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Over the past four decades, prion diseases have received considerable research attention owing to their potential to be transmitted within and across species as well as their consequences for human and animal health. The unprecedented nature of prions has led to the discovery of a paradigm of templated protein misfolding that underlies a diverse range of both disease-related and normal biological processes. Indeed, the "prion-like" misfolding and propagation of protein aggregates is now recognized as a common underlying disease mechanism in human neurodegenerative disorders such as Alzheimer's and Parkinson's disease and the prion principle has led to the development of novel diagnostic and therapeutic strategies for these illnesses. Despite these advances, research into the fundamental biology of prion diseases has declined, likely due to their rarity and the absence of an acute human health crisis. Given the past translational influence, continued research on the etiology, pathogenesis, and transmission of prion disease should remain a priority. In this review we highlight several important "unsolved mysteries" in the prion disease research field and how solving them may be crucial for the development of effective therapeutics, preventing future outbreaks of prion disease, and understanding the pathobiology of more common human neurodegenerative disorders.
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BACKGROUND AND AIM: The incidence of cancer colon has increased dramatically. In addition, the database lacks a review to analyze the outcomes of surgeries for mid-transverse colon cancer with several recent controversial studies. We aimed to compare the outcomes of extended hemicolectomy versus transverse colectomy for mid-transverse colon cancer. METHOD: PubMed, Scopes, Web of Science and Cochrane Library were searched for eligible studies from inception to 1 December 2022 and a systematic review and meta-analysis were done to detect. RESULTS: According to eligibility criteria, 8 studies (2237 patients) were included in our study. The pooled results of the included studies showed no difference in the 5-year OS, 3-year DFS and 5-year DFS between the two types of surgery (5-year OS, RR = 1.15, 95% CI 0.94-1.39, P = 0.17), (3-year OS, RR = 0.96, 95% CI 0.88-1.06, P = 0.42) and (5-year DFS, RR = 1.21, 95% CI 0.91-1.62, P = 0.20). In addition to that, the recurrence rate and the incidence of complications were similar in the two groups (Recurrence rate, RR = 1.08, 95% CI 0.62-1.89, P = 0.79) and (Complications, RR = 1.07, 95% CI 0.74-1.54, P = 0.72). However, the number of LN harvest and the time of the operation were more in case of extended hemicolectomy. CONCLUSION: Despite harvesting less LN, transverse colectomy has similar oncological outcomes to extended hemicolectomy for mid-transverse colon cancer. In addition to that, there was no significant difference in the incidence of complications between the two surgeries.
Subject(s)
Colectomy , Colonic Neoplasms , Humans , Colectomy/methods , Colectomy/adverse effects , Colon, Transverse/surgery , Colon, Transverse/pathology , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Neoplasm Recurrence, Local , Postoperative Complications/epidemiology , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to assess the mid-term outcomes of the use of drug-coated balloons (DCBs) to treat infrainguinal peripheral arterial disease (PAD) in patients with dyslipidemia. METHODS: BIOLUX P-III is a prospective, international, multicenter, all-comers registry-based study that was conducted at 44 sites with follow-ups at 6, 12 and 24 months. The present study is a subgroup analysis comparing the outcomes associated with endovascular revascularization with those associated with Passeo-18 lux DCBs in patients with and without dyslipidemia. The proportions of patients free from major adverse events (defined as device- or procedure-related mortality within 30 days, clinically driven target lesion revascularization (CD-TLR) and major target limb amputation), target vessel revascularization, and patient-reported outcomes within 24 months postintervention were compared between the two groups. RESULTS: A total of 876 patients with symptomatic PAD who underwent peripheral revascularization with DCBs and had information on their dyslipidemia status were included; 588 of those patients had dyslipidemia. There was no difference in the proportion of patients free from MAEs between the groups. The percentages of patients who were 6, 12 and 24 months free from CD-TLR were significantly lower in the dyslipidemia group than in the nondyslipidemia group (86.3% vs 91.9% at 2 years, p = .0183). Similarly, the percentage of patients free from target vessel revascularization was lower in the dyslipidemia group at all timepoints (83.3% vs 89.3% at 2 years, p = .0203). There was no difference in mortality or major or minor limb amputation rates. Other secondary outcomes were similar between the groups. CONCLUSIONS: Compared to those without dyslipidemia, patients with symptomatic PAD and dyslipidemia who underwent revascularization with a Passeo-18 lux DCB had greater rates of CD-TLR and TVR. However, having dyslipidemia did not increase the risk of mortality or limb amputation. CLINICAL TRIAL REGISTRATION: NCT02276313.
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OBJECTIVE: To investigate effectiveness of two different educational methods to improve inhaler techniques in patients with prior diagnosis of asthma, hospitalized with a non-asthma-related diagnosis. METHODS: We undertook a real-world, opportunistic quality-improvement project. Inhaler technique in hospitalized patients with prior diagnosis of asthma was assessed in two cohorts over two 12-week cycles using a standardized device-specific proforma of seven-step inhaler technique, classed: "good" if 6/7 steps achieved; "fair" if 5/7 compliant; "poor" for others. Baseline data was collected in both cycles. Cycle one involved face-to-face education by a healthcare professional; cycle two involved additional use of an electronic device to show device-specific videos (asthma.org.uk). In both cycles, patients were reassessed within two days for improvements and the two methods compared for effectiveness. RESULTS: During cycle one 32/40 patients were reassessed within 48 h; eight lost to follow-up. During cycle two 38/40 patients were reassessed within 48 h; two lost to follow-up During cycle one, two and 12 had good/fair baseline technique respectively, and 26 poor. Most commonly missed steps were no expiry check/not rinsing mouth after steroid use. On reassessment 17% patients improved from poor to fair/good. During cycle two, initial technique assessment identified: 23 poor; 12 fair; five good. Post-videos, 35% of patients improved from poor to fair/good. Proportion of patients improving from poor to fair, or poor/fair to good increased in cycle two vs one (52.5% vs 33%). CONCLUSION: Visual instruction is associated with improved technique compared to verbal feedback. This is a user-friendly and cost-effective approach to patient education.
Subject(s)
Asthma , Humans , Adult , Asthma/drug therapy , Nebulizers and Vaporizers , Patient Compliance , Educational Status , Electronics , Administration, InhalationABSTRACT
OBJECTIVES: The aim of this study was to evaluate the impact of sex on mid-term outcomes following stenting for aorto-iliac occlusive disease (AIOD). METHODS: The Covered versus Balloon Expandable Stent Trial (COBEST) compared the safety and efficacy of the covered stent (CS) with those of the bare metal stent (BMS) in the treatment of hemodynamically significant AIOD. It was identified that CS provided a significant benefit. The primary endpoint of our analysis was the rate of primary patency 5 years following stenting for AIOD (inclusive of both CS and BMS) in both sexes. RESULTS: Of the 168 lesions treated, 103 (61%) were present in men and 65 (39%) were present in women. Of the concomitant comorbidities, diabetes mellitus was significantly more common in women (17.5% vs 41.5%, p = .006). Although chronic limb threatening ischemia (CLTI) at the time of intervention was more common in women, the difference was not significant (16.5% vs 24.6%, p = .395). Sex was not associated with the primary patency rate (male; 0.70, 95% confidence interval [CI]: 0.23-2.19, p = .543). When considering both male sex and the utilization of BMS, no significant impact was found on the primary patency rate (hazard ratio [HR]: 3.43, 95% CI: 0.69-17.10, p = .133). All-cause mortality at 60 months was 22.6% in men compared to 19.4% in women (p = .695). CONCLUSIONS: No significant difference was identified in the primary patency rate between the sexes. Further investigation is warranted to ascertain whether sex-specific interventional guidelines are required in this regard.
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Our study aims to determine whether the beta-adrenergic system is involved in the regulation of lymphatic drainage from the eye. For this purpose, we assessed the effect of 2 topical beta-adrenergic blockers, timolol and betaxolol, commonly used as glaucoma drugs, on lymphatic clearance of albumin from the aqueous humor to neck lymph nodes. Adult mice were treated with either topical timolol, a non-selective ß-blocker, 0.5% (n = 8), or topical betaxolol, a selective ß1-adrenergic blocker, 0.5% (n = 6) twice daily for 14 days and compared to respective control groups (n = 5 and n = 7). Changes in lymphatic clearance from the eye were assessed using a quantitative in vivo photoacoustic imaging approach. In all subjects, right eye and neck lymph nodes were longitudinally assessed by sequential photoacoustic imaging just prior to near-infrared dye injection into the anterior chamber of the eye, and 20 min, 2 and 4 h after injection. Repeat measurements of mean pixel intensities (MPIs) of right eyes and nodes were performed at all timepoints. The areas under the curves (AUC) were calculated and the AUC of the treated-group was compared to that of controls using the Mann-Whitney U test. The slopes of MPI of each region of interest over time were compared using the linear mixed model after adjusting for IOP decrease after treatment and other parameters such as sex and body weight. In the timolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.003), and significant decrease in slope of MPI compared with controls (P = 0.0025). In the betaxolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.02), and significant decrease in slope of MPI compared with controls (P = 0.0069). Topical treatment with timolol and betaxolol reduced lymphatic clearance of albumin from the aqueous humor to the neck lymph nodes. This finding may be relevant for the management of secondary glaucomas and inflammatory eye disease in which the clearance of accumulated proteins and antigen from the eye is important to disease recovery and sight protection. This study suggests that the beta-adrenergic system plays a role in the regulation of lymphatic clearance from the eye.
Subject(s)
Aqueous Humor/metabolism , Glaucoma/drug therapy , Intraocular Pressure/drug effects , Photoacoustic Techniques/methods , Timolol/pharmacokinetics , Administration, Topical , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/pharmacokinetics , Animals , Disease Models, Animal , Female , Glaucoma/diagnosis , Glaucoma/metabolism , Lymphatic Vessels , Male , Mice , Timolol/administration & dosageABSTRACT
OBJECTIVES/BACKGROUND: Expand the differential diagnosis of sentinel headache to include spontaneous spinal epidural hematoma (SSEH) and reinforce the need for lumbar puncture in the evaluation of thunderclap headache. SSEH is a rare clinical presentation especially in the absence of bleeding tendencies. Clinicians recognize SSEH with typical presenting signs and symptoms including regional paraspinal muscular contraction and pain along with myelopathy. Although thunderclap headache usually does not connote vascular rupture in the spinal epidural compartment, SSEH may rarely present with sentinel headache and later evolve into a myelopathy. RESULTS AND CONCLUSION: Sentinel headache may be the sole symptom following spontaneous spinal epidural hemorrhage preceding both myelopathic and meningeal signs and symptoms. SSEH can best be diagnosed by lumbar puncture at this early moment potentially averting spinal cord injury.
Subject(s)
Headache/etiology , Hematoma, Epidural, Spinal/diagnostic imaging , Diagnosis, Differential , Female , Hematoma, Epidural, Spinal/complications , Humans , Magnetic Resonance Imaging , Middle Aged , Spinal PunctureABSTRACT
BACKGROUND: Although interest in global surgery is increasing among medical students,1 several questions remain unanswered such as: the association of demographics with said interest, the extent that global surgical burden education has been integrated into medical education, and the availability of global surgery electives. This study aimed to assess the current state of global surgery education in the United States (U.S.) to support recommendations for future curriculum development. MATERIALS AND METHODS: An anonymous online survey was distributed to medical students currently enrolled in the U.S. Descriptive data were compiled regarding interest in and access to global surgery programs; demographic data were analyzed using chi-squared testing for categorical variables. RESULTS: A total of 754 students from 18 medical schools throughout the U.S. responded to the survey. Only complete responses were included in final analysis (n = 658). Most of the respondents (66%) reported interest in global surgery, with a higher proportion of those interested being in their preclinical years. However, the majority (79%) reported that global surgery issues are rarely or never addressed in their required curriculum. Over half of respondents were unaware of whether their school even offers such programs. CONCLUSIONS: Although interest in global surgery is on the rise among medical students, results suggest that many currently lack exposure to global surgery concepts in their medical education. To that end, early exposure may be most effective during the preclinical years, so that the next generation may align global surgery participation with clinical aspirations, with the ultimate goal of addressing global disparities.
Subject(s)
Career Choice , Education, Medical/organization & administration , International Cooperation , Students, Medical/statistics & numerical data , Surgeons/education , Curriculum/statistics & numerical data , Curriculum/trends , Education, Medical/statistics & numerical data , Education, Medical/trends , Global Health , Healthcare Disparities , Humans , Schools, Medical/organization & administration , Schools, Medical/statistics & numerical data , Schools, Medical/trends , Surveys and Questionnaires/statistics & numerical data , United StatesABSTRACT
B cells are activated in vivo after the B cell receptors (BCRs) bind to antigens captured on the surfaces of antigen-presenting cells. Antigen binding results in BCR microclustering and signaling; however, the molecular nature of the signaling-active BCR clusters is not well understood. Using single-molecule imaging techniques, we provide evidence that within microclusters, the binding of monovalent membrane antigens results in the assembly of immobile signaling-active BCR oligomers. The oligomerization depends on interactions between the membrane-proximal Cmicro4 domains of the membrane immunoglobulin that are both necessary and sufficient for assembly. Antigen-bound BCRs that lacked the Cmicro4 domain failed to cluster and signal, and conversely, Cmicro4 domains alone clustered spontaneously and activated B cells. These results support a unique mechanism for the initiation of BCR signaling in which antigen binding induces a conformational change in the Fc portion of the BCR, revealing an interface that promotes BCR clustering.
Subject(s)
B-Lymphocytes/immunology , Cell Membrane/physiology , Immunoglobulin Constant Regions/physiology , Intercellular Adhesion Molecule-1/metabolism , Nitrohydroxyiodophenylacetate/metabolism , Receptors, Antigen, B-Cell/physiology , Animals , Intracellular Signaling Peptides and Proteins/metabolism , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Mice, Knockout , Protein-Tyrosine Kinases/metabolism , Signal Transduction , Syk KinaseABSTRACT
BACKGROUND: Over the past decade, there have been substantial changes in landline and mobile phone ownership, with a substantial increase in the proportion of mobile-only households. Estimates of daily smoking rates for the mobile phone only (MPO) population have been found to be substantially higher than the rest of the population and telephone surveys that use a dual sampling frame (landline and mobile phones) are now considered best practice. Smoking is seen as an undesirable behaviour; measuring such behaviours using an interviewer may lead to lower estimates when using telephone based surveys compared to self-administered approaches. This study aims to assess whether higher daily smoking estimates observed for the mobile phone only population can be explained by administrative features of surveys, after accounting for differences in the phone ownership population groups. METHODS: Data on New South Wales (NSW) residents aged 18 years or older from the NSW Population Health Survey (PHS), a telephone survey, and the National Drug Strategy Household Survey (NDSHS), a self-administered survey, were combined, with weights adjusted to match the 2013 population. Design-adjusted prevalence estimates and odds ratios were calculated using survey analysis procedures available in SAS 9.4. RESULTS: Both the PHS and NDSHS gave the same estimates for daily smoking (12%) and similar estimates for MPO users (20% and 18% respectively). Pooled data showed that daily smoking was 19% for MPO users, compared to 10% for dual phone owners, and 12% for landline phone only users. Prevalence estimates for MPO users across both surveys were consistently higher than other phone ownership groups. Differences in estimates for the MPO population compared to other phone ownership groups persisted even after adjustment for the mode of collection and demographic factors. CONCLUSIONS: Daily smoking rates were consistently higher for the mobile phone only population and this was not driven by the mode of survey collection. This supports the assertion that the use of a dual sampling frame addresses coverage issues that would otherwise be present in telephone surveys that only made use of a landline sampling frame.
Subject(s)
Cell Phone/statistics & numerical data , Smoking/epidemiology , Adolescent , Adult , Aged , Female , Health Surveys/methods , Humans , Male , Middle Aged , New South Wales/epidemiology , Sampling Studies , Young AdultABSTRACT
Syncope is a common presentation to emergency departments. Arrhythmias account for 14% of those presentations [1], which requires careful assessment due to the potential for sudden cardiac death (SCD). QTc prolongation either due to congenital channelopathy or acquired aetiology can lead to polymorphic ventricular tachycardia and SCD, and should be excluded on electrocardiography. On the other hand, detailed history and thorough clinical examination are the most important tools in reaching the diagnosis, even in the presence of QTC prolongation.
Subject(s)
Channelopathies , Electrocardiography , Long QT Syndrome , Syncope , Tachycardia, Ventricular , Adult , Channelopathies/complications , Channelopathies/congenital , Channelopathies/diagnosis , Channelopathies/physiopathology , Female , Humans , Long QT Syndrome/complications , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Syncope/complications , Syncope/diagnosis , Syncope/physiopathology , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathologyABSTRACT
BACKGROUND: The Australian population is ageing, with an increasing number of patients diagnosed with colorectal cancer in their eighth decade. This group represents a challenging cohort to deliver multidisciplinary care, with increased morbidity and mortality related to surgical and oncological therapies. This project aimed to compare surgical and oncological outcomes in octogenarian and non-octogenarian patients with colorectal cancer. METHODS: A matched case-control retrospective review of a prospectively maintained institutional database of colorectal cancer patients treated between 2005 and 2021 was conducted. Patient demographics, treatment details, peri-operative complications, and long-term survival were reported. The primary outcome, cancer-specific survival, was investigated using time-to-event analysis and interrogated with multivariate regression. RESULTS: There were 747 patients included in the study. There was no difference in five-year cancer-specific survival and recurrence-free survival between cohorts. Multivariate analysis for octogenarians confirmed a significant hazard signal associated with worsening cancer stage and a survival benefit associated with the administration of adjuvant therapy. However, we noted that stage-matched octogenarian patients received less adjuvant treatment compared to non-octogenarians. CONCLUSION: Octogenarians undergoing treatment for colorectal cancer have similar cancer-specific survival and recurrence-free survival to non-octogenarians. Our study demonstrates a survival benefit when adjuvant therapy is provided to octogenarians, despite only half of this cohort receiving therapy compared to their younger peers. Further research into adjuvant therapy with surgical resection for CRC in older Australians is required.
Subject(s)
Adenocarcinoma , Australasian People , Colorectal Neoplasms , Aged, 80 and over , Humans , Aged , Octogenarians , Australia/epidemiology , Colorectal Neoplasms/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Retrospective Studies , Chemotherapy, Adjuvant , Treatment OutcomeABSTRACT
Total hip arthroplasty (THA) is a common but major surgery performed in the United Kingdom and around the globe. THA is associated with several postoperative complications, with one of the most common being venous thromboembolism (VTE) in the form of deep venous thrombosis (DVT) or pulmonary embolism (PE). VTE following orthopaedic surgery can have major consequences in terms of patient morbidity and may even cause mortality. It carries a significant cost to the health service, and thromboprophylactic agents are used to decrease the risk. Several different options are available for chemical thromboprophylaxis, including aspirin, low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and warfarin. This study aims to review the literature to determine if aspirin is less superior to the other available chemical thromboprophylaxis in postoperative patients following THA. The primary outcome assessed in this review is rates of symptomatic 90-day VTE in the form of PE or DVT. A literature review was conducted using PubMed, Scopus, and Google Scholar using the following terms: 'Aspirin AND (low molecular weight heparin OR LMWH OR Enoxaparin OR Apixaban OR DOAC OR direct oral anticoagulant OR warfarin) AND (orthopaedic OR orthopedic) AND (Total hip replacement OR THR OR THA OR total hip arthroplasty) AND ('venous thromboembolism' OR VTE).' Aspirin appears to have promising results as thromboprophylaxis in cases of THA. However, it is still up for debate as to whether it is non-inferior to other forms of thromboprophylaxis.
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Pediatric septic arthritis (SA), an intra-articular infection in children, is considered a surgical emergency. The most commonly affected joints are the lower limb joints. It is more common in children below five years old and in males. Several scoring systems aid in the prediction of the disease and help differentiate it from similar differential diagnoses (such as transient synovitis (TS)). The first and most famous scoring system is Kocher's Criteria (KC), which utilizes a mixture of clinical signs, symptoms, and laboratory markers to predict the likelihood of the diagnosis. This review aims to assess the current literature to look at primary papers comparing the predicted probability of KC to the original probability described therefore evaluating its efficacy and usefulness in today's pediatric population. PubMed was searched using the terms "septic arthritis AND hip AND (Kocher OR Kocher's criteria)," 27 studies resulted, and each study was screened by reading the abstracts. Six studies were included in this review. Inclusion criteria were any study that looked at SA of the hip in the pediatric population prospectively or retrospectively, using KC to help make a diagnosis and looking at the predicted probability of KC. Exclusion criteria included studies looking at adults, joints other than the hip, and papers not assessing the predicted probability. The efficacy of KC for diagnosing SA is not well-supported by current literature. Studies indicate that KC have low specificity for SA, suggesting it should not replace arthrocentesis as the diagnostic gold standard. Clinicians should use this model cautiously, and more extensive, prospective studies are needed to validate its effectiveness.
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Pelvic congestion syndrome (PCS) poses a significant health, diagnostic, and economic challenges. Transcatheter embolisation has emerged as a promising treatment for PCS. A systematic review was performed in order to assess the safety and efficacy of transcatheter embolisation in the treatment of PCS. A systematic search of electronic databases was performed using 'PubMed', 'Embase', 'Medline (OVID)', and 'Web of Science', for articles pertaining to efficacy of embolotherapy for the treatment of pelvic congestion syndrome. A total of 25 studies were included in this systematic review with a combined total of 2038 patients. All patients included were female with a mean average age of 37.65 (31-51). Of the 25 studies, 18/25 studies reported pre- and post-procedural pelvic pain outcomes using a visual analogue scale (VAS). All studies showed a reduction in VAS post-procedure. Transcatheter embolisation had a high technical success rate (94%) and an overall complication rate of 9.0%, of which 10.4% were major and 89.6% were minor. Fifteen out of 19 (78.9%) major complications required a subsequent intervention. Transcatheter embolisation using various techniques is effective and safe in treating PCS. A low quality of evidence limits the currently available literature; however, embolisation has shown to improve symptoms in the majority of patients with low complication rates and recurrence rates.
Subject(s)
Embolization, Therapeutic , Pelvic Pain , Adult , Female , Humans , Middle Aged , Embolization, Therapeutic/methods , Pelvic Pain/therapy , Pelvis/blood supply , Syndrome , Treatment OutcomeABSTRACT
Background: The BIO REACT study is designed to investigate the incremental value of Extravascular UltraSound (EVUS) added to conventional angiography, compared to conventional angiography only for the identification of Flow-Limiting Dissections (FLD) and to evaluate the safety and efficacy of the REsponse Adapted Combination Therapy (REACT) for the treatment of femoropopliteal lesions. Methods: The primary endpoints were the specificity and sensitivity of EVUS added to angiography for the detection of FLD. Secondary endpoints were primary patency of the REACT therapy within 12 months, fCD-TLR, freedom from MAE, major target limb amputations (mTLA) and survival rates within 24 months. Results: A total of 150 patients were included. EVUS added to angiography had an overall sensitivity of 29% and specificity of 93% for the detection of FLD. There was no PSVR cut-off offering a clinically acceptable trade-off between meaningful sensitivity and specificity values for the detection of FLD. At 12 months, treatment with the REACT resulted in primary patency and fCD-TLR of 81.6% and 94.3%, respectively. In addition, freedom from MAE was 94.3% at 12 months. At 24 months, the survival rate was 94.0%. No mTLA was reported up to the 24-month follow-up. Conclusions: The addition of DUS to angiography showed limited value for detecting FLD in femoropopliteal artery disease.
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Background: Traumatic injury is a leading cause of death for those under the age of 45, with 40% occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality. Objectives: We aimed to quantify changes in clot formation and mechanics occurring after traumatic injury and the relationship to coagulation kinetics, and fibrinolysis. Methods: Plasma was isolated from injured patients upon arrival to the emergency department. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidimetric and thrombin generation assays. ELISA's were performed to determine tissue plasminogen activator (tPA) and D-dimer concentration, as fibrinolytic markers. Results: Sixty-three patients were included in the study. The median injury severity score (ISS) was 17, median age was 37.5 years old, and mortality rate was 30%. Rheological, turbidimetric and thrombin generation assays indicated that trauma patients on average, and especially deceased patients, exhibited reduced clot stiffness, increased fibrinolysis and reduced thrombin generation compared to healthy donors. Fibrinogen concentration, clot stiffness, D-dimer and tPA all demonstrated significant direct correlation to increasing ISS. Machine learning algorithms identified and highlighted the importance of clinical factors on determining patient outcomes. Conclusions: Viscoelastic and biochemical assays indicate significant contributors and predictors of mortality for improved patient treatment and therapeutic target detection. ESSENTIALS: Traumatic injury may lead to alterations in a patient's ability to form stable blood clotsA study was performed to assess how trauma severity affects coagulation kineticsKey alterations were observed in trauma patients, who exhibit weaker and slower forming clotsPaired with machine learning methods, the results indicate key aspects contributing to mortality.
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The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.
Subject(s)
Amacrine Cells , Cell Adhesion , Endocytosis , PTEN Phosphohydrolase , Retina , Wnt Signaling Pathway , Animals , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , Retina/metabolism , Mice , Amacrine Cells/metabolism , Mice, Knockout , Protein Transport , Wnt Proteins/metabolism , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/geneticsABSTRACT
Here we present a rare case of life-threatening spontaneous renal haemorrhage following elective vascular surgery. A 73-year-old gentleman presents to the ED with acute onset right sided flank pain, 24 hours post bilateral renal artery stent insertion for renal artery stenosis. Subsequent angiography demonstrated bilateral renal artery stent occlusion with near complete bilateral kidney infarction. The patient urgently underwent bilateral renal artery thrombectomy. Post-operatively the patient developed severe unilateral flank pain and became haemodynamically unstable. Subsequent imaging revealed a large right sided retroperitoneal haematoma with active arterial bleeding. The patient ultimately underwent a right sided trauma nephrectomy for haemorrhage control.