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OBJECTIVE: To evaluate if gait biomechanics are associated with increased risk of structurally diagnosed disease onset or progression of lower limb osteoarthritis (OA). METHOD: A systematic review of Medline and Embase was conducted from inception to July 2021. Two reviewers independently screened records, extracted data and assessed risk of bias. Included studies reported gait biomechanics at baseline, and either structural imaging or joint replacement occurrence in the lower limb at follow-up. The primary outcome was the Odds Ratio (OR) (95% confidence interval (CI)) of the association between biomechanics and structural OA outcomes with data pooled for meta-analysis. RESULTS: Twenty-three studies reporting 25 different biomechanical metrics and 11 OA imaging outcomes were included (quality scores ranged 12-20/21). Twenty studies investigated knee OA progression; three studies investigated knee OA onset. Two studies investigated hip OA progression. 91% of studies reported a significant association between at least one biomechanical variable and OA onset or progression. There was an association between frontal plane biomechanics with medial tibiofemoral and hip OA progression and sagittal plane biomechanics with patellofemoral OA progression. Meta-analyses demonstrated increased odds of medial tibiofemoral OA progression with greater baseline peak knee adduction moment (KAM) (OR: 1.88 [95%CI: 1.08, 3.29]) and varus thrust presence (OR: 1.97 [95%CI: 1.32, 2.96]). CONCLUSION: Evidence suggests that certain gait biomechanics are associated with an increased odds of OA onset and progression in the knee, and progression in the hip. REGISTRATION NUMBER: PROSPERO CRD42019133920.
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Marcha/fisiologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Fenômenos Biomecânicos , Progressão da Doença , Humanos , Fatores de RiscoRESUMO
We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.
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BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS. METHODS: Consecutive adult patients (>18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control. RESULTS: 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count >0.455 x109/L was 9.27 times more likely to require for systemic medication. CONCLUSION: Pre-operative blood eosinophil count >0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.
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Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Adulto , Doença Crônica , Eosinofilia/tratamento farmacológico , Eosinófilos , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/cirurgia , Rinite/tratamento farmacológico , Rinite/cirurgia , Sinusite/tratamento farmacológico , Sinusite/cirurgiaRESUMO
A key aim of biocatalysis is to mimic the ability of eukaryotic cells to carry out multistep cascades in a controlled and selective way. As biocatalytic cascades get more complex, reactions become unattainable under typical batch conditions. Here a number of continuous flow systems were used to overcome batch incompatibility, thus allowing for successful biocatalytic cascades. As proof-of-principle, reactive carbonyl intermediates were generated in situ using alcohol oxidases, then passed directly to a series of packed-bed modules containing different aminating biocatalysts which accordingly produced a range of structurally distinct amines. The method was expanded to employ a batch incompatible sequential amination cascade via an oxidase/transaminase/imine reductase sequence, introducing different amine reagents at each step without cross-reactivity. The combined approaches allowed for the biocatalytic synthesis of the natural product 4O-methylnorbelladine.
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Oxirredutases do Álcool/metabolismo , Aminas/metabolismo , Produtos Biológicos/metabolismo , Aminas/química , Biocatálise , Produtos Biológicos/química , Estrutura MolecularRESUMO
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be a novel intervention to improve cardiopulmonary resuscitation (CPR) quality during cardiac arrest. Zone 1 supraceliac aortic occlusion improves coronary and cerebral blood flow. It is unknown if Zone 3 occlusion distal to the renal arteries offers a similar physiologic benefit while maintaining blood flow to organs above the point of occlusion. METHODS: Fifteen swine were anesthetized, instrumented, and placed into ventricular fibrillation. Mechanical CPR was immediately initiated. After 5 min of CPR, Zone 1 REBOA, Zone 3 REBOA, or no intervention (control) was initiated. Hemodynamic variables were continuously recorded for 30 min. RESULTS: There were no significant differences between groups before REBOA deployment. Once REBOA was deployed, Zone 1 animals had statistically greater diastolic blood pressure compared to control (median [IQR]: 19.9 mmHg [9.5-20.5] vs 3.9 mmHg [2.4-4.8], p = .006). There were no differences in diastolic blood pressure between Zone 1 and Zone 3 (8.6 mmHg [5.1-13.1], p = .10) or between Zone 3 and control (p = .10). There were no significant differences in systolic blood pressure, cerebral blood flow, or time to return of spontaneous circulation (ROSC) between groups. CONCLUSION: In our swine model of cardiac arrest, Zone 1 REBOA improved diastolic blood pressure when compared to control. Zone 3 does not offer a hemodynamic benefit when compared to no occlusion. Unlike prior studies, immediate use of REBOA after arrest did not result in an increase in ROSC rate, suggesting REBOA may be more beneficial in patients with prolonged no-flow time. INSTITUTIONAL PROTOCOL NUMBER: FDG20180024A.
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Aorta , Oclusão com Balão/métodos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/terapia , Hemodinâmica , Animais , Aorta/fisiopatologia , Modelos Animais de Doenças , Feminino , Parada Cardíaca/fisiopatologia , Masculino , SuínosRESUMO
A method is presented for tracking the internal deformation of self-oscillating vocal fold models using magnetic resonance imaging (MRI). Silicone models scaled to four times life-size to lower the flow-induced vibration frequency were embedded with fiducial markers in a coronal plane. Candidate marker materials were tested using static specimens, and two materials, cupric sulfate and glass, were chosen for testing in the vibrating vocal fold models. The vibrating models were imaged using a gated MRI protocol wherein MRI acquisition was triggered using the subglottal pressure signal. Two-dimensional image slices at different phases during self-oscillation were captured, and in each phase the fiducial markers were clearly visible. The process was also demonstrated using a three-dimensional scan at two phases. The benefit of averaging to increase signal-to-noise ratio was explored. The results demonstrate the ability to use MRI to acquire quantitative deformation data that could be used, for example, to validate computational models of flow-induced vocal fold vibration and quantify deformation fields encountered by cells in bioreactor studies.
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Imageamento por Ressonância Magnética/métodos , Modelos Biológicos , Prega Vocal/diagnóstico por imagem , Desenho de Equipamento , Marcadores Fiduciais , Humanos , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Processamento de Sinais Assistido por Computador , Silicones , VibraçãoRESUMO
We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at 220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.
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BACKGROUND AND PURPOSE: Some symptoms of multiple sclerosis (MS) affect driving. In a recent study, performance on five cognitive tests predicted the on-road test performance of individuals with relapsing-remitting MS with 91% accuracy, 70% sensitivity and 97% specificity. However, the accuracy with which the battery will predict the driving performance of a different cohort that includes all types of MS is unknown. METHODS: Participants (n = 118; 48 ± 9 years of age; 97 females) performed a comprehensive off-road evaluation that lasted about 3 h and a standardized on-road test that lasted approximately 45 min over a 2-day period within the same week. Performance on the five cognitive tests was used to predict participants' performance on the standardized on-road test. RESULTS: Performance on the five tests together predicted outcome of the on-road test with 82% accuracy, 42% sensitivity and 90% specificity. CONCLUSIONS: The accuracy of predicting the on-road performance of a new MS cohort using performance on the battery of five cognitive tests remained very high (82%). The battery, which was administrable in <45 min and cost ~$150, was better at identifying those who actually passed the on-road test (90% specificity). The sensitivity (42%) of the battery indicated that it should not be used as the sole determinant of poor driving-related cognitive skills. A fail performance on the battery should only imply that more comprehensive testing is warranted.
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Exame para Habilitação de Motoristas , Condução de Veículo/psicologia , Cognição/fisiologia , Esclerose Múltipla/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Large muscular or musculotendinous defects present a dilemma because of the inadequacies of current treatment strategies. Extracellular matrices (ECM) are potential clinically applicable regenerative biomaterials. This review summarizes information from the preclinical literature evaluating the use of ECM for muscle regeneration in animal models of volumetric muscle loss (VML). STUDY DESIGN: Literature review. SAMPLE POPULATION: Animal models of VML in which surgical repair was performed with an ECM product, with or without added cell populations. METHODS: PubMed, Google Scholar, CAB abstracts, and Scopus were searched for preclinical studies using ECM in animal models of VML. The search terms "extracellular matrix," "VML," "muscle regeneration," "cell seeded," and "scaffold" identified 40 articles that met inclusion criteria of an animal model of VML in which surgical repair was performed with an ECM product, with or without added cell populations. Key skeletal muscle repair mechanisms and experimental findings on scaffold type, VML location, and experimental animal species were summarized. CONCLUSIONS: Satellite cells and basal lamina are key endogenous contributors to skeletal muscle regeneration. ECM as a dynamic tissue component may provide structural integrity, signaling molecules, and a 3-dimensional topography conducive to muscle regeneration. Preclinical models of muscle repair most commonly used mice and rats (88%). Most experimental lesions were created in abdominal wall (33%), anterior tibialis (33%), latissimus dorsi (10%), or quadriceps (10%) muscles. Matrices varied markedly in source and preparation. Experimental outcomes of ECM and cell-seeded ECM implantation for muscle regeneration in VML were highly variable and dependent on matrix tissue source, preparation method, and anatomic site of injury. Scar tissue formation likely contributes to load transfer. Nonappendicular lesions had better regenerative results compared with appendicular VML. CLINICAL SIGNIFICANCE: The preponderance of current evidence supports the use of ECM for muscle defect repair only in specific instances, such as nonappendicular and/or partial-thickness defects. Consequently, clinical use of ECM in veterinary patients requires careful consideration of the specific ECM product, lesion size and location, and loading circumstances.
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Matriz Extracelular , Músculo Esquelético/lesões , Alicerces Teciduais , Cicatrização , Animais , Músculo Esquelético/fisiologiaRESUMO
We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross-spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed ΛCDM is detected at modest significance in the 95×150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23×95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23×353. We take the likelihood of all the spectra for a multicomponent model including lensed ΛCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves.
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BACKGROUND: Although the incidence of acute death related to coronary artery disease has decreased with the advent of new interventional therapies, myocardial infarction remains one of the leading causes of death in the US. Current animal models developed to replicate this phenomenon have been associated with unacceptably high morbidity and mortality. A new model utilizing the first diagonal branch of the left anterior descending artery (D1-LAD) was developed to provide a clinically relevant lesion, while attempting to minimize the incidence of adverse complications associated with infarct creation. METHODS: Eight Yucatan miniature pigs underwent percutaneous embolization of the D1-LAD via injection of 90 µm polystyrene micro-spheres. Cardiac structure and function were monitored at baseline, immediately post-operatively, and at 8-weeks post-infarct using transthoracic echocardiography. Post-mortem histopathology and biochemical analyses were performed to evaluate for changes in myocardial structure and extracellular matrix (ECM) composition respectively. Echocardiographic data were evaluated using a repeated measures analysis of variance followed by Tukey's HSD post hoc test. Biochemical analyses of infarcted to non-infarcted myocardium were compared using analysis of variance. RESULTS: All eight pigs successfully underwent echocardiography prior to catheterization. Overall procedural survival rate was 83% (5/6) with one pig excluded due to failure of infarction and another due to deviation from protocol. Ejection fraction significantly decreased from 69.7 ± 7.8% prior to infarction to 50.6 ± 14.7% immediately post-infarction, and progressed to 48.7 ± 8.9% after 8-weeks (p = 0.011). Left ventricular diameter in systole significantly increased from 22.6 ± 3.8 mm pre-operatively to 30.9 ± 5.0 mm at 8 weeks (p = 0.016). Histopathology showed the presence of disorganized fibrosis on hematoxylin and eosin and Picro Sirius red stains. Collagen I and sulfated glycosaminoglycan content were significantly greater in the infarcted region than in normal myocardium (p = 0.007 and p = 0.018, respectively); however, pyridinoline crosslink content per collagen I content in the infarcted region was significantly less than normal myocardium (p = 0.048). CONCLUSION: Systolic dysfunction and changes in ECM composition induced via embolization of the D1-LAD closely mimic those found in individuals with chronic myocardial infarction (MI), and represents a location visible without the need for anesthesia. As a result, this method represents a useful model for studying chronic MI.
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Vasos Coronários/patologia , Embolização Terapêutica , Infarto do Miocárdio/terapia , Animais , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Modelos Animais de Doenças , Feminino , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Reprodutibilidade dos Testes , Volume Sistólico , Suínos , Porco Miniatura , Sístole , UltrassonografiaRESUMO
BACKGROUND: Severe hepatic injuries may be highly lethal, and perihepatic packing remains the mainstay of treatment. This is not always successful, particularly in the setting of hypothermia and coagulopathy. Kaolin-impregnated Combat Gauze (CG) is an effective hemostatic dressing used primarily to treat external wounds. The objective of this study was to determine the ability of CG to control severe hemorrhage in hypothermic, coagulopathic swine with a high-grade hepatic injury. METHODS: Anesthetized animals underwent splenectomy and were cooled to 32°C while undergoing a 60% exchange transfusion with Hextend. A grade V liver injury was created in the left middle hepatic lobe. Animals were allowed to freely bleed for 30 s and then randomized to treatment with CG or plain gauze laparotomy pads (PG) applied to the injury site. Animals were then resuscitated with warmed Hextend. RESULTS: There was no difference between groups in preinjury hemodynamic or laboratory values. Animals packed with CG had less blood loss when compared with standard packing (CG = 25 mL/kg versus PG = 58 mL/kg, P = 0.05). There was a trend towards lower hetastarch resuscitation requirements in the CG group (CG = 7 mL/kg versus PG = 44 mL/kg, P = 0.06) but no statistically significant difference in mortality (CG = 13% versus PG = 50%, P = 0.11). Histology of the injury sites revealed more adherent clot in the CG group, but no inflammation, tissue necrosis, or residual material. CONCLUSION: In pigs with severe hepatic injury, Combat Gauze reduced blood loss and resuscitation requirements when compared with plain laparotomy pads. Combat Gauze may be safe and effective for use on severe liver injuries.
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Bandagens , Transtornos da Coagulação Sanguínea/complicações , Hemorragia/prevenção & controle , Técnicas Hemostáticas , Hipotermia Induzida/efeitos adversos , Caulim/uso terapêutico , Fígado/lesões , Animais , Modelos Animais de Doenças , Feminino , Hemostáticos/administração & dosagem , Hemostáticos/uso terapêutico , Incidência , Inflamação/epidemiologia , Caulim/administração & dosagem , Masculino , Necrose/epidemiologia , Projetos Piloto , Suínos , Resultado do TratamentoRESUMO
Iminosugar scaffolds are highly sought-after pharmaceutical targets, but their chemical synthesis is lengthy and can suffer from poor scalability and purification. Here we report protecting-group-free chemoenzymatic and biocatalytic cascades to synthesize iminosugars from sugar-derived aminopolyols in two steps. Using galactose oxidase variant F2 followed by a chemical or enzymatic reduction provided an efficient one-pot route to these targets, with product formation >70%. Key to success of this strategy was the application of genome mining, which identified bacterial shikimate dehydrogenases as promiscuous iminosugar reductases. The cell-free protocols allowed for isolation of highly polar iminosugar products from biotransformations in a single step through development of a gradient-elution cation exchange purification. The two-step pathway provides a short synthetic route that can be used as a cell-free platform for broader iminosugar synthesis.
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Despite the increasing use of biocatalysis for organic synthesis, there are currently no databases that adequately capture synthetic biotransformations. The lack of a biocatalysis database prevents accelerating biocatalyst characterization efforts from being leveraged to quickly identify candidate enzymes for reactions or cascades, slowing their development. The RetroBioCat Database (available at retrobiocat.com) addresses this gap by capturing information on synthetic biotransformations and providing an analysis platform that allows biocatalysis data to be searched and explored through a range of highly interactive data visualization tools. This database makes it simple to explore available enzymes, their substrate scopes, and how characterized enzymes are related to each other and the wider sequence space. Data entry is facilitated through an openly accessible curation platform, featuring automated tools to accelerate the process. The RetroBioCat Database democratizes biocatalysis knowledge and has the potential to accelerate biocatalytic reaction development, making it a valuable resource for the community.
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BACKGROUND: Burnout, anxiety and depression are commonly reported among surgical residents and faculty members. Resident training programmes are encouraged to implement structured wellness initiatives, to address emotional stress. METHODS: Thirty otolaryngology residents and faculty members were invited to participate in this prospective pilot trial. Participants were randomised to either the intervention group, which involved completing 10 mobile meditation sessions, or the control group. Outcomes were measured with the Generalized Anxiety Disorder scale-7, Patient Health Questionnaire and Professional Quality of Life scale. RESULTS: Nineteen participants completed the study. Participants in the intervention group had a significantly greater mean change in Generalized Anxiety Disorder scale-7 score (-2.7 ± 3.335 vs 0.33 ± 1.225; p = 0.04). There was no significant difference in average change in Patient Health Questionnaire-9 scores or Professional Quality of Life scale sub-scores between the intervention and control groups. CONCLUSION: Short meditation sessions can significantly improve anxiety in surgical residents and faculty members, and they offer a simple, attainable and effective wellness intervention.
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Internato e Residência , Meditação , Humanos , Qualidade de Vida , Depressão/terapia , Estudos Prospectivos , Ansiedade/prevenção & controle , DocentesRESUMO
Amino-polyols represent attractive chemical building blocks but can be challenging to synthesize because of the high density of asymmetric functionalities and the need for extensive protecting-group strategies. Here we present a three-component strategy for the stereoselective enzymatic synthesis of amino-diols and amino-polyols using a diverse set of prochiral aldehydes, hydroxy ketones, and amines as starting materials. We were able to combine biocatalytic aldol reactions, using variants of d-fructose-6-phosphate aldolase (FSA), with reductive aminations catalyzed by IRED-259, identified from a metagenomic library. A two-step process, without the need for intermediate isolation, was developed to avoid cross-reactivity of the carbonyl components. Stereoselective formation of the 2R,3R,4R enantiomers of amino-polyols was observed and confirmed by X-ray crystallography.
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To determine the relative contributions of DC subsets in the development of protective immunity to Listeria monocytogenes we examined the relationship between maturation, bacterial burden, and T cell priming capacity of four well characterized subsets of splenic DC following infection with Lm. CD8α(+), CD4(+), and CD8α(-)CD4(-) DC and the B220(+) plasmacytoid DC (pDC) were compared for abundance and costimulatory molecule expression at 24, 48, and 72h post i.v. infection. We further determined the bacterial burden associated with each DC subset and their relative capacities to prime CD8(+) T cells at 24hpi. The CD8α(+) DC displayed the highest level of maturation, association with live bacteria, and T cell activation potential. Second, the CD4(+) DC were also mature, yet were associated with fewer bacteria, and stimulated T cell proliferation, but not IFN-γ production. The CD8α(-)CD4(-) DC showed a modest maturation response and were associated with a high number of bacteria, but failed to induce T cell proliferation ex vivo. pDC displayed a strong maturation response, but were not associated with detectable bacteria and also failed to stimulate T cell activation. Finally, we measured the cytokine responses in these subsets and determined that IL-12 was produced predominantly by the CD8(+) DC, correlating with the ability of this subset DC to induce IFN-γ production in T cells. We conclude that Listeria-specific CD8(+) T cell activation in the spleen is most effectively achieved by infection-induced maturation of the CD8α(+) DC subset.
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Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Baço/imunologia , Animais , Carga Bacteriana/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/microbiologia , Sobrevivência Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/microbiologia , Citometria de Fluxo , Listeriose/microbiologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Baço/citologiaRESUMO
Compared to the other Anglo-American democracies, when they start job searches, Canadian post-secondary graduates likely confront more competition from similarly educated youth, and experience a relatively high unemployment rate. In addition, should they find work, there is no guarantee for graduates that it will be in their area of specialization. There is an added possibility that employment will be precarious. By comparison, in the mid-sixties, labour market conditions were more accommodating to university graduates. Are these different labour market conditions consistent with students' expectations, goals, and campus experiences prior to graduation? An answer to this question was found through a comparison of those entering Glendon College, York University, in 1963, and in 2013. The examination was based on surveys students completed in 1963, 1967, 2013, and 2017. Data from these sources was. supplemented by information obtained through interviews with students, archival materials, and by analyzing the contents of the student newspaper. Overall, the expectations of Glendon students in the 1960s, and 50 years later, were in keeping with respective favourable and unfavorable labour market conditions. For students' experiences this was not the case. Despite considerable changes in the labour market, the way in which students experienced their time on campus was comparable in the two eras.
Lorsqu'ils se lancent dans la recherche d'un emploi, les diplômés canadiens de niveau postsecondaire sont susceptibles d'être confrontés à une plus grande concurrence de la part de jeunes ayant un niveau d'éducation similaire, et connaissent un taux de chômage relativement élevé. De plus, s'ils trouvent du travail, rien ne garantit que ce sera dans leur domaine de spécialisation. Il est également possible que l'emploi soit précaire. En comparaison, au milieu des années 60, les conditions du marché du travail étaient plus favorables aux diplômés universitaires. Ces différentes conditions du marché du travail correspondent-elles aux attentes, aux objectifs et aux expériences des étudiants sur le campus avant l'obtention du diplôme ? Une réponse à cette question a été trouvée en comparant les étudiants entrés au Glendon College de l'Université York en 1963 et en 2013. L'examen s'est appuyé sur les enquêtes auxquelles les étudiants ont répondu en 1963, 1967, 2013 et 2017, et a été complété par des informations obtenues lors d'entretiens avec des étudiants, des documents d'archives et par l'analyse du contenu du journal étudiant. Dans l'ensemble, les attentes des étudiants de Glendon dans les années 1960, et cinquante ans plus tard, correspondaient aux conditions favorables et défavorables respectives du marché du travail. En ce qui concerne les expériences des étudiants, ce n'était pas le cas. Malgré des changements considérables sur le marché du travail, la manière dont les étudiants ont vécu leur séjour sur le campus était comparable aux deux époques.
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OBJECTIVE: Dialysis patients may not have access to conventional renal replacement therapy (RRT) following disasters. We hypothesized that improvised renal replacement therapy (ImpRRT) would be comparable to continuous renal replacement therapy (CRRT) in a porcine acute kidney injury model. METHODS: Following bilateral nephrectomies and 2 hours of caudal aortic occlusion, 12 pigs were randomized to 4 hours of ImpRRT or CRRT. In the ImpRRT group, blood was circulated through a dialysis filter using a rapid infuser to collect the ultrafiltrate. Improvised replacement fluid, made with stock solutions, was infused pre-pump. In the CRRT group, commercial replacement fluid was used. During RRT, animals received isotonic crystalloids and norepinephrine. RESULTS: There were no differences in serum creatinine, calcium, magnesium, or phosphorus concentrations. While there was a difference between groups in serum potassium concentration over time (P < 0.001), significance was lost in pairwise comparison at specific time points. Replacement fluids or ultrafiltrate flows did not differ between groups. There were no differences in lactate concentration, isotonic crystalloid requirement, or norepinephrine doses. No difference was found in electrolyte concentrations between the commercial and improvised replacement solutions. CONCLUSION: The ImpRRT system achieved similar performance to CRRT and may represent a potential option for temporary RRT following disasters.