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This article uses storytelling to examine the importance of seeing beyond measurement. It looks at efficacy related to the measurement and valuation of human potential. Using the lenses of power, knowledge, class, and systems theories, it examines the lived experience of a first-generation U.S. immigrant. As a result, it demonstrates that human potential is difficult to accurately measure.Ribonucleotide reductase (RNR) is a central enzyme for the synthesis of DNA building blocks. Most aerobic organisms, including nearly all eukaryotes, have class I RNRs consisting of R1 and R2 subunits. The catalytic R1 subunit contains an overall activity site that can allosterically turn the enzyme on or off by the binding of ATP or dATP, respectively. The mechanism behind the ability to turn the enzyme off via the R1 subunit involves the formation of different types of R1 oligomers in most studied species and R1-R2 octamers in Escherichia coli To better understand the distribution of different oligomerization mechanisms, we characterized the enzyme from Clostridium botulinum, which belongs to a subclass of class I RNRs not studied before. The recombinantly expressed enzyme was analyzed by size-exclusion chromatography, gas-phase electrophoretic mobility macromolecular analysis, EM, X-ray crystallography, and enzyme assays. Interestingly, it shares the ability of the E. coli RNR to form inhibited R1-R2 octamers in the presence of dATP but, unlike the E. coli enzyme, cannot be turned off by combinations of ATP and dGTP/dTTP. A phylogenetic analysis of class I RNRs suggests that activity regulation is not ancestral but was gained after the first subclasses diverged and that RNR subclasses with inhibition mechanisms involving R1 oligomerization belong to a clade separated from the two subclasses forming R1-R2 octamers. These results give further insight into activity regulation in class I RNRs as an evolutionarily dynamic process.Clear-cell renal cell carcinoma (ccRCC), the most common subtype of renal cancer, has a poor clinical outcome. A hallmark of ccRCC is genetic loss-of-function of VHL (von Hippel-Lindau) that leads to a highly vascularized tumor microenvironment. Although many ccRCC patients initially respond to antiangiogenic therapies, virtually all develop progressive, drug-refractory disease. Given the role of dysregulated expressions of cytoskeletal and cytoskeleton-regulatory proteins in tumor progression, we performed analyses of The Cancer Genome Atlas (TCGA) transcriptome data for different classes of actin-binding proteins to demonstrate that increased mRNA expression of profilin1 (Pfn1), Arp3, cofilin1, Ena/VASP, and CapZ, is an indicator of poor prognosis in ccRCC. Focusing further on Pfn1, we performed immunohistochemistry-based classification of Pfn1 staining in tissue microarrays, which indicated Pfn1 positivity in both tumor and stromal cells; however, the vast majority of ccRCC tumors tend to be Pfn1-positive selectively in stromal cells only. This finding is further supported by evidence for dramatic transcriptional up-regulation of Pfn1 in tumor-associated vascular endothelial cells in the clinical specimens of ccRCC. In vitro studies support the importance of Pfn1 in proliferation and migration of RCC cells and in soluble Pfn1's involvement in vascular endothelial cell tumor cell cross-talk. Furthermore, proof-of-concept studies demonstrate that treatment with a novel computationally designed Pfn1-actin interaction inhibitor identified herein reduces proliferation and migration of RCC cells in vitro and RCC tumor growth in vivo Based on these findings, we propose a potentiating role for Pfn1 in promoting tumor cell aggressiveness in the setting of ccRCC.Widespread testing for the presence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise, and/or instrumentation necessary to detect the virus by quantitative RT-PCR (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages. The Georgia Tech COVID-19 Test Kit Support Group, composed of faculty, staff, and trainees across the biotechnology quad at Georgia Institute of Technology, synthesized multiplexed primers and probes and formulated a master mix composed of enzymes and proteins produced in-house. Our in-house kit compares favorably with a commercial product used for diagnostic testing. We also developed an environmental testing protocol to readily monitor surfaces for the presence of SARS-CoV-2. Our blueprint should be readily reproducible by research teams at other institutions, and our protocols may be modified and adapted to enable SARS-CoV-2 detection in more resource-limited settings.
Children with isolated neutropenia (absolute neutrophil count [ANC] <1500/μL) are frequently referred to pediatric hematology and oncology clinics for further diagnostic evaluation. Scant literature exists on interventions and outcomes for isolated neutropenia. We hypothesized that children will have resolution of their neutropenia without the need for intervention(s) by a pediatric hematologist and oncologist.
We performed a 5.5-year institutional review board-approved retrospective chart review of children referred to our pediatric hematology and oncology clinics for isolated neutropenia. Neutropenia was categorized as mild (ANC of 1001-1500/μL), moderate (ANC of 500-1000 μL), severe (ANC of 201-500/μL), or very severe (ANC of ≤200/μL).
Among 155 children referred with isolated neutropenia, 45 (29%) had mild neutropenia, 65 (42%) had moderate neutropenia, 30 (19%) had severe neutropenia, and 15 (10%) had very severe neutropenia. Only 29 (19%) children changed to an ANC category lower than their initial referral category. At a median follow-up of 12 months, 101 children had resolution of neutropenia, 40 children had mild neutropenia, 10 children had moderate neutropenia, 3 children had severe neutropenia, and 1 patient had very severe neutropenia. A specific diagnosis was not identified in most (54%) children. The most common etiologies were viral suppression (16%), autoimmune neutropenia (14%), and drug-induced neutropenia (8%). Black children had a 3.5 higher odds of having persistent mild neutropenia. Six (4%) children received granulocyte colony-stimulating factor therapy.
Most children referred for isolated neutropenia do not progress in severity and do not require subspecialty interventions or hospitalizations.
Most children referred for isolated neutropenia do not progress in severity and do not require subspecialty interventions or hospitalizations.
To determine impact of a primary care-based child obesity prevention intervention beginning during pregnancy on early childhood weight outcomes in low-income Hispanic families.
A randomized controlled trial comparing mother-infant pairs receiving either standard care or the Starting Early Program providing prenatal and postpartum nutrition counseling and nutrition parenting support groups targeting key obesity-related feeding practices in low-income groups. Primary outcomes were reduction in weight-for-age
-scores (WFAzs) from clinical anthropometric measures, obesity prevalence (weight for age ≥95th percentile), and excess weight gain (WFAz trajectory) from birth to age 3 years. Secondary outcomes included dose effects.
Pregnant women (
= 566) were enrolled in the third trimester; 533 randomized to intervention (
= 266) or control (
= 267). Also, 358 children had their weight measured at age 2 years; 285 children had weight measured at age 3 years. Intervention infants had lower mean WFAz at 18 months (0.49 vs 0.73,
= .04) and 2 years (0.56 vs 0.81,
= .03) but not at 3 years (0.63 vs 0.59,
= .76). No group differences in obesity prevalence were found. When generalized estimating equations were used, significant average treatment effects were detected between 10-26 months (B = -0.19,
= .047), although not through age 3 years. In within group dose analyses at 3 years, obesity rates (26.4%, 22.5%, 8.0%,
= .02) decreased as attendance increased with low, medium, and high attendance.
Mean WFAz and growth trajectories were lower for the intervention group through age 2 years, but there were no group differences at age 3. Further study is needed to enhance sustainability of effects beyond age 2.
Mean WFAz and growth trajectories were lower for the intervention group through age 2 years, but there were no group differences at age 3. Further study is needed to enhance sustainability of effects beyond age 2.
Catheter-associated urinary tract infections (CAUTIs) are a leading cause of health care-associated infection. Catheter insertion bundles (IBs) and maintenance bundles (MBs) have been developed to prevent CAUTIs but have not been extensively validated for use in pediatric populations. We report the CAUTI prevention efforts of a large network of children's hospitals.
Children's hospitals joined the Children's Hospitals' Solutions for Patient Safety engagement network from 2011 to 2017, using an open start time engagement approach, and elected to participate in CAUTI prevention efforts, with 26 submitting data initially and 128 at the end. CAUTI prevention recommendations were first released in May 2012, and IBs and MBs were released in May 2014. Hospitals reported on CAUTIs, patient-days, and urinary catheter-line days and tracked reliability to each bundle. find more For the network, run charts or control charts were used to plot CAUTI rates, urinary catheter use, and reliability to each bundle component.
After the introduction of the pediatric CAUTI IBs and MBs, CAUTI rates across the network decreased 61.6%, from 2.55 to 0.98 infections per 1000 catheter-line days. Centerline shifts occurred both before and after the 2015 Centers for Disease Control and Prevention CAUTI definition change. Urinary catheter use rates did not decline during the intervention period. Network reliability to the IBs and MBs increased to 95.4% and 86.9%, respectively.
IBs and MBs aimed at preventing CAUTIs were introduced across a large network of children's hospitals. Across the network, the rate of urinary tract infections among hospitalized children with indwelling urinary catheters decreased 61.6%.
IBs and MBs aimed at preventing CAUTIs were introduced across a large network of children's hospitals. Across the network, the rate of urinary tract infections among hospitalized children with indwelling urinary catheters decreased 61.6%.Plasmodium, the malaria parasite, undergoes a complex life cycle alternating between a vertebrate host and a mosquito vector of the genus Anopheles In red blood cells of the vertebrate host, Plasmodium multiplies asexually or differentiates into gamete precursors, the male and female gametocytes, responsible for parasite transmission. Sexual stage maturation occurs in the midgut of the mosquito vector, where male and female gametes egress from the host erythrocytes to fuse and form a zygote. Gamete egress entails the successive rupture of two membranes surrounding the parasite, the parasitophorous vacuole membrane and the erythrocyte plasma membrane. In this study, we used the rodent model parasite Plasmodium berghei to design a label-free quantitative proteomic approach aimed at identifying gender-related proteins differentially released/secreted by purified mature gametocytes when activated to form gametes. We compared the abundance of molecules secreted by wild type gametocytes of both genders with that of a transgenic line defective in male gamete maturation and egress.
