Active and highly durable supported catalysts for proton exchange membrane electrolysers.

The design and development of supported catalysts for the oxygen evolution reaction (OER) is a promising pathway to reducing iridium loading in proton exchange membrane water electrolysers. However, supported catalysts often suffer from poor activity and durability, particularly when deployed in membrane electrode assemblies. In this work, we deploy iridium coated hollow titanium dioxide particles as OER catalysts to achieve higher Ir mass activities than the leading commercial catalysts. Critically, we demonstrate state-of-the-art durabilities for supported iridium catalysts when compared against the previously reported values for analogous device architectures, operating conditions and accelerated stress test profiles. Through extensive materials characterisations alongside rotating disk electrode measurements, we investigate the role of conductivity, morphology, oxidation state and crystallinity on the OER electrochemical performance. Our work highlights a new supported catalyst design that unlocks high-performance OER activity and durability in commercially relevant testing configurations.

Black titanium oxide: synthesis, modification, characterization, physiochemical properties, and emerging applications for energy conversion and storage, and environmental sustainability.

Since its advent in 2011, black titanium oxide (B-TiOx) has garnered significant attention due to its exceptional optical characteristics, notably its enhanced absorption spectrum ranging from 200 to 2000 nm, in stark contrast to its unmodified counterpart. The escalating urgency to address global climate change has spurred intensified research into this material for sustainable hydrogen production through thermal, photocatalytic, electrocatalytic, or hybrid water-splitting techniques. The rapid advancements in this dynamic field necessitate a comprehensive update. In this review, we endeavor to provide a detailed examination and forward-looking insights into the captivating attributes, synthesis methods, modifications, and characterizations of B-TiOx, as well as a nuanced understanding of its physicochemical properties. We place particular emphasis on the potential integration of B-TiOx into solar and electrochemical energy systems, highlighting its applications in green hydrogen generation, CO2 reduction, and supercapacitor technology, among others. Recent breakthroughs in the structure-property relationship of B-TiOx and its applications, grounded in both theoretical and empirical studies, are underscored. Additionally, we will address the challenges of scaling up B-TiOx production, its long-term stability, and economic viability to align with ambitious future objectives.

Entrustable professional activities, emergency medicine and medical education: a systematic review.

INTRODUCTION: Entrustable professional activities (EPAs) are one way to assess competencies, and are designed to bridge the gap between theoretical competencies and real world clinical practice. AIMS: This was a systematic review which aims to answer the question: "Which EPAs related to Emergency Medicine are described for medical schools?". METHODS: We included original qualitative, interventional and observational studies (cross-sectional, case-control, and cohort studies) that described EPAs relevant to Emergency Medicine for Medical School. The search strategy was created using a combination of keywords and standardized index terms related to EPAs and Emergency Medicine. RESULTS: The search strategy identified 991 citations. After screening the titles and abstracts, we identified 85 potentially relevant studies. After the full-text review, a total of 11 reports met the criteria for inclusion. CONCLUSION: Recognizing a patient requiring urgent or emergent care and initiating evaluation and management is the most common EPA related to Emergency Medicine described at Medical Schools. Use of EPAs is associated with increased student satisfaction and improved competences. However, there is a lack of undergraduate EM specific EPAs being systematically developed and published, and this should be an area to be explored in future studies.

IFEM model curriculum: emergency medicine learning outcomes for undergraduate medical education.

BACKGROUND: The International Federation for Emergency Medicine (IFEM) published its model curriculum for medical student education in emergency medicine in 2009. Because of the evolving principles of emergency medicine and medical education, driven by societal, professional, and educational developments, there was a need for an update on IFEM recommendations. The main objective of the update process was creating Intended Learning Outcomes (ILOs) and providing tier-based recommendations. METHOD: A consensus methodology combining nominal group and modified Delphi methods was used. The nominal group had 15 members representing eight countries in six regions. The process began with a review of the 2009 curriculum by IFEM Core Curriculum and Education Committee (CCEC) members, followed by a three-phase update process involving survey creation [The final survey document included 55 items in 4 sections, namely, participant & context information (16 items), intended learning outcomes (6 items), principles unique to emergency medicine (20 items), and content unique to emergency medicine (13 items)], participant selection from IFEM member countries and survey implementation, and data analysis to create the recommendations. RESULTS: Out of 112 invitees (CCEC members and IFEM member country nominees), 57 (50.9%) participants from 27 countries participated. Eighteen (31.6%) participants were from LMICs, while 39 (68.4%) were from HICs. Forty-four (77.2%) participants have been involved with medical students' emergency medicine training for more than five years in their careers, and 56 (98.2%) have been involved with medical students' training in the last five years. Thirty-five (61.4%) participants have completed a form of training in medical education. The exercise resulted in the formulation of tiered ILO recommendations. Tier 1 ILOs are recommended for all medical schools, Tier 2 ILOs are recommended for medical schools based on perceived local healthcare system needs and/or adequate resources, and Tier 3 ILOs should be considered for medical schools based on perceived local healthcare system needs and/or adequate resources. CONCLUSION: The updated IFEM ILO recommendations are designed to be applicable across diverse educational and healthcare settings. These recommendations aim to provide a clear framework for medical schools to prepare graduates with essential emergency care capabilities immediately after completing medical school. The successful distribution and implementation of these recommendations hinge on support from faculty and administrators, ensuring that future healthcare professionals are well-prepared for emergency medical care.

TBP facilitates RNA Polymerase I transcription following mitosis.

The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II and III). Although TBP is central to transcription by the three RNA Pols in various species, the emergence of TBP paralogs throughout evolution has expanded the complexity in transcription initiation. Furthermore, recent studies have emerged that questioned the centrality of TBP in mammalian cells, particularly in Pol II transcription, but the role of TBP and its paralogs in Pol I transcription remains to be re-evaluated. In this report, we show that in murine embryonic stem cells TBP localizes onto Pol I promoters, whereas the TBP paralog TRF2 only weakly associates to the Spacer Promoter of rDNA, suggesting that it may not be able to replace TBP for Pol I transcription. Importantly, acute TBP depletion does not fully disrupt Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.

Harnessing ultrasound-derived hydroxyl radicals for the selective oxidation of aldehyde functions.

Ultrasonic irradiation holds potential for the selective oxidation of non-volatile organic substrates in the aqueous phase by harnessing hydroxyl radicals as chemical initiators. Here, a mechanistic description of hydroxyl radical-initiated glyoxal oxidation is constructed by gleaning insights from photolysis and radiation chemistry to explain the yields and kinetic trends for oxidation products. The mechanistic description and kinetic measurements reported herein reveal that increasing the formation rate of hydroxyl radicals by changing the ultrasound frequency increases both the rates of glyoxal consumption and the selectivity towards C2 acid products over those from C-C cleavage. Glyoxal consumption also occurs more rapidly and with greater selectivity towards C2 acids under acidic conditions, which favor the protonation of carboxylate intermediates into their less reactive acidic forms. Leveraging such pH and frequency effects is crucial to mitigating product degradation by secondary reactions with hydroxyl radicals and oxidation products (specifically hydrogen peroxide and superoxide). These findings demonstrate the potential of ultrasound as a driver for the selective oxidation of aldehyde functions to carboxylic acids, offering a sustainable route for valorizing biomass-derived platform molecules.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study.

PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.

Efficient sonochemical catalytic degradation of tetracycline using TiO2 fractured nanoshells.

Overexposure to antibiotics originating in wastewater has profound environmental and health implications. Conventional treatment methods are not fully effective in removing certain antibiotics, such as the commonly used antibiotic, tetracycline, leading to its accumulation in water catchments. Alternative antibiotic removal strategies are garnering attention, including sonocatalytic oxidative processes. In this work, we investigated the degradation of tetracycline using a combination of TiO2 fractured nanoshells (TFNs) and an advanced sonochemical reactor design. The study encompassed an examination of multiple process parameters to understand their effects on the degradation of tetracycline. These included tetracycline adsorption on TFNs, reaction time, initial tetracycline concentration, solvent pH, acoustic pressure amplitude, number of acoustic cycles, catalyst dosage, TFNs' reusability, and the impact of adjuvants such as light and H2O2. Though TFNs adsorbed tetracycline, the addition of ultrasound was able to degrade tetracycline completely (with 100% degradation) within six minutes. Under the optimal operating conditions, the proposed sonocatalytic system consumed 80% less energy compared to the values reported in recently published sonocatalytic research. It also had the lowest CO2 footprint when compared to the other sono-/photo-based technologies. This study suggests that optimizing the reaction system and operating the reaction under low power and at a lower duty cycle are effective in achieving efficient cavitation for sonocatalytic reactions.

Cavitation-Enhanced Drug Delivery and Immunotherapy.

Welcome to this special issue on Cavitation-Enhanced Drug Delivery and Immunotherapy-a rapidly evolving area that has been buoyed in recent years by the development of methods harnessing the activity of ultrasound-stimulated bubbles known as cavitation [...].

Enhancement of sonochemical production of hydroxyl radicals from pulsed cylindrically converging ultrasound waves.

Sonochemistry is the use of ultrasound to generate highly reactive radical species through the inertial collapse of a gas/vapour cavity and is a green alternative for hydrogen production, wastewater treatment, and chemical synthesis and modifications. Yet, current sonochemical reactors often are limited by their design, resulting in low efficacy and yields with slow reaction kinetics. Here, we constructed a novel sonochemical reactor design that creates cylindrically converging ultrasound waves to create an intense localised region of high acoustic pressure amplitudes (15 MPaPKPK) capable of spontaneously nucleating cavitation. Using a novel dosimetry technique, we determined the effect of acoustic parameters on the yield of hydroxyl radicals (HO), HO production rate, and ultimately the sonochemical efficiency (SE) of our reactor. Our reactor design had a significantly higher HO production rate and SE compared to other conventional reactors and across literature.

Papilledema and retinopathy lead to diagnosis of IgA nephropathy: a case report.

This case features a young healthy male who was diagnosed with immunoglobulin A (IgA) nephropathy after presenting with blurry vision that was caused by hypertensive retinopathy and papilledema. In this report, we examine the relationship between hypertension and increased intracranial pressure (ICP), along with the ocular signs of IgA nephropathy that may present in the setting of kidney disease.

Immunoglobulin A (IgA) nephropathy is an immune-mediated inflammatory condition that affects the kidneys and is characterized by deposits of IgA antibodies across the body. Nephropathy in general is defined as the deterioration of kidney function. Hypertension is a common complication because of the resultant kidney damage. IgA can also deposit widely across the body, including within the eyes, and may lead to various inflammatory manifestations affecting the front and back of the eyes. We present a case of a 38-year-old male with 2 weeks of worsening vision and headaches. His blood pressure was extremely high (206/116 mmHg) and he was found to have acute kidney injury. Examination of his eye revealed hypertensive retinopathy but also significant swelling of both of his optic discs, concerning for increased intracranial pressure (ICP), which is unusual in a young, otherwise healthy male. The investigation for the cause of increased ICP led to the diagnosis of IgA nephropathy. Treatment of his increased ICP and blood pressure resulted in improvement of his vision. It is important to consider increased ICP as a cause of optic disc swelling in patients with very high blood pressures. Prompt evaluation and management of elevated ICP is important to preserve vision, prevent brain complications and diagnose the underlying disease process. Especially important is the communication and coordination across medical specialties to ensure safe treatment given the multisystem organ involvement. In this article, we also review the eye findings associated with IgA nephropathy, as well as other immune-mediated complications of this rare disease.

Heat shock transcription factors demonstrate a distinct mode of interaction with mitotic chromosomes.

A large number of transcription factors have been shown to bind and interact with mitotic chromosomes, which may promote the efficient reactivation of transcriptional programs following cell division. Although the DNA-binding domain (DBD) contributes strongly to TF behavior, the mitotic behaviors of TFs from the same DBD family may vary. To define the mechanisms governing TF behavior during mitosis in mouse embryonic stem cells, we examined two related TFs: Heat Shock Factor 1 and 2 (HSF1 and HSF2). We found that HSF2 maintains site-specific binding genome-wide during mitosis, whereas HSF1 binding is somewhat decreased. Surprisingly, live-cell imaging shows that both factors appear excluded from mitotic chromosomes to the same degree, and are similarly more dynamic in mitosis than in interphase. Exclusion from mitotic DNA is not due to extrinsic factors like nuclear import and export mechanisms. Rather, we found that the HSF DBDs can coat mitotic chromosomes, and that HSF2 DBD is able to establish site-specific binding. These data further confirm that site-specific binding and chromosome coating are independent properties, and that for some TFs, mitotic behavior is largely determined by the non-DBD regions.

RNA Polymerase II transcription independent of TBP in murine embryonic stem cells.

Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the pre-initiation complex onto promoter DNA. Decades of research have shown that the TATA-box binding protein (TBP) is essential for Pol II loading and initiation. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells has no global effect on ongoing Pol II transcription. In contrast, acute TBP depletion severely impairs RNA Polymerase III initiation. Furthermore, Pol II transcriptional induction occurs normally upon TBP depletion. This TBP-independent transcription mechanism is not due to a functional redundancy with the TBP paralog TRF2, though TRF2 also binds to promoters of transcribed genes. Rather, we show that the TFIID complex can form and, despite having reduced TAF4 and TFIIA binding when TBP is depleted, the Pol II machinery is sufficiently robust in sustaining TBP-independent transcription.

Fluorescence-based chemical tools for monitoring ultrasound-induced hydroxyl radical production in aqueous solution and in cells.

We report the synthesis of hydroxyl-radical (˙OH) responsive fluorescent probes that utilise the 3,5-dihydroxybenzyl (DHB) functionality. 4-Methylumbeliferone-DHB (Umb-DHB) and resorufin-DHB (Res-DHB) in the presence of ˙OH radicals resulted in significant increases in their respective fluorescent emission intensities at 460 nm and 585 nm. The incubation of Res-DHB in HeLa cells followed by therapeutic ultrasound (1 MHz) resulted in a significant increase in fluorescence emission intensity thus permitting the ability to monitor ultrasound-induced ˙OH production in live cells.

Ocular involvement in Mycoplasma induced rash and mucositis: A systematic review of the literature.

Mycoplasma pneumoniae induced rash and mucositis (MIRM) is a relatively newly identified clinical entity which is characterized by mucocutaneous manifestations in the setting of Mycoplasma infection. Though a clinically distinct disease, MIRM exists on a diagnostic continuum with entities including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and the recently described reactive infectious mucocutaneous eruption (RIME). In this systematic review, we discuss published findings on the epidemiology, clinical manifestations, diagnosis, and management of MIRM, with an emphasis on ocular disease. Lastly, we discuss some of the most recent developments and challenges in characterizing MIRM with respect to the related diagnosis of RIME.

Relationship between Atopic Disease and Acute Ocular and Systemic Outcomes in Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

OBJECTIVE: To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). METHODS: Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared. RESULTS: In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system's general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN. CONCLUSION: Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population.

Multimodal image alignment aids in the evaluation and monitoring of sector retinitis pigmentosa.

PURPOSE: To present a semi-automated method of image alignment to aid in monitoring the progression of inherited retinal degenerations (IRDs). RESULTS: A 22-year-old woman presented with nyctalopia and a family history of retinitis pigmentosa (RP), but with no prior genetic testing. Fundus examination showed a sectoral retinal degeneration involving the inferior and nasal retina with rare, pigmented deposits. Goldmann kinetic perimetry demonstrated corresponding superotemporal visual field defects. The best-corrected visual acuity was 20/20 in both eyes. Multimodal imaging delineated geographically restricted peripheral retinal degeneration extending to the inferior edge of the macula. Central visual function remained intact with normal multifocal electroretinography findings. Optical coherence tomography (OCT) through the leading edge of the retinal degeneration confirmed loss of the photoreceptor layer and associated retinal pigment epithelium. In the region of retinal degeneration, loss of vascular flow density was noted on optical coherence tomography angiography (OCTA). Genetic testing identified a pathologic sequence variant in RHO (c.68C>A, p.Pro23His), confirming autosomal dominant sector retinitis pigmentosa (SRP). Image alignment allowed for precise measurement of the progression of SRP over a period of 18 months. CONCLUSION: SRP is a rare subtype of RP characterized by focal, typically inferior and nasal, retinal degeneration of the peripheral retina. Although the onset and extent of peripheral retinal degeneration varies, compared with RP, SRP typically progresses more slowly to involve the macula. In this report, we highlight the utility of image registration and alignment to aid in monitoring disease progression in IRDs by means of multimodal imaging.

Keeping an eye on the diabetic foot: The connection between diabetic eye disease and wound healing in the lower extremity.

Diabetic eye disease is strongly associated with the development of diabetic foot ulcers (DFUs). DFUs are a common and significant complication of diabetes mellitus (DM) that arise from a combination of micro- and macrovascular compromise. Hyperglycemia and associated metabolic dysfunction in DM lead to impaired wound healing, immune dysregulation, peripheral vascular disease, and diabetic neuropathy that predisposes the lower extremities to repetitive injury and progressive tissue damage that may ultimately necessitate amputation. Diabetic retinopathy (DR) is caused by cumulative damage to the retinal mic-rovasculature from hyperglycemia and other diabetes-associated factors. The severity of DR is closely associated with the development of DFUs and the need for lower extremity revascularization procedures and/or amputation. Like the lower extremity, the eye may also suffer end-organ damage from macrovascular compromise in the form of cranial neuropathies that impair its motility, cause optic neuropathy, or result in partial or complete blindness. Additionally, poor perfusion of the eye can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy or neovascular glaucoma, both serious, vision-threatening conditions. Finally, diabetic corneal ulcers and DFUs share many aspects of impaired wound healing resulting from neurovascular, sensory, and immunologic compromise. Notably, alterations in serum biomarkers, such as hemoglobin A1c, ceruloplasmin, creatinine, low-density lipoprotein, and high-density lipoprotein, are associated with both DR and DFUs. Monitoring these parameters can aid in prognosticating long-term outcomes and shed light on shared pathogenic mechanisms that lead to end-organ damage. The frequent co-occurrence of diabetic eye and foot problems mandate that patients affected by either condition undergo reciprocal comprehensive eye and foot evaluations in addition to optimizing diabetes management.

An alternative model for assessing mortality risk in Stevens Johnson syndrome/toxic epidermal necrolysis using a random forests classifier: A pilot study.

Introduction: Mortality risk prediction is an important part of the clinical assessment in the Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) patient. The SCORTEN and ABCD-10 scoring systems have been used as predictive clinical tools for assessing this risk. However, some of the metrics required in calculating these scores, such as the total body surface area (TBSA) involvement, are difficult to calculate. In addition, TBSA involvement is calculated in a variety of ways and is observer dependent and subjective. The goal of this study was to develop an alternative method to predict mortality in patients with SJS/TEN. Methods: Data was split into training and test datasets and preprocessed. Models were trained using five-fold cross validation. Out of several possible candidates, a random forests model was evaluated as being the most robust in predictive power for this dataset. Upon feature selection, a final random forests model was developed which was used for comparison against SCORTEN. Results: The differences in both accuracy (p = 0.324) and area under the receiver operating characteristic curve (AUROC) (p = 0.318) between the final random forests model and the SCORTEN and ABCD-10 models were not statistically significant. As such, this alternative method performs similarly to SCORTEN while only requiring simple laboratory tests from the day of admission. Discussion: This new alternative can make the mortality prediction process more efficient, along with providing a seamless implementation of the patient laboratory tests directly into the model from existing electronic health record (EHR) systems. Once the model was developed, a web application was built to deploy the model which integrates with the Epic EHR system on the Fast Healthcare Interoperability Resources (FHIR) Application Programming Interface (API); this only requires the patient medical record number and a date of the lab tests as parameters. This model ultimately allows clinicians to calculate patient mortality risk with only a few clicks. Further studies are needed for validation of this tool.

Corneal stromal deposits in connective tissue disease, a case series.

PURPOSE: We report two cases of refractile, peripheral, corneal stromal deposition in two patients with arterial tortuosity syndrome (ATS) and Ehlers-Danlos syndrome (EDS), two closely related connective tissue diseases (CTDs). OBSERVATIONS: Patient 1: A 21-year-old man with history of ATS and keratoectasia presented with bilateral peripheral corneal neovascularization with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the inferotemporal cornea. After 3 years of follow-up, the corneal deposits did not progress, but the ectasia did, with significant bilateral corneal steepening and thinning for which the patient was recommended to undergo repeat corneal collagen cross linking. Patient 2: A 26-year-old man with presumed diagnosis of EDS presented with numerous whitish brown, refractile, deep stromal opacities that were circumferential along the temporal cornea in the right eye, and superiorly in the left eye. The left eye had a pseudopterygium involving 50% of the cornea. After 2 years of follow-up, the corneal opacities did not progress; however, the patient underwent primary excision of the pseudopterygium and subsequently had conjunctivalization of the entire cornea. The lesions in both cases resembled those seen in Terrien's marginal degeneration. CONCLUSIONS AND IMPORTANCE: Peripheral corneal stromal deposits have never been reported before in EDS or ATS or other connective tissue diseases. This case series may prompt further inquiry and characterization of these findings in patients with CTDs.