Colon and rectal cancer (CRC) remains a major cause of cancer mortality in older adults, and dietary factors are important, potentially preventable contributors. Here, we assessed nationwide trends in CRC mortality and dietary risk-attributable burden among Japanese adults aged ≥60 years from 2010 to 2023. CRC deaths rose from 48,208 in 2010 to 70,327 in 2023, and the death rate increased from 121.9 to 159.4 per 100,000 population (EAPC 1.75). Mortality increased in both sexes, remained consistently higher in males, and showed the largest growth in the oldest age groups, especially those aged ≥85 years. Roughly two-fifths of CRC deaths over the study period were attributable to dietary risks; the attributable proportion increased from 39.75% to 40.66%, and dietary-attributable deaths rose from 19,156 to 28,582. Diets low in whole grains and milk were the leading contributors across sexes, age groups, and prefectures, followed by diets high in red meat, while contributions from processed meat consumption and low fiber intake increased over time. CRC mortality and dietary-attributable burden varied markedly across prefectures, although attributable proportions were relatively stable. These findings highlight a growing CRC burden in Japan's aging population and support age- and region-tailored dietary prevention strategies.

The residues and migration of nanoplastics (NPs) and plasticizers in agricultural products are critical issues in the field of food safety. This study focused on rye to systematically investigate the effects of individual and combined contamination by polystyrene NPs and diethyl phthalate (DEP) on its nutritional quality, metabolic profiles, and pollutant accumulation. The results showed that combined contamination significantly altered the nutritional composition of rye: crude fat content decreased by 34.67% (p < 0.05), while neutral detergent fiber and acid detergent fiber increased by 7.20% (p < 0.05) and 8.63% (p < 0.05), respectively; crude protein (+6.57%) and nitrogen-free extract (+7.33%, p < 0.05) also changed significantly, ultimately leading to a decline in relative feeding value (p < 0.05). Metabolomic analysis revealed that the combined treatment induced metabolic reprogramming, with significant accumulation of key metabolites in the phenylpropanoid pathway (e.g., sinapic acid, coumarin) and osmoregulatory substances (e.g., L-proline, ergothioneine), alongside disturbances in lipid and amino acid metabolism. Elemental analysis indicated that the pollutants disrupted ion homeostasis, such as inhibited absorption of magnesium and phosphorus, and increased levels of sodium and calcium. Fluorescence tracing confirmed that DEP promotes the migration and accumulation of NPs within rye roots and vascular tissues. At the molecular level, DEP exhibited high-affinity binding to cellulose synthase, providing a mechanistic explanation for the changes in fiber components. From the perspectives of nutritional quality, metabolic response, and pollutant accumulation, this study reveals the food safety risks posed by combined contamination of NPs and plasticizers in crops, offering scientific insights for the safe production of agricultural products and pollution prevention and control.

Approximately 85-90% of all rhabdomyosarcoma (RMS) cases occur in children and adolescents. In adults, RMS accounts for only 2-5% of all soft tissue sarcomas. The annual incidence in adults is 0.3-0.5 per 1,000,000 and is classified as a "very rare tumor." More than 95% of RMSs are extragastric. Primary gastric RMS is reported extremely rarely in adults, and the estimated incidence is <0.01/1,000,000/year. This rate is <0.01% of all gastric malignancies and <1% of all adult RMSs. We report the [18]F-fluorodeoxyglucose positron emission tomography/computed tomography findings in an adult with primary gastric alveolar RMS, highlighting the metabolic characteristics of this extraordinarily rare malignancy.

Articular cartilage repair in osteoarthritis (OA) remains a major clinical challenge. Although approaches using mesenchymal stem cells (MSCs) have demonstrated partial efficacy in OA, the regenerated tissue is often unable to form stable hyaline-like cartilage phenotype. Here, we introduce immunity-and-matrix-regulatory cells (IMRCs), derived from human embryonic stem cells (ESCs), as an alternative cell source for OA therapy. Using a multiple-level platform including 2D chondrocytes, 3D OA cartilage organoids (OCOs), rabbit cartilage explants, and a rat OA model, we demonstrate that IMRCs significantly enhance hyaline-like matrix formation while suppressing inflammation, angiogenesis, and fibrotic remodeling. Mechanistically, IMRC-mediated cartilage repair is partially associated with MMP1-dependent matrix remodeling. This study establishes a translational evaluation strategy for IMRCs and points to their potential as an alternative cell source for inducing cartilage repair in OA. Notably, the OCOs established in this study provide a pathologically relevant in vitro platform for evaluating cartilage regeneration in OA.

Background: In routine clinical practice, patient's management may differ from scientific organizations' guidelines and compromise patient's safety. This discrepancy indicates either an educational gap to fill or a need to adapt the guidelines to better reflect the real-world practice. Aims: Describe the management of venous thromboembolism (VTE): deep vein thrombosis (DVT) and pulmonary embolism (PE) among Vascular Medicine Specialists (VMS) practicing in France between 2020 and 2023 and compare it to national and international VTE guidelines. Materials and methods: A random selection of VMS from the national VMS directory were asked to 1) complete a questionnaire on their own management of patients with VTE (VMS survey) and 2) report their personal management of five consecutive patients with acute VTE (VTE case series). The study period partly overlapped with the COVID-19 pandemic, during which outpatient management strategies were increasingly promoted. Results: Among the 163 VMS contacted, 85 agreed to participate. We found that a direct oral anticoagulant (DOAC) was preferentially prescribed as first line anticoagulant in VTE: 65% in the VTE case series and 80% in the VMS survey. Low molecular weight heparins (LMWH) was preferred in case of high-risk PE (60%) or ilio-femoral DVT (35%) and in cancer-associated thrombosis (91%) in the VMS survey. After the first 6 months therapy, 30% of the VMS taper to a reduced-dose DOAC. This management was consistent with the VTE case series. Conclusions: DOAC is the standard of care to treat most VTE conditions in routine clinical practice, in line with VTE guidelines. LMWH is still preferred in case of high risk-PE and cancer-associated thrombosis. ECS use to prevent post-thrombotic syndrome remains frequent after DVT. Outpatient management of PE was common during the study period, reflecting evolving care models that were reinforced during the COVID-19 pandemic.

PURPOSE: To compare short-term clinical outcomes, inflammatory response, and patient-reported quality of life after open versus robotic-assisted ventral hernia repair (oVHR vs. rVHR). METHODS: This randomized controlled trial included adults with midline ventral hernias (2–8 cm). Patients were randomized to oVHR or rVHR. The primary endpoint was postoperative length of stay (LOS). Secondary outcomes included operative time, complications, quality of life, and inflammatory response measured by CRP. The primary outcome was analyzed using Poisson regression adjusted for defect size, repeated measures with linear mixed-effects models, and binary outcomes with logistic regression. RESULTS: Fifty-six patients were analyzed (rVHR = 29, oVHR = 27). Median operative time was longer for rVHR (129 min) than oVHR (80 min, p < 0.001). Mean LOS was significantly shorter after rVHR (0.46 days, 95 % CI 0.21–0.72) than oVHR (1.96 days, 95 % CI 1.43–2.49, p < 0.001). The benefit increased with defect size, corresponding to a predicted one-day difference at 17 cm². Postoperative CRP levels were lower after rVHR on both day 1 (23 vs 46 mg/L, p < 0.001) and day 3 (33 vs 70 mg/L, p < 0.001). Complication rates were similar (21 % vs 26 %, p = 0.6). Quality-of-life improvements at 3 and 6 months were comparable between groups. CONCLUSION: Robotic-assisted ventral hernia repair was associated with shorter hospitalization particularly for larger defects. The surgical stress response was also significantly lower following rVHR, but with longer operative time and no differences in complications or patient-reported outcomes. ClinicalTrials.gov NCT05906017, registered May 23 2023.

Invasive pulmonary fungal infections remain a major cause of morbidity and mortality among immunocompromised and critically ill patients. Rapid and accurate diagnosis is crucial for improving outcomes, yet conventional methods such as culture and histopathology suffer from limited sensitivity and slow turnaround times. Recently, significant progress has been made in the development and standardization of serological and molecular biomarkers that enhance the early detection of the key pulmonary fungal diseases, particularly invasive pulmonary aspergillosis and pneumocystosis. Diagnostic tools for mucormycosis, however, remain scarce. PCR tools have strong potential to significantly improve early detection, but they are not yet widely implemented, and standardized commercial assays remain limited. Accessible antigen-based tests with robust performance are highly anticipated and expected to become available soon. This review summarizes the current evidence regarding the optimal use of galactomannan, β-D-glucan and PCR-based assays, emphasizing how their performance varies according to the pathogen, the type of specimen and the host population. Specific challenges, such as differentiating colonization from infection in non-HIV Pneumocystis pneumonia or interpreting galactomannan and PCR in patients receiving mold-active prophylaxis, are highlighted. We also discuss how combining biomarkers can enhance diagnostic accuracy and support timely therapeutic decisions. A clear understanding of the strengths, limitations and appropriate interpretation of these diagnostic tools is crucial in an era of increasing host complexity, shifting fungal epidemiology, and expanding antifungal options.

The earliest references to association between mechanical jaundice and non-cirrhotic portal hypertension (NCPH) are by Fraser et al. (1944) and Gibson et al. (1965). The term "portal hypertension biliopathy" was proposed by Dhiman et al. (1999). The incidence of asymptomatic form of portal hypertension biliopathy (PHB) in patients with NCPH ranges from 81% to 100% that is significantly higher compared to patients with hepatic block (0-33%). Symptomatic form of PHB occurs only in 5-33% of patients. Any intervention on biliary tract in patients with PHB may result in significant blood loss due to coagulopathy. Currently, there is no consensus on optimal treatment algorithm for patients with symptomatic PHB. The authors present several patients with PHB complicated by mechanical jaundice and variants for correction of this complication.

Solitary plasmacytoma of the spine is an uncommon plasma cell neoplasm that typically arises from the vertebral body and is associated with osteolytic changes. Presentation as a predominantly extradural mass with minimal osseous involvement is rare and poses a diagnostic challenge due to nonspecific imaging features. We present the case of a 52-year-old female who presented with severe low back pain and bilateral radiculopathy without motor deficit or sphincter dysfunction. MRI revealed a well-defined, homogeneously enhancing anterior extradural mass at the L5 level, causing significant thecal sac compression. Whole-body [18]F-fluorodeoxyglucose PET-CT demonstrated a small focal lytic lesion involving the superior endplate of L5, without evidence of additional skeletal or extramedullary disease. The patient underwent surgical decompression with gross total excision. Histopathology and immunohistochemistry confirmed plasmacytoma. Systemic evaluation revealed monoclonal gammopathy with minimal marrow plasma cell infiltration and absence of CRAB features, consistent with a solitary spinal plasmacytoma with minimal vertebral involvement. This case highlights the importance of considering plasmacytoma in the differential diagnosis of enhancing epidural spinal lesions and emphasizes the role of surgery for diagnosis and decompression, followed by long-term surveillance due to the risk of progression to multiple myeloma.

Renal fibrosis is a critical pathological hallmark of chronic kidney disease. Although nonalcoholic fatty liver disease (NAFLD) has been implicated in kidney disease progression, its specific role and underlying mechanisms in renal fibrosis remain poorly understood. This study aims to investigate these mechanisms by establishing a mouse model of renal fibrosis through unilateral ureteral obstruction (UUO) combined with a high-fat diet-induced NAFLD. Single-cell RNA sequencing, untargeted metabolomics, flow cytometry, and immunofluorescence are performed, along with in vitro experiments involving primary renal macrophages and coculture models. It is demonstrated that NAFLD exacerbates renal fibrosis, as HFD-induced hepatocytes release significant levels of ANGPTL8, which activates renal CCR2[+]PIRB[+] macrophages. These specialized macrophages disrupt linoleic acid metabolism and increase the production of inflammatory cytokines, aggravating renal fibrosis. In addition, CCR2[+]PIRB[+] macrophages promote the activation and proliferation of Th17 cells, which can further contribute to the worsening of renal fibrosis. Thus, the ANGPTL8/PIRB/ALOX5AP axis is a crucial signaling pathway between the liver and kidneys, and CCR2[+]PIRB[+] macrophages play a pivotal role in the progression of NAFLD-induced renal fibrosis. These findings suggest potential therapeutic targets to treat NAFLD-related renal fibrosis.

Autoimmune diseases (AIDs) are multifaceted, chronic illnesses characterized by immune dysregulation and systemic inflammation. Newer evidence has pointed a finger at the human gut microbiota, a trillion-fold population of microorganisms that inhabits the human GI tract, as a major influential modulator of immune reactivity and a significant contributor to autoimmune pathogenesis. This systematic review will seek to address how the literature correlates with systematic changes in the gut microbiota in AIDs as well as explore mechanistic associations with biological processes like intestinal permeability and modulation of the immune system, coupled with determining the effectiveness of microbiota-directed interventions. An extensive literature search was conducted in PubMed, Embase, Cochrane Central, and Web of Science, involving the availability of studies until May 2025. The eligible studies included observational studies, randomized controlled trials, and relevant mechanistic research regarding autoimmune diseases and alterations of the gut microbiome or administered interventions. Data extraction and risk of bias (ROB) assessments were performed by two independent reviewers, and a narrative synthesis with an illustrative meta-analysis was applied. Inclusion criteria were met by 10 studies, encompassing various autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases (AITDs), and psoriasis. Familiar patterns of microbiome dysbiosis were identified, such as a reduction in microbial diversity, increased intestinal permeability, and the expansion of pro-inflammatory species like Ruminococcus gnavus. Dietary interventions, fecal microbiota transplantation, and probiotics demonstrated positive effects on clinical outcomes and immune measures across multiple studies. The meta-analysis revealed that microbiota-directed interventions significantly improved disease activity and immune response markers in AIDs, indicating a robust link between gut microbiota composition and autoimmune pathology. In autoimmune disorders, gut microbiota is a key factor in immunopathology. Gut biology as an adjunct interventional strategy provides potential in managing these diseases. Additional studies are required to help standardize methods and identify microbial targets specific to diseases that can then be addressed through therapeutic interventions.

A wearable electrochemical biosensor for real-time monitoring of neurotransmitters in sweat during physical exercise is presented. The biosensor utilizes a CuMOF@InMOF architecture, enhanced with gold nanoparticles (AuNPs), to improve electron transfer, surface area, and overall stability. Thiolate nucleic acid aptamers, highly specific to dopamine, serotonin, and epinephrine, are immobilized on the biosensor surface, enabling precise and simultaneous detection of these key neurotransmitters. The flexible, multi-electrode platform is integrated into a microfluidic patch that adheres to the skin, facilitating seamless sweat collection and continuous neurochemical analysis. Structural validation confirmed the successful synthesis of the CuMOF@InMOF architecture with enhanced surface area, stability, and electron transfer properties, contributing to the biosensor's high sensitivity and selectivity. Impressively, the biosensor achieved detection limits of 0.18 nM for dopamine, 0.33 nM for serotonin, and 0.27 nM for epinephrine, with a broad dynamic range from 1 nM to 10 µM. Performance was validated through square wave voltammetry and amperometry, demonstrating exceptional sensitivity, selectivity, and stability. This innovative biosensor offers a powerful tool for non-invasive, real-time neurochemical monitoring, with significant potential in personalized healthcare.

Decreased expression of sirtuin 1 (SirT1) has been implicated in Alzheimer's disease (AD), and as we previously reported, is related to transcriptional repression by the major risk factor for sporadic AD, apolipoprotein E4 (ApoE4). Herein we describe the discovery of an orally brain-permeable small-molecule, DDL-218, that enhanced SirT1 in ApoE4-expressing neuronal cells and a murine AD model. DDL-218 increased the transcription factor NFYb resulting in upregulation of PRMT5. Mechanistic and modeling studies show that binding of ApoE4 to the SirT1 gene promoter can be displaced by PRMT5 leading to increased SirT1 transcription. DDL-218 treatment elicited improvement in memory in the AD model, suggesting that DDL-218 enhancement of neurotrophic SirT1 in the brain has potential to modulate neuronal activity that may clinically provide an improvement in cognitive function and complement the current anti-Aβ antibody monotherapy. Our findings support further development of DDL-218 as a novel ApoE4-targeted therapeutic candidate for AD.

Carbon dots (CDs) are new types of fluorescent nanomaterials with particle diameters of 1∼10 nm and have excellent photoluminescence (PL) properties, good biocompatibility, simple preparation methods and numerous raw materials; consequently, they are promising in the biomedical field. In recent years, to overcome drug resistance and toxic side effects of traditional organic drugs, the synthesis of CDs from drug molecules has become an effective strategy, which produces CDs with the same therapeutic effects as the raw drugs and even possessing new properties. At present, many CDs derived from organic drugs have been developed, which can be classified according to their sources such as antibiotics, anti-inflammatory drugs, and guanidine drugs. This article focuses on the progress of the above-mentioned drug-derived CDs compared with their drug precursors in terms of therapeutic efficacy, enhanced performance and new additional functions, with special attention to the structure-activity relationship between the drug precursors and the CD-based therapeutic agents. It demonstrates the feasibility of designing new drug-derived CDs for clinical applications, summarizes the shortcomings and research gaps of the existing work, and provides a reference for related work in the future.

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT on outcomes, and ongoing and future trials and methodologies to help identify patients who are at an increased risk of SCD and who may benefit from an ICD. The authors also propose a pragmatic guidance for clinicians when they engage in the shared decision-making discussions for primary ICD implantation.

The prevalence of morbid obesity in today's population around the world is alarming. Morbid obesity involves substantial changes in body composition and function, which can affect the pharmacodynamics and pharmacokinetics of many drugs. This paper aims to discuss the application of muscle relaxants and their reversing agents in patients with morbid obesity. This work is based both on the available literature and the author's personal experience. Dosage recommendations for muscle relaxants in morbidly obese patients are as follows: non-depolarizing relaxants like rocuronium, vecuronium, atracurium, and cisatracurium should be based on ideal body weight. Succinylcholine dosage should be adjusted to total body weight with a 200 mg maximum, while mivacurium should also be based on total body weight. Pancuronium is not used due to its long duration. Neostigmine dosing remains uncertain, but some suggest using total body weight. When it comes to Sugammadex opinions of the authors are divided, some indicate that it should be dosed based on ideal body weight, but more recent studies show that it should be based on 40% of corrected body weight.

Vernal keratoconjunctivitis (VKC) is a rare yet severe form of allergic conjunctivitis predominantly affecting children, mainly boys, with a global prevalence and a higher incidence in certain geographical regions. The disease is characterized by seasonal exacerbations. VKC presents with ocular surface inflammation leading to various distressing symptoms such as itching, redness, mucous discharge, and pain. The disease primarily manifests bilaterally, though it may initially appear unilaterally. If left untreated, VKC can result in corneal complications, including shield ulcers and vision impairment, affecting daily activities and psychosocial well-being, especially in children. The diagnosis of VKC involves identifying key clinical findings on the ocular surface such as Tranta dots, giant papillae, or shield ulcers. Management follows a stepwise approach, including anti-allergic eye drops, steroid eye drops, and topical medications like cyclosporine, which may take up to 3 months to show efficacy. Allergic sensitization, often to inhaled allergens like pollen and house dust mites, is associated with VKC in half of the cases. Understanding and managing these allergies through measures such as avoidance, sensitization control, and co-treatment of associated conditions like asthma and rhinoconjunctivitis are essential in VKC management. Atopic keratoconjunctivitis (AKC), a related condition associated with atopic dermatitis and asthma, shares similarities with VKC but typically affects young adults. However, there is an observed spectrum between the two diseases, indicating similar treatment strategies for both. VKC treatment requires a patient-centered approach, involving informed and supported parents, considering economic factors due to costly eye drops, and ensuring accessibility and practicality of treatment, especially in children. A multidisciplinary team collaboration, including ophthalmologists, pediatricians, and dermatologists, optimizes patient care. The rewarding aspect of VKC treatment lies in witnessing children regain their quality of life, overcome vision challenges, and thrive in their daily activities. In conclusion, understanding VKC, its associated allergies, and employing a comprehensive, patient-centered approach are crucial in managing this challenging condition, particularly in children, to enhance their vision and overall well-being.

Kidney disease is a critical and potentially life-threatening degenerative condition that poses a significant global public health challenge due to its elevated rates of morbidity and mortality. It manifests primarily in two distinct clinical forms: acute kidney injury (AKI) and chronic kidney disease (CKD). The development of these conditions hinges on a multitude of factors, including the etiological agents and the presence of coexisting medical conditions. Despite disparities in their underlying pathogenic mechanisms, both AKI and CKD can progress to end-stage kidney disease (ESKD). This advanced stage is characterized by organ failure and its associated complications, greatly increasing the risk of mortality. There is an urgent need to delve into the pathogenic mechanisms underlying these diseases and to identify novel biomarkers that can facilitate earlier diagnosis. Such early detection is crucial for enhancing the efficacy of therapy and impeding disease progression. In this context, proteomic approaches have emerged as invaluable tools for uncovering potential new markers of different pathological conditions, including kidney diseases. In this chapter, we overview the recent discoveries achieved through diverse proteomic techniques aimed at identifying novel molecules that may play a pivotal role in kidney diseases such as diabetic kidney disease (DKD), IgA nephropathy (IgAN), CKD of unknown origin (CKDu), autosomal dominant polycystic kidney disease (ADPKD), lupus nephritis (LN), hypertensive nephropathy (HN), and COVID-19-associated acute kidney injury (COVID-AKI).

Total Colonic Hirschsprung Disease (HD) can be challenging from a diagnostic and management standpoint and occurs in around 8% of cases of HD. Long term outcomes are difficult to compare due to variation in length of aganglionosis, chosen surgical techniques, and terminology utilized in the literature. In this review we highlight some of the management controversies and clinical challenges and emphasize future areas of suggested collaboration and research.

Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.

‘Nothing to be done’ (Beckett 2012: 11). Samuel Beckett’s play Waiting for Godot is not about healthcare, but its first line seems to hover between prognosis and diagnosis, suggesting that some kind of existential ‘doctoring’ is afoot, even as it is clear that no prescriptions are going to be dispensed. For the play’s two central characters, Vladimir and Estragon, ‘nothing to be done’ empties out the urgency of curative political action from Vladimir Lenin’s famous question: ‘What is to be done?’ Every possibility of change on the horizon of the play is derailed by the inertia of the fixing refrain: ‘we’re waiting for Godot’. Waiting is the nothing that famously happened twice (Mercier 1956: 6), and came to be figured, in many early critical receptions of Beckett, as a representation of the existential human condition (Graver and Federman 1979). In the early 1950s, when the play was first performed, perhaps abstractions were more available for critical absorption than the possibility that postwar Europe was still in a present denuded of an inhabitable future (Kenner 1973: 133; Gibson 2010: 108) – an endless time of living on without any real hope of change in the wake of an unspecified disaster. Beckett’s play materializes a waiting that becomes a form of endurance through the promise of what might come to change the present for there is always some orientation towards the future in such practices. But the clear unavailability of Godot decouples the for (Schweizer 2008: 11), the most obvious preposition or relation, from the action of waiting. Neither weak enough to cease and desist nor strong enough to leave, Vladimir and Estragon endure and persist, not, in the end, waiting for Godot but waiting with and sometimes even on one another. Although in this chapter we will pay close attention to existential claims about the place of waiting in human experience, we will suggest that waiting is significantly shaped by the promises and narratives of particular historical moments and lifeworlds, and their distinct ways of understanding time. Indeed, if tarrying in Godot’s waiting room seems to speak to the existential human condition, we would argue that it is because the audiences the play found and continues to find persist in a time when the promises of the future feel increasingly unavailable. Godot’s characters, alongside their audiences, wait with their diagnosis, which is also their prognosis: ‘nothing to be done’. Perhaps one reason the slow modernism of Godot found and made its mark so sharply was its insistence on attending to the disavowed underside of the dominant timescapes of modernity. In 1931, Aldous Huxley was able to state that ‘[s]peed […] provides the one genuinely modern pleasure’ (Huxley 2001: 263), and it has been a critical commonplace to read aesthetic modernism as a reflection of the shock of the new and a pacing, racing present. Planes, trains, and automobiles; ragtime and jazz; epiphanies and revolutions; telegraphs and telephones; production lines and new mass media: humanities scholarship has thoroughly mined how the modernity of the early and mid-twentieth century produced, for better and worse, accelerated lives and shaped technologies capable of both registering and increasing sensations of speed (Duffy 2009). Engaged with a more contemporary moment and less concerned with aesthetic practices, Paul Virilio (2006) has described how a logic of acceleration that has compressed, foreshortened, and fractured time still sits at the heart of modernity and its drives towards destruction; while Jonathan Crary (2013) has critiqued a culture of 24/7 availability fuelled by unsleeping technologies that has turned even the slowing of rest into an act of embodied resistance. But there were always other times folded into the modern, as Elisabeth Kirtsoglou and Bob Simpson’s idea of ‘chronocracy’ suggests (this volume). For example, the managed and mechanized time of the working classes in a newly industrialized Europe was consistently used to service a version of a progressive future that was not shaped in their interests (Thompson 1967). Craig Jeffery has also identified ‘chronic, fruitless waiting’ (Jeffery 2010: 3) as a particular temporal experience of those colonized populations who provided much of the material resources for acceleration of Empire and modernity, noting it as a prominent feature of the experience of subaltern peoples globally since the 1960s. Bendixsen and Eriksen indeed point out that for certain groups waiting can be an expression of power and domination, generating vulnerability and humiliation (2018: 92). And while a ‘new chronic’ temporal imaginary has become more generally palpable in the late liberalism of the contemporary global north (Cazdyn 2012), many of the most acute experiences of ‘chronic, fruitless waiting’ remain ‘zoned’ in specifically gendered, raced, and classed ways. As Lisa Baraitser has argued in Enduring Time (2017), despite an ever-increasing sense of acceleration, because the spooling of time towards a possible future seems to have come unravelled in the contemporary moment, experiences of interruption, suspension, delay, and slowness strongly insist in affective life in highly differential ways. Here, however, we track this sense of time enduring rather than passing back to an earlier moment in the twentieth century, noting the ways in which waiting uncoupled from a future into which one might step came to be understood as a key feature of the affective condition termed ‘melancholia’, or, in its more contemporary configuration, ‘depression’. This is not to claim that either condition is simply a response to modern times or, more strongly still, a social construction; nor is it to seek to medicalize distress that may be the result of other social relations of inequality or injustice (Thomas et al. 2018). Rather, we are interested in exploring how understandings of melancholia in twentieth-century Europe came to be focalized through particular ideas and sensations of stuck, suspended, impeded, or ungraspable time that shaped and continue to mould the contours of the temporal landscapes and psychological imaginaries of (late) modernity. Furthermore, we argue that care in the context of depression, which we understand as imbricated with psychosocial relations and experiences and therefore ‘more than biomedical’ or psychological in constitution (Hinchliffe et al. 2018), may turn out to hinge around the offer and use of extended periods of time and the capacity to stay with those whose experience is that of a temporality that no longer flows. Although the disciplinary perspective here is not anthropological, our concern with examining melancholia and depression through experiences and practices of waiting brings our chapter into contact with an important body of anthropological literature. In his interdisciplinary volume, Ghassen Hage describes waiting as an experience that is always both existential and historically articulated or situational (Hage 2009: 4, 6). Manpreet Janeja and Andreas Bandak similarly suggest that analysing waiting requires a capacity to shuttle between existential and more clearly social or institutional perspectives, as they demonstrate how focussed ethnographic work can illuminate both waiting’s poetics and its politics (Janeja and Bandak 2018: 3). But this chapter uses a more dispersed, eclectic, and textual archive of experience to open up a theoretical account of melancholia/depression as a condition fundamentally entangled with existential, cultural, and socio-historical experiences and theorisations of European (late) modernity. Remaining broadly within the climate of these anthropological approaches to waiting, however, we propose that the remarkable tradition of phenomenological psychiatry from the late nineteenth and early twentieth century provides a significant opportunity to trace the relationship between accounts of lived experience of mental distress that emerged explicitly alongside existential philosophies, and more broadly socio-historical accounts of time. As time became a topic of intense debate across the sciences and arts and humanities in early twentieth century Europe and North America, multiple disciplines explored the tension between accounts of intuitive/subjective time and understandings of mathematical/objective time (Fryxell 2019: 5–6). Phenomenological psychiatry established its distinctive approach in this context by refusing the dominant third-person approach to psychopathology exemplified by Emil Kraepelin (Broome et al. 2012: 90) in favour of paying careful attention to the first person, subjective experience of disruptions of well-being. The discipline was profoundly influenced by the new philosophies of temporality of Henri Bergson and Martin Heidegger in the first three decades of the twentieth century and one of its key insights was that chronic mental distress can be understood as a disturbance of a sense of lived time. However, phenomenological psychiatry paid scant explicit attention to the temporal demands of treatment (Fryxell 2019: 23) – the time bound up in the intersubjectivity of the clinical encounter or simply the time that treatment takes. But psychoanalysis, which emerged alongside phenomenological psychiatry in historical terms, insisted on reflecting, with particular self-consciousness, on the complex, often seemingly interminable temporality of treatment (Freud 1937). Both phenomenological psychiatry and psychoanalysis developed in explicit dialogue with the conditions of modernity and alongside the devastating experiences of industrialized warfare, but while phenomenology negatively articulated a temporal attitude of normalcy that recedes in experiences of mental illness, psychoanalysis used the rhythms of psychopathology and the inevitability of falling ill as a way of illuminating the structures of all mental life and of a psychic life of time that can never be simply linear, teleological, or smoothly flowing. Instead of suggesting that sensations of waiting without a for break apart what is proper to lived time, psychoanalysis comes to understand such experiences to be part of the inevitable conditions of psychic life. Psychoanalysis thus offers up a specifically chronic cure – the offer of time and care, and of remembering, repeating and working through (Freud 2014) – to contain, understand, and ameliorate the chronic condition of mental distress. By highlighting this link between the chronicity of the mind and the broader psychosocial contexts in which endurance plays out, this paper aims to open up a historically nuanced sense of the value of psychoanalytic temporal practices of waiting not for but with. We also suggest that by attending specifically to the relationships between depression, temporality, and historical and psychosocial experience, the urgent debates about uses of time in contemporary mental healthcare delivered by the UK’s National Health Service might tentatively be reframed.

Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery.

Background The reliability of intraoperative evaluation of ganglion cells in the appendix as a guide to a diagnosis of total colonic aganglionosis is unclear. Objective To evaluate the diagnostic utility of appendicular innervation in colonic Hirschsprung disease (HD) and TCA. Methods Prospective, systematic study of ganglion cells and the neural plexii in appendices from cases (HD and TCA) and age matched controls with frozen and paraffin sections, rapid acetylcholinesterase (AChE) and immunohistochemistry. Results A total of 48 appendices (28 controls, 20 cases; 19 frozen) were evaluated. Of these 48, 30 were neonates. Ganglion cell clusters were smaller in controls (28) and HD (6) than those in the rectum, distorted at places and mimicked lymphocytes and endothelial cells, especially in neonates. Complete study of 13 appendices in TCA showed absence of ganglion cells, hypertrophic nerves, AChE activity, and calretinin staining. In 2/13 TCA, an erroneous frozen section identification of ganglia was later corrected based on AChE histochemistry and a panel of IHC stains. Ileal biopsies guided the placement of a ganglionic ileostomy in all. One case each of skip segment aganglionosis in a TCA and variable hypoganglionosis in long segment colonic HD is reported. Conclusion Intraoperative characterization of appendicular innervation as a guide to the diagnosis of TCA is unreliable, in part because of the possibility of skip segment disease/variable hypoganglionosis. We propose terminal ileal biopsies for diagnosis and leveling of aganglionosis. AChE on frozen/calretinin on paraffin tissue is the best approach to avoid diagnostic errors.

The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations.

In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes.

The restoration of the degenerated articular cartilage in patients with osteoarthritis (OA) is still a challenge for researchers and clinicians. Drug interventions and surgical treatments have been widely attempted for cartilage regeneration in OA. However, the results were largely unsatisfactory. Autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI) offers potential for the regeneration of cartilage over the long-term. However, due to the limitations and disadvantages of ACI, alternative therapies for cartilage regeneration are in need. The availability of large quantities of mesenchymal stem cells (MSCs) and the multilineage differentiation, especially their chondrogenic differentiation property, have made MSCs the most promising cell source for cartilage regeneration. In addition, MSCs have been shown the ability to undergo site-specific differentiation. MSCs can be obtained as MSC sheets using the temperature-responsive culture dish method. The MSC sheet can provide amounts of cells and extracellular matrix, which might provide the continuity between the implant and host cartilage, thus improving integrative cartilage repair. Moreover, OA is associated with progressive and often severe inflammation. MSCs not only have the ability to contribute structurally to tissue repair, but also possess potent immunomodulatory and anti-inflammatory effects. Taken together, these properties make MSC sheet promising candidate for cartilage repair in OA. We hypothesize that MSC sheet encapsulated cartilage debris can efficiently promote cartilage repair in OA patients. Chondrocytes can be obtained and cultured from small cartilage debris in vitro. Therefore, the chondrocytes may grow from the debris in cartilage defect and improve cartilage regeneration. MSC sheet provide amounts of cells, ECM and protein for cartilage regeneration and integration, and may play some roles of periosteum. The operation of MSC sheet encapsulated cartilage debris for cartilage repair is simple and practical. Moreover, the cell sheet/cartilage debris constructs can be easily shaped based on the size and shape of cartilage defects. The new method might have great potential in treating cartilage defects clinically, especially for OA patients.

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease <or=1 cm). A preoperative serum CA-125 level of 500 U/ml was found to be the value with the most predictive power. Optimal cytoreduction was obtained in 16 of the 21 cases (76%) with a CA-125 <500 U/ml compared to only 6 of the 19 cases (32%) with a CA-125 >500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.

The effect of cisapride on plasma concentrations of paracetamol was investigated with respect to hepatic metabolism. Paracetamol (1 g) together with cisapride (7.5 mg) or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after administration. Plasma paracetamol and its glucuronide and sulfate conjugates were measured by HPLC. The pharmacokinetic variables were calculated from the plasma concentration-time curves of each volunteer. The area under the plasma paracetamol concentration-time curve from 0 to 180 min (mean +/- s.d.) increased from 1875.0 +/- 112.8 micrg min mL(-1) (placebo coadministration) to 2238.8 +/- 125.8 microg min mL(-1) (cisapride coadministration) (P < 0.01). The mean maximum plasma paracetamol concentration(18.2 microg mL(-1))with placebo was reached 30 min after administration, whereas mean maximum plasma paracetamol concentration (21.2 microg mL(-1)) with cisapride occurred 45 min after administration. The plasma paracetamol concentrations with cisapride were significantly greater at 45 to 120 min after administration compared with placebo. Plasma paracetamol glucuronide conjugate concentrations with cisapride were decreased at 15 to 60 min compared with placebo (P< 0.05), whereas plasma paracetamol sulfate conjugate concentrations did not change significantly. Hence the coadministration of paracetamol with cisapride reduced plasma paracetamol glucuronide concentrations and increased plasma paracetamol concentrations, presumably due to inhibition of paracetamol metabolism via paracetamol glucuronyltransferase. Thus, care is necessary when paracetamol and cisapride are coadministered.

Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

Meningococcal conjunctivitis is typically described as an acute purulent infection. An atypical case of mild catarrhal conjunctivitis occurred in a 19-year-old college student. The meningococci were identified as Neisseria meningitidis, group A, and were isolated from the throats of the patient and her roommate. The conjunctivitis responded rapidly to treatment with sodium sulfacetamide, and it was not treated systemically. A short review of the literature of meningococcal conjunctivitis is presented, and the current recommendation for prophylaxis is discussed.

Artificial air pouches in the connective tissue of mice were evaluated as a means of studying Neisseria gonorrhoeae infections. Animals inoculated with type-1 N. gonorrhoeae cells developed an infection characterised by infiltration of polymorphonuclear leucocytes. Viable cocci could be recovered from the air pouches for up to 10 days after infection and intracellular cocci were evident in electronmicrographs within connective-tissue fibroblasts for at least 35 days, indicating that a persistent infection had been established. The mouse air pouch should be of value in the study of gonococcal and other infections.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.

The authors describe the fibro-granulomatous lesions with scar formation on a splenectomy specimen removed for familial spherocytosis, eight weeks after the onset of cat scratch disease. This original observation, apparently unique in the literature, is in favour of the blood spread of the agent responsible for benign inoculation lymphoreticulosis, and suggests a pathogenic theory for the unusual visceral manifestations.

Kidney fibrosis, a progressive outcome of various chronic kidney diseases (CKD), features tubule atrophy, chronic interstitial inflammation, and abnormal metabolic changes. Urolithin A (UA), a gut microbiome metabolite derived from ellagic acid and ellagitannins, has anti-inflammatory and anti-obesity effects and enhances cellular health by promoting mitophagy and mitochondrial function. This study aimed to evaluate the protective effects of UA against renal fibrosis in mice with unilateral ureteral obstruction (UUO) and to investigate its underlying mechanisms. UA significantly reduced lipid deposition and mitigated renal fibrosis in the kidneys of UUO mice and TGFβ1-induced HK-2 cells. Mechanistically, UA alleviated renal fibrosis by inhibiting GSK3β/β-catenin signaling to promote FAO, rather than through the canonical TGF-β1/Smad or Notch1 signaling pathways. Furthermore, UA activates GSK3β to inhibit β-catenin via AKT1 but independent of SIRT3 or PP2A. Altogether, UA significantly mitigated kidney fibrosis by restoring fatty acid oxidation metabolism through inactivation of the GSK3β/β-catenin axis, offering potential as an alternative therapy to combat renal fibrosis.

Sulphated glycosaminoglycan (sGAG) is a major component of cartilage and known to be involved in cell signaling processes, but little is known about expression and localization in different cartilage types. Using common histochemical staining methods to assess regional sGAG distribution in bovine articular, meniscal, auricular, and nasal cartilage, different staining patterns were found for alcian blue, Safranin O and thionine. Immunohistochemistry to identify expression and location of different epitopes of chondroitin sulfate (C-0-S, C-4-S and C-6-S), dermatan sulfate, keratan sulfate, and heparan sulfate, also demonstrated regional differences which could not explain the differences in histochemical staining. Chondroitin sulfate and keratan sulfate were expressed in all cartilage types investigated, however keratan sulfate was not expressed in the superficial zone of articular cartilage. Dermatan sulfate was only present in tensile load-bearing zones of articular and meniscal cartilage, and in the perichondrium of auricular and nasal cartilage. Despite being hyaline, nasal cartilage and articular cartilage showed dissimilar sGAG expressions. In conclusion, sGAG localization in different types of cartilage is distinctly different, suggesting diverse structural and mechanical functions governed by GAGs. These differences are important for our understanding of the role of sGAG in cartilage function and in cartilage tissue engineering strategies.

Background/Objectives: The thermal stability and degradation kinetics of β-lactam antibiotics are critical for understanding their behavior under processing and storage conditions. This study investigates the thermal decomposition of meropenem, ceftriaxone sodium, and cefazolin sodium in order to evaluate their kinetic parameters, assess the presence of the compensation effect, and determine isokinetic temperatures. Methods: Thermal analysis was performed using simultaneous TG/DTG/DSC measurements. Non-isothermal degradation experiments were conducted at four different heating rates. Kinetic parameters were evaluated using two isoconversional methods (Friedman and Flynn-Wall-Ozawa) and ASTM E698-based approach to obtain average activation energies. To determine the pre-exponential factor (A), the Coats-Redfern method was applied using multiple kinetic models. The resulting lnA-Ea pairs obtained from different models were used to construct lnA = f(Ea) correlations, enabling the evaluation of the compensation effect and calculation of isokinetic temperatures (Tiso). Results: All three β-lactam antibiotics exhibited consistent kinetic behavior across the applied models, with the F3 reaction model providing the best fit based on R[2] values. A clear linear relationship between lnA and Ea was observed, confirming the presence of an enthalpy-entropy compensation effect. However, significant differences in isokinetic temperatures were obtained indicating variability in kinetic compensation behavior among the studied compounds. Conclusions: The thermal degradation of the investigated β-lactam antibiotics follows a consistent kinetic framework, supported by isoconversional and model-fitting approaches. Nevertheless, the absence of a unique isokinetic temperature suggests differences in transition-state stabilization and enthalpy-entropy balance, likely driven by structural variations among the compounds.

Marine molluscs produce a class of proteinaceous materials, byssal proteins that possess unique mechanical and adhesive properties. In this sense, the extraordinary adhesion of mussel byssal proteins is inspiring a new class of surgical glues and sealants designed to perform in wet, dynamic physiological environments. Beyond their performance, these materials represent a sustainable and biodegradable alternative to conventional synthetic polymers. In parallel, sea-silk is most admirable biomaterials with high biocompatibility in the tissue engineering field. With its fibre-like structure and excellent biocompatibility, sea silk is emerging as a transformative scaffold for regenerative medicine, capable of guiding cell differentiation and accelerating wound repair. Polymeric glues and hydrogels inspired by mussel foot proteins achieve higher shear adhesion on biological tissues. These adhesives have successfully sealed wounds, supported transplanted cells, and repaired fetal membranes, highlighting the translational potential of marine byssal proteins and sea-silk in regenerative medicine, surgery, and eco-friendly adhesives. The critical challenge now lies in translating these natural wonders from the ocean to the clinic through scalable and cost-effective production. This review provides a critical overview of the chemistry, structure, and biomedical applications of these marine proteins, outlining their potential to revolutionize the field of advanced biomaterials.

Mind‑body practices, such as meditation and yoga, involve paying attention to breathing sensations. During these practices, individuals report "interoceptive lapses," moments when attention drifts away from internal bodily sensations. While lapses in attention to the external world have been widely studied, little is known about the physiological and neural mechanisms of interoceptive lapses. Interoceptive lapses may share markers with exteroceptive lapses-such as reaction time variability and default-mode network (DMN) connectivity-but may also depend on distinct brain systems and breathing physiology. We examined behavioral, physiological, and neural signals preceding lapses in a sample of 93 adolescents enriched for GAD and depression symptoms. Participants performed a 20-min breath counting task in the fMRI scanner with simultaneous breath recordings. Lapses were defined as moments when counting errors occurred. The sample was split into training and validation sets to test machine learning models predicting attentional lapses. The strongest predictors were timing and variability of button responses (AUCs > 0.75). Breathing variability and breathing-behavior synchronization showed smaller but generalizable predictive value (AUCs < 0.65). Whole-brain connectivity models also predicted lapses (AUC ≈ 0.65), incorporating the DMN, dorsal and ventral attention, and somatomotor networks. Furthermore, models that included brain connectivity marginally outperformed behavior-only models. Comparisons to previous exteroceptive findings indicate some common markers (e.g., reaction time variability) and some unique markers (e.g., selective perceptual coupling with attentional networks). Although limited by the clinical sample and lack of a control task, these results highlight brain-body markers of interoceptive attention that may inform real-time monitoring during mind-body interventions.

Splenic cysts are rare and are often detected incidentally or until the cyst reaches a certain size, causing clinical symptoms. They are classified into primary (true) and secondary (false) splenic cysts. False cysts often pose diagnostic and therapeutic challenges due to their nonspecific clinical presentation and overlapping imaging features with true cysts. Here, we present the case of a 36-year-old female who presented with symptoms of intermittent left-sided abdominal pain, nausea, loss of appetite, and low-grade fever. Clinical examination revealed a palpable mass in the left hypochondrium. Contrast-enhanced computed tomography showed a large, well-defined cystic lesion arising from the inferior pole of the spleen. Based on clinical, serological, cytological, and radiological findings, a nonparasitic splenic cyst was suspected preoperatively. As the cyst was large (>8 cm) and involved >75% of the splenic parenchyma, a total splenectomy was performed. Histopathological examination revealed the absence of an epithelial lining, confirming a nonparasitic secondary (false) splenic pseudocyst. The postoperative course was uneventful. A systematic diagnostic workup and total splenectomy remain safe and effective options for splenic cysts with significant size and rupture risk. Histopathological examination continues to be the gold standard for definitive diagnosis.

Automatic segmentation using convolutional neural networks (CNNs) has become a key tool in musculoskeletal imaging, offering substantial reductions in processing time. However, concerns about reliability often necessitate manual inspection and correction. We present a method that leverages network-derived uncertainty to automatically identify and localise segmentation errors, reducing the need for exhaustive manual review. A 3D nnU-Net was trained on delayed gadolinium-enhanced MRI of hip cartilage. Voxel-wise uncertainty scores, computed from the SoftMax outputs of ensembled sub-networks, were aggregated over feature-based supervoxels. Each region was then evaluated for its potential impact on clinically relevant metrics, generating sensitivity scores. A logistic model combined these with uncertainty data to assign risk scores, guiding attention to areas most likely to affect clinical metrics during the initial correction steps. Using these risk scores, guided supervoxel correction of just 50 supervoxels reduced the mean absolute relative error by 2.1-fold. Guided manual correction within these regions achieved a 3.5-fold reduction, an approximate 62% supervoxel correction efficiency. Correcting the top 10 regions yielded up to 88% efficiency. This approach serves as a proof-of-concept for targeted correction in hip MRI, enhancing the clinical utility of CNN-based segmentation by demonstrating that 3D feature-derived uncertainty aggregation has the potential to reduce correction burden compared to traditional 2D methods.

Introduction Kangaroo care (KC), defined as the first, sustained skin-to-skin contact between parents and their neonates, is widely recognized as a key family-centered intervention in the Neonatal Intensive Care Unit (NICU). Beyond its physiological characteristics, including improved thermoregulation, cardiorespiratory stability, and breastfeeding, KC has demonstrated significant psychosocial benefits, particularly in reducing parental stress and enhancing parent-neonate bonding. Despite strong international evidence, there is limited data from the Greek NICU setting on the association of KC with parental stress and satisfaction. This study aimed to evaluate the effect of KC in reducing parental stress and increasing parental satisfaction with neonatal care. Methods A quasi-experimental two-group design (intervention versus control) was implemented in a Greek NICU. A total of 80 parents of preterm or full-term neonates (gestational age 24-40 weeks) participated. Parents in the intervention group (n=40) applied KC for 1 hour daily throughout the hospitalization, while the control group (n=40) received regular care with limited physical contact. Parental stress was assessed using the Parental Stress Scale: NICU (PSS: NICU) at baseline and at the end of hospitalization, and parental satisfaction using the NICU Parent Satisfaction Form (NICU-PSF). The clinical status of the neonate was assessed using the ALPS-Neo scale. Independent t-tests and Chi-square tests were used for comparisons between groups, and Spearman's rho correlations examined associations between demographic/clinical variables and parental outcomes. Results Parents in the KC group showed significantly lower total scores compared to controls (107.69 ± 9.45 vs. 121.40 ± 14.68, p = 0.015). Stress related to the change in parental role was also significantly reduced (32.92 ± 2.89 vs. 38.60 ± 6.08, p = 0.002). No significant differences were observed in stress related to NICU sounds (p = 0.46) or the appearance of the newborn (p = 0.11). Overall parenting satisfaction was high in both groups (KC group: 4.14 ± 0.44 vs control group: 4.18 ± 0.02, p=0.572). Maternal age was negatively associated with anxiety across all domains (rho = -0.337 to -0.389, p < 0.01). Perceived family support showed a strong positive association with anxiety related to the NICU environment and neonate appearance (rho = 0.61-0.73, p < 0.001). Neonatal clinical status (ALPS-Neo) was positively associated with both parenting satisfaction (rho = 0.473, p < 0.001) and stress related to neonate appearance (rho = 0.383, p = 0.001). Conclusion KC was associated with significantly lower parental stress, particularly regarding parental role disruption, reinforcing its value in enhancing parental involvement and emotional well-being in the NICU. Parental satisfaction remained high in all groups, further influenced by the clinical status of the neonates. The findings support the extensive, systematic integration of KC in Greek NICUs, aligned with international recommendations, to improve both parental psychological outcomes and overall quality of neonatal care.

Inhibin is a dimeric glycoprotein hormone consisting of α and β subunits. Inhibin has gained significant interest as a biomarker for ovarian and testicular malignancies. While existing inhibin immunoassays have demonstrated efficacy, assays specifically targeting the free α subunit are not yet available. This study aimed to generate monoclonal antibodies against inhibin-α using hybridoma technology, targeting distinct epitopes within the N-region of the α subunit. These epitopes were chosen using bioinformatic analysis to ensure strong antigenicity and successful antibody production. To screen the antibodies, an ELISA was developed using plates coated with recombinant inhibin-α protein. This ELISA confirmed that the antibodies were reactive and could effectively detect inhibin-α in vitro. The antibodies were further evaluated for specificity and immunoreactivity using Western blotting, and IHC methods. Western blot analysis showed that the antibodies specifically recognized the free inhibin-α, demonstrating high specificity under both reducing and non-reducing conditions. IHC studies on normal mouse tissue sections further confirmed the localization of inhibin-α in granulosa, theca, Sertoli, and Leydig cells. The developed antibodies showed significant potential for use in vitro assays for cancer diagnosis. Further validation is needed to ensure their successful clinical application.

Utilizing lignin as a complete substitute for petroleum-derived phenol to synthesize non-toxic lignin-based resin adhesives with bio-based aldehydes holds substantial significance for advancing sustainable development in the wood-based panel industry. Nevertheless, the poor bonding strength, toughness, and water resistance of phenol-free lignin-based resins hinder their practical application. Herein, inspired by the hyperbranched structures of loose connective tissue, borate chemistry of plant cell walls, and Fe3+-phenol coordination bonds of mussel foot proteins, a tough, strong, water-resistant, and multifunctional lignin-based resin adhesive is fabricated through introducing phenylboronic acid-grafted hyperbranched polyamide (HBPB), Fe2(SO4)3, and furfural into the lignin matrix to construct lignin-based supramolecular networks. HBPB-induced microphase separation structure disperses mechanical stress and inhibits crack evolution. Meanwhile, hyperbranched phenylboronic ester bonds optimize the crosslinking strength and cohesive force. Furthermore, Fe3+-phenol coordination bonds facilitate the formation of hydrophobic structures to prevent moisture intrusion. Consequently, the fracture toughness, bonding strength, and wet bonding strength of the resin are 23.4, 6.1, and 5.4 times higher than those of the unmodified resin. Moreover, the resin exhibits excellent flame retardancy, recyclability, degradability, biosafety, and plant-growth promotion after degradation. This biomimetic design provides an effective approach to develop tough, strong, water-resistant, and multifunctional bio-based adhesives.

Rosacea is a common chronic dermatosis. Clinically, rosacea can present with flushing, erythema, papules, pustules, telangiectasias, phymatous changes, pruritus, burning, and stinging. In 2017, the National Rosacea Society Expert Committee recommended a phenotype-based classification for therapy. In this review, we identify monotherapies and multimodal treatment approaches for the clinical management of rosacea including topical, systemic, laser and light, alternative, and combination therapies.

Broussonetia papyrifera is a multifunctional deciduous tree that is both a food and a source of traditional Chinese medicine for both humans and animals. Further analysis of the UGT gene family is of great significance to the utilization of B. papyrifera. The substrates of plant UGT genes include highly diverse and complex chemicals, such as flavonoids and terpenes. In order to deepen our understanding of this family, a comprehensive analysis was performed. Phylogenetic analysis showed that 155 BpUGTs were divided into 15 subgroups. A conserved motif analysis showed that BpUGT proteins in the same subgroups possessed similar motif structures. Tandem duplication was the primary driving force for the expansion of the BpUGT gene family. The global promoter analysis indicated that they were associated with complex hormone regulatory networks and the stress response, as well as the synthesis of secondary metabolites. The expression pattern analysis showed that the expression level of BpUGTs in leaves and roots was higher than that in fruits and stems. Next, we determined the composition and content of flavonoids, the main products of the BpUGT reaction. A total of 19 compounds were isolated and analyzed by UPLC-ESI-MS/MS in 3 species of Broussonetia including B. kazinoki, B. papyrifera, and B. kazinoki × B. papyrifera, and the number of compounds was different in these 3 species. The total flavonoid content and antioxidant capacities of the three species were analyzed respectively. All assays exhibited the same trend: the hybrid paper mulberry showed a higher total flavonoid content, a higher total phenol content and higher antioxidant activity than the other two species. Overall, our study provides valuable information for understanding the function of BpUGTs in the biosynthesis of flavonoids.

Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998-2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.