Obesity is a heterogeneous chronic disease in which eating behavior phenotypes may influence treatment response. Yet, anti-obesity medication (AOM) selection is still largely guided by anthropometric and metabolic parameters, with limited use of behavioral phenotyping in routine practice. We evaluated whether multidimensional eating behavior changes, measured by the Brazilian Eating Behavior Phenotype Scale (Escala de Fenótipos do Comportamento Alimentar, EFCA), differ across commonly used AOMs in a real-world cohort. We conducted a retrospective, observational, real-world study in obesity outpatient care settings in São Paulo, Brazil. Adults with obesity (18-65 years) treated with a single principal AOM for 6 months and paired baseline/6-month follow-up EFCA and anthropometric data were included. Analyses focused on early responders (≥5% total body weight loss at 3 months). Five AOM groups available in Brazil were analyzed: semaglutide (oral or subcutaneous), naltrexone/bupropion, sibutramine, topiramate, and tirzepatide. Outcomes included percent weight loss, EFCA total score, and five EFCA subscales (hedonic, emotional, compulsive, hyperphagic, disorganized). Within-medication behavioral changes were assessed using paired tests and standardized effect sizes (Cohen's dz, 95% CI), summarized in heatmap form. The analytical cohort comprised 66 early responders with paired EFCA assessments at baseline and 6 months. EFCA profiling revealed distinct behavioral response fingerprints across AOMs. Effect size mapping showed predominantly large behavioral effects (many dz ≥ 0.8) in hedonic, emotional, hyperphagic, and compulsive domains. Strongest signals included emotional eating reductions with naltrexone/bupropion (dz 2.04), tirzepatide (dz 1.77), semaglutide (dz 1.52), and topiramate (dz 1.54); hedonic reductions with tirzepatide (dz 2.06), semaglutide (dz 1.55), and naltrexone/bupropion (dz 1.52); hyperphagic reductions with tirzepatide (dz 1.50) and semaglutide (dz 1.34); and compulsive reductions with topiramate (dz 1.41) and consistent effects across tirzepatide, semaglutide, and sibutramine (≈dz 0.95-0.96). Disorganized eating showed heterogeneous/attenuated responsiveness, from near-null with tirzepatide (dz 0.03) to large but imprecise effects in smaller groups (e.g., topiramate dz 1.24, wide CI). In this responder-enriched real-world cohort, AOMs showed distinct and reproducible EFCA behavioral signatures, supporting a clinically actionable phenotype-informed framework to prioritize, sequence, and monitor obesity pharmacotherapy beyond nonspecific weight reduction, while highlighting disorganization as a potential target for adjunctive behavioral strategies.
Disruption of social behavior is a core feature of autism spectrum disorder (ASD), yet the molecular and cellular mechanisms governing social behavior development are not well understood. We previously identified topoisomerase IIα (Top2a) as a critical regulator of social behavior and restricted and repetitive behavior through antagonism of polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), based mainly on pharmacological perturbations during embryogenesis in zebrafish and mouse. However, whether neuronal Top2a is genetically required for social behavior in mammals, and whether PRC2 inhibition can rescue genetically induced social deficits, remain untested. Here, we establish a neuron-specific Top2a conditional knockout mouse model and demonstrate that neuronal Top2a haploinsufficiency selectively impairs social interaction without inducing restricted and repetitive behaviors or cognitive deficits. Pharmacological inhibition of PRC2 using the EZH2 inhibitor tazemetostat, combined with elacridar to facilitated blood-brain barrier penetration, robustly rescues social deficits in Top2a conditional knockout mice. Strikingly, a one-week oral dosing regimen produced a rescue effect that persisted for up to two months after treatment cessation, far exceeding the temporal window typically observed for neuromodulatory drugs targeting neurotransmitter systems. These results showcase the unique capability of epigenetic modulatory therapy to induce durable behavioral improvements and their therapeutic potential for treating social dysfunction in neuropsychiatric disorders. Together, our results provide direct genetic evidence that neuronal Top2a governs social behavior in mice and establish the neuronal Top2a-PRC2 axis as a conserved, targetable epigenetic pathway regulating social behavior.
There is strong evidence supporting the efficacy of cognitive behavioral therapy (CBT) for the treatment of numerous clinical conditions commonly present in primary care. CBT interventions are time limited and goal directed, which allows them to be implemented within primary care settings. CBT techniques can be implemented effectively at the bedside at each stage of care throughout the lifespan to enhance mental and physical functioning. It is important for primary care clinicians to be empowered to utilize nonpharmacological techniques such as CBT while also recognizing the limits of their expertise and training in CBT.
This study examined whether a four-week mindful exercise intervention could enhance affective responses and promote exercise intention and behavior. We also tested whether affective valence during exercise and post-exercise enjoyment predicted these outcomes. Ninety-seven insufficiently active adults in the intention or preparation stage of exercise behavior were randomly assigned to mindfulness, distraction, or control conditions. Participants engaged in low- to moderate-intensity exercise two to three times per week for four weeks while receiving a guided mindfulness audio, a neutral podcast, or no audio, respectively. Affective valence, post-exercise enjoyment, exercise intention, and exercise behavior were assessed at baseline, post-intervention, and one-month follow-up. Linear mixed-effects models showed that mindfulness was associated with higher affective valence than distraction and control, and higher enjoyment and exercise intention than distraction, with smaller or nonsignificant differences relative to control. Exercise behavior increased at post-intervention and declined at follow-up, while remaining above baseline. Mediation analyses indicated that post-exercise enjoyment, but not affective valence, significantly mediated the intervention's effect on exercise intention. Findings suggest that mindfulness during exercise enhances affective experiences and exercise intention, which may support engagement in physical activity. However, behavior changes were not sustained at follow-up, underscoring the need for strategies that maintain long-term effects.
The management of type 2 diabetes requires sustained self-management across diet, physical activity, medication adherence, and blood glucose monitoring; however, maintaining these behaviors in daily life remains difficult for many patients. Artificial intelligence-enabled and mobile health interventions have shown promise in supporting diabetes education and self-management, but evidence on how patients actually experience and use such systems in real-world primary care remains limited. This study aimed to explore patients' experiences with the Artificial Intelligence-Based Health Education Accurately Linking System (AI-HEALS) and its perceived influence on self-management behaviors among patients with type 2 diabetes. This explanatory qualitative study was nested within the intervention arm of a cluster randomized controlled trial of AI-HEALS. Purposive maximum-variation sampling was used to recruit participants who varied by sex, age, diabetes duration, hemoglobin A1c level, digital literacy, and level of platform use. Of the 25 patients approached from the intervention arm, 17 agreed to participate. Semistructured interviews were conducted 3 months after the intervention (August to December 2023) with participants recruited from 45 communities in the Daxing and Shunyi districts of Beijing, China. The qualitative component was designed to explain perceived mechanisms of behavior change, contextual facilitators and barriers, and implementation-related experiences not captured by trial outcomes alone. Interview transcripts were analyzed thematically in NVivo 12 by 2 independent researchers using consensus coding, an audit trail, and member checking. Participants' experiences with AI-HEALS were reflected in four themes: (1) catalyzing health awareness and concern, (2) empowering self-management practices, (3) navigating usability and engagement, and (4) enhancing psychological adaptation. Participants perceived that AI-HEALS made diabetes more visible in daily life through repeated reminders and accessible educational content; supported practical self-management decisions related to diet, physical activity, medication adherence, and glucose monitoring; and, in some cases, improved confidence while reducing uncertainty and diabetes-related stress. The findings also suggested meaningful variation in how the intervention was experienced, particularly in relation to prior illness experience, routine stability, social support, and digital confidence. Many participants mainly engaged with lower-burden features such as pushed articles and reminders, whereas more interactive functions, such as the chatbot, were used less often. Patients generally perceived AI-HEALS as a useful source of ongoing education, behavioral prompting, and everyday support for diabetes self-management. The findings suggest that artificial intelligence-enabled education may work not only by increasing knowledge but also by reinforcing awareness, translating guidance into feasible daily action, and supporting psychological adaptation. At the same time, the intervention's perceived usefulness depended on whether its content was understandable, low burden, and compatible with users' routines. These results support further refinement of literacy-sensitive, layered digital interventions and their integration into routine community-based primary care.
Background/Objectives: Chronic inflammation is a fundamental biological process underlying aging and frailty. We recently demonstrated that an anti-inflammatory diet, assessed using the Dietary Inflammatory Index (DII), was associated with serum high-sensitivity C-reactive protein levels and frailty incidence among community-dwelling older adults. The present study aimed to co-produce behavior change intervention promoting an anti-inflammatory diet by participatory action research with older adults. Particularly, increasing intake of dietary fiber was targeted as it represents a nutrient with the highest anti-inflammatory potential within the DII framework. Methods: Participants were community-dwelling older adults engaged in frailty checkup activity. Six co-production workshops were conducted between May 2022 and February 2023, integrating semi-structured group work and scientific evidence. Participant satisfaction was assessed after each session. Changes in dietary behavior were evaluated using DII score and dietary intake assessed by the Brief Self-Administered Diet History Questionnaire (BDHQ). Results: A cumulative total of 66 participants was involved (mean age, 73.7 ± 4.8 years; 80.0% women). When compared before and after co-production workshops, total DII scores and DII scores calculated by anti-inflammatory nutrients significantly decreased (p = 0.031 and p = 0.020, respectively). Dietary fiber intake also significantly increased following the workshop (p = 0.044). Among dietary fiber-rich food groups, mushroom consumption showed a particularly significant increase (p = 0.048). Conclusions: Co-production workshops integrating group work and scientific evidence were effective in promoting behavioral changes toward an anti-inflammatory diet among community-dwelling older adults. This developed intervention may represent a feasible and practical dietary strategy for frailty prevention in community settings.
Baichuan Baile (BCBL) is a novel herbal formula composed of three herbs and a food additive with proven antidepressant-like effects. However, its unclear bioactive constituents hinder quality control. This study evaluated BCBL-CP, a fraction extracted via ethanol precipitation and macroporous resin chromatography, mainly comprising coumarins (5-hydroxyxanthotoxin, oxypeucedanin hydrate, byakangelicin) and phthalides (senkyunolides H and I). We rapidly assessed BCBL-CP's efficacy using behavioral despair and 5-hydroxytryptophan-induced head-twitch tests. Subsequently, therapeutic effects on a reserpine-induced depression-like mouse model were evaluated through behavioral assessments. Its effects on the monoaminergic system, cerebral pathology, brain-derived neurotrophic factor (BDNF), and gut microbiota were detected through enzyme-linked immunosorbent assay, hematoxylin and eosin staining, immunofluorescence, and 16S rDNA sequencing. Results showed BCBL-CP exhibited significant antidepressant-like activity in both acute behavioral screening and chronic reserpine-induced depression studies. Mechanistically, BCBL-CP selectively increased prefrontal norepinephrine (p < 0.05), attenuated neuronal damage (p < 0.001), and showed a trend toward BDNF upregulation (p = 0.083). Uniquely, it restored gut microbiota α-diversity (p < 0.01), normalized β-diversity, and modulated eight key bacterial taxa (p < 0.01 or p < 0.05). These findings confirm that these five compounds constitute the major characteristic bioactive constituents of BCBL, providing quality-control markers for developing this prospective antidepressant.
Cholangiocarcinoma (CCA) is an aggressive malignant tumor with extremely poor prognosis, and its global incidence is increasing, posing a growing public health burden. Behavioral factors, such as diet, alcohol consumption, smoking, physical activity, and psychological status, are closely associated with the development of CCA. This narrative review delves into the multidimensional burden of CCA, including psychological distress, symptom profiles, and socioeconomic impacts. It also summarizes evidence from related gastrointestinal cancers to explain the biological mechanisms through which lifestyle modifications may improve prognosis, including immunomodulation, inflammatory cascades, and metabolic reprogramming. Furthermore, we propose an integrated framework for behavioral medicine and hepatobiliary care, emphasizing the pivotal role of behavioral interventions in enhancing CCA prevention and clinical outcomes.
Retinitis pigmentosa (RP) is a leading cause of inherited blindness, yet current gene supplementation strategies are limited by heterogeneous responses, with more than 40% of patients showing insufficient rescue. Moreover, oxidative stress constitutes a defining pathological feature of RP and critically impairs the efficacy of gene therapy. Consistently, transcriptomic and ultrastructural analyses of Pde6brd10/rd10 (rd10) retinas revealed early and progressive dysregulation of oxidative stress-related pathways and photoreceptor degeneration. To overcome this barrier, we engineered an adeno-associated virus (AAV) vector covalently conjugated with a catalytic G-quadruplex-hemin DNAzyme (CoG4) via genetic code expansion and click chemistry. This design enables synchronized delivery of CoG4 and therapeutic Pde6b into photoreceptors, where CoG4 directly scavenges excess ROS and restores mitochondrial homeostasis, thereby creating a favorable microenvironment for gene supplementation. In rd10 mice, AAV-CoG4 treatment resulted in sustained expression of Pde6b, preservation of photoreceptor morphology, restoration of rod and cone function as evidenced by electroretinogram, and improved visual behavior, outperforming AAV or CoG4 monotherapies. Our findings establish oxidative stress as a major barrier to retinal gene therapy and demonstrate a dual-function platform that couples microenvironment modulation with genetic correction, offering a broadly applicable strategy for treating degenerative retinal diseases.
To date, only one behavior analytic study has systematically examined the use of functional analysis to assess arranging and ordering, which is a form of higher level restricted and repetitive behavior (Rodriguez et al., 2012). The researchers found that arranging and ordering was automatically maintained and developed efficacious interventions that involved some form of prompting and response disruption. The current study applied the Hagopian et al. (2020) treatment model (i.e., augmented competing stimulus assessments) for automatically maintained self-injury to higher level repetitive behavior. A variety of pretreatment assessments including preference assessments, functional analyses, process-versus-product analyses, and augmented competing stimulus assessments were conducted to inform treatment. Following treatment, generalization probes were conducted. For all four participants, efficacious treatments were identified that consisted of providing competing stimuli identified via the augmented competing stimulus assessment.
A rare spindle cell tumor with skeletal muscle phenotype, male predilection, exclusive involvement of the head and neck region, particularly the tongue, and a suggested indolent course has been previously reported as VGLL3-rearranged spindle cell rhabdomyosarcoma (SRMS). We report 18 cases with extended clinical follow up, detailed molecular results, and methylation profiling. Tumors occurred in 5 females, 12 males, and 1 patient of unknown sex with median age of 58 years (range: 22-71). Tumors involved tongue (n=13), lower lip (2), retropharyngeal region (n=1), thyroid/parathyroid (n=1), and palatine tonsil (1) with median size of 1.2 cm. Treatment details (15 patients) revealed that 13 patients underwent excision only, while 1 patient underwent adjuvant chemotherapy and 1 adjuvant radiation therapy. Follow-up (11 patients) showed no local recurrence or metastases. At last follow-up (median: 45 months, range: 1- 326 months) all patients were alive without evidence of disease. Histologically, tumors showed spindled to histiocytoid cells arranged in a fascicular, storiform or haphazard architecture with variably collagenous stroma, rounded to infiltrative borders and often diffusely growing through skeletal muscle, adipose tissue, and entrapped nerves. Necrosis was consistently absent with a median mitotic rate of 1/10 HPFs (range: 0-7/10). By immunohistochemistry, tumors diffusely expressed desmin (n=18), multifocal MyoD1 (n=15) and/or myogenin (n=12), and sometimes SMA (n=7). Molecular testing revealed EP300::VGLL3 (n=6), TCF12::VGLL3 (n=5), and PPARGC1A::VGLL3 (n=1) fusions with VGLL3-rearrangement by fluorescence in situ hybridization (FISH) in 3 cases. One archival tumor failed molecular and methylation testing despite multiple attempts, likely due to decreased DNA/RNA integrity, yet was included given classic morphological features. Methylation data (n=12) revealed all but 1 tumor to form a distinct group separate from other fusion-driven rhabdomyosarcomas, including 5 infantile/congenital SRMS. We describe a well-characterized series of these rare tumors with extended follow-up data confirming lack of progression or recurrence. Further, our DNA methylation profiling data supports these tumors to form a distinct cluster, regardless of VGLL3 fusion partner, and separate from morphologic mimics and other fusion-driven SRMS, including 5 cases of congenital SRMS. We propose that these neoplasms may be better classified as VGLL3-rearranged spindle cell rhabdomyoblastic tumors to reflect their indolent behavior and to prevent overtreatment.
This study aimed to explore the possibility of using a novel eye drop for ocular pain in dry eyes by examining the effect of tramadol eye drops on nocifensive behavior in normal and dry eye rats. Dry eye model rats were generated by the unilateral surgical excision of the extraorbital lacrimal glands. The effect of tramadol eye drops on ocular pain in normal and dry eye model rats was assessed using the eye closure time induced by a hyperosmolar (5 M NaCl) solution and the transient receptor potential vanilloid 1 (TRPV1) agonist (1 mM capsaicin). The current response induced by 1 μM capsaicin in the primary sensory neurons was measured by whole-cell recording using cultured trigeminal ganglion neurons. Extraorbital lacrimal gland excision (LGE) significantly enhanced the ocular nocifensive response induced by a 5 M NaCl solution. Pretreatment with tramadol eye drops transiently suppressed nocifensive behavior on the ocular surface in sham-operated and dry eye rats. The suppressive effect of tramadol was only effective on the ipsilateral eye and was not canceled by a μ-opioid receptor antagonist. Furthermore, the capsaicin-induced nocifensive behavior and current responses in primary sensory neurons were suppressed by tramadol treatment. Tramadol eye drops have been shown to temporarily relieve ocular pain in normal and hyperalgesic conditions, such as dry eye. The underlying mechanism may be a decrease in TRPV1-mediated responses at the peripheral sensory nerves on the ocular surface, not primarily mediated by μ-opioid receptor activation.
A growing body of original research has recently investigated virtual reality (VR)-based interventions for physical activity and self-management, yet yielded inconsistent results. This systematic review and meta-analysis aims to evaluate the effectiveness of VR-based physical activity and self-management interventions in improving glycemic control and modifying health-related behaviors among patients with type 2 diabetes mellitus (T2DM). A total of 10 studies involving 1,005 adults with T2DM were included, comprising 5 randomized controlled trials (RCTs), 1 non-randomized controlled trial (nRCT), and 4 self-controlled before-after studies. Of these, participants in the intervention groups received VR-based interventions, including immersive or interactive VR programs for diabetes self-management education or physical activity promotion, with most intervention durations ranging from 8 to 24 weeks. Control groups received traditional approaches, including routine care, in-person diabetes self-management programs, and content-equivalent 2D websites. The pre-post intervention analysis revealed that glycated hemoglobin (HbA1c) levels decreased significantly post-intervention (mean difference (MD) = -0.50, 95% CI: -0.92 to -0.08, p = 0.02). While VR-based physical activity and self-management interventions did not demonstrate superior efficacy to traditional intervention methods in glycemic control or behavioral outcomes, their unique advantages - including enhanced adherence, greater accessibility, and reduced spatiotemporal constraints - position them as a viable alternative for diabetes management. Nevertheless, the field requires more rigorously designed RCTs to establish efficacy and a systematic exploration of VR implementation protocols to maximize therapeutic benefits.
Multiple sclerosis (MS) is a chronic demyelinating and autoimmune disorder of the central nervous system characterized by immune-mediated damage to oligodendrocytes and myelin sheaths. To model demyelination, we used the cuprizone paradigm in male C57BL/6 mice, in which copper chelation induces selective oligodendrocyte toxicity and glial activation. This model produces behavioral and motor disturbances, including cognitive impairment, anxiety-like behavior, and reduced motor performance. Vortioxetine, a multimodal serotonergic antidepressant, acts through inhibition of the serotonin transporter and modulation of multiple neurotransmitter systems. Emerging evidence suggests that vortioxetine may exert neuroprotective and anti-inflammatory effects, making it a potential candidate for neuroinflammatory conditions. In this study, male C57BL/6 mice were administered cuprizone for five weeks to induce demyelination, and vortioxetine was delivered intraperitoneally to evaluate its effects on neuroinflammation, anxiety-like behavior, spatial memory, and object recognition. Cytokine levels (TNF-α, IL-1β) were quantified using ELISA, and behavioral performance was assessed using the open-field, elevated plus maze, Y-maze, and object location recognition tests. Vortioxetine significantly attenuated cuprizone-induced increases in proinflammatory cytokines in cortical tissue and improved anxiety-like behavior and cognitive performance without altering general locomotor activity. These findings demonstrate that vortioxetine exerts anti-inflammatory and neurobehavioral effects in the cuprizone-induced demyelination model. The observed modulation of cytokine levels and behavioral outcomes suggests potential relevance to neuroinflammatory conditions such as MS; however, further studies are required to establish its therapeutic efficacy in clinical settings.
Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors that impair functioning. Although selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are first-line treatments, 40-60% of patients achieve only partial remission, with persistent symptoms and adverse effects. This highlights the need for alternative approaches such as phytotherapy, which has shown potential neuroprotective and neurotransmitter-modulating properties. A structured narrative review with a systematic search was conducted across PubMed, Scopus, Web of Science, and Google Scholar up to April 2025. Studies evaluating medicinal plants or phytochemicals in OCD or OCD-like behavior were included. Both preclinical in vivo and human studies were assessed. A total of 26 studies (14 preclinical, 12 clinical) were included and appraised using a multi-domain quality framework and evidence hierarchy. Preclinical studies indicated that several plant-derived compounds influence serotonergic, dopaminergic, and GABAergic systems and reduce OCD-like behaviors. However, most relied on non-specific models such as marble-burying, limiting interpretability. Clinical evidence was limited, with few randomized controlled trials and several low-quality or observational studies. While some interventions showed symptom improvement, methodological weaknesses and small sample sizes reduced reliability. Current evidence does not support clinical recommendations for phytotherapy in OCD. Findings remain preliminary and hypothesis-generating. Future research should focus on well-designed clinical trials, standardized formulations, and translationally valid models to establish efficacy and safety.
Cancer is among the fatal diseases that affect individuals worldwide. According to World Health Organization statistics, if the current trends continue, the world will see a significant increase in cancer cases over the next two decades, leading to a staggering number of deaths by 2040. Therefore, finding innovative strategies for cancer treatment has become a critical priority. Recently, magnetic nanoparticles (MNPs) have been widely applied in cancer diagnosis via magnetic resonance imaging, in hyperthermia, and in drug delivery to specific organs due to their unique physicochemical properties. However, the most significant challenge of using MNPs is ensuring compliance with in vivo nano-safety regulations. This review discusses the MNP characteristics necessary for biomedical applications, followed by a description of their physical, chemical, and magnetic properties. Additionally, the preparation of MNPs and the development of a superior method suitable for magnetic drug delivery and hyperthermia applications are surveyed. Furthermore, their physicochemical properties and their effects on biocompatibility, biodistribution, and pharmacokinetic behavior, are reported. The functionalization and surface modification of MNPs, which are intensively exploited in cancer treatment, particularly for drug delivery and hyperthermia, are demonstrated. Some studies of the incorporation of MNPs in the diagnosis, treatment, and imaging of cancer are summarized. Furthermore, the effects of combining antineoplastic drugs via drug delivery systems with hyperthermia treatment to achieve an efficient synergetic effect are extensively reviewed. This review article provides an overview of recent innovations, future challenges, prospects, and developments that advance MNP therapeutic applications, particularly in oncology.
Although berberine possesses notable anti-inflammatory and antioxidant properties for ulcerative colitis (UC) treatment, its clinical utility is limited by poor oral bioavailability. To enhance berberine delivery, we engineered Eudragit® S100/Bletilla striata polysaccharide(EB)-coated berberine hydrochloride (BH)- hydrogenated soy phosphatidylcholine complex(HSPC) microspheres(MPs) a colon-targeted mucoadhesive micro‑nanocomposite. This system encapsulates a solubility-enhanced berberine‑phospholipid complex within microspheres coated with Eudragit® S100 and Bletilla striata polysaccharide (BSP). BSP serves a dual role as a bioadhesive carrier for prolonged mucosal retention and an immunoregulatory agent that synergizes with berberine. Utilizing electrospray and fluidized‑bed coating, the formulation achieved pH‑responsive, colon‑specific release. In vitro, the formulation exhibited favorable pH-dependent controlled release behavior, effectively scavenged reactive oxygen species, and promoted macrophage polarization towards the anti-inflammatory M2 phenotype. In DSS-induced acute and FXY-DSS-induced Spleen Deficiency chronic colitis models, EB@BH-HSPC significantly alleviated inflammation, restored intestinal barrier function, and attenuated oxidative stress, achieving improved therapeutic outcomes. It could be attributed to the synergy of berberine and BSP, combined with the integrated delivery advantages of improved solubility, precise colon targeting, and extended mucosal retention. In this system, BSP functions not only as an excipient but also as a synergistic therapeutic component with berberine. With its colon-targeting and mucoadhesive properties, the system provides a potent and integrated strategy for the treatment of ulcerative colitis.
Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive sarcoma that predominantly affects adolescents and young adults. It is defined by a characteristic chromosomal translocation, t(11;22) (p13;q12), resulting in the EWS-WT1 fusion gene. Owing to its rarity and aggressive behavior, optimal treatment strategies remain poorly established. We report the case of a 35-year-old male who presented with progressive abdominal pain, bloating, and early satiety. Imaging revealed an intra-abdominal mass, and histopathological evaluation with immunohistochemistry confirmed the diagnosis of DSRCT. Molecular confirmation of the EWS-WT1 fusion was not performed. The patient underwent cytoreductive surgery followed by early postoperative intraperitoneal chemotherapy (EPIC) and intensive systemic chemotherapy. Although initial disease control was achieved, the patient subsequently developed peritoneal recurrence and isolated liver metastasis requiring multiple lines of salvage chemotherapy and liver metastasectomy. Despite aggressive multimodal management, the disease demonstrated progressive chemoresistance. DSRCT is characterized by an aggressive clinical course with a high risk of recurrence and distant metastasis. This case is distinguished by adult age at presentation, the use of EPIC combined with systemic therapy, liver metastasectomy, and a relatively prolonged survival compared with historical series. It highlights the limitations of current treatment strategies and the urgent need for novel systemic and targeted therapies in DSRCT.
Sexual attractiveness of neutered male dogs to other male dogs is a frequently reported phenomenon of unknown pathophysiology. As gonadectomized dogs exhibit elevated luteinizing hormone (LH) concentrations, this study evaluated the efficacy of deslorelin implants in a double-blinded randomized controlled trial (RCT) to mitigate sexual attractiveness. Thirty gonadectomized male dogs attractive to other dogs were recruited for this RCT. One group (n = 15) received a 4.7 mg deslorelin implant (Suprelorin® 4.7 mg, Virbac, France) and another group (n = 15) received a placebo implant. Following the implantation, owners documented behavior after 30-45, 90, 180 and 270 days. Additionally, blood samples were collected on days 0, 30-45 and 270 to determine follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. Sexual attractiveness developed within 12 months after castration in all dogs. Reduced attractiveness was observed in 11 of the 15 deslorelin-treated dogs compared to 5 of the 15 placebo-treated dogs. The overall treatment effect for behavioral improvement (across all timepoints) amounted to an odds ratio (OR) of 5.47 (p = 0.017). The LH concentration decreased to basal levels in the deslorelin group but remained unchanged in the placebo group, whereas FSH concentrations stayed elevated in both groups. Deslorelin implants are a promising option, reducing sexual attractiveness in approximately three quarters of affected dogs. Additionally, our study revealed that deslorelin reduces elevated LH but not FSH concentrations in gonadectomized dogs. Further research is needed to validate long-term efficacy, determine optimal dosages and implantation intervals, and consider the use of additional behavioral therapy.
Insomnia is a common reason for patients to seek medical care. A careful history should be obtained to identify predisposing, precipitating, and perpetuating factors contributing to sleep disturbance. Cognitive behavioral therapy for insomnia is the first-line treatment for chronic insomnia, offering effectiveness with minimal risk, though access may be limited by availability. Pharmacologic therapy should ideally be reserved for short-term use and initiated only after setting clear expectations and considering potential risks. Evidence-based medication options include low-dose doxepin, melatonin receptor agonists, dual orexin receptor antagonists, and nonbenzodiazepine benzodiazepine receptor agonists. Ongoing follow-up is essential to monitor treatment response.