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Odontocetes produce clicks for echolocation and communication. Most odontocetes are thought to produce either broadband (BB) or narrowband high-frequency (NBHF) clicks. Here, we show that the click repertoire of Hector's dolphin (Cephalorhynchus hectori) comprises highly stereotypical NBHF clicks and far more variable broadband clicks, with some that are intermediate between these two categories. Both NBHF and broadband clicks were made in trains, buzzes, and burst-pulses. Most clicks within click trains were typical NBHF clicks, which had a median centroid frequency of 130.3 kHz (median -10 dB bandwidth = 29.8 kHz). Some, however, while having only marginally lower centroid frequency (median = 123.8 kHz), had significant energy below 100 kHz and approximately double the bandwidth (median -10 dB bandwidth = 69.8 kHz); we refer to these as broadband. Broadband clicks in buzzes and burst-pulses had lower median centroid frequencies (120.7 and 121.8 kHz, respectively) compared to NBHF buzzes and burst-pulses (129.5 and 130.3 kHz, respectively). Source levels of NBHF clicks, estimated by using a drone to measure ranges from a single hydrophone and by computing time-of-arrival differences at a vertical hydrophone array, ranged from 116 to 171 dB re 1 µPa at 1 m, whereas source levels of broadband clicks, obtained from array data only, ranged from 138 to 184 dB re 1 µPa at 1 m. Our findings challenge the grouping of toothed whales as either NBHF or broadband species.
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Delfines , Ecolocación , Animales , Acústica , Vocalización Animal , Espectrografía del SonidoRESUMEN
Considering procurement process performance assessment, measurement systems such as balance scorecard and capability maturity models are used to assess procurement performance to give a reasonable indication of actual performance. These tools are ideal for practical applications that depend on other performance criteria but are short of comparing planned to actual timelines set for procurement processes. This fosters persistent delays in public procurement. Six Sigma implementation benefits including addressing process delays have fostered its implementation for service improvements. Unfortunately, Six Sigma implementation in public procurement is very rare largely due to its expensive nature. The objective of this study is to develop a Procurement Delay Index (PDindex): a performance measure in the context of a Six Sigma methodology that provides a specific value to describe the delays in the procurement process. To enhance uniformity in performance measurement of process timeliness, a rating scale for determining the timeliness of the procurement process is proposed. A practical demonstration of the application of PDindex for use by procurement professionals is also presented. PDindex serves as a standard by which to determine procurement processes' timeliness and is less expensive to implement. A PDindex of 3σ has been recommended as the acceptable limit for procurement process delays.
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Artemisinin (ART) combination therapies have been critical in reducing malaria morbidity and mortality, but these important drugs are threatened by growing resistance associated with mutations in Pfcoronin and Pfkelch13 . Here, we describe the mechanism of Pfcoronin -mediated ART resistance. Pf Coronin interacts with Pf Actin and localizes to the parasite plasma membrane (PPM), the digestive vacuole (DV) membrane, and membrane of a newly identified preDV compartment-all structures involved in the trafficking of hemoglobin from the RBC for degradation in the DV. Pfcoronin mutations alter Pf Actin homeostasis and impair the development and morphology of the preDV. Ultimately, these changes are associated with decreased uptake of red blood cell cytosolic contents by ring-stage Plasmodium falciparum . Previous work has identified decreased hemoglobin uptake as the mechanism of Pfkelch 13-mediated ART resistance. This work demonstrates that Pf Coronin appears to act via a parallel pathway. For both Pfkelch13 -mediated and Pfcoronin -mediated ART resistance, we hypothesize that the decreased hemoglobin uptake in ring stage parasites results in less heme-based activation of the artemisinin endoperoxide ring and reduced cytocidal activity. This study deepens our understanding of ART resistance, as well as hemoglobin uptake and development of the DV in early-stage parasites.
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A patient's preoperative satisfaction with their breasts and baseline psychosocial, sexual, and physical well-being are important considerations when planning breast reconstruction. We sought to elucidate variances in preoperative responses among patients undergoing postmastectomy breast reconstruction. Methods: Preoperative BREAST-Q responses and demographic data, including race, generation, median household incomeinstitutional review board and body mass index (BMI) were collected from breast cancer patients scheduled for mastectomy. Associations between demographic group and survey response were analyzed by chi-square or independent t-tests. Results: In total, 646 of 826 patients identified had complete data and were included in the final analysis. Patients in BMI group 1 (16-24.9) were more likely to report feeling "very satisfied" with how they looked unclothed compared with patients in other BMI groups (P = 0.031). Conversely, patients in groups 3 and 4 (35+), reported lower satisfaction (P = 0.037) and felt less attractive without clothes (P = 0.034). Asian women were less likely to feel attractive (P = 0.007), and Black patients were less likely to feel of equal worth to other women (P < 0.001). Finally, patients were less likely to report confidence in social settings if they were Black (P < 0.001), Asian (P < 0.001), from the millennial generation (P = 0.017), or living in zip codes with median household income less than $55,000 (P = 0.042). Conclusions: Breast cancer patients' feelings toward their natural breasts vary widely between demographic groups. Understanding baseline psychosocial factors in this population is key to informing preoperative discussions and interpreting postoperative satisfaction.
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In derived bony vertebrates, activation of the melanocortin-2 receptor (Mc2r) by its ACTH ligand requires chaperoning by the Mc2r accessory protein (Mrap1). The N-terminal domain of the non-mammalian tetrapod MRAP1 from chicken (c; Gallus gallus) has the putative activation motif, W18D19Y20I21, and the N-terminal domain in the neopterygian ray-finned fish Mrap1 from bowfin (bf; Amia calva) has the putative activation motif, Y18D19Y20I21. The current study used an alanine-substitution paradigm to test the hypothesis that only the Y20 position in the Mrap1 ortholog of these non-mammalian vertebrates is required for activation of the respective Mc2r ortholog. Instead, we found that for cMRAP1, single alanine-substitution resulted in a gradient of inhibition of activation (Y20 >> D19 = W18 > I21). For bfMrap1, single alanine-substitution also resulted in a gradient of inhibition of activation (Y20 >> D19 > I21 > Y18). This study also included an analysis of Mc2r activation in an older lineage of ray-finned fish, the paddlefish (p), Polyodon spathula (subclass Chondronstei). Currently no mrap1 gene has been found in the paddlefish genome. When pmc2r was expressed alone in our CHO cell/cAMP reporter gene assay, no activation was observed following stimulation with ACTH. However, when pmc2r was co-expressed with either cmrap1 or bfmrap1 robust dose response curves were generated. These results indicate that the formation of an Mc2r/Mrap1 heterodimer emerged early in the radiation of the bony vertebrates.
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Hormona Adrenocorticotrópica , Receptor de Melanocortina Tipo 2 , Cricetinae , Animales , Filogenia , Hormona Adrenocorticotrópica/metabolismo , Receptor de Melanocortina Tipo 2/genética , Receptor de Melanocortina Tipo 2/metabolismo , Peces/genética , Peces/metabolismo , Cricetulus , AlaninaRESUMEN
BACKGROUND: Minority patients and those from low socioeconomic backgrounds are faced with barriers to care regarding breast reconstruction. With this study, we seek to elucidate variances in demographics to determine predictors of complications in implant-based breast reconstruction. METHODS: Patients who underwent breast reconstruction with either direct to implant or immediate expander reconstruction by 1 surgeon were identified using the preoperative Breast-Q.Current income statistics available from the US Census Bureau by self-reported zip code were used to determine the median household income (MHI) to stratify differing socioeconomic backgrounds. Demographics were compared with body mass index, comorbidities, overall rate of postoperative complications, rate of implant infection, and type of reconstruction. RESULTS: Two hundred ninety-five patients met inclusion criteria. Overall rate of complications and rate of breast implant infection was higher for MHI of less than $50,000 compared with greater than $50,000 (P = 0.043 overall complications 40.20% vs 28.8%) (P = 0.04 implant infection 14.4% vs 7.1%). African American patients had higher body mass index (P = <0.001), rates of HTN (P = <0.001), and diabetes (P = 0.001), and were more likely to have a lower income (P = <0.001). There was, however, no difference in overall complications (P = 0.26), implant infection rate (P = 0.994), or capsular contracture (0.367) based on race. There was no difference in rate of comorbidities between low and high socioeconomic areas. CONCLUSION: This cohort demonstrates a higher rate of overall complications and infection in patients with a lower MHI and no difference based on race despite having higher risk factors for complications.Socioeconomic status is a multifaceted barrier to care that must be addressed in the perioperative period to decrease breast implant associated complications.
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Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Mamoplastia , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Neoplasias de la Mama/complicaciones , Femenino , Humanos , Mamoplastia/efectos adversos , Mastectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Clase Social , Dispositivos de Expansión Tisular/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: Induction of labour has become more common over the last decade, together with an increase in the number of systematic reviews of the subject. However, with multiple systematic reviews it is necessary to evaluate the methodological rigor to ensure the reliability of conclusions and recommendations for clinical practice. Therefore, the aim of this study was to appraise the quality of systematic reviews that examined the efficacy and/or safety of labour induction methods. METHODS: An electronic search of MEDLINE, Embase, and the Cochrane Library from 2000 to 2020 was conducted. Study selection, data extraction and quality assessment were conducted using A Measurement Tool to Assess Systematic Reviews (AMSTAR) by two independent reviewers, in duplicate. RESULTS: The search identified 387 publications, of which 48 studies (13%) met the a priori inclusion criteria. No significant relationships were found between study quality and number of citations, journal impact factor, or publication year. CONCLUSION: Methodological quality for systematic reviews on the induction of labour were ranked as moderate with no significant changes in quality over the past 2 decades. Publication characteristics are not significantly associated with methodological quality, indicating that healthcare professionals should critically appraise studies before applying them to practice.
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Trabajo de Parto Inducido , Revisiones Sistemáticas como Asunto , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Bystanders play a significant role in the immediate management of life-threatening hemorrhage. The Stop the Bleed (STB) program was designed to train lay rescuers (LRs) to identify and control life-threatening bleeding. The aim of this study was to evaluate the efficacy of STB training for rescuers from different backgrounds. We hypothesized that STB training would be appropriate to increase skills and knowledge of bleeding control techniques for all providers, regardless of level of medical training. STUDY DESIGN: Course participants anonymously self-reported confidence in six major areas. A five-point Likert scale was used to quantitate participant's self-reported performance. Results were stratified into medical rescuers (MR) and LRs. Students' ability to perform STB skills were objectively assessed using an internally validated 15-point objective assessment tool. Data were pooled and analyzed using Student's t-test and chi-Squared test with P < 0.05 considered significant. Results are presented as average with standard deviation (SD) unless otherwise stated. RESULTS: A total of 1974 participants were included in the study. Precourse confidence was lowest for both groups in management of active severe bleeding and ability to pack a bleeding wound. Postcourse confidence improved significantly for both groups in all 6 core areas measured (P < 0.001). The most significant increases were reported in the two previous areas of lowest precourse confidence-management of active severe bleeding-LRs 2.0 (SD 1.2) versus 4.2 (SD 0.9) and MRs 2.6 (SD 1.4) versus 4.6 (SD 0.6), P < 0.001-and ability to pack a bleeding wound-LR 2.1 (SD 1.3) versus 4.4 (SD 0.8) and MR 2.7 (SD 1.3) versus 4.7 (SD 0.05), P < 0.001. Objective assessment of LR skills at the end of the course demonstrated combined 99.3% proficiency on postcourse objective assessments. CONCLUSIONS: This study provides quantitative evidence that Stop the Bleed training is effective, with both LRs and MRs demonstrating improved confidence and skill proficiency after a 1-h course. Future program development should focus on building a pool of instructors, continued training of LRs, and determining how often skills should be recertified.
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Competencia Clínica , Medicina de Emergencia/educación , Conocimientos, Actitudes y Práctica en Salud , Hemorragia/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Evaluación Educacional , Femenino , Técnicas Hemostáticas , Humanos , Masculino , Persona de Mediana Edad , Estudiantes de Medicina , Adulto JovenRESUMEN
The costs of predation may exert significant pressure on the mode of communication used by an animal, and many species balance the benefits of communication (e.g. mate attraction) against the potential risk of predation. Four groups of toothed whales have independently evolved narrowband high-frequency (NBHF) echolocation signals. These signals help NBHF species avoid predation through acoustic crypsis by echolocating and communicating at frequencies inaudible to predators such as mammal-eating killer whales. Heaviside's dolphins (Cephalorhynchus heavisidii) are thought to exclusively produce NBHF echolocation clicks with a centroid frequency around 125 kHz and little to no energy below 100 kHz. To test this, we recorded wild Heaviside's dolphins in a sheltered bay in Namibia. We demonstrate that Heaviside's dolphins produce a second type of click with lower frequency and broader bandwidth in a frequency range that is audible to killer whales. These clicks are used in burst-pulses and occasional click series but not foraging buzzes. We evaluate three different hypotheses and conclude that the most likely benefit of these clicks is to decrease transmission directivity and increase conspecific communication range. The expected increase in active space depends on background noise but ranges from 2.5 (Wenz Sea State 6) to 5 times (Wenz Sea State 1) the active space of NBHF signals. This dual click strategy therefore allows these social dolphins to maintain acoustic crypsis during navigation and foraging, and to selectively relax their crypsis to facilitate communication with conspecifics.
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Delfines/fisiología , Ecolocación , Conducta Alimentaria , Cadena Alimentaria , Animales , Océano Atlántico , Namibia , OrcaRESUMEN
PURPOSE: Patients undergoing breast augmentation are treated with multiple combinations of medications for pain control including ketorolac, liposomal bupivacaine, bupivacaine, and intravenous and oral narcotics. There is no current consensus on the optimal combination; therefore, all are used at the discretion of the surgeon. METHODS: This was a single-center, retrospective study. The total number of patients included was 132. Comparisons were made between 4 groups: bupivacaine only (B); bupivacaine and liposomal bupivacaine (BL); bupivacaine and liposomal bupivacaine plus intraoperative ketorolac (BLKi); and bupivacaine and liposomal bupivacaine plus postoperative ketorolac (BLKp). Average pain scores immediately postoperative and before discharge were recorded and correlated to percentage of patients who received narcotic in the post-anesthesia care unit (PACU). Additional end points noted were side effects including nausea and time spent in PACU postoperatively. RESULTS: Those receiving intraoperative ketorolac had the lowest pain on discharge (P < 0.0001) and the lowest percentage of patients receiving narcotics (P = 0.009) out of all 4 groups. There was no significant difference between the 4 groups in terms of time spent in PACU, pain immediately after the procedure, or amount of antiemetic given. No bleeding complications were noted for those who did or did not receive ketorolac. CONCLUSIONS: When given options for pain control in breast augmentation, intraoperative ketorolac should be considered, because its inclusion was significant in decreasing use of narcotics and pain upon discharge. Addition of other costly drugs such as liposomal bupivacaine may not provide additional benefit in the immediate postoperative setting for procedures with a short recovery period such as breast augmentation.
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Analgésicos/administración & dosificación , Bupivacaína/administración & dosificación , Ketorolaco/administración & dosificación , Mamoplastia/métodos , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Implantación de Mama/métodos , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Cuidados Intraoperatorios/métodos , Liposomas , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Resultado del TratamientoRESUMEN
Background. We describe the unusual case of a recently transplanted cadaveric renal transplant recipient who presented with recurrent pulmonary mucormycosis. Case Report. An 18-year-old man with end stage renal disease secondary to congenital renal agenesis status after cadaveric kidney transplant 4 months before presented with acute onset of fever, hemoptysis, and back pain. The patient underwent an emergent left lower lobectomy due to the critical nature of his illness. He was also treated with amphotericin with resolution of his symptoms. One week later, he had evidence of recurrent disease on imaging with a surgical site infection. He underwent reexploration with evacuation of an empyema and debridement of a surgical site infection. He was continued on IV antifungal therapy with isavuconazonium and amphotericin. Radiographic clearance of disease with three months of treatment was apparent with no evidence of recurrence at seven-month follow-up. Discussion. Opportunistic infections in solid organ transplant patients represent a significant source of morbidity and mortality. Most patients are treated with prophylactic anti-infective agents. However, rare infections such as pulmonary mucormycosis remain a risk. The transplant physician must be aware of these uncommon infections and their treatment strategies, including the management of uncommon recurrent disease.
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Schizophrenia has generally been viewed as having a unique preschizophrenia personality or destructive to the personality post-onset. This view is reflected in the scarcity of studies of personality in schizophrenia with the exception of schizotypal personality considered by many as an endophenotype of schizophrenia. What is missing is the study of personality as independent of schizophrenia and as a potential source of schizophrenia heterogeneity. In this study we examine sex versus gender as an initial effort to introduce personality as a normal variant that influences how schizophrenia is expressed. Gender, a personality construct, was associated with the presence of depression in a large sample of schizophrenia patients controlling for sex, age of onset, severity of disorder, and education. The results suggest that gender, rather than sex, as a representative personality trait may yield important insights into how schizophrenia is expressed.
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Identidad de Género , Personalidad , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Caracteres Sexuales , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/psicología , Inventario de Personalidad , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicologíaRESUMEN
INTRODUCTION: All-terrain vehicles (ATVs) are associated with injury, mortality, and healthcare costs. ATV related injuries are less severe when consistent safety practices are followed, however, ATV safety regulations are varied among states. This study sought to survey Kansas ATV dealers and track owners to determine safety promotion practices. METHODS: A cross-sectional telephone survey was conducted of Kansas ATV dealers and tracks. Survey questions included promotion and sale of safety equipment, provision of ATV safety information, and respondent characteristics. RESULTS: Of those contacted, 32% of dealers and 31% of tracks responded to the survey. Most ATV dealers sell safety gear (70% - 100%) and all recommend safety gear to buyers and riders. All ATV tracks reported requiring helmets (100%) but were varied regarding other forms of safety gear. The majority of ATV dealers (77%) recommended safety courses, but only 31% of dealers and 40% of tracks offered courses. Eighty percent of ATV tracks and 52% of dealers felt they had a professional responsibility to educate riders/owners on safety. CONCLUSION: Safety promotion by ATV dealers in Kansas consistently was recommended, but often limited to the sales of safety gear (helmets and gloves) or the provision of manufacturer provided safety materials. Further, ATV dealers reported rarely offering skills tests or safety courses to buyers. In Kansas, safety promotion at the point of sale or track level could be improved to increase public awareness of ATV safety practices.
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Keloids and hypertrophic scars are common lesions, which typically present as a cosmetic concern; however, they also can cause significant pruritus and pain. These lesions pose as a particular therapeutic challenge among clinicians due to a lack of complete knowledge of the formation of keloids and hypertrophic scars. Multiple treatments are widely accepted, yet all have shown limited benefit. In this case, we describe the treatment combination of the Affirm CO2 fractional laser (10 600 nm, Cynosure), Cynergy Pulsed dye laser (585 nm, Cynosure), and triamcinolone acetonide injection for keloids refractory to solitary treatments of triamcinolone acetonide injection and other laser modalities.
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Antiinflamatorios/uso terapéutico , Cicatriz Hipertrófica/terapia , Queloide/terapia , Láseres de Colorantes/uso terapéutico , Láseres de Gas/uso terapéutico , Triamcinolona Acetonida/uso terapéutico , Adulto , Dorso , Cicatriz Hipertrófica/patología , Terapia Combinada , Femenino , Humanos , Queloide/patología , Terapia por Luz de Baja Intensidad/métodosRESUMEN
The amyloid ß-peptide (Aß), strongly implicated in the pathogenesis of Alzheimer's disease (AD), is produced from the amyloid ß-protein precursor (APP) through consecutive proteolysis by ß- and γ-secretases. The latter protease contains presenilin as the catalytic component of a membrane-embedded aspartyl protease complex. Missense mutations in presenilin are associated with early-onset familial AD, and these mutations generally both decrease Aß production and increase the ratio of the aggregation-prone 42-residue form (Aß42) to the 40-residue form (Aß40). The connection between these two effects is not understood. Besides Aß40 and Aß42, γ-secretase produces a range of Aß peptides, the result of initial cutting at the ε site to form Aß48 or Aß49 and subsequent trimming every three or four residues. Thus, γ-secretase displays both overall proteolytic activity (ε cutting) and processivity (trimming) toward its substrate APP. Here we tested whether a decrease in total activity correlates with decreased processivity using wild-type and AD-mutant presenilin-containing protease complexes. Changes in pH, temperature, and salt concentration that reduced the overall activity of the wild-type enzyme did not consistently result in increased proportions of longer Aß peptides. Low salt concentrations and acidic pH were notable exceptions that subtly alter the proportion of individual Aß peptides, suggesting that the charged state of certain residues may influence processivity. Five different AD mutant complexes, representing a broad range of effects on overall activity, Aß42:Aß40 ratios, and ages of disease onset, were also tested, revealing again that changes in total activity and processivity can be dissociated. Factors that control initial proteolysis of APP at the ε site apparently differ significantly from factors affecting subsequent trimming and the distribution of Aß peptides.
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Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/química , Secretasas de la Proteína Precursora del Amiloide/genética , Mutagénesis Sitio-Dirigida , Presenilina-1/química , Presenilina-1/genética , Procesamiento Proteico-Postraduccional/genética , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/biosíntesis , Precursor de Proteína beta-Amiloide/biosíntesis , Precursor de Proteína beta-Amiloide/química , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Células CHO , Dominio Catalítico/genética , Línea Celular , Cricetinae , Activación Enzimática/genética , Humanos , Fragmentos de Péptidos/biosíntesis , Presenilina-1/metabolismo , Presenilina-2/química , Presenilina-2/genética , Presenilina-2/metabolismo , Proteolisis , Especificidad por Sustrato/genéticaRESUMEN
The need to identify anti-Flaviviridae agents has resulted in intensive biochemical study of recombinant nonstructural (NS) viral proteases; however, experimentation on viral protease-associated replication complexes in host cells is extremely challenging and therefore limited. It remains to be determined if membrane anchoring and/or association to replicase-membrane complexes of proteases, such as hepatitis C virus (HCV) NS3-4A, plays a regulatory role in the substrate selectivity of the protease. In this study, we examined trans-endoproteolytic cleavage activities of membrane-anchored and replicase-associated NS3-4A using an internally consistent set of membrane-anchored protein substrates mimicking all known HCV NS3-4A polyprotein cleavage sequences. Interestingly, we detected cleavage of substrates encoding for the NS4B/NS5A and NS5A/NS5B junctions, but not for the NS3/NS4A and NS4A/NS4B substrates. This stringent substrate recognition profile was also observed for the replicase-associated NS3-4A and is not genotype-specific. Our study also reveals that ER-anchoring of the substrate is critical for its cleavage by NS3-4A. Importantly, we demonstrate that in HCV-infected cells, the NS4B/NS5A substrate was cleaved efficiently. The unique ability of our membrane-anchored substrates to detect NS3-4A activity alone, in replication complexes, or within the course of infection, shows them to be powerful tools for drug discovery and for the study of HCV biology.
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Hepacivirus/enzimología , Hepatitis C/virología , Proteínas no Estructurales Virales/metabolismo , Secuencia de Aminoácidos , Línea Celular , Especificidad por SustratoRESUMEN
BACKGROUND: Preventable harm to mothers and infants during labor and birth is a significant patient safety and professional liability issue. A Michigan Health & Hospital Association Keystone Center for Patient Safety & Quality Obstetric Collaborative Project involved perinatal teams from 15 Michigan hospitals during an 11-month period in 2009. The purpose of the project was to promote safe care practices during labor and birth using the Comprehensive Unit-based Safety Program (CUSP). Consistent with the CUSP model, this project's components included assessing and promoting a culture of safety; interdisciplinary team building; case review; learning from defects through multiple methods of education; team and individual coaching and peer encouragement; administrative support for the establishment of a fundamental safety infrastructure; and ongoing evaluation of care processes and outcomes. METHODS: Study measures included 32 components of a perinatal patient infrastructure, 6 care processes during labor and birth, and 4 neonatal outcomes. RESULTS: Significant improvements were found in the safety culture (Safety Attitudes Questionnaire), the perinatal patient safety infrastructure components, and all care processes. CONCLUSIONS: Although the project was successful, getting buy-in from all members of the clinical team in each hospital for all of the measures was challenging at times. There was initial resistance to some of the measures and their various expected aspects of care. For example, some of the clinicians were initially reluctant to adopt the recommended standardized oxytocin protocol. Peer encouragement and unit-based feedback on progress in minimizing early elective births proved useful in many hospitals. A CUSP in obstetrics can be beneficial in improving the care of mothers and infants during labor and birth.
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Obstetricia , Seguridad del Paciente , Conducta Cooperativa , Femenino , Hospitales , Humanos , Michigan , Grupo de Atención al Paciente , Embarazo , Administración de la SeguridadRESUMEN
Flaviviral NS2B/NS3 heterocomplex serine proteases are a primary target for anti-flavivirus drug discovery. To gain insights into the enzymatic properties and molecular determinants of flaviviral NS2B/NS3 protease substrate specificity in host cells, we developed and applied a novel series of membrane-anchored red-shifted fluorescent protein substrates to detect West Nile virus (WNV) NS2B/NS3 endoproteolytic activity in human cells. The substrate consists of a fluorescent reporter group (DsRed) tethered to the endoplasmic reticulum membrane by a membrane-anchoring domain. Between the two domains is a specific peptide linker that corresponds to the NS2A/NS2B, NS2B/NS3, NS3/NS4A, and NS4B/NS5 protein junctions within the WNV polyprotein precursor. When the protease cleaves the peptide linker, the DsRed reporter group is released, changing its localization in the cell from membrane-bound punctate perinuclear to diffuse cytoplasmic. This change in protein location can be monitored by fluorescent microscopy, and cleavage products can be quantified by Western blotting. Our data demonstrate the robustness of our trans-cleavage fluorescence assay to capture single-cell imaging of membrane-associated WNV NS2B/NS3 endoproteolytic activity and to perform in-cell selectivity profiling of the NS2B/NS3 protease. Our study is the first to provide cellular insights into the biological and enzymatic properties of a prime target for inhibitors of WNV replication.