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1.
Psychol Trauma ; 16(2): 233-241, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37326538

ABSTRACT

OBJECTIVE: Given the dearth of literature examining the link between trauma exposure and sleep among youth and young adults of color, the current study examined the association between individual types of trauma exposure, accumulation within subtypes of trauma exposure, and overall cumulative trauma exposure with sleep problems in a sample of Black students attending an alternative high school. METHOD: Participants were recruited from an alternative high school in a large, southeastern city in the United States, of which all students qualify for free/reduced lunch. The sample included 101 students (53% female) ages 16-24 (M = 17.86 years, SD = 1.36) who identified as Black. RESULTS: Participants reported a high rate of trauma exposure (M = 6.03 unique traumatic experiences, SD = 2.63). Linear regression models showed that exposure to more overall cumulative trauma and to interpersonal loss was significantly associated with higher levels of insomnia symptoms. Threats to health were significantly related to daytime sleepiness. Other threats to safety were associated with restless legs syndrome symptoms. CONCLUSIONS: Adolescence and young adulthood are a time of complex sleep-related issues. Black youth and young adults have elevated risk of trauma exposure and sleep problems; therefore, targeted assessment and intervention are warranted. Clinicians and researchers addressing sleep in youth and young adults, and those working within alternative school settings, should also consider a trauma-informed lens to optimize outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Humans , Adolescent , Female , Young Adult , United States , Adult , Male , Schools , Students , Sleep , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/etiology
2.
Open Forum Infect Dis ; 10(12): ofad606, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38111751

ABSTRACT

The optimal laboratory monitoring frequency for outpatient parenteral antimicrobial therapy-related adverse events (OPAT-AEs) during cefazolin and ceftriaxone therapy is not well defined. We identified 2.7 OPAT-AEs per 1000 sets of weekly laboratory tests in this population, suggesting that less intensive laboratory monitoring may be safe and reasonable.

3.
Article in English | MEDLINE | ID: mdl-38028906

ABSTRACT

Our institution sought to evaluate our antimicrobial stewardship empiric treatment recommendations for Salmonella. Results from 36 isolates demonstrated reduced susceptibilities to fluoroquinolones with 1 isolate susceptible only to ceftriaxone. Analysis supports the current recommendation of empiric ceftriaxone therapy for severe infection and updated recommendation for sulfamethoxazole-trimethoprim in non-severe infections.

4.
JBI Evid Synth ; 21(12): 2465-2473, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37700609

ABSTRACT

OBJECTIVE: This review will identify and summarize the literature on the integrated treatment of comorbid eating disorders and substance use disorders, focusing on clinical practice guidelines and treatment studies. INTRODUCTION: Eating disorders and substance use disorders are the deadliest psychiatric conditions, frequently co-occur, and are linked to greater symptom severity and poorer treatment outcomes. Despite repeated calls for their integrated treatment, such an approach has rarely been empirically evaluated. To advance the development of integrated treatments for comorbid eating disorders and substance use disorders, a critical first step is to describe existing treatment guidelines and summarize research evidence for this approach. INCLUSION CRITERIA: This review will consider all peer-reviewed and gray literature describing the integrated treatment of comorbid eating disorders and substance use disorders, focusing on i) clinical practice guidelines; and ii) treatment studies. We will not place limitations on populations, types of eating disorders, types of substance use disorders, or other contextual factors. METHODS: Databases to be searched will include MEDLINE (Ovid), Embase, CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Scopus, and clinical practice guidelines databases identified by CADTH Grey Matters. No date or language limits will be applied to the search. At the screening stage, we will only consider literature in English or French. Two independent reviewers will screen studies at the title/abstract and full-text levels, and extract relevant studies. Disagreements will be resolved through discussion. Findings will be presented in tabular format and a narrative summary. REVIEW REGISTRATION: Open Science Framework https://osf.io/za35j/.


Subject(s)
Feeding and Eating Disorders , Substance-Related Disorders , Humans , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy , Databases, Factual , Feeding and Eating Disorders/epidemiology , Feeding and Eating Disorders/therapy , Review Literature as Topic
5.
Open Forum Infect Dis ; 10(8): ofad382, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37564742

ABSTRACT

Background: Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic de-escalation in critically ill patients treated for pneumonia at an academic medical center. Methods: This retrospective, quasi-experimental study included adult intensive care unit (ICU) patients with respiratory culture results from 1 May to 15 August 2019 (pre-PNP group) and adult ICU patients with PNP results from 1 May to 15 August 2020 (PNP group) at Nebraska Medical Center. Patients were excluded for the following reasons: any preceding positive coronavirus disease 2019 PCR test, lack of antibiotic receipt, or non-respiratory tract infection indications for antibiotics. The primary outcome was time to discontinuation of anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy. Secondary outcomes included time to discontinuation of antipseudomonal therapy, frequency of early discontinuation for atypical coverage, and overall duration (in days) of antibiotic therapy for pneumonia. Results: Sixty-six patients in the pre-PNP group and 58 in the PNP group were included. There were significant differences in patient characteristics between groups. The median time to anti-MRSA agent discontinuation was 49.1 hours in the pre-PNP and 41.8 hours in the PNP group (P = .28). The median time to discontinuation of antipseudomonal agents was 134.4 hours in the pre-PNP versus 98.1 hours in the PNP group (P = .47). Other outcomes were numerically but not significantly improved in our sample. Conclusions: This early look at implementation of a multiplex PNP did not demonstrate a statistically significant difference in antibiotic use but lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia.

6.
Front Allergy ; 4: 1161683, 2023.
Article in English | MEDLINE | ID: mdl-37588449

ABSTRACT

Background: The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available. Methods: Following multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018-6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed. Results: Overall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges. Conclusion: Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process.

7.
Article in English | MEDLINE | ID: mdl-36970426

ABSTRACT

Background: No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience. Objective: To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non-infectious diseases clinicians (NIDCs). Design: Open-access survey. Participants: Clinicians caring for hospitalized patients receiving antibiotics. Methods: An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups. Results: Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219). Conclusions: Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.

8.
BMJ Glob Health ; 6(Suppl 5)2023 03.
Article in English | MEDLINE | ID: mdl-36958740

ABSTRACT

INTRODUCTION: Kilkari is the largest maternal messaging programme of its kind globally. Between its initiation in 2012 in Bihar and its transition to the government in 2019, Kilkari was scaled to 13 states across India and reached over 10 million new and expectant mothers and their families. This study aims to determine the cost-effectiveness of exposure to Kilkari as compared with no exposure across 13 states in India. METHODS: The study was conducted from a programme perspective using an analytic time horizon aligned with national scale-up efforts from December 2014 to April 2019. Economic costs were derived from the financial records of implementing partners. Data on incremental changes in the practice of reproductive maternal newborn and child health (RMNCH) outcomes were drawn from an individually randomised controlled trial in Madhya Pradesh and inputted into the Lives Saved Tool to yield estimates of maternal and child lives saved. One-way and probabilistic sensitivity analyses were carried out to assess uncertainty. RESULTS: Inflation adjusted programme costs were US$8.4 million for the period of December 2014-April 2019, corresponding to an average cost of US$264 298 per year of implementation in each state. An estimated 13 842 lives were saved across 13 states, 96% among children and 4% among mothers. The cost per life saved ranged by year of implementation and with the addition of new states from US$392 ($385-$393) to US$953 ($889-$1092). Key drivers included call costs and incremental changes in coverage for key RMNCH practices. CONCLUSION: Kilkari is highly cost-effective using a threshold of India's national gross domestic product of US$1998. Study findings provide important evidence on the cost-effectiveness of a national maternal messaging programme in India. TRIAL REGISTRATION: NCT03576157.


Subject(s)
Communication , Mothers , Infant, Newborn , Female , Humans , Child , Cost-Benefit Analysis , India , Outcome Assessment, Health Care
9.
Metabolites ; 12(9)2022 Sep 10.
Article in English | MEDLINE | ID: mdl-36144256

ABSTRACT

The purpose of the present study was to determine fasting and high-fat meal (HFM)-induced post-prandial systemic inflammation and airway inflammation (exhaled nitric oxide (eNO)) in older adults (OAs) compared to younger adults (YAs) before and after acute exercise. Twelve YAs (23.3 ± 3.9 y n = 5 M/7 F) and 12 OAs (67.7 ± 6 y, n = 8 M/4 F) completed two HFM challenges. After an overnight fast, participants underwent an HFM session or pre-prandial exercise (EX, 65% VO2Peak to expend 75% of the caloric content of the HFM) plus HFM (EX + HFM) in a randomized order. Systemic inflammatory cytokines were collected at 0, 3, and 6 h, while eNO was determined at 0, 2, and 4 h after the HFM (12 kcal/kg body weight: 61% fat, 35% CHO, 4% PRO). TNF-α was higher in OAs compared to YAs (p = 0.005) and decreased across time from baseline to 6 h post-HFM (p = 0.007). In response to the HFM, IL-6 decreased from 0 to 3 h but increased at 6 h regardless of age or exercise (p = 0.018). IL-8 or IL-1ß did not change over the HFM by age or exercise (p > 0.05). eNO was also elevated in OAs compared to YAs (p = 0.003) but was not altered by exercise (p = 0.108). There was a trend, however, towards significance post-prandially in OAs and YAs from 0 to 2 h (p = 0.072). TNF-α and eNO are higher in OAs compared to YAs but are not elevated more in OAs post-prandially compared to YAs. Primary systemic inflammatory cytokines and eNO were not modified by acute exercise prior to an HFM.

10.
J Allied Health ; 49(4): 263-268, 2020.
Article in English | MEDLINE | ID: mdl-33259571

ABSTRACT

BACKGROUND: Assisted living facilities are a housing option commonly used for aging adults to promote independence and successful aging. As the older adult population increases, so will the population of older adults residing in assisted living facilities. OBJECTIVE: To identify the facilitators and barriers to social participation among a cohort of older adults residing in an assisted living facility. METHODS: The qualitative study employed a phenomenological approach using semi-structured interviews. Using convenience sampling, 20 older adults residing in an assisted living facility took part in the study. The research team transcribed the audio recording verbatim following each interview and conducted a line-by-line analysis using concept coding to identify emerging themes. RESULTS: Themes involving factors serving as facilitators to social participation included health benefit, camaraderie, and resilience. Themes related to barriers to social participation included health limitations, lack of meaningful activities, and adapted activities. CONCLUSION: The study provides insight into the facilitators and barriers impacting social participation for older adults residing in an assisted living facility. Study findings support the need for an increased presence of occupational therapy services in assisted living facilities.


Subject(s)
Social Participation , Aged , Humans , Qualitative Research
11.
Nat Med ; 26(12): 1852-1858, 2020 12.
Article in English | MEDLINE | ID: mdl-33106665

ABSTRACT

Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome1,2. AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Currently, AML treatment is initiated rapidly, precluding the ability to consider the mutational profile of a patient's leukemia for treatment decisions. Untreated patients with AML ≥ 60 years were prospectively enrolled on the ongoing Beat AML trial (ClinicalTrials.gov NCT03013998 ), which aims to provide cytogenetic and mutational data within 7 days (d) from sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. A total of 487 patients with suspected AML were enrolled; 395 were eligible. Median age was 72 years (range 60-92 years; 38% ≥75 years); 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 d and were centrally assigned to a Beat AML sub-study; 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected standard of care (SOC) (103), investigational therapy (28) or palliative care (40); 9 died before treatment assignment. Demographic, laboratory and molecular characteristics were not significantly different between patients on the Beat AML sub-studies and those receiving SOC (induction with cytarabine + daunorubicin (7 + 3 or equivalent) or hypomethylation agent). Thirty-day mortality was less frequent and overall survival was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected SOC. A precision medicine therapy strategy in AML is feasible within 7 d, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival.


Subject(s)
Biomarkers, Tumor/genetics , Genomics , Leukemia, Myeloid, Acute/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Daunorubicin/administration & dosage , Daunorubicin/adverse effects , Female , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Mutation/genetics , Precision Medicine , Survival Analysis , Treatment Outcome
12.
J Abnorm Child Psychol ; 48(6): 851-863, 2020 06.
Article in English | MEDLINE | ID: mdl-32240458

ABSTRACT

Research suggests co-rumination during adolescence has developmental tradeoffs that result in elevated self-disclosure and intimacy between friends but also can be associated with increases in depression (Rose et al. 2007; Rose 2002). The current study further examined this paradox by assessing the role of emotional competencies in co-rumination as they predict depressive symptoms over a 2-year period. We tested whether co-rumination moderated the relation between emotional awareness and emotion regulation and depressive symptoms in reciprocated best friend dyads. At Time 1, 202 adolescents (101 same-sex best friend dyads; Mage = 12.68, 52.5% girls, 76.6% White, middle-class) reported on their emotional competencies (i.e., emotional awareness and perceptions of their friend's anger and sadness regulation), and depressive symptoms as well as engaged in a discussion task where co-rumination was observed. Multilevel modeling (Actor-Partner Interdependence Modeling) was used to account for similarity within friend dyads. The results indicated that when girls engaged in high levels of co-rumination, poor emotional awareness was related to greater depressive symptoms in their friend. Regarding the analyses of emotion regulation, at high levels of co-rumination, Friend A's perceptions of stronger anger regulation by Friend B predicted fewer depressive symptoms in Friend A. Stronger sadness regulation in Friend B at high levels of co-rumination predicted fewer depressive symptoms in Friend B. Our findings highlight the potentially adaptive nature of emotional competencies that may ameliorate the negative sequelae of co-rumination as adolescents are afforded the opportunity to discuss problems, better understand their emotions, skills that are then associated with fewer depressive symptoms over time.


Subject(s)
Depression/psychology , Emotions , Friends/psychology , Rumination, Cognitive , Adolescent , Anger , Child , Female , Humans , Longitudinal Studies , Male , Sadness
13.
J Abnorm Child Psychol ; 47(8): 1339-1350, 2019 08.
Article in English | MEDLINE | ID: mdl-30729378

ABSTRACT

This study examined whether emotional reactivity was associated with violent juvenile offending in a sample of detained boys (N = 198). It was predicted that Latent Profile Analysis (LPA) would reveal a "low reactivity" group, characterized by symptoms of emotional numbing and callous-unemotional (CU) traits, and a "high reactivity" group, characterized by symptoms of hyperarousal and emotional dysregulation. It was hypothesized that the low reactivity group would have higher rates of violent offending and proactive aggression than the high reactivity group. Contrary to expectations, results indicated that the presence of both emotional numbing and hyperarousal symptoms, but not hyperarousal symptoms alone, were associated with higher rates of violent offending, CU traits, and proactive aggression. Results indicate that the risk of serious aggressive behavior and violent offending may be highest among youth who are easily provoked to respond aggressively (i.e., hyperarousal symptoms) while simultaneously able to maintain emotional detachment (i.e., elevated emotional numbing symptoms and CU traits).


Subject(s)
Adolescent Behavior/physiology , Affective Symptoms/physiopathology , Aggression/physiology , Emotional Regulation/physiology , Juvenile Delinquency , Social Behavior Disorders/physiopathology , Stress Disorders, Post-Traumatic/physiopathology , Violence , Adolescent , Adult , Child , Humans , Male , Young Adult
14.
Am J Orthopsychiatry ; 89(4): 508-517, 2019.
Article in English | MEDLINE | ID: mdl-29355362

ABSTRACT

Adolescents attending alternative high schools often present with high rates of academic and behavior problems. They are also at increased risk of poor health behaviors and engaging in physical violence compared with students in traditional high school settings. To address the needs of students in these educational settings, examining factors that influence academic problems in this population is essential. Research has established that both bullying/victimization and sleep problems increase adolescents' risk for academic problems. Little is known about how these 2 factors together may exacerbate risk for academic problems among students attending an alternative high school. The current study investigated the interaction between teacher-reported bullying, victimization and daytime sleepiness on academic concerns (attention and learning problems) among a sample of 172 students (56% female; age M = 18.07 years, SD = 1.42) attending an alternative high school in a large, Southeastern U.S. city. Findings from path models indicated that daytime sleepiness, bullying, and victimization were uniquely associated with attention and learning problems. Further, significant interactions indicated that the association between victimization/bullying and attention/learning problems weakened as levels of daytime sleepiness increased. Results suggest the importance of assessing and addressing multiple contextual risk factors in adolescents attending alternative high schools to provide comprehensive intervention for students in these settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Subject(s)
Academic Success , Bullying/statistics & numerical data , Crime Victims/statistics & numerical data , Problem Behavior/psychology , Sleepiness , Students/statistics & numerical data , Adolescent , Female , Humans , Male , Schools , Southeastern United States , Surveys and Questionnaires
15.
J Community Psychol ; 47(3): 628-640, 2019 04.
Article in English | MEDLINE | ID: mdl-30447003

ABSTRACT

This study examined the sleep environment and its association with externalizing problems in adolescents attending an alternative high school. Participants included 114 students (56% female, 91% Black, mean age = 18.03, standard deviation [SD] = 1.49) from an alternative high school in a southeastern city. Most participants reported sleeping in a bed (83%) and at their house (72%) for 7 nights in the past week. Participants reported an average of 2.34 (SD = 1.86) past-week ambient sleep disruptions. Sleeping fewer nights in their own home and experiencing higher levels of ambient sleep disruptions were associated with delinquency engagement. Fewer nights sleeping in a bed and higher levels of ambient sleep disruptions were associated with a significant arrest history. The sleep environment is important to consider when assessing sleep problems, particularly among low-income adolescents living in urban environments. This information may inform comprehensive interventions to address behavioral health concerns.


Subject(s)
Juvenile Delinquency/psychology , Sleep , Sleepiness , Students/statistics & numerical data , Adolescent , Black or African American , Beds , Female , Housing , Humans , Internal-External Control , Male , Schools , Socioeconomic Factors , Young Adult
16.
Processes (Basel) ; 6(5)2018 May.
Article in English | MEDLINE | ID: mdl-30197877

ABSTRACT

RNA editing by RNA specific adenosine deaminase acting on RNA (ADAR) is increasingly being found to alter microRNA (miRNA) regulation. Editing of miRNA transcripts can affect their processing, as well as which messenger RNAs (mRNAs) they target. Further, editing of target mRNAs can also affect their complementarity to miRNAs. Notably, ADAR editing is often increased in malignancy with the effect of these RNA changes being largely unclear. In addition, numerous reports have now identified an array of miRNAs that directly contribute to various malignancies although the majority of their targets remain largely undefined. Here we propose that modulating the targets of miRNAs via mRNA editing is a frequent occurrence in cancer and an underappreciated participant in pathology. In order to more accurately characterize the relationship between these two regulatory processes, this study examined RNA editing events within mRNA sequences of two breast cancer cell lines (MCF-7 and MDA-MB-231) and determined whether or not these edits could modulate miRNA associations. Computational analyses of RNA-Seq data from these two cell lines identified over 50,000 recurrent editing sites within human mRNAs, and many of these were located in 3' untranslated regions (UTRs). When these locations were screened against the list of currently-annotated miRNAs we discovered that editing caused a subset (~9%) to have significant alterations to mRNA complementarity. One miRNA in particular, miR-140-3p, is known to be misexpressed in many breast cancers, and we found that mRNA editing allowed this miRNA to directly target the apoptosis inducing gene DFFA in MCF-7, but not in MDA-MB-231 cells. As these two cell lines are known to have distinct characteristics in terms of morphology, invasiveness and physiological responses, we hypothesized that the differential RNA editing of DFFA in these two cell lines could contribute to their phenotypic differences. Indeed, we confirmed through western blotting that inhibiting miR-140-3p increases expression of the DFFA protein product in MCF-7, but not MDA-MB-231, and further that inhibition of miR-140-3p also increases cellular growth in MCF-7, but not MDA-MB-231. Broadly, these results suggest that the creation of miRNA targets may be an underappreciated function of ADAR and may help further elucidate the role of RNA editing in tumor pathogenicity.

17.
NPJ Breast Cancer ; 3: 25, 2017.
Article in English | MEDLINE | ID: mdl-28702505

ABSTRACT

Genetic searches for tumor suppressors have recently linked small nucleolar RNA misregulations with tumorigenesis. In addition to their classically defined functions, several small nucleolar RNAs are now known to be processed into short microRNA-like fragments called small nucleolar RNA-derived RNAs. To determine if any small nucleolar RNA-derived RNAs contribute to breast malignancy, we recently performed a RNA-seq-based comparison of the small nucleolar RNA-derived RNAs of two breast cancer cell lines (MCF-7 and MDA-MB-231) and identified small nucleolar RNA-derived RNAs derived from 13 small nucleolar RNAs overexpressed in MDA-MB-231s. Importantly, we find that inhibiting the most differentially expressed of these small nucleolar RNA-derived RNAs (sdRNA-93) in MDA-MB-231 cells results primarily in a loss of invasiveness, whereas increased sdRNA-93 expression in either cell line conversely results in strikingly enhanced invasion. Excitingly, we recently determined sdRNA-93 expressions in small RNA-seq data corresponding to 116 patient tumors and normal breast controls, and while we find little sdRNA-93 expression in any of the controls and only sporadic expression in most subtypes, we find robust expression of sdRNA-93 in 92.8% of Luminal B Her2+tumors. Of note, our analyses also indicate that at least one of sdRNA-93's endogenous roles is to regulate the expression of Pipox, a sarcosine metabolism-related protein whose expression significantly correlates with distinct molecular subtypes of breast cancer. We find sdRNA-93 can regulate the Pipox 3'UTR via standard reporter assays and that manipulating endogenous sdRNA-93 levels inversely correlates with altered Pipox expression. In summary, our results strongly indicate that sdRNA-93 expression actively contributes to the malignant phenotype of breast cancer through participating in microRNA-like regulation.

18.
J Phys Chem B ; 109(46): 21556-65, 2005 Nov 24.
Article in English | MEDLINE | ID: mdl-16853799

ABSTRACT

Electrodynamic simulations of gold nanoparticle spectra were used to investigate the sensitivity of localized surface plasmon band position to the refractive index, n, of the medium for nanoparticles of various shapes and nanoshells of various structures. Among single-component nanoparticles less than 130 nm in size, sensitivities of dipole resonance positions to bulk refractive index are found to depend only upon the wavelength of the resonance and the dielectric properties of the metal and the medium. Among particle plasmons that peak in the frequency range where the real part of the metal dielectric function varies linearly with wavelength and the imaginary part is small and slowly varying, the sensitivity of the peak wavelength, lambda, to refractive index, n, is found to be a linearly increasing function of lambda, regardless of the structural features of the particle that determine lambda. Quasistatic theory is used to derive an analytical expression for the refractive index sensitivity of small particle plasmon peaks. Through this analysis, the dependence of sensitivity on band position is found to be determined by the wavelength dependence of the real part, epsilon', of the particle dielectric function, and the sensitivity results are found to extend to all particles with resonance conditions of the form, epsilon' = -2chin(2), where chi is a function of geometric parameters and other constants. The sensitivity results observed using accurate computational methods for dipolar plasmon bands of gold nanodisks, nanorods, and hollow nanoshells extend, therefore, to particles of other shapes (such as hexagonal and chopped tetrahedral), composed of other metals, and to higher-order modes. The bulk refractive index sensitivity yielded by the theory serves as an upper bound to sensitivities of nanoparticles on dielectric substrates and sensitivities of nanoparticles to local refractive index changes, such as those associated with biomolecule sensing.


Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Surface Plasmon Resonance/methods , Computer Simulation , Electrochemistry , Sensitivity and Specificity
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