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1.
Health Aff (Millwood) ; : 101377hlthaff202000598, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32437224

RESUMO

As the coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health care system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from January 1-April 8, 2020. Among our findings, we observed that, compared with non-Hispanic white patients, African Americans had 2.7 times the odds of hospitalization, after adjusting for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence that there are racial and ethnic disparities in the presentation of COVID-19. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].

2.
Int J Cancer ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32285932

RESUMO

Patients diagnosed with keratinocyte cancer experience heightened risk for melanoma, yet patients who go on to develop this malignancy have not been well-characterized. We followed a population-based cohort of 2243 participants with histologically confirmed KC identified from dermatology and pathology practices who did not have a history of internal malignancy (1363 BCC, 880 SCC). A total of 77 participants went on to develop melanoma. Individual-level data were collected via personal interviews including demographic information and skin cancer risk factors, as well as KC tumor characteristics such as anatomic site and histologic subtype. Using adjusted Cox proportionate hazards models, older patients (age 61 or older vs 60 or younger) were at twofold increased risk for developing melanoma following KC (age 61-65 HR = 2.5; 95% CI = 1.3-4.6) (age > 65 HR = 2.0; 95% CI = 1.2-3.4) and women were at reduced risk compared to men (HR = 0.5; 95% CI = 0.3-0.8). Among patients with BCC, those with tumors on the trunk/limbs compared to the head/neck were at greater risk for subsequent melanoma (HR = 2.7; 95% CI = 1.3-5.7). Subsequent risk of melanoma also related to established risk factors including blond/red vs dark hair (HR = 1.9; 95% CI = 1.1-3.4), tendency to burn rather than tan (HR = 1.7; 95% CI = 1.0-2.7), ≥1 nevi on their back compared to no nevi (HR = 2.2; 95% CI = 1.2-3.8) and a history of ≥1 painful childhood sunburns vs none (HR = 2.1; 95% CI = 1.2-3.6). Thus, in addition to pigmentary traits, ultraviolet radiation (UVR)-related factors and clinical features of KC such as anatomic site may be useful in identifying patients at increased risk for melanoma after KC.

3.
mSphere ; 5(2)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295867

RESUMO

Although the term "microbiome" refers to all microorganisms, the majority of microbiome studies focus on the bacteriome. Here, we characterize the oral mycobiome, including mycobiome-bacteriome interactions, in the setting of remission-induction chemotherapy (RIC) for acute myeloid leukemia (AML). Oral samples (n = 299) were prospectively collected twice weekly from 39 AML patients during RIC until neutrophil recovery. Illumina MiSeq 16S rRNA gene (V4) and internal transcribed spacer 2 (ITS2) sequencing were used to determine bacterial and fungal diversity and community composition. Intrakingdom and interkingdom network connectivity at baseline (T1) and at midpoint (T3) and a later time point (T6) were assessed via SPIEC-EASI (sparse inverse covariance estimation for ecological association inference). In this exploratory study, mycobiome α-diversity was not significantly associated with antibiotic or antifungal receipt. However, postchemotherapy mycobiome α-diversity was lower in subjects receiving high-intensity chemotherapy. Additionally, greater decreases in Malassezia levels were seen over time among patients on high-intensity RIC compared to low-intensity RIC (P = 0.003). A significantly higher relative abundance of Candida was found among patients who had infection (P = 0.008), while a significantly higher relative abundance of Fusarium was found among patients who did not get an infection (P = 0.03). Analyses of intrakingdom and interkingdom relationships at T1, T3, and T6 indicated that interkingdom connectivity increased over the course of IC as bacterial α-diversity diminished. In (to our knowledge) the first longitudinal mycobiome study performed during AML RIC, we found that mycobiome-bacteriome interactions are highly dynamic. Our study data suggest that inclusion of mycobiome analysis in the design of microbiome studies may be necessary to optimally understand the ecological and functional role of microbial communities in clinical outcomes.IMPORTANCE This report highlights the importance of longitudinal, parallel characterization of oral fungi and bacteria in order to better elucidate the dynamic changes in microbial community structure and interkingdom functional interactions during the injury of chemotherapy and antibiotic exposure as well as the clinical consequences of these interrelated alterations.

4.
J Hazard Mater ; 395: 122687, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32330784

RESUMO

In assessing the biological impact of airborne particles in vitro, air-liquid interface (ALI) exposure chambers are increasingly preferred over classical submerged exposure techniques, albeit historically limited by their inability to deliver sufficient aerosolized dose. A novel ALI system, the Dosimetric Aerosol in Vitro Inhalation Device (DAVID), bioinspired by the human respiratory system, uses water-based condensation for highly efficient aerosol deposition to ALI cell culture. Here, welding fumes (well-studied and inherently toxic ultrafine particles) were used to assess the ability of DAVID to generate toxicological responses between differing welding conditions. After fume exposure, ALI-cultured cells showed reductions in viability that were both distinct between welding conditions and linearly dose-dependent with respect to exposure time; comparatively, submerged cell cultures ran in parallel did not show these trends across exposure levels. DAVID delivers a substantial dose in minutes (> 100 µg/cm2), making it preferable over previous ALI systems, which require hours of exposure to deliver sufficient dose, and over submerged techniques, which lack comparable physiological relevance. DAVID has the potential to provide the most accurate assessment of in vitro toxicity yet from the perspectives of physiological relevance to the human respiratory system and efficiency in collecting ultrafine aerosol common to hazardous exposure conditions.

5.
Trauma Violence Abuse ; : 1524838020916254, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32266870

RESUMO

For individuals experiencing intimate partner violence (IPV), formal services, including community agencies, health services, or the criminal justice system, are critical resources. Understanding the specific barriers that hinder or prevent survivors from seeking help from formal services could reveal important implications for the development of services for IPV as well as for members of other organizations who encounter survivors. The authors conducted a systematic review of the literature to identify barriers to help-seeking from formal services for survivors. Ten electronic databases were searched for key terms related to IPV, help seeking from formal services, and barriers to help seeking. Articles were included in the review if they were U.S.-based, contained samples that were adults who had experienced IPV, and discussed barriers to seeking help from formal services. An initial search yielded 1,155 articles and after screening, 29 articles were included in the review. Data were extracted to reveal the state of the literature regarding help-seeking barriers for survivors. Six barriers to help seeking were identified as follows: (1) lack of awareness, (2) access challenges, (3) consequences of disclosure, (4) lack of material resources, (5) personal barriers, and (6) system failures. These findings demonstrate the need for continued education surrounding available services for IPV as well as the continued development of resources that can mitigate personal barriers that survivors may face. Furthermore, these findings illuminate the necessity to increase the access of services, particularly for non-English speakers, immigrants and refugees, individuals with disabilities, men, and LGBTQIA identified individuals.

6.
J Microsc ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943175

RESUMO

Both plants and animals sense and respond to mechanical stresses that arise internally or are externally imposed. In many cases, tissues respond by changing their gene expression or their mechanical properties, which has an impact on how they develop. Many tools have been developed to measure mechanical properties and to investigate responses to mechanical stress. Here we review the state of microscope-coupled tensile testing at the single-cell and tissue scale and give a view on future opportunities for extending the technology. Uniaxial tensile testing involves quantifying the deformation of a sample when a force is applied. By varying the amount of force, the speed at which the force is applied or the length of time that it is applied for, many characteristics of the mechanical properties of the sample can be calculated. Tensile testing has been used extensively to measure the mechanical properties of whole tissues or organs. The need for higher resolution data resulted in more researchers using indentation tests to measure mechanical properties instead. Indentation tests provide information at a different scale and are not suitable for answering the same type of questions as tensile testing. Here we discuss that by coupling tensile-testing machinery with microscopes such as is the case for the Automated Confocal Micro-Extensometer (ACME) it is possible to obtain tissue-scale measurements of mechanical properties with cellular resolution. Moreover, to understand and identify the biological processes cells and tissues use to respond to mechanical stress, we need to be able to apply mechanical perturbations to plant samples while recording the induced biological changes with microscopy. LAY DESCRIPTION: Plants, like most living organisms, are sensitive to their environment. This includes mechanical stresses imposed upon them by gravity or wind. Mechanical stress can also arise from internal tissue tension, which can build up if different parts of a tissue grow at different rates. In many cases, the cells respond to mechanical stress by changing their mechanical properties, which can affect their growth and their final shape. There is thus a critical need to develop tools for measuring mechanical properties and the response to mechanical stress. Mechanical properties cannot be visualised directly but must be inferred by looking at how a tissue deforms when a force is applied or vice versa. This is more challenging when one wishes to achieve this at the cellular scale, as the forces and deformations are much smaller. There are a range of methods available that have advantages and disadvantages. Here we review some of these methods. In particular, we focus on methods that cause deformation in the main axis of the tissue. This type of test can be coupled with conventional and state-of-the-art microscopes. Coupling with microscopes increases the resolution of the tests that can be performed and facilitates the simultaneous observation of responses to the mechanical stresses.

7.
Org Lett ; 21(22): 9099-9103, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31668077

RESUMO

We report herein an efficient, stereocontrolled, and chromatography-free synthesis of the novel broad spectrum antibiotic GDC-5338. The route features the construction of a functionalized tripeptide backbone, a high-yielding macrocyclization via a Pd-catalyzed Suzuki-Miyaura reaction, and the late-stage elaboration of key amide bonds with minimal stereochemical erosion. Through extensive reaction development and analytical understanding, these key advancements allowed the preparation of GDC-5338 in 17 steps, 15% overall yield, >99 A % HPLC, and >99:1 dr.

8.
J Obstet Gynecol Neonatal Nurs ; 48(6): 604-614, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479629

RESUMO

OBJECTIVE: To describe the perspectives of women who experienced intimate partner violence (IPV) during pregnancy through a qualitative, interpretive metasynthesis. DATA SOURCES: We searched 12 electronic databases to identify articles on qualitative studies pertaining to women's experiences of IPV during pregnancy. We searched Academic Search Complete, AgeLine, CINAHL Complete, Family Studies Abstracts, MEDLINE, PsycARTICLES, Psychology and Behavioral Sciences, PsycINFO, Social Work Abstracts, Health Source-Consumer Edition, Health Source-Nursing/Academic Edition, and Humanities Full Text for articles published from 2008 through 2018. DATA EXTRACTION: We used inclusion and exclusion criteria to identify eight reports of qualitative studies that contained direct quotations in which women described their experiences of IPV. DATA SYNTHESIS: We used a methodologic reduction to provide a theoretical context that helped us synthesize the data to five key themes: Pregnancy Escalates Abuse, Concern for Unborn Fetus, Importance ofSupport, My Child Saved Me, and Pregnancy Is a Catalyst for Reflection. CONCLUSION: The results of our synthesis illustrate the unique perspectives of women who experienced IPV during pregnancy. Understanding these experiences can help health care providers assist pregnant women through enhanced screenings and education. Health care providers can also help women identify resources for emotional and financial support as they determine the best courses of action for themselves and their children.

9.
Clin Infect Dis ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31437269

RESUMO

BACKGROUND: Urinary tract infections (UTIs) occur commonly, but recent data on UTI rates are scarce. It is unknown how the growth of virtual health care delivery affects outpatient UTI management and trends in the United States. PATIENTS AND METHODS: From January 1, 2008 to December 31, 2017, UTIs from outpatient settings (office, emergency, and virtual visits) were identified from electronic health records at Kaiser Permanente Southern California using multiple UTI definitions. Annual rates estimated by Poisson regression were stratified by sex, care setting, age, and race/ethnicity. Annual trends were estimated by linear or piecewise Poisson regression. RESULTS: UTIs occurred in 1,065,955 individuals. Rates per 1000 person-years were 53.7 (95% CI: 50.6 to 57.0) by diagnosis code with antibiotic and 25.8 (95% CI: 24.7 to 26.9) by positive culture. Compared to office and emergency visits, UTIs were increasingly diagnosed in virtual visits, where rates by diagnosis code with antibiotic increased annually by 21.2% (95% CI: 16.5% to 26.2%) in females and 29.3% (95% CI: 23.7% to 35.3%) in males. Only 32% of virtual care diagnoses had a culture order. Overall, UTI rates were highest and increased the most in older adults. Rates were also higher in Hispanic and White females and Black and White males. CONCLUSION: Outpatient UTI rates increased from 2008 to 2017, especially in virtual care and among older adults. Virtual care is important for expanding access to health services, but strategies are needed in all outpatient care settings to ensure accurate UTI diagnosis and reduce inappropriate antibiotic treatment.

10.
Nanotoxicology ; 13(9): 1176-1196, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31328592

RESUMO

Exposure of lung cells in vitro or mice to single-walled carbon nanotubes (SWCNTs) directly to the respiratory tract leads to a reduced host anti-viral immune response to infection with influenza A virus H1N1 (IAV), resulting in significant increases in viral titers. This suggests that unintended exposure to nanotubes via inhalation may increase susceptibility to notorious respiratory viruses that carry a high social and economic burden globally. However, the molecular mechanisms that contribute to viral susceptibility have not been elucidated. In the present study, we identified the retinoic acid-induced gene I (RIG-I) like receptors (RLRs)/mitochondrial antiviral signaling (MAVS) pathway as a target of SWCNT-induced oxidative stress in small airway epithelial cells (SAEC) that contribute to significantly enhanced influenza viral titers. Exposure of SAEC to SWCNTs increases viral titers while repressing several aspects of the RLR pathway, including mRNA expression of key genes (e.g. IFITs, RIG-I, MDA5, IFNß1, CCL5). SWCNTs also reduce mitochondrial membrane potential without altering oxygen consumption rates. Our findings also indicate that SWCNTs can impair formation of MAVS prion-like aggregates, which is known to impede downstream activation of the RLR pathway and hence the transcriptional production of interferon-regulated anti-viral genes and cytokines. Furthermore, application of the antioxidant NAC alleviates inhibition of gene expression levels by SWCNTs, as well as MAVS signalosome formation, and increased viral titers. These data provide evidence of targeted impairment of anti-viral signaling networks that are vital to immune defense mechanisms in lung cells, contributing to increased susceptibility to IAV infections by SWCNTs.

11.
J Pharm Biomed Anal ; 174: 518-524, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252308

RESUMO

Identification and localization of modifications in peptides containing multiple disulfide bonds is challenging due to inefficient fragmentation in mass spectrometry (MS) analysis. In cases where MS fragmentation techniques such as electron capture dissociation (ECD), electron transfer dissociation (ETD), and ultraviolet photodissociation (UVPD) fail to achieve efficient fragmentation, off-line disulfide bond reduction techniques are typically employed prior to MS analysis. Some commonly used reducing agents include dithiothreitol (DTT) and tris(2-carboxyethyl)phosphine (TCEP). In this work, we describe the detection and identification of an unexpected impurity that formed during the reduction of Peptide A, containing multiple disulfide bonds, while using DTT or TCEP as reducing agents and acetonitrile as a co-solvent. The DTT reduced products were found to be a mixture of the expected linear Peptide A (fully reduced) and an unknown product (>50%) with a mass corresponding to linear Peptide A plus 41 Da ([reduced-M + 41]). A series of experiments were subsequently performed to investigate the identity and origin of this impurity. Disulfide bond reduction with DTT was performed in aqueous mixtures containing acetonitrile, methanol, and deuterated acetonitrile; and with TCEP in aqueous mixtures containing acetonitrile. Additionally, glycine amino acid was used as a surrogate to investigate the mechanism. The liquid chromatography-mass spectrometry (LCMSMS) results demonstrated that the [reduced-M + 41] impurity was an acetonitrile addition on the peptide's N-terminal glycine. The corresponding impurity [M + 41] was also found in the native Peptide A (non-reduced), suggesting that small amounts of this impurity may also be generated during the synthesis in the upstream process steps. By understanding the formation of this process-related impurity [M + 41], one could potentially reduce or eliminate its presence in Peptide A through chemical controls. Finally, this observation provides caution against using acetonitrile as a co-solvent during DTT- or TCEP-promoted reduction of peptides with an uncapped N-terminus primary amine.


Assuntos
Acetonitrilos/química , Dissulfetos/química , Ditiotreitol/química , Peptídeos/química , Fosfinas/química , Aminas/química , Cromatografia Líquida , Glicina/química , Proteína Oncogênica pp60(v-src)/química , Oxirredução , Fragmentos de Peptídeos/química , Domínios Proteicos , Substâncias Redutoras/química , Espectrometria de Massas por Ionização por Electrospray , Raios Ultravioleta
12.
PLoS One ; 14(5): e0216417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31083672

RESUMO

Dopamine (DA) is a neurotransmitter with actions across phylogeny that modulate core behaviors such as motor activity, reward, attention, and cognition. Perturbed DA signaling in humans is associated with multiple disorders, including addiction, ADHD, schizophrenia, and Parkinson's disease. The presynaptic DA transporter exerts powerful control on DA signaling by efficient clearance of the neurotransmitter following release. As in vertebrates, Caenorhabditis elegans DAT (DAT-1) constrains DA signaling and loss of function mutations in the dat-1 gene result in slowed crawling on solid media and swimming-induced paralysis (Swip) in water. Previously, we identified a mutant line, vt34, that exhibits robust DA-dependent Swip. vt34 exhibits biochemical and behavioral phenotypes consistent with reduced DAT-1 function though vt34; dat-1 double mutants exhibit an enhanced Swip phenotype, suggesting contributions of the vt34-associated mutation to additional mechanisms that lead to excess DA signaling. SNP mapping and whole genome sequencing of vt34 identified the site of the molecular lesion in the gene B0412.2 that encodes the Runx transcription factor ortholog RNT-1. Unlike dat-1 animals, but similar to other loss of function rnt-1 mutants, vt34 exhibits altered male tail morphology and reduced body size. Deletion mutations in both rnt-1 and the bro-1 gene, which encodes a RNT-1 binding partner also exhibit Swip. Both vt34 and rnt-1 mutations exhibit reduced levels of dat-1 mRNA as well as the tyrosine hydroxylase ortholog cat-2. Although reporter studies indicate that rnt-1 is expressed in DA neurons, its re-expression in DA neurons of vt34 animals fails to fully rescue Swip. Moreover, as shown for vt34, rnt-1 mutation exhibits additivity with dat-1 in generating Swip, as do rnt-1 and bro-1 mutations, and vt34 exhibits altered capacity for acetylcholine signaling at the neuromuscular junction. Together, these findings identify a novel role for rnt-1 in limiting DA neurotransmission and suggest that loss of RNT-1 may disrupt function of both DA neurons and body wall muscle to drive Swip.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Dopamina/metabolismo , Mutação com Perda de Função , Paralisia , Natação , Fatores de Transcrição , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Dopamina/genética , Neurônios Dopaminérgicos/metabolismo , Paralisia/genética , Paralisia/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo
13.
J Pediatr ; 211: 152-158, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103258

RESUMO

OBJECTIVE: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children. STUDY DESIGN: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole. RESULTS: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001). CONCLUSIONS: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

14.
Health Equity ; 3(1): 92-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30963142

RESUMO

Disparities in outcomes for preventive and primary health care services often result when vulnerable patients rely on episodic encounters for emergency services that do not meet their long-term health needs. Understanding health outcomes in socially or economically disadvantaged subgroups is crucial to improving community health, and it requires innovative analytics and dynamic application of clinical and population data. While it is common practice to use proxy indicators, such as quality of life and mortality, when discussing health equity, these have shown limited utility and are rarely applied at a population-level within a health system. Therefore, we designed and implemented an index, calculated as the ratio of observed-to-expected encounters, to identify and quantify health inequalities in health care systems. Providing equitable care, as measured by health outcomes, is analogous to precision medicine applied to social determinants. For health systems, the use of this index will facilitate the development of specially-tailored interventions to address inequity and provides a tool to measure the impact of such programs.

15.
Biosensors (Basel) ; 9(2)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013753

RESUMO

Development of technologies for rapid screening of DNA secondary structure thermal stability and the effects on stability for binding of small molecule drugs is important to the drug discovery process. In this report, we describe the capabilities of an electrochemical, microdevice-based approach for determining the melting temperatures (Tm) of electrode-bound duplex DNA structures. We also highlight new features of the technology that are compatible with array development and adaptation for high-throughput screening. As a foundational study to exhibit device performance and capabilities, melting-curve analyses were performed on 12-mer DNA duplexes in the presence/absence of two binding ligands: diminazene aceturate (DMZ) and proflavine. By measuring electrochemical current as a function of temperature, our measurement platform has the ability to determine the effect of binding ligands on Tm values with high signal-to-noise ratios and good reproducibility. We also demonstrate that heating our three-electrode cell with either an embedded microheater or a thermoelectric module produces similar results. The ΔTm values we report show the stabilizing ability of DMZ and proflavine when bound to duplex DNA structures. These initial proof-of-concept studies highlight the operating characteristics of the microdevice platform and the potential for future application toward other immobilized samples.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Diminazena/análogos & derivados , Diminazena/química , Ligantes , Proflavina/química , Temperatura de Transição
16.
Cent Asian J Glob Health ; 8(1): 341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881758

RESUMO

Introduction: The sisterhood method of maternal mortality data collection and analysis provides a validated framework for estimating maternal mortality ratios in situations of limited infrastructure. The aim of this study is to assess sub-national maternal mortality in the Badakhshan region of Tajikistan using the sisterhood method as part of a larger ethnographic study on maternal risk. Methods: In 2006-2007, 1004 married women of reproductive age in Gorno-Badakhshan Autonomous Oblast, Tajikistan were surveyed using the sisterhood method. Respondents were asked eleven questions about the sex, age and survivorship of all children born to the respondent's mother. Results: Using a national total fertility rate (TFR) estimate of 4.88, the maternal mortality ratio (MMR) in Tajik Badakhshan was 141 maternal deaths per 100,000 live births (95% CI 49-235). The lifetime risk of maternal death was 1 in 141 (95% CI 34-103). Conclusion: Given the inherent time-lag of the sisterhood method, precise estimates of maternal mortality are dependent on accurate TFRs, which may vary based upon regional experiences of demographic transitions. Socio-political instability and the dismantling of Soviet welfare programs and civil war following Tajikistan's independence from the Soviet Union in 1991 likely impacted TFR in Tajik Badakhshan. Socio-political trends influencing TFR in rural regions compared to urban, and the investigation of factors associated with maternal mortality, require additional investigation.

17.
Health Soc Care Community ; 27(3): e23-e36, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30178901

RESUMO

Postpartum depression (PPD) is a significant public health concern due to the physical, emotional, economic, and life course outcomes. Rates of PPD are significantly higher for marginalised populations and can impact low-income, minority, and/or immigrant women differently when compared to white middle-class women. Commonly studied negative effects of PPD include poor health outcomes, mother-child bonding challenges, and negative child educational outcomes. However, research surveying the postpartum experience and negative outcomes among marginalised women is sparse. This study implemented a qualitative meta-interpretive synthesis (QIMS) methodology to synthesise themes across 12 qualitative research articles surveying postpartum experiences of marginalised women in North American countries. Articles included in the QIMS were extracted from online databases from a 10-year window spanning January 2008-2018. The guiding research question was "What are the PPD experiences of women belonging to marginalized populations?" Constant comparative analysis was used with coding in atlas.ti and themes were synthesised with input of all three authors. Five main themes emerged. The themes are (a) intersections of PPD and poverty, (b) culture and PPD, (c) pressures of mothering, (d) strengths and coping, and (e) abuse affects my PPD experience. Subthemes such as "I keep it to myself" relating to cultural response to PPD and idealised mothering were also discovered. Implications for social workers, nurses, and future research are discussed.

18.
Lang Speech Hear Serv Sch ; 50(1): 83-98, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30453331

RESUMO

Purpose This study examined how lexical representations and intervention intensity affect phonological acquisition and generalization in children with speech sound disorders. Method Using a single-subject multiple baseline design, 24 children with speech sound disorders (3;6 to 6;10 [years;months]) were split into 3 word lexicality types targeting word-initial complex singleton phonemes: /ɹ l ʧ θ/. Specifically, academic vocabulary words, nonwords (NWs), and high-frequency (HF) words were contrasted. Intervention intensity was examined by comparing the performance of 12 children who completed eleven 50-min sessions (4 children/word type) to the performance of 12 who completed 19 sessions (4 children/word type). Children's production accuracy of their treated phonemes and overall percent consonants correct values were used to measure phonological generalization via percentage accuracy scores and d scores. Results All word lexicality conditions elicited phonological change, suggesting that academic vocabulary words, NWs, and HF words are viable intervention targets. Group mean averages were similarly high for the NWs and HF words, although children in the NW condition demonstrated more consistent phonological gains. Children who received 19 intervention sessions achieved 6 times more gains in treated sound accuracy than did children who received 11 sessions. Conclusions Word lexicality did not significantly influence children's intervention outcomes. More intensive intervention, as characterized by the number sessions, resulted in greater phonological change than did a shorter intervention program. Intervention intensity outcomes should be considered when establishing best practices for speech intervention scheduling. Supplemental Material https://doi.org/10.23641/asha.7336055.


Assuntos
Fonética , Transtorno Fonológico/terapia , Fonoterapia/métodos , Fala , Vocabulário , Criança , Pré-Escolar , Feminino , Humanos , Intenção , Masculino , Percepção da Fala , Medida da Produção da Fala , Resultado do Tratamento
19.
PLoS Biol ; 16(11): e2005952, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30383040

RESUMO

A developing plant organ exhibits complex spatiotemporal patterns of growth, cell division, cell size, cell shape, and organ shape. Explaining these patterns presents a challenge because of their dynamics and cross-correlations, which can make it difficult to disentangle causes from effects. To address these problems, we used live imaging to determine the spatiotemporal patterns of leaf growth and division in different genetic and tissue contexts. In the simplifying background of the speechless (spch) mutant, which lacks stomatal lineages, the epidermal cell layer exhibits defined patterns of division, cell size, cell shape, and growth along the proximodistal and mediolateral axes. The patterns and correlations are distinctive from those observed in the connected subepidermal layer and also different from the epidermal layer of wild type. Through computational modelling we show that the results can be accounted for by a dual control model in which spatiotemporal control operates on both growth and cell division, with cross-connections between them. The interactions between resulting growth and division patterns lead to a dynamic distributions of cell sizes and shapes within a deforming leaf. By modulating parameters of the model, we illustrate how phenotypes with correlated changes in cell size, cell number, and organ size may be generated. The model thus provides an integrated view of growth and division that can act as a framework for further experimental study.


Assuntos
Divisão Celular/fisiologia , Proliferação de Células/fisiologia , Desenvolvimento Vegetal/fisiologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Tamanho Celular , Regulação da Expressão Gênica de Plantas/genética , Modelos Biológicos , Folhas de Planta/crescimento & desenvolvimento , Estômatos de Plantas/genética , Estômatos de Plantas/crescimento & desenvolvimento , Análise Espaço-Temporal
20.
Respir Res ; 19(1): 160, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30165855

RESUMO

BACKGROUND: Sex differences in idiopathic pulmonary fibrosis (IPF) suggest a protective role for estrogen (E2); however, mechanistic studies in animal models have produced mixed results. Reports using cell lines have investigated molecular interactions between transforming growth factor beta1 (TGF-ß1) and estrogen receptor (ESR) pathways in breast, prostate, and skin cells, but no such interactions have been described in human lung cells. To address this gap in the literature, we investigated a role for E2 in modulating TGF-ß1-induced signaling mechanisms and identified novel pathways impacted by estrogen in bronchial epithelial cells. METHODS: We investigated a role for E2 in modulating TGF-ß1-induced epithelial to mesenchymal transition (EMT) in bronchial epithelial cells (BEAS-2Bs) and characterized the effect of TGF-ß1 on ESR mRNA and protein expression in BEAS-2Bs. We also quantified mRNA expression of ESRs in lung tissue from individuals with IPF and identified potential downstream targets of E2 signaling in BEAS-2Bs using RNA-Seq and gene set enrichment analysis. RESULTS: E2 negligibly modulated TGF-ß1-induced EMT; however, we report the novel observation that TGF-ß1 repressed ESR expression, most notably estrogen receptor alpha (ESR1). Results of the RNA-Seq analysis showed that TGF-ß1 and E2 inversely modulated the expression of several genes involved in processes such as extracellular matrix (ECM) turnover, airway smooth muscle cell contraction, and calcium flux regulation. We also report that E2 specifically modulated the expression of genes involved in chromatin remodeling pathways and that this regulation was absent in the presence of TGF-ß1. CONCLUSIONS: Collectively, these results suggest that E2 influences unexplored pathways that may be relevant to pulmonary disease and highlights potential roles for E2 in the lung that may contribute to sex-specific differences.


Assuntos
Receptores Estrogênicos/biossíntese , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Idoso , Células Cultivadas , Relação Dose-Resposta a Droga , Estrogênios/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia
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