Tissue Disruption Research Articles

Pathogenesis of Human Adenomyosis: Current Understanding and Its Association with Infertility.

The aim of this review article was to summarize our current understanding on the etiologies and pathogenesis of human adenomyosis and to clarify the relative association between adenomyosis and infertility. The exact pathogenesis of adenomyosis is still elusive. Among different reported concepts, direction invagination of gland cells from the basalis endometrium deep into myometrium is the most widely accepted opinion on the development of adenomyosis. According to this concept, endometrial epithelial cells and changed fibroblasts, abnormally found in the myometrium in response to repeated tissue injury and/or disruption at the endometrium-myometrium interface (EMI), elicit hyperplasia and hypertrophy of the surrounding smooth muscle cells. In this review, a comprehensive review was performed with a literature search using PubMed for all publications in English and Japanese (abstract in English), related to adenomyosis and infertility, from inception to April 2021. As an estrogen-regulated factor, hepatocyte growth factor (HGF) exhibits multiple functions in endometriosis, a disease commonly believed to arise from the functionalis endometrium. As a mechanistic basis of gland invagination, we investigated the role of HGF, either alone or in combination with estrogen, in the occurrence of epithelial-mesenchymal transition (EMT) in adenomyosis. Aside from microtrauma at the EMI, metaplasia of displaced Müllerian remnants, differentiation of endometrial stem/progenitor cells within the myometrium and somatic mutation of some target genes have been put forward to explain how adenomyosis develops. In addition, the possible role of microRNAs in adenomyosis is also discussed. Besides our knowledge on the conventional classification (focal and diffuse), two recently proposed classifications (intrinsic and extrinsic) of adenomyosis and the biological differences between them have been described. Although the mechanistic basis is unclear, the influence of adenomyosis on fertility outcome is important, especially considering the recent tendency to delay pregnancy among women. Besides other proposed mechanisms, a recent transmission election microscopic (TEM) study indicated that microvilli damage and an axonemal alteration in the apical endometria of human adenomyosis, in response to endometrial inflammation, may be involved in negative fertility outcomes. We present a critical analysis of the literature data concerning the mechanistic basis of infertility in women with adenomyosis and its impact on fertility outcome.

Powering morphogenesis: multiscale challenges at the interface of cell adhesion and the cytoskeleton.

Among the defining features of the animal kingdom is the ability of cells to change shape and move. This underlies embryonic and postembryonic development, tissue homeostasis, regeneration, and wound healing. Cell shape change and motility require linkage of the cell's force-generating machinery to the plasma membrane at cell-cell and cell-extracellular matrix junctions. Connections of the actomyosin cytoskeleton to cell-cell adherens junctions need to be both resilient and dynamic, preventing tissue disruption during the dramatic events of embryonic morphogenesis. In the past decade, new insights radically altered the earlier simple paradigm that suggested simple linear linkage via the cadherin-catenin complex as the molecular mechanism of junction-cytoskeleton interaction. In this Perspective we provide a brief overview of our current state of knowledge and then focus on selected examples highlighting what we view as the major unanswered questions in our field and the approaches that offer exciting new insights at multiple scales from atomic structure to tissue mechanics.

Abstract 59: Optimization of high-throughput, high-depth, targeted single-cell DNA sequencing to pancreatic ductal adenocarcinoma

Abstract Purpose of study: Despite insights gained by bulk DNA sequencing of cancer it remains challenging to resolve “mixed signals”, i.e. the admixture of normal and tumor cells, and/or of distinct tumor subclones. Bulk sequencing of pancreatic ductal adenocarcinoma (PDAC) has been particularly problematic due to the high stromal content and resulting low tumor cellularity. Strategies to account for this have included laser capture microdissection yet this is a laborious process not amenable to high-throughput pipelines. We sought to develop and apply a high-throughput, high-depth, targeted single-cell DNA sequencing (scDNA-seq) method to account for these issues, including the ability to extract high quality genomic information from low purity and archival samples. Experimental procedures: Bulk whole exome sequencing (WES) was performed on 29 biologically distinct samples. For single cell sequencing, we developed a custom panel containing 186 amplicons covering 93 genes that represent the most common germline and somatic targets reported in PDAC. Based on a commercially available system that enables automatic enzymatic and mechanical tissue disruption with integrated fluidic processes, we optimized a nuclei extraction workflow from frozen tissues that is highly compatible with downstream microdroplet-based single-cell encapsulation and library preparation. With it we generated scDNA-seq data from archival tissues of 15 PDAC patients at varying stages of the disease. Results were compared to that found in matched bulk sequencing data. Summary of new, unpublished data and conclusions: 42 samples were analyzed by single cell sequencing. Our nuclei extraction workflow generated on average 2867 single cell libraries per sample at >80X read depth. The single-cell results aligned well with matched bulk data in terms of the detection of key genetic variants and their variant allele frequency (VAF). We also identified additional driver variants not seen by WES, some with direct clinical evidence. Benefits of this workflow over preexisting methods are its speed of sample preparation, efficiency of sample use (particularly for small samples), flexibility by allowing for storage of excess extracted nuclei, and economy of scale. Together, these features support preparation of large numbers of cancer samples in a relatively short period of time. Citation Format: Haochen Zhang, Elias-Ramzey Karnoub, Ronan Chaligné, Ignas Masilionis, Alvin Makohon-Moore, Jungeui Hong, Christine Iacobuzio-Donahue. Optimization of high-throughput, high-depth, targeted single-cell DNA sequencing to pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 59.

A Preclinical Pilot Study on the Effects of Thermal Ablation on Lamb Growth Plates.

(1) Background: Thermal ablation has been demonstrated to affect the bone growth of osteoid osteoma in adolescents. Growth modulation due to thermal heat in children is conceivable, but has not yet been established. We used lamb extremities as a preclinical model to examine the effect of thermal ablation on growth plates in order to evaluate its potential for axial or longitudinal growth modulation in pediatric patients. (2) Methods: Thermal ablation was performed by electrocautery on eight different growth plates of the legs and distal radii of a stillborn lamb. After treatment, target hits and the physical extent of the growth plate lesions were monitored using micro-computed tomography (micro-CT) and histology. (3) Results: Lesions and their physical extent could be quantified in 75% of the treated extremities. The histological analysis revealed that the disruption of tissue was confined to a small area and the applied heat did not cause the entire growth plate to be disrupted or obviously damaged. (4) Conclusions: Thermal ablation by electrocautery is minimally invasive and can be used for targeted disruption of small areas in growth plates in the animal model. The results suggest that thermal ablation can be developed into a suitable method to influence epiphyseal growth in children.

An adult zebrafish model for adherent-invasive Escherichia coli indicates protection from AIEC infection by probiotic E. coli Nissle

SummaryAdherent-invasive Escherichia coli (AIEC) is an opportunistic pathogen associated with major inflammatory bowel disease, Crohn disease, and ulcerative colitis. Unfavorable conditions push commensal AIEC to induce gut inflammation, sometimes progressing to inflammation-induced colon cancer. Recently, zebrafish have emerged as a useful model to study human intestinal pathogens. Here, a zebrafish model to study AIEC infection was developed. Bath inoculation with AIEC resulted in colonization and tissue disruption in the zebrafish intestine. Gene expression of pro-inflammatory markers including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNFα), interferon-γ (IFNγ), and S100A-10b (akin to human calprotectin) in the zebrafish intestine was significantly induced by AIEC infection. The probiotic E. coli Nissle 1917 (EcN) was tested as a therapeutic and prophylactic against AIEC infection and reduced AIEC colonization, tissue damage, and pro-inflammatory responses in zebrafish. Furthermore, EcN diminished the propionic-acid-augmented hyperinfection of AIEC in zebrafish. Thus, this study shows the efficacy of EcN against AIEC in an AIEC-zebrafish model.

Dental Management of Maxillofacial Ballistic Trauma.

Maxillofacial ballistic trauma represents a devastating functional and aesthetic trauma. The extensive damage to soft and hard tissue is unpredictable, and because of the diversity and the complexity of these traumas, a systematic algorithm is essential. This study attempts to define the best management of maxillofacial ballistic injuries and to describe a standardized, surgical and prosthetic rehabilitation protocol from the first emergency stage up until the complete aesthetic and functional rehabilitation. In low-velocity ballistic injuries (bullet speed <600 m/s), the wound is usually less severe and not-fatal, and the management should be based on early and definitive surgery associated with reconstruction, followed by oral rehabilitation. High-velocity ballistic injuries (bullet speed >600 m/s) are associated with an extensive hard and soft tissue disruption, and the management should be based on a three-stage reconstructive algorithm: debridement and fixation, reconstruction, and final revision. Rehabilitating a patient with ballistic trauma is a multi-step challenging treatment procedure that requires a long time and a multidisciplinary team to ensure successful results. The prosthodontic treatment outcome is one of the most important parameters by which a patient measures the restoration of aesthetic, functional, and psychological deficits. This study is a retrospective review: twenty-two patients diagnosed with outcomes of ballistic traumas were identified from the department database, and eleven patients met the inclusion criteria and were enrolled.

Sonoporation of Human Renal Proximal Tubular Epithelial Cells In Vitro to Enhance the Liberation of Intracellular miRNA Biomarkers.

Ultrasound has previously been demonstrated to non-invasively cause tissue disruption. Small animal studies have demonstrated that this effect can be enhanced by contrast microbubbles and has the potential to be clinically beneficial in techniques such as targeted drug delivery or enhancing liquid biopsies when a physical biopsy may be inappropriate. Cavitating microbubbles in close proximity to cells increases membrane permeability, allowing small intracellular molecules to leak into the extracellular space. This study sought to establish whether cavitating microbubbles could liberate cell-specific miRNAs, augmenting biomarker detection for non-invasive liquid biopsies. Insonating human polarized renal proximal tubular epithelial cells (RPTECs), in the presence of SonoVue microbubbles, revealed that cellular health could be maintained while achieving the release of miRNAs, miR-21, miR-30e, miR-192 and miR-194 (respectively, 10.9-fold, 7.17-fold, 5.95-fold and 5.36-fold). To examine the mechanism of release, RPTECs expressing enhanced green fluorescent protein were generated and the protein successfully liberated. Cell polarization, cellular phenotype and cell viability after sonoporation were measured by a number of techniques. Ultrastructural studies using electron microscopy showed gap-junction disruption and pore formation on cellular surfaces. These studies revealed that cell-specific miRNAs can be non-specifically liberated from RPTECs by sonoporation without a significant decrease in cell viability.

Jet-Induced Tissue Disruption for Blood Release.

Needle-free jet injection is a drug delivery technique that uses the momentum of the fluid drug to break through the skin. This technique has recently also been applied to blood release, aiming to collect samples from capillaries in the skin without needing a lancet prick. This work provides new information about the wound geometry and tissue disruption caused by shallow jet injection with circular-shaped and slot-shaped jets. We use histological analysis to compare the disruption of tissue, including blood vessels, caused by lancet-pricking and jet injection with a circular-shaped jet and a lancet-inspired slot-shaped jet. Intradermal injection into porcine skin using a slot-shaped jet disrupted more vascular endothelium in the tissue than a circular-shaped jet and did so at a smaller penetration depth with smaller wound volume. Our results suggest that shallow jet injections may have the potential to release more capillary blood than a lancet prick. These findings demonstrate that a reversible jet injector might be used in diabetes management as a device to release and collect blood samples, in addition to being used to deliver insulin. Tissue disruption is crucial to consider when using jet injection to deliver drugs and release capillary blood.

Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles

Salicylic acid phenylethyl ester (SAPE) was synthesized by Zn(OTf)2-catalyzed selective esterification of salicylic acid and phenylethyl alcohol and studied for its role as an immunomodulatory and anticancer agent. Low toxicity and favorable physical, Lipinski-type, and solubility properties were elucidated by ADME-tox studies. Molecular docking of SAPE against COX-2 revealed favorable MolDockscore, rerank score, interaction energy, internal pose energy, and hydrogen bonding as compared to ibuprofen and indomethacin. An average RMSD of ~ 0.13 nm for the docked complex with stable dynamic equilibrium condition was noted during the 20 ns MD simulation. A low band gap predicting a strong binding affinity at the enzyme’s active site was further predicted by DFT analysis. The ester caused a reduction in the percentage of erythrocyte hemolysis and was shown to be non-cytotoxic against human lymphocytes, CaCo-2, and HepG-2 cells by the MTT assay. Moreover, it’s in vitro efficacy in inhibiting COX-2 enzyme under both LPS stimulated intestinal cells and direct sequestration assays was found to be higher than salicylic acid and indomethacin. The anticancer activity of SAPE was tested on the breast cancer cell line MCF-7, and potential efficacy was exhibited in terms of decreased cell viability. Flow cytometry analysis exhibited the arrest of the cell cycle at G1/G0 and S phases, during which induction of autophagic vesicle formation and decrease in mitochondrial membrane potential was observed owing to increased ROS production. Furthermore, at these phases, the onset of apoptosis along with DNA damage was also observed. Pre-treatment with SAPE in colitis-induced Wistar rats displayed low disease activity index and reduction in the extent of intestinal tissue disruption and lipid peroxidation. A marked increase of anti-oxidative enzymes viz., catalase, GGT, and GST, and a decrease of pro-inflammatory cytokines IL-6 and TNF-α in the intestinal tissue extracts of the treated groups was noted. The results of this study have sufficient credence to support that the synthesised ester (SAPE) be considered as an anti-oxidative and anti-inflammatory compound with therapeutic potential for the effective management of cancer.

Comparative Toxicotranscriptomics of Single Cell RNA-Seq and Conventional RNA-Seq in TCDD-Exposed Testicular Tissue.

In this report, we compare the outcomes and limitations of two methods of transcriptomic inquiry on adult zebrafish testes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during sexual differentiation: conventional or bulk RNA-seq (bulk-seq) and single cell RNA sequencing (scRNA-seq) data. scRNA-seq has emerged as a valuable tool for uncovering cell type-specific transcriptome dynamics which exist in heterogeneous tissue. Our lab previously showed the toxicological value of the scRNA-seq pipeline to characterize the sequelae of TCDD exposure in testes, demonstrating that loss of spermatids and spermatozoa, but not other cell types, contributed to the pathology of infertility in adult male zebrafish exposed during sexual differentiation. To investigate the potential for technical artifacts in scRNA-seq such as cell dissociation effects and reduced transcriptome coverage, we compared bulk-sequenced and scRNA-seq-paired samples from control and TCDD-exposed samples to understand what is gained and lost in scRNA-seq vs bulk-seq, both transcriptomically and toxicologically. We hypothesized that the testes may be sensitive to tissue disruption as they contain multiple cell types under constant division and/or maturation, and that TCDD exposure may mediate the extent of sensitivity. Thus, we sought to understand the extent to which this dissociation impacts the toxicological value of data returned from scRNA-seq. We confirm that the required dissociation of individual cells from intact tissue has a significant impact on gene expression, affecting gene pathways with the potential to confound toxicogenomics studies on exposures if findings are not well-controlled and well-situated in context. Additionally, a common scRNA-seq method using cDNA amplified from the 3’ end of mRNA under-detects low-expressing transcripts including transcription factors. We confirm this, and show TCDD-related genes may be overlooked by scRNA-seq, however, this under-detection effect is not mediated by TCDD exposure. Even so, scRNA-seq generally extracted toxicologically relevant information better than the bulk-seq method in the present study. This report aims to inform future experimental design for transcriptomic investigation in the growing field of toxicogenomics by demonstrating the differential information extracted from sequencing cells—despite being from the same tissue and exposure scheme—is influenced by the specific protocol used, with implications for the interpretation of exposure-induced risk.

Transgenic mice encoding modern imaging probes: Properties and applications.

SUMMARYModern biology is increasingly reliant on optical technologies, including visualization and longitudinal monitoring of cellular processes. The major limitation here is the availability of animal models to track the molecules and cells in their natural environment in vivo. Owing to the integrity of the studied tissue and the high stability of transgene expression throughout life, transgenic mice encoding fluorescent proteins and biosensors represent unique tools for in vivo studies in norm and pathology. We review the strategies for targeting probe expression in specific tissues, cell subtypes, or cellular compartments. We describe the application of transgenic mice expressing fluorescent proteins for tracking protein expression patterns, apoptotic events, tissue differentiation and regeneration, neurogenesis, tumorigenesis, and cell fate mapping. We overview the possibilities of functional imaging of secondary messengers, neurotransmitters, and ion fluxes. Finally, we provide the rationale and perspectives for the use of transgenic imaging probes in translational research and drug discovery.

Older Mice Show Decreased Regeneration of Neuromuscular Junctions Following Lengthening‐Contraction Injury

Progressive muscle atrophy and loss of muscle strength associated with old age have been well documented. Although impairments in the ability of old mice to regenerate skeletal muscle following injury have been demonstrated, less is known about the way age modulates the regenerative response of motor neurons and the neuromuscular junctions (NMJ) of mice following contraction‐induced injury. The inability for NMJs to effectively regenerate following an injury could lead to the death of the denervated muscle fibers and therefore play a contributing role to age‐related sarcopenia. To investigate the relationship between age and NMJ regeneration following injury, extensor digitorum longus (EDL) muscles of adult (8‐9 months), middle‐aged (18‐19 months), and old mice (27‐28 months) were subjected to a protocol of repeated lengthening‐contractions that resulted in an acute force deficit of ~70%. After 28 days, muscles were evaluated for maximum force generating capacity, muscle mass, NMJ innervation, and endplate fragmentation. Cross sections of muscles taken at three days post injury showed extensive infiltration of mononuclear cells and widespread tissue disruption consistent with the induction of severe injury to the muscles. At 28 days, maximum isometric force recovered completely in adult mice, but was significantly reduced in middle aged and old mice when compared to muscles of adult mice. In each case, approximately 29% of fibers in the cross sections displayed containing central nuclei, whereas controls showed only 2.9%, indicating that the injured muscle fibers had undergone degeneration and regeneration. Analysis of the innervation of the NMJs in the regenerated muscles showed a moderate decrease in the number of fully innervated endplates in old mice as compared to adult and middle‐aged mice. When the architecture of the endplates in regenerated muscles was examined, the relative number of NMJs with intact postsynaptic structure varied little between the age groups, although control muscles of old mice showed an increase in the number of fragmented endplates compared with the adult and middle aged mice. Thus, the diminished ability of the skeletal muscle of old mice to recover following injury may be, in part, due to an age‐related decrease in the ability to adequately regenerate motor neurons and perhaps form NMJs in the injured muscle.

USP13 deficiency aggravates cigarette smoke‐induced alveolar space enlargement through stabilization of TXNIP

Deubiquitinating enzymes regulate cellular function through deubiquitination and stabilization of substrate proteins. We have shown that USP13 deficiency promotes lung inflammation. Cigarette smoke (CS) causes lung connective tissue disruption and oxidative stress in lung cells, resulting in the development of emphysema; however, the role of USP13 in the CS exposure‐induced emphysema has not been well studied. USP13‐deficient mice and wild type mice were exposed to 4 unfiltered cigarettes for 5 days each week, over the course of 6 months. While emphysema was not observed in wild type mice, CS exposure increased γ‐H2AX levels in lung tissues, suggesting a model of mild smoke exposure was established. Under the mild CS exposure condition, USP13‐deficient mice show significant increases in alveolar CL, indicating that USP13‐deficient mice are susceptible to CS‐induced alveolar enlargement. We have shown that USP13 knockout reduced fibronectin expression in lungs. Further, we found that collagen levels were reduced in USP13‐siRNA‐transfected lung fibroblast cells. It is possible that a loss of connective tissue function contributes to alveolar enlargement in USP13‐deficient mice. Oxidative stress is a hallmark of CS‐induced emphysema. We investigated the role of USP13 in the expression of an oxidative stress markers, named thioredoxin interacting protein (TXNIP), which modulates cellular redox states and NLRP3 inflammasome activity. TXNIP expression levels have been shown to be decreased in smokers compared with non‐smokers. TXNIP is unstable in the presence of protein synthesis inhibitor cycloheximide (CHX). Pretreatment with proteasome inhibitor, MG‐132, attenuated TXNIP degradation, suggesting that TXNIP degradation is mediated by the proteasome. Knockout or knockdown of USP13 in lungs or lung fibroblast cells significantly reduced TXNIP levels. TXNIP degradation is increased in USP13 knockdown cells. Further, the reduction of TXNIP was observed in USP13‐inhibitor‐treated mouse lung epithelial cells. This study provides evidence showing that USP13 deficiency plays a role in alveolar space enlargement.

Minimal invasive mini-rail external fixation for surgical treatment of calcaneal fractures

The purpose of this study is to evaluate and promote the application of percutaneous minimal invasive uniplanar mini-rail external fixation for definitive fixation for displaced calcaneal fractures. This technique has been promoted to avoid soft tissue complications commonly seen with calcaneal open reduction internal fixation, and allows to apply skeletal traction and fracture reduction through ligamentotaxis with percutaneous fixation of the posterior facet fragments without the need to delay surgery secondary to edema. ​In this retrospective study, application of four 3.0mm stainless steel partially threaded half pins were applied across an intra-articular calcaneal fracture, 2 proximal and two distal, allowing for longitudinal traction and stabilization following reduction. Clinical outcomes were determined with a minimal 12-month follow up and a American Orthopedic Foot and Ankle Score (AOFAS) hindfoot score questionnaire. We evaluated and surgically managed 21 patients who presented to the emergency department with closed calcaneal fractures in a 6-year period, beginning from the year 2014 to 2020 with mini-rail fixation. Of the 21 patients, 12 (57%) participated in this study and were also evaluated by physical examination. Regarding patient satisfaction with minimal invasive percutaneous mini-rail fixation, patients reported an average AOFAS score of 82.1, 91% (11/12 patients) and were able to return to work, and only 1 patient required an additional surgery. The clinical results are comparable with traditional open reduction internal fixation with no soft tissue disruption, avoidance of internal fixation plates/screws, and allows for early mobilization.

Effects of Buffalo Milk and Cow Milk on Lipid Metabolism in Obese Mice Induced by High Fat.

The aim of this study was to evaluate the effects of buffalo milk and cow milk on lipid metabolism in obese mice. Milk composition analysis showed fat, protein, and total solid content in buffalo milk was higher than cow milk, while the lactose content of buffalo milk was lower than cow milk. After milk metabolite extraction and LC-MS/MS analysis, differential metabolites were mainly enriched in “linoleic acid metabolism pathways,” “pentose and glucuronate interconversion pathways,” and “metabolism of xenobiotics by cytochrome P450 pathways.” We fed three groups of C57BL/6J mice (n = 6 per group) for 5 weeks: (1) high-fat diet group (HFD group); (2) high-fat diet + buffalo milk group (HBM group); and (3) high-fat diet + cow milk group (HCM group). Our results showed that body weight of mice was significantly decreased in HBM and HCM groups from 1 to 4 weeks compared with the HFD group. The mRNA expression of ACAA2, ACACB, and SLC27A5 genes involved in the lipid metabolism in liver tissue were significantly elevated in HCM group, relatively to HFD and HBM group. In addition, the adipocyte number, size and lipid accumulation in the liver were significantly decreased in HCM group compared with the HFD group by H&E staining and oil red O staining, but was not change in HBM group. The mRNA levels of TNF-α and IL-1β inflammatory genes were significantly increased in HBM group, relatively to HFD and HCM group, which is consistent with results from inflammatory cell infiltration and tissue disruption by colon tissue sections. In conclusion, dietary supplementation of cow milk has beneficial effects on loss of weight and lipid metabolism in obese mice.

Arthroscopically Assisted Acromioclavicular and Coracoclavicular Reconstruction with a Looped Braided Polyester Suture Band and Buckle Device

Acromioclavicular (AC) joint injuries occur with a traumatic load to the lateral aspect of the shoulder and account for 9% of all shoulder girdle injuries. Rockwood classified AC joint injuries as type I though type VI, based on severity of injury, radiographic findings, and reducibility of the AC joint. Type I and II injuries are typically managed nonoperatively, whereas type IV, V, and VI are managed operatively to address the significant soft tissue disruption, persistent AC joint instability, and apical shoulder deformation. Treatment of type III injuries remain controversial. Several techniques have been described to treat AC joint injuries with no consensus for optimal treatment. “Anatomic” double-tunnel coracoclavicular ligament reconstruction is one currently popular technique to address AC joint injuries; however, clavicle and coracoid fractures are well-described complications of this technique. The objective of this technical report is to describe our preferred technique to address AC joint injuries. This technique involves using a looped braided polyester prosthetic band and low-profile buckle with allograft augmentation using a device to pass materials around the coracoid process.

Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature.

Ehlers–Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12026-022-09280-1.

Novel transformation products from glucosinolate-derived thioglucose and isothiocyanates formed during cooking

Glucosinolates are plant secondary metabolites occurring in Brassicaceae plants. Upon tissue disruption, these compounds can be enzymatically hydrolyzed into isothiocyanates, which are very reactive and can react with nucleophiles during thermal processes such as boiling. Here, a novel type of glucosinolate degradation product was identified resulting from the reaction of thioglucose with the isothiocyanates sulforaphane or allyl isothiocyanate during aqueous heating. The two heterocyclic compounds 4-hydroxy-3-(4-(methylsulfinyl)butyl)thiazolidine-2-thione and 3-allyl-4-hydroxythiazolidine-2-thione were isolated and their structure elucidated by NMR spectroscopy and high-resolution mass spectrometry. Based on a set of chemical experiments, a reaction mechanism was proposed. Finally, the formation of the two 3-alk(en)yl-4-hydroxythiazolidine-2-thiones was quantified in boiled cabbage samples using a standard addition method in which 92 pmol/g and 19 pmol/g fresh weight of the sulforaphane and allyl isothiocyanate derivatives were found, respectively.

Survivorship and Outcomes of Femoral Neck Preserving Stems in Primary Total Hip Arthroplasty

BackgroundShort-stem femoral implants (SSFIs) promote the preservation of bone in the femoral neck, reduce soft tissue disruption, and facilitate minimally invasive surgical techniques. The purpose of this study was to report the revision rate, complication rate, patient satisfaction, patient-reported outcomes, and radiographic outcomes of patients who underwent total hip arthroplasty (THA) with the Alteon Neck Preserving Femoral Stem (ANPS). MethodsA prospectively maintained database was reviewed which analyzed 92 THAs between the years 2016 and 2018. Patient-reported outcomes, patient satisfaction, complication rates, and radiographic outcomes were assessed at 2-5 years postoperatively. ResultsThe final cohort consisted of 63 hips. Five patients (7.9%) underwent revision surgery and 2 (3.2%) had other complications not requiring revision. Survivorship when considering only the femoral component was 93.7% at an average of 41.4 months of follow-up. The average postoperative Oxford Hip Score (41.5 ± 8.3) and Harris Hip Score (77.9 ± 16.6) demonstrated significant improvement among our nonrevised patients, respectively (P < .001). Radiographs demonstrated spot welding in 56% of arthroplasties most commonly in Gruen Zones 2, 3, and 13 and that femur radiolucencies were visualized in 58% predominantly along the distal aspect of the stem. Radiographic femoral component subsidence was present in 9.7% of patients. ConclusionThe ANPS may be less reliable than previously reported. Our cohort’s revision rate was unacceptably high with 6.3% requiring revision surgery for femoral component loosening in less than 5 years. Surgeons should consider the challenges and prohibitive failure rate associated with SSFIs before routine usage in THA.

Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality?

Chronic obstructive pulmonary disease (COPD) is a complex disease which consists in the reduction of the airflow and leads to the disruption of the pulmonary tissue due to a chronic inflammation. The progression of the disease is characterized by an exacerbation of the symptoms and the presence of life-threatening systemic complications, such as stroke and ischemic heart disease, with a progressive decline in lung function which can deeply impact the quality of life. Mortality represents the most important COPD outcome, with an increased risk in patients with cardiovascular comorbidities. The efficacy and safety of triple inhaled therapy were demonstrated by numerous controlled trials. Above all, many robust data are now available on the effectiveness of the triple therapy to reduce mortality in COPD patients.