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176 papers

Patients with chronic kidney disease stage 3b: do general practitioners and nephrologists follow KDIGO guidelines?

Macedo JG et al. · Jul 1, 2026

Background Appropriate referral and management of patients with chronic kidney disease (CKD) from primary care to nephrologists are essential to prevent disease progression and complications. Objectives To describe the demographic and follow-up characteristics of patients with CKD stage 3b at the time of nephrology referral, the medical care offered by general practitioners, and the initial care provided by nephrologists in the Brazilian Unified Health System (SUS). Methods This retrospective cohort study included all patients with CKD stage 3b on the waiting list for nephrology consultation between January 2018 and January 2020 in a large city in southern Brazil. Sociodemographic data, comorbidities, and adherence to follow-up recommendations based on the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were analyzed. Laboratory test requests and results were compared between the periods of general practitioner care and the period following nephrology consultation. Results A total of 211 patients (mean age 74 ± 12 years) were included; 76.0% were hypertensive and 46.9% had diabetes. Approximately half had an adequate number of primary care appointments. Laboratory monitoring was suboptimal in both primary and specialized care. Before nephrology consultation, hemoglobin and urinalysis were available for 32.2% and 19.4% of patients, respectively. After consultation, hemoglobin and potassium results were documented in 68.3% and 58.8% of patients, respectively. Conclusion Although patients with CKD stage 3b were regularly followed, low adherence to KDIGO testing recommendations raises concerns about the adequacy of care. Strengthening communication and guideline implementation between primary care and nephrology services is crucial to improve CKD management within the SUS.

Medicine

RagC and Map4K3 deficiency in high-grade gliomas drives proliferation and modulates mTORC1-dependent cellular functions.

Kahr J et al. · Jul 1, 2026

Cellular growth and homeostasis via amino acid-responsive pathways are mediated by the mTOR signaling pathway. Rag GTPases and Map4K3 modify mTOR signaling as amino acid sensors. Altered mTOR signaling in relation to amino acid sensors might represent factors that modify proliferation and treatment responses in astrocytic tumors. To investigate this hypothesis, RagC and Map4K3 expression was studied in human gliomas, glioma cells (U87MG/U138MG), and nonglial cells (MCF-7, IOMM-Lee). RagC and Map4K3 knockout in glioma cells was generated using CRISPR-Cas and shRNA. High-grade astrocytomas had significantly reduced immunoreactivity for RagC and Map4K3 compared to low-grade astrocytomas. RagC- and Map4K3-deficient glioma cells had significantly increased proliferation and showed altered morphology and motility. Induced amino acid deficiency (leucine deprivation) reduced proliferation in Map4K3- but not in RagC-deficient cells. mTOR signaling in RagC- and Map4K3-deficient U87 cells was altered with increased phosphorylation of p70S6K and increased expression of RagD and transcription factor EB. In this context, uncoupled, exaggerated autophagy occurred in Map4K3-deficient U87 cells. In contrast, RagC-deficient U87 cells showed increased senescence but no autophagy induction. These data show that losses of RagC and Map4K3 in malignant gliomas have proliferation-inducing effects and differentially modulate key mTOR signaling-dependent cellular mechanisms.

Medicine

Cardiac output measurement in Malawian children ages 2 months-12 years hospitalised with severe anaemia (COM-TRACT).

Chintolo E et al. · Jul 1, 2026

Background Little is known about myocardial perturbations in African children hospitalised with severe anaemia. Methods An observational study nested within a clinical trial of blood transfusion was conducted on the paediatric ward in Blantyre, Malawi. Children were ages 2 months-12 years hospitalized with uncomplicated severe anaemia (haemoglobin 4-6 g/dl). By randomisation, 13 children received 30 ml/kg whole blood, 13 received 20 ml/kg whole blood and 26 had no immediate transfusion (usual care). We measured standard parameters of cardiac function using ultrasonic cardiac output monitoring (USCOM) at enrolment, 8 and 24 hours and discharge. Results Fifty-two children, median age 39 months (interquartile range [IQR] 25-58) and median haemoglobin 5.1 g/dl (IQR 4.8-5.6) were studied. Severe tachycardia and tachypnoea over time corrected faster in the transfused arms than the controls. At enrolment, the stroke volume index was within the normal range and 26/52 (50%) had a cardiac output index (COI) >97.5% the standard centile. The COI decreased in all arms by discharge but was greatest in the transfusion arms (p=0.05 for 20 ml/kg and p=0.009 for 30 ml/kg). A higher volume or receipt of whole blood did not worsen cardiac function. No child required diuretics. Conclusions The data generated by this small but granular study of haemodynamic and cardiac function provide reassuring physiological evidence showing the safety of higher doses of blood transfusion than currently recommended. It also supports the findings of a secondary analysis of the Transfusion and Treatment of Severe Anaemia in African Children trial indicating that whole blood transfusions are safe. These data support the new evidence-based paediatric transfusion algorithm for anaemic African children and its recommendation for safe use.

Medicine

Macro Monte Carlo dose calculation for very high energy electron (VHEE) radiotherapy.

Zhu C et al. · Jul 1, 2026

Background Very high energy electron (VHEE) radiotherapy has gained growing interest owing to its potential to reach deep-seated targets and induce FLASH effect. Dose calculations can be performed using analytical or Monte Carlo (MC) methods. Analytical approaches enable rapid dose computation but suffer from limited accuracy in heterogeneous media, whereas MC methods provide high accuracy at the expense of substantial computational cost. Macro Monte Carlo (MMC) is a local-to-global method designed to improve dose calculation efficiency compared to general-purpose MC methods. In MMC, particle transport is based on precalculated transport data generated with general-purpose MC simulations on specific geometries, which is subsequently used to model particle transport over macroscopic steps within the absorber, avoiding computationally expensive microscopic tracking. MMC made it to a standard electron dose calculation engine in a commercial treatment planning system. However, to date, MMC has not been investigated for electron energies above 25 MeV. Purpose To develop and validate an MMC framework for VHEE radiotherapy that improves dose calculation efficiency while preserving accuracy compared to general-purpose MC methods for electron energies up to 250 MeV. Methods Local simulations were performed using EGSnrc with monoenergetic electron pencil beams incident perpendicularly on spherical geometries (0.2-25 MeV) with radii of 0.5-3 mm, and slab geometries (25-250 MeV) of 2 mm thickness, composed of various materials. Physical quantities including energy loss, lateral displacement, and angular distributions of primary and secondary particles were scored and stored in a database. This database was subsequently used to transport electrons step-by-step in the global simulations, employing slab-based transport at energies ≥25 MeV and switching to spherical geometries for electron energies 2 . MMC and EGSnrc dose calculations were also performed for two patient CT datasets. Comparisons between MMC and EGSnrc were conducted using integrated depth dose curves, lateral dose profiles, and 3D gamma analysis with 2%/1 mm and 2%/2 mm (global) criteria and a 10% dose threshold. All simulations were performed with statistical uncertainties below 1%, and computation times were recorded. Results Integrated depth dose curves and lateral dose profiles agreed within 2% of the maximum dose for all cases considered. For homogeneous and heterogeneous phantoms, MMC dose distributions yielded gamma passing rates above 97% (2%/1 mm) and 99% (2%/2 mm), respectively, compared to EGSnrc. For patient CT datasets, gamma passing rates exceeded 94% (2%/1 mm) and 97% (2%/2 mm). Overall, MMC achieved up to a 27-fold improvement in dose calculation efficiency compared to EGSnrc. Conclusions An MMC framework for VHEE dose calculation was successfully developed and validated for electron energies up to 250 MeV. The method demonstrated good agreement with EGSnrc while providing up to an order-of-magnitude improvement in dose calculation efficiency for the studied cases.

Medicine

Survey on Inter- and Intra-Observer Variations of the Ultrasound Assessment of Dog Pancreases.

Turner RBS et al. · Jul 1, 2026

Abdominal ultrasonography (AUS) is considered an important diagnostic tool for assessing pancreatic disease in dogs. However, AUS interpretation is highly subjective and operator-dependent, with no prior studies evaluating observer variability in assessing the canine pancreas. This survey-based, observer agreement study aimed to assess inter- and intra-observer variability in the ultrasonographic evaluation of canine pancreases. Fifteen ultrasound images of dog pancreases were independently reviewed by 104 veterinary radiologists and radiology residents. Twenty-four veterinary radiologists repeated the review approximately 2.5 months later. Assessments included relative echogenicity, echotexture, margination, and clinical interpretation. Agreement was quantified using Krippendorff's alpha (Kα), prevalence-adjusted bias-adjusted kappa (PABAK), Cohen's kappa (κ), and intraclass correlation coefficient (ICC). Average inter-observer agreement was poor (Kα = 0.34), whereas intra-observer agreement was moderate (PABAK = 0.49). Global pancreatic echogenicity and echogenicity relative to mesenteric fat had the highest inter-observer agreement (Kα = 0.58 and 0.53, respectively) as did echotexture assessed by a semi-objective scale (Kα = 0.50). However, veterinary radiologists demonstrated poor inter-observer agreement on the clinical significance (Kα = 0.35) and prioritized cause (Kα = 0.14) of the pancreatic heterogeneity. Observer variables (age, training level, experience, primary practice, and accrediting organization) had minimal effect on inter-observer agreement, apart from experience, where early-career radiologists (<10 years' experience) demonstrated the highest inter-observer agreement among all groups, with moderate agreement for global echogenicity (Kα = 0.71). These findings highlight substantial variability in the ultrasonographic interpretation of the canine pancreas, particularly in clinical decision-making. Standardization of assessment criteria is necessary to improve consistency, clinical validity, and reduce diagnostic uncertainty.

Medicine

Evaluation of Short Videos Supporting Healthy Eating and Physical Activity in Early Childhood Education: The Small Bites for Big Steps Pilot Randomised Controlled Trial.

Jones RA et al. · Jul 1, 2026

Issue addressed Early childhood education and care (ECEC) centres are an ideal setting to promote key healthy eating and active living (HEAL) practices. Redesigning messages around such practices to be digital could help engage ECEC educators and assist with long-term implementation and reach. The aim of this study was to evaluate the potential impact of a HEAL-focused video initiative (Small Bites for Big Steps) on precursors to behaviour change including educators' self-efficacy, perceived behavioural control and behavioural intentions and the acceptability of the videos. Method A pilot randomised controlled trial was conducted with early childhood educators (56% aged 25-44 years, 98% female). Participants randomised to the intervention group received on average 3-4 weekly videos promoting HEAL practices, whilst participants in the control group maintained usual practice. Educators' self-efficacy, perceived behavioural control, and behavioural intention were assessed using questionnaires at baseline and post-intervention (9 weeks). Data were analysed using Mann Whitney U tests in SPSS and thematic analysis. Acceptability data were collected using questionnaires, focus groups, interviews, and Vimeo analytics. Results One hundred and six educators from 16 ECEC services were recruited. Exploratory efficacy analysis found significant improvements from baseline to post-intervention between groups for healthy eating/drinking perceived behavioural control. At post-intervention, there was a significant difference between intervention and control groups for healthy eating/drinking behavioural intention, physical activity behavioural intention, and overall behavioural intention. No significant between group differences were observed for changes in perceived behavioural control relating to physical activity or for any self-efficacy measures. Educators valued the content, length and approach of the videos. Limitations identified from the qualitative data included technical difficulties and cultural appropriateness. Conclusions This video-based intervention positively influenced educators' perceived behavioural control and behavioural intentions, key precursors to behaviour change. The video suite was acceptable to educators. SO WHAT?: Redesigning HEAL messages into video resources may support ECEC educators to promote and implement these practices to young children and their families/carers.

Medicine

Socio-Structural Factors as Predictors of Parents' Intentions to Enrol Their Children in Swimming Lessons.

Hamilton K et al. · Jul 1, 2026

Issue addressed Swimming lessons are an effective drowning prevention strategy, yet uptake remains socially patterned. Socio-structural factors such as parent age, sex and family income may shape parents' decisions to enrol their children in swimming lessons. According to the Theory of Planned Behaviour (TPB), people's beliefs, reflected in their attitudes, subjective norms and perceived control, drive health-related intentions. Socio-structural characteristics may therefore influence parents' intentions indirectly by shaping these underlying beliefs. This study examined an untested pathway, assessing whether socio-structural factors shape parents' beliefs and, in turn, their intentions to enrol children in swimming lessons. Methods Parents (N = 323) of primary school-aged children without prior formal lessons completed an online survey. Latent variable structural equation modelling in R (Lavaan) tested direct and indirect relationships between socio-structural factors, TPB constructs and intention. Results The model demonstrated good fit. Parent age predicted attitudes, subjective norms and perceived control. Sex directly predicted intention, while income predicted perceived control. All three TPB constructs significantly predicted intention, mediating the effects of age and income. The model explained 70% of variance in intention. Conclusions Parents' intention to enrol their children in swimming lessons is shaped indirectly by socio-structural characteristics through belief-based TPB constructs. This highlights the importance of integrating structural determinants into social cognition models to better understand inequities in preventive health behaviours. SO WHAT?: Strengthening positive attitudes, supportive social norms and parental confidence, while reducing financial and structural barriers to participation, may improve equitable access to swimming lessons and contribute to drowning prevention.

Medicine

Impact of Breath Holding on Spleen Stiffness Measured by 100 Hz Vibration Controlled Transient Elastography.

Atzori S et al. · Jul 1, 2026

Backgrounds and aims Ultrasound-based spleen stiffness measurement (SSM) is a valid non-invasive tool to assess portal hypertension (PH) in chronic liver disease. Whereas the role of the respiratory phase during liver stiffness measurements is established, no study has specifically addressed how respiration influences SSM by transient elastography. Aims To evaluate the influence of respiration on SSM assessed with FibroScan 630 (Echosens, Paris, France). Methods Eighty-three patients with chronic liver disease of different aetiologies underwent SSM using vibration-controlled transient elastography (VCTE). Results SSM acquired during a normal respiratory cycle showed better diagnostic accuracy than measurements obtained during breath-hold after deep inspiration (AUROC 0.835 [95% CI 0.743-0.928] vs. 0.798 [95% CI 0.697-0.899]). Conclusion SSM by VCTE should be performed during quiet breathing, as it showed good diagnostic accuracy for predicting the presence of oesophageal varices (OV) in patients with chronic liver disease.

Medicine

Clinical Features and Surgical Outcomes of Cats With Presumed Primary Lens Instability: A Retrospective Study of 34 Cases (2018-2022).

Sarfaty H et al. · Jul 1, 2026

Objective Describe the clinical features, disease progression, and outcomes of presumed primary lens instability (PLI) in cats, and to assess its association with glaucoma. Animals studied Thirty-four cats (68 eyes). Procedures Medical records were reviewed for signalment, clinical history, ophthalmic findings, and treatment. Eyes were classified as anterior lens luxation (ALL) or subluxated lens (SLL). Clinical monitoring included intraocular pressure (IOP), menace response, absence/presence of blepharospasm, and complications. Surgical eyes underwent intracapsular lens extraction or phacoemulsification, with or without vitrectomy. Results Cats were 1-13 years old (median 3 years) and predominantly male (82%). At presentation, 68% of eyes had ALL and 32% of eyes had SLL. Blepharospasm was observed in 25% of eyes, mostly in ALL. IOP was elevated (> 25 mmHg) in 38% of eyes overall, comprised of 62% SLL eyes (33 ± 5.7 mmHg) and 25% ALL eyes (54.8 ± 24.1 mmHg). Of SLL eyes followed ≥ 90 days, 73% progressed to ALL within a median of 15 days (5-174 days). Forty-four eyes underwent surgery and, of 42 with follow-up (median 284 days), 95% achieved comfort and 85% retained vision; however, 70% developed postoperative glaucoma within 68 ± 51 days that was still present in 35% of eyes at last recheck. Retinal complications occurred in 14% of operated eyes. Nonsurgical eyes also showed a high risk for IOP elevation. Conclusions Presumed PLI presents bilaterally in generally young cats, often with limited signs of ocular discomfort, but with a high risk of concurrent or delayed glaucoma. Lens extraction restores comfort and can preserve vision but does not prevent future IOP elevation.

Medicine

Oromucosal Administration of a Cannabidiol-Enriched Cannabis sp. Extract for 2 Weeks Moderately Reduces Cold Hyperalgesia in Rats With Neuropathic Pain.

Campos RMP et al. · Jul 1, 2026

Background Chronic neuropathic pain (CNP) involves complex interactions between resident and peripheral immune cells, as well as modulation of the endocannabinoid system. Cannabis-based products have emerged as promising therapeutic options, but their effects on immune cells remain unclear. This study evaluated the effects of a cannabidiol (CBD)-enriched Cannabis sp. extract administered via the oral mucosa in a CNP model. Methods Two-month-old Wistar rats of both sexes were randomly assigned to four groups. Two groups underwent chronic constriction injury (CCI) of the sciatic nerve, while the remaining groups underwent sham surgery (SHAM). Starting at Day 7 post-CCI, rats received either the CBD-enriched extract (10 mg/kg) or vehicle for 15 days. Mechanical and thermal sensitivity were assessed using the von Frey, acetone and hot plate tests. Ipsilateral spinal cord segments were analysed by flow cytometry, immunohistochemistry and western blotting. Results CCI induced thermal hyperalgesia and mechanical allodynia. Treatment with the CBD-enriched extract modestly reduced cold sensitivity in CCI rats of both sexes but did not improve heat sensitivity and had a significant but minor effect on mechanical thresholds. CCI increased spinal cord microglial cell numbers, particularly in females, an effect not modulated by treatment. No significant changes were detected in immune cell infiltration or CB1R, CB2R, or TRPV1 protein expression across groups. Conclusion Oromucosal treatment with a CBD-enriched extract modestly alleviates cold hypersensitivity in both sexes. Neuroimmune alterations in the spinal cord at 22 days post-CCI indicate a predominance of microglia, with no detectable peripheral immune cell infiltration, regardless of treatment. Significance statement This manuscript contributes to addressing gaps in the literature regarding preclinical models evaluating Cannabis sp. based products using treatment protocols that more closely reflect patient use, as commercially available cannabidiol-enriched extract and the oromucosal route, consistent with the route commonly used by patients. In addition, all experiments were conducted in animals of both sexes, addressing a well-recognised limitation of many preclinical studies in chronic pain research. Notably, the International Association for the Study of Pain has emphasised the need for further research in this area before endorsing the use of Cannabis sp. based products for the treatment of chronic pain.

Medicine