Protein-losing enteropathy (PLE) is a rare but serious complication of the Fontan procedure in patients with single-ventricle physiology. It results from excessive loss of plasma proteins into the gastrointestinal tract, leading to hypoalbuminemia, edema, and ascites. We report the case of a 10-year-old girl with hypoplastic left heart syndrome who underwent staged surgical palliation including the Norwood procedure, bidirectional Glenn shunt, and extracardiac Fontan completion. She presented with progressive abdominal distension, peripheral edema, and severe hypoalbuminemia (albumin 2.3 g/dl). Echocardiography and cardiac catheterization demonstrated a patent Fontan circuit with normal pulmonary artery pressures and no significant obstruction, although the inferior vena cava pressure was mildly elevated at approximately 16 mmHg. The patient was managed with intravenous albumin replacement, diuretics, anticoagulation, sildenafil, and oral budesonide. This case highlights the diagnostic challenges of PLE and emphasizes the importance of early recognition and multidisciplinary management, even in the absence of significant Fontan circuit obstruction, as elevated systemic venous pressure and lymphatic dysfunction may both contribute to disease development. Protein-losing enteropathy is a rare but potentially life-threatening complication of Fontan circulation. It should be suspected in patients with a history of Fontan palliation who present with unexplained hypoalbuminemia, edema, or ascites, even when no significant Fontan circuit obstruction is identified, as elevated systemic venous pressure and lymphatic abnormalities may contribute to disease development. Early recognition and multidisciplinary management are essential to improve clinical outcomes and guide further evaluation of underlying lymphatic abnormalities.
Protein-losing enteropathy (PLE) is a rare syndrome characterized by excessive, nonspecific loss of serum proteins through the gastrointestinal tract. More than 60 distinct conditions across organ systems have been associated with PLE. The presentation is often nonspecific-manifesting as edema, diarrhea, or malnutrition-leading to delayed recognition. Protein-losing enteropathy arises through mucosal injury or lymphatic dysfunction. Evaluation requires exclusion of hepatic, renal, and nutritional causes, followed by targeted testing with stool α1-antitrypsin and upper or lower endoscopy. Early identification enables prompt management of nutritional, immune, and thrombotic complications while also facilitating the detection of secondary causes that may be treatable or reversible. This review provides a practical overview of PLE's pathophysiologic mechanisms, clinical features, diagnostic approach, and indications for subspeciality referral.
The purpose of this study was to describe the experiences of women with pelvic congestion syndrome (PCS). We aimed to (1) explore the experiences before receiving a PCS diagnosis, (2) describe the experience of being diagnosed and living with PCS, and (3) identify challenges with ongoing pelvic pain after PCS treatment. A descriptive qualitative design with a purposive sampling method was used. Women with PCS were recruited from a Facebook PCS support group between October 2023 and February 2024. Participants completed a demographic survey, then participated in a semi-structured interview via Zoom. Data were transcribed verbatim and verified for accuracy. A modified iterative seven-step descriptive data analysis method was used to examine data, compare codes, challenge patterns, and inductively and deductively develop themes. Nine women completed the study. Six essential themes characterized the experience of living with CPP after treatment for PCS: (1) life before diagnosis; (2) diagnosis journey; (3) pain descriptors and co-occurring symptoms; (4) impaired quality of life; (5) being a burden to family and friends; and (6) losing all faith in women's healthcare and the system. This was the first qualitative study of women with ongoing and recurring pelvic pain after treatment for PCS. Findings highlighted the significant challenges women faced even after treatment for PCS, indicating a need for improved assessment strategies that better capture the severity and complexity of PCS symptoms.
Continuity of care with a family physician (FP) is a core attribute of effective primary care and is associated with improved health outcomes, reduced service use and lower healthcare costs. In Canada, an ageing FP workforce has led to an increasing number of patients losing their FP, raising concerns about access to care and disruptions in care trajectories. While the benefits of continuity are well documented, evidence on the consequences of discontinuity in primary care, particularly from the patient perspective, remains limited. Relational discontinuity occurs when there is a disruption in the relationship between an FP and a patient, which may be related to the FP's retirement or relocation or to the closure of a clinic. This study aims to assess the effects of a disruption in the relational continuity with an FP on patient's experience and their patterns of healthcare service use. A descriptive cross-sectional survey will be administered to adults residing in Quebec, Canada's second most populous province. A total sample of 1000 respondents will be recruited, including approximately 500 individuals who have lost their FP within the past 3 years, and 500 individuals currently registered with an FP. The questionnaire covers sociodemographic characteristics, health status, access to care, use of healthcare services, out-of-pocket costs and perceived impacts of discontinuity. Descriptive and regression analyses will be used to compare experiences and perceived effects between groups and to explore equity-related differences. The study has received ethical approval from the Research Ethics Board involving human participants at Université Laval. Findings will be shared with policymakers and healthcare stakeholders to inform them on the patient-reported consequences of primary care discontinuity and support the development of strategies to mitigate its impacts.
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The generation of highly plastic cell states in colorectal cancer that are prone to metastatic dissemination involves complex epigenetic reprogramming, rather than new genetic traits. Goto et al.1 implement a serial orthotopic organoid transplantation framework to uncover the idea that losing Gata6, a guardian of the colonic lineage, promotes metastatic competence.
Taking photos is a ubiquitous everyday activity, woven into social life from classrooms and meetings to travel and social gatherings. Photography is known to impair memory for photographed experiences, a phenomenon termed the photo-taking impairment effect (PTIE), but prior work has focused solely on the photographer. The present research introduces and tests a social extension of this phenomenon: One person's photo-taking activity can impair a nearby companion's memory for the same event, which we term the companion-PTIE. Across four experiments spanning controlled laboratory tasks and a simulated art exhibition, we show that photo-taking reduces a nonphotographing companion's subsequent memory to a degree comparable to taking photos oneself. Mechanistically, we dissociate cognitive offloading from attentional disengagement. Instructing photographers to delete each photo immediately, thereby removing any expectation of later access, left both the self- and companion-PTIE unchanged, arguing against cognitive offloading as a primary driver. By contrast, preventing a nonphotographing companion from seeing the act of photo-taking with an opaque barrier abolished the companion-PTIE, implicating attentional disengagement as the causal pathway. Robust Bayesian meta-analyses estimated a reliable companion-PTIE with no meaningful difference in magnitude from the self-PTIE. These findings reframe the PTIE as a social phenomenon: The memory costs of ubiquitous photography extend beyond photographers to copresent others, revealing how everyday technologies reshape collective memory for shared experiences. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
In this narrative medicine essay, a psychiatric resident tries to process the loss of a patient to suicide.
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This study examined bidirectional longitudinal associations between grit dimensions (consistency of interest [CI] and perseverance of effort [PE]) and problematic smartphone use (PSU) and tested cognitive flexibility as a mediating mechanism. A sample of 1,641 Chinese university students (55.2 percent female; Mage = 20.1 years) completed measures at two time points 6 months apart. A four-variable cross-lagged panel model revealed that CI and PSU negatively predicted each other over time, whereas PSU unidirectionally predicted decreased PE. Cognitive flexibility partially mediated the PSU-to-PE pathway (indirect effect = -0.004, 95 percent bootstrap CI [-0.010, -0.0001]). Competing models analysis confirmed this directionality: the forward mediation (PSU → cognitive flexibility → PE) was significant, whereas the reverse was not. These findings demonstrate that grit dimensions exhibit distinct longitudinal patterns with PSU and identify cognitive flexibility as a cognitive mechanism through which PSU specifically undermines effort persistence. Implications for dimensional approaches to grit and targeted interventions are discussed.
This study aimed to describe the phenomenon of losing human life by suicide, based on the lived experiences of suicide survivors and professionals. Phenomenological participatory action research was conducted, comprising 50 group sessions with 51 participants including suicide survivors, registered nurses, response police officers, and general practitioners. The essence of losing human life through suicide is characterized by profound emotional vulnerability when confronted with an existential tragedy. This means a powerlessness and an abrupt shift in existence, awakening the instinct to escape and the responsibility to act. Being the messenger of death is a heavy burden, and a sense of abandonment arises when survivors are left alone. Simply being together as human beings awakens a sense of vulnerability and a strong impulse to uphold human dignity. These findings underscore that everyone involved is vulnerable to existential challenges following suicide and provide insight into the fragility of humanity. Professionals need awareness of their own vulnerability and moral courage to encounter survivors as fellow human beings. Support for survivors should acknowledge that grief and existential suffering do not follow fixed timelines. The methodological combination of phenomenology and participatory action research proved fruitful, generating rich insights and offering a promising approach for future studies.
Cancer disrupts AYAs' school/work-related opportunities during a developmental phase when learning-related experiences are central to AYAs' growth and future outcomes. The National Comprehensive Cancer Network (NCCN) recommends clinics implement school/work support, but guidance is needed on what types of support to implement feasibly. We aimed to understand AYAs' needs by comparing narrative accounts from AYAs, parents, and clinicians. A secondary thematic analysis was conducted on two interview study datasets combined to compare three stakeholder groups' experiences: Parents of diagnosed AYAs (age 15-29), AYAs, and clinicians. Data from each group were inductively analyzed and triangulated to capture similarities/differences. 32 interviews represented three stakeholder groups: 10 AYAs, 15 parents, 7 clinicians. All groups described school/work-related challenges in four areas: advocating for accommodations, losing extracurricular activities, navigating disrupted expected trajectories, and losing peer social connection. Parents and AYAs stressed a positive impact (school/work promoting empowerment) heightening the importance of protecting school/work experiences. Findings highlighted specific supports to implement in each area, with distinct insights made by each stakeholder group. Findings offer a roadmap to implementing the NCCN's "educational and career services" directive by identifying the types of supports to implement and how. AYAs and families would benefit from oncology teams providing accommodation guidance with integrated clinical advocacy tools, flexible practices that prioritize AYAs' socialization, and psychosocial support for grief coping, social skill development, and career decision making. Prioritizing school/work-related supportive care can be a feasible, patient-centered way to improve quality of life across the AYA cancer trajectory.
Failing Fontan is an increasingly recognised complication after total cavopulmonary connection, yet longitudinal biomarker data remain scarce. We aimed to characterise the incidence, biomarker trajectories, and prognostic determinants of failing Fontan. All patients who underwent primary total cavopulmonary connection (n = 650) or conversion to total cavopulmonary connection (n = 19) at our centre between 1994 and 2022 were reviewed. Lymphocyte count, N-terminal pro-brain natriuretic peptide and its zlog value, and Fibrosis-4 index were assessed at 1 year before, 6 months before, at onset, and at last follow-up. Patients were classified into protein-losing enteropathy/plastic bronchitis and heart failure phenotypes. Failing Fontan developed in 78 primary total cavopulmonary connection patients (12.0%) and 12 conversion patients (63.2%). Conversion patients developed failing Fontan earlier (P < 0.001), but survival after onset survival was comparable. Lymphocyte counts declined before onset (2.49 to 0.89 ×10³/µL, P < 0.001) and Fibrosis-4 index increased (0.060 to 0.330, P < 0.001). Phenotypes showed divergent profiles: zlog-N-terminal pro-brain natriuretic peptide at onset was 0.71 in protein-losing enteropathy/plastic bronchitis versus 5.34 in heart failure (P < 0.001). Lymphocytopenia predicted mortality early (hazard ratio 6.77, P = 0.013) but appeared protective at last follow-up (hazard ratio 0.18, P = 0.049), reflecting a phenotypic shift. On multivariable analysis, lower lymphocyte count independently predicted mortality (hazard ratio 2.44, P = 0.041), while stent implantation was independently associated with lower mortality (hazard ratio 0.32, P = 0.040). Lymphocyte counts and Fibrosis-4 index change progressively before clinical onset and may serve as early warning biomarkers. The prognostic interpretation of lymphocytopenia depends on the underlying phenotype, underscoring the need for phenotype-aware monitoring.
After what most Kenyans experienced as the "end of Covid" in 2021-22, material remains of anti-epidemic measures, biological traces such as long covid, and memories of deaths persisted. While infection itself left few visible material traces, paraphernalia of its control - masks, tests, handwashing stations, and routines - proved more durable, although often losing or changing their function and meaning. This paper examines Covid-19 residues in western Kenya, their state and use, the meanings people assign, and how they disappear or sediment among leftovers of other epidemics, shaping future pathways unpredictably. We reflect on the afterlives of epidemics in Kenya and elsewhere.
Endothelial-to-Mesenchymal Transition (EndMT) is a significant contributor to Blood- Brain Barrier (BBB) dysfunction in various brain diseases. The majority of current therapies, aimed at reducing BBB dysfunction, focus on preventing inflammation or stabilizing tight junctions. In most cases, these therapies do not provide adequate or long-lasting vascular protection. Endothelial cells undergo phenotypic programming, losing their barrier-forming capacity and developing features of mesenchymal and extracellular matrix-producing cells as the disease progresses. The change leads to chronic vascular leakage, neuroinflammation, microvascular fibrosis, and dysfunctional neurovascular coupling. Several upstream stimuli, including inflammatory cytokines, TGF-β/BMP-Smad signaling, and oxidative damage, converge to drive EndMT within the distinctive, specialized environment of the brain endothelium. Ischemic stroke, multiple sclerosis, cerebral cavernous malformations, arteriovenous malformations, glioblastoma, brain metastasis, and Alzheimer's disease indicate that EndMT is not a rare or unique process but a shared and common pathologic process that may result in disease progression and eventual resistance to treatment. Recent single-cell and spatial transcriptomic data have shown that partial EndMT states exist and may be precursors to irreversible microvascular remodeling. It is necessary to identify therapeutic approaches that go beyond short-term stabilization of the BBB and target the molecular programs underlying the loss of endothelial identity. This review synthesizes mechanistic, disease-related, and therapeutic evidence indicating that EndMT is a leading cause of BBB failure and highlights therapeutic opportunities for targeting this endothelial plasticity in brain diseases.
Insulin edema syndrome is a rare and underrecognized complication of insulin initiation or intensification, characterized by peripheral or generalized edema. Its pathophysiology is multifactorial, involving renal salt retention, increased capillary permeability, and vasodilation, and it is often a diagnosis of exclusion. We report the case of a 41-year-old man with newly diagnosed type 2 diabetes mellitus presenting with hyperglycemia (772 mg/dL) and marked weight loss. After initiation of insulin glargine and lispro, he developed rapid-onset generalized edema, including scrotal and lower extremity swelling, weight gain of 32 pounds, dyspnea, and pleural effusions. An extensive workup excluded cardiac, renal, hepatic, infectious, autoimmune, and protein-losing enteropathy etiologies. The edema worsened with higher insulin doses despite treatment with diuretics and corticosteroids. Transition to NPH (neutral protamine Hagedorn) and regular insulin, with adjunct dapagliflozin, resulted in rapid resolution of the edema, allowing discontinuation of the diuretics. Risk factors for insulin edema include newly diagnosed diabetes, rapid glycemic correction, low body weight, and high insulin doses. While generally self-limiting, severe or refractory cases may require diuretics or modification of the insulin regimen. Recognition is critical to avoid unnecessary interventions and to manage symptoms effectively. Insulin edema syndrome should be considered in patients presenting with unexplained edema after insulin initiation. Dose adjustment or switching insulin analogs, combined with supportive management, can lead to rapid improvement. Awareness of this condition may help prevent misdiagnosis and unnecessary invasive procedures.
Cellular processes are compartmentalized within immiscible heterotypic condensates, yet the functional consequences of losing their physical segregation remain unclear. Here, we show that genetic inactivation of the RNA chaperone SMN forces the aberrant intermixing of the two most prominent nuclear condensates: nucleolus and Cajal Body (CB). Upon SMN depletion, CB components invade the nucleolus and undergo reduced mobility and solubility consistent with a liquid-to-gel-like hardening transition. The CB-scaffold coilin aberrantly enriches at the nucleolar FC/DFC boundary and occupies rDNA chromatin, thereby locally suppressing rRNA production. Concurrently, this sequestration globally impairs coilin targeting to snRNA/snoRNA loci and limits telomerase access to telomeres, reducing telomeric synthesis. Crucially, genetic coilin depletion alone alleviates this mistargeting and rescues these functional impairments across condensates. Our findings reveal an inter-condensate rheostat model in which the loss of CB-nucleolar immiscibility is directly sensed, communicated, and executed by CB remnants, thereby proportionally coupling the functional outputs of otherwise distinct RNPs essential for splicing, translation, and genomic integrity.
Background: With the increase in the middle-aged population and sedentary lifestyle, a high incidence of obesity has been observed in humans and in animals. Obesity is consequent or correlated to multiple diseases, such as metabolic-dysfunction-associated fatty liver disease (MASLD), diabetes, dyslipidemia, etc. The attention of many researchers is focused on understanding the specific cellular mechanism and the role of inflammation, particularly chronic, in the development of this pathology as well as its link with dysmetabolic conditions, which seriously affect the survival of both humans and animals. Objective: The aim of this review is to discuss the mechanism responsible for obesity, the specific drugs used in the treatment of this disease, and, considering the link between obesity and inflammation, the possible employment of Palmitoylethanolamide (PEA), a natural lipidic mediator with anti-obesity activity in humans and animals. Materials and Methods: The selection of articles chosen for this review paper was performed through the most important electronic databases (PubMed, Scopus, Web of Science, and Google Scholar); the specific inclusion criteria were applied systematically each time to ensure that the selection of papers closely aligned. Results: The treatment of obesity is focused on the management of weight through dietary caloric restriction, sustainable nutritional behaviors and long life therapy, which are also useful to prevent comorbidities. Several specific drugs for the treatment of this pathologic condition are available in both human and veterinary medicine. However, considering the documented link between inflammation and obesity, the possible use of PEA, authorized in veterinary medicine as a food supplement, could represent a valid therapeutic strategy in the treatment of human obesity. Conclusions: From studies present in the literature on obesity and its therapeutic approach in both human and veterinary medicine, and considering the importance of natural molecules in health management, the use of PEA as a dietary supplement, for its anorexic and fat-losing properties, could be considered a valid tool to counteract overweight and obesity in humans and animals and to avoid the onset of consequent comorbidities.
Ischemic stroke results from the occlusion of a cerebral artery and is a leading cause of mortality and disability worldwide. Multimodal computed tomography (CT), including CT perfusion (CTP) and CT angiography, is crucial to acute stroke evaluation but involves higher radiation exposure than non-contrast CT due to repeated volumetric imaging. Reducing CTP radiation dose without losing image quality remains important challenge. This study proposes a machine-learning-based denoising autoencoder (DAE) to reduce noise introduced by dose reduction while preserving the quality of CTP images and perfusion parameter maps. CTP images from 48 acute ischemic stroke patients from the PRove-IT trial were used. Low-dose conditions were simulated by adding Gaussian and Poisson noise at varying strengths, with Poisson noise applied in the sinogram domain and Gaussian noise in the image domain. The DAE was trained using paired noisy and original images. Performance was evaluated by assessing structural similarity of CTP source images and perfusion maps, as well as clinical accuracy based on infarct core volumes derived from cerebral blood flow maps. The DAE restored strong structural similarity in CTP source images at dose reductions up to 90% (SSIM 0.81, PSNR 43 dB). Perfusion maps showed slightly lower similarity. Clinically, denoising substantially improved the accuracy of CBF-derived infarct core volumes, reducing mean absolute error from 10-30 mL in noisy images to approximately 4-16 mL and restoring high agreement with reference volumes (R2 > 0.85). These findings demonstrate that substantial simulated radiation dose reductions can be compensated by the DAE while preserving clinically meaningful perfusion-derived biomarkers.