Dawn of diverse shelled and carbonaceous animal microfossils at ~ 571 Ma.

The Ediacaran-Cambrian transition documents a critical stage in the diversification of animals. The global fossil record documents the appearance of cloudinomorphs and other shelled tubular organisms followed by non-biomineralized small carbonaceous fossils and by the highly diversified small shelly fossils between ~ 550 and 530 Ma. Here, we report diverse microfossils in thin sections and hand samples from the Ediacaran Bocaina Formation, Brazil, separated into five descriptive categories: elongate solid structures (ES); elongate filled structures (EF); two types of equidimensional structures (EQ 1 and 2) and elongate hollow structures with coiled ends (CE). These specimens, interpreted as diversified candidate metazoans, predate the latest Ediacaran biomineralized index macrofossils of the Cloudina-Corumbella-Namacalathus biozone in the overlying Tamengo Formation. Our new carbonate U-Pb ages for the Bocaina Formation, position this novel fossil record at 571 ± 9 Ma (weighted mean age). Thus, our data point to diversification of metazoans, including biomineralized specimens reminiscent of sections of cloudinids, protoconodonts, anabaritids, and hyolithids, in addition to organo-phosphatic surficial coverings of animals, demonstrably earlier than the record of the earliest known skeletonized metazoan fossils.

Parity Quantum Computing as yz-Plane Measurement-Based Quantum Computing.

We show that universal parity quantum computing employing a recently introduced constant depth decoding procedure is equivalent to measurement-based quantum computation (MBQC) on a bipartite graph using only yz-plane measurements. We further show that any unitary MBQC using only yz-plane measurements must occur on a bipartite graph. These results have a number of consequences and open new research avenues for both frameworks.

Evaluating Factors Associated With Telehealth Appropriateness in Outpatient Rheumatoid Arthritis Encounters Using the Encounter Appropriateness Score for You (EASY).

OBJECTIVE: Telehealth has been proposed as a safe and effective alternative to in-person care for rheumatoid arthritis (RA). The purpose of this study was to evaluate factors associated with telehealth appropriateness in outpatient RA encounters. METHODS: A prospective cohort study (January 1, 2021, to August 31, 2021) was conducted using electronic health record data from outpatient RA encounters in a single academic rheumatology practice. Rheumatology providers rated the telehealth appropriateness of their own encounters using the Encounter Appropriateness Score for You (EASY) immediately following each encounter. Robust Poisson regression with generalized estimating equations modeling was used to evaluate the association of telehealth appropriateness with patient demographics, RA clinical characteristics, comorbid noninflammatory causes of joint pain, previous and current encounter characteristics, and provider characteristics. RESULTS: During the study period, 1823 outpatient encounters with 1177 unique patients with RA received an EASY score from 25 rheumatology providers. In the final multivariate model, factors associated with increased telehealth appropriateness included higher average provider preference for telehealth in prior encounters (relative risk [RR] 1.26, 95% CI 1.21-1.31), telehealth as the current encounter modality (RR 2.27, 95% CI 1.95-2.64), and increased patient age (RR 1.05, 95% CI 1.01-1.09). Factors associated with decreased telehealth appropriateness included moderate (RR 0.81, 95% CI 0.68-0.96) and high (RR 0.57, 95% CI 0.46-0.70) RA disease activity and if the previous encounters were conducted by telehealth (RR 0.83, 95% CI 0.73-0.95). CONCLUSION: In this study, telehealth appropriateness was most associated with provider preference, the current and previous encounter modality, and RA disease activity. Other factors like patient demographics, RA medications, and comorbid noninflammatory causes of joint pain were not associated with telehealth appropriateness.

Modern In Vitro Techniques for Modeling Hearing Loss.

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear's architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.

Optimisation of analytical methods for tuberculosis drug detection in wastewater: A multinational study.

Wastewater-based epidemiology (WBE) is a robust tool for disease surveillance and monitoring of pharmaceutical consumption. However, monitoring tuberculosis (TB) drug consumption faces challenges due to limited data availability. This study aimed to optimise methods for detecting TB drugs in treated and untreated wastewater from four African countries: South Africa, Nigeria, Kenya, and Cameroon. The limit of detection (LOD) for these drugs ranged from a minimum of 2.20 (±1.02) for rifampicin to a maximum of 2.95 (±0.79) for pyrazinamide. A parallel trend was observed concerning the limit of quantification (LOQ), with rifampicin reporting the lowest average LOQ of 7.33 (±3.44) and pyrazinamide showing the highest average LOQ of 9.81 (±2.64). The variance in LOD and LOQ values could be attributed to factors such as drug polarity. Erythromycin and rifampicin exhibited moderately polar LogP values (2.6 and 2.95), indicating higher lipid affinity and lower water affinity. Conversely, ethambutol, pyrazinamide, and isoniazid displayed polar LogP values (-0.059, -0.6, and -0.7), suggesting lower lipid affinity and greater water affinity. The study revealed that storing wastewater samples for up to 5 days did not result in significant drug concentration loss, with concentration reduction remaining below 1 log throughout the storage period. Application of the optimised method for drug detection and quantification in both treated and untreated wastewater unveiled varied results. Detection frequencies varied among drugs, with ethambutol consistently most detected, while pyrazinamide and isoniazid were least detected in wastewater from only two countries. Most untreated wastewater samples had undetectable drug concentrations, ranging from 1.21 ng/mL for erythromycin to 54.61 ng/mL for isoniazid. This variability may suggest differences in drug consumption within connected communities. In treated wastewater samples, detectable drug concentrations ranged from 1.27 ng/mL for isoniazid to 10.20 ng/mL for ethambutol. Wastewater treatment plants exhibited variable removal efficiencies for different drugs, emphasising the need for further optimisation. Detecting these drugs in treated wastewater suggests potential surface water contamination and subsequent risks of human exposure, underscoring continued research's importance.

Continuous white noise exposure during sleep and childhood development: A scoping review.

BACKGROUND: White noise machines are widely used as a sleep aid for young children and may lead to poor hearing, speech, and learning outcomes if used incorrectly. OBJECTIVE: Characterize the potential impact of chronic white noise exposure on early childhood development. METHODS: Embase, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science were searched from inception through June 2022 for publications addressing the effects of chronic noise exposure during sleep on early development in animals and children. PRISMA-ScR guidelines were followed. Among 644 retrieved publications, 20 met inclusion criteria after review by multiple authors. Seven studies evaluated animal models and 13 studies examined pediatric subjects, including 83 animal and 9428 human subjects. RESULTS: White noise machines can exceed 91 dB on maximum volume, which exceeds the National Institute for Occupational Safety and Health noise exposure guidelines for a 2-h work shift in adults. Evidence suggests deleterious effects of continuous moderate-intensity white noise exposure on early development in animal models. Human subject data generally corroborates these models; however, studies also suggest low-intensity noise exposure may be beneficial during sleep. CONCLUSIONS: Existing data support the limitation of maximal sound intensity and duration on commercially available white noise devices. Further research into the optimal intensity and duration of white noise exposure in children is needed.

Diagnosing arsenic-mediated biochemical responses in rice cultivars using Raman spectroscopy.

Rice (Oryza sativa) is the primary crop for nearly half of the world's population. Groundwater in many rice-growing parts of the world often has elevated levels of arsenite and arsenate. At the same time, rice can accumulate up to 20 times more arsenic compared to other staple crops. This places an enormous amount of people at risk of chronic arsenic poisoning. In this study, we investigated whether Raman spectroscopy (RS) could be used to diagnose arsenic toxicity in rice based on biochemical changes that were induced by arsenic accumulation. We modeled arsenite and arsenate stresses in four different rice cultivars grown in hydroponics over a nine-day window. Our results demonstrate that Raman spectra acquired from rice leaves, coupled with partial least squares-discriminant analysis, enabled accurate detection and identification of arsenic stress with approximately 89% accuracy. We also performed high-performance liquid chromatography (HPLC)-analysis of rice leaves to identify the key molecular analytes sensed by RS in confirming arsenic poisoning. We found that RS primarily detected a decrease in the concentration of lutein and an increase in the concentration of vanillic and ferulic acids due to the accumulation of arsenite and arsenate in rice. This showed that these molecules are detectable indicators of biochemical response to arsenic accumulation. Finally, a cross-correlation of RS with HPLC and ICP-MS demonstrated RS's potential for a label-free, non-invasive, and non-destructive quantification of arsenic accumulation in rice.

Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

OBJECTIVE: Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. PATIENTS: Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. INTERVENTIONS: Surgical excision of tophaceous middle ear lesions. MAIN OUTCOME MEASURE: Improvements in facial weakness and conductive hearing loss. RESULTS: The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. CONCLUSION: Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.

Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits.

Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented for immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing and normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved therapies (bevacizumab and losartan, respectively) can be repurposed as HDTs to normalize blood vessels and extracellular matrix (ECM), improve drug delivery, and reduce bacterial loads in TB granulomas. Granulomas feature an overabundance of ECM and compressed blood vessels, both of which are effectively reduced by losartan treatment in the rabbit model of TB. Combining both HDTs promotes secretion of proinflammatory cytokines and improves anti-TB drug delivery. Finally, alone and in combination with second-line antitubercular agents (moxifloxacin or bedaquiline), these HDTs significantly reduce bacterial burden. RNA sequencing analysis of HDT-treated lung and granuloma tissues implicates up-regulated antimicrobial peptide and proinflammatory gene expression by ciliated epithelial airway cells as a putative mechanism of the observed antitubercular benefits in the absence of chemotherapy. These findings demonstrate that bevacizumab and losartan are well-tolerated stroma-targeting HDTs, normalize the granuloma microenvironment, and improve TB outcomes, providing the rationale to clinically test this combination in TB patients.

Sequestosome 1 (p62) mitigates hypoxia-induced cardiac dysfunction by stabilizing hypoxia-inducible factor 1α and nuclear factor erythroid 2-related factor 2.

AIMS: Heart failure due to ischaemic heart disease (IHD) is a leading cause of mortality worldwide. A major contributing factor to IHD-induced cardiac damage is hypoxia. Sequestosome 1 (p62) is a multi-functional adaptor protein with pleiotropic roles in autophagy, proteostasis, inflammation, and cancer. Despite abundant expression in cardiomyocytes, the role of p62 in cardiac physiology is not well understood. We hypothesized that cardiomyocyte-specific p62 deletion evokes hypoxia-induced cardiac pathology by impairing hypoxia-inducible factor 1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling. METHODS AND RESULTS: Adult mice with germline deletion of cardiomyocyte p62 exhibited mild cardiac dysfunction under normoxic conditions. Transcriptomic analyses revealed a selective impairment in Nrf2 target genes in the hearts from these mice. Demonstrating the functional importance of this adaptor protein, adult mice with inducible depletion of cardiomyocyte p62 displayed hypoxia-induced contractile dysfunction, oxidative stress, and cell death. Mechanistically, p62-depleted hearts exhibit impaired Hif-1α and Nrf2 transcriptional activity. Because findings from these two murine models suggested a cardioprotective role for p62, mechanisms were evaluated using H9c2 cardiomyoblasts. Loss of p62 in H9c2 cells exposed to hypoxia reduced Hif-1α and Nrf2 protein levels. Further, the lack of p62 decreased Nrf2 protein expression, nuclear translocation, and transcriptional activity. Repressed Nrf2 activity associated with heightened Nrf2-Keap1 co-localization in p62-deficient cells, which was concurrent with increased Nrf2 ubiquitination facilitated by the E3 ligase Cullin 3, followed by proteasomal-mediated degradation. Substantiating our results, a gain of p62 in H9c2 cells stabilized Nrf2 and increased the transcriptional activity of Nrf2 downstream targets. CONCLUSION: Cardiac p62 mitigates hypoxia-induced cardiac dysfunction by stabilizing Hif-1α and Nrf2.

Leveraging Technology for Vestibular Assessment and Rehabilitation in the Operational Environment: A Scoping Review.

INTRODUCTION: The vestibular system, essential for gaze and postural stability, can be damaged by threats on the battlefield. Technology can aid in vestibular assessment and rehabilitation; however, not all devices are conducive to the delivery of healthcare in an austere setting. This scoping review aimed to examine the literature for technologies that can be utilized for vestibular assessment and rehabilitation in operational environments. MATERIALS AND METHODS: A comprehensive search of PubMed was performed. Articles were included if they related to central or peripheral vestibular disorders, addressed assessment or rehabilitation, leveraged technology, and were written in English. Articles were excluded if they discussed health conditions other than vestibular disorders, focused on devices or techniques not conducive to the operational environment, or were written in a language other than English. RESULTS: Our search strategy yielded 32 articles: 8 articles met our inclusion and exclusion criteria whereas the other 24 articles were rejected. DISCUSSION: There is untapped potential for leveraging technology for vestibular assessment and rehabilitation in the operational environment. Few studies were found in the peer-reviewed literature that described the application of technology to improve the identification of central and/or peripheral vestibular system impairments; triage of acutely injured patients; diagnosis; delivery and monitoring of rehabilitation; and determination of readiness for return to duty. CONCLUSIONS: This scoping review highlighted technology for vestibular assessment and rehabilitation feasible for use in an austere setting. Such technology may be leveraged for prevention; monitoring exposure to mechanisms of injury; vestibular-ocular motor evaluation; assessment, treatment, and monitoring of rehabilitation progress; and return-to-duty determination after vestibular injury. FUTURE DIRECTIONS: The future of vestibular assessment and rehabilitation may be shaped by austere manufacturing and 3D printing; artificial intelligence; drug delivery in combination with vestibular implantation; organ-on-chip and organoids; cell and gene therapy; and bioprinting.

Elucidation of sex from mature Palmer amaranth (Amaranthus palmeri) leaves using a portable Raman spectrometer.

Palmer amaranth (Amaranthus palmeri) is a pervasive and troublesome weed species that poses significant challenges to agriculture in the United States. Identifying the sex of Palmer amaranth plants is crucial for developing tailored control measures due to the distinct characteristics and reproductive strategies exhibited by male and female plants. Traditional methods for sex determination are expensive and time-consuming, but recent advancements in spectroscopic techniques offer new possibilities. This study explores the potential of portable Raman spectroscopy for determining the sex of mature Palmer amaranth plants in-field. Raman analysis of the plant leaves reveals spectral differences associated with nitrate salts, lipids, carotenoids, and terpenoids, allowing for high accuracy and reliable identification of the plant's sex; male plants had higher concentrations of these compounds compared to females. It was also found that male plants had higher concentrations of these compounds compared to the females. Raman spectra were analyzed using a machine learning tool, partial least squares discriminant analysis (PLS-DA), to generate accuracies of no less than 83.7% when elucidating sex from acquired spectra. These findings provide insights into the sex-specific characteristics of Palmer amaranth and suggest that Raman analysis, combined with PLS-DA, can be a promising, non-destructive, and efficient method for sex determination in field settings. This approach has implications for developing sex-specific management strategies to monitor and control this invasive weed in real-world environments, benefiting farmers, agronomists, researchers, and master gardeners.

Modern Trends in Otologic Surgery and Implications for Residency Training.

OBJECTIVE: Placing a middle ear prosthesis is considered a key competency for the general otolaryngologist, but surgeons struggle to obtain and maintain this skill. The current study aims to characterize pre-coronavirus disease 2019 trends in stapedectomy and ossiculoplasty. STUDY DESIGN: Database review. SETTING: Tricare beneficiaries are treated at civilian and military facilities. METHODS: The Department of Defense beneficiary population of more than nine million persons per year was reviewed for patients undergoing either stapedectomy or ossiculoplasty between 2010 and 2019, identified by the current procedural terminology code. RESULTS: A total of 3052 stapedectomies and 7197 ossiculoplasties were performed. Over the 10-year study period, stapedectomy decreased by 23%, with an average annual rate of -2.7% per year (Pearson r = -.91, P = .0003). Ossiculoplasties declined by 18%, an average annual rate of -1.9% (r = -.8, P = .006). In combination, cases declined by 20%, an average annual rate of -2.2% (r = -.87, P = .001). CONCLUSION: While declines in stapedectomy surgery have been well reported, here we show steady declines in ossiculoplasty as well. If these trends continue, more cochlear implantations may be performed annually than stapedectomy and ossiculoplasty combined, with cochlear implantation likely to overtake ossicular chain surgery in the near future. These changes in surgical volume have a direct implication on resident education and general otolaryngology expectations after graduation. Strong consideration should be made to replace "Stapedectomy/Ossiculoplasty" as resident key indicator with "Cochlear Implantation," a more professionally meaningful skill.

Evaluating Provider Perceptions of Telehealth Utility in Outpatient Rheumatology Telehealth Encounters.

OBJECTIVE: This study aims to explore the factors associated with rheumatology providers' perceptions of telehealth utility in real-world telehealth encounters. METHODS: From September 14, 2020 to January 31, 2021, 6 providers at an academic medical center rated their telehealth visits according to perceived utility in making treatment decisions using the following Telehealth Utility Score (TUS) (1 = very low utility to 5 = very high utility). Modified Poisson regression models were used to assess the association between TUS scores and encounter diagnoses, disease activity measures, and immunomodulatory therapy changes during the encounter. RESULTS: A total of 481 telehealth encounters were examined, of which 191 (39.7%) were rated as "low telehealth utility" (TUS 1-3) and 290 (60.3%) were rated as "high telehealth utility" (TUS 4-5). Encounters with a diagnosis of inflammatory arthritis were significantly less likely to be rated as high telehealth utility (adjusted relative risk [aRR], 0.8061; p = 0.004), especially in those with a concurrent noninflammatory musculoskeletal diagnosis (aRR, 0.54; p = 0.006). Other factors significantly associated with low telehealth utility included higher disease activity according to current and prior RAPID3 scores (aRR, 0.87 and aRR, 0.89, respectively; p < 0.001) and provider global scores (aRR, 0.83; p < 0.001), as well as an increase in immunomodulatory therapy (aRR, 0.70; p = 0.015). CONCLUSIONS: Provider perceptions of telehealth utility in real-world encounters are significantly associated with patient diagnoses, current and prior disease activity, and the need for changes in immunomodulatory therapy. These findings inform efforts to optimize the appropriate utilization of telehealth in rheumatology.

Profiling pathogenic protozoan and their functional pathways in wastewater using 18S rRNA and shotgun metagenomics.

Despite extensive research, little is known about the composition of eukaryotic protists in environmental samples. This is due to low parasite concentrations, the complexity of parasite diversity, and a lack of suitable reference databases and standardized protocols. To bridge this knowledge gap, this study used 18S rRNA short amplicon and shotgun metagenomic sequencing approaches to profile protozoan microbial communities as well as their functional pathways in treated and untreated wastewater samples collected from different regions of South Africa. Results demonstrated that protozoan diversity (Shannon index P-value = 0.03) and taxonomic composition (PERMANOVA, P-value = 0.02) was mainly driven by the type of wastewater samples (treated & untreated) and geographic location. However, these WWTPs were also found to contain a core community of protozoan parasites. The untreated wastewater samples revealed a predominant presence of free-living, parasitic, and potentially pathogenic protists typically found in humans and animals, ranging from Alveolata (27 %) phylum (Apicomplexa and Ciliophora) to Excavata (3.88 %) (Discoba and Parasalia) and Amoebozoa (2.84 %) (Entamoeba and Acanthamoeba). Shotgun metagenomics analyses in a subset of the untreated wastewater samples confirmed the presence of public health-importance protozoa, including Cryptosporidium species (3.48 %), Entamoeba hystolitica (6.58 %), Blastocystis hominis (2.91 %), Naegleria gruberi (2.37 %), Toxoplasma gondii (1.98 %), Cyclospora cayetanensis (1.30 %), and Giardia intestinalis (0.31 %). Virulent gene families linked to pathogenic protozoa, such as serine/threonine protein phosphatase and mucin-desulfating sulfatase were identified. Additionally, enriched pathways included thiamine diphosphate biosynthesis III, heme biosynthesis, Methylerythritol 4-Phosphate Pathway, methyl erythritol phosphate (MEP), and pentose phosphate pathways. These findings suggest that protozoan pathogens may possess metabolic and growth potential within WWTPs, posing a severe risk of transmission to humans and animals if inadequately disinfected before release. This study provides a baseline for the future investigation of diverse protozoal communities in wastewater, which are of public health importance.

WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN WAGNER SYNDROME.

PURPOSE: To describe novel clinical and angiographic findings in Wagner syndrome. METHODS: A retrospective case series of three related patients with Wagner syndrome. Patients underwent standard optical coherence tomography (OCT), B-scan ultrasonography, and fluorescein angiography in addition to wide field swept-source OCT angiography (WF SS-OCTA) (PLEX Elite 9000, Carl Zeiss Meditec Inc). Patients underwent genetic testing for a panel of hereditary vitreoretinopathies. RESULTS: Three related patients with Wagner syndrome were identified. All were found to have prominent vitreous strands, abnormal vitreoretinal adhesions, peripheral retinal holes, and varying degrees of myopia. A mid-peripheral tractional ridge was identified in all six eyes. All patients were positive for a known pathologic intron variant in the VCAN gene (4004-5T-A). Wide field swept-source OCT angiography (12 mm × 12 mm) was performed in two patients and demonstrated perivascular capillary loss in the superficial capillary plexus along the arcades bilaterally. One patient demonstrated associated retinal atrophy within the area of capillary loss. The capillary loss extended beyond the margin of retinal atrophy. CONCLUSION: The unusual finding of a mid-peripheral tractional ridge of the retina associated with myopia led to a genetic diagnosis of Wagner syndrome. Widefield swept-source OCT angiography demonstrated a novel feature of perivascular loss of the superficial retinal capillary plexus. This result suggests that vitreous traction may cause localized microvasculature dysfunction and subsequent retinal atrophy in Wagner syndrome. This is the first known evaluation of Wagner syndrome using OCT angiography.

De novo design of high-affinity binders of bioactive helical peptides.

Many peptide hormones form an α-helix on binding their receptors1-4, and sensitive methods for their detection could contribute to better clinical management of disease5. De novo protein design can now generate binders with high affinity and specificity to structured proteins6,7. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that by extending RFdiffusion8 to enable binder design to flexible targets, and to refining input structure models by successive noising and denoising (partial diffusion), picomolar-affinity binders can be generated to helical peptide targets by either refining designs generated with other methods, or completely de novo starting from random noise distributions without any subsequent experimental optimization. The RFdiffusion designs enable the enrichment and subsequent detection of parathyroid hormone and glucagon by mass spectrometry, and the construction of bioluminescence-based protein biosensors. The ability to design binders to conformationally variable targets, and to optimize by partial diffusion both natural and designed proteins, should be broadly useful.

Ureteral Stents Do Not Increase the Risk for Acute Kidney Injury After Colorectal Surgery.

BACKGROUND: Ureteral stents are thought to prevent or help identify ureteral injuries. Studies suggesting that ureteral stents increase the risk of postoperative acute kidney injury show inconsistent conclusions. The large ureteral stenting volume at our institution provided a unique opportunity for granular analysis not previously reported. OBJECTIVE: To determine whether prophylactic ureteral stenting at colorectal surgery increases acute kidney injury. DESIGN: Retrospective analysis of colorectal operations with prophylactic ureteral stents was compared to operations without stents. Adjusted analysis was performed with inverse probability treatment weighting. SETTINGS: Single institution enhanced recovery colorectal surgery service. PATIENTS: Prospective institutional database between July 1, 2018, and December 31, 2021. MAIN OUTCOME MEASURE: The primary outcome was acute kidney injury, defined as increase in creatinine ≥0. 3 mg/dL (definition 1) and 1.5-fold increase in creatinine (definition 2) within 48 hours postoperatively. RESULTS: There were 410 patients in the study population: 310 patients in the stent group and 100 in the no-stent group. There were 8 operative ureteral injuries: 4 (1.29%) in the stent group and 4 (4.0%) in the no-stent group ( p = 0.103). Unadjusted analysis revealed no significant difference in acute kidney injury between groups. After adjustment, there was still no significant difference in acute kidney injury between groups when defined as definition 1 (no-stent 23.76% vs stent 26.19%, p = 0.745) and as definition 2 (no-stent 15.86% vs stent 14.8%, p = 0.867). Subgroup analysis showed that lighted stents were associated with significantly more acute kidney injury than no-stent patients when defined as definition 1 ( p = 0.017) but not when defined as definition 2 ( p = 0.311). LIMITATIONS: Single-institution results may not be generalizable. CONCLUSION: Prophylactic ureteral stenting does not increase the risk of acute kidney injury for patients undergoing enhanced recovery colorectal surgery, although caution and further study may be warranted for lighted stents. Studies further examining contrasting roles of ureter stenting and imaging in open and minimally invasive colorectal surgery are warranted. See Video Abstract. LOS STENTS URETERALES NO AUMENTAN EL RIESGO DE LESIN RENAL AGUDA DESPUS DE LA CIRUGA COLORECTAL: ANTECEDENTES:Se cree que los stents ureterales previenen o ayudan a identificar las lesiones ureterales. Los estudios que sugieren que los stents ureterales aumentan el riesgo de lesión renal aguda post operatoria muestran conclusiones contradictorias. El gran volumen de endoprótesis ureterales en nuestra institución brindó una oportunidad única para el análisis granular que no se informó anteriormente.OBJETIVO:Determinar si la colocación de stent ureteral profiláctico en cirugía colorrectal aumenta el daño renal agudo.DISEÑO:El análisis retrospectivo de operaciones colorrectales con stents ureterales profilácticos se comparó con operaciones sin stents. El análisis ajustado se realizó con ponderación de tratamiento de probabilidad inversa.AJUSTES:Cirugía colorrectal de recuperación mejorada de una sola instituciónPACIENTES:Base de datos institucional prospectiva entre el 01/07/2018 y el 31/12/2021.MEDIDA DE RESULTADO PRINCIPAL:El resultado primario fue la lesión renal aguda definida como un aumento en la creatinina ≥ 0,3 mg/dL (Definición n.° 1) y un aumento de 1,5 veces en la creatinina (Definición n.° 2) dentro de las 48 horas posteriores a la operación.RESULTADOS:Hubo 410 pacientes en la población de estudio: 310 pacientes en el grupo Stent y 100 en el grupo No-Stent. Hubo 8 lesiones ureterales operatorias, 4 (1,29%) en el grupo Stent y 4 (4,0%) en el grupo No-Stent (p = 0,103). El análisis no ajustado no reveló diferencias significativas en la lesión renal aguda entre los grupos. Después del ajuste, todavía no hubo una diferencia significativa en la lesión renal aguda entre los grupos cuando se definió como Definición n.º 1 (sin stent 23,76 % frente a stent 26,19 %, p = 0,745) y por definición n.º 2 (sin stent 15,86 % frente a stent 14,8 %, p = 0,867). El análisis de sub grupos mostró que los stents iluminados se asociaron con una lesión renal aguda significativamente mayor que los pacientes sin stent cuando se definieron como Definición n.º 1 (p = 0,017), pero no cuando se los definió como Definición n.º 2 (p = 0,311).LIMITACIONES:Los resultados de una sola institución pueden no ser generalizables.CONCLUSIÓN:La colocación profiláctica de endoprótesis ureterales no aumenta el riesgo de lesión renal aguda en pacientes que se someten a cirugía colorrectal de recuperación mejorada, aunque es posible que se requiera precaución y estudios adicionales para las endoprótesis iluminadas. Se justifican estudios que examinen más a fondo las funciones contrastantes de la colocación de stents de uréter y las imágenes en la cirugía colorrectal abierta y mínimamente invasiva. (Traducción-Dr. Mauricio Santamaria ).

Ecological forecasts for marine resource management during climate extremes.

Forecasting weather has become commonplace, but as society faces novel and uncertain environmental conditions there is a critical need to forecast ecology. Forewarning of ecosystem conditions during climate extremes can support proactive decision-making, yet applications of ecological forecasts are still limited. We showcase the capacity for existing marine management tools to transition to a forecasting configuration and provide skilful ecological forecasts up to 12 months in advance. The management tools use ocean temperature anomalies to help mitigate whale entanglements and sea turtle bycatch, and we show that forecasts can forewarn of human-wildlife interactions caused by unprecedented climate extremes. We further show that regionally downscaled forecasts are not a necessity for ecological forecasting and can be less skilful than global forecasts if they have fewer ensemble members. Our results highlight capacity for ecological forecasts to be explored for regions without the infrastructure or capacity to regionally downscale, ultimately helping to improve marine resource management and climate adaptation globally.