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Affinity protein-oligonucleotide conjugates are increasingly being explored as diagnostic and therapeutic tools. Despite growing interest, these probes are typically constructed using outdated, non-selective chemistries, and little has been done to investigate how conjugation to oligonucleotides influences the function of affinity proteins. Herein, we report a novel site-selective conjugation method for furnishing affinity protein-oligonucleotide conjugates in a 93% yield within fifteen minutes. Using SPR, we explore how the choice of affinity protein, conjugation strategy, and DNA length impact target binding and reveal the deleterious effects of non-specific conjugation methods. Furthermore, we show that these adverse effects can be minimised by employing our site-selective conjugation strategy, leading to improved performance in an immuno-PCR assay. Finally, we investigate the interactions between affinity protein-oligonucleotide conjugates and live cells, demonstrating the benefits of site-selective conjugation. This work provides critical insight into the importance of conjugation strategy when constructing affinity protein-oligonucleotide conjugates.
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The effect of an alternative source of silica, based on class F fly ash mixed with blast furnace slag and activated by rice husk ash (RHA), to produce concrete exposed to marine environments was evaluated. Four mixtures activated by the combination of 85% NaOH 14M + 15% RHA were manufactured to achieve a liquid/solid ratio of 0.20. Fly ash was incorporated into the steel slag mixture at addition percentages of 20, 40, 60, and 80%, and evaluated at 28, 900, and 1800 days for pore and chloride ion absorption. In general, including rice husk ash in the mixture of fly ash and steel slag significantly affected mechanical performance because it was possible to obtain concrete with high mechanical resistance. Concerning the durability evaluation, the effect of the activator generated by rice husk ash was observed, and the increase in steel slag added to the cementitious samples improved the capacity of the material to resist the penetration and diffusion of chloride ions.
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Glioblastoma (GBM) is amongst the deadliest types of cancers, with no resolutive cure currently available. GBM cell proliferation in the patient's brain is a complex phenomenon controlled by multiple mechanisms. The aim of this study was to determine whether the ionic fluxes controlling cell duplication could represent a target for GBM therapy. In this work, we combined multi-channel Ca2+ and Cl- imaging, optical tweezers, electrophysiology and immunohistochemistry to describe the role of ion fluxes in mediating the cell volume changes that accompany mitosis of U87 GBM cells. We identified three main steps: (i) in round GBM cells undergoing mitosis, during the transition from anaphase to telophase and cytokinesis, large Ca2+ flares occur, reaching values of 0.5-1 µM; (ii) these Ca2+ flares activate Ca2+-dependent Cl- channels, allowing the entry of Cl- ions; (iii) to maintain osmotic balance, GBM cells swell to complete mitosis. This sequence of steps was validated by electrophysiological experiments showing that Cl- channels are activated either directly or indirectly by Ca2+, and by additional live-cell imaging experiments. Cl- channel blockers with different molecular structures, such as niflumic acid and carbenoxolone, blocked GBM replication by arresting GBM cells in a round configuration. These results describe the central role of Ca2+ flares and Cl- fluxes during mitosis and show that inhibition of Ca2+-activated Cl- channels blocks GBM replication, opening the way to new approaches for the clinical treatment of GBM. Implications: Our work identifies ionic fluxes occurring during cell division as targets for devising novel therapies for the glioblastoma treatment.
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This paper introduces a novel framework for estimating the spectral power distribution of daylight illuminants in uncalibrated hyperspectral images, particularly beneficial for drone-based applications in agriculture and forestry. The proposed method uniquely combines image-dependent plausible spectra with a database of physically possible spectra, utilizing an image-independent principal component space (PCS) for estimations. This approach effectively narrows the search space in the spectral domain and employs a random walk methodology to generate spectral candidates, which are then intersected with a pre-trained PCS to predict the illuminant. We demonstrate superior performance compared to existing statistics-based methods across various metrics, validating the framework's efficacy in accurately estimating illuminants and recovering reflectance values from radiance data. The method is validated within the spectral range of 382-1002 nm and shows potential for extension to broader spectral ranges.
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Background: Glomus jugulare tumors (GJTs) are rare and mainly affect women between the 5th and 6th decades of life. Its localization and anatomic relationships make conventional surgical treatment difficult and with a considerable risk of complications. This manuscript aims to describe the results of Gamma Knife radiosurgery (GKR) in patients with GJT treated in a single center in Latin America, as well as to systematically review the literature to determine the clinical and radiological effectiveness of this technique. Methods: A search of information from January 1995 to June 2023 was performed. Twenty-two articles reporting 721 GJT patients treated with GKR were included in the study. Variables such as symptomatic control, control of tumor size, and complications were evaluated. These variables were described using measures of central tendency and proportions. For the institutional experience, 77 patients with GJT tumors were included in the study. Pre-treatment clinical variables and follow-up data were collected from medical charts and phone interviews. The Short Form-36 scale was applied to assess the quality of life. The data were analyzed using the statistical program STATA17.0. Results: A total of 721 patients were considered. The median of patients included in these studies was 18.5. The mean age was 58.4 years. The median of symptom control was 89%, and the median of imaging control was 95.7%. In our institution, 77 patients were included in the study. The mean age was 53.2 years. The median hospital stay was 4.92 hours. For the clinical follow-up, information on 47 patients was obtained. An improvement in pre-treatment symptoms was described in 58%, with general symptomatic control of 97%. The tumor-control rate was 95%, and there were statistically significant differences in six of the nine Short Form-36 scale domains. Conclusion: GKR is an effective, safe, and cost-effective technique that offers a high degree of symptomatic and tumor size control in patients with GJT.
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INTRODUCCIÓN: El absceso hepático (AH) es el tipo mas común de abscesos viscerales. Se estima que el perfil epidemiológico de esta enfermedad ha cambiado con el aumento de la resistencia de los microorganismos y el uso de nuevos medicamentos. OBJETIVO: Describir las características demográficas y clínicas de los pacientes hospitalizados con diagnóstico de AH en un hospital universitario del suroccidente colombiano. MÉTODOS: Se realizó un estudio observacional retrospectivo, en la Fundación Valle del Lili, Cali, Colombia. Se incluyeron pacientes mayores de 18 años con diagnóstico de AH hospitalizados entre 2011-2020. RESULTADOS: Se incluyeron 182 pacientes. La mediana de edad fUe 56 años (rango intercuartílico, 45-67) y 62,1% fueron hombres. El microrganismo mas común fue Klebsiella pneumoniae (17,6%). La mayoría requirió drenaje percutáneo (58,2%). El 58,8% tuvo un absceso único y 54,4% fue manejado en cuidados intensivos. El 7,1% de los pacientes falleció. Al comparar los casos que fueron manejados en cuidados intensivos vs. aquellos que no lo fueron, hubo más hepatomegalia (28,3 vs. 11,0%, p = 0,004), derrame pleural derecho (48,5 vs. 28,1%, p = 0,010), cirugía (42,4 vs. 13,4%, p < 0,001), falla terapéutica (22,2 vs. 7,3%, p = 0,007) y muerte (12,1 vs. 1,2%, p = 0,005) en los atendidos en UCI. CONCLUSIÓN: Las Enterobacterales son la principal causa de AH en nuestra población. La mortalidad ha disminuido, pero la hospitalización en cuidados intensivos sigue siendo alta.
BACKGROUND: Liver abscess (LA) is the most common type of visceral abscess. It is estimated that the epidemiological profile of this disease has changed with the increase in resistance and the use of new drugs. AIM: To describe the demographic and clinical characteristics of hospitalized patients with a diagnosis of LA in a university hospital in the southwestern region of Colombia. METHODS: A. retrospective observational study was conducted at Fundación Valle del Lili, Cali, Colombia. Patients older than 18 years with a diagnosis of LA hospitalized between 2011-2020 were included. RESULTS: A total of 182 patients were included. The median age was 56 years (interquartile range, 45-67) and 62.1% were men. The most common microorganism was Klebsiella pneumoniae (17.6%). The majority required percutaneous drainage (58.2%). A 58.8% had a single abscess and 54.4% were treated in ICU. A 7.1% of the patients died. When comparing cases treated in the ICU vs. those who did not, there was more hepatomegaly (28.3 vs. 11.0%, p = 0.004), right pleural effusion (48.5 vs. 28.1%, p = 0.010), surgery (42.4 vs. 13.4%, p < 0.001), therapeutic failure (22.2 vs. 7.3%, p = 0.007) and death (12.1 vs. 1.2%, p = 0.005) in patients treated in ICU. CONCLUSION: Enterobacterales are the main cause of LA in our population. Mortality has decreased, but intensive care hospitalization remains high.
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Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Liver Abscess/epidemiology , Drainage/methods , Retrospective Studies , Colombia , Critical Care , Hospitals, University , Klebsiella pneumoniae , Liver Abscess/microbiology , Liver Abscess/mortality , Liver Abscess/therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.
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Catastrophe bonds (cat bond in short) are an alternative risk-transfer instrument used to transfer peril-specific financial risk from governments, financial institutions, or (re)insurers, to the capital market. Current approaches for cat bond pricing are calibrated on seismic mainshocks, and thus do not account for potential effects induced by earthquake sequences. This simplifying assumption implies that damage arises from mainshocks only, while aftershocks yield no damage. Postearthquake field surveys reveal that this assumption is inaccurate. For example, in the 2011 Christchurch Earthquake sequence and 2016-2017 Central Italy Earthquake sequence, aftershocks were responsible for higher economic losses when compared to those caused by mainshocks. This article proposes a time-dependent aggregate loss model that takes into account seismicity clustering and damage accumulation effects in the computation of damage. The model is calibrated on the seismic events recorded during the recent 2016-2017 Central Italy Earthquake sequence. Furthermore, the effects of earthquake sequence on cat bond pricing is explored by implementing the proposed model on five Italian municipalities. The investigation showed that neglecting time-dependency may lead to higher difference (up to 45%) in the cat bond price when compared to standard approaches.
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BACKGROUND: Few epidemiologic studies have focused on the specific source of ambient air pollution and adverse health effects in early life. Here, we investigated whether air pollutants from different emission sources were associated with decreased birth anthropometry parameters and increased DNA adduct formation in mother-child pairs residing in the Mexico City Metropolitan Area (MCMA). METHODS: This cross-sectional study included 190 pregnant women recruited during their last trimester of pregnancy from two hospitals at MCMA, and a Modeling Emissions Inventory (MEI) to calculate exposure to ambient air pollutants from different emissions sources (area, point, mobile, and natural) for two geographical buffers 250 and 750 m radii around the participants households. RESULTS: Contaminants were positively correlated with umbilical cord blood (UCB) adducts, but not with maternal blood (MB) adducts. PM10 emissions (area and point sources, overall emissions), PM2.5 (point sources), volatile organic compounds (VOC), total organic compounds (TOC) from point sources were positively correlated with UCB adducts. Air pollutants emitted from natural sources were correlated with a decrease in MB and UCB adducts. PM10 and PM2.5 were correlated (p < 0.05) with a decrease in birth weight (BW), birth length (BL) and gestational age at term (GA). In multivariate analyses adjusted for potential confounders, PM10 was associated with an increase in UCB adducts. PM10 and PM2.5 from overall emissions were associated with a decrease in BW, BL and GA at term. IMPACT: Results suggested higher susceptibility of newborns compared to mothers to damage related to ambient air pollution. PMs are associated with birth anthropometry parameters and DNA damage in adjusted models, highlighting the need for more strict regulation of PM emissions.
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Chronodisruption, commonly displayed by people living with obesity (PLO), is linked to colonic microbiota dysbiosis, and may increase the risk of many chronic non-communicable diseases, whereas dietary interventions-called chrononutrition may mitigate it. We evaluated the in vitro effects of spent coffee grounds (SCG), and their antioxidant dietary fiber (SCG-DF) on the colonic microbiota of an obese donor displaying dysbiosis and chronodisruption. Basal microbiota pattern was associated with an increased risk of non-communicable chronic diseases. Both samples decrease species richness and increase microbiota diversity (p < 0.05; Chao and Shannon index, respectively), positively enhancing Firmicutes/Bacteroidetes index (SCG, p < 0.04; SCG-DF, p < 0.02). SCG and SCG-DF modulated the microbiota, but SCG-DF induced greater changes, significantly increasing. p_Actonobacterias (SCG p < 0.04; SCG-DF, p < 0.02), and reducing g_Alistipes; s_putredinis, g_Prevotella;s_copri. The highest increase was displayed by p_Proteobacteria (f_Desulfovibrionaceae and f_Alcanigenaceae, p < 0.05), while g_Haemophilus; s_parainfluenzae decreased (p < 0.05). However, neither SCG nor SCG-DF modulated g_Alistipes (evening-type colonic microbial marker) beneficially. SCG and SCG-DF reduced (p < 0.05) g_Lachnospira, a microbial evening-type marker, among other microbial populations, of an obese donor displaying chronodisruption and dysbiosis. SCG and SCG-DF displayed a prebiotic effect with the potential to mitigate diseases linked to chronodisruption.
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Antioxidants , Coffee , Humans , Dysbiosis , Dietary Fiber , ObesityABSTRACT
Background: Breasts are considered one of the most physically and sexually appealing features of the female body. Reduction/augmentation techniques have greatly evolved in the last decades.We are reporting our experience with an innovative technique for mastopexy that recovers the aesthetics of the breast and avoids over-resection of its lower pole. Methods: Inclusion criteria were women who underwent kite mastopexy with or without implants between January 2018 and May 2022 in a single center (Bogota, Colombia). Exclusion criteria were patients with American Society of Anesthesiology score more than II, with any uncontrolled chronic illness and/or medical history of diabetic mellitus, metabolic syndrome, body mass index more than 32 kg per m2, and active smokers. Results: We found 133 consecutive female patients. Age range was 18 and 67 years (median 39). Breast implants were used for the purpose of kite mastopexy in 52% cases. Patients were divided into two groups: implants (group 1) versus no implants (group 2). Procedure 1 involved mastopexy without implants; procedure 2 included current implant users who underwent either implant removal or in whom implants were not used for the sake of mastopexy. Procedures 3 and 4 included patients who underwent either new implant placement or implant exchange, respectively. Average time of surgery was 1.5 hours. Minor complications were mostly related to wound dehiscence. No major complications were reported. Conclusions: Kite mastopexy restores the breast aesthetics by following specific markings, a new plication of breast pillars, and a reduced scar. Our technique demonstrates a very low rate of complications while entailing natural and appealing results.
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BACKGROUND: To evaluate factors associated with better outcomes from optical treatment alone in amblyopic children from 3 up to 7 years. METHODS: Data extracted from two studies with similar protocols, Amblyopic Treatment Studies 5 (n = 152) and 13 (n = 128) from the Pediatric Eye Disease Investigator Group database, were used to determine by regression analysis the factors associated with improvements in visual acuity in the amblyopic eye, inter-ocular visual acuity difference and stereoacuity. Input variables were aetiology of amblyopia (anisometropic, strabismic and combined-mechanism amblyopia), treatment compliance, visual acuity, interocular visual acuity difference, stereoacuity, tropia size at distance and near, age and refractive error at baseline. RESULTS: Despite the range of clinical factors considered, our models explain only a modest proportion of the variance in optical treatment outcomes. The better predictors of the degree of optical treatment success in amblyopic children are visual acuity of the amblyopic eye, interocular visual acuity difference, stereoacuity, treatment compliance and the amblyopic eye spherical-equivalent refractive error. While the aetiology of the amblyopia does not exert a major influence upon treatment outcome, combined-mechanism amblyopes experience the smallest improvement in visual acuity, tropia and stereoacuity and may need longer optical treatment periods. CONCLUSIONS: While results identify the factors influencing optical treatment outcome in amblyopic children, clinicians will be unable to predict accurately the benefits of optical treatment in individual patients. Whether this is because relevant clinical or non-clinical factors (e.g. nature and volume of daily activities undertaken) influences the outcomes from optical treatment has not yet been identified and remains to be discovered.
Subject(s)
Amblyopia , Refractive Errors , Child , Humans , Amblyopia/therapy , Amblyopia/complications , Visual Acuity , Refractive Errors/complications , Treatment Outcome , EyeglassesABSTRACT
Stress fractures belong to the group of atraumatic fractures. A low-impact and repetitive load is the underlying cause and no fracture would occur under physiological circumstances. The conventional Xray examination remains the initial imaging modality when a stress fracture is suspected. In contrast, magnetic resonance imaging (MRI) is the gold standard and is also used to rule out other pathological changes. Computed tomography (CT) should be included if the MRI findings are unclear. New techniques, such as dual energy computed tomography (DECT) and magnetic resonance bone imaging (MR bone) should be used more frequently in practice in the future and become increasingly more important for the correct diagnosis.
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Fractures, Stress , Humans , Fractures, Stress/diagnosis , Tomography, X-Ray Computed/methods , Radiography , Magnetic Resonance Imaging/methods , Edema/diagnostic imagingABSTRACT
BACKGROUND: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. METHODS: A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. RESULTS: Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. CONCLUSIONS: The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.
Subject(s)
Neoplasms , Protein Serine-Threonine Kinases , Humans , Animals , Mice , Protein Serine-Threonine Kinases/genetics , Aurora Kinase B/genetics , Aurora Kinase B/metabolism , M Phase Cell Cycle Checkpoints , Cell Line, Tumor , RNA, Messenger , Neoplasms/drug therapy , Neoplasms/genetics , Protein-Tyrosine Kinases/metabolism , Cell Cycle Proteins/geneticsABSTRACT
There is a broad spectrum of pathology in traumatic vascular injury. Arteriovenous fistula (AVF) is an abnormal communication between the high-flow arterial system and the low-flow venous network, directly connecting the afferent artery and nearby draining veins without the regular intervention of the capillary bed. Most of these fistulas occur due to incidental or iatrogenic injury. A retrospective review of procedures performed by an endovascular surgeon in a tertiary center identified 15 cases of vascular injuries that encompassed all these different clinical scenarios, including post-traumatic, iatrogenic, or spontaneous origin. The information collected, including patient age, sex, previous symptoms, and treatment, was gathered from medical records. In addition, information on procedural technique, endovascular devices used, and specific intraprocedural details were collected from procedure notes and angiographic images. A broad spectrum of injuries can present as late trauma complications (over three months); endovascular treatment is a safe and effective approach for intracranial and extracranial injuries. Endovascular treatment can be a sole option or adjuvant to other hybrid therapies and has emerged as essential for treating these lesions as a first option. We have described standard techniques to treat different vascular pathologies, sometimes with limited resources.
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Planktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains ~22,000, ~157,000, ~9,000, ~400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century.
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Foraminifera , Censuses , Climate Change , Oceans and Seas , PlanktonABSTRACT
OBJECTIVE: To compare dedicated MRI with targeted fluoroscopic guided symphyseal contrast agent injection regarding the assessment of symphyseal cleft signs in men with athletic groin pain and assessment of radiographic pelvic ring instability. METHODS: Sixty-six athletic men were prospectively included after an initial clinical examination by an experienced surgeon using a standardized procedure. Diagnostic fluoroscopic symphyseal injection of a contrast agent was performed. Additionally, standing single-leg stance radiography and dedicated 3-Tesla MRI protocol were employed. The presence of cleft injuries (superior, secondary, combined, atypical) and osteitis pubis was recorded. RESULTS: Symphyseal bone marrow edema (BME) was present in 50 patients, bilaterally in 41 patients and in 28 with an asymmetrical distribution. Comparison of MRI and symphysography was as followed: no clefts: 14 cases (MRI) vs. 24 cases (symphysography), isolated superior cleft sign: 13 vs. 10, isolated secondary cleft sign: 15 vs. 21 cases and combined injuries: 18 vs. 11 cases. In 7 cases a combined cleft sign was observed in MRI but only an isolated secondary cleft sign was visible in symphysography. Anterior pelvic ring instability was observed in 25 patients and was linked to a cleft sign in 23 cases (7 superior cleft sign, 8 secondary cleft signs, 6 combined clefts, 2 atypical cleft injuries). Additional BME could be diagnosed in 18 of those 23. CONCLUSION: Dedicated 3-Tesla MRI outmatches symphysography for purely diagnostic purposes of cleft injuries. Microtearing at the prepubic aponeurotic complex and the presence of BME is a prerequisite for the development of anterior pelvic ring instability. CLINICAL RELEVANCE STATEMENT: For diagnostic of symphyseal cleft injuries dedicated 3-T MRI protocols outmatch fluoroscopic symphysography. Prior specific clinical examination is highly beneficial and additional flamingo view x-rays are recommended for assessment of pelvic ring instability in these patients. KEY POINTS: ⢠Assessment of symphyseal cleft injuries is more accurate by use of dedicated MRI as compared to fluoroscopic symphysography. ⢠Additional fluoroscopy may be important for therapeutic injections. ⢠The presence of cleft injury might be a prerequisite for the development of pelvic ring instability.
Subject(s)
Athletic Injuries , Pubic Symphysis , Sports , Male , Humans , Contrast Media/pharmacology , Groin/injuries , Pubic Symphysis/diagnostic imaging , Pubic Symphysis/injuries , Athletic Injuries/diagnosis , Magnetic Resonance Imaging/methods , Fluoroscopy , PainABSTRACT
BACKGROUND: Acute kidney injury (AKI) is common in sick neonates and associated with poor pulmonary outcomes, however, the mechanisms responsible remain unknown. We present two novel neonatal rodent models of AKI to investigate the pulmonary effects of AKI. METHODS: In rat pups, AKI was induced surgically via bilateral ischemia-reperfusion injury (bIRI) or pharmacologically using aristolochic acid (AA). AKI was confirmed with plasma blood urea nitrogen and creatinine measurements and kidney injury molecule-1 staining on renal immunohistochemistry. Lung morphometrics were quantified with radial alveolar count and mean linear intercept, and angiogenesis investigated by pulmonary vessel density (PVD) and vascular endothelial growth factor (VEGF) protein expression. For the surgical model, bIRI, sham, and non-surgical pups were compared. For the pharmacologic model, AA pups were compared to vehicle controls. RESULTS: AKI occurred in bIRI and AA pups, and they demonstrated decreased alveolarization, PVD, and VEGF protein expression compared controls. Sham pups did not experience AKI, however, demonstrated decreased alveolarization, PVD, and VEGF protein expression compared to controls. CONCLUSION: Pharmacologic AKI and surgery in neonatal rat pups, with or without AKI, decreased alveolarization and angiogenesis, producing a bronchopulmonary dysplasia phenotype. These models provide a framework for elucidating the relationship between AKI and adverse pulmonary outcomes. IMPACT: There are no published neonatal rodent models investigating the pulmonary effects after neonatal acute kidney injury, despite known clinical associations. We present two novel neonatal rodent models of acute kidney injury to study the impact of acute kidney injury on the developing lung. We demonstrate the pulmonary effects of both ischemia-reperfusion injury and nephrotoxin-induced AKI on the developing lung, with decreased alveolarization and angiogenesis, mimicking the lung phenotype of bronchopulmonary dysplasia. Neonatal rodent models of acute kidney injury provide opportunities to study mechanisms of kidney-lung crosstalk and novel therapeutics in the context of acute kidney injury in a premature infant.