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1.
J Community Health ; 46(1): 165-173, 2021 02.
Article in English | MEDLINE | ID: mdl-32594413

ABSTRACT

National lung cancer screening with low dose computed tomography (LDCT) uptake is suboptimal. One factor contributing to slow uptake is lack of awareness. Trained Community Health Workers (CHWs) may be effective in increasing lung cancer screening awareness among disparate populations, however little is known about the processes necessary to scale an intervention for implementation by CHWs in a new area. We examined implementation processes with the RE-AIM framework and pilot tested a CHW-delivered lung cancer education intervention based on the Health Belief Model. We measured pre-post participant knowledge, attitudes and beliefs regarding cancer screening, lung cancer stigma, and intent to obtain LDCT screening. We used community-engaged strategies to collaborate with a local health system, to identify CHWs. CHWs were trained to recruit participants and deliver the one-session lung cancer education intervention. Seven CHWs and eight community sites participated. Participants (n = 77) were female (53%) primarily low income (62.9%); tobacco use was high (36.9%). Post intervention changes in lung cancer screening knowledge (p = < .0001), attitudes regarding lung cancer screening benefit (p = .034) and lung cancer stigma. (p = .024) We learned important lessons that will be useful in subsequent scaling. Collaborating with a local health system is a promising method to disseminate a lung cancer screening education intervention.


Subject(s)
Community Health Workers/education , Early Detection of Cancer/methods , Health Education/methods , Implementation Science , Lung Neoplasms/prevention & control , Mass Screening/methods , Community Health Workers/statistics & numerical data , Female , Humans , Male , Poverty/statistics & numerical data
2.
Res Nurs Health ; 44(5): 767-775, 2021 10.
Article in English | MEDLINE | ID: mdl-34227136

ABSTRACT

The COVID-19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID-19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID-19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID-19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory of Planned Behavior models. The majority of the 942 respondents were ≥36 years. A total of 54% were from central Kentucky, while 47.5% were from Appalachia. Among all participants, the pandemic worsened anxiety and depression and delayed access to medical care. There were no associations between sociodemographics and practicing COVID-19 prevention behaviors. Appalachian region was associated with financial burden and delay in medical care (p = 0.03). Appalachian respondents had lower perceived benefit and attitude for COVID-19 prevention behaviors (p = 0.004 and <0.001, respectively). Among all respondents, the perceived risk of contracting COVID was high (54%), yet 33.2% indicated unlikeliness to receive the COVID-19 vaccine if offered. The COVID-19 pandemic had a differential impact on White rural and Black nonrural populations. Nurses and public health officials should assess knowledge and explore patient's attitudes regarding COVID-19 prevention behaviors, as well as advocate for public health resources to reduce the differential impact of COVID-19 on these at-risk populations.


Subject(s)
COVID-19/prevention & control , Protestantism/psychology , Rural Population/statistics & numerical data , Adult , Aged , Black People/ethnology , Black People/psychology , Black People/statistics & numerical data , COVID-19/ethnology , COVID-19/psychology , Cross-Sectional Studies , Female , Humans , Kentucky , Male , Middle Aged , Rural Population/trends , Surveys and Questionnaires
3.
Retina ; 39(10): 2022-2031, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30015764

ABSTRACT

PURPOSE: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer. METHODS: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader. RESULTS: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05). CONCLUSION: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.


Subject(s)
Diabetes Mellitus/diagnosis , Fluorescein Angiography/methods , Macula Lutea/diagnostic imaging , Tomography, Optical Coherence/methods , Visual Acuity , Adult , Aged , Aged, 80 and over , Diabetes Mellitus/physiopathology , Diabetic Retinopathy , Female , Fundus Oculi , Humans , Male , Middle Aged , Retinal Vessels/diagnostic imaging , Retrospective Studies
4.
Diabetes Spectr ; 31(4): 324-329, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30510387

ABSTRACT

IN BRIEF Women with a history of gestational diabetes mellitus (GDM) are at higher risk for type 2 diabetes. This project piloted the National Diabetes Prevention Program lifestyle change program in cohorts of women with a history of GDM. The article describes recruitment efforts, challenges, and study participation and provides recommendations for future program implementation.

5.
J Public Health Manag Pract ; 22(6): 576-85, 2016.
Article in English | MEDLINE | ID: mdl-27682726

ABSTRACT

CONTEXT: Findings from the Centers for Disease Control and Prevention suggest that addressing persistent health disparities based on race and ethnicity must become a national priority. The field of cultural and linguistic competency has gained national attention by improving access to and quality of health care, patient-provider communication, health outcomes, and health equity for minority groups and other vulnerable or special needs populations. OBJECTIVES: (1) To measure how local health departments (LHDs) in Kentucky comply with the National Standards for Culturally and Linguistically Appropriate Services (CLAS); and (2) to provide policy recommendation based on the findings. This study is the first to assess a statewide public health system under the lens of CLAS. DESIGN: Analysis of cross-sectional survey. SETTING: Electronic surveys administered to LHD administrators in Kentucky. PARTICIPANTS: Public health directors, nurse leaders, and program managers. MAIN OUTCOME MEASURE: Levels of compliance with various CLAS standards were examined for rural and urban counties using a novel scoring method. RESULTS: A total of 159 LHD administrators received the survey. Response rate was 67% (106 participants). Rural and urban LHDs achieved moderate compliance on domains of plans and policies, quality monitoring and improvement for needs assessment, management information systems for clients, and staff training and development. Both geographic groups exhibited lesser compliance on domains of organizational governance, culturally inclusive health care environment for educational materials, and diversity of personnel recruitment. CONCLUSION: County and district LHDs in Kentucky have implemented activities and policies that comply with CLAS standards at levels that vary by domain. Areas requiring particular attention include organizational governance, culturally inclusive health care environment for educational materials, and diversity of personnel. Improvements in these areas may help LHDs better meet the needs of vulnerable populations, racial and ethnic minorities, and special needs groups. CLAS practices may allow organizations to adhere to national public health accreditation standards.


Subject(s)
Healthcare Disparities/statistics & numerical data , Local Government , Public Health/methods , Public Health/standards , Standard of Care/standards , Adult , Communication Barriers , Cross-Sectional Studies , Cultural Competency , Female , Health Services Accessibility , Hispanic or Latino , Humans , Male , Middle Aged , Quality of Health Care/standards , Racial Groups/ethnology , Racial Groups/statistics & numerical data , Rural Population/statistics & numerical data , Surveys and Questionnaires , Urban Population/statistics & numerical data
6.
J Photochem Photobiol B ; 257: 112971, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38955081

ABSTRACT

Bovine mastitis (BM) represents a significant challenge in the dairy industry. Limitations of conventional treatments have prompted the exploration of alternative approaches, such as photodynamic inactivation (PDI). In this study, we developed a PDI protocol to eliminate BM-associated pathogens using porphyrin-doped conjugated polymer nanoparticles (CPN). The PDI-CPN protocol was evaluated in four mastitis isolates of Staphylococcus and in a hyper-biofilm-forming reference strain. The results in planktonic cultures demonstrated that PDI-CPN exhibited a bactericidal profile upon relatively low light doses (∼9.6 J/cm2). Furthermore, following a seven-hour incubation period, no evidence of cellular reactivation was observed, indicating a highly efficient post-photodynamic inactivation effect. The successful elimination of bacterial suspensions encouraged us to test the PDI-CPN protocol on mature biofilms. Treatment using moderate light dose (∼64.8 J/cm2) reduced biofilm biomass and metabolic activity by up to 74% and 88%, respectively. The impact of PDI-CPN therapy on biofilms was investigated using scanning electron microscopy (SEM), which revealed nearly complete removal of the extracellular matrix and cocci. Moreover, ex vivo studies conducted on bovine udder skin demonstrated the efficacy of the therapy in eliminating bacteria from these scaffolds and its potential as a prophylactic method. Notably, the histological analysis of skin revealed no signs of cellular degeneration, suggesting that the protocol is safe and effective for BM treatment. Overall, this study demonstrates the potential of PDI-CPN in treating and preventing BM pathogens. It also provides insights into the effects of PDI-CPN on bacterial growth, metabolism, and survival over extended periods, aiding the development of effective control strategies and the optimization of future treatments.


Subject(s)
Biofilms , Light , Mastitis, Bovine , Nanoparticles , Polymers , Animals , Cattle , Nanoparticles/chemistry , Mastitis, Bovine/microbiology , Mastitis, Bovine/drug therapy , Biofilms/drug effects , Biofilms/radiation effects , Female , Polymers/chemistry , Polymers/pharmacology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Porphyrins/chemistry , Porphyrins/pharmacology , Staphylococcus/drug effects , Staphylococcus/radiation effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Microscopy, Electron, Scanning , Photochemotherapy
7.
J Morphol ; 284(8): e21611, 2023 08.
Article in English | MEDLINE | ID: mdl-37458081

ABSTRACT

Among anurans, Bufonids are recognized for their retarded sex differentiation. However, few studies have addressed gonadal morphogenesis in this family. Here, we analyzed the early gonadogenesis in laboratory-reared Rhinella arenarum. Few germ cells were identified in the genital ridge at Gosner stage 26. At metamorphosis, somatic cells and germ cells were observed in the outer region of the undifferentiated gonad, whereas the central region was occupied by stromal tissue. A cortico-medullary organization was first recognized on Day 7 postmetamorphosis. The cortex was composed of germ cells and encompassing epithelial cells, whereas the medulla contained cells presumptively derived from the coelomic epithelium. Medullary somatic cells formed metameric knots along the length of the undifferentiated gonad. Consequently, a series of 12-14 gonomeres became recognizable externally. The first sign of ovarian differentiation was observed on Day 15 postmetamorphosis, when a cavity was formed within each gonomere. In contrast, testes were recognized by a uniform distribution of germ cells and intermingled somatic cells, as the division into cortex and medulla was lost. By Day 50 postmetamorphosis, the gonadal metameric organization was still apparent both in the ovaries and testes. Follicles containing diplotene oocytes were observed within the ovary. In the testis, an incipient lobular architecture was recognized without initiation of meiosis within the seminiferous cords. These observations reveal an extremely delayed gonadal development in R. arenarum, not reported previously for other anuran species. In addition, the late differentiation of the gonads contrasted with the early appearance of follicles in the Bidder's organ. Lastly, we observed that delayed metamorphs exhibited an undifferentiated gonad, demonstrating that gonadogenesis in this species is more dependent on somatic development than on age.


Subject(s)
Bufonidae , Sex Differentiation , Male , Female , Animals , Gonads , Testis , Morphogenesis , South America
8.
Biomater Adv ; 149: 213399, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37011423

ABSTRACT

In recent years significant efforts have been made to develop new materials for wound dressing with improved healing properties. However, the synthesis methods usually employed to this end are often complex or require several steps. We describe here the synthesis and characterization of antimicrobial reusable dermatological wound dressings based on N-isopropylacrylamide co-polymerized with [2-(Methacryloyloxy) ethyl] trimethylammonium chloride hydrogels (NIPAM-co-METAC). The dressings were obtained with a very efficient single-step synthesis procedure based on visible light (455 nm) by photopolymerization. To this end, F8BT nanoparticles of the conjugated polymer (poly(9,9-dioctylfluorene-alt-benzothiadiazole) - F8BT) were used as macro-photoinitiators, and a modified silsesquioxane was employed as crosslinker. Dressings obtained by this simple and gentle method show antimicrobial and wound healing properties, without the incorporation of antibiotics or any other additives. The physical and mechanical properties of these hydrogel-based dressings were evaluated, as well as their microbiological properties, through in vitro experiments. Results show that dressings with a molar ratio of METAC of 0.5 or higher exhibit high swelling capacity, appropriate water vapor transmission rate values, stability and thermal response, high ductility and adhesiveness. In addition, biological tests showed that the dressings have significant antimicrobial capacity. The best inactivation performance was found for hydrogels synthesized with the highest METAC content. The dressings were tested several times with fresh bacterial cultures, showing a bacterial kill efficiency of 99.99 % even after three repetitions in a row, employing the same dressing, demonstrating the intrinsic bactericidal property of the materials and their reusability. In addition, the gels show low hemolytic effect, high dermal biocompatibility and noticeable wound healing effects. Overall results demonstrate that some specific hydrogel formulations have potential application as dermatological dressings for wound healing and disinfection.


Subject(s)
Anti-Bacterial Agents , Anti-Infective Agents , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Wound Healing , Bandages , Hydrogels/pharmacology
9.
Retina ; 32(8): 1492-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22481478

ABSTRACT

PURPOSE: To evaluate the integrity of photoreceptor inner segment/outer segment (IS/OS) junction after change of drusen size in age-related macular degeneration using spectral-domain optical coherence tomography. METHODS: Drusen volume raster scans were performed with the Spectralis spectral-domain optical coherence tomography (Heidelberg Engineering) through 2,624 drusen in 14 eyes with clinically dry age-related macular degeneration, which had been longitudinally followed-up between 23 and 28 months without intervention (mean, 26.3 months). All eyes had Early Treatment Diabetic Retinopathy Study visual acuity. A total of 416 of 2,624 drusen were analyzed. RESULTS: Of 416 drusen, 83 (20%) were found to have regressed spontaneously (Group A), 212 (51%) showed no change in size (Group B), and 121 (29%) progressed (Group C). Mean drusen size of all drusen was 63.7 ± 25.7 µm. Cross-sectional analysis of drusen morphology showed a correlation between drusen size and disrupted IS/OS junction/photoreceptor integrity (r = -0.48, P < 0.001). Of the drusen that regressed over time, there was intact IS/OS junction integrity. Even drusen that caused a major disruption showed IS/OS restoration in 74% of the drusen (P < 0.001). CONCLUSION: Progression of drusen shows structural disruption of the IS/OS junction. After drusen regression, the IS/OS junction is either able to restore as drusen regress or was artifactitiously compressed and not initially visible because of the initial drusen compression of the IS/OS junctional line. Therefore, drusen evolution may play an important role in affecting the photoreceptor IS/OS junction integrity.


Subject(s)
Geographic Atrophy/diagnosis , Retinal Drusen/diagnosis , Retinal Photoreceptor Cell Inner Segment/pathology , Retinal Photoreceptor Cell Outer Segment/pathology , Humans , Tomography, Optical Coherence , Visual Acuity/physiology
10.
J Appalach Health ; 4(2): 45-64, 2022.
Article in English | MEDLINE | ID: mdl-38028329

ABSTRACT

Introduction: The COVID-19 pandemic has had detrimental impacts in non-rural Black and rural Appalachian populations. Yet despite the pandemic's magnitude, there is a scarcity of research exploring potential influences of attitudes and social influences within these populations on their adherence to COVID-19 public health preventive behaviors. Purpose: This study examines the intention, attitudes, and social influences to adhere to COVID-19 preventive behaviors among non-rural Black and rural Appalachian congregants in Kentucky by integrating the Theory of Planned Behavior (TPB). Methods: Secondary analysis of cross-sectional data was used to assess the association between the TPB constructs and four key public health behaviors: obeying a stay-at-home order, social distancing, good hygiene practices, and wearing a mask in public. Generalized estimating equation-type logistic regression models were fit for all binary outcomes. Results: A total of 942 respondents completed the survey. Eighty-nine per cent were older than 36 years, and 73% were female. Of the respondents who were White, 97.7% lived in rural Appalachia Kentucky, and of those who were Black, 93.5% lived in non-rural Kentucky. Attitude towards the behavior was negatively associated with the stay-at-home order ( p=0.003). Both attitude toward the behavior ( p<0.001) and the subjective norm ( p=0.025) were negatively associated with mask wearing. Perceived behavioral control was positively associated with mask wearing ( p=0.023) with non-rural respondents more likely to wear a mask than rural ones ( p<0.001). None of the TPB constructs showed significant association with hygiene practices or with social distancing. Implications: This study provides further insight into the cultural and societal influences that intersect during a global pandemic. The intention to comply with public health recommendations may vary at favorable and unfavorable levels. The results lend support to the importance of designing effective, culturally tailored communication for future public health preparedness.

11.
ACS Macro Lett ; 11(3): 303-309, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35575369

ABSTRACT

A new photoinitiator system (PIS) based on riboflavin (Rf), triethanolamine, and multiwalled carbon nanobutes (MWCNTs) is presented for visible-light-induced photopolymerization of acrylic monomers. Using this PIS, photopolymerization of acrylamide and other acrylic monomers was quantitative in seconds. The intervention mechanism of CNTs in the PIS was studied deeply, proposing a surface interaction of MWCNTs with Rf which favors the radical generation and the initiation step. As a result, polyacrylamide/MWCNT hydrogel nanocomposites could be obtained with varying amounts of CNTs showing excellent mechanical, thermal, and electrical properties. The presence of the MWCNTs negatively influences the swelling properties of the hydrogel but significantly improves its mechanical properties (Young modulus values) and electric conductivity. The new PIS was tested for 3D printing in a LCD 3D printer. Due to the fast polymerizations, 3D-printed objects based on the conductive polyacrylamide/CNT nanocomposites could be manufactured in minutes.


Subject(s)
Nanocomposites , Nanotubes, Carbon , Electric Conductivity , Hydrogels , Printing, Three-Dimensional
12.
Retina ; 31(7): 1323-31, 2011.
Article in English | MEDLINE | ID: mdl-21540764

ABSTRACT

PURPOSE: To determine the effect of drusen and geographic atrophy (GA) in dry age-related macular degeneration on retinal sensitivity using an eye tracking scanning laser ophthalmoscope microperimetry. METHODS: A total of 44 eyes from 22 patients with dry age-related macular degeneration and drusen and 11 patients with GA were imaged with scanning laser ophthalmoscope microperimetry (OPKO Health, Miami, FL). A custom microperimetry pattern was used to evaluate retinal sensitivity to a Goldmann III size target (108 µm on the retina). The perimetry used a 4-2 stepladder algorithm to determine maximal sensitivity. Microperimetry and optical coherence tomography were performed using a standardized protocol. Twenty-eight eyes with drusen and 16 eyes with GA were analyzed. RESULTS: Retinal sensitivity overlying drusen was significantly reduced compared with the adjacent uninvolved retina. There was a significant correlation between retinal sensitivity and drusen volume, as well as the grading of the photoreceptor inner segment/outer segment junction score. In patients with GA, an absolute scotoma was confirmed. Retinal sensitivity at the margin of GA was significantly decreased compared with the adjacent uninvolved retina. CONCLUSION: Scanning laser ophthalmoscope microperimetry is able to detect changes in retinal sensitivity in AMD patients overlying drusen and at the margin of GA. It is a useful device to grade focal retinal sensitivity in patients with dry age-related macular degeneration.


Subject(s)
Geographic Atrophy/physiopathology , Macular Degeneration/physiopathology , Ophthalmoscopy , Retina/physiopathology , Retinal Drusen/physiopathology , Visual Field Tests/methods , Visual Fields/physiology , Aged , Aged, 80 and over , Algorithms , Female , Geographic Atrophy/diagnosis , Humans , Lasers , Macular Degeneration/diagnosis , Male , Middle Aged , Retinal Drusen/diagnosis , Scotoma/physiopathology , Tomography, Optical Coherence , Visual Acuity/physiology
13.
Front Microbiol ; 11: 1485, 2020.
Article in English | MEDLINE | ID: mdl-32765440

ABSTRACT

The attachment of foodborne pathogens to leaf surfaces is a complex process that involves multiple physical, chemical, and biological factors. Here, we report the results from a study designed to specifically determine the contribution of spinach leaf surface topography as it relates to leaf axis (abaxial and adaxial) and leaf age (15, 45, and 75 days old) to the ability of Escherichia coli to resist removal by surface wash, to avoid inactivation by chlorine, and to disperse through splash impact. We used fresh spinach leaves, as well as so-called "replicasts" of spinach leaf surfaces in the elastomer polydimethylsiloxane to show that leaf vein density correlated positively with the failure to recover E. coli from surfaces, not only using a simple water wash and rinse, but also a more stringent wash protocol involving a detergent. Such failure was more pronounced when E. coli was surface-incubated at 24°C compared to 4°C, and in the presence, rather than absence, of nutrients. Leaf venation also contributed to the ability of E. coli to survive a 50 ppm available chlorine wash and to laterally disperse by splash impact. Our findings suggest that the topographical properties of the leafy green surface, which vary by leaf age and axis, may need to be taken into consideration when developing prevention or intervention strategies to enhance the microbial safety of leafy greens.

14.
PLoS One ; 15(6): e0234556, 2020.
Article in English | MEDLINE | ID: mdl-32555622

ABSTRACT

OBJECTIVE: The prevalence of psoriatic arthritis (PsA) is very heterogeneous. There are no data on its frequency in the general population in Spain. The aim of EPISER2016 study was to estimate the prevalence of PsA in people aged ≥20 years in Spain. METHODS: Cross-sectional multicenter population-based study. Subjects from all the autonomous communities in Spain were randomly selected using multistage stratified cluster sampling. Participants in each of the municipalities randomly selected for the study were administered a telephone-based questionnaire to screen for the study diseases. If the participant reported being previously diagnosed, rheumatologists from the participant's reference hospital confirmed the diagnosis based on a review of the clinical history. Subjects not previously diagnosed but whose screening result was positive based on symptoms received a second telephone call from the investigating rheumatologist in order to evaluate the suspicion. If the suspicion remained, an appointment was made at the reference hospital to complete the diagnostic confirmation process according to CASPAR criteria. To calculate the prevalence and its 95% confidence interval (CI), the sample design was taken into account and weighing was calculated considering age, sex and geographic origin. RESULTS: The sample comprised 4916 subjects. The prevalence of PsA was 0.58% (95%CI: 0.38-0.87). All but 1 of the 27 cases (96.30%) had been diagnosed prior to EPISER2016. CONCLUSION: The prevalence of PsA in Spain was among the highest reported to date, only below that reported in Norway (0.67%) and slightly higher than that reported in Italy (0.42%).


Subject(s)
Arthritis, Psoriatic/epidemiology , Adult , Arthritis, Psoriatic/diagnosis , Cross-Sectional Studies , Humans , Italy , Middle Aged , Norway , Prevalence , Rheumatologists , Spain/epidemiology , Surveys and Questionnaires
15.
Cancer Res ; 79(24): 6057-6066, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31484668

ABSTRACT

The discovery of the Warburg effect, the preference of cancer cells to generate ATP via glycolysis rather than oxidative phosphorylation, has fostered the misconception that cancer cells become independent of the electron transport chain (ETC) for survival. This is inconsistent with the need of ETC function for the generation of pyrimidines. Along with this misconception, a large body of literature has reported numerous mutations in mitochondrial DNA (mtDNA), further fueling the notion of nonfunctional ETC in cancer cells. More recent findings, however, suggest that cancers maintain oxidative phosphorylation capacity and that the role of mtDNA mutations in cancer is likely far more nuanced in light of the remarkable complexity of mitochondrial genetics. This review aims at describing the various model systems that were developed to dissect the role of mtDNA in cancer, including cybrids, and more recently mitochondrial-nuclear exchange and conplastic mice. Furthermore, we put forward the notion of mtDNA landscapes, where the surrounding nonsynonymous mutations and variants can enhance or repress the biological effect of specific mtDNA mutations. Notably, we review recent studies describing the ability of some mtDNA landscapes to activate the mitochondrial unfolded protein response (UPRmt) but not others. Furthermore, the role of the UPRmt in maintaining cancer cells in the mitohormetic zone to provide selective adaptation to stress is discussed. Among the genes activated by the UPRmt, we suggest that the dismutases SOD2 and SOD1 may play key roles in the establishment of the mitohormetic zone. Finally, we propose that using a UPRmt nuclear gene expression signature may be a more reliable readout than mtDNA landscapes, given their diversity and complexity.


Subject(s)
Cell Nucleus/pathology , DNA, Mitochondrial/genetics , Mitochondria/pathology , Neoplasms/genetics , Unfolded Protein Response/genetics , Animals , Cell Nucleus/genetics , DNA, Mitochondrial/metabolism , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Hormesis/genetics , Humans , Mice , Mitochondria/genetics , Models, Biological , Mutation , Neoplasms/pathology , Superoxide Dismutase/metabolism , Superoxide Dismutase-1/metabolism
16.
Ocul Surf ; 17(3): 440-446, 2019 07.
Article in English | MEDLINE | ID: mdl-31152804

ABSTRACT

PURPOSE: To investigate the association between partial blinking during spontaneous blinking as measured by interferometry and ocular exams for the assessment of dry eye disease (DED). METHODS: This retrospective study included 58 eyes of patients previously diagnosed with DED. Ocular surface assessment included ocular surface disease index (OSDI) score, tear film osmolarity, tear breakup time (TBUT), grading of corneal fluorescein staining, Schirmer I test, and dry eye parameters by the LipiView™ interferometer (TearScience, Morrisville, NC, USA), including lipid layer thickness of the tear film (LLT), meibomian gland dropout (MGd), number of incomplete and complete blinks per 20 s and the partial blinking rate (PBR). Generalized estimation equations (GEE) were used for association testing between each variable of interest. The working correlation for each GEE model was selected using the Corrected Quasi-likelihood under the Independence Model Criterion. RESULTS: The number of incomplete blinks was significantly associated with TBUT (P = 0.006), OSDI (P = 0.000) and MGd (P = 0.000). PBR was significantly associated with OSDI (P = 0.032) and MGd (P = 0.000). The number of complete blinks was significantly associated with TBUT (P = 0.032), but not with other ocular surface parameters. MGd was significantly associated with TBUT (P = 0.002) and OSDI (P = 0.001). LLT was significantly associated with tear film osmolarity (P = 0.007), and tear film osmolarity was significantly associated with LLT (P = 0.000). CONCLUSIONS: Incomplete blinking is associated with decreased TBUT, increased OSDI, and increased MGd possibly through its contribution to meibomian gland obstruction and subsequent loss of tear film homeostasis. It may, therefore, be considered an additive measure for mild-to-moderate DED assessment.


Subject(s)
Blinking/physiology , Dry Eye Syndromes/diagnosis , Meibomian Glands/metabolism , Tears/metabolism , Dry Eye Syndromes/physiopathology , Female , Humans , Interferometry , Male , Middle Aged , Osmolar Concentration , Retrospective Studies
17.
Oncogene ; 38(29): 5751-5765, 2019 07.
Article in English | MEDLINE | ID: mdl-31222103

ABSTRACT

We previously reported that the dismutase SOD1 is overexpressed in breast cancer. However, whether SOD1 plays an active role in tumor formation in vivo has never been demonstrated. Further, as luminal cells of normal breast epithelial cells are enriched in SOD1, whether SOD1 is essential for normal mammary gland development has never been determined. We initiated this study to investigate the role of SOD1 in mammary gland tumorigenesis as well as in normal mammary gland development. We crossed the inducible erbB2 (MMTV-iErbB2) and Wnt (MMTV-Wnt) transgenic mice to the SOD1 heterozygote or knockout mice. Our results show that SOD1 is essential for oncogene-driven proliferation, but not normal proliferation of the mammary gland associated with pregnancy or other normal proliferative tissues such as skin and intestines. We show that activation of the oncogene ErbB2 is associated with increased ROS and that high ROS sub-population of ErbB2 cancer cells show elevated SOD1. In the same cells, decrease in SOD1 is associated with an elevation in both apoptosis as well as oncogene-induced senescence. Based on these results, we suggest that SOD1 carries a housekeeping function that maintains ROS levels below a threshold that supports oncogene-dependent proliferation, while allowing escape from oncogene-induced senescence, independently of the oncogene driving tumor formation. These results identify SOD1 as an ideal target for cancer therapy as SOD1 inhibitors hold the potential to prevent the growth of cancers cells of diverse genotypes, activate multiple modes of cell death therefore making acquired resistance more difficult, while sparing normal tissues.


Subject(s)
Carcinogenesis/genetics , Cell Proliferation , Mammary Neoplasms, Animal/genetics , Oncogenes , Superoxide Dismutase-1/genetics , Animals , Apoptosis/genetics , Female , Genes, Essential , Humans , Mammary Glands, Animal/pathology , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Animal/pathology , Mice , Mice, Transgenic , Oxidative Stress , Pregnancy , Receptor, ErbB-2/genetics , Superoxides/metabolism
18.
Methods Appl Fluoresc ; 5(2): 024001, 2017 03 29.
Article in English | MEDLINE | ID: mdl-28352000

ABSTRACT

Conjugated polymer nanoparticles are widely used in fluorescent labeling and sensing, as they have mean radii between 5 and 100 nm, narrow size dispersion, high brightness, and are photochemically stable, allowing single particle detection with high spatial and temporal resolution. Highly crosslinked polymers formed by linking individual chains through covalent bonds yield high-strength rigid materials capable of withstanding dissolution by organic solvents. Hence, the combination of crosslinked polymers and conjugated polymers in a nanoparticulated material presents the possibility of interesting applications that require the combined properties of constituent polymers and nanosized dimension. In the present work, F8BT@pEGDMA nanoparticles composed of poly(ethylene glycol dimethacrylate) (pEGDMA; a crosslinked polymer) and containing the commercial conjugated polymer poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) were synthesized and characterized. Microemulsion polymerization was applied to produce F8BT@pEDGMA particles with nanosized dimensions in a ∼25% yield. Photophysical and size distribution properties of F8BT@pEDGMA nanoparticles were evaluated by various methods, in particular single particle fluorescence microscopy techniques. The results demonstrate that the crosslinking/polymerization process imparts structural rigidity to the F8BT@pEDGMA particles by providing resistance against dissolution/disintegration in organic solvents. The synthesized fluorescent crosslinked nanoparticles contain (for the most part) single F8BT chains and can be detected at the single particle level, using fluorescence microscopy, which bodes well for their potential application as molecularly imprinted polymer fluorescent nanosensors with high spatial and temporal resolution.

19.
Dalton Trans ; 46(5): 1567-1576, 2017 Jan 31.
Article in English | MEDLINE | ID: mdl-28091640

ABSTRACT

Lithium diphenylphosphide unexpectedly provokes the ring-opening of tetrahydrofuran (THF) and by reaction with 3,6-dichloropyridazine leads to the formation of the ligand 3-chloro-6-(4-diphenylphosphinyl)butoxypyridazine (P⋯N), which was isolated. The reaction of this ligand with the (Re(CO)3(THF)Br)2 dimer yields the novel complex [Br(CO)3Re(µ-3-chloro-6-(4-diphenylphosphinyl)butoxypyridazine)2Re(CO)3Br] (BrRe(P⋯N)(N⋯P)ReBr), which was crystallized in the form of a chloroform solvate, (C46H40Br2Cl2N4O8P2Re2)·(CHCl3). The monoclinic crystal (P21/n) displays a bimetallic cage structure with a symmetry inversion centre in the middle of the rhenium to rhenium line. The molecule shows two oxidation signals occurring at +1.50 V and +1.76 V which were assigned to the ReI/ReII and ReII/ReIII metal-centered couples, respectively, while signals observed at -1.38 V and -1.68 V were assigned to ligand centered reductions. Experimental and DFT/TDDFT results indicate that the UV-Vis absorption maximum of BrRe(P⋯N)(N⋯P)ReBr occurring near 380 nm displays a metal to ligand charge transfer (MLCT) character, which is consistent with CV results. Upon excitation at this wavelength, a weak emission (Φem < 1 × 10-3) is observed around 580 nm (in dichloromethane) which decays with two distinct lifetimes τ1 and τ2 of 24 and 4.7 ns, respectively. The prevalence of non-radiative deactivation pathways is consistent with efficient internal conversion induced by the high conformational flexibility of the P⋯N ligand's long carbon chain. Measurements in a frozen solvent at 77 K, where vibrational deactivation is hindered, show intense emission associated with the 3MLCT state. These results demonstrate that BrRe(P⋯N)(N⋯P)ReBr preserves the dual emitting nature previously reported for the mononuclear complex RePNBr, with emission associated with and states.

20.
Pediatr Infect Dis J ; 35(6): e171-6, 2016 06.
Article in English | MEDLINE | ID: mdl-26910591

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is considered an independent risk factor for developing cardiovascular disease. It is well known that the prevalence of metabolic disorders have increased in pediatric HIV-infected children. The objective of this study is to assess the prevalence and characteristics of MetS in HIV-infected children and adolescents in Spain. METHODS: A cross-sectional multicenter study in 152 patients from the pediatric cohort of the Spanish AIDS Research Network (CoRISpe) was performed. MetS was defined according to the new International Diabetes Federation (IDF) diagnostic criteria and the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin and lipodystrophy assessment. Demographic, clinical, immunological, virological and antiretroviral therapy data were obtained from the Network database. RESULTS: An abnormally low high-density lipoprotein-cholesterol level was the most prevalent disturbance (21.05%) found. Three patients met IDF criteria for MetS (1.97%), and MetS was significantly associated with lipohypertrophy (P=0.029) in the analysis. When the modified NCEP-ATP III criteria were used, the prevalence of MetS was 5.92% (9 patients), and MetS was significantly associated with Tanner stage ≥2 (P=0.041), lipohypertrophy (P=0.001) and higher Z scores for weight and body mass index (P=0.002 and P<0.001). Insulin resistance was observed in 17 patients (11.18%) and was associated with MetS (as per the modified NCEP-ATP III criteria) (P=0.03) and lower high-density lipoprotein-cholesterol values (P=0.036). CONCLUSIONS: The prevalence of MetS in our cohort was 1.97% or 5.92%, depending on the diagnostic criteria used. MetS should be actively assessed, particularly in children who show lipohypertrophy.


Subject(s)
HIV Infections/complications , Metabolic Syndrome/epidemiology , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Spain/epidemiology
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