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1.
Small ; 20(26): e2308166, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38321841

ABSTRACT

The formation mechanism(s) of high-index facets in metal oxides is not widely understood but remains a topic of interest owing to the challenges of stabilizing high-energy surfaces. These metal oxide crystal surfaces are expected to provide unique physicochemical characteristics; therefore, understanding crystallization pathways may enable the rational design of materials with controlled properties. Here the crystallization of NiO via thermal decomposition of a nickel source in excess of alkali chlorides is examined, focusing on KCl, which produces trapezohedral NiO (311) particles that are difficult to achieve through alternative methods. Trapezohedral NiO crystals are confirmed to grow via a molten eutectic where NiO nucleation is followed by nonclassical crystallization through processes resembling colloidal assembly. Aggregates comprised of NiO nanocrystals form mesostructures that ripen with heating time and exhibit fewer grain boundaries as they transition into single-crystalline particles. At temperatures higher than those of NiO crystallization, there is a restructuring of (311) facets into microfacets exposing (111) and (100) surfaces. These findings illustrate the complex crystallization processes taking place during molten salt synthesis. The ability to generate metal oxide particles with high-index facets has the potential to be a more generalized approach to unlock the physicochemical properties of materials for diverse applications.

2.
Am Heart J ; 270: 44-54, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38253305

ABSTRACT

OBJECTIVE: To compare the clinical outcomes of radial artery (RA) grafts during CABG to those of right internal mammary artery (RIMA) grafts. METHODS: This was a retrospective, single-institution cohort study of isolated CABG with multiple grafts between 2010-2022. To balance graft cohorts, propensity score matching (PSM) was performed using a 1:1 match ratio. Long-term postoperative survival was compared among RA and RIMA groups. Similarly, major adverse cardiac and cerebrovascular events (MACCE) were compared among both cohorts, with MACCE comprising death, myocardial infarction (MI), coronary revascularization, and stroke. Kaplan-Meier estimation was performed for mortality, while cumulative incidence estimation was utilized for MACCE. RESULTS: A total of 8,774 patients underwent CABG. Of those, 1,674 (19.1%) patients who underwent multiarterial CABG were included in this analysis. 326 (19.5%) patients received RA grafts and 1,348 (80.5%) received RIMA grafts. PSM yielded a cohort of 323 RA patients and 323 RIMA patients. After matching, groups were well-balanced across all baseline variables. No significant differences were observed in immediate postoperative complications or long-term survival, with 5-year survival estimates of 89.5% for the RA group vs 90.1% for the RIMA group. There was a nonsignificant trend toward a higher incidence of MACCE at 5 years in the RA group compared to the RIMA group (31.3% in the RA group vs 24.1% in the RIMA group), especially after 1-year follow-up (21.6% in the RA group vs 15.1% in the RIMA group). Specifically, for RA patients, there were higher rates of repeat revascularization in the 5-year postoperative period (14.7% in the RA group vs 5.3% in the RIMA group), particularly in the territory revascularized by the RA during the index operation (45.7% in the RA group vs 10.3% in the RIMA group). CONCLUSION: Overall, RA and RIMA secondary conduits for CABG were associated with comparable immediate postoperative complications, 5-year MACCE, and 5-year survival after PSM. RA grafting was associated with significantly higher rates of repeat coronary revascularization at 5 years, specifically in the territory revascularized by the RA during the index operation.


Subject(s)
Coronary Artery Disease , Mammary Arteries , Humans , Retrospective Studies , Cohort Studies , Radial Artery/transplantation , Mammary Arteries/transplantation , Treatment Outcome , Coronary Artery Bypass/adverse effects , Postoperative Complications/etiology
3.
Aust Crit Care ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38797583

ABSTRACT

BACKGROUND: There is growing interest in the use of point-of-care ultrasound during cardiac arrest, but few studies document its use in the intensive care unit. OBJECTIVE: We hypothesised this may reflect a low prevalence of use of point-of-care ultrasound during cardiac arrest or negative attitudes towards its use. We aimed to determine the self-reported prevalence, attitudes towards, and barriers to use of point-of-care ultrasound during cardiac arrest in the intensive care unit. METHODS: We conducted a web-based survey over 3 months (08/08/2022-06/11/2022), of intensive care unit consultants and registrars in Victoria, Australia. Descriptive and mixed-methods analyses of Likert-type and free-text answers were performed. RESULTS: The response rate was 91/398 (22.8%), split evenly between consultants and registrars. There was a broad range of clinical and ultrasound experience. Only 22.4% (22/91) of respondents reported using point-of-care ultrasound 75-100% of the time during their management of cardiac arrest. Respondents rated the value they place in point-of-care ultrasound during cardiac arrest 3 (interquartile range: 3-4) and that of a "skilled operator" 4 ((interquartile range; 4-5) on a 5-point scale. Free-text analysis suggested exclusion of "tamponade" (40/80 [50%] comments) as the most valuable use-case and "skill" as a personal barrier (20/73 [27.4%] comments). Personal and departmental barriers were not rated highly, although registrars perceived "lack of a structured training program" as a barrier. Respondents were equivocal in the value they gave point-of-care ultrasound during cardiac arrest but saw greater value when conducted by a skilled operator. CONCLUSIONS: Point-of-care ultrasound was reported to be infrequently used in cardiac arrest, mostly due to self-perceived skill and lack of a structured training program.

4.
Intern Med J ; 53(5): 745-752, 2023 05.
Article in English | MEDLINE | ID: mdl-34865306

ABSTRACT

BACKGROUND: Inhospital cardiac arrest (IHCA) is an uncommon but challenging problem. AIMS: To investigate the management and outcomes of IHCA, and to investigate the effect of introducing a medical emergency team (MET) on IHCA prevalence. METHODS: Retrospective medical record review of 176 adult IHCA episodes at Box Hill Hospital, a university-affiliated public hospital in metropolitan Melbourne, from July 2012 to June 2017. Inpatients receiving cardiopulmonary resuscitation for IHCA, in inpatient wards, intensive care unit, cardiac catheterisation laboratory and operating theatres were included. Data collected included demographics, resuscitation management and outcomes. Average treatment effect (ATE) was derived from margins estimates and linear regression fitted to hospital outcome, adjusted for IHCA factors. An exponentially weighed moving average control chart was used to explore IHCA prevalence over time. RESULTS: There were 65.3% of IHCA patients who died in hospital. IHCA prevalence was unchanged after the introduction of a dedicated MET service. Factors associated with higher likelihood of survival to discharge were initial cardiac of rhythm ventricular tachycardia (VT) (ATE 0.10 (95% CI = -0.03 to 0.25)) or ventricular fibrillation (VF) (ATE 0.28 (95% CI = 0.11-0.46)), cardiac monitoring at the time of arrest (ATE 0.06 (95%CI = -0.04 to 0.16)) and time to return of spontaneous circulation (ATE 0.023 (95% CI = 0.015-0.031)). CONCLUSIONS: IHCA is uncommon and is associated with high mortality. IHCA prevalence was unchanged after the introduction of a dedicated MET service. Factors associated with improved survival to hospital discharge were initial rhythm VT or VF, cardiac monitoring and shorter resuscitation times.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Tachycardia, Ventricular , Adult , Humans , Retrospective Studies , Heart Arrest/therapy , Ventricular Fibrillation , Hospitals, Urban
5.
Exp Physiol ; 106(6): 1373-1379, 2021 06.
Article in English | MEDLINE | ID: mdl-33866617

ABSTRACT

NEW FINDINGS: What is the central question of this study? Pregnancy requires marked renal sodium and potassium retention and cumulative plasma volume expansion, in the setting of reduced blood pressure. Research in male rodents has shown that activation of PAR2 can produce peripheral vasodilatation, stimulate renal sodium chloride reabsorption and inhibit renal potassium secretion. Here, we investigate PAR2 activation in virgin and normal pregnant rats. What is the main finding and its importance? PAR2 expression and sensitivity to activation are increased in pregnancy. This implicates a possible role for PAR2 in supporting the renal/vascular adaptations of pregnancy required for normal maternal plasma volume expansion. ABSTRACT: A healthy pregnancy involves renal and systemic haemodynamic adaptations, which allow renal sodium and potassium retention and cumulative plasma volume expansion, accompanied by a decline in blood pressure attributable to a reduction in the total peripheral vascular resistance. When these adaptations do not occur, pregnancy is compromised. The mechanisms permitting these opposing adaptations are largely unknown. Research in male rodents has shown that activation of PAR2 can produce peripheral vasodilatation, stimulate renal sodium chloride reabsorption and inhibit renal potassium secretion. Here, we investigate PAR2 activation in female virgin and normal late pregnant (LP) rats. We measured the mRNA expression of PAR2 in the renal cortex, outer medulla and inner medulla of virgin and LP rats using quantitative real-time PCR. We also measured in vivo blood pressure, natriuretic and kaliuretic responses to PAR2-activating peptide (SLIGRL-NH2 ) in anaesthetized virgin and LP rats. We found that PAR2 mRNA was increased in the inner medulla of LP rats. We also found that LP rats had larger decreases in blood pressure and increases in net sodium retention compared with virgin rats. These findings suggest that pregnancy enhances sensitivity to the blood pressure-lowering and sodium-retaining effects of PAR2.


Subject(s)
Blood Pressure , Electrolytes , Receptor, PAR-2 , Sodium , Animals , Electrolytes/metabolism , Female , Pregnancy , Rats , Receptor, PAR-2/metabolism , Sodium/metabolism
6.
Angew Chem Int Ed Engl ; 60(48): 25391-25396, 2021 Nov 22.
Article in English | MEDLINE | ID: mdl-34406684

ABSTRACT

Given the strong influence of surface structure on the reactivity of heterogeneous catalysts, understanding the mechanisms that control crystal morphology is an important component of designing catalytic materials with targeted shape and functionality. Herein, we employ density functional theory to examine the impact of growth media on NiO crystal faceting in line with experimental findings, showing that molten-salt synthesis in alkali chlorides (KCl, LiCl, and NaCl) imposes shape selectivity on NiO particles. We find that the production of NiO octahedra is attributed to the dissociative adsorption of H2 O, whereas the formation of trapezohedral particles is associated with the control of the growth kinetics exerted by ordered salt structures on high-index facets. To our knowledge, this is the first observation that growth inhibition of metal-oxide facets occurs by a localized ordering of molten salts at the crystal-solvent interface. These findings provide new molecular-level insight on kinetics and thermodynamics of molten-salt synthesis as a predictive route to shape-engineer metal-oxide crystals.

7.
Angew Chem Int Ed Engl ; 59(35): 15119-15123, 2020 Aug 24.
Article in English | MEDLINE | ID: mdl-32302436

ABSTRACT

Metal oxides exposing high-index facets are potentially impactful in catalysis and adsorption processes owing to under-coordinated ions and polarities that alter their interfacial properties compared to low-index facets. Here, we report molten-salt syntheses of NiO particles exposing a variety of crystal facets. We show that for a given anion (nitrate or chloride), the alkali cation has a notable impact on the formation of crystals exposing {311}, {611}, {100}, and {111} faces. Based on a parametric analysis of synthesis conditions, we postulate that the crystallization mechanism is governed by the formation of growth units consisting of NiII complexes whose coordination numbers are determined by temperature and the selection of anion (associated to the coordination sphere) and alkali cation (associated with the outer coordination sphere). Notably, our findings reveal that high-index facets are particularly favored in chloride media and are stable under prolonged periods of catalysis and steaming.

8.
Am J Physiol Renal Physiol ; 317(3): F572-F583, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31241996

ABSTRACT

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg-1·day-1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group (n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group (n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.


Subject(s)
Arterial Pressure , Diet, Sodium-Restricted , Hypertension/prevention & control , Kidney/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Antihypertensive Agents/pharmacology , Arterial Pressure/drug effects , Disease Models, Animal , Female , Heart Rate , Hydralazine/pharmacology , Hypertension/immunology , Hypertension/physiopathology , Kidney/drug effects , Lymph Nodes/immunology , Rats, Inbred Dahl , Spleen/immunology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Regulatory/drug effects , Vasodilator Agents/pharmacology
9.
PLoS Genet ; 12(2): e1005691, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26839965

ABSTRACT

The unintended consequences of gene targeting in mouse models have not been thoroughly studied and a more systematic analysis is needed to understand the frequency and characteristics of off-target effects. Using RNA-seq, we evaluated targeted and neighboring gene expression in tissues from 44 homozygous mutants compared with C57BL/6N control mice. Two allele types were evaluated: 15 targeted trap mutations (TRAP); and 29 deletion alleles (DEL), usually a deletion between the translational start and the 3' UTR. Both targeting strategies insert a bacterial beta-galactosidase reporter (LacZ) and a neomycin resistance selection cassette. Evaluating transcription of genes in +/- 500 kb of flanking DNA around the targeted gene, we found up-regulated genes more frequently around DEL compared with TRAP alleles, however the frequency of alleles with local down-regulated genes flanking DEL and TRAP targets was similar. Down-regulated genes around both DEL and TRAP targets were found at a higher frequency than expected from a genome-wide survey. However, only around DEL targets were up-regulated genes found with a significantly higher frequency compared with genome-wide sampling. Transcriptome analysis confirms targeting in 97% of DEL alleles, but in only 47% of TRAP alleles probably due to non-functional splice variants, and some splicing around the gene trap. Local effects on gene expression are likely due to a number of factors including compensatory regulation, loss or disruption of intragenic regulatory elements, the exogenous promoter in the neo selection cassette, removal of insulating DNA in the DEL mutants, and local silencing due to disruption of normal chromatin organization or presence of exogenous DNA. An understanding of local position effects is important for understanding and interpreting any phenotype attributed to targeted gene mutations, or to spontaneous indels.


Subject(s)
Gene Expression Profiling/methods , Gene Expression Regulation , Gene Targeting , Mutation/genetics , Animals , Down-Regulation/genetics , Gene Deletion , Gene Library , Genome , Homozygote , Mice, Inbred C57BL , Up-Regulation/genetics
10.
Am J Physiol Renal Physiol ; 314(2): F251-F259, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29046297

ABSTRACT

Gestational potassium retention, most of which occurs during late pregnancy, is essential for fetal development. The purpose of this study was to examine mechanisms underlying changes in potassium handling by the kidney and colon in pregnancy. We found that potassium intake and renal excretion increased in late pregnancy while fecal potassium excretion remained unchanged and that pregnant rats exhibited net potassium retention. By quantitative PCR we found markedly increased H+-K+-ATPase type 2 (HKA2) mRNA expression in the cortex and outer medullary of late pregnant vs. virgin. Renal outer medullary potassium channel (ROMK) mRNA was unchanged in the cortex, but apical ROMK abundance (by immunofluorescence) was decreased in pregnant vs. virgin in the distal convoluted tubule (DCT) and connecting tubule (CNT). Big potassium-α (BKα) channel-α protein abundance in intercalated cells in the cortex and outer medullary collecting ducts (by immunohistochemistry) fell in late pregnancy. In the distal colon we found increased HKA2 mRNA and protein abundance (Western blot) and decreased BKα protein with no observed changes in mRNA. Therefore, the potassium retention of pregnancy is likely to be due to increased collecting duct potassium reabsorption (via increased HKA2), decreased potassium secretion (via decreased ROMK and BK), as well as increased colonic reabsorption via HKA2.


Subject(s)
Colon/metabolism , H(+)-K(+)-Exchanging ATPase/metabolism , Kidney Tubules, Collecting/metabolism , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Potassium Channels, Inwardly Rectifying/metabolism , Potassium/metabolism , Animals , Biological Transport , Female , Gestational Age , H(+)-K(+)-Exchanging ATPase/genetics , Intestinal Reabsorption , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics , Potassium/blood , Potassium/urine , Potassium Channels, Inwardly Rectifying/genetics , Pregnancy , Rats, Sprague-Dawley , Renal Elimination , Renal Reabsorption
11.
Genome Res ; 25(4): 598-607, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25591789

ABSTRACT

Expression of the bacterial beta-galactosidase reporter gene (lacZ) in the vector used for the Knockout Mouse Project (KOMP) is driven by the endogenous promoter of the target gene. In tissues from KOMP mice, histochemical staining for LacZ enzyme activity can be used to determine gene expression patterns. With this technique, we have produced a comprehensive resource of gene expression using both whole mount (WM) and frozen section (FS) LacZ staining in 313 unique KOMP mutant mouse lines. Of these, ∼ 80% of mutants showed specific staining in one or more tissues, while ∼ 20% showed no specific staining, ∼ 13% had staining in only one tissue, and ∼ 25% had staining in >6 tissues. The highest frequency of specific staining occurred in the brain (∼ 50%), male gonads (42%), and kidney (39%). The WM method was useful for rapidly identifying whole organ and some substructure staining, while the FS method often revealed substructure and cellular staining specificity. Both staining methods had >90% repeatability in biological replicates. Nonspecific LacZ staining occurs in some tissues due to the presence of bacteria or endogenous enzyme activity. However, this can be effectively distinguished from reporter gene activity by the combination of the WM and FS methods. After careful annotation, LacZ staining patterns in a high percentage of mutants revealed a unique structure-function not previously reported for many of these genes. The validation of methods for LacZ staining, annotation, and expression analysis reported here provides unique insights into the function of genes for which little is currently known.


Subject(s)
Gene Expression Regulation/genetics , Genes, Reporter/genetics , Lac Operon/genetics , Promoter Regions, Genetic/genetics , Animals , Atlases as Topic , Female , Gene Expression , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Staining and Labeling , Structure-Activity Relationship
12.
Am J Physiol Regul Integr Comp Physiol ; 315(5): R915-R924, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30024774

ABSTRACT

Inbred salt-sensitive (SS) rats developed by John Rapp and distributed by Harlan (SS/JrHsd) were shown to model ovariectomy-induced hypertension because on a low-sodium (LS) diet, ovariectomized SS (SS-OVX) animals became hypertensive in contrast to their sham-operated (SS-SHAM) normotensive littermates. After Harlan merged with Envigo in 2015, inconsistencies in the LS normotensive phenotype were reported. To further investigate these inconsistencies, we studied the effects of ovariectomy on SS and salt-resistant (SR) rats purchased from Envigo (SS/JrHsd/Env) between 2015 and 2017. The mean arterial pressure (MAP) in SS rats on a LS diet exceeded 160 mmHg at 7 mo old. Ovariectomy at 3 mo had no detectable effect on MAP from 4 to 7 mo, nor did ovariectomy at 1.5 mo significantly affect MAP at 10 mo in either strain; only strain differences in MAP were observed [MAP: SR-SHAM ( n = 7 rats), 102 ± 3 mmHg; SR-OVX ( n = 6 rats), 114 ± 1 mmHg; SS-SHAM ( n = 7 rats), 177 ± 6 mmHg; SS-OVX ( n = 5 rats), 190 ± 12 mmHg; where P < 0.0001 vs. SR, same ovarian-status for SS-SHAM and SS-OVX, respectively]. Whole genome sequencing revealed more genomic variants of SS/JrHsd/Env, including single nucleotide and insertion deletion polymorphisms and higher heterozygous/homozygous ratios compared with the reference genome, than for SS/JrHsd/Mcwi and SS/Jr rats maintained in Milwaukee, WI and Toledo, OH, respectively, and which still exhibit normal blood pressure on a LS diet. These findings demonstrate that the female SS/JrHsd/Env rat has genetically diverged from the original phenotype, which was normotensive on a LS diet when the ovaries were intact but rapidly developed hypertension when the ovaries were removed. Nonetheless, the SS/JrHsd/Env rat could be a valuable model that complements other animal models of spontaneous hypertension used to investigate mechanisms of essential hypertension.


Subject(s)
Hypertension/etiology , Ovariectomy/adverse effects , Sodium Chloride, Dietary/pharmacology , Sodium Chloride/pharmacology , Animals , Blood Pressure/drug effects , Diet, Sodium-Restricted/methods , Female , Hypertension/physiopathology , Rats , Sodium, Dietary/pharmacology
13.
PLoS Biol ; 13(5): e1002151, 2015 May.
Article in English | MEDLINE | ID: mdl-25992600

ABSTRACT

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC), whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future.


Subject(s)
Animal Experimentation/standards , Databases as Topic , Guidelines as Topic , Phenotype , Animals , Mice
14.
Article in English | MEDLINE | ID: mdl-34877146

ABSTRACT

Results from tests of radiation detection instruments with radionuclide identification capabilities will depend on the sources used for the tests. Radionuclide identification detectors are designed to measure photons and provide an identification of the source being measured. High-resolution spectra need to be acquired to determine all the observable peaks in the source spectra before testing these types of instruments. These peaks may be due to impurities and/or scatter peaks in the sources. This paper discusses the issues encountered with the response of a radioisotope identification device due to scatter peaks in one type of source used for testing. In addition, it provides spectra for different source types and source constructions to compare the differences in scatter, allowing for a better source type selection for instrument testing.

15.
Transgenic Res ; 26(2): 263-277, 2017 04.
Article in English | MEDLINE | ID: mdl-27905063

ABSTRACT

The CRISPR/Cas9 system has rapidly advanced targeted genome editing technologies. However, its efficiency in targeting with constructs in mouse zygotes via homology directed repair (HDR) remains low. Here, we systematically explored optimal parameters for targeting constructs in mouse zygotes via HDR using mouse embryonic stem cells as a model system. We characterized several parameters, including single guide RNA cleavage activity and the length and symmetry of homology arms in the construct, and we compared the targeting efficiency between Cas9, Cas9nickase, and dCas9-FokI. We then applied the optimized conditions to zygotes, delivering Cas9 as either mRNA or protein. We found that Cas9 nucleo-protein complex promotes highly efficient, multiplexed targeting of circular constructs containing reporter genes and floxed exons. This approach allows for a one-step zygote injection procedure targeting multiple genes to generate conditional alleles via homologous recombination, and simultaneous knockout of corresponding genes in non-targeted alleles via non-homologous end joining.


Subject(s)
CRISPR-Cas Systems/genetics , Gene Targeting/methods , Homologous Recombination/genetics , Alleles , Animals , DNA End-Joining Repair/genetics , Exons , Mice , RNA, Guide, Kinetoplastida/genetics , RNA, Messenger/genetics , Zygote/growth & development
16.
Paediatr Anaesth ; 27(6): 596-603, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28321993

ABSTRACT

BACKGROUND: Metatropic dysplasia is a rare form of skeletal dysplasia requiring multiple anesthetics for surgical and imaging procedures, most of which are orthopedic procedures. We provide centralized care to patients with skeletal dysplasia at our tertiary care pediatric hospital, and we were able to collect the largest number of metatropic dysplasia patients reported to date. AIM: The aim of this retrospective study was to describe and characterize the anesthetic difficulties in this high-risk population. METHODS: Medical charts of all patients with metatropic dysplasia were reviewed to collect data, including anesthetics performed, difficulties, and complications related to the anesthetic care, co-morbid conditions, and related events. RESULTS: Twenty-three patients with metatropic dysplasia underwent 188 anesthetics with 61% of the anesthetics having been administered for orthopedic procedures. Fourteen of 23 (60.8%) progressively became difficult to intubate over the course of their care, with 12 out of 14 having undergone cervical spine fusion. These 14 patients had a total of 133 procedures. Sixty procedures (45.1%) had an airway described as difficult. Glidescope was the difficult airway tool most commonly used (68%) with flexible fiberoptic scope used 12% and Miller or Macintosh blade used 18% of the time. In addition to the airway difficulties, spinal canal narrowing or stenosis was widely prevalent, and no neuraxial anesthetic was performed in any of our patients. CONCLUSION: Difficult airway is the most common co-morbid condition present in patients with metatropic dysplasia, especially if their cervical spine has been fused. Familiarity with the difficulties involving the airway and its management is critical in safe and successful management of anesthesia in this high-risk population.


Subject(s)
Airway Management/methods , Anesthesia/methods , Dwarfism/complications , Osteochondrodysplasias/complications , Adolescent , Adult , Airway Management/instrumentation , Anesthesia, Spinal , Cervical Vertebrae/surgery , Child , Child, Preschool , Female , Fiber Optic Technology , Humans , Infant , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Male , Retrospective Studies , Spinal Fusion/methods , Spinal Stenosis/complications , Young Adult
17.
J Gen Intern Med ; 30(4): 476-82, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25472509

ABSTRACT

BACKGROUND: Efforts to improve primary care diabetes management have assessed strategies across heterogeneous groups of patients and practices. However, there is substantial variability in how well practices implement interventions and achieve desired outcomes. OBJECTIVE: To examine practice contextual features that moderate intervention effectiveness. DESIGN: Secondary analysis of data from a cluster randomized trial of three approaches for implementing the Chronic Care Model to improve diabetes care. PARTICIPANTS: Forty small to mid-sized primary care practices participated, with 522 clinician and staff member surveys. Outcomes were assessed for 822 established patients with a diagnosis of type 2 diabetes who had at least one visit to the practice in the 18 months following enrollment. MAIN MEASURES: The primary outcome was a composite measure of diabetes process of care, ascertained by chart audit, regarding nine quality measures from the American Diabetes Association Physician Recognition Program: HgA1c, foot exam, blood pressure, dilated eye exam, cholesterol, nephropathy screen, flu shot, nutrition counseling, and self-management support. Data from practices included structural and demographic characteristics and Practice Culture Assessment survey subscales (Change Culture, Work Culture, Chaos). KEY RESULTS: Across the three implementation approaches, demographic/structural characteristics (rural vs. urban + .70(p = .006), +2.44(p < .001), -.75(p = .004)); Medicaid: < 20 % vs. ≥ 20 % (-.20(p = .48), +.75 (p = .08), +.60(p = .02)); practice size: < 4 clinicians vs. ≥ 4 clinicians (+.56(p = .02), +1.96(p < .001), +.02(p = .91)); practice Change Culture (high vs. low: -.86(p = .048), +1.71(p = .005), +.34(p = .22)), Work Culture (high vs. low: -.67(p = .18), +2.41(p < .001), +.67(p = .005)) and variability in practice Change Culture (high vs. low: -.24(p = .006), -.20(p = .0771), -.44(p = .0019) and Work Culture (high vs. low: +.56(p = .3160), -1.0(p = .008), -.25 (p = .0216) were associated with trajectories of change in diabetes process of care, either directly or differentially by study arm. CONCLUSIONS: This study supports the need for broader use of methodological approaches to better examine contextual effects on implementation and effectiveness of quality improvement interventions in primary care settings.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Patient Care/trends , Physicians, Primary Care/trends , Primary Health Care/trends , Aged , Cluster Analysis , Diabetes Mellitus, Type 2/diagnosis , Female , Humans , Male , Middle Aged , Patient Care/methods , Primary Health Care/methods
18.
J Health Commun ; 20 Suppl 2: 69-76, 2015.
Article in English | MEDLINE | ID: mdl-26513033

ABSTRACT

Patient materials are often written above the reading level of most adults. Tool 11 of the Health Literacy Universal Precautions Toolkit ("Design Easy-to-Read Material") provides guidance on ensuring that written patient materials are easy to understand. As part of a pragmatic demonstration of the Toolkit, we examined how four primary care practices implemented Tool 11 and whether written materials improved as a result. We conducted interviews to learn about practices' implementation activities and assessed the readability, understandability, and actionability of patient education materials collected during pre- and postimplementation site visits. Interview data indicated that practices followed many action steps recommended in Tool 11, including training staff, assessing readability, and developing or revising materials, typically focusing on brief documents such as patient letters and information sheets. Many of the revised and newly developed documents had reading levels appropriate for most patients and--in the case of revised documents--better readability than the original materials. In contrast, the readability, understandability, and actionability of lengthier patient education materials were poor and did not improve over the 6-month implementation period. Findings guided revisions to Tool 11 and highlighted the importance of engaging multiple stakeholders in improving the quality of patient materials.


Subject(s)
Health Literacy , Patient Education as Topic , Teaching Materials/standards , Total Quality Management/methods , Aged , Comprehension , Health Literacy/statistics & numerical data , Health Plan Implementation , Humans , Qualitative Research
19.
J Emerg Med ; 49(6): 984-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26482830

ABSTRACT

BACKGROUND: The Affordable Care Act has added millions of new Medicaid enrollees to the health care system. These patients account for a large proportion of emergency department (ED) utilization. OBJECTIVE: Our aim was to characterize this population and their ED use at a national level. METHODS: We used the 2010 National Hospital Ambulatory Medical Care Survey (NHAMCS) to describe demographics and clinical characteristics of nonelderly adults (≥18 years old and ≤64 years old) with Medicaid-covered ED visits. We defined frequent ED users as individuals who make ≥4 ED visits/year and business hours as 8 am to 5 pm. We used descriptive statistics to describe the epidemiology of Medicaid-covered ED visits. RESULTS: NHAMCS included 21,800 ED visits by nonelderly adults in 2010, of which 5,659 (24.09%) were covered by Medicaid insurance. Most ED visits covered by Medicaid were made by patients who are young (25 and 44 years old) and female (67.95%; 95% confidence interval [CI] 66.00-69.89). A large proportion of the ED visits covered by Medicaid were revisits within 72 h (14.66%; 95% CI 9.13-20.19) and from frequent ED users (32.32%; 95% CI 24.29-40.35). Almost half of all ED visits covered by Medicaid occurred during business hours (45.44%; 95% CI 43.45-47.43). CONCLUSIONS: The vast majority of Medicaid enrollees who used the ED were young females, with a large proportion of visits occurring during business hours. Almost one-third of all visits were from frequent ED users.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Medicaid , Adolescent , Adult , Female , Health Care Surveys , Humans , Male , Middle Aged , United States
20.
Ann Fam Med ; 12(1): 8-16, 2014.
Article in English | MEDLINE | ID: mdl-24445098

ABSTRACT

PURPOSE: We investigated 3 approaches for implementing the Chronic Care Model to improve diabetes care: (1) practice facilitation over 6 months using a reflective adaptive process (RAP) approach; (2) practice facilitation for up to 18 months using a continuous quality improvement (CQI) approach; and (3) providing self-directed (SD) practices with model information and resources, without facilitation. METHODS: We conducted a cluster-randomized trial, called Enhancing Practice, Improving Care (EPIC), that compared these approaches among 40 small to midsized primary care practices. At baseline and 9 months and 18 months after enrollment, we assessed practice diabetes quality measures from chart audits and Practice Culture Assessment scores from clinician and staff surveys. RESULTS: Although measures of the quality of diabetes care improved in all 3 groups (all P <.05), improvement was greater in CQI practices compared with both SD practices (P <.0001) and RAP practices (P <.0001); additionally, improvement was greater in SD practices compared with RAP practices (P <.05). In RAP practices, Change Culture scores showed a trend toward improvement at 9 months (P = .07) but decreased below baseline at 18 months (P <.05), while Work Culture scores decreased from 9 to 18 months (P <.05). Both scores were stable over time in SD and CQI practices. CONCLUSIONS: Traditional CQI interventions are effective at improving measures of the quality of diabetes care, but may not improve practice change and work culture. Short-term practice facilitation based on RAP principles produced less improvement in quality measures than CQI or SD interventions and also did not produce sustained improvements in practice culture.


Subject(s)
Diabetes Mellitus/therapy , Family Practice/methods , Primary Health Care/methods , Aged , Family Practice/organization & administration , Family Practice/standards , Female , Humans , Male , Middle Aged , Outcome and Process Assessment, Health Care , Patient-Centered Care/methods , Patient-Centered Care/organization & administration , Patient-Centered Care/standards , Primary Health Care/organization & administration , Primary Health Care/standards , Quality Improvement
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