HoLEP Learning Curve-Resident Perspective: Survey of Senior Residents from High-Volume Tertiary Center.

Objective: We aim to report the learning curve and experience performing holmium laser enucleation of the prostate (HoLEP) from a resident standpoint trained at a tertiary high-volume center. Methods: An electronic survey was distributed to 10 surveyees that included recently graduated chief residents trained at Indiana University in the past 3 years i.e., between 2020 and 2022 with a 100% response rate. The questionnaire focused on HoLEP training experience based on a recently established mentorship curriculum in training the residents through each individual step of the surgery. Results: The average learning curve for performing HoLEP was reported to be greater than 25 cases with 50% of the residents reporting >50 cases to master the technique. The surgical difficulty of steps of the HoLEP were rated on a subjective scale of 1-5: 1 = very easy, 2 = easy, 3 = neutral, 4 = hard, and 5 = very hard. The common challenging steps in decreasing the order of difficulty as reported are performing apical enucleation, joining anterior and posterior planes, and dividing anterior commissure with a mean rating of 3.5, 3.1, and 3.1, respectively. The most difficult aspect of the surgery to master was performing apical dissection (60%). Comparing operative parameters for HoLEP with transurethral resection of the prostate in aspects of resection volume and times, 70% of candidates reported it better for HoLEP whereas 20% had similar times for both procedures. A total of 90% of the residents felt confident to offer HoLEP as part of their practice without the need for any further training. Regarding the initial challenge of including HoLEP surgery in practice, the majority (60%) reported difficulty with equipment set up in their practice while 20% reported difficulty maintaining efficient operating room (OR) times and turnover. Conclusion: We believe HoLEP can be performed immediately after residency training and incorporated into practice with high volume, repeated exposure to HoLEP surgery throughout residency based on study results. The average learning curve reported for performing HoLEP was greater than 25 cases.

The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1ß in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1ß. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.

Ethical and Professional Decision-Making Capabilities of Artificial Intelligence Chatbots: Evaluating ChatGPT's Professional Competencies in Medicine.

Purpose: We examined the performance of artificial intelligence chatbots on the PREview Practice Exam, an online situational judgment test for professionalism and ethics. Methods: We used validated methodologies to calculate scores and descriptive statistics, χ2 tests, and Fisher's exact tests to compare scores by model and competency. Results: GPT-3.5 and GPT-4 scored 6/9 (76th percentile) and 7/9 (92nd percentile), respectively, higher than medical school applicant averages of 5/9 (56th percentile). Both models answered 95 + % of questions correctly. Conclusions: Chatbots outperformed the average applicant on PREview, suggesting their potential for healthcare training and decision-making and highlighting risks of online assessment delivery.

Genetically Fusing Order-Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials.

The unique biophysical and biochemical properties of intrinsically disordered proteins (IDPs) and their recombinant derivatives, intrinsically disordered protein polymers (IDPPs) offer opportunities for producing multistimuli-responsive materials; their sequence-encoded disorder and tendency for phase separation facilitate the development of multifunctional materials. This review highlights the strategies for enhancing the structural diversity of elastin-like polypeptides (ELPs) and resilin-like polypeptides (RLPs), and their self-assembled structures via genetic fusion to ordered motifs such as helical or beta sheet domains. In particular, this review describes approaches that harness the synergistic interplay between order-promoting and thermoresponsive building blocks to design hybrid biomaterials, resulting in well-structured, stimuli-responsive supramolecular materials ordered on the nanoscale.

A simple three-cylinder radiometer and low-speed anemometer to characterize human extreme heat exposure.

As populations and temperatures of urban areas swell, more people face extreme heat and are at increasing risk of adverse health outcomes. Radiation accounts for much of human heat exposure but is rarely used as heat metric due to a lack of cost-effective and accurate sensors. To this end, we fuse the concepts of a three-globe radiometer-anemometer with a cylindrical human body shape representation, which is more realistic than a spherical representation. Using cost-effective and readily available materials, we fabricated two combinations of three cylinders with varying surface properties. These simple devices measure the convection coefficient and the shortwave and longwave radiative fluxes. We tested the devices in a wind tunnel and at fourteen outdoor sites during July 2023's record-setting heat wave in Tempe, Arizona. The average difference between pedestrian-level mean radiant temperature (MRT) measured using research-grade 3-way net radiometers and the three-cylinder setup was 0.4 ± 3.0 °C ( ±  1 SD). At most, we observed a 10 °C MRT difference on a white roof site with extreme MRT values (70 °C to 80 °C), which will be addressed through discussed design changes to the system. The measured heat transfer coefficient can be used to calculate wind speed below 2 m·s-1; thus, the three cylinders combined also serve as a low-speed anemometer. The novel setup could be used in affordable biometeorological stations and deployed across urban landscapes to build human-relevant heat sensing networks.

Genetically Fused Resilin-like Polypeptide-Coiled Coil Bundlemer Conjugates Exhibit Tunable Multistimuli-Responsiveness and Undergo Nanofibrillar Assembly.

Peptide-based materials are diverse candidates for self-assembly into modularly designed and stimuli-responsive nanostructures with precisely tunable compositions. Here, we genetically fused computationally designed coiled coil-forming peptides to the N- and C-termini of compositionally distinct multistimuli-responsive resilin-like polypeptides (RLPs) of various lengths. The successful expression of these hybrid polypeptides in bacterial hosts was confirmed through techniques such as gel electrophoresis, mass spectrometry, and amino acid analysis. Circular dichroism spectroscopy and ultraviolet-visible turbidimetry demonstrated that despite the fusion of disparate structural and responsive units, the coiled coils remained stable in the hybrid polypeptides, and the sequence-encoded differences in thermoresponsive phase separation of the RLPs were preserved. Cryogenic transmission electron microscopy and coarse-grained modeling showed that after thermal annealing in solution, the hybrid polypeptides adopted a closed loop conformation and assembled into nanofibrils capable of further hierarchically organizing into cluster structures and ribbon-like structures mediated by the self-association tendency of the RLPs.

Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy.

BACKGROUND: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges. METHODS: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients. FINDINGS: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data. INTERPRETATION: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination. FUNDING: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01).

Polariton design and modulation via van der Waals/doped semiconductor heterostructures.

Hyperbolic phonon polaritons (HPhPs) can be supported in materials where the real parts of their permittivities along different directions are opposite in sign. HPhPs offer confinements of long-wavelength light to deeply subdiffractional scales, while the evanescent field allows for interactions with substrates, enabling the tuning of HPhPs by altering the underlying materials. Yet, conventionally used noble metal and dielectric substrates restrict the tunability of this approach. To overcome this challenge, here we show that doped semiconductor substrates, e.g., InAs and CdO, enable a significant tuning effect and dynamic modulations. We elucidated HPhP tuning with the InAs plasma frequency in the near-field, with a maximum difference of 8.3 times. Moreover, the system can be dynamically modulated by photo-injecting carriers into the InAs substrate, leading to a wavevector change of ~20%. Overall, the demonstrated hBN/doped semiconductor platform offers significant improvements towards manipulating HPhPs, and potential for engineered and modulated polaritonic systems.

A Case of Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalaemia (BRASH) Syndrome in an Elderly Male and Its Management: A Case Report and Literature Review.

BRASH syndrome, characterized by bradycardia, renal dysfunction, atrioventricular (AV) nodal blockage, shock, and hyperkalemia, is a rare but potentially life-threatening condition resulting from the interplay between AV nodal blockers and hyperkalemia. This complex syndrome poses significant challenges in diagnosis and management, with patients often presenting with bradycardia and high potassium levels. This case report highlights the need for increased awareness of BRASH syndrome, especially in an aging population and evolving cardiovascular treatments. Early recognition and a comprehensive, multidisciplinary approach are crucial for improving outcomes in affected patients.

Observational Study on the Effect of Duration from Pediatric Advanced Life Support (PALS) Certification on PALS Performance in Pediatric Interns in Simulated Cardiopulmonary Arrest.

Pediatric advanced life support (PALS) training is critical for pediatric residents. It is unclear how well PALS skills are developed during this course or maintained overtime. This study evaluated PALS skills of pediatric interns using a validated PALS performance score following their initial PALS certification. All pediatric interns were invited to a 45-minute rapid cycle deliberate practice (RCDP) training session following their initial PALS certification from July 2017 to June 2019. The PALS score and times for key events were recorded for participants prior to RCDP training. We then compared performance scores for those who took PALS ≥3 months, between 3 days to 3 months and 3 days after PALS. There were 72 participants, 30 (of 30) in 3 days, 18 in 3 days to 3 months, and 24 in ≥3 months groups (42 total of 52 residents, 81%). The average PALS performance score was 53 ± 20%. There was no significant difference between the groups (3 days, 53 ± 15%; 3 days-3 months, 51 ± 19%; ≥3 months, 54 ± 26%, p = 0.922). Chest compressions started later in the ≥3 months groups compared with the 3 days or ≤3 months groups ( p = 0.036). Time to defibrillation was longer in the 3 days group than the other groups ( p = 0.008). Defibrillation was asked for in 3 days group at 97%, 73% in 3 days to 3 months and 68% in ≥3 months groups. PALS performance skills were poor in pediatric interns after PALS certification and was unchanged regardless of when training occurred. Our study supports the importance of supplemental resuscitation training in addition to the traditional PALS course.

Gilchrist's Hollow Lung.

Blastomycosis is an endemic mycosis in certain parts of North America. The dimorphic fungus can manifest with both pulmonary and extrapulmonary features. We present the case of a 24-year-old African American male with a history of vaping and daily marijuana who presented with hemoptysis and a cough of one-week duration. He was initially treated as community-acquired pneumonia (CAP). The patient had a bronchoscopy with bronchoalveolar lavage (BAL) done in the posterior segment of the right upper lobe. Cultures grew methicillin-resistant Staphylococcus aureus (MRSA), followed by Blastomyces dermatitidis in the histopathologic examination. Chronic pulmonary blastomycosis may present with hemoptysis, weight loss, chronic cough, and night sweats, along with upper lobe predominant cavitation. We have to exclude tuberculosis (TB), lung cancer, and chronic pulmonary histoplasmosis. This case epitomizes many classic perils in the identification of pulmonary blastomycosis. The patient was being treated with itraconazole 200 mg BID for 12 months as per infectious disease suggestion. The patient is nine months into treatment. At six months, his chest computed tomography (CT) revealed a reduction in size from 5.0 × 5.3 cm to 4.2 × 4.0 cm. Although there are no articles supporting increased secondary bacterial infections with underlying fungal infections, more research needs to be done to find any associated features.

The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection.

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1ß in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1ß. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.

Systematic analysis of proximal midgut- and anorectal-originating contractions in larval zebrafish using event feature detection and supervised machine learning algorithms.

BACKGROUND: Zebrafish larvae are translucent, allowing in vivo analysis of gut development and physiology, including gut motility. While recent progress has been made in measuring gut motility in larvae, challenges remain which can influence results, such as how data are interpreted, opportunities for technical user error, and inconsistencies in methods. METHODS: To overcome these challenges, we noninvasively introduced Nile Red fluorescent dye to fill the intraluminal gut space in zebrafish larvae and collected serial confocal microscopic images of gut fluorescence. We automated the detection of fluorescent-contrasted contraction events against the median-subtracted signal and compared it to manually annotated gut contraction events across anatomically defined gut regions. Supervised machine learning (multiple logistic regression) was then used to discriminate between true contraction events and noise. To demonstrate, we analyzed motility in larvae under control and reserpine-treated conditions. We also used automated event detection analysis to compare unfed and fed larvae. KEY RESULTS: Automated analysis retained event features for proximal midgut-originating retrograde and anterograde contractions and anorectal-originating retrograde contractions. While manual annotation showed reserpine disrupted gut motility, machine learning only achieved equivalent contraction discrimination in controls and failed to accurately identify contractions after reserpine due to insufficient intraluminal fluorescence. Automated analysis also showed feeding had no effect on the frequency of anorectal-originating contractions. CONCLUSIONS & INFERENCES: Automated event detection analysis rapidly and accurately annotated contraction events, including the previously neglected phenomenon of anorectal contractions. However, challenges remain to discriminate contraction events based on intraluminal fluorescence under treatment conditions that disrupt functional motility.

A Heat Transfer Model and Supporting Experiments to Guide the Uniform Gelation of Molecular Oleogels During Scale-up.

The quest for novel vegetable oil structuring strategies has been progressing since the discovery of the deleterious impacts of trans fats. Although oleogelation using bioderived molecular gelators has been proven to be successful as an alternative to traditional hydrogenation methods, efforts are needed to meet the industrial requirements. A major constraint during the fabrication of oleogels is to achieve consistency in physical properties during scale-up. Experiments showed that gelation fails to occur when larger volumes were prepared based on the minimum gelation concentration (MGC) of gelators, determined using the smallest oil volume (1 mL), a general laboratory practice. This observation was consistent with all the molecular gelators used in this study; sorbitol dioctanoate, mannitol dioctanoate, and 12-hydroxystearic acid. To understand this behavior, a mathematical model was developed since gelator network propagation is governed by the cooling rate. The model indicates that maintenance of a minimal thermal gradient via uniform heat dissipation and gelation time is necessary to achieve homogeneous gel propagation across the vial. With these predictions, we hypothesized and confirmed that oleogels with constant surface area-to-volume ratio could result in identical gelation times and consistent physical properties (MGC, melting temperature, melting enthalpy, yield stress, solid phase content, and oil binding capacity) during scale-up.

Sequence-Encoded Differences in Phase Separation Enable Formation of Resilin-like Polypeptide-Based Microstructured Hydrogels.

Microstructured hydrogels are promising platforms to mimic structural and compositional heterogeneities of the native extracellular matrix (ECM). The current state-of-the-art soft matter patterning techniques for generating ECM mimics can be limited owing to their reliance on specialized equipment and multiple time- and energy-intensive steps. Here, a photocross-linking methodology that traps various morphologies of phase-separated multicomponent formulations of compositionally distinct resilin-like polypeptides (RLPs) is reported. Turbidimetry and quantitative 1H NMR spectroscopy were utilized to investigate the sequence-dependent liquid-liquid phase separation of multicomponent solutions of RLPs. Differences between the intermolecular interactions of two different photocross-linkable RLPs and a phase-separating templating RLP were exploited for producing microstructured hydrogels with tunable control over pore diameters (ranging from 1.5 to 150 µm) and shear storage moduli (ranging from 0.2 to 5 kPa). The culture of human mesenchymal stem cells demonstrated high viability and attachment on microstructured hydrogels, suggesting their potential for developing customizable platforms for regenerative medicine applications.

Simplified soft tissue coverage of the distal lower extremity: The reverse sural flap.

Soft tissue defects involving the distal lower extremity present challenging problems for orthopaedic surgeons to manage. Historically, wounds not amenable to primary closure have necessitated assistance from multidisciplinary teams using plastic surgeons to obtain adequate soft tissue coverage through rotational flap or free tissue transfer procedures. Techniques related to soft tissue rearrangement and local rotational flap coverage have advanced over the years with a growing knowledge of local anatomy and vasculature. The reverse sural flap may be performed to cover soft tissue defects within 10 cm of the foot or ankle region, negating the need for microvascular intervention. The simplistic nature of the reverse sural flap is appealing to orthopaedic surgeons as a means to provide timely patient care without additional support because it does not require microvasculature work or the need for intraoperative microscopes and has been popularized among orthopaedic trauma surgeons as a necessary tool to possess. Here, we discuss the reverse sural flap to include history, relevant anatomy, clinical indications, and a description of the technique for application.

Towards clinical applicability and computational efficiency in automatic cranial implant design: An overview of the AutoImplant 2021 cranial implant design challenge.

Cranial implants are commonly used for surgical repair of craniectomy-induced skull defects. These implants are usually generated offline and may require days to weeks to be available. An automated implant design process combined with onsite manufacturing facilities can guarantee immediate implant availability and avoid secondary intervention. To address this need, the AutoImplant II challenge was organized in conjunction with MICCAI 2021, catering for the unmet clinical and computational requirements of automatic cranial implant design. The first edition of AutoImplant (AutoImplant I, 2020) demonstrated the general capabilities and effectiveness of data-driven approaches, including deep learning, for a skull shape completion task on synthetic defects. The second AutoImplant challenge (i.e., AutoImplant II, 2021) built upon the first by adding real clinical craniectomy cases as well as additional synthetic imaging data. The AutoImplant II challenge consisted of three tracks. Tracks 1 and 3 used skull images with synthetic defects to evaluate the ability of submitted approaches to generate implants that recreate the original skull shape. Track 3 consisted of the data from the first challenge (i.e., 100 cases for training, and 110 for evaluation), and Track 1 provided 570 training and 100 validation cases aimed at evaluating skull shape completion algorithms at diverse defect patterns. Track 2 also made progress over the first challenge by providing 11 clinically defective skulls and evaluating the submitted implant designs on these clinical cases. The submitted designs were evaluated quantitatively against imaging data from post-craniectomy as well as by an experienced neurosurgeon. Submissions to these challenge tasks made substantial progress in addressing issues such as generalizability, computational efficiency, data augmentation, and implant refinement. This paper serves as a comprehensive summary and comparison of the submissions to the AutoImplant II challenge. Codes and models are available at https://github.com/Jianningli/Autoimplant_II.