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1.
Front Vet Sci ; 11: 1284097, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655537

RESUMO

Objective: To determine if a single brain biopsy utilizing a freeze-core needle harvest system Cassi II under ultrasound guidance provides a diagnostic sample; to evaluate the technique's efficacy in procuring diagnostic samples in comparison with "open" surgical biopsies; and to describe intraoperative complications associated with the technique. Study design: Experimental clinical study. Animals: Seventeen dogs and four cats with magnetic resonance imaging (MRI) diagnoses of readily surgically accessible intracranial masses. Methods: Immediately prior to surgical biopsy (SB), freeze-core biopsy (FCB) sample was obtained from each patient under ultrasound guidance. Results: Histopathology results from single FCB samples were found to be in 100% agreement with the SB samples. Freezing artifact was minimal and did not interfere with histopathologic interpretation. There were no intraoperative complications specifically attributable to the use of the FCB system. Conclusion: Based on the results of this small experimental study, the FCB system is expected to safely yield diagnostic quality intracranial masses biopsy specimens. Clinical significance: This system has the potential of obtaining diagnostic biopsies of more deeply seated brain lesions (i.e., intra-axial tumors considered inaccessible or with large risks/difficulties by standard surgical means) which would provide a definitive diagnosis to guide appropriate therapy.

2.
Mol Biol Rep ; 51(1): 502, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598020

RESUMO

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Sulfonas , Neoplasias da Glândula Tireoide , Uridina/análogos & derivados , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Alelos , Proteínas Proto-Oncogênicas c-ret/genética
3.
Exp Biol Med (Maywood) ; 249: 10120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463392

RESUMO

Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, or infection, persistent neuroinflammation results in a heightened presence of cytokines, chemokines, and reactive oxygen species that result in tissue damage. In the CNS, the surrounding microglia normally contain macrophages and other innate immune cells that perform active immune surveillance. The resulting cytokines produced by these macrophages affect the growth, development, and responsiveness of the microglia present in both white and gray matter regions of the CNS. Controlling the levels of these cytokines ultimately improves neurocognitive function and results in the repair of lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators of the genome and subsequently control the activity of inflammatory responses crucial in sustaining a robust and acute immunological response towards an acute infection while dampening pathways that result in heightened levels of cytokines and chemokines associated with chronic neuroinflammation. Numerous reports have directly implicated miRNAs in controlling the abundance and activity of interleukins, TGF-B, NF-kB, and toll-like receptor-signaling intrinsically linked with the development of neurological disorders such as Parkinson's, ALS, epilepsy, Alzheimer's, and neuromuscular degeneration. This review is focused on discussing the role miRNAs play in regulating or initiating these chronic neurological states, many of which maintain the level and/or activity of neuron-specific secondary messengers. Dysregulated miRNAs present in the microglia, astrocytes, oligodendrocytes, and epididymal cells, contribute to an overall glial-specific inflammatory niche that impacts the activity of neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, and neuron-muscular connections. Understanding which miRNAs regulate microglial activation is a crucial step forward in developing non-coding RNA-based therapeutics to treat and potentially correct the behavioral and cognitive deficits typically found in patients suffering from chronic neuroinflammation.


Assuntos
MicroRNAs , Doenças do Sistema Nervoso , Humanos , Doenças Neuroinflamatórias , Doenças do Sistema Nervoso/genética , Microglia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Citocinas/metabolismo , Quimiocinas/metabolismo
4.
Prev Sci ; 25(4): 590-602, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38214789

RESUMO

Sexual violence (SV) on college campuses disproportionately affects cisgender (nontransgender) women, sexual minorities (e.g., gays/lesbians, bisexuals), and gender minority (e.g., transgender/nonbinary) people. This study investigates gender and sexual behavior differences in common SV intervention targets-SV-related knowledge, prevention behaviors, and care-seeking. We analyzed cross-sectional survey data, collected in 9/2015-3/2017, from 2202 students aged 18-24 years attending college health and counseling centers at 28 Pennsylvania and West Virginia campuses. Multivariable multilevel models tested gender and sexual behavior differences in SV history; recognition of SV; prevention behaviors (self-efficacy to obtain sexual consent, intentions to intervene, positive bystander behaviors); and care-seeking behaviors (knowledge of, self-efficacy to use, and actual use of SV services). Adjusting for lifetime exposure to SV, compared with cisgender men, cisgender women had higher recognition of SV and reproductive coercion, prevention behaviors, and care-seeking self-efficacy (beta range 0.19-1.36) and gender minority people had higher recognition of SV and intentions to intervene (beta range 0.33-0.61). Cisgender men with any same-gender sexual partners had higher SV knowledge (beta = 0.23) and self-efficacy to use SV services (beta = 0.52) than cisgender men with only opposite-gender partners. SV history did not explain these differences. Populations most vulnerable to SV generally have higher SV knowledge, prevention behaviors, and care-seeking behaviors than cisgender men with only opposite-gender sexual partners. Innovative SV intervention approaches are necessary to increase SV-related knowledge among heterosexual cisgender men and may need to target alternative mechanisms to effectively reduce inequities for sexual and gender minority people.


Assuntos
Delitos Sexuais , Humanos , Masculino , Feminino , Adulto Jovem , Adolescente , Estudos Transversais , Delitos Sexuais/prevenção & controle , Comportamento Sexual , Conhecimentos, Atitudes e Prática em Saúde , Minorias Sexuais e de Gênero , Pennsylvania , West Virginia , Universidades , Aceitação pelo Paciente de Cuidados de Saúde
5.
Mol Biol Rep ; 50(7): 6087-6096, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37300745

RESUMO

BACKGROUND: Single nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. METHODS: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. RESULTS: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (p < 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. CONCLUSION: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Paquistão , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Proteína Supressora de Tumor p53/genética , Proteína BRCA1/genética , Proteína BRCA2/genética
6.
J Interpers Violence ; 38(3-4): 3950-3978, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36004529

RESUMO

Black, lesbian, gay, bisexual, and transgender (LGBT), individuals experience higher rates of violent victimization compared to their cisgender heterosexual counterparts over their life course. Among Black LGBT people, witnessing and experiencing violence have been related to poor health outcomes, including depression, risky sexual behavior, substance use, and lower engagement in healthcare services. We engaged in research to better understand the effects of violence experienced by the Black LGBT youth community. We conducted a qualitative, phenomenological study focused on the causes of violence occurring in the lives of Black LGBT youth engaged in a recreation-based community health program. The study consisted of four focus groups with Black LGBT youth (N = 24) and in-depth individual interviews with medical and social service providers who work with Black LGBT youth (N = 4). Data analysis presented three themes: (1) causes of violence, (2) the context of intracommunity violence, and (3) solutions to violence. The first theme describes the reasoning, motivation, or explanation for violence experienced by the Black LGBT youth community. The second theme, the context of intracommunity violence, describes how violence occurs specifically within Black LGBT young adult communities. The third theme, solutions to violence, describes the recommendations for addressing, reducing, and/or eliminating violence within the Black LGBT youth community. Our findings highlight the need for safe spaces, culturally-relevant services, and trusted figures for Black LGBT young adults, which can serve as mechanisms for mitigating violence.


Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Pessoas Transgênero , Feminino , Adulto Jovem , Adolescente , Humanos , Comportamento Sexual , Violência
7.
BMJ Open ; 12(11): e061029, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36418127

RESUMO

INTRODUCTION: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. METHODS AND ANALYSIS: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. ETHICS AND DISSEMINATION: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (#NCT05145803).


Assuntos
COVID-19 , Máscaras , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Observacionais como Assunto , Equipamento de Proteção Individual , Estudos Prospectivos , SARS-CoV-2
8.
J Hand Surg Glob Online ; 4(6): 348-354, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36425373

RESUMO

Purpose: The advent of total wrist arthroplasty has allowed for motion-sparing surgical treatment for wrist arthritis. The Integra Freedom Total Wrist Arthroplasty recently incorporated locking caps into its distal component fixation to minimize implant micromotion and improve osseous integration. The purpose of this study was to assess the kinematic effect of locking caps in a cadaveric model. Methods: The Integra Freedom was implanted in 4 matched-pair cadavers and tested with and without the use of the locking caps, with the testing order randomized. Each specimen was tested on a custom testing system in a position of 15° of radial deviation, neutral position, and 15° of ulnar deviation with 25 N, 50 N, 75 N, and 100 N of compressive force. The rotation of the capitate, trapezoid, and hamate at all positions was measured using a 3-dimensional digitizer. Results: Statistical analysis showed no difference in carpal rotation between the nonlocking cap and locking cap groups at all testing loads and wrist positions. The absolute motion of the distal row was minimal. However, of the total 216 loads/positions tested, only 4 (1.8%) showed a rotation of greater than 2° and only 34 (15.7%) showed a rotation of greater than 1°. Conclusions: This study shows that in a time zero cadaveric model, the initial osseous fixation of the distal component in the Integra Freedom is robust with or without locking caps. The addition of locking caps did not have a kinematic effect on distal carpal row fixation. However, further investigation into its clinical role is necessary. Clinical Relevance: At time zero, there is minimal carpal motion after implantation of the Integra Freedom Total Wrist with functional loading. The addition of locking caps did not lead to any decrease in carpal motion.

9.
Am J Infect Control ; 50(8): 890-897, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35908828

RESUMO

BACKGROUND: SARS-CoV-2 emerged in 2019 and resulted in a pandemic causing millions of infections worldwide. Gold-standard for SARS-CoV-2 detection uses quantitative RT-qPCR on respiratory secretions to detect viral RNA (vRNA). Acquiring these samples is invasive, can be painful for those with xerostomia and other health conditions, and sample quality can vary greatly. Frequently only symptomatic individuals are tested even though asymptomatic individuals can have comparable viral loads and efficiently transmit virus. METHODS: We utilized a non-invasive approach to detect SARS-CoV-2 in individuals, using polyvinyl alcohol (PVA) strips embedded in KN95 masks. PVA strips were tested for SARS-CoV-2 vRNA via qRT-PCR and infectious virus. RESULTS: We show efficient recovery of vRNA and infectious virus from virus-spiked PVA with detection limits comparable to nasal swab samples. In infected individuals, we detect both human and SARS-CoV-2 RNA on PVA strips, however, these levels are not correlated with length of time mask was worn, number of times coughed or sneezed, or level of virus in nasal swab samples. We successfully cultured and deep-sequenced PVA-associated virus. CONCLUSIONS: These results demonstrate the feasibility of using PVA-embedded masks as a non-invasive platform for detecting SARS-CoV-2 in exhaled air in COVID-positive individuals regardless of symptom status.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Pandemias , RNA Viral/análise , RNA Viral/genética
10.
J Sex Res ; 59(7): 920-930, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35580257

RESUMO

Black men who have sex with men (BMSM) in the United States experience a disproportionate burden of violence, substance use, physical and mental health conditions relative to other racial groups. BMSM who engage in sex work (BMSM-SW) experience a high burden of psychosocial conditions, sexually transmitted infections, including HIV, and intersectional stigma. This analysis characterizes remuneration and client typologies for BMSM-SW, documents intersectional stigma experienced by BMSM-SW relative to other BMSM, and explores the impact of experienced intersectional stigma on the relationship between sex work engagement and psychosocial syndemic conditions (violence, polydrug use, and depression symptoms). Results show that a majority of BMSM-SW in the sample had female clients and that sex workers were more likely than other BMSM to hire another sex worker. BMSM-SW were more likely than other BMSM to report stigma attributed to race; sexuality; HIV status; socioeconomic status; and "other" attributes, and were more likely to report experiencing stigma across all settings assessed (schools; healthcare; employment; housing; police/courts; and in public/community). Intersectional stigma mediated the relationship between sex work engagement and psychosocial syndemic conditions, accounting for 49% (95% CI: 47.6-50.0%) of the relationship. Interventions for BMSM-SW should include resilience-building components to counteract the effects of intersectional stigma.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Negro ou Afro-Americano/psicologia , Cidades , Feminino , Infecções por HIV/psicologia , Homossexualidade Masculina/psicologia , Humanos , Masculino , Trabalho Sexual , Estigma Social , Transtornos Relacionados ao Uso de Substâncias/psicologia , Sindemia , Estados Unidos/epidemiologia
11.
Sci Rep ; 11(1): 20777, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34675235

RESUMO

This study reports the phase transformation behaviour associated with electrolytic manganese dioxide (EMD) utilized as the positive electrode active material for aqueous zinc-ion batteries. Electrochemical techniques, including galvanostatic charge-discharge and rotating ring-disk electrode measurements, and microstructural techniques, using X-ray powder diffraction, scanning electron microscopy, and transmission/scanning transmission electron microscopy, were utilized to characterize the positive electrode at different stages of discharge and charge of zinc-ion cells. The results indicate that, during discharge, a fraction of EMD undergoes a transformation to ZnMn2O4 (spinel-type) and Zn2+ is intercalated into the tunnels of the γ- and ε-MnO2 phases, forming ZnxMnO2 (tunnel-type). When a critical concentration of Mn3+ in the intercalated ZnxMnO2 species is reached, a disproportionation/dissolution reaction is triggered leading to the formation of soluble Mn2+ and hydroxide (OH-) ions; the latter precipitates as zinc hydroxide sulfate (ZHS, Zn4(OH)6(SO4)·5H2O) by combination with the ZnSO4/H2O electrolyte. During charge, Zn2+ is reversibly deintercalated from the intergrown tunneled phases (γ-/ε-ZnxMnO2), Mn2+ is redeposited as layered chalcophanite (ZnMn3O7·3H2O), and ZHS is decomposed by protons (H+) formed during the electrochemical deposition of chalcophanite.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33669672

RESUMO

Homelessness is a persistent problem in the United States in general and in Southern California especially. While progress has been made in reducing the number of people experiencing homelessness in the United States from 2007 (647,000) to 2019 (567,000), it remains an entrenched problem. The purpose of this paper is to outline a novel, interdisciplinary academic-practice partnership model to address homelessness. Where singular disciplinary approaches may fall short in substantially reducing homelessness at the community and population level, our model draws from a collective impact model which coordinates discipline-specific approaches through mutually reinforcing activities and shared metrics of progress and impact to foster synergy and sustainability of efforts. This paper describes the necessary capacity-building at the institution and community level for the model, the complementary strengths and contributions of each stakeholder discipline in the proposed model, and future goals for implementation to address homelessness in the Southern California region.


Assuntos
Pessoas Mal Alojadas , Fortalecimento Institucional , Humanos , Estados Unidos
13.
AIDS Behav ; 25(9): 2929-2940, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33606134

RESUMO

Black transgender women (BTW) in the United States experience disproportionate rates of HIV despite biomedical prevention interventions such as pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP). Using a sample of 490 BTW collected from 2014 to 2017, bivariate, multivariable, and multinomial analyses were conducted to determine factors associated with awareness and use of PrEP and nPEP. BTW living with HIV were more aware of PrEP than HIV-negative BTW. Structural, demographic, and trans-specific factors (e.g., experiences of homelessness, violence, and current hormone use) related to HIV risk were associated with PrEP and nPEP awareness. PrEP use was associated with behavioral HIV risks (e.g., STI diagnosis, having an HIV-positive partner, and needle-sharing) and may demonstrate risk recognition among BTW. Knowing someone using PrEP was significantly positively associated with PrEP use. Development of guidelines for PrEP and nPEP use for BTW should leverage the strengths of guidelines for other populations, while also acknowledging the unique risks for this population.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Pessoas Transgênero , Negro ou Afro-Americano , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Profilaxia Pós-Exposição , Estados Unidos/epidemiologia
16.
Prev Sci ; 22(2): 227-236, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33219902

RESUMO

Intimate partner violence (IPV) impacts sexual minority adolescents at rates equal to or greater than the rate it impacts heterosexual adolescents. We investigated whether reports of physical and sexual IPV were less frequent in school jurisdictions with more affirming climates for lesbian, gay, bisexual, transgender, and queer (LGBTQ) students; and whether these associations varied for sexual orientation subgroups. We combined student-level data from the 2015 Youth Risk Behavior Surveys on demographics and experiences with physical and sexual IPV with jurisdiction-level data from the 2014 School Health Profiles on LGBTQ-affirming school climate. Multilevel logistic regression models examined associations between LGBTQ-affirming school climates and IPV. We stratified our data by sex and examined whether these associations differed by sexual orientation subgroups using cross-level interaction terms between school climate and sexual orientation (assessed via sexual identity and behavior). Sexual minority youth were more likely to report experiencing past-year physical and sexual IPV than their heterosexual counterparts. Attending schools with more LGBTQ-affirming climates reduced the likelihood of reporting physical IPV, but not sexual IPV, for female students. More LGBTQ-affirming school climates increased risk for sexual IPV among gay male students. Establishing LGBTQ-affirming school climates may reduce physical IPV for female students, but may have unintended consequences on sexual IPV prevalence for gay male students. More work is necessary to ensure that these climates are affirming for all sexual minority students and to address sexual violence prevention.


Assuntos
Bullying , Vítimas de Crime , Violência por Parceiro Íntimo , Cultura Organizacional , Minorias Sexuais e de Gênero , Adolescente , Bullying/prevenção & controle , Feminino , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Masculino , Instituições Acadêmicas
17.
Hand Clin ; 36(4): 443-453, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040956

RESUMO

The distal radioulnar joint is inherently unstable, relying primarily on ligaments for stability. Disruption of the joint-stabilizing structures can occur in isolation or concomitantly with osseous trauma. Instability can result from dislocations, fractures, ligament injuries, or malunions. Untreated instability alters wrist and forearm kinematics, leading to pain, weakness, and possibly arthritis. In chronic instability, the native ligaments may not be reparable, necessitating a reconstructive procedure.


Assuntos
Instabilidade Articular/fisiopatologia , Instabilidade Articular/cirurgia , Articulação do Punho/fisiopatologia , Articulação do Punho/cirurgia , Diagnóstico por Imagem , Humanos , Ligamentos Articulares/lesões , Ligamentos Articulares/fisiopatologia , Procedimentos Ortopédicos , Exame Físico , Fibrocartilagem Triangular/lesões , Fibrocartilagem Triangular/fisiopatologia
18.
iScience ; 23(2): 100878, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32062455

RESUMO

MicroRNA-34 (miR-34) is one of the major families of tumor suppressor miRNAs often lost in cancers. Delivery of miR-34a mimics to affected tumors as a therapeutic strategy has been tried in pre-clinical studies and in a phase I clinical trial. One approach to increase efficacy and reduce toxicity is to rationally identify drug combinations with small molecules that synergize with miR-34a. In this study we performed a high-throughput screen of a large panel of small molecules with known biological activity and identified ouabain as a candidate small molecule that synergized with miR-34a in killing lung cancer cells. We elucidated autophagy activation as a key mechanism by which miR-34a and ouabain causes increased cytotoxicity in cells. We posit that this combinatorial approach could reduce the active dose of miR-34a needed in vivo to observe tumor shrinkage and potentiate the development of miR-34a combination therapies in the future.

19.
Clin Psychol Sci ; 8(5): 825-838, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33758685

RESUMO

Despite strong evidence for the efficacy of PTSD treatments, most affected individuals are not receiving these treatments, in part because they may not know that evidence-based treatments exist. The American Psychological Association published a website to disseminate information about their Clinical Practice Guideline for treating PTSD. In Study 1, Google Optimize was used in a field study to examine whether altering the subheadings to three of the website pages would increase site visitor engagement. On the main page and page describing treatments, no subheading alterations improved engagement. On the Patients and Families page, the subheading "say goodbye to symptoms" improved engagement on three outcome variables, including clicking a link to find a psychologist (though there were a small number of clicks). In a preregistered conceptual replication in a sample not actively seeking information about the PTSD guideline (N=578), results did not replicate. Results highlight challenges of evidence-based treatment information dissemination.

20.
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