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Distal radius fractures with severely osteoporotic bone or articular comminution can provide challenges to fixation with traditional volar locked plating alone. The purpose of this study was to evaluate the clinical, radiographic, and patient reported outcomes of patients undergoing distal radius fixation with volar locked plating and adjunctive dorsal bridge plating.

The purpose of this study is to evaluate the outcomes of operatively treated Mason Type III radial head fractures. Additionally, this project seeks to assess efficacy of PROMIS in evaluating post-operative outcomes for this patient population.

Coronal Plane Alignment of the Knee (CPAK), is an informative way to classify native knee alignment types, but does not consider posterior tibial slope, an important variable in knee kinematics. We hypothesized that tibial slope would have a significant effect on knee kinematics and warrant consideration in addition to the CPAK system.

Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48–K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48–K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48–K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48–K63-linked Ub, these results suggest a function for K48–K63-branched chains in VCP/p97-related processes.

COVID-19 had numerous objective and subjective effects on resident physician education. We intended to examine objective changes in orthopedic education that occurred during the COVID pandemic and other trends from 2018 to 2022 by analyzing surgical case logs from Accreditation Counsel for Graduate Medical Education (ACGME) approved American orthopedics programs. We hypothesized that surgical case load during the COVID pandemic would remain similar to pre-pandemic levels and case logs would show a general upward trend.

Brain region-specific degeneration and somatic expansions of the mutant Huntingtin (mHTT) CAG tract are key features of Huntington’s disease (HD). However, the relationships among CAG expansions, death of specific cell types and molecular events associated with these processes are not established. Here, we used fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. CAG expansions arise at mHTTin striatal medium spiny neurons (MSNs), cholinergic interneurons and cerebellar Purkinje neurons, and at mutant ATXN3in MSNs from SCA3 donors. CAG expansions in MSNs are associated with higher levels of MSH2 and MSH3 (forming MutSβ), which can inhibit nucleolytic excision of CAG slip-outs by FAN1. Our data support a model in which CAG expansions are necessary but may not be sufficient for cell death and identify transcriptional changes associated with somatic CAG expansions and striatal toxicity.

•We found a telehealth-delivered SICP to be feasible and usable for older adults with AML and MDS.•The majority of patients found the telehealth SICP to be worthwhile and would recommend it to others.

Oncogenic KRAS activation, inflammation and p53 mutation are key drivers of pancreatic cancer (PC) development. Here we report iASPP, an inhibitor of p53, as a paradoxical suppressor of inflammation and oncogenic KRASG12D-driven PC tumorigenesis. iASPP suppresses PC onset driven by KRASG12Dalone or KRASG12Din combination with mutant p53R172H. iASPP deletion limits acinar-to-ductal metaplasia (ADM) in vitro but accelerates inflammation and KRASG12D-induced ADM, pancreatitis and PC tumorigenesis in vivo. KRASG12D/iASPPΔ8/Δ8tumours are well-differentiated classical PCs and their derivative cell lines form subcutaneous tumours in syngeneic and nude mice. Transcriptomically, either iASPP deletion or p53 mutation in the KRASG12Dbackground altered the expression of an extensively overlapping gene set, comprised primarily of NF-κB and AP1-regulated inflammatory genes. All these identify iASPP as a suppressor of inflammation and a p53-independent oncosuppressor of PC tumorigenesis.

Background: First tarsometatarsal joint arthrodesis is a common procedure performed by podiatrists and orthopedic surgeons. There remains debate on how useful CT scans are in assessing fusion status in the post-operative patient. The purpose of our study was to determine the reliability among both orthopedic surgeons and radiologists in reviewing both postoperative radiographs and CT in order to determine if fusion had occurred in patients undergoing 1st tarsometatarsal arthrodesis. A secondary purpose of this study was to determine if CT offered improved inter- and intra-rater reliability when compared to plain radiographs. Methods: Patients who underwent 1st tarsometatarsal arthrodesis were retrospectively reviewed and those who underwent CT post-operatively for persistent pain were identified. Orthopedic surgeons and radiologists then analyzed the radiographs and CT of these patients for union with a threshold for union being set at 50% of the joint being fused. Imaging was then re-evaluated by the same provider 6 months later. Results: 24 patients were identified meeting inclusion criteria. Inter-rater reliability and intra-rater reliability for assessment of 1st tarsometatarsal arthrodesis were better with CT compared to radiographs; however, this association was not deemed reliable. Both imaging modalities were not able to assess union status confidently and reliably across reviewers, although CT scan had better intra-rater reliability. Conclusions: While CT is frequently used to assess fusion in patients who have underwent 1st tarsometatarsal arthrodesis, it was not found to be better than radiographs. Practitioners should reconsider the use CT as the gold standard when assessing fusion in this population.

Insect societies are tightly integrated, complex biological systems in which group-level properties arise from the interactions between individuals1–4. However, these interactions have not been studied systematically and therefore remain incompletely known. Here, using a reverse engineering approach, we reveal that unlike solitary insects, ant pupae extrude a secretion derived from the moulting fluid that is rich in nutrients, hormones and neuroactive substances. This secretion elicits parental care behaviour and is rapidly removed and consumed by the adults. This behaviour is crucial for pupal survival; if the secretion is not removed, pupae develop fungal infections and die. Analogous to mammalian milk, the secretion is also an important source of early larval nutrition, and young larvae exhibit stunted growth and decreased survival without access to the fluid. We show that this derived social function of the moulting fluid generalizes across the ants. This secretion thus forms the basis of a central and hitherto overlooked interaction network in ant societies, and constitutes a rare example of how a conserved developmental process can be co-opted to provide the mechanistic basis of social interactions. These results implicate moulting fluids in having a major role in the evolution of ant eusociality.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1–3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4–7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8(SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9(HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.

The ATR kinase protects cells against DNA damage and replication stress and represents a promising anti-cancer drug target. The ATR inhibitors (ATRi) berzosertib and gartisertib are both in clinical trials for the treatment of advanced solid tumors as monotherapy or in combination with genotoxic agents. We carried out quantitative phospho-proteomic screening for ATR biomarkers that are highly sensitive to berzosertib and gartisertib, using an optimized mass spectrometry pipeline. Screening identified a range of novel ATR-dependent phosphorylation events, which were grouped into three broad classes: (i) targets whose phosphorylation is highly sensitive to ATRi and which could be the next generation of ATR biomarkers; (ii) proteins with known genome maintenance roles not previously known to be regulated by ATR; (iii) novel targets whose cellular roles are unclear. Class iii targets represent candidate DNA damage response proteins and, with this in mind, proteins in this class were subjected to secondary screening for recruitment to DNA damage sites. We show that one of the proteins recruited, SCAF1, interacts with RNAPII in a phospho-dependent manner and recruitment requires PARP activity and interaction with RNAPII. We also show that SCAF1 deficiency partly rescues RAD51 loading in cells lacking the BRCA1tumor suppressor. Taken together these data reveal potential new ATR biomarkers and new genome maintenance factors.

Embryonic renal interstitial cells give rise to multiple cell types in the adult, including fibroblasts, myofibroblasts, mural cells, and smooth muscle. How the different cell types arise from a multipotent progenitor is unknown. In this study, the authors identified a subpopulation of stromal cells in mouse embryonic kidneys with enriched activity in the transcriptional regulators YAP and TAZ, and show that YAP/TAZ and the transcriptional regulator SRF have independent and codependent roles in the specification of unique subsets of interstitial cells. These findings offer insights into the role of the interstitium in kidney development and may inform efforts aimed at regenerating renal tissue and may aid efforts to understand the drivers of kidney fibrosis.

For years, New Jersey Transit (NJ Transit) looked for a suitable site to build a rail yard layover facility beyond the western limit of its New Jersey commuter rail service [...]

Objective: To describe a case of laryngeal Langerhans cell histiocytosis, discuss its characteristic features and management, and provide a review of the available literature.Methods: A patient presenting to a tertiary care medical center with dyspnea and hoarseness is described. A literature review of laryngeal Langerhans cell histiocytosis cases was performed through a search of articles indexed in the National Institutes of Health PubMed system.Results: We report a case of a 69-year old male, who presented with a laryngeal mass highly suspicious for laryngeal squamous cell carcinoma, was treated with laser excision, and was subsequently found to have laryngeal Langerhans cell histiocytosis upon histological analysis. Including our current case, we found six prior reported cases of laryngeal Langerhans cell histiocytosis in the literature. Of the six cases, four were in adults, while two were in children. Dyspnea is a common presenting complaint present in all cases. Smoking may be a potential risk factor.Conclusions: Laryngeal Langerhans cell histiocytosis is a rare condition and an important consideration in the differential diagnosis of patients presenting with a laryngeal mass and symptoms of dyspnea or hoarseness. Biopsy and histopathological analysis are key to the diagnosis. Surgical excision and radiotherapy are successful treatments used in clinical practice.

Our study sought to determine outcomes of patients who underwent non-operative and surgical treatment of distal biceps ruptures utilizing both PROMIS and Patient Acceptable Symptoms State (PASS).

The Colorado General Assembly passed three laws in 2016 that affect Colorado employers. This article briefly describes the new laws and suggests steps employers should take to assure future compliance. [...]

The industry is in trouble, and everybody is focused on cost containment. Grasping for the 'low hanging fruit,' a number of painful initiatives have been implemented with limited success. However, [...]

Here, Infarinato et al. investigated the signaling factors regulating activation of quiescent melanocyte stem cells (McSCs) to generate proliferative progeny that differentiate into pigment-producing melanocytes. Using conditional lineage-specific genetic ablation studies in mice, they found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation, and furthermore show that following WNT-mediated activation of McSCs, BMP, and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation.

Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by ‘reader’ proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood. We previously identified the ENL protein as a reader of histone acetylation via its YEATS domain, linking it to the expression of cancer-driving genes in acute leukaemia1. Recurrent hotspot mutations have been found in the ENL YEATS domain in Wilms tumour2,3, the most common type of paediatric kidney cancer. Here we show, using human and mouse cells, that these mutations impair cell-fate regulation by conferring gain-of-function in chromatin recruitment and transcriptional control. ENL mutants induce gene-expression changes that favour a premalignant cell fate, and, in an assay for nephrogenesis using murine cells, result in undifferentiated structures resembling those observed in human Wilms tumour. Mechanistically, although bound to largely similar genomic loci as the wild-type protein, ENL mutants exhibit increased occupancy at a subset of targets, leading to a marked increase in the recruitment and activity of transcription elongation machinery that enforces active transcription from target loci. Furthermore, ectopically expressed ENL mutants exhibit greater self-association and form discrete and dynamic nuclear puncta that are characteristic of biomolecular hubs consisting of local high concentrations of regulatory factors. Such mutation-driven ENL self-association is functionally linked to enhanced chromatin occupancy and gene activation. Collectively, our findings show that hotspot mutations in a chromatin-reader domain drive self-reinforced recruitment, derailing normal cell-fate control during development and leading to an oncogenic outcome.

In multicellular organisms, duplicated genes can diverge through tissue-specific gene expression patterns, as exemplified by highly regulated expression of RUNX transcription factor paralogs with apparent functional redundancy. Here we asked what cell-type-specific biologies might be supported by the selective expression of RUNX paralogs during Langerhans cell and inducible regulatory T cell differentiation. We uncovered functional nonequivalence between RUNX paralogs. Selective expression of native paralogs allowed integration of transcription factor activity with extrinsic signals, while non-native paralogs enforced differentiation even in the absence of exogenous inducers. DNA binding affinity was controlled by divergent amino acids within the otherwise highly conserved RUNT domain and evolutionary reconstruction suggested convergence of RUNT domain residues toward submaximal strength. Hence, the selective expression of gene duplicates in specialized cell types can synergize with the acquisition of functional differences to enable appropriate gene expression, lineage choice and differentiation in the mammalian immune system.

Introduction:Older patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) often feel shocked and bewildered about their diagnosis. Serious illness conversations (SICs) may increase patient's disease understanding and better prepare them for the future. However, SICs currently tend to happen late in the disease course. One reason is clinician-perceived patient discomfort. Telehealth may promote patient comfort by allowing SICs to take place from home. We previously conducted a qualitative study to adapt the Serious Illness Care Program (SICP) for delivery via telehealth to promote early SICs among older adults with AML and MDS. The purpose of this study was to assess the feasibility and usability of the telehealth-delivered SICP for older patients with AML and MDS.

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The use of slurry wall panels during the construction of the 15th street underpass in the Central Platte Valley in Denver is discussed. Slurry walls were required to protect adjacent historic buildings from drawdown and to keep the railroad tracks above 15th street active during excavation and temporary dewatering. Slurry wall movements and groundwater flow and levels were monitored during and after underpass construction., IN 1982 Denver began an ambitious program to revitalize major elements of its aging infrastructure. One focal point of this program was the Central Platte Valley, a 600-acre area adjacent [...]

We present a rare case report of a patient with chronic subdural haematoma presenting with sudden onset blindness secondary to severe acute bilateral papilloedema. Following prompt surgical evacuation, the patient's visual acuity returned back to almost normal. Previous reported cases in the literature of blindness following subdural haematomas were related to bilateral homonymous hemianopia due to compression of the posterior cerebral artery following tentorial herniation. These patients were either left blind or developed significant visual deficit despite surgical evacuation. Our case is the first in the literature where the blindness was reversible and due to severe acute papilloedema. There was also no evidence of posterior cerebral artery territory ischaemia. We discuss the importance of visual symptoms in subdural haematoma and emphasize the importance of prompt early intervention. Keywords: blindness | subdural haematoma | papilloedema | chronic subdural haematoma, Clinical presentation A 21 years old man was transferred as an emergency from the regional district general hospital after he presented with sudden onset of complete blindness in both eyes [...]

We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range allows us to study and disentangle shake processes and intramolecular inelastic scattering effects. In this gas-phase study, relative intensities of the carbon 1s photoelectron lines from chemically inequivalent carbon atoms in the same molecule have been measured as a function of the incident photon energy in the range of 300–6000 eV. We present relative cross sections for the chemically shifted carbon 1s lines in the photoelectron spectra of ethyl trifluoroacetate (the “ESCA” molecule). The results are compared with those of methyl trifluoroacetate and S-ethyl trifluorothioacetate as well as a series of chloro-substituted ethanes and 2-butyne. In the soft X-ray energy range, the cross sections show an extended X-ray absorption fine structure type of wiggles, as was previously observed for a series of chloroethanes. The oscillations are damped in the hard X-ray energy range, but deviations of cross-section ratios from stoichiometry persist, even at high energies. The current findings are supported by theoretical calculations based on a multiple scattering model. The use of soft and tender X-rays provides a more complete picture of the dominant processes accompanying photoionization. Such processes reduce the main photoelectron line intensities by 20–60%. Using both energy ranges enabled us to discern the process of intramolecular inelastic scattering of the outgoing electron, whose significance is otherwise difficult to assess for isolated molecules. This effect relates to the notion of the inelastic mean free path commonly used in photoemission studies of clusters and condensed matter.

Dysphonia is often blamed on laryngopharyngeal reflux (LPR) in the face of a normal flexible laryngoscopic examination. LPR remains primarily (and unfortunately) a diagnosis of exclusion rather than inclusion in the face of vague throat complaints and laryngeal signs attributed to reflux. LPR remains misdiagnosed and overdiagnosed as the cause of many identical, vague throat symptoms and laryngeal complaints. Despite LPR being commonly implicated as the cause of a myriad of nonspecific pharyngeal symptoms, LPR as a physiologic process is common. Whether or not it is a contributor to a patient’s symptoms, especially dysphonia, is the focus of this article.

Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1–dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K–phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2–PI3K–p-Akt signalling pathway. Hervera et al. show that extracellular vesicles containing NOX2 complexes are released from macrophages and incorporated into injured axons, leading to axonal regeneration through PI3K–p-Akt signalling.

Objectives: Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar.Methods: Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation.Results: Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 (P< .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5).Conclusions: A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

Loss of function of the DIS3L2 exoribonuclease is associated with Wilms tumor and the Perlman congenital overgrowth syndrome. Here, Hunter et al.’s analysis of Dis3l2-null nephron progenitor cells reveals up-regulation of Igf2, a growth-promoting gene strongly associated with Wilms tumorigenesis.

Work by Corron et al. [1,2] represented a chaotic signal as a set of basis functions, and built a matched filter for the resulting signal. This paper makes use of basis functions without an underlying chaotic system. Matched filtering is still possible, allowing communication in noisy environments, but the resulting signals can be broad band, which is useful for producing signals that are hard to detect. The receiver design retains the simplicity of Corron et al. [1,2], which is good when weight, power consumption or bandwidth are constraints on the receiver. [ABSTRACT FROM AUTHOR]

Many methods for using chaos as a communications signal have been suggested, but all suffer from the difficulty in synchronizing the transmitter and receiver. Chaotic signals are broad band and unpredictable, making them potentially useful when the goal is low interference communications or even low probability of detection (LPD) communications. In this work, a set of randomly chosen chaotic sequences is used to synchronize a chaotic transmitter to a receiver. Once synchronization is achieved, two methods are presented for encoding information. Simply multiplying the chaotic signal by ±1 is used to encode the binary signals 1 or 0. The binary information is recovered by cross correlating the transmitted signal with the synchronized signal in the receiver. This encoding technique offers the same bit error performance as binary phase shift keying (BPSK). The data rate can be increased by creating orthogonal signals from different components of a multidimensional chaotic system. Cyclostationary properties of these signals and differential chaos shift keying (DCSK) are analyzed to show possible signatures that would make the signal easily detectable. [ABSTRACT FROM AUTHOR]

Due to the increased spectrum congestion, there has been a tremendous interest in radar and communication devices operating on a shared platform. Therefore, the waveform design for joint radar communication (JRC) systems has recently gained significant attention. Despite several efforts, most state-of-the-art waveforms are far from achieving ideal radar and communication performance. To address this issue, we design a family of chaotic maps whose output yields waveforms with optimal JRC features. We adopt the antipodal chaos shift keying (ACSK) scheme, where the segments of the chaotic signal are multiplied by ± 1 to encode the binary information. This ACSK waveform is further used for the JRC system transmission. Once the synchronization between the receiver and transmitter is established, the information is recovered by cross-correlating the received and the synchronized waveforms. This technique yields bit error rates (BER) similar to the theoretical values of the BPSK waveform. The same transmitted waveform results in a thumb-tack ambiguity function which is essential for high-resolution radar imaging. The variance analysis of the ambiguity function shows that the proposed waveform is comparable to the noise-modulated waveforms. We also show that the multiplexed ACSK waveforms yield similar optimal behavior. Furthermore, we demonstrate the potential of the family of chaotic maps for multiple-input, multiple-output (MIMO) JRC systems. • Design a rule for a chaotic map using control parameters to produce a broad spectrum. • The autocorrelation of a chaotic map is of high quality with extremely low sidelobes. • The information is encoded using antipodal chaos shift keying. • Transmit the encoded chaotic signal in the JCR setting. • Achieved optimal performance both for radar and communications simultaneously. [ABSTRACT FROM AUTHOR]

Reports on a demonstration of how two chaotic systems can be synchronized. Use of such device for encrypted communications; Computer simulation and construction of electrical circuits by the authors; Driving circuit and synchronized circuit.