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OBJECTIVES: Acknowledging that a successful career in hospital medicine (HM) requires specialized skills, residency programs have developed hospital medicine-focused education (HMFE) programs. Surveys of Internal Medicine residency leaders have described HMFE curricula but are limited to that specialty and lack perspectives from early career hospitalists (ECHs) who recently completed this training. As such, we surveyed multispecialty ECHs to evaluate their preferences for HMFE and to identify gaps in standard residency training and career development that HMFE can bridge. The objectives of our study were to describe multispecialty ECH needs and preferences for HMFE and to identify gaps in standard residency training and career development that HMFE can bridge. METHODS: From February to March 2021, ECHs (defined as hospitalists within 0-5 years from residency) were surveyed using the Society of Hospital Medicine's listserv. Respondents identified as having participated in HMFE or not during residency (defining them as HMFE participants or non-HMFE participants). RESULTS: From 257 respondents, 84 (33%) ECHs met inclusion criteria. Half (n = 42) were HMFE participants. ECHs ranked clinical hospitalist career preparation (86%) and mentorship from HM faculty (85%) as the most important gaps in standard residency training and career development that HMFE can bridge. Other key components of HMFE included exposure to quality improvement, patient safety, and high-value care (67%); provision of autonomy through independent rounding (54%); and preparation for the job application process (70%). CONCLUSIONS: Multispecialty ECHs describe HMFE as positively influencing their decision to pursue a hospitalist career and increasing their preparedness for practice. HMFE may be particularly well suited to foster advanced clinical skills such as independent rounding, critical thinking, and self-reflection. We propose an organizing framework for HMFE in residency that may assist in the implementation and innovation of HMFE programs nationwide and in the development of standardized HMFE competencies.
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Medicina Hospitalar , Médicos Hospitalarios , Medicina , Humanos , Escolaridad , Hospitales de EnseñanzaRESUMEN
We demonstrate that single-walled carbon nanotube (SWCNT) membranes can be successfully utilized as nanometer-thick substrates for enhanced visualization and facilitated study of individual nanoparticles. As model objects, we transfer optically resonant 200 nm silicon nanoparticles onto pristine and ethanol-densified SWCNT membranes by the femtosecond laser printing method. We image nanoparticles by scanning electron and bright-field optical microscopy, and characterize by linear and Raman scattering spectroscopy. The use of a pristine SWCNT membrane allows to achieve an order-of-magnitude enhancement of the optical contrast of the nanoparticle bright field image over the results shown in the case of the glass substrate use. The observed optical contrast enhancement is in agreement with the spectrophotometric measurements showing an extremely low specular reflectance of the pristine membrane (≤0.1%). Owing to the high transparency, negligibly small reflectance and thickness, SWCNT membranes offer a variety of perspective applications in nanophotonics, bioimaging and synchrotron radiation studies.
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The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the proarrhythmic effect of EAT. EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-h EAT culture media (n = 8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Coculture with ß-adrenergic agonists isoproterenol (n = 4) and BRL37344 (n = 13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae (n = 10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula-developed force (maximal 2.9-fold increase, P < 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P = 0.002) and relaxation (1.8-fold increase, P = 0.007). Additionally, the postrest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca2+ handling. EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behavior in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect.
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Arritmias Cardíacas/inducido químicamente , Atrios Cardíacos/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Resistina/fisiología , Tejido Adiposo/metabolismo , Anciano , Anciano de 80 o más Años , Calcio/metabolismo , Cardiotónicos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Isoproterenol/farmacología , Masculino , Persona de Mediana Edad , Pericardio/metabolismo , Resistina/sangre , Retículo Sarcoplasmático/metabolismo , Malla Trabecular/metabolismoRESUMEN
Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery (n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, ß-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with ß1/2 (isoproterenol) or ß3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and ß1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute ß3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific ß3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the ß3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on ß3-adrenergic rather than ß1/2-adrenergic stimulation of EAT.
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Tejido Adiposo/fisiopatología , Arritmias Cardíacas/fisiopatología , Atrios Cardíacos/fisiopatología , Corazón/fisiopatología , Pericardio/fisiopatología , Agonistas de Receptores Adrenérgicos beta 3/farmacología , Agonistas Adrenérgicos beta/farmacología , Anciano , Etanolaminas/farmacología , Femenino , Humanos , Isoproterenol/farmacología , Masculino , Contracción Miocárdica , Miocardio/metabolismoRESUMEN
Materials with electrically tunable optical properties offer a wide range of opportunities for photonic applications. The optical properties of the single-walled carbon nanotubes (SWCNTs) can be significantly altered in the near-infrared region by means of electrochemical doping. The states' filling, which is responsible for the optical absorption suppression under doping, also alters the nonlinear optical response of the material. Here, for the first time we report that the electrochemical doping can tailor the nonlinear optical absorption of SWCNT films and demonstrate its application to control pulsed fiber laser generation. With a pump-probe technique, we show that under an applied voltage below 2 V the photobleaching of the material can be gradually reduced and even turned to photoinduced absorption. Furthermore, we integrated a carbon nanotube electrochemical cell on a side-polished fiber to tune the absorption saturation and implemented it into the fully polarization-maintaining fiber laser. We show that the pulse generation regime can be reversibly switched between femtosecond mode-locking and microsecond Q-switching using different gate voltages. This approach paves the road toward carbon nanotube optical devices with tunable nonlinearity.
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This work focuses on the study of multimeric alpha-lactalbumin oleic acid and lactoferrin oleic acid complexes. The purpose of the research is to study possible mechanisms involved in their pro-apoptotic activities, as seen in some tumor cell cultures. Complexes featuring oleic acid (OA) with human alpha-lactalbumin (hAl) or with bovine alpha-lactalbumin (bAl), and human lactoferrin (hLf) were investigated using small-angle neutron scattering (SANS). It was shown that while alpha-lactalbumin protein complexes were formed on the surface of polydisperse OA micelles, the lactoferrin complexes comprised a monodisperse system of nanoscale particles. Both hAl and hLf complexes appeared to interact with the chromatin of isolated nuclei affecting chromatin structural organization. The possible roles of these processes in the specific anti-tumor activity of these complexes are discussed.
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Núcleo Celular/química , Cromatina/química , Lactalbúmina/química , Lactoferrina/química , Micelas , Ácido Oléico/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Bovinos , Células HeLa , Humanos , Ácidos Oléicos/química , Dispersión del Ángulo PequeñoRESUMEN
Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with NRAS-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in RAS-mutated tumors.
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Single-agent immune checkpoint inhibitors (ICIs) are the standard option for chemotherapy-pretreated metastatic non-small cell lung cancer (NSCLC), however only a subset of patients responds to this treatment. The present study aimed at the development of a tool for personalized prediction of the efficacy of ICIs. The study included 181 epidermal growth factor receptor/anaplastic lymphoma kinase-negative patients with metastatic NSCLC receiving single-agent ICI in the second or later line of therapy. For the comparison, a total of 63 metastatic patients with NSCLC treated by chemotherapy were also analyzed. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, never-smoking status and the baseline neutrophil-to-lymphocyte ratio (NLR) ≥4.3 were associated with reduced progression-free survival (PFS) and overall survival (OS) [ECOG PS: Hazard ratio (HR)=2.09; P=0.028 and HR=2.02; P=0.035, respectively; never-smoking: HR=3.53; P=0.007 and HR=1.80; P=0.004, respectively; NLR ≥4.3: HR=4.34; P<0.0001 and HR=4.89; P<0.0001 respectively]. Patients with an NLR <4.3, who had a favorable ECOG PS (0-1) and smoking history in the past, derived the utmost benefit from ICI [n=77; objective response rate (ORR)=35%; PFS and OS: 17.1 and 33.7 months, respectively]. The worst efficacy of ICI was observed in patients who had an NLR ≥4.3 coupled with poor ECOG PS and/or never-smoking status (n=38; ORR=8%; PFS=3.2 months and OS=7.2 months). The remaining patients belonged to the group with intermediate outcomes (n=66; ORR=17%; PFS and OS: 4.3 and 12.2 months, respectively). While combination of these factors was highly predictive for ICIs, it was not associated with outcomes of chemotherapy treatment. Easily available characteristics of the patients allow for highly accurate predictions of outcomes of single-agent ICI therapy in chemotherapy-pretreated NSCLC.
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Using atomic level simulation we aimed to investigate various intermediate phases of the long chain alkyl sulfonate/water system. Overall, about 800 ns parallel molecular dynamics simulation study was conducted for a surfactant/water system consisting of 128 sodium pentadecyl sulfonate and 2251 water molecules. The GROMACS software code with united atom force field was applied. Despite some differences, the analysis of main structural parameters is in agreement with X-ray experimental findings. The mechanism of self-assembly of SPDS molecules was also examined. At T = 323 K we obtained both tilted fully interdigitated and liquid crystalline-like disordered hydrocarbon chains; hence, the presence of either gel phase that coexists with a lamellar phase or metastable gel phase with fraction of gauche configuration can be assumed. Further increase of temperature revealed that the system underwent a transition to a lamellar phase, which was clearly identified by the presence of fully disordered hydrocarbon chains. The transition from gel-to-fluid phase was implemented by simulated annealing treatment, and the phase transition point at T = 335 K was identified. The surfactant force field in its presented set is surely enabled to fully demonstrate the mechanism of self-assembly and the behavior of phase transition making it possible to get important information around the phase transition point.
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Alcanosulfonatos/química , Simulación de Dinámica Molecular , Agua/química , Estructura Molecular , Tensoactivos/químicaRESUMEN
OBJECTIVE: This study compares the physical properties and clinical performance of short fiber reinforced composites (SFRC) to those of particulate-filled resin-based composites (PFRC) for class I and II direct restorations in permanent dentition. METHODS: Systematic review and meta-analysis was conducted using PubMed, Embase (Elsevier), and Dentistry and Oral Sciences Source (EBSCO) databases. The outcomes evaluated were physical properties including flexural strength, flexural modulus, elastic modulus, microhardness, shrinkage, fracture toughness, degree of conversion, and depth of cure. Clinical performance was evaluated with a systematic review. RESULTS: The meta-analyses favored SFRC for flexural strength and fracture toughness compared to every PFRC subgroup, with a high quality of evidence. For all other properties, the meta-analyses favored SFRC to overall PFRC, with some non-significant differences with certain PFRC subgroups. The most recent clinical trial showed SFRC performed similarly to PFRC, however older studies suggest inferior surface texture and discoloration of SFRC compared to PFRC. CONCLUSION: This study can aid dental professionals in clinical decision making, supporting that SFRC offers improved physical properties, especially fracture resistance and flexural strength, compared to PFRC.
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Materiales Dentales , Dentición , Módulo de Elasticidad , Resistencia FlexionalRESUMEN
To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture.
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Bacillus cereus , Semen , Masculino , Humanos , Bacillus cereus/genética , Biopelículas , Carbonato de Calcio , ADNRESUMEN
Our objective was to assess the utility of an assessment battery capturing health literacy (HL) and biopsychosocial determinants of health in predicting 30-day readmission in comparison to a currently well-adopted readmission risk calculator. We also sought to capture the distribution of inpatient HL, with emphasis on inadequate and marginal HL (an intermediate HL level). A prospective observational study was conducted to obtain HL and biopsychosocial data on general medicine inpatients admitted to the UCLA health system. Five hundred thirty-seven subjects were tracked prospectively for 30-day readmission after index hospitalization. HL was significantly better at predicting readmission compared to LACE + (Length, admission acuity, comorbidities, emergency room visits) alone (P = .013). A multivariate model including education, insurance, and language comfort was a strong predictor of adequate HL (P < .001). In conclusion, HL offered significant improvement in risk stratification in comparison to LACE + alone. Patients with marginal HL were high-risk, albeit difficult to characterize. Incorporating robust HL and biopsychosocial determinant assessments may allow hospital systems to allocate educational resources towards at-risk patients, thereby mitigating readmission risk.
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Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy. In groups 1 and 2 ß-2 microglobulin (B2-MG), neopterin (NPT), IL-6, IL-18, HLA-DRB1 and autoantibodies were assessed after two months of ICI, and before the start of next administration in group 3. In group 1 low level of B2-MG (P<0.0001), NPT (P<0.0001), IL-6 (P<0.0001), IL-18 (P=0.0003), HLA-DRB1*03 (P=0.016) and anti-TPO antibodies (P=0.016) were associated with response >six months. In group 2 high level of B2-MG (P=0.0001), NPT (P=0.0016), IL-6 (P=0.013) and IL-18 (P=0.032) were associated with early disease progression (
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Transcription of eukaryotic genes is regulated by phosphorylation of serine residues of heptapeptide repeats of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII). We previously reported that protein phosphatase-1 (PP1) dephosphorylates RNAPII CTD in vitro and inhibition of nuclear PP1-blocked viral transcription. In this article, we analyzed the targeting of RNAPII by PP1 using biochemical and mass spectrometry analysis of RNAPII-associated regulatory subunits of PP1. Immunoblotting showed that PP1 co-elutes with RNAPII. Mass spectrometry approach showed the presence of U2 snRNP. Co-immunoprecipitation analysis points to NIPP1 and PNUTS as candidate regulatory subunits. Because NIPP1 was previously shown to target PP1 to U2 snRNP, we analyzed the effect of NIPP1 on RNAPII phosphorylation in cultured cells. Expression of mutant NIPP1 promoted RNAPII phosphorylation suggesting that the deregulation of cellular NIPP1/PP1 holoenzyme affects RNAPII phosphorylation and pointing to NIPP1 as a potential regulatory factor in RNAPII-mediated transcription.
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Espectrometría de Masas , Proteína Fosfatasa 1/metabolismo , ARN Polimerasa II/química , ARN Polimerasa II/metabolismo , Dominio Catalítico , Proteínas de Unión al ADN/metabolismo , Células HEK293 , Células HeLa , Humanos , Inmunoprecipitación , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Mutantes/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación , Estructura Terciaria de Proteína , Proteínas de Unión al ARN/metabolismoRESUMEN
Background: Spearman's law of diminishing returns (SLODR) states that intercorrelations between scores on tests of intellectual abilities were higher when the data set was comprised of subjects with lower intellectual abilities and vice versa. After almost a hundred years of research, this trend has only been detected on average. Objective: To determine whether the very different results were obtained due to variations in scaling and the selection of subjects. Design: We used three methods for SLODR detection based on moderated factor analysis (MFCA) to test real data and three sets of simulated data. Of the latter group, the first one simulated a real SLODR effect. The second one simulated the case of a different density of tasks of varying difficulty; it did not have a real SLODR effect. The third one simulated a skewed selection of respondents with different abilities and also did not have a real SLODR effect. We selected the simulation parameters so that the correlation matrix of the simulated data was similar to the matrix created from the real data, and all distributions had similar skewness parameters (about -0.3). Results: The results of MFCA are contradictory and we cannot clearly distinguish by this method the dataset with real SLODR from datasets with similar correlation structure and skewness, but without a real SLODR effect. The results allow us to conclude that when effects like SLODR are very subtle and can be identified only with a large sample, then features of the psychometric scale become very important, because small variations of scale metrics may lead either to masking of real SLODR or to false identification of SLODR.
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Microsecond timescale explicit-solvent atomistic simulations were carried out to investigate how anionic surfactants modulate protein structure and dynamics. We found that lysozyme undergoes near-complete denaturation at the high concentration (> 0.1 M) of sodium pentadecyl sulfonate (SPDS), while only partial denaturation occurs at the concentration slightly below 0.1 M. In large part, protein denaturation is structurally manifested by disappearance of helical segments and loss of tertiary interactions. The computational prediction of the extent of burial of cysteine residues was experimentally validated by measuring the accessibility of the respective sulfhydryl groups. Overall, our work indicates an interesting synergy between electrostatic and hydrophobic contributions to lysozyme's denaturation process by anionic surfactants. In fact, first disulfide bridges and hydrogen bonds from protein surface to SPDS head groups loosen the protein globule followed by fuller denaturation via insertion of the surfactant's hydrophobic tails into the protein core.
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Simulación de Dinámica Molecular , Muramidasa/química , Desnaturalización Proteica , Ácidos Sulfónicos/química , Tensoactivos/químicaRESUMEN
Introduction Work-related musculoskeletal disorders (WMSD) are defined as conditions that the environment contributes significantly to / worsens due to work conditions. WMSD comes second in the source of disability in both developed and developing countries. The aim of this study is to measure the prevalence, patterns, and risk factors of musculoskeletal pain disorders among teachers in the Qassim region, Saudi Arabia. Methods A cross-sectional study was conducted among school teachers in the Qassim region, Saudi Arabia. A validated online Arabic questionnaire was distributed among teachers living in the Qassim region through multiple social networking applications like Facebook, WhatsApp, and Telegram. The questionnaire consisted of Socio-demographic characteristics, the Nordic Musculoskeletal Questionnaire, and a modified version of the Örebro Musculoskeletal Pain Screening questionnaire. Results A total of 503 school teachers were recruited. The proportion of musculoskeletal pain was 91%, and the most common site of pain was back (74.4%), followed by the shoulder (57.5%) and leg (51.5%). The proportion of disabling pain was (80.1%) while the rest was non-disabling pain (19.9%). In the multiple regression model, the predictors of increased disabling pain were back pain, leg pain, neck pain, and those with 51-70 kg weight. In comparison, the predictors of decreased disabling pain were having more than 7 hours of sleep and those with 20-30 classes per week. Conclusion Musculoskeletal pain disorders were widely prevalent among school teachers in the Qassim region, Saudi Arabia. Most teachers considered pain as disabling, which negatively affected their attendance. The back, shoulder, and neck were the most painful sites associated with disabling pain.
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One of the main functions of alpha-2-macroglobulin (A2M) in human blood serum is the binding of all classes of protease. It is known that trypsin, after such interaction, possesses modified proteolytic activity. Trypsin first hydrolyzes two bonds in A2M's 'bait region', and the peptide 705VGFYESDVMGR715 is released from A2M. In this work, specifics of the A2M-trypsin interaction were used to determine A2M concentration directly in human blood serum using MALDI mass-spectrometry. Following exogenous addition of trypsin to human blood serum in vitro, the concentration of the VGFYESDVMGR peptide was measured, using its isotopically-labeled analogue (18O), and A2M concentration was calculated. The optimized mass spectrometric approach was verified using a standard method for A2M concentration determination (ELISA) and the relevant statistical analysis methods. It was also shown that trypsin's modified proteolytic activity in the presence of serum A2M can be used to analyze other serum proteins, including potential biomarkers of pathological processes. Thus, this work describes a promising approach to serum biomarker analysis that can be technically extended in several useful directions.
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Péptidos/sangre , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Tripsina/sangre , Biomarcadores/sangre , Humanos , alfa-MacroglobulinasRESUMEN
BACKGROUND: The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models. In this double blinded randomised controlled trial (identifier: ACTRN12614000755639), we examined whether thiamine would improve CPC function in humans. METHODS AND RESULTS: High dose oral thiamine (one gram twice daily) or matching placebo was administered 3-5 days prior to coronary artery bypass surgery (CABG). Right atrial appendages were collected at the time of CABG, and CPCs isolated. There was no difference in the primary outcome (proliferation ability of CPCs) between treatment groups. Older age was not associated with decreased proliferation ability. In exploratory analyses, isolated CPCs in the thiamine group showed an increase in the proportion of CD34-/CD105+ (endoglin) cells, but no difference in CD34-/CD90+ or CD34+ cells. Thiamine increased maximum force developed by isolated trabeculae, with no difference in relaxation time or beta-adrenergic responsiveness. CONCLUSION: Thiamine does not improve proliferation ability of CPC in patients undergoing CABG, but increases the proportion of CD34-/CD105+ cells. Having not met its primary endpoint, this study provides the impetus to re-examine CPC biology prior to any clinical outcome-based trial examining potential beneficial cardiovascular effects of thiamine.
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Células Madre , Tiamina , Anciano , Endoglina , Atrios Cardíacos , Humanos , Transducción de SeñalRESUMEN
CONTEXT: Providing patient care at the end of a patient's life is a humbling and sacred experience for both patient and provider. Without a truthful and meaningful conversation about end-of-life care preferences, the care that is delivered may not be the care that the patient prefers. OBJECTIVES: Determine if there is a relationship between level of training, confidence, and presence of decisional conflict in making an accurate prognosis for 2 standardized cases. Additionally, we evaluated the correctness of the prognosis as measured against survival outcomes for patients with similar diagnoses. METHODS: Decisional conflict was measured with the SURE tool, a validated 4-item tool that has been used in assessing for the presence of decisional conflict. RESULTS: Following analysis of data, it was found that providers with no decisional conflict were much more likely to be attendings with more than 5 years' experience. Providers were more conflicted overall when confronted with a case with a more grave prognosis. It was determined that providers with a lower level of training were more likely to have decisional conflict. CONCLUSIONS: Provider confidence increases and decisional conflict decreases as one increases their level of training. However, the degree in which the provider is correct in their prognosis does not change as one increases their level of training. These findings have broad implications on patients, providers, and the health-care system.