Beliefs and experiences of educators when involved in the design of a Learning-by-concordance tool: A qualitative interpretative study.

BACKGROUND: Based on the involvement of qualified educators in its design, the Learning-by-Concordance tool aims to promote the learning of reasoning in contexts of uncertainty. However, data are still scarce on the experience of educators in terms of sharing and exposing their reasoning processes using this tool. PURPOSE: This study sought to explore the beliefs and experiences of educators when involved in the design of a Learning-by-Concordance tool. METHOD: This research used a descriptive qualitative design. Four dialogue groups were conducted with educators with different roles and responsibilities while designing a Learning-by-Concordance tool. A descriptive interpretative analysis of educators' verbatim quotes was done. FINDINGS: A total of 14 participants took part in the study. The results show the discomfort of educators despite their recognized expertise. Three themes emerged: 1- the need to be reassured by the opinions of colleagues; 2-feeling like impostors; and 3- concerns for the quality of instructional supports. CONCLUSIONS: The role taken by educators for teaching reasoning in contexts of uncertainty is to draw on practical experience where different types of knowledge intersect and are mobilized, to overcome feelings of insecurity, and to engage in close and authentic conversation with learners.

Hypospadias Reconstruction Training: Development of an Ex-Vivo Model for Objective Evaluation of Surgical Skills.

OBJECTIVES: To objectively evaluate technical skill acquisition in hypospadias repair procedures during surgical training using non-invasive wearable sensor technology. METHODS: We combined subjective video evaluations with objective electromyography (EMG) measurements in a hands-on hypospadias training course. Surgeons wore wireless EMG and accelerometer sensors on their dominant hand while performing tasks on ex-vivo cadaveric calf penises. The study focused on four skills: urethral mobilization, dorsal inlay graft harvest/implantation, meatal-based flap urethroplasty, and dorsal plication. Machine learning techniques analyzed muscle activation patterns and attributes for assessing surgical precision. RESULTS: The course included 18 participants (10 female, 8 males; average age 40.18 ± 8.46 years) categorized as novice (n=10, <3 years' experience), intermediate (n=5, 3-5 years), and expert (n=3, >5 years). Video evaluations did not reveal significant differences due to short-term training. However, EMG measurements showed significant reductions in average EMG power, total time, dominant frequency, and cumulative muscle workload after training. Additionally, the mean power spectral density of the EMG signal decreased notably post-training. CONCLUSIONS: This study presents a structured approach for hypospadias training and highlights the effectiveness of wearable sensor technology for objective skill assessment. While video evaluations did not detect significant changes, EMG data provided measurable differences in skill acquisition, suggesting that wearable sensors could enhance objective evaluations of surgical proficiency in residency programs.

Limits of Stability during a Therapeutic Exercise Intervention for Instability: Progression, Responders' and Non-Responders' Analysis and Predictors.

Background/Objectives: Instability is one of the main symptoms in patients with vestibular and neurological disorders and therapeutic exercise interventions are increasing in popularity as a form of treatment. Additionally, the limits of stability measurement are known to be a good tool for balance evaluation and monitoring of these interventions. The aim of this work is to better understand how a specific protocol provokes changes on this variable and to study the characteristics of those who do and do not respond to it. Methods: A retrospective study was developed with the data of 40 patients treated in the Otorhinolaryngology department in Clínica Universidad de Navarra (Madrid, Spain). They had an initial reduction in limits of stability, completed the proposed protocol with home-based and hospital-based exercises and with frequent limits of stability remeasurement, and were assisted to a follow-up retest after 1-2 months. Results: A progressive improvement in limits of stability measure was developed through the intervention and was partially retained at follow-up visit. Several differences were found between those patients who improved with the treatment (responders) and those who did not improve (non-responders). More specifically an initial measure of the limits of stability was able to differentiate those groups with a cut-off data of 56 cm2. Conclusions: The proposed protocol was able to induce motor learning in patients included in this study with good retention after 1-2 months. Furthermore, there is some variability in how patients respond to the treatment. Age and diagnosis should be considered and an interesting cut-off data for clinal decision making was found.

Advancements in Hypospadias Management: Trends, Techniques, Training, and Patient-Centric Outcomes.

Hypospadias has drawn increasing attention due to its prevalence, complex etiology, and significant impacts on psychological and sexual quality of life. This comprehensive review delves into the facets of hypospadias management, exploring pivotal themes that shape present understanding and practice. We demonstrate potential explanatory factors for its incidence through an analysis of geographic, genetic, and environmental influences. We then contextualize care by exploring historical and evolving surgical techniques, and highlight that advances in surgical approaches employ a spectrum of repair strategies. Innovation in surgical training, with a focus on simulation-based methodologies, offers a bridge between didactic learning and real-world application, which is particularly relevant due to the demonstrated effect of personal experience with hypospadias repair outcomes. Considering the importance of mentorship, case exposure, and hands-on practice, a holistic understanding of expertise cultivation at each training stage is essential. Lastly, patient-centric outcomes research must take center stage, particularly as the impact of our interventions on children with hypospadias will be judged by them as adults. Shifting from solely surgeon-reported outcomes to patient-reported outcomes is emphasized in the review, allowing for a more comprehensive assessment of the influence of surgical interventions across the lifespan. Integrating patients' perspectives refines surgical decision-making to align with expectations, ultimately enhancing overall satisfaction. Our multi-pronged exploration of advancements in hypospadias underscores the symbiotic relationship between evolving surgical techniques, training methodologies, personal experience, and patientreported outcomes. As the field progresses, these insights will collectively contribute to optimizing hypospadias care, advancing both medical practice and patient well-being.

Expert classification of hypospadias: an external validation and evaluation of agreement for Glans-Urethral Meatus-Shaft (GMS) and Hypospadias Objective Penile Evaluation (HOPE) scores.

PURPOSE: This study evaluates the inter-rater agreements of both the Glans-Urethral Meatus-Shaft (GMS) hypospadias score and Hypospadias Objective Penile Evaluation (HOPE) score, aiming to standardize disease classification for consistent agreement in clinically relevant characteristics of hypospadias. METHODS: Photos of hypospadias in children were collected from two separate institutions. Three raters scored the photos using GMS and HOPE, excluding penile torsion and curvature assessment in HOPE due to photo limitations. RESULTS: A total of 528 photos were included. With GMS, Fleiss' multi-rater kappa showed an agreement of 0.745 for glans-urethral plate, 0.869 for meatus, and 0.745 for shaft. For HOPE scores, the agreements were 0.888 for position of meatus, 0.669 for shape of meatus, 0.730 for shape of glans, and 0.708 for the shape of the skin. The lower agreement in the shape of the meatus evaluation may be attributed to the lack of a quantitative classification method in HOPE. Experts rely on their subjective judgment based on the provided example photos and their index patient. CONCLUSIONS: While there is high agreement among experts when evaluating hypospadias using the GMS and HOPE scoring criteria, only the position of the meatus achieved nearly perfect agreement highlighting that the current scoring systems entail a subjective element in disease classification.

Insights from therapeutic strategies in superior canal dehiscence syndrome: is there anything beyond surgical treatment?

INTRODUCTION: Superior semicircular canal dehiscence syndrome (SCDS) is a clinical syndrome that can cause instability, vertigo, fullness, tinnitus, autophony, hearing loss (HL), Tullio phenomenon, or Hennebert's sign. Historically, surgery has been the primary treatment reported in the literature, although some medical treatments may also be proposed. This study aims to comprehensively characterize SCDS in a large series of patients from clinical, auditory, and vestibular perspectives, and explore medical alternatives to conventional surgical treatments by comparing their results and evolution. METHODS: A retrospective observational study was designed in a tertiary care center. Audiovestibular tests evaluated included pure-tone audiometry (PTA), VEMPs, video head impulse test (vHIT), and CT imaging. Improvement was assessed over a follow-up period of up to 6 months for seven cardinal symptoms to verify the efficacy of the proposed treatments. RESULTS: 71 subjects with SCDS and a mean age of 51.20 ± 12.22 years were included in the study. The most common symptom found in our sample was instability in 31 patients (43.66%), followed by aural fullness or tinnitus in 29 subjects (40.85%). 36 patients (43.66%) received medical treatment, with 28 of them (77.78%) showing symptom reduction. Surgical repair was indicated in five patients, with all showing symptom improvement. Statistically significant improvement (p < 0.05) was observed, particularly with surgical treatment and acetazolamide, in both symptoms and objective tests such as pure-tone audiometry and VEMPs. CONCLUSION: SCDS shows significant similarities with other otic capsule dehiscences. It is essential to perform VEMPs and CT scans to complete the diagnosis, which is usually accompanied by clearly recognizable clinical criteria. Surgery for SCDS is effective, safe, and without complications. However, in cases where symptoms are mild to moderate, addressing this condition with medical treatment using diuretics such as acetazolamide has shown promising results.

Using learning-by-concordance to develop reasoning in epistaxis management with online feedback: A pilot study.

BACKGROUND: Epistaxis is a recurring cause for referral to emergency departments. Its management can be complex; hence, it is critical to provide appropriate support to Otolaryngology-Head and Neck Surgery (OHNS) residents to develop clinical reasoning skills to manage such cases. Learning-by-Concordance (LbC) is a recently developed educational tool that encourages learners to think through simulated clinical scenarios. A panel of ENTs provides insightful feedback to residents, reflecting a diversity of opinions about practice. Our study aimed to assess LbC's feasibility and perceived value for training OHNS residents in epistaxis management. METHODS: In this qualitative study, three OHNS surgeons, including two faculty members and one resident, wrote the LbC scenarios. The LbC tool was made available to participants through an online platform. A panel of four OHNS faculty provided feedback on answers to LbC questions. Otolaryngology-Head and Neck Surgery residents participated and provided their opinion on the value of this educational tool through an online questionnaire. RESULTS: A total of 10 one-hour sessions were required to create and upload the training tool. To provide insightful feedback embedded in the learning tool, the four panelists needed 60 min each. Of the 37 participating residents, 25 (68%) completed the training. Overall satisfaction was high: 88% appreciated the training method, and 92% wanted to use this type of training again. Most residents felt the training enabled them to improve their clinical reasoning when encountering a patient with epistaxis (92%) and their knowledge about epistaxis (96%). CONCLUSION: Findings suggest that OHNS residents could benefit from clinical reasoning exercises with panelist feedback using the LbC approach for clinical presentations that require complex approaches to manage conditions such as epistaxis.

Designing and validating a clinical decision support algorithm for diabetic nephroprotection in older patients.

BACKGROUND: Older patients with diabetic kidney disease (DKD) often do not receive optimal pharmacological treatment. Current clinical practice guidelines (CPGs) do not incorporate the concept of personalised care. Clinical decision support (CDS) algorithms that consider both evidence and personalised care to improve patient outcomes can improve the care of older adults. The aim of this research is to design and validate a CDS algorithm for prescribing renin-angiotensin-aldosterone system inhibitors (RAASi) for older patients with diabetes. METHODS: The design of the CDS tool included the following phases: (1) gathering evidence from systematic reviews and meta-analyses of randomised clinical trials to determine the number needed to treat (NNT) and time-to-benefit (TTB) values applicable to our target population for use in the algorithm. (2) Building a list of potential cases that addressed different prescribing scenarios (starting, adding or switching to RAASi). (3) Reviewing relevant guidelines and extracting all recommendations related to prescribing RAASi for DKD. (4) Matching NNT and TTB with specific clinical cases. (5) Validating the CDS algorithm using Delphi technique. RESULTS: We created a CDS algorithm that covered 15 possible scenarios and we generated 36 personalised and nine general recommendations based on the calculated and matched NNT and TTB values and considering the patient's life expectancy and functional capacity. The algorithm was validated by experts in three rounds of Delphi study. CONCLUSION: We designed an evidence-informed CDS algorithm that integrates considerations often overlooked in CPGs. The next steps include testing the CDS algorithm in a clinical trial.

Clinical Profile, Trends, and Management in Pediatric Patients with Audiovestibular Disorders: Can We Predict Emotional Disability in Pediatric Patients with Episodes of Vertigo and Dizziness?

BACKGROUND: Audiovestibular disorders in childhood occur with considerable frequency. However, the difficulty of obtaining medical history, the nonspecificity of symptoms, and the lack of cooperation during complementary tests often contribute significantly to diagnostic biases, attributing clinical presentations to psychosomatic disorders. The objectives of this work are, firstly, to characterize, from an auditory and vestibular perspective, the most frequent causes of vertigo in childhood and a possible relationship with emotional symptoms. On the other hand, to propose the usefulness of the MSSQ-Short questionnaire as a predictive variable in the evolution of children diagnosed with recurrent vertigo of childhood (RVC). METHODS: An observational cross-sectional study was designed with retrospective data collection at three tertiary hospitals. RESULTS: Among the 117 patients recruited between 2016 and 2024, 32 patients (27.35%) were diagnosed with an anxious-depressive syndrome prior to audiovestibular testing. The mean age was 11.19 ± 5.61 years and the most frequent final diagnoses were vestibular migraine (VM) with 41.03% and RVC with 23.93%. Patients with VM, compared with RVC, are approximately 1.12 times more likely to have psychosomatic pathology (CI 0.39 to 3.25). The most sensitive and frequently altered test was VEMPS (39.32%), with statistical significance in VM and otic capsule dehiscence, while regarding the MSSQ-Short questionnaire, the linear regression of 0.28 indicates an increase in clinical duration with high questionnaire scores. CONCLUSIONS: Vestibular disorders causing dizziness and vertigo are challenging to diagnose, often due to lack of cooperation and/or symptom nonspecificity. A thorough medical history and complementary tests, including audiovestibular and imaging studies, are advisable, thus avoiding systematically attributing children's complaints to other psychosomatic disorders.

A New Suppression Index Calculation Using the Visually Enhanced Vestibulo-Ocular Reflex and Vestibulo-Ocular Reflex Suppression Paradigms in the Video Head Impulse Test.

The aim of this study is to calculate the gains of the quantified visually enhanced vestibulo-ocular reflex (qVVOR) and the quantified vestibulo-ocular reflex suppression (qVORS), using a specific system to generate a visual suppression index (SI) in healthy subjects obtained through the gains of qVVOR and qVORS, and to determine the normal values of the index, as well as the influence of age and sex variables on the SI. METHODS: This prospective observational clinical study includes 83 healthy subjects who underwent the head impulse and suppression tests (HIMP and SHIMP, respectively), qVVOR, and qVORS tests, all of the vHIT. The sinusoidal tests (qVVOR and qVORS) were conducted at an intended frequency of 0.75 Hz. The gains of these tests were calculated using a system specifically designed for this purpose. A formula for the SI was established using a ratio of the gains from these tests. Two SI values are presented: unilateral, distinct for each direction of head movement, and bilateral, representing the suppression of both sides simultaneously. RESULTS: Mean gains for the qVVORs were 0.981 ± 0.070 and 0.978 ± 0.077 for the rightwards and leftwards qVVORs, respectively. The gains for the suppressed tests were 0.334 ± 0.112 and 0.353 ± 0.110 for the rightwards and leftwards qVORSs, respectively. A difference of 0.05 Hz was observed between the expected (0.75 Hz) and the obtained frequency of head movement, which is statistically significant (p < 0.001). The SI was 0.342 ± 0.118 for the right side (right SI) and 0.363 ± 0.117 for the left side (left SI). The bilateral SI had a mean value of 0.295 ± 0.104. No significant differences in the SI were noted according to the subject's age. The SI for women was lower than in the case of males. CONCLUSIONS: The VVOR/VORS quantification algorithm allows for the reliable calculation of the numerical gain of qVVOR and qVORS with mathematical soundness and consistency of results. Our data support the use of a single or specific measure for direction of head movement; although significant differences exist, these differences are not clinically relevant.

Critical reflection in team-based practice: A narrative review.

INTRODUCTION: Research on critical reflection (a process of recognising and challenging assumptions that frame health care practice) has demonstrated strong potential for making health care more collaborative and equitable, yet its enactment within team-based health care remains underexplored. We conducted a narrative review to advance understanding of how critical reflection develops, occurs in and impacts team-based practice and care. METHODS: We searched three databases (Medline, CINAHL and Scopus) for articles related to the concepts of critical reflection and/or critically reflective practice in the context of team-based health care and examined how teams engage with those theoretical concepts, to inform ideas for a new approach to support critically reflective practice. FINDINGS: The search identified 974 citations of which nine articles showed elements of critical reflection in team-based practice. However, since only one of the nine included articles explicitly used the term 'critical reflection' in their research, critical reflection as a theoretical concept was found to be largely missing from the current team-based health care literature. Instead, aspects of critical reflection were evident in terms of challenging power hierarchies and questioning practice assumptions through dialogue, with a goal of collaborative practice. This sharing of knowledge and skills allowed teams to push boundaries and innovate together in practice. The included articles also emphasised the importance of creating a purposeful environment for open dialogue and practice change to occur. CONCLUSION: To support equitable care through collaborative practices, we suggest dialogue as and for critical reflection should be explicitly developed and researched within team-based health care.

Posterior urethral valves and kidney transplantation: Identifying opportunities for improvement.

BACKGROUND: Posterior urethral valves (PUV) represents a heterogenous spectrum in which guidelines for management are lacking particularly for those patients facing end-stage kidney disease and transplant. In this study we aim to 1) evaluate our long term PUV pediatric transplant outcomes compared to those without lower urinary tract dysfunction and 2) assess our PUV cohort for trends in bladder management and evaluate outcomes to inform development of institutional guidelines. MATERIALS AND METHODS: A retrospective cohort analysis of all patients with a diagnosis of PUV who underwent kidney transplant from 2000 to 2023 was completed. A matched cohort of patients without lower urinary tract dysfunction was identified for comparison of graft function. Charts of PUV patients were reviewed for both sociodemographic and clinical variables. Patients were classified by bladder management at the time of transplantation into three separate groups for analysis: voiding, clean intermittent catheterization, and incontinent diversion. Primary outcomes of interest were eGFR, graft failure, and UTIs post-transplant. RESULTS: 45 patients met inclusion criteria. 69% were on dialysis prior to transplant. 51% of grafts were from a deceased donor. Bladder management consisted of voiding (62%), CIC (4 via urethra, 10 via channel) (31%), and incontinent diversion (7%). 20% underwent augmentation cystoplasty (5 = ureter, 2 = gastric, 1 = colon, and 1 = ileum) prior to or at the time of transplant. Median follow up duration was 5.4 years (3.0, 10.8). Patients on CIC had higher rates of UTI; however, we found no significant difference in graft function outcomes (eGFR, graft failure) between bladder management groups or year of transplant. VUR in the transplant kidney was associated with vesicostomy (p = 0.028). 2 of 2 gastric augments developed malignancy, one of which was cause of death. Graft failure rate was 22% in both the PUV group and matched cohort, with median interval times to failure of 6.7 years and 3.7 years, respectively (p = 0.71). There were no differences in eGFR at follow-up time points between the PUV and matched cohort. CONCLUSIONS: Patients with PUV represent a spectrum of disease with heterogeneous management before and after kidney transplant. Overall, graft function outcomes were similar when compared to matched cohort without lower urinary tract dysfunction. Patients on CIC had higher rates of UTI but without impact on graft function. Gastric augmentation cystoplasty should be avoided given risk for malignancy. Guidelines to standardize evaluation and management would be helpful for patient care and outcomes.

Visual Fixation of Skull-Vibration-Induced Nystagmus in Patients with Peripheral Vestibulopathy.

Nystagmus induced by applying an intense vibratory stimulus to the skull (SVIN) indicates vestibular functional asymmetry. In unilateral vestibular loss, a 100 Hz bone-conducted vibration given to either mastoid immediately causes a primarily horizontal nystagmus. The test is performed in darkness to avoid visual fixation (VF) but there are no data about how much VF affects the often-intense SVIN. The aim is to analyze the amount of reduction in SVIN when VF is allowed during testing. Thus, all patients seen in a tertiary hospital for vertigo or dizziness with positive SVIN were included. SVIN was recorded for 10 s for each condition: without VF (aSVINwo) and with VF (aSVINw). We obtained an aSVINwo and an aSVINw as average slow-phase velocities (SPV) without and with VF. VF index (FISVIN) was calculated as the ratio of SPV. Among the 124 patients included, spontaneous nystagmus (SN) was found in 25% and the median slow phase velocity (mSPV) (without VF) of SN was 2.6 ± 2.4°/s. Mean FISVIN was 0.27 ± 0.29. FISVIN was 0 in 42 patients, and FISVIN between 0 and 1 was found in 82 (mean FISVIN 0.39 ± 0.02). Fixation suppression was found in all patients with SVIN in cases of peripheral vestibulopathy. FISVIN clearly delineates two populations of patients: with or without a complete visual reduction in nystagmus.

Lymphatic Vessels in the Inner Ear of Patients With Meniere Disease: A Novel Pathological Finding.

Background: Meniere disease, characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure, is a common cause of vertigo in humans. The pathogenesis of Meniere disease remains unknown. The current study aimed to describe a novel pathological change discovered in the inner ears of patients with Meniere disease who underwent labyrinthectomy. Methods: This retrospective case-control study was conducted with 21 patients with MD who underwent labyrinthectomy. A total of 15 patients diagnosed with acoustic neuroma or glomus jugular tumor were review over the same period of time as control. The clinical information of the patients and the pathological features of the membrane are described. Results: The new pathological tissue was a morbid membrane structure sealing the round window, characterized by the formation of lymphatic capillaries. Histochemical and immunofluorescent staining was positive for D2-40, LYVE-1, podoplanin, and PROX1, which are the classical markers of the lymphatic vessels. Transmission electron microscopy revealed that the lymph capillaries lacked a typical basement membrane and that their ends were blind, composed of a single layer of endothelial cells with valval connection structures between adjacent capillary epithelial cells. Conclusion: This is the first report of lymphatic vessels in the human inner ear, and this pathological structure is a completely new discovery. The lymphatic vessels may develop due to inflammation or decompensation of pressure in the inner ear, suggesting that the inner ear can reactively form lymphatic vessels in some inflammation and fluid flow-dependent pathological conditions. The current findings help in improving our understanding of the pathogenesis of Meniere disease.

The black box of the relationship between breast cancer patients and accompanying patients: the accompanied patients' point of view.

BACKGROUND: The PAROLE-Onco program was introduced in the province of Quebec, Canada in 2019. It integrates accompanying patients (APs), i.e., people who have been affected by cancer, into the clinical team as full members. These APs use their experiential knowledge with people undergoing treatment and with clinical teams. The aim of this paper is to evaluate, within the framework of two university medical centers, the perceptions of breast cancer patients who receive support from APs, particularly in terms of their active involvement in their care trajectory. METHODS: A qualitative study based on semi-structured interviews with accompanied patients was performed. Fourteen individual interviews were conducted between July and September 2021 with women presenting different profiles in terms of age, education, professional status, type of treatment, family situation, and clinical background. The data were analyzed using thematic analysis, focusing on patients' perceptions of APs' contributions and suggested improvements for accessing AP support. RESULTS: Three themes emerged from the semi-structured interviews: communication modalities used to connect patients with their APs, the characteristics of the support provided by APs, and the perceived effects of this support on the patients. Patients expressed a preference for telephone communication, highlighting its convenience and accessibility. The support provided by APs included emotional and informational support, neutrality, and adaptability. This relationship improved patient communication, reduced anxiety, helped regain control, and enhanced overall quality of life. The results emphasized the added value of APs in complementing the support offered by healthcare professionals. Patients noted the critical role of APs in helping them navigate the healthcare system, better understand their treatment processes, and manage their emotions. The ability of APs to provide practical advice and emotional reassurance was particularly valued. Overall, the findings underscored the significant impact of AP support on patients' experiences and highlighted areas for enhancing this service. CONCLUSION: This study highlights, during the care trajectory of people affected by breast cancer, APs' contribution to patients' emotional well-being because they improve, in particular, the management of emotions and communication with health professionals.

In 2019, we initiated the PAROLE-Onco program in Quebec, Canada, to support cancer patients by integrating Accompanying Patients (APs) into the medical team. These individuals, who have personally experienced cancer, join as full team members, sharing their insights with both patients and medical staff. Our study delved into the perceptions of breast cancer patients at two university hospitals regarding APs' involvement in their care trajectory. Through interviews with 14 women of diverse backgrounds and cancer experiences, we found that APs were instrumental in enhancing communication with doctors, facilitating the expression of challenging emotions, and aiding in treatment decisions. Patients valued the inclusion of APs in their care team and expressed gratitude for their support. Nonetheless, some encountered difficulties in reaching out to APs due to a lack of awareness or challenges involved in connecting. Overall, our research underscores the positive impact of involving APs in the care of breast cancer patients, and of enhancing emotional well-being and communication throughout the treatment journey.

A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study.

BACKGROUND: The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques. RESULTS: Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster. CONCLUSIONS: VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.

Epigenetic insights to pediatric uropathology: Celebrating the fundamental biology vision of Tony Khoury.

INTRODUCTION: Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically. In this commentary, we highlight work on the critical role that epigenetic machinery, such as DNA methyltransferases (DNMTs), Enhancer of Zeste Polycomb Repressive Complex 2 Subunit (EZH2), and others play in regulating gene expression and cellular functions in three urological contexts. DESIGN: Animal and cellular constructs were used to model clinical pediatric uropathology. The hypertrophy, trabeculation, and fibrosis of the chronically obstructed bladder was explored using smooth muscle cell models employing disorganised vs. normal extracellular matrix (ECM), as well as a new animal model of chronic obstructive bladder disease (COBD) which retains its pathologic features even after bladder de-obstruction. Cell models from human and murine hypospadias or genital tubercles (GT) were used to illustrate developmental responses and epigenetic dependency of key developmental genes. Finally, using bladder urothelial and organoid culture systems, we examined activity of epigenetic machinery in response to non uropathogenic vs. uropathogenic E.coli (UPEC). DNMT and EZH2 expression and function were interrogated in these model systems. RESULTS: Disordered ECM exerted a principal mitogenic and epigenetic role for on bladder smooth muscle both in vitro and in CODB in vivo. Key genes, e.g., BDNF and KCNB2 were under epigenetic regulation in actively evolving obstruction and COBD, though each condition showed distinct epigenetic responses. In models of hypospadias, estrogen strongly dysregulated WNT and Hox expression, which was normalized by epigenetic inhibition. Finally, DNA methylation machinery in the urothelium showed specific activation when challenged by uropathogenic E.coli. Similarly, UPEC induces hypermethylation and downregulation of the growth suppressor p16INK4A. Moreover, host cells exposed to UPEC produced secreted factors inducing epigenetic responses transmissible from one affected cell to another without ongoing bacterial presence. DISCUSSION: Microenvironmental influences altered epigenetic activity in the three described urologic contexts. Considering that many obstructed bladders continue to display abnormal architecture and dysfunction despite relief of obstruction similar to after resection of posterior valves or BPH, the epigenetic mechanisms described highlight novel approaches for understanding the underlying smooth muscle myopathy of this crucial clinical problem. Similarly, there is evidence for an epigenetic basis of xenoestrogen on development of hypospadias, and UTI-induced pan-urothelial alteration of epigenetic marks and propensity for subsequent (recurrent) UTI. The impact of mechanical, hormonal, infectious triggers on genitourinary epigenetic machinery activity invite novel avenues for targeting epigenetic modifications associated with these non-cancer diseases in urology. This includes the use of deactivated CRISPR-based technologies for precise epigenome targeting and editing. Overall, we underscore the importance of understanding epigenetic regulation in pediatric urology for the development of innovative therapeutic and management strategies.

A Nationwide Online Tracking System of pediatric ICU demand and capacity during a respiratory epidemic in Uruguay / Desarrollo de un Sistema Nacional de Monitoreo En Línea de Capacidad y Demanda de las Unidades de Cuidados Intensivos Pediátricas Durante Una Epidemia Respiratoria

Monitoring national capacity of pediatric intensive care (PICU) beds is important for resource allocation. We describe the development and application of an online tool for bed occupancy monitoring during the respiratory epidemic of 2023 in Uruguay. A 5-minute survey was sent out daily to each PICU designated staff utilizing an instant messaging application, throughout the 12-week of 2023 winter season. The survey gathered information on staffed bed capacity, occupancy rates, invasive mechanical ventilation (IMV) demand and number of children admitted for lower respiratory tract infections (LRTIs). Data was manually entered using the REDcap Software platform. A comparison between PICUs from the capital city Montevideo (MVD) and the inland region (INN) was performed. Participating PICUs had access to a daily dashboard with nationwide data. We collected data from 100% (n=20) of Uruguayan PICUs, 68% in MVD (2.72 PICU beds per-10,000 <18 years) and 32% in the INN (0.86 PICU beds per-10,000 <18 years). National average bed occupancy rate was 55.5%, without differences between MVD and INN. However, LRTI admissions and IMV incidence were notably higher among INN PICUs compared with MVD PICUs, 83.0% vs. 71% (P<0.01) and 19.9% vs. 14.7% (P<0.01) respectively. During one week occupancy exceeded 80% without differences between MVD and INN. The implementation of a nationwide PICU bed monitoring tool was possible. Although occupancy rates did not reach critical levels at a national grade, regional differences were found that merit further study to improve vital PICUs resource allocation.

Monitorear la capacidad nacional de camas de cuidados intensivos pediátricos (UCIP) es importante para la asignación de recursos. Describimos el desarrollo y aplicación de una herramienta online para el seguimiento de la ocupación de camas durante la epidemia respiratoria de 2023 en Uruguay. Se envió diariamente una encuesta de 5 minutos a cada personal designado de la UCIP mediante una aplicación de mensajería instantánea, durante las 12 semanas de la temporada de invierno de 2023. La encuesta recopiló información sobre la capacidad de camas con personal, las tasas de ocupación, la demanda de ventilación mecánica invasiva (IMV) y el número de niños admitidos por infecciones del tracto respiratorio inferior (LRTI). Los datos se ingresaron manualmente utilizando la plataforma del software REDcap. Se realizó una comparación entre UCIP de la capital Montevideo (MVD) y del interior (INN). Las UCIP participantes tuvieron acceso a un panel diario con datos a nivel nacional. Se recolectaron datos del 100% (n=20) de las UCIP uruguayas, el 68% en MVD (2,72 camas UCIP por 10.000 <18 años) y el 32% en el INN (0,86 camas UCIP por 10.000 <18 años). La tasa de ocupación de camas promedio nacional fue del 55,5%, sin diferencias entre MVD e INN. Sin embargo, los ingresos por LRTI y la incidencia de IMV fueron notablemente mayores entre las UCIP INN en comparación con las UCIP MVD, 83,0% frente a 71% (P<0,01) y 19,9% frente a 14,7% (P<0,01), respectivamente. Durante una semana la ocupación superó el 80% sin diferencias entre MVD y INN. Fue posible implementar una herramienta de monitoreo de camas UCIP a nivel nacional. Aunque las tasas de ocupación no alcanzaron niveles críticos a nivel nacional, se encontraron diferencias regionales que merecen más estudios para mejorar la asignación de recursos vitales de las UCIP.

Two distinct regulatory systems control pulcherrimin biosynthesis in Bacillus subtilis.

Regulation of transcription is a fundamental process that allows bacteria to respond to external stimuli with appropriate timing and magnitude of response. In the soil bacterium Bacillus subtilis, transcriptional regulation is at the core of developmental processes needed for cell survival. Gene expression in cells transitioning from exponential phase to stationary phase is under the control of a group of transcription factors called transition state regulators (TSRs). TSRs influence numerous developmental processes including the decision between biofilm formation and motility, genetic competence, and sporulation, but the extent to which TSRs influence bacterial physiology remains to be fully elucidated. Here, we demonstrate two TSRs, ScoC and AbrB, along with the MarR-family transcription factor PchR negatively regulate production of the iron chelator pulcherrimin in B. subtilis. Genetic analysis of the relationship between the three transcription factors indicate that all are necessary to limit pulcherrimin production during exponential phase and influence the rate and total amount of pulcherrimin produced. Similarly, expression of the pulcherrimin biosynthesis gene yvmC was found to be under control of ScoC, AbrB, and PchR and correlated with the amount of pulcherrimin produced by each background. Lastly, our in vitro data indicate a weak direct role for ScoC in controlling pulcherrimin production along with AbrB and PchR. The layered regulation by two distinct regulatory systems underscores the important role for pulcherrimin in B. subtilis physiology.

Comparison of hypospadias phenotype pixel segmentation to GMS score.

BACKGROUND: Hypospadias phenotype assessment determines if the anatomy is favorable for reconstruction. Glans-Urethral Meatus-Shaft (GMS) has been adopted in an effort to standardize hypospadias classification. While extremely subjective, GMS has been widely used to classify the severity of the phenotype to predict surgical outcomes. The use of digital image analysis has proven to be feasible and prior efforts by our team have demonstrated that machine learning algorithms can emulate an expert's assessment of the phenotype. Nonetheless, the creation of these image recognition algorithms is highly subjective. In order to reduce a subjective input in the evaluation of the phenotype, we propose a novel approach to analyze the anatomy using digital image pixel analysis and to compare the results using the GMS score. Our hypothesis is that pixel cluster segmentation can discriminate between favorable and unfavorable anatomy. OBJECTIVE: To evaluate whether image segmentation and digital pixel analysis are able to analyze favorable vs unfavorable hypospadias anatomy in a less subjective manner than GMS score. METHODS: A total of 148 patients with different types of hypospadias were classified by 1 of 5 independent experts following the GMS score into "favorable" (GG), "moderately favorable" (GM) and "unfavorable" (GP) glans. From there, 592 images were generated using digital image segmentation. 584 were included for final analysis due to certain images being excluded for poor image quality or inadequate capture of target anatomy. For each image, the region of interest was segmented separately by two evaluators into "glans," "urethral plate," "foreskin" and "periurethral plate". The values obtained for each segmented region using machine-learning statistical pixel k-means cluster analysis were analyzed and compared to the GMS score given to that image using an ANOVA analysis. RESULTS: Analysis of image segmentation demonstrated that k-means pixel cluster analysis discriminated "favorable" vs "unfavorable" urethral plates. There was a significant difference between scores when comparing the GG and GM groups (p = 0.03) and GG and GP groups (p = 0.05). Pixel cluster analysis could not discriminate between "moderately favorable" and "unfavorable" urethral plates. CONCLUSIONS: Through our analysis, we found significant pairwise difference for different tissue qualities. Digital image segmentation and statistical k-means cluster analysis can discriminate anatomical features in a similar way to the GMS score. Future research can target discerning between different tissue qualities in an effort to predict surgical outcomes for hypospadias repair.