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Vesicoureteral reflux (VUR) is associated with recurrent febrile urinary tract infections (FUTIs) and renal scarring in children. Uromodulin (UMOD), one of&#xa0;the most abundant urinary proteins, has been proposed as a protective factor against UTIs and a marker of tubular function. Whether urinary UMOD (uUMOD) concentrations differ between children with VUR with and without renal scars remains unexplored. This was an exploratory, hypothesis-generating pilot study. We enrolled 42 children with VUR, at least one documented FUTI, normal eGFR, and no other urinary tract malformation, along with 17 age- and sex-matched healthy controls. uUMOD concentration (&#xb5;g/ml) was measured in first-morning spot urine by ELISA. Children with renal scars on DMSA scintigraphy were classified as Group A (n = 22); those without scars as Group B (n = 20). The uUMOD/urinary creatinine ratio (uUMOD/uCre, expressed as mg/g) was used as the primary creatinine-corrected biomarker endpoint to adjust for urinary dilution. No formal a priori power calculation was feasible given the absence of prior pediatric data in this specific setting; sample size was determined by convenience sampling. Absolute uUMOD concentrations were significantly lower in children with VUR compared to controls (p = 0.005), and lowest in Group A. However, the uUMOD/uCre ratio did not differ significantly among the three groups (Group A: 29.0 mg/g; Group B: 38.5 mg/g; controls: 36.5 mg/g; p = NS). Multivariate analysis confirmed strong collinearity between uUMOD and urinary creatinine (p<0.0001): when both were included in the regression model, only uCre retained independent significance (p = 0.01), while uUMOD did not (p = 0.18). No significant association was found between uUMOD/uCre and renal scarring, FUTI frequency, or VUR grade. In children with VUR, the reduction in absolute uUMOD most likely reflects impaired tubular concentrating capacity rather than an independent downregulation of uromodulin secretion. This conclusion is inferred from the strong collinearity pattern and should be confirmed in future studies including direct measures of urinary concentrating ability (osmolality, specific gravity). Spot uUMOD should not be used as a standalone biomarker for renal scar risk stratification in VUR. Future prospective studies should adopt creatinine-corrected measurements or timed urine collections as primary endpoints, with adequate sample sizes, to properly evaluate uromodulin as a clinical biomarker in this population.

Fibrotic scar formation constitutes a significant pathological obstacle that impedes neural regeneration and long-term functional recovery following spinal cord injury (SCI). However, the spatial distribution of key pro-fibrotic mediators within lesion scars and the upstream regulatory mechanisms driving fibroblast activation remain inadequately defined. This study aims to characterize CD36-associated fibrotic remodeling after SCI and to determine whether targeting the c-Jun-Irf8-CD36 axis could attenuate scar formation, improve the regenerative microenvironment, and promote functional recovery. This study integrated single-cell ribonucleic acid sequencing and spatial transcriptomic profiling to characterize CD36 expression patterns and identify fibroblast subpopulations within SCI scars. Pharmacological interventions were administered in mouse SCI models, using salvianolic acid B (SAB) to inhibit CD36 and T5224 to block AP-1/c-Jun activity. Histological and immunofluorescence analyses were performed to assess fibroblast accumulation, extracellular matrix deposition, angiogenesis, and axonal regeneration, alongside longitudinal behavioral evaluations of locomotor function. Mechanistic validation of the regulatory pathway was achieved through CUT&Tag and dual-luciferase reporter assays to investigate c-Jun-Irf8-CD36 transcriptional regulation, complemented by integrated single-cell/spatial analyses to assess fibroblast subcluster remodeling post-treatment. Spatial and single-cell analyses demonstrated that CD36 is predominantly localized within lesion scars, correlating with fibrotic progression and preferentially upregulated in specific fibroblast subclusters. SAB-mediated CD36 inhibition markedly reduced P4HB+ fibroblast accumulation, alleviated fibrotic deposition, enhanced angiogenesis and axonal regeneration, and improved hindlimb functional recovery. Mechanistically, c-Jun was upregulated in scar regions and indirectly promoted CD36 transcription through Irf8 activation, establishing a c-Jun-Irf8-CD36 signaling axis. CUT&Tag and reporter assays confirmed c-Jun binding to the Irf8 promoter, leading to Irf8-driven CD36 transcription. Similarly, T5224 downregulated CD36 expression, reduced fibroblast aggregation and matrix deposition, facilitated vascular remodeling, and promoted early functional recovery. These findings demonstrate that modulating this signaling pathway can significantly inhibit pathological scar formation and facilitate approximately scar-free healing, thereby providing an ideal microenvironment for tissue regeneration. Multi-omic analyses further revealed that T5224 selectively inhibited the aberrant expansion of CD36+ fibroblast subclusters and reprogrammed their transcriptional states toward a less fibrotic phenotype. The c-Jun-Irf8-CD36 axis serves as a pivotal regulator of fibrotic scar formation after SCI. Targeting this pathway through CD36 inhibition (SAB) or AP-1/c-Jun blockade (T5224) attenuates fibrosis, remodels the scar microenvironment, enhances tissue repair, and promotes functional recovery, highlighting a promising therapeutic strategy for central nervous system injury.

Conventional alar base excision, which places incisions anterior to the alar-facial groove, frequently leads to conspicuous scarring and iatrogenic nostril deformities. This technical note describes a modified combined sill and alar excision technique in which the incision is precisely positioned within the natural alar-facial groove and closed exclusively with intracutaneous sutures. Key surgical steps include (1) preoperative marking of the nasal sill and alar-facial groove; (2) incision placement strictly within the alar-facial groove; (3) customized tissue resection based on individual anatomic assessment; (4) medial rotation of the alar flap to optimize contour and projection; and (5) layered wound closure, with intracutaneous suturing reserved exclusively for the alar component. Outcome measures comprised the interalar-to-intercanthal distance ratio, qualitative assessment of nostril shape and symmetry, scar evaluation using the visual analog scale (VAS), and incidence of postoperative complications. A statistically significant reduction in the interalar-to-intercanthal distance ratio was observed. Horizontal nostril configuration decreased markedly, whereas the proportion of ideal pear-shaped nostrils increased significantly. Nostril symmetry improved across all cases. VAS scoring indicated that the majority of patients reported their scars as imperceptible or nearly imperceptible. No cases of alar deformity, infection, or hypertrophic scarring were observed. The modified combined sill and alar excision technique-featuring groove-precise incision placement and exclusive intracutaneous closure-provides a safe, effective, and reproducible solution for concurrent alar base narrowing and nostril refinement in Asian patients. It delivers predictable aesthetic outcomes, well-concealed scars, and harmonious, natural-looking nostril geometry.

Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare variant of cutaneous squamous cell carcinoma that can clinically mimic scar change and histologically overlap with other cutaneous spindle cell neoplasms. We report a 60-year-old woman with a nonhealing ulcerated lesion arising within a longstanding childhood abdominal burn scar. Histopathology demonstrated a mitotically active dermal spindle cell tumor with pancytokeratin positivity and patchy cytokeratin 5/6 expression. This rare case highlights that spindle cell squamous cell carcinoma can arise as a late malignant transformation within longstanding burn scars decades after the initial injury. We also review key histopathologic/immunohistochemical diagnostic pitfalls and summarize practical oncologic and surgical management considerations for treating cutaneous spindle cell squamous cell carcinoma in burn scars as a high-risk cutaneous squamous cell carcinoma.

Non-exudative retinal fluid in age-related macular degeneration (AMD) challenges the long-standing paradigm that any fluid on structural optical coherence tomography necessarily reflects neovascular exudation. Advances in multimodal imaging have revealed that both intraretinal fluid and subretinal fluid (SRF) may arise from non-neovascular mechanisms across intermediate AMD and geographic atrophy (GA). Non-exudative IRF encompasses 3 distinct processes: (1) degenerative mechanisms occurring in progressive atrophy, (2) "burnt-out" contraction with cavitation overlying chronic fibrotic scars, and (3) mechanical stress induced by underlying lesions (e.g., drusenoid pigment epithelium detachment [PED]), subretinal hyperreflective material) or traction at the vitreomacular interface. Non-exudative SRF reflects retinal pigment epithelium pump failure over drusen or drusenoid PEDs, but may also result from alterations within the photoreceptor outer segments (subretinal pseudocysts). Integrating these mechanisms into clinical interpretation shifts management from a fluid-based to a pathophysiology-based approach, recognizing that non-exudative fluid does not respond to anti-vascular endothelial growth factor therapy and instead signals advanced tissue stress and increased risk of GA progression.

The aim of this study was to determine the frequency, clinical forms and complications of Inherited epidermolysis bullosa in Dakar. we conducted a descriptive cross-sectional study with data collection from medical records of patients followed up for Inherited epidermolysis bullosa in the dermatology department of the Albert Royer Children's Hospital over an 11-year period. 36 patients were registered, representing a hospital frequency of 0.16% and a sex ratio of 0.6. Clinical forms were: dystrophic in 44%, simple in 33%, junctional in 17%, associated with congenital cutaneous aplasia in 6% (Bart's syndrome), Kindler's syndrome in 6%. Complications occurred in 39% of cases, including infections in 28%, hemodynamic disorders in 17% and digestive complications in 11%. Death was recorded in 11% as a result of infectious and anemia. We report a series of 36 cases of inherited epidermolysis bullosa, representing a hospital frequency of 0.16%. The most frequent clinical form is dystrophic. Complications are mainly infectious and hemodynamic. We emphasize the importance of follow-up in these patients, given the risk of skin cancer associated with the long-term prognosis of scars in dystrophic forms.

Skin fibrosis is a complex and progressive disorder characterized by excessive extracellular matrix deposition, persistent fibroblast activation and pathological tissue stiffening. Its clinical manifestations such as keloids, hypertrophic scars and systemic sclerosis, can lead to functional impairment, aesthetic disfigurement and significant psychosocial burden. Unfortunately, there are currently no efficient therapies that can halt or reverse skin fibrosis, largely due to our incomplete understanding of the dynamic molecular and cellular mechanisms driving fibrosis progression. Here, we review the advances on bioengineered models of skin fibrosis and discuss their emerging role in elucidating fibrotic pathways and enabling the identification and screening of therapeutic targets. We examine how multicellular and three-dimensional complexity, biochemical cues, mechanomodulatory biomaterials and advanced biofabrication strategies contribute to enhancing the human biomimicry of engineered models. Finally, we outline the challenges and future directions for the development of next-generation in vitro models that better recapitulate skin fibrosis dynamics and enhance translational relevance.

Solitons-localized wave packets that travel without spreading-play a central role in understanding transport and properties of nonlinear systems. In quantum many-body systems, however, such robust excitations are typically destroyed by thermalization. Here, we theoretically demonstrate the existence of solitonic excitations in high-energy states of Rydberg atom chains in the regime of strong nearest-neighbor Rydberg blockade. These localized wave packets propagate directionally atop a special class of reviving initial states related to quantum many-body scars and are capable of carrying energy. Exhibiting long coherence times, these states constitute a form of non-ergodic quantum dynamics and can be efficiently implemented on Rydberg atom simulators. In this work, in addition to a phenomenological description of solitons, we identify their counterpart in a classical nonlinear dynamical system, demonstrate their potential use in quantum information transfer, and conjecture their relevance for anomalous energy transport reported in numerical studies of Rydberg atom arrays.

In the Brazilian Amazon, most snakebites are caused by Bothrops atrox. Although pediatric cases are less frequent, children are more vulnerable to severe complications and long-term disabilities. This study aims to describe the clinical profile of B. atrox envenomation in children treated at a tertiary hospital in Manaus, in Western Brazilian Amazon, and to characterize the resulting long-term musculoskeletal impairments in a subgroup of these patients. We retrospectively analyzed sociodemographic and clinical data from patients up to 12 years and 11 months of age treated between January 2010 and December 2023. A total of 258 children who were victims of B. atrox envenoming were eligible; however, a subgroup of 27 children underwent in-person musculoskeletal evaluations starting three months after hospital discharge. In the subgroup of children evaluated, the majority were male (63%), were aged over ten years (59.3%), and were from rural areas (96.3%). Over half (51.8%) received medical care within six hours after the bite. The lower limbs were most frequently affected (96.3%). Common local symptoms included pain (100%), edema (96.3%), bleeding (37%), and bruising (29.6%). Secondary infections occurred in 18.5% of cases. Most envenomations were classified as moderate in severity (44.4%). In this subgroup, long-term disabilities were identified in 21 children (77.7%), who presented primarily with intermittent chronic pain (55.5%). Physical examination revealed scars (59.3%), edema (22.2%), and deformities (3.7%). Sensory alterations were noted in tactile (11.1%), pain (25.9%), thermal (22.2%), and vibratory (29.6%) sensitivity. Range of motion was impaired in 37% of cases, and one child exhibited abnormal posture and reflexes. This study highlights a broad spectrum of persistent musculoskeletal sequelae following Bothrops envenomation in children. Our findings underscore the urgent need for comprehensive care, follow-up, and rehabilitation programs for pediatric snakebite victims in the Amazon region.

Ocular toxoplasmosis (OT) is a parasitic ocular disorder triggered by Toxoplasma gondii infection, ranking as a leading cause of posterior uveitis. This pathogen spreads globally, with nearly one-third of the world's population having previous infection evidence, and OT may cause irreversible severe visual loss; its typical fundus features include vitreous opacities and focal yellowish-white inflammatory chorioretinal lesions, while active lesions often emerge beside old pigmented chorioretinal scars, and lesions involving the macula or optic disc usually lead to poor visual outcomes. Human immune function changes with age: it is immature in infancy, matures in young adulthood, and declines in the elderly via immunosenescence, which weakens innate and adaptive immunity, induces chronic low-grade inflammation, and raises infection risk. OT diagnosis mainly relies on typical fundus manifestations, while atypical cases require combined serological detection, Goldmann-Witmer coefficient detection and intraocular fluid PCR tests. The classic triple therapy carries obvious adverse reactions damaging bone marrow, liver and kidneys, so trimethoprim-sulfamethoxazole serves as a common alternative anti-parasite drug, with corticosteroids added as needed to suppress inflammation. For severe complications such as dense vitreous opacification, retinal detachment, retinal breaks and vitreous hemorrhage, pars plana vitrectomy combined with intraoperative laser photocoagulation is the primary surgical option. This paper reports an immunocompetent elderly OT patient who achieved a favorable prognosis after combined surgical intervention and postoperative anti-Toxoplasma medication, and further summarizes the core diagnostic essentials of OT as well as the clinical indications and value of vitrectomy.

Giant retinal tears are full-thickness retinal breaks extending 90&#xb0; or more circumferentially and are typically associated with a high risk of rhegmatogenous retinal detachment and proliferative vitreoretinopathy. Surgical intervention remains the standard&#xa0;treatment in most cases. We report two cases of giant retinal tears without retinal detachment treated with primary argon laser photocoagulation. A 56-year-old man presented with a superotemporal retinal tear in the left eye extending from 12 to 4 o'clock, while a 56-year-old woman presented with a temporal retinal tear in the right eye extending from 7 to 11 o'clock. In both cases, the retina remained attached, with no subretinal fluid or macular involvement. Treatment consisted of barrier laser photocoagulation around the tear combined with 360&#xb0; peripheral laser cerclage and prophylactic laser treatment of the fellow eye. At 12 and 18 months of follow-up, respectively, both patients maintained a best-corrected visual acuity with stable retinal attachment, well-formed laser scars, and no evidence of proliferative vitreoretinopathy or other complications. To our knowledge, this is among the few reported cases of GRT without retinal detachment successfully managed with laser photocoagulation alone combined with 360&#xb0; peripheral laser cerclage.

Procedures addressing the external genitalia, particularly labia minora, have become increasingly popular in aesthetic surgery. However, the labia majora is often overlooked despite its essential contribution to the overall genital harmony. This study presents a multivector modification technique for labia majoraplasty aimed at restoring a youthful, smooth contour. Twenty-four patients presenting with sagging, wrinkling, and loss of adipose volume in the labia majora were included. A longitudinal incision along the interlabial sulcus and a transverse incision along the anogenital junction were combined. Deep tissue plication with delayed-absorbable sutures was performed for contouring before skin trimming and layered closure. Patient age ranged from 39 to 58 years, and 12 patients (50%) were active smokers. The median operative time was 55 minutes. No intraoperative or postoperative complications were observed during the follow-up period. Mild postoperative edema resolved spontaneously within 4 weeks. At follow-up, patients reported subjective improvement in aesthetic appearance and functional comfort, while preserved sensation and well-concealed scars were noted clinically. The described multivector labia majoraplasty technique appears to be a feasible approach for addressing labia majora ptosis and contour deformity by combining multidirectional skin excision with deep tissue support. Early outcomes in this preliminary case series were encouraging; however, larger comparative studies with validated outcome measures and longer follow-up are required to confirm long-term efficacy and durability. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.