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1.
Brain Inj ; : 1-4, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066895

RESUMEN

Moyamoya disease (MMD) is a rare progressive condition of unknown etiology that affects the blood vessels in the brain and is characterized by narrowing or stenosis of the distal parts of the internal carotid and major intracranial arteries, leading to the development of fragile collateral supplies. This makes it a significant causative factor for both ischemic strokes as well as intracerebral hemorrhages. As per the recommendations by the Research Committee on Moyamoya disease in 2021, the diagnostic criteria for MMD are essentially based on indicative radiological findings on cerebral angiography or MRI Brain and MRA, after excluding possible differentials. In this case report, we present the case of a 45-year-old Asian lady who presented with sudden-onset headaches and right-sided weakness. Her admission non-contrast CT brain scan was undiagnostic. MRI brain and MRA scans revealed bilateral anterior circulation watershed infarcts of variable age along with supra-clinoid stenosis. She was initially treated with steroids for vasculitis after discussions with a multidisciplinary team involving neurologists, stroke physicians and neuro-radiologists; however, further imaging revealed a diagnosis of MMD, and she was subsequently referred for revascularization surgery. Given the limited number of similarly documented cases, we hope this report will contribute to the knowledge base.

2.
Appl Physiol Nutr Metab ; 49(7): 1002-1007, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38507778

RESUMEN

Interval walking training (IWT) is a free-living training intervention involving alternating fast and slow walking cycles. IWT is efficacious in improving physical fitness and muscle strength, and reducing factors associated with lifestyle-related diseases. In individuals with type 2 diabetes, IWT improves glycemic control directly through enhanced glucose effectiveness, challenging conventional views on mechanisms behind training-induced improvements in glycemic control. Whereas adherence to IWT in short-term studies is high, ensuring long-term adherence remains a challenge, particularly in populations with chronic diseases and/or overweight/obesity. Long-term studies in real-world settings are imperative to ascertain the widespread effectiveness of IWT and elucidate its impact on hard endpoints.


Asunto(s)
Diabetes Mellitus Tipo 2 , Caminata , Humanos , Caminata/fisiología , Diabetes Mellitus Tipo 2/terapia , Fuerza Muscular/fisiología , Aptitud Física/fisiología , Entrenamiento de Intervalos de Alta Intensidad/métodos
3.
AEM Educ Train ; 8(1)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38235393

RESUMEN

Objective: The study objective was to determine the effect of a rapid cycle deliberate practice (RCDP) program on simulated and actual airway skills by pediatric emergency medicine (PEM) fellows. Methods: We designed and implemented a 12-month RCDP airway skills curriculum for PEM fellows at an academic pediatric institution. The curriculum was designed using airway training literature, RCDP principals, and internal quality assurance airway video review program. Simulation training scenarios increased in complexity throughout the curriculum. PEM fellows participated in monthly sessions. Two PEM faculty facilitated the sessions, utilizing a step-by-step objective structured clinical evaluation (OSCE)-style tool for each scenario. Data were collected for all four levels of the Kirkpatrick Model of Training Evaluation-participant response (reaction, pre-post session survey), skills performance in the simulation setting (learning, pre-post OSCE), skills performance for actual patients (behavior, video review), and patient outcomes (results, video review). Results: During the study period (August 2021 to June 2022), 13 PEM fellows participated in 112 sessions (mean nine sessions per fellow). PEM fellows reported improved comfort in all domains of airway management, including intubation performance. Participant OSCE scores improved posttraining (pretraining median score for trainees 57 [IQR 57-59], posttraining median 61 [IQR 61-62], p = 0.0005). Over the 12 months, PEM fellows performed 45 intubation attempts in the pediatric emergency department (median patient age 4 years [IQR 1-9 years]). Compared to a 5-year historical cohort, participants had higher first-pass success (87% vs. 71%, p = 0.028) and shorter attempt duration (22 s vs. 29 s, p = 0.018). There was no significant difference in the frequency of oxyhemoglobin desaturation in the training period versus the historical period (7% vs. 15%, p = 0.231). Conclusions: At multiple levels of educational outcomes, including participant behavior and patient outcomes, an RCDP program was associated with improved airway skills and performance of PEM fellows.

4.
J Orthop Trauma ; 38(1): e20-e27, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37853554

RESUMEN

OBJECTIVES: To determine whether a nonoperative management protocol results in equivalent outcomes in isolated OTA/AO 44B (Weber B) fractures without initial medial clear space (MCS) widening regardless of stress radiography findings. DESIGN: Prospective cohort. SETTING: Level 1 academic trauma center. PATIENT SELECTION CRITERIA: Nonoperatively managed patients with isolated OTA/AO 44B fractures and MCS ≤4 mm on initial non-weightbearing injury radiographs between from January 2018 and January 2022 were included. All patients underwent emergency department gravity stress radiographs and those with widening were considered the widening cohort and those without the non-widening cohort. OUTCOME MEASURE AND COMPARISONS: MCS measurements on weightbearing radiographs were obtained at first follow-up, 6 weeks, 12 weeks, and 6 months postinjury, were considered indicative of instability if >4 mm and were compared between cohorts.; American Orthopaedic Foot and Ankle Society ankle-hindfoot scores were also compared between cohorts. RESULTS: Sixty-nine patients were studied. None of the 38 patients (55%) with widening on gravity stress radiographs demonstrated widening with weightbearing radiographs at any time point. Mean MCS measurement differences between the 2 cohorts were statistically significant for all time points ( P = 0.012); however, with a model adjusted mean MCS value of 2.7 mm for the nonwidening cohort and 2.9 mm for the widening cohort, these are not clinically significant. There was no statistically significant difference in overall final American Orthopaedic Foot and Ankle Society scores between the 2 groups ( P = 0.451). In addition, statistical equivalence using Schuirmann 2 one-sided tests was achieved between the 2 groups. Both cohorts had mean American Orthopaedic Foot and Ankle Society scores representing excellent outcomes at the final follow-up. CONCLUSIONS: Patients with isolated OTA/AO 44B fractures without MCS widening on initial injury radiographs did not demonstrate instability on subsequent weightbearing radiographs and had equivalent outcomes regardless of gravity stress radiography findings when treated nonoperatively. Weightbearing radiographs at the initial follow-up appear to be a reliable assessment of ankle stability in these injuries and are an appropriate alternative to painful and time-consuming stress radiography. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Fracturas de Tobillo , Fracturas Óseas , Humanos , Peroné/lesiones , Estudios Prospectivos , Fracturas Óseas/cirugía , Radiografía , Soporte de Peso , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/terapia
5.
Ann Emerg Med ; 81(6): 658-666, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36797132

RESUMEN

STUDY OBJECTIVE: Our study objective was to determine if the location of laryngoscope blade tip placement is associated with clinically important tracheal intubation outcomes in a pediatric emergency department. METHODS: We conducted a video-based observational study of pediatric emergency department patients undergoing tracheal intubation with standard geometry Macintosh and Miller video laryngoscope blades (Storz C-MAC, Karl Storz). Our main exposures were direct lifting of the epiglottis versus blade tip placement within the vallecula and median glossoepiglottic fold engagement versus not when the blade tip was placed in the vallecula. Our main outcomes were glottic visualization and procedural success. We compared measures of glottic visualization between successful and unsuccessful attempts using generalized linear mixed models. RESULTS: Proceduralists placed the blade tip in the vallecula (indirectly lifting the epiglottis) during 123 (71.9%) of 171 attempts. When compared with indirectly lifting the epiglottis, directly lifting the epiglottis was associated with improved visualization-by percentage of glottic opening (POGO) (adjusted odds ratio [AOR], 11.0; 95% confidence interval [CI], 5.1 to 23.6) and modified Cormack-Lehane (AOR, 21.5; 95% CI, 6.6 to 69.9). When in the vallecula, engagement of the median glossoepiglottic fold was associated with improved POGO (AOR, 3.6; 95% CI, 1.9 to 6.8), modified Cormack-Lehane (AOR, 3.9; 95% CI, 1.1 to 14.1), and success (AOR, 9.9; 95% CI, 2.3 to 43.7). CONCLUSIONS: Emergency tracheal intubation can be performed in children at a high level by directly or indirectly lifting the epiglottis. If indirectly lifting the epiglottis, median glossoepiglottic fold engagement is helpful in maximizing glottic visualization and procedural success.


Asunto(s)
Laringoscopios , Laringe , Humanos , Niño , Laringoscopía , Intubación Intratraqueal , Glotis
7.
Ann Emerg Med ; 81(2): 113-122, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36253297

RESUMEN

STUDY OBJECTIVE: To explore the association between video-assisted laryngoscopy (use of a videolaryngoscope regardless of where laryngoscopists direct their gaze), first-attempt success, and adverse airway outcomes. METHODS: We conducted an observational study using data from 2 airway consortiums that perform prospective surveillance: the National Emergency Airway Registry for Children (NEAR4KIDS) and a pediatric emergency medicine airway education collaborative. Data collected included patient and procedural characteristics and procedural outcomes. We performed multivariable analyses of the association of video-assisted laryngoscopy with individual patient outcomes and evaluated the association between site-level video-assisted laryngoscopy use and tracheal intubation outcomes. RESULTS: The study cohort included 1,412 tracheal intubation encounters performed from January 2017 to March 2021 across 11 participating sites. Overall, the first-attempt success was 70.0%. Video-assisted laryngoscopy was associated with increased odds of first-attempt success (odds ratio [OR] 2.01; 95% confidence interval [CI], 1.48 to 2.73) and decreased odds of severe adverse airway outcomes (OR 0.70; 95% CI, 0.58 to 0.85) including decreased severe hypoxia (OR 0.69; 95% CI, 0.55 to 0.87). Sites varied substantially in the use of video-assisted laryngoscopy (range from 12.9% to 97.8%), and sites with high use of video-assisted laryngoscopy (> 80%) experienced increased first-attempt success even after adjusting for individual patient laryngoscope use (OR 2.30; 95% CI, 1.79 to 2.95). CONCLUSION: Video-assisted laryngoscopy is associated with increased first-attempt success and fewer adverse airway outcomes for patients intubated in the pediatric emergency department. There is wide variability in the use of video-assisted laryngoscopy, and the high use is associated with increased odds of first-attempt success.


Asunto(s)
Laringoscopios , Laringoscopía , Humanos , Niño , Estudios Prospectivos , Intubación Intratraqueal , Servicio de Urgencia en Hospital , Grabación en Video
8.
AEM Educ Train ; 6(6): e10830, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36562026

RESUMEN

Background: Decisions about who should perform tracheal intubation in academic settings must balance the needs of trainees to develop competency in pediatric intubation with patient safety. Airway protocols during the COVID-19 pandemic may have reduced opportunities for trainees, representing an opportunity to examine the impact of shifting laryngoscopy responsibilities away from trainees. Methods: This observational study combined data from 11 pediatric emergency departments in North America participating in either the National Emergency Airway Registry for Children (NEAR4KIDS) or a national pediatric emergency medicine airway education collaborative. Sites provided information on airway protocols, patient and procedural characteristics, and clinical outcomes. For the pre-pandemic (January 2017 to March 2020) and pandemic (March 2020 to March 2021) periods, we compared tracheal intubation opportunities by laryngoscopist level of training and specialty. We also compared first-attempt success and adverse airway outcomes between the two periods. Results: There were 1129 intubations performed pre-pandemic and 283 during the pandemic. Ten of 11 sites reported a COVID-19 airway protocol-8 specified which clinician performs tracheal intubation and 10 advocated for videolaryngoscopy. Both pediatric residents and pediatric emergency medicine fellows performed proportionally fewer tracheal intubation attempts during the pandemic: 1.1% of all first attempts versus 6.4% pre-pandemic for residents (p < 0.01) and 38.4% versus 47.2% pre-pandemic for fellows (p = 0.01). Pediatric emergency medicine fellows had greater decrease in monthly intubation opportunities for patients <1 year (incidence rate ratio = 0.35, 95% CI: 0.2, 0.57) than for older patients (incidence rate ratio = 0.79, 95% CI: 0.62, 0.99). Neither the rate of first-attempt success nor adverse airway outcomes differed between pre-pandemic and pandemic periods. Conclusions: The COVID-19 pandemic led to pediatric institutional changes in airway management protocols and resulted in decreased intubation opportunities for pediatric residents and pediatric emergency medicine fellows, without apparent change in clinical outcomes.

9.
Arch Bone Jt Surg ; 10(10): 818-826, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36452420

RESUMEN

Medial knee injuries are prevalent, especially in young athletes. A detailed history and physical examination are needed to accurately diagnose injuries to the superficial medial collateral ligament (sMCL), deep medial collateral ligament (dMCL), and posterior oblique ligament (POL). The mechanism of medial knee injury often involves a coupled valgus and external rotation force with pain and tenderness across the medial joint line. Valgus stress radiographs assist with the diagnosis of medial knee injuries based on the quantitative extent of medial joint gapping. Specifically, 3.2 mm of increased medial gapping is observed with an isolated grade-III sMCL injury and greater than 9.8 mm of gapping indicates a complete medial knee injury. Nonoperative treatment is recommended for grade-I and II medial knee injuries. Patients with chronic medial knee instability, or a complete tear of the medial knee structures, may require operative treatment. Anatomic surgical techniques have proven to be highly effective in restoring functional knee stability.

10.
BMJ Case Rep ; 14(10)2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34697088

RESUMEN

Ganglion cysts of the psoas tendon are uncommon and rarely reported in the literature. Often they remain asymptomatic and are found incidentally or can be a cause of atypical groin/hip pain. We present a rare case of ganglion cyst in a child arising from the psoas tendon, causing symptomatic hip pain, which failed non-surgical treatment and eventually successfully treated with surgical excision.


Asunto(s)
Ganglión , Quiste Sinovial , Artralgia , Niño , Ganglión/complicaciones , Ganglión/diagnóstico por imagen , Ganglión/cirugía , Humanos , Dolor/etiología , Tendones
11.
Food Res Int ; 141: 110126, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33641993

RESUMEN

Cold atmospheric plasma (CAP) is a minimal food processing technology of increasing interest in the food industry, as it is mild in nature compared to traditional methods (e.g. pasteurisation) and thus can maintain the food's desirable qualities. However, due to this mild nature, the potential exists for post-treatment microbial survival and/or stress adaptation. Furthermore, biofilm inactivation by CAP is underexplored and mostly studied on specific foods or on plastic/polymer surfaces. Co-culture effects, biofilm age, and innate biofilm-associated resistance could all impact CAP efficacy, while studies on real foods are limited to the food product investigated without accounting for structural complexity. The effect of a Remote and Enclosed CAP device (Fourth State Medicine Ltd) was investigated on Escherichia coli and Listeria innocua grown as planktonic cells and as single or mixed bacterial biofilms of variable age, on a biphasic viscoelastic food model of controlled rheological and structural complexity. Post-CAP viability was assessed by plate counts, cell sublethal injury was quantified using flow cytometry, and biofilms were characterised and assessed using total protein content and microscopy techniques. A greater impact of CAP on planktonic cells was observed at higher air flow rates, where the ReCAP device operates in a mode more favourable to reactive oxygen species than reactive nitrogen species. Although planktonic E. coli was more susceptible to CAP than planktonic L. innocua, the opposite was observed in biofilm form. The efficacy of CAP was reduced with increasing biofilm age. Furthermore, E. coli produced much higher protein content in both single and mixed biofilms than L. innocua. Consequently, greater survival of L. innocua in mixed biofilms was attributed to a protective effect from E. coli. These results show that biofilm susceptibility to CAP is age and bacteria dependent, and that in mixed biofilms bacteria may become less susceptible to CAP. These findings are of significance to the food industry for the development of effective food decontamination methods using CAP.


Asunto(s)
Gases em Plasma , Bacterias , Biopelículas , Escherichia coli , Microbiología de Alimentos , Listeria , Gases em Plasma/farmacología
12.
Biol Reprod ; 103(4): 880-891, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32678429

RESUMEN

Spermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell's ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood-testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT's role in Sertoli cells and its contribution to the structural integrity of the BTB.


Asunto(s)
Barrera Hematotesticular/fisiología , Proteínas de Ciclo Celular/metabolismo , Chaperonas Moleculares/metabolismo , Células de Sertoli/metabolismo , Animales , Adhesión Celular , Proteínas de Ciclo Celular/genética , Regulación hacia Abajo , Eliminación de Gen , Regulación de la Expresión Génica , Células Germinativas/fisiología , Masculino , Ratones , Chaperonas Moleculares/genética , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo
13.
J Surg Educ ; 76(6): 1640-1644, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31447182

RESUMEN

BACKGROUND: The Accreditation Council for Graduate Medical Education and the American Board of Orthopaedic Surgery have implemented "milestones" to evaluate residents during their progression in medical education. The purpose of this study was to determine whether a validated evaluation tool correlates with surgical experience, year in training, and progression over time. DESIGN: This was a retrospective study of already collected curriculum assessment data where 2 unbiased, blinded orthopedic surgeons evaluated resident performance on basic diagnostic knee arthroscopy using the Arthroscopic Surgical Skills Evaluation Tool (ASSET) over 3 years. Residents also gained arthroscopy experience through a structured arthroscopy curriculum and clinical experience. SETTING: The study was conducted at the TRIA Orthopaedic Center (Bloomington, Minnesota, USA), an institutional site for The University of Minnesota orthopedic surgery residency program. PARTICIPANTS: Eleven orthopedic surgery residents at postgraduate years 2 to 5 were evaluated using the ASSET. RESULTS: The Pearson's Correlation Coefficient was used to validate both the number of arthroscopic procedures performed by residents (r = 0.946) and their level in training (r = 0.89). Residents who were re-evaluated after undergoing the arthroscopy curriculum throughout the year displayed significant increases in total ASSET scores (p < 0.01). CONCLUSION: Resident performance on the ASSET correlated with arthroscopic experience based on year-in training. More importantly, performance improved with additional years of training, demonstrating validity over time. The data also demonstrates interobserver reliability. Due to these correlations between exposure to surgery and score on the ASSET, we believe the tool could serve as a suitable means for assessing residents' technical proficiency as required by The Accreditation Council for Graduate Medical Education program guidelines.


Asunto(s)
Artroscopía/educación , Competencia Clínica , Evaluación Educacional/métodos , Ortopedia/educación , Correlación de Datos , Curriculum , Estudios Retrospectivos
14.
Artículo en Inglés | MEDLINE | ID: mdl-30774413

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. PATIENTS AND METHODS: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. RESULTS: AKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). CONCLUSION: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management.

15.
Oncotarget ; 10(7): 707-716, 2019 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-30774773

RESUMEN

Ubiquitously-expressed, prefoldin-like chaperone (UXT) also called Androgen Receptor Trapped clone-27 (ART-27) is widely expressed in human tissues. Our previous studies showed that UXT regulates transcription repression including androgen receptor (AR) signaling in prostate cancer. Here we analyzed a tissue microarray consisting of normal prostate, benign prostatic hyperplasia, high grade prostatic intraepithelial neoplasia (HGPIN) and primary prostate cancer cases for UXT protein expression. We found that HGPIN and malignant tumors have significantly decreased UXT expression compared to the normal prostate. Loss of UXT expression in primary prostate cancer is positively associated with high Gleason grade and poor relapse-free survival. We engineered prostate-specific Uxt KO mice that developed a hyperplastic phenotype with apparent prostate secretion fluid blockage as well as PIN by 4-6 months. Doubly mutant Uxt KO /Pten KO mice developed a more aggressive PIN phenotype. UXT depletion in prostate cancer cells also increased retroelements expression, including LINE-1 and Alu. Consistent with this finding Uxt KO mice have increased LINE-1 protein levels in the prostate compared to control mice. In addition, cancer cells with UXT depletion have increased retrotransposition activity and accumulated DNA damage. Our findings demonstrate that loss of UXT is an early event during prostate cancer progression, which may contribute to genome instability.

16.
Adv Exp Med Biol ; 1106: 85-94, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30484154

RESUMEN

The Unconventional prefoldin RPB5 interacting protein (URI), also known as RPB5-Mediating Protein (RMP) has been shown to play several regulatory roles in different cellular compartments including the mitochondria, as a phosphatase binding protein; in the cytoplasm, as a chaperone-like protein; and in the nucleus, as a transcriptional regulator through binding to RPB5 and RNA polymerase II (polII). This chapter focuses on the role URI plays in transcriptional regulation in the prostate cell. In prostate cells, URI is tightly bound to another prefoldin-like protein called UXT, a known androgen receptor (AR) cofactor. Part of a multiprotein complex, URI and UXT act as transcriptional repressors, and URI regulates KAP1 through PP2A phosphatase activity. The discovery of the interaction of URI and UXT with KAP1, AR, and PP2A, as well as the numerous interactions between URI and components of the R2TP/prefoldin-like complex, RPB5, and nuclear proteins involved in DNA damage response, chromatin remodeling and gene transcription, reveal a pleiotropic effect of the URI/UXT complex on nuclear processes. The mechanisms by which URI/UXT affect transcription, chromatin structure and regulation, and genome stability, remain to be elucidated but will be of fundamental importance considering the many processes affected by alterations of URI/UXT and other prefoldins and prefoldin-like proteins.


Asunto(s)
ARN Polimerasas Dirigidas por ADN/química , Regulación de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/química , Chaperonas Moleculares/química , Proteínas de Neoplasias/química , Proteínas de Ciclo Celular , Humanos , Masculino , Próstata , Proteínas Represoras
17.
J Chem Phys ; 149(6): 064108, 2018 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-30111157

RESUMEN

We use a direct product basis, basis vectors computed by evaluating matrix-vector products, and rank reduction to calculate vibrational energy levels of uracil and naphthalene, with 12 and 18 atoms, respectively. A matrix representing the Hamiltonian in the direct product basis and vectors with as many components as there are direct product basis functions are neither calculated nor stored. We also introduce an improvement of the Hierarchical Intertwined Reduced-Rank Block Power Method (HI-RRBPM), proposed previously in Thomas and Carrington, Jr. [J. Chem. Phys. 146, 204110 (2017)]. It decreases the memory cost of the HI-RRBPM and enables one to compute vibrational spectra of molecules with over a dozen atoms with a typical desktop computer.

18.
PLoS One ; 13(4): e0195747, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29649254

RESUMEN

Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Constitutive deletion of Uxt is embryonic lethal, while conditional knockout in the male germline results in a Sertoli cell-only phenotype during the first wave of spermatogenesis that does not recover in the adult. This phenotype begins to manifest between 6 and 7 days post-partum, just before meiotic entry. Gene expression analysis revealed that Uxt deletion downregulates the transcription of genes governing SSC self-renewal, differentiation, and meiosis, consistent with its previously defined role as a transcriptional co-factor. Our study has revealed the first in vivo function for UXT in the mammalian germline as a regulator of distinct transcriptional programs in SSCs and differentiating spermatogonia.


Asunto(s)
Chaperonas Moleculares/genética , Espermatogénesis/genética , Animales , Caspasa 3/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular , Diferenciación Celular/genética , Eliminación de Gen , Genes Letales , Inmunohistoquímica , Aprendizaje Automático , Masculino , Meiosis/genética , Ratones , Ratones Noqueados , Chaperonas Moleculares/metabolismo , Fenotipo , Espermatogonias/metabolismo , Testículo/metabolismo , Testículo/patología
19.
BMC Nephrol ; 19(1): 34, 2018 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-29426301

RESUMEN

BACKGROUND: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery. METHODS: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed. RESULTS: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7%, Met/Met 29.3%, Val/Val 21.3%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5%) of the total cohort, and no differences were evident between the COMT genotypes (20.5% Met/Met, 24.7% Val/Met, 25.0% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay. CONCLUSIONS: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.


Asunto(s)
Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/genética , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Catecol O-Metiltransferasa/genética , Polimorfismo de Nucleótido Simple/genética , Lesión Renal Aguda/diagnóstico , Anciano , Procedimientos Quirúrgicos Cardíacos/tendencias , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/genética , Estudios Prospectivos
20.
Open Heart ; 4(2): e000562, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28761676

RESUMEN

BACKGROUND: Coronary artery disease (CAD) is associated with an increased prothrombotic tendency and is also linked to unfavourably altered clot microstructure. We have previously described a biomarker of clot microstructure (df) that is unfavourably altered in acute myocardial infarction. The df biomarker assesses whether the blood will form denser or looser microstructures when it clots. In this study we assessed in patients with stable chest pain whether df can differentiate between obstructed and unobstructed CAD. METHODS: A blood sample prior to angiography was obtained from 251 consecutive patients undergoing diagnostic coronary angiography. Patients were categorised based on angiographic findings as presence or absence of obstructive CAD (stenosis ≥50%). The blood sample was assessed using the df biomarker, standard laboratory markers and platelet aggregometry (Multiplate). RESULTS: A significant difference (p=0.028) in df was observed between obstructive CAD (1.748±0.057, n=83) and unobstructive CAD (1.732±0.052, n=168), where patients with significant CAD produce denser, more tightly packed clots. df was also raised in men with obstructive CAD compared with women (1.745±0.055 vs 1.723±0.052, p=0.007). Additionally df significantly correlated with the platelets response to arachidonic acid as measured by the ASPItest area under the curve readings from platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of the ASPItest indicating effective aspirin use was associated with looser, less dense clots. CONCLUSIONS: For the first time, we characterise clot microstructure, as measured by df, in patients with stable CAD. df can potentially be used to risk-stratify patients with stable CAD and assess the efficacy of therapeutic interventions by measuring changes in clot microstructure.

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