Publications by authors named "Lisa Smith"

320 Publications

Direct interaction of HIV gp120 with neuronal CXCR4 and CCR5 receptors induces cofilin-actin rod pathology via a cellular prion protein- and NOX-dependent mechanism.

PLoS One 2021 11;16(3):e0248309. Epub 2021 Mar 11.

Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.

Nearly 50% of individuals with long-term HIV infection are affected by the onset of progressive HIV-associated neurocognitive disorders (HAND). HIV infiltrates the central nervous system (CNS) early during primary infection where it establishes persistent infection in microglia (resident macrophages) and astrocytes that in turn release inflammatory cytokines, small neurotoxic mediators, and viral proteins. While the molecular mechanisms underlying pathology in HAND remain poorly understood, synaptodendritic damage has emerged as a hallmark of HIV infection of the CNS. Here, we report that the HIV viral envelope glycoprotein gp120 induces the formation of aberrant, rod-shaped cofilin-actin inclusions (rods) in cultured mouse hippocampal neurons via a signaling pathway common to other neurodegenerative stimuli including oligomeric, soluble amyloid-β and proinflammatory cytokines. Previous studies showed that synaptic function is impaired preferentially in the distal proximity of rods within dendrites. Our studies demonstrate gp120 binding to either chemokine co-receptor CCR5 or CXCR4 is capable of inducing rod formation, and signaling through this pathway requires active NADPH oxidase presumably through the formation of superoxide (O2-) and the expression of cellular prion protein (PrPC). These findings link gp120-mediated oxidative stress to the generation of rods, which may underlie early synaptic dysfunction observed in HAND.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248309PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951892PMC
March 2021

A multicenter, prospective randomized trial of negative pressure wound therapy for infrainguinal revascularization with a groin incision.

J Vasc Surg 2021 Feb 4. Epub 2021 Feb 4.

Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, Mass.

Background: Wound complications after open infrainguinal revascularization are a frequent cause of patient morbidity, resulting in increased healthcare costs. The purpose of the present study was to assess the effects of closed incision negative pressure therapy (ciNPT) on groin wound complications after infrainguinal bypass and femoral endarterectomy.

Methods: A total of 242 patients who had undergone infrainguinal bypass (n = 124) or femoral endarterectomy (n = 118) at five academic medical centers in New England from April 2015 to August 2019 were randomized to ciNPT (PREVENA; 3M KCI, St Paul, Minn; n = 118) or standard gauze (n = 124). The primary outcome measure was a composite endpoint of groin wound complications, including surgical site infections (SSIs), major noninfectious wound complications, or graft infections within 30 days after surgery. The secondary outcome measures included 30-day SSIs, 30-day noninfectious wound complications, readmission for wound complications, significant adverse events, and health-related quality of life using the EuroQoL 5D-3L survey.

Results: The ciNPT and control groups had similar demographics (age, 67 vs 67 years, P = .98; male gender, 71% vs 70%, P = .86; white race, 93% vs 93%, P = .97), comorbidities (previous or current smoking, 93% vs 94%, P = .46; diabetes, 41% vs 48%, P = .20; renal insufficiency, 4% vs 7%, P = .31), and operative characteristics, including procedure type, autogenous conduit, and operative time. No differences were found in the primary composite outcome at 30 days between the two groups (ciNPT vs control: 31% vs 28%; P = .55). The incidence of SSI at 30 days was similar between the two groups (ciNPT vs control: 11% vs 12%; P = .58). Infectious (13.9% vs 12.6%; P = .77) and noninfectious (20.9% vs 17.6%; P = .53) wound complications at 30 days were also similar for the ciNPT and control groups. Wound complications requiring readmission also similar between the two groups (ciNPT vs control: 9% vs 7%; P = .54). The significant adverse event rates were not different between the two groups (ciNPT vs control: 13% vs 16%; P = .53). The mean length of the initial hospitalization was the same for the ciNPT and control groups (5.2 vs 5.7 days; P = .63). The overall health-related quality of life was similar at baseline and at 14 and 30 days postoperatively for the two groups. Although not powered for stratification, we found no differences among the subgroups in gender, obesity, diabetes, smoking, claudication, chronic limb threatening ischemia, bypass, or endarterectomy. On multivariable analysis, no differences were found in wound complications at 30 days for the ciNPT vs gauze groups (odds ratio, 1.4; 95% confidence interval, 0.8-2.6; P = .234).

Conclusions: In contrast to other randomized studies, our multicenter trial of infrainguinal revascularization found no differences in the 30-day groin wound complications for patients treated with ciNPT vs standard gauze dressings. However, the SSI rate was lower in the control group than reported in other studies, suggesting other practice patterns and processes of care might have reduced the rate of groin infections. Further study might identify the subsets of high-risk patients that could benefit from ciNPT.
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http://dx.doi.org/10.1016/j.jvs.2020.12.100DOI Listing
February 2021

Part-time positions in Caseload Midwifery Group Practice: Impact on satisfaction and quality of care.

Women Birth 2020 Nov 18. Epub 2020 Nov 18.

Centre for Quality and Patient Safety Research, Western Health Partnership, Victoria, Australia.

Background: Caseload continuity of care models of midwifery are associated with benefits for both mothers and babies. For midwifery staff, caseload models offer flexibility, supportive work partnerships, and one-to-one care with women. However, most caseload models require midwives to be employed 0.7 full-time equivalent or more.

Aim: To evaluate the satisfaction of women and staff with 0.5 full-time equivalent part-time caseload midwifery group practice care.

Methods: A mixed-methods survey study was undertaken. Women, part-time and full-time caseload midwifery staff completed an online survey regarding their experiences. Descriptive statistics were calculated and thematic analysis of qualitative responses was undertaken.

Findings: Women were highly satisfied with the part-time model of care. They indicated a number of advantages including excellent support, flexibility, and responsiveness in receiving care from two primary midwives. Similarly, caseload team midwives were satisfied with the part-time model and valued the flexibility that it offers. Improved coverage of hours and being part of a workplace that promoted work-life balance were perceived as key advantages of having part-time staff in the caseload team.

Discussion: The part-time model facilitated continuity of care and was received positively by women. For staff, part-time roles enhanced work satisfaction and reduced burnout. Most staff encouraged greater expansion of part-time roles. Organisations may reduce midwife burnout and associated costs by implementing part-time roles to support work-life balance and staff satisfaction.

Conclusion: Part-time caseload midwifery models offered greater flexibility and work-life-balance for staff compared to full-time models and were well received by women.
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http://dx.doi.org/10.1016/j.wombi.2020.11.001DOI Listing
November 2020

Varying levels of depressive symptoms and lifestyle health behaviors in a low income, urban population.

J Behav Med 2021 Apr 16;44(2):212-221. Epub 2020 Sep 16.

Division of Chronic Disease and Injury Prevention, Los Angeles County Department of Public Health, 3530 Wilshire Blvd., 8th Floor, Los Angeles, CA, 90010, USA.

This study examined the relationships between varying levels of depressive symptoms and key dietary indicators of chronic disease risk, sugar-sweetened beverage (SSB) and fruit and vegetable (F + V) consumption, among a racially/ethnically diverse urban population in Los Angeles County (LAC). Analyses were carried out using data from a 2012 cross-sectional health survey of 1401 low-income public health center clients. Participants with a high level of depressive symptoms consumed 30% more SSBs (IRR = 1.30, 95% CI = 1.08, 1.55) than participants with a lower level of these symptoms. Other predictors of higher SSB consumption included being African American/Black (IRR = 1.65, 95% CI = 1.32, 2.05), male (IRR = 1.20, 95% CI = 1.06, 1.35), U.S. born (IRR = 1.32, 95% CI = 1.11, 1.57), and using tobacco (IRR = 1.26, 95% CI = 1.11, 1.43). Similar associations with F + V consumption were not found. Findings suggest that depressive symptoms may influence certain health behaviors in certain groups under certain situations. Policy and practice implications are discussed within this context.
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http://dx.doi.org/10.1007/s10865-020-00179-6DOI Listing
April 2021

Silencing integrated SIV proviral DNA with TAR-specific CRISPR tools.

J Med Primatol 2020 10 9;49(5):269-279. Epub 2020 Sep 9.

Host-Pathogen Interactions Program, Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA.

Background: One approach for a functional HIV cure is to prevent transcription from integrated proviral DNA. A critical step in HIV transcription is the Tat protein interaction with the TAR element viral RNA. We tested the strategy of blocking this Tat-TAR interaction in the SIVmac model.

Methods: We designed five CRISPR short guiding RNAs (sgRNAs) targeting the SIVmac TAR element, along with inactive versions of Cas9 (dCas9). These sgRNA constructs were delivered as ribonucleoproteins or plasmid DNA, along with SIV DNA. The constructs were also tested in integrated viral DNA in a cell line chronically infected by SIV.

Results: The sgRNAs targeting the coding strand of the TAR element inhibited SIV RNA transcription in association with dCas9-KRAB, but not with dCas9.

Conclusions: Induction of epigenetic modifications may be more effective in inactivating provirus than transcriptional interference and thus may be a better strategy to achieve a functional cure in vivo.
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http://dx.doi.org/10.1111/jmp.12494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869755PMC
October 2020

Living with the financial consequences of cancer: A life course perspective.

J Psychosoc Oncol 2021 2;39(1):17-34. Epub 2020 Sep 2.

University of Louisville School of Medicine, Louisville, KY, USA.

Purpose: Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients' financial hardship from diagnosis to post-treatment.

Methods: In-depth interviews were conducted with 26 cancer survivors who reported financial hardship during and/or after treatment. The interviews were analyzed using Dedoose as an organizational tool, the life course perspective as an organizing theoretical framework, and a thematic analysis tool to answer our research questions. Our analysis identified that timing and sequencing of life transitions and stress proliferation furthered the process of financial stress over time.

Findings: Cancer survivors do not experience financial toxicity as a singular process; the experience can be quite different depending on age and life transitions.

Practice/policy Implications: These findings provide psychosocial oncology providers with a framework for identifying patients at risk for financial distress and addressing the critical needs related to their life stage.
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http://dx.doi.org/10.1080/07347332.2020.1814933DOI Listing
September 2020

Discovery of a Potent and Selective Covalent Inhibitor and Activity-Based Probe for the Deubiquitylating Enzyme UCHL1, with Antifibrotic Activity.

J Am Chem Soc 2020 07 1;142(28):12020-12026. Epub 2020 Jul 1.

Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, W12 0BZ, U.K.

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitylating enzyme that is proposed as a potential therapeutic target in neurodegeneration, cancer, and liver and lung fibrosis. Herein we report the discovery of the most potent and selective UCHL1 probe (IMP-1710) to date based on a covalent inhibitor scaffold and apply this probe to identify and quantify target proteins in intact human cells. IMP-1710 stereoselectively labels the catalytic cysteine of UCHL1 at low nanomolar concentration in cells. We further demonstrate that potent and selective UCHL1 inhibitors block pro-fibrotic responses in a cellular model of idiopathic pulmonary fibrosis, supporting the potential of UCHL1 as a potential therapeutic target in fibrotic diseases.
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http://dx.doi.org/10.1021/jacs.0c04527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366380PMC
July 2020

Quantitative measurements of prostate capsule and gland density and their correlation to prostate size: possible clinical implications in prostate cancer.

Int Urol Nephrol 2020 Oct 6;52(10):1829-1837. Epub 2020 Jun 6.

Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, MS7260, Lubbock, TX, 79430-7260, USA.

Purpose: To study histo-anatomical imaging features and possible association between prostate volume, capsule thickness and glandular density within the peripheral zone (PZ) of prostates of different sizes.

Methods: Patients were selected who had undergone radical prostatectomy. Specimen selection was based on two factors: first, easy reconstruction of prostate anatomy by the histological slides; and second, based on prostate size. Specimens were chosen with small (< 35 cc) and also with large size (> 80 cc). A total of 20 patients were selected. None of these patients had undergone previous treatment. Computer-based imaging for quantitative measurements of capsule thickness and glandular density within the PZ were performed. Multiple regression analysis was performed to determine the relationship between these measured parameters and the clinical characteristics of these patients.

Results: Multiple regression analysis revealed a strong, positive association between prostate size and average capsule thickness; on the contrary, we found a negative correlation between prostate volume and average glandular density. Fibrotic thickness of the capsule was associated with gland atrophy and decreased gland density within the PZ.

Conclusions: The results suggest that BPH may be associated with the development of fibrosis and gland atrophy within the peripheral zone. As 80% of prostate cancer originates from the glandular epithelium within the peripheral zone, this observed phenomenon may explain the inverse relationship between BPH and incidence of prostate cancer well documented in the literature.
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http://dx.doi.org/10.1007/s11255-020-02527-6DOI Listing
October 2020

Spatial and developmental synthesis of endogenous sesquiterpene lactones supports function in growth regulation of sunflower.

Planta 2020 Jun 5;252(1). Epub 2020 Jun 5.

Institute of Biology, University of Hohenheim, Garbenstraße 30, 70593, Stuttgart, Germany.

Main Conclusion: Tissue-specific occurrence and formation of endogenous sesquiterpene lactones has been assessed and suggests physiological function as antagonists of auxin-induced plant growth in sunflower. Sunflower, Helianthus annuus, accumulate high concentrations of bioactive sesquiterpene lactones (STL) in glandular trichomes, but in addition, structurally different STL occur in only trace amounts in the inner tissues. The spatial and temporal production of these endogenous STL during early phases of plant development is widely unknown and their physiological function as putative natural growth regulators is yet speculative. By means of HPLC and MS analysis it was shown that costunolide, dehydrocostuslactone, 8-epixanthatin and tomentosin are already present in dry seeds and can be extracted in low amounts from cotyledons, hypocotyls and roots of seedlings during the first days after germination. Semi-quantitative and RT-qPCR experiments with genes of the key enzymes of two independent routes of the endogenous STL biosynthesis confirmed the early and individual expression in these organs and revealed a gradual down regulation during the first 72-96 h after germination. Light irradiation of the plants led to a fast, but transient increase of STL in parts of the hypocotyl which correlated with growth retardation of the stem. One-sided external application of costunolide on hypocotyls conferred reduced growth of the treated side, thus resulting in the curving of the stem towards the side of the application. This indicates the inhibiting effects of STL on plant growth. The putative function of endogenous STL in sunflower as antagonists of auxin in growth processes is discussed.
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http://dx.doi.org/10.1007/s00425-020-03409-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275010PMC
June 2020

Achieving more with less: A critical review of protocols for forensic investigation of sexual violence in low-resource environments.

Forensic Sci Int Synerg 2019 12;1:108-113. Epub 2019 Jul 12.

Wangu Kanja Foundation, Nairobi, Kenya.

Sexual and gender based violence (SGBV) is notoriously difficult to investigate and prosecute. SGBV occurs in varied contexts and requires flexibility in the investigative approach in order to develop a strong evidence base to enable successful prosecutions. In this paper we focus on the need for innovation and development of training protocols for gathering testimonial and forensic evidence in SGBV cases, particularly in low resource environments, such as developing countries, displaced communities, and conflict and post-conflict societies. We discuss existing international guidelines that have been developed for improving the documentation and investigation of SGBV in these contexts, and argue there are significant gaps in the knowledge base that impede the effective implementation of such guidelines. In particular, collaborative research between academics, practitioners and NGOs is needed to address several priority areas. These include the development of programmes geared towards training non-specialist practitioners who work in low resource environments, as well as research programmes that evaluate the implementation of the programmes. This research will improve access to justice for victims and accountability for perpetrators of sexual violence.
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http://dx.doi.org/10.1016/j.fsisyn.2019.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219185PMC
July 2019

Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia.

Cancer Genet 2020 05 21;243:52-72. Epub 2020 Mar 21.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.

Clinical management and risk stratification of B-lymphoblastic leukemia/ lymphoma (B-ALL/LBL) depend largely on identification of chromosomal abnormalities obtained using conventional cytogenetics and Fluorescence In Situ Hybridization (FISH) testing. In the last few decades, testing algorithms have been implemented to support an optimal risk-oriented therapy, leading to a large improvement in overall survival. In addition, large scale genomic studies have identified multiple aberrations of prognostic significance that are not routinely tested by existing modalities. However, as chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) technologies are increasingly used in clinical management of hematologic malignancies, these abnormalities may be more readily detected. In this article, we have compiled a comprehensive, evidence-based review of the current B-ALL literature, focusing on known and published subtypes described to date. More specifically, we describe the role of various testing modalities in the diagnosis, prognosis, and therapeutic relevance. In addition, we propose a testing algorithm aimed at assisting laboratories in the most effective detection of the underlying genomic abnormalities.
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http://dx.doi.org/10.1016/j.cancergen.2020.03.001DOI Listing
May 2020

Effective Practices and Recommendations for Drive-Through Clinic Points of Dispensing: A Systematic Review.

Disaster Med Public Health Prep 2020 Apr 1:1-15. Epub 2020 Apr 1.

Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Jiann Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA.

Objective: Drive-through clinics (DTCs) are a novel type of point of dispensing where participants drive to a designated location and receive prophylaxis while remaining inside their vehicle. The objective of this review was to identify effective practices and recommendations for implementing DTCs for mass prophylaxis dispensing during emergency events.

Methods: A systematic review was conducted for articles covering DTCs published between 1990 and 2019. Inclusion criteria were peer-reviewed, written in English, and addressed DTCs sufficiently. Effective practices and recommendations identified in the literature were presented by theme.

Results: A total of 13 articles met inclusion criteria. The themes identified were (1) optimal DTC design and planning via decision support systems and decision support tools; (2) clinic layouts, locations, and design aspects; (3) staffing, training, and DTC communication; (4) throughput time; (5) community outreach methods; (6) DTC equipment; (7) infection prevention and personal protective equipment; and (8) adverse events prevention and traffic management.

Conclusions: DTCs are an essential component of emergency preparedness and must be optimally designed and implemented to successfully dispense mass prophylaxis to a community within 48 hours. The effective practices and recommendations presented can be used for the development, implementation, and improvement of DTCs for their target populations.
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http://dx.doi.org/10.1017/dmp.2020.15DOI Listing
April 2020

Towards an understanding of the physical activity-BDNF-cognition triumvirate: A review of associations and dosage.

Ageing Res Rev 2020 07 13;60:101044. Epub 2020 Mar 13.

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, 54 Mills Road, Australian National University, Acton, ACT, 2615, Australia. Electronic address:

Physical activity has received substantial research attention due to its beneficial impact on cognition in ageing, particularly via the action of brain-derived neurotrophic factor (BDNF). It is well established that physical activity can elevate circulating levels of BDNF, and that BDNF has neurotrophic, neuroprotective and cognitively beneficial properties. Yet, practical implementation of this knowledge is limited by a lack of clarity on context and dose-effect. Against a shifting backdrop of gradually diminishing physical and cognitive capacity in normal ageing, the type, intensity, and duration of physical activity required to elicit elevations in BDNF, and more importantly, the magnitude of BDNF elevation required for detectable neuroprotection remains poorly characterised. The purpose of this review is to provide an overview of the association between physical activity, BDNF, and cognition, with a focus on clarifying the magnitude of these effects in the context of normative ageing. We discuss the implications of the available evidence for the design of physical activity interventions intended to promote healthy cognitive ageing.
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http://dx.doi.org/10.1016/j.arr.2020.101044DOI Listing
July 2020

Investigations into Enhancing Yersinia pestis Cells Viability following Environmental Sampling for Forensic Analysis.

J Forensic Sci 2020 Jul 3;65(4):1315-1323. Epub 2020 Feb 3.

U.S. Army - Combat Capabilities Development Command - Chemical Biological Center, Aberdeen Proving Ground, MD, 21010.

Following an intentional or accidental bio-warfare agent (BWA) release, environmental sample analysis is absolutely critical to determine the extent of contamination. When dealing with nonspore forming BWA (e.g., Yersinia pestis), retention of cell viability is central to such analyses. Even though significant advances have been achieved in DNA sequencing technologies, a positive identification of BWAs in environmental samples must be made through the ability of cells to form colony-forming units upon culturing. Inability to revive the cells between collection and analysis renders such studies inconclusive. Commercial kits designed to preserve the viability of pathogens contained within clinical samples are available, but many of them have not been examined for their ability to preserve samples containing suspected BWAs. The study was initiated to examine the applicability of commercial solutions aiding in retention of Y. pestis viability in samples stored under nonpermissive temperatures, that is, 40 and 37°C. While none of the tested solutions sustained cell viability at 40°C, the results show five out of 17 tested preservatives were capable of supporting viability of Y. pestis at 37°C.
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http://dx.doi.org/10.1111/1556-4029.14293DOI Listing
July 2020

A malectin domain kinesin functions in pollen and seed development in Arabidopsis.

J Exp Bot 2020 03;71(6):1828-1841

Department of Animal and Plant Sciences and The Plant Production and Protection (P3) Centre, University of Sheffield, Western Bank, Sheffield, UK.

The kinesin family is greatly expanded in plants compared with animals and, with more than a third up-regulated in expression during cell division, it has been suggested that this expansion facilitated complex plant-specific cytoskeletal rearrangements. The cell cycle-regulated kinesins include two with an N-terminal malectin domain, a protein domain that has been shown to bind polysaccharides and peptides when found extracellularly in receptor-like kinases. Although malectin domain kinesins are evolutionarily deep rooted, their function in plants remains unclear. Here we show that loss of MALECTIN DOMAIN KINESIN 2 (MDKIN2) results in stochastic developmental defects in pollen, embryo, and endosperm. High rates of seed abnormalities and abortion occur in mdkin2 mutants through a partial maternal effect. No additive effect or additional developmental defects were noted in mdkin1 mdkin2 double mutants. MDKIN2 is expressed in regions of cell division throughout the plant. Subcellular localization of MDKIN2 indicates a role in cell division, with a possible secondary function in the nuclei. Our results reveal a non-essential but important role for a malectin domain kinesin during development in plants.
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http://dx.doi.org/10.1093/jxb/eraa023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094084PMC
March 2020

Small History, Big Future.

Authors:
Lisa Smith

Small 2020 01;16(1):e1907143

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http://dx.doi.org/10.1002/smll.201907143DOI Listing
January 2020

CrRLK1L receptor-like kinases HERK1 and ANJEA are female determinants of pollen tube reception.

EMBO Rep 2020 02 23;21(2):e48466. Epub 2019 Dec 23.

Department of Animal and Plant Sciences and the Plant Production and Protection Centre, University of Sheffield, Sheffield, UK.

Communication between the gametophytes is vital for angiosperm fertilisation. Multiple CrRLK1L-type receptor kinases prevent premature pollen tube burst, while another CrRLK1L protein, FERONIA (FER), is required for pollen tube reception in the female gametophyte. We report here the identification of two additional CrRLK1L homologues, HERCULES RECEPTOR KINASE 1 (HERK1) and ANJEA (ANJ), which act redundantly to promote pollen tube growth arrest at the synergid cells. HERK1 and ANJ localise to the filiform apparatus of the synergid cells in unfertilised ovules, and in herk1 anj mutants, a majority of ovules remain unfertilised due to pollen tube overgrowth, together indicating that HERK1 and ANJ act as female determinants for fertilisation. As in fer mutants, the synergid cell-specific, endomembrane protein NORTIA (NTA) is not relocalised after pollen tube reception; however, unlike fer mutants, reactive oxygen species levels are unaffected in herk1 anj double mutants. Both ANJ and HERK1 associate with FER and its proposed co-receptor LORELEI (LRE) in planta. Together, our data indicate that HERK1 and ANJ act with FER to mediate female-male gametophyte interactions during plant fertilisation.
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http://dx.doi.org/10.15252/embr.201948466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001495PMC
February 2020

A Novel Upstream Regulator of Trichome Development Inhibitors.

Plant Physiol 2019 12;181(4):1398-1400

Department of Animal and Plant Sciences and the Plant Production and Protection Centre, University of Sheffield, Sheffield S10 2TN, United Kingdom

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http://dx.doi.org/10.1104/pp.19.01269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878029PMC
December 2019

A Community-Based Participatory Approach to Promote Healthy Eating Among Marshallese.

Hawaii J Health Soc Welf 2019 11;78(11):332-337

Office of Community Health and Research, University of Arkansas for Medical Sciences, Fayetteville, AR.

This article describes changes made to the menu served during the 2015 Marshallese May Day celebration in Northwest Arkansas, an annual Marshallese community event. The menu changes were part of a community-based participatory collaborative to improve nutrition and health in the Marshallese community. The 2015 May Day menu significantly reduced the 2014 May Day menu amount of calories, fat, carbohydrates, sodium, and cholesterol of foods offered by incorporating healthier ingredients and reducing portion sizes. Compared to the 2014 May Day menu, the total caloric value of the revised menu was reduced by more than 63%, declining from 1369 calories to 499 calories. The menu change affected an estimated 1,800 Marshallese in attendance for the 2015 May Day celebration. The successful implementation of the menu changes, which resulted in reductions in calories, fat, carbohydrates, sodium, and cholesterol offered to participants demonstrates the effectiveness of community-based participatory approaches in the implementation of policy, systems, and environmental strategies to promote health.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848001PMC
November 2019

Authors' response.

J Am Dent Assoc 2019 11;150(11):901-902

Adjunct Associate Professor of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA; Health Sciences Associate Professor of Family Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA; Co-program Leader, UCLA Clinical and Translational Science Institute, Los Angeles, CA; Director, Division of Chronic Disease and Injury Prevention, Los Angeles County Department of Public Health, Los Angeles, CA.

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http://dx.doi.org/10.1016/j.adaj.2019.09.006DOI Listing
November 2019

The Heat Is On: Maize Pollen Development after a Heat Wave.

Authors:
Lisa M Smith

Plant Physiol 2019 10;181(2):387-388

Department of Animal and Plant Sciences and The Plant Production and Protection (P3) Centre, University of Sheffield, Sheffield S10 2TN, Uinted Kingdom

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http://dx.doi.org/10.1104/pp.19.01025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776864PMC
October 2019

Surviving in a Hostile World: Plant Strategies to Resist Pests and Diseases.

Annu Rev Phytopathol 2019 08;57:505-529

Plant Production and Protection Institute and Department of Animal and Plant Sciences, The University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom; email:

As primary producers, plants are under constant pressure to defend themselves against potentially deadly pathogens and herbivores. In this review, we describe short- and long-term strategies that enable plants to cope with these stresses. Apart from internal immunological strategies that involve physiological and (epi)genetic modifications at the cellular level, plants also employ external strategies that rely on recruitment of beneficial organisms. We discuss these strategies along a gradient of increasing timescales, ranging from rapid immune responses that are initiated within seconds to (epi)genetic adaptations that occur over multiple plant generations. We cover the latest insights into the mechanistic and evolutionary underpinnings of these strategies and present explanatory models. Finally, we discuss how knowledge from short-lived model species can be translated to economically and ecologically important perennials to exploit adaptive plant strategies and mitigate future impacts of pests and diseases in an increasingly interconnected and changing world.
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http://dx.doi.org/10.1146/annurev-phyto-082718-095959DOI Listing
August 2019

Helicase-like transcription factor (Hltf) gene-deletion promotes oxidative phosphorylation (OXPHOS) in colorectal tumors of AOM/DSS-treated mice.

PLoS One 2019 28;14(8):e0221751. Epub 2019 Aug 28.

Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.

The helicase-like transcription factor (HLTF) gene-a tumor suppressor in human colorectal cancer (CRC)-is regulated by alternative splicing and promoter hypermethylation. In this study, we used the AOM/DSS-induced mouse model to show Hltf-deletion caused poor survival concomitant with increased tumor multiplicity, and dramatically shifted the topographic distribution of lesions into the rectum. Differential isoform expression analysis revealed both the truncated isoform that lacks a DNA-repair domain and the full length isoform capable of DNA damage repair are present during adenocarcinoma formation in controls. iPathwayGuide identified 51 dynamically regulated genes of 10,967 total genes with measured expression. Oxidative Phosphorylation (Kegg: 00190), the top biological pathway perturbed by Hltf-deletion, resulted from increased transcription of Atp5e, Cox7c, Uqcr11, Ndufa4 and Ndufb6 genes, concomitant with increased endogenous levels of ATP (p = 0.0062). Upregulation of gene expression, as validated with qRT-PCR, accompanied a stable mtDNA/nDNA ratio. This is the first study to show Hltf-deletion in an inflammation-associated CRC model elevates mitochondrial bioenergetics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221751PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713344PMC
March 2020

Driving Distractions Among Public Health Center Clients: A Look at Local Patterns During the Infancy of Distracted Driving Laws in California.

Front Public Health 2019 8;7:207. Epub 2019 Aug 8.

Division of Chronic Disease and Injury Prevention, Los Angeles County Department of Public Health, Los Angeles, CA, United States.

To provide a baseline of various driving behaviors and to identify opportunities for prevention of distracted driving during the infancy of state laws that prohibited cellphone use while operating a motor vehicle, the 2010-2011 Distracted Driving Survey collected information on multiple distracted driving behaviors from lower-income clients of three designated, multi-purpose public health centers in Los Angeles County. Descriptive and multivariable negative binomial regression analyses were performed to examine patterns of driving distractions using the Distracted Driving Survey dataset ( = 1,051). The most common distractions included talking to other passengers ( = 912, 86.8%); adjusting the radio, MP3, or cassette player ( = 873, 83.1%); and adjusting other car controls ( = 838, 79.7%). The median number of distinct distractions per survey participant was 11 (range: 0-32). Factors predicting the number of distinct distractions included being male [incidence rate ratio (IRR): 1.14; 95% confidence interval (CI): 1.06, 1.23], having a lower education (IRR: 0.73; 95% CI: 0.62, 0.84), and having more years of driving experience (IRR: 1.67; 95% CI: 1.33, 2.11). A variety of distractions, including cellphone use and texting, were predictive of increased motor vehicle crashes in the prior 12 months ( < 0.05). Distracted driving beyond cellphone use and texting were common in the survey sample, suggesting a need for additional public education and more inclusive distracted driving laws that cover these other activity types.
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http://dx.doi.org/10.3389/fpubh.2019.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694288PMC
August 2019

A Rice Transcription Factor Controls Grain Length through Cell Number.

Plant Physiol 2019 08;180(4):1781-1783

Department of Animal and Plant Sciences, The Plant Production and Protection (P3) Centre, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom

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http://dx.doi.org/10.1104/pp.19.00730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670101PMC
August 2019

Prediabetes, diabetes, and other CVD-related conditions among Asian populations in Los Angeles County, 2014.

Ethn Health 2019 10 4;24(7):779-789. Epub 2017 Sep 4.

d Department of Epidemiology, University of California, Los Angeles (UCLA) Jonathan and Karin Fielding School of Public Health , Los Angeles , CA , USA.

To assess the prevalence of four common health conditions related to cardiovascular disease risk among Asians in Los Angeles County. A survey of Asians in Los Angeles County was conducted utilizing purposive sampling to recruit from the region's Service Planning Areas 3 and 4; these underserved areas contain high density of Asian populations. Descriptive and multivariable regression analyses were performed to explore and describe potential associations between self-reported diagnoses of prediabetes, diabetes, hypertension, and high cholesterol and body mass index (measured with non-Asian versus Asian cut points) by race/ethnicity (Chinese/Filipino/Korean/Taiwanese/Thai/Vietnamese). The survey response rate was nearly 60%. The analysis included 1,377 Asians, self-identified as either Chinese ( = 700), Filipino ( = 69), Korean ( = 339), Taiwanese ( = 48), Thai ( = 115), or Vietnamese ( = 106). Results showed that, in comparison to other Asians, Filipinos had the highest risks for two of the four conditions described. Other results by subgroup affirmed a similar heterogeneous pattern of Asian health locally. These and other results from the survey point to potential gaps in healthcare needs of Asians, and to opportunities where local public health efforts could help increase these populations' access to cardiovascular disease-related health and social services.
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http://dx.doi.org/10.1080/13557858.2017.1373076DOI Listing
October 2019

Possible clinical implications of peripheral zone changes depending on prostate size.

Int Urol Nephrol 2019 Oct 18;51(10):1721-1726. Epub 2019 Jul 18.

Department of Urology, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430-7260, USA.

Purpose: Although numerous studies have observed an inverse relationship between the size of benign prostate hypertrophy (BPH) and the incidence of prostate cancer (PCa), few studies have explored specific mechanisms by which BPH and PCa may influence one another. In a recent study, one possibility has been brought up that growth in the transition zone due to BPH may cause pressure-induced fibrotic changes in the peripheral zone, an area where 80% of cancer occurs, leading to gland atrophy and the thickening of the prostatic capsule. To shed more light on this phenomenon, we conducted a pilot study examining the quantitative and qualitative histo-anatomical changes that occur in the peripheral zone associated with BPH.

Methods: Thirty-nine prostate specimens of various sizes were selected from patients who had undergone radical prostatectomies. Each prostate was evaluated in six different locations along the dorsal aspect of the peripheral zone by measuring the thickness of the peripheral fibrotic zone (prostate capsule) and its association with gland atrophy. Multiple regression analysis was performed to determine the relationship between prostate size and the average thickness of the prostate capsule.

Results: Multiple regression analysis revealed a strong, positive relationship between prostate size and average capsule thickness with a Pearson coefficient of 0.707 (p < 0.05). Fibrotic histo-anatomical changes were spatially associated with gland atrophy: glands found within the peripheral fibrotic zone appeared elongated and atrophic.

Conclusion: The results suggest that BPH may be associated with the development of fibrotic material and atrophy of glands within the peripheral zone. Because this atrophy involves glands where 80% of prostate cancer originates, this potentially explains the inverse relationship between PCa and BPH.
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http://dx.doi.org/10.1007/s11255-019-02221-2DOI Listing
October 2019

Eμ-TCL1xMyc: A Novel Mouse Model for Concurrent CLL and B-Cell Lymphoma.

Clin Cancer Res 2019 10 11;25(20):6260-6273. Epub 2019 Jul 11.

Division of Hematology, The Ohio State University, Columbus, Ohio.

Purpose: Aberrant Myc expression is a major factor in the pathogenesis of aggressive lymphoma, and these lymphomas, while clinically heterogeneous, often are resistant to currently available treatments and have poor survival. Myc expression can also be seen in aggressive lymphomas that are observed in the context of CLL, and we sought to develop a mouse model that could be used to study therapeutic strategies for aggressive lymphoma in the context of CLL.

Experimental Design: We crossed the Eμ-TCL1 mouse model with the Eμ-Myc mouse model to investigate the clinical phenotype associated with B-cell-restricted expression of these oncogenes. The resulting malignancy was then extensively characterized, from both a clinical and biologic perspective.

Results: Eμ-TCL1xMyc mice uniformly developed highly aggressive lymphoid disease with histologically, immunophenotypically, and molecularly distinct concurrent CLL and B-cell lymphoma, leading to a significantly reduced lifespan. Injection of cells from diseased Eμ-TCL1xMyc into WT mice established a disease similar to that in the double-transgenic mice. Both Eμ-TCL1xMyc mice and mice with disease after adoptive transfer failed to respond to ibrutinib. Effective and durable disease control was, however, observed by selective inhibition of nuclear export protein exportin-1 (XPO1) using a compound currently in clinical development for relapsed/refractory malignancies, including CLL and lymphoma.

Conclusions: The Eμ-TCL1xMyc mouse is a new preclinical tool for testing experimental drugs for aggressive B-cell lymphoma, including in the context of CLL.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-0273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801062PMC
October 2019

A semester-long critical thinking course in the first semester of pharmacy school: Impact on critical thinking skills.

Curr Pharm Teach Learn 2019 05 6;11(5):499-504. Epub 2019 May 6.

Wingate University School of Pharmacy, 515 N. Main Street, Wingate, NC 28174, United States. Electronic address:

Introduction: To determine whether critical thinking improved after student-pharmacists participated in a semester-long critical thinking course in the first semester of pharmacy school.

Methods: Students took the Health Sciences Reasoning Test-Numeracy (HSRT-N) on the first and last day of the course. The overall HSRT-N score, percentile ranking, and eight sub-categories within the HSRT-N (analysis, interpretation, inference, evaluation, explanation, induction, deduction, and numeracy) were evaluated. A multivariable quantile regression model evaluated the association between the post-test percentile and student age, at which campus the student was enrolled, and how many minutes the students required to take the test.

Results: There were no significant differences in overall scores, percentile, or the sub-category scores with the exception of a significant increase in the analysis score and a significant decrease in the induction score. There was a greater increase for students in the lower quartiles on the pre-test compared to students in the higher quartiles on the pre-test. The largest percentile change occurred in students in the 25th-50th percentiles.

Conclusion: A statistically significant improvement in the analysis category of the HSRT-N and a greater increase for students in the lower quartiles on the pre-test to the post-test suggests students with the lowest quartiles on the HSRT-N would benefit the most from a critical thinking course.
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http://dx.doi.org/10.1016/j.cptl.2019.02.014DOI Listing
May 2019