in the home, marking a critical step toward practical assistive technology for people with severe motor impairment.
An appropriate stress response is essential for properly responding to, coping with, and subsequently recovering from disturbing environmental stimuli. However, how the brain dynamically encodes the scalability of stress responses remains poorly understood. Here, we found that, GABAergic neurons in the arcuate nucleus (Arc, denoted as ArcGABA neurons) send direct inputs to corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVH, denoted as PVHCRH neurons), the primary regulators of the hypothalamic-pituitary-adrenal (HPA) axis. Although PVHCRH neurons exhibited time-locked activation in response to various environmental stressors, both GABA release onto PVHCRH neurons and the activity of PVHCRH-projecting ArcGABA neurons were selectively reduced during exposure to prolonged, high-intensity stressors, but not following exposure to transient, low-intensity stressors. Notably, GABA release onto PVHCRH neurons was positively correlated with PVHCRH-projecting ArcGABA neuron activity, yet anticorrelated with PVHCRH neuronal activity in response to the same prolonged, high-intensity stressors. Selective silencing of PVHCRH- projecting ArcGABA neurons was sufficient to elevate HPA axis activity and stress levels, phenocopying the effect of direct of PVHCRH neuron activation. Conversely, selective activation of PVHCRH-projecting ArcGABA neurons reduced both HPA axis activity and stress levels, this effect was completely abolished by concurrent excitation of PVHCRH neurons. Molecular identity screening further revealed that these PVHCRH-projecting ArcGABA neurons are not subsets expressing agouti-related peptide (AgRP) and tyrosine hydroxylase (TH) markers. Collectively, these findings indicate that the non-AgRP/TH ArcGABA→PVHCRH neurocircuit serves as a critical neural substrate that directly encodes the scalability of stress responses to environmental stressors by modulating inhibitory GABA release in a stimulus intensity-dependent manner.
Evaluating clinical practices in the management of non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) among pediatric gastroenterologists in Latin America. A cross-sectional descriptive study was conducted using a survey distributed via the REDCap platform. A total of 309 pediatric gastroenterologists and trainees from 17 Latin American countries (excluding Nicaragua and Bolivia) participated in the study. Data collection took place between March and May 2024. Sixty-five percent of respondents reported seeing fewer than five cases per year. Only 17.8% consistently collaborate with allergists. While 92.2% perform biopsies in all segments during endoscopy, just 80.9% send specimens in separate containers. Systematic endoscopic monitoring is carried out by 48.9% of practitioners. Ancillary tests such as fecal calprotectin (10.0%) and peripheral eosinophilia (19.4%) are infrequently used. The most common treatment strategies were proton pump inhibitors (44.4%) and elimination diets (40.1%), with systemic corticosteroids (17.4%), viscous budesonide (16.4%), and biologics (11.1%) being less frequently employed. There is considerable variability in clinical practice regarding non-EoE EGIDs across Latin America. These findings underscore the urgent need for consensus-based diagnostic and therapeutic guidelines and highlight the importance of ongoing medical education to improve patient care in this emerging field of pediatric gastroenterology.
Tuberculosis is a leading cause of death in South Africa, with poor adherence undermining treatment success. Findings from recent research on the impact of mHealth (mobile health) interventions on tuberculosis treatment outcomes show promise, yet many interventions remain untested in African contexts. Rising smartphone ownership in South Africa enables more complex mHealth interventions, offering an opportunity to deploy behavioral tools within high-burden, resource-constrained settings. This pilot study evaluates the feasibility and effectiveness, among low-income patients at a South African clinic, of a WhatsApp (Meta)-based conversational mHealth platform designed to tackle specific behavioral barriers to adherence. Aims include the following: (1) evaluating coverage by studying the proportion of patients within the target group who own smartphones, (2) describing patterns of engagement with the platform and the role of mobile data scarcity as a barrier to use, and (3) producing evidence on the impact that a behavioral mHealth intervention can have on tuberculosis treatment success. Patients newly diagnosed with drug-susceptible pulmonary tuberculosis between August 2022 and October 2023 completed a screening survey. Those owning compatible mobile phones were invited to enroll. The platform provided reminders alongside behavioral support features. Coverage was studied by estimating smartphone ownership among screened patients and comparing characteristics between enrolled patients (n=42) and those receiving standard care (n=102) using standardized differences. Engagement was analyzed using local polynomial regressions for usage trends and logistic regressions to estimate the impact of mobile data top-ups. The marginal effect of enrollment on the probability of successfully completing tuberculosis treatment was studied using a t test and logistic regressions with and without covariates. A total of 34% (49/146) of screened participants owned a phone that could use WhatsApp. There were differences in characteristics by enrollment status. Further, 50% of patients engaged with the platform each day until the end of treatment. Overcoming an initial inability to send unprompted messages to inactive patients was associated with an immediate 13-percentage-point increase in aggregate engagement the following month. Mobile data scarcity hindered use-receiving mobile data top-ups within the previous week was associated with a 3.37-percentage-point increase (95% CI 0.0007 to 0.0666) in platform engagement. The estimated marginal effect of enrollment was a 17.6-percentage-point (95% CI 0.003 to 0.348) increase in treatment completion, becoming attenuated after adjusting for patient characteristics (12.8 percentage points, 95% CI -0.048 to 0.304). While phone ownership and mobile data constraints represent barriers to feasibility, findings suggest that smartphone-based mHealth interventions may aid successful treatment completion-alleviating health system burdens by automating care for less vulnerable patients. Engagement with the platform throughout tuberculosis treatment was high and stable, and enrolled users experienced a higher success rate. A randomized controlled trial is required for impact evaluation.
Plant growth systems tested on the International Space Station (ISS) are small-area growth units that mostly use solid media. With NASA's plan to send astronauts on long-duration exploration missions, there is a need to produce larger amounts of fresh food with limited upmass and resources. The eXposed Root On-Orbit Test System (XROOTS) is an aeroponic-hydroponic nutrient delivery system designed for exploration missions and was tested on the ISS. Post-harvest samples were returned for microbiological analyses of the plant leaves, roots, and fruit from lettuce, mizuna mustard, wheat, radish, tomato, and pea plants grown in the XROOTS. The microbiological food safety of crops was evaluated through culture-based microbial enumeration and identification. The microbial communities were compared between different plants and plant tissues by sequencing the prokaryotic V4 variable region of the 16S ribosomal RNA (rRNA) gene amplicons and fungal internal transcribed spacer (ITS) region. The microbial counts from the root module surface samples demonstrated a reduction after cleansing. The bacterial counts in the nutrient solution ranged from 65 to 3,800 CFU/ml. The bacterial counts in the distal leaf sections were lower than those in the leaf proximal, wick, and roots in all plant samples. The tomato fruit and the pea pod samples had the lowest average counts. The microbial counts from the leaves and wicks harvested from XROOTS were similar to the ranges found on previous Veggie (Vegetable Production System)-grown leafy greens. All screening tests for potential foodborne pathogenic bacteria were negative. Sequencing analyses showed that diversity was low in the leaves and higher in the roots, and the microbial community was more diversified in the XROOTS samples compared with previous Veggie experiments. Pseudomonas had the highest relative abundance in the majority of samples. Although some microbes were shared in the majority of plant tissues, unique microbes were identified for each plant type grown in XROOTS and when compared with previous Veggie demonstrations. Microbial surveys of ISS-grown plants and the associated hardware provide valuable data that can reveal potential challenges in deep-space crop production operations and ensure the quality of crops intended for crew consumption.