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Per- and polyfluoroalkyl substances (PFAS) bioaccumulate in different organ systems, including bone. While existing research highlights the adverse impact of PFAS on bone density, a critical gap remains in understanding the specific effects on the bone marrow microenvironment, especially the bone marrow adipose tissue (BMAT). Changes in BMAT have been linked to various health consequences, such as the development of osteoporosis and the progression of metastatic tumors in bone. Studies presented herein demonstrate that exposure to a mixture of five environmentally relevant PFAS compounds promotes marrow adipogenesis in vitro and in vivo. We show that among the components of the mixture, PFHxS, an alternative to PFOS, has the highest propensity to accumulate in bone and effectively promote marrow adipogenesis. Utilizing RNAseq approaches, we identified the peroxisome proliferator-activated receptor (PPAR) signaling as a top pathway modulated by PFHxS exposure. Furthermore, we provide results suggesting the activation and involvement of PPAR-gamma (PPARγ) in PFHxS-mediated bone marrow adipogenesis, especially in combination with high-fat diet. In conclusion, our findings demonstrate the potential impact of elevated PFHxS levels, particularly in occupational settings, on bone health, and specifically bone marrow adiposity. This study contributes new insights into the health risks of PFHxS exposure, urging further research on the relationship between environmental factors, diet, and adipose tissue dynamics.
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INTRODUCTION: This is a systematic review on patient-provider satisfaction in U.S. prenatal care by addressing the following research question: What factors influence patient-provider satisfaction during prenatal care? METHODS: Thirty six online databases were searched for peer-reviewed research from February to September of 2018 using 10 key terms published in English on U.S. populations between the years 1993-2018 on the topic of provider communication skills and patient satisfaction in the prenatal context. Searches yielded 2563 articles. After duplicates were reviewed and eligibility determined, 32 articles met criteria and were included in the final content analysis. All reported study variables were entered into EXCEL, data reported in each study were analyzed by two people for inter-rater reliability and included in the qualitative content analysis. Two researchers also utilized assessment tools to assess the quality of the articles. RESULTS: Results indicate the importance of good patient-provider communication, that patients have a need for more information on a plethora of topics, and that Hispanic and African American women reported less satisfaction. DISCUSSION: We recommend that future studies measure potentially significant themes not adequately present in the reviewed studies such as practitioner demographics (e.g. gender, years of experience, or race/ethnicity), mothers under 18 years of age, inclusion of religious minorities, patients with differing immigration statuses, and patients with disabilities.
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BACKGROUND: Ultraviolet (UV) radiation leads to deoxyribonucleic acid (DNA) damage and changes in gene expression. Topical DNA repair enzymes in liposomes are capable of undoing this damage. OBJECTIVE: To evaluate gene expression changes induced by ultraviolent B-rays (UVB) light and assess the effect of topical DNA repair enzymes extracted from Micrococcus luteus (M. luteus) and photolyase in modifying these changes. METHODS: Non-invasive, adhesive patch collection kits were used to sample skin on the right and left post-auricular areas before and 24 hours after UVB exposure (n=48). Subjects applied topical DNA repair enzymes to the right post-auricular area daily for 2 weeks. Subjects returned 2 weeks later for repeat non-invasive skin sample collection. RESULTS: Eight of 18 tested genes demonstrated significant changes 24 hours following UVB exposure. DNA repair enzymes from M. luteus or photolyase had no significant effect on genetic expression compared with the control at 2 weeks post UV exposure. CONCLUSION: UVB exposure causes acute changes in gene expression, which may play roles in photo-aging damage and skin cancer growth and regulation. While non-invasive gene expression testing can detect UV damage, additional genomic studies investigating recovery from UV damage at different time periods are needed to establish the potential of DNA repair enzymes to minimize or reverse this damage. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7070.
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Desoxirribodipirimidina Fotoliase , Neoplasias Cutâneas , Humanos , Dano ao DNA , Desoxirribodipirimidina Fotoliase/genética , Reparo do DNA , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Enzimas Reparadoras do DNA/genéticaRESUMO
Even though drought impacts on tree physiology have been identified, whether drought affects leaf litter chemistry that, in turn, influences litter decay rates is still poorly understood. We compared litter quality and decomposition for two cohorts of leaves from five co-occurring seasonally deciduous tree species: Acer saccharum, Tilia americana, Quercus rubra, Quercus alba, and Ostrya virginiana. One cohort experienced a growing-season drought, and the other cohort came from the same trees in the ensuing, post-drought growing season. Leaf litter production was greater for drought litter than post-drought litter for all five species. Specific leaf area and nitrogen concentrations were 20% greater for the drought cohort than the post-drought cohort. Concentrations of non-structural carbohydrates were about 14% greater for the drought cohort, except for greater values for post-drought A. saccharum litter. Pectin in the middle lamella of leaf litter was 31% lower for the drought cohort compared to post-drought cohort. We found few differences in litter decay rates between drought and post-drought cohorts, although Q. rubra litter had more decomposition for the post-drought cohort than the drought cohort, whereas A. saccharum litter had more decomposition for the drought cohort than the post-drought cohort. Leaf litter decay rates for the drought cohort were related to litter nitrogen and lignin concentrations, whereas decay rates for the post-drought cohort were related to litter carbohydrate concentrations. Our findings suggest that the role of drought events on seasonally deciduous forest ecosystems must recognize species-specific, idiosyncratic responses in leaf litter quality and decomposition.
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Ecossistema , Quercus , Secas , Florestas , Humanos , Lignina/análise , Nitrogênio/análise , Pectinas/análise , Folhas de Planta/química , Árvores/fisiologiaRESUMO
OBJECTIVE: Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients' comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability. METHODS: In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. RESULTS: Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six "level-1A" scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31-0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17-1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology). CONCLUSION: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.
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Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Comorbidade , Feminino , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
The Southwestern United States has a legacy of industrial mining due to the presence of rich mineral ore deposits. The relationship between environmental inhaled particulate matter (PM) exposures and neurological outcomes within an autoimmune context is understudied. The aim of this study was to compare two regionally-relevant dusts from high-priority abandoned mine-sites, Claim 28 PM, from Blue Gap Tachee, AZ and St. Anthony mine PM, from the Pueblo of Laguna, NM and to expose autoimmune-prone mice (NZBWF1/J). Mice were randomly assigned to one of three groups (n = 8/group): DM (dispersion media, control), Claim 28 PM, or St. Anthony PM, subjected to oropharyngeal aspiration of (100 µg/50 µl), once per week for a total of 4 consecutive doses. A battery of immunological and neurological endpoints was assessed at 24 weeks of age including: bronchoalveolar lavage cell counts, lung gene expression, brain immunohistochemistry, behavioral tasks and serum autoimmune biomarkers. Bronchoalveolar lavage results demonstrated a significant increase in number of polymorphonuclear neutrophils following Claim 28 and St. Anthony mine PM aspiration. Lung mRNA expression showed significant upregulation in CCL-2 and IL-1ß following St. Anthony mine PM aspiration. In addition, neuroinflammation was present in both Claim 28 and St. Anthony mine-site derived PM exposure groups. Behavioral tasks resulted in significant deficits as determined by Y-maze new arm frequency following Claim 28 aspiration. Neutrophil elastase was significantly upregulated in the St. Anthony mine exposure group. Interestingly, there were no significant changes in serum autoantigens suggesting systemic inflammatory effects may be mediated through other molecular mechanisms following low-dose PM exposures.
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Poluentes Atmosféricos/toxicidade , Poeira/análise , Encefalite/fisiopatologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Material Particulado/toxicidade , Pneumonia/fisiopatologia , Animais , Arizona , Doenças Autoimunes/etiologia , Biomarcadores/metabolismo , Modelos Animais de Doenças , Poeira/imunologia , Encefalite/induzido quimicamente , Feminino , Exposição por Inalação/efeitos adversos , Camundongos , Mineração , New Mexico , Tamanho da Partícula , Pneumonia/induzido quimicamente , Distribuição AleatóriaRESUMO
Background and Purpose- The mobile stroke unit (MSU) brings imaging and thrombolysis to patients in the field. The MSU has the potential to decrease time from onset to thrombolysis; however, this depends on the location of the patient, the MSU, and the hospital. The MSU will only be able to treat a small subset of patients it is dispatched to. Using conditional probability modeling, we evaluate in which scenarios the MSU exhibits clear benefit over the direct-to-mothership method. Methods- Previously published conditional probability models for drip-and-ship versus mothership transport were modified to reflect MSU workflow. It was assumed that the MSU was dispatched from the endovascular therapy center. Eight scenarios were generated, varying treatment efficiency on the MSU and at the endovascular therapy center and the threshold for dispatching the MSU (low threshold: low treatment rate but few missed patients; high threshold: higher treatment rate, potential for missed treatment opportunities). Results- The relative difference in outcomes between the MSU and mothership was small. Geographic areas where the MSU is superior to mothership increase in size as treatment time on the MSU decreases. When a high-threshold dispatch system is used, the area where the MSU is superior decreases, but the relative difference in predicted outcomes between the MSU and mothership increases. The largest relative difference favoring the MSU was found in areas where the patient would forgo access to alteplase, based upon a 4.5-hour treatment threshold, using mothership transport. Conclusions- There are few scenarios where MSU transport predicts substantially superior outcomes to the mothership method when the MSU is dispatched from the endovascular therapy center. Outcomes using the MSU are maximized when dispatch criteria that maximize patients eligible for thrombolysis treatment are used and treatment times on the MSU are short relative to those of the endovascular therapy center.
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Isquemia Encefálica , Unidades Móveis de Saúde , Modelos Teóricos , Acidente Vascular Cerebral , Terapia Trombolítica , Tempo para o Tratamento , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Current stroke treatment guidelines restrict level 1A recommendations for endovascular therapy to patients with baseline ASPECTS score > 5. However, a recent meta-analysis from the HERMES-group showed treatment benefit in patients with ASPECTS ≤ 5. We aimed to explore how physicians across different specialties and countries approach endovascular treatment decision-making in acute ischemic stroke patients with low baseline ASPECTS. METHODS: In a multidisciplinary survey, 607 stroke physicians were randomly assigned 10 out of a pool of 22 case-scenarios, 3 of which involved patients with low baseline ASPECTS (A:40-year old with ASPECTS 4, B:33-year old with ASPECTS 2 C:72-year old with ASPECTS 3), otherwise fulfilling all EVT-eligibility criteria. Participants were asked how they would treat the patient A) under their current local resources and B) under assumed ideal conditions, without any external (monetary, policy-related or infrastructural) restraints. Overall and scenario-specific decision rates were calculated. Clustered multivariable logistic regression analysis was used to determine the association of baseline ASPECTS with endovascular treatment-decision. RESULTS: Baseline ASPECTS score was significantly associated with current (OR:1.09, CI 1.05-1.13) and ideal endovascular treatment-decision (OR:1.12, CI 1.08-1.16). Overall current and ideal treatment decision-rates for the low ASPECTS scenarios were 57.1% and 57.6%. Current and ideal rates for the two younger patients were higher (scenario A:69.9/60.4%, scenario B:60.0/61.5%) compared to the 72-year old patient (41.3/40.2%). CONCLUSION: Most physicians decided to proceed with endovascular treatment despite low baseline ASPECTS, particularly in younger patients. This may have implications on the design and execution of low ASPECTS randomized trials.
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Regras de Decisão Clínica , Tomada de Decisão Clínica , Procedimentos Endovasculares , Seleção de Pacientes , Acidente Vascular Cerebral/terapia , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
Background and Purpose- The American Heart Association and the American Stroke Association guidelines for early management of patients with ischemic stroke offer guidance to physicians involved in acute stroke care and clarify endovascular treatment indications. The purpose of this study was to assess concordance of physicians' endovascular treatment decision-making with current American Heart Association and the American Stroke Association stroke treatment guidelines using a survey-approach and to explore how decision-making in the absence of guideline recommendations is approached. Methods- In an international cross-sectional survey (UNMASK-EVT), physicians were randomly assigned 10 of 22 case scenarios (8 constructed with level 1A and 11 with level 2B evidence for endovascular treatment and 3 scenarios without guideline coverage) and asked to declare their treatment approach (1) under their current local resources and (2) assuming there were no external constraints. The proportion of physicians offering endovascular therapy (EVT) was calculated. Subgroup analysis was performed for different specialties, geographic regions, with regard to physicians' age, endovascular, and general stroke treatment experience. Results- When facing level 1A evidence, participants decided in favor of EVT in 86.8% under current local resources and in 90.6% under assumed ideal conditions, that is, 9.4% decided against EVT even under assumed ideal conditions. In case scenarios with level 2B evidence, 66.3% decided to proceed with EVT under current local resources and 69.7% under assumed ideal conditions. Conclusions- There is potential for improving thinking around the decision to offer endovascular treatment, since physicians did not offer EVT even under assumed ideal conditions in 9.4% despite facing level 1A evidence. A majority of physicians would offer EVT even for level 2B evidence cases.
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Isquemia Encefálica/terapia , Tomada de Decisão Clínica , Procedimentos Endovasculares/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Adulto , Medicina Baseada em Evidências , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Neurologistas , Neurocirurgiões , Radiologia Intervencionista , Inquéritos e QuestionáriosRESUMO
Background and Purpose- Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods- We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results- Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient's age (21.6%), and clinicians' experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions- In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients' age and physicians' experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.
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Isquemia Encefálica/cirurgia , Tomada de Decisão Clínica/métodos , Procedimentos Endovasculares/métodos , Médicos , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Adulto , Isquemia Encefálica/diagnóstico por imagem , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Acidente Vascular Cerebral/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
Background: DNA repair enzymes have been shown to reduce actinic keratoses and non-melanoma skin cancers, but their use for the treatment of actinic cheilitis has not been studied. Objective: The purpose of this pilot study was to examine the efficacy of a DNA repair enzyme lip balm containing T4 endonuclease in reducing the severity of actinic cheilitis in patients who applied the lip balm twice daily for 3 months. Methods: We performed a prospective study in which 29 patients with a diagnosis of actinic cheilitis underwent a 3-month trial using a topical DNA repair enzyme lip balm containing T4 endonuclease applied to the lips twice daily. The primary, objective outcome was percent of actinic lip involvement, measured using computer software by dividing the calculated affected surface area by the calculated total surface area. Additional outcomes included pre- and post-intervention determination of an actinic cheilitis score on the Actinic Cheilitis Scale, which visually and tactilely quantifies the percentage of lip involvement, amount of roughness, erythema, and tenderness as well as a physician assessment using the Global Aesthetic Improvement Scale. Results: Twenty-five of the 29 enrolled patients completed the trial. The lip balm significantly decreased the percentage of affected lip surface area (P<0.0001). According to the Actinic Cheilitis Scale, data demonstrate that the lip balm significantly decreased the percentage of lip involvement (P=0.002), amount of roughness (P=0.0012)), erythema (P=0.0020), and tenderness (P=0.0175). The total Actinic Cheilitis Scale score also significantly improved after the 3-month treatment period (P<0.0001). According to the Global Aesthetic Improvement Scale, the average score for all 26 patients was 1.04. Conclusion: This study suggests that topical DNA repair enzyme lip balm containing T4 Endonuclease could potentially be a safe and efficacious way to improve and treat actinic cheilitis. J Drugs Dermatol. 2019;18(6):576-579
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Queilite/tratamento farmacológico , Enzimas Reparadoras do DNA/administração & dosagem , Desoxirribonuclease (Dímero de Pirimidina)/administração & dosagem , Proteínas Virais/administração & dosagem , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Queilite/diagnóstico , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Multiple motor channel theory posits that skilled hand movements arise from the coordinated activation of separable neural circuits in parietofrontal cortex, each of which produces a distinct movement and responds to different sensory inputs. Prehension, the act of reaching to grasp an object, consists of at least two movements: a reach movement that transports the hand to a target location and a grasp movement that shapes and closes the hand for target acquisition. During early development, discrete pre-reach and pre-grasp movements are refined based on proprioceptive and tactile feedback, but are gradually coordinated together into a singular hand preshaping movement under feedforward visual control. The neural and behavioural factors that enable this transition are currently unknown. In an attempt to identify such factors, the present descriptive study used frame-by-frame video analysis to examine 9-, 12-, and 15-month-old infants, along with sighted and unsighted adults, as they reached to grasp small ring-shaped pieces of cereal (Cheerios) resting on a table. Compared to sighted adults, infants and unsighted adults were more likely to make initial contact with the underlying table before they contacted the target. The way in which they did so was also similar in that they generally contacted the table with the tip of the thumb and/or pinky finger, a relatively open hand, and poor reach accuracy. Despite this, infants were similar to sighted adults in that they tended to use a pincer digit, defined as the tip of the thumb or index finger, to subsequently contact the target. Only in infants was this ability related to their having made prior contact with the underlying table. The results are discussed in relation to the idea that initial contact with an underlying table or surface may assist infants in learning to use feedforward visual control to direct their digits towards a precise visual target.
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Força da Mão/fisiologia , Movimento/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Tato/fisiologia , Fatores Etários , Fenômenos Biomecânicos , Desenvolvimento Infantil/fisiologia , Feminino , Mãos , Humanos , Lactente , Masculino , Adulto JovemRESUMO
Monounsaturated fatty acids (MUFAs) play a pivotal role in maintaining endoplasmic reticulum (ER) homeostasis, an emerging hallmark of cancer. However, the role of polyunsaturated fatty acid (PUFAs) desaturation in persistent ER stress driven by oncogenic abnormalities remains elusive. Fatty Acid Desaturase 1 (FADS1) is a rate-limiting enzyme controlling the bioproduction of long-chain PUFAs. Our previous research has demonstrated the significant role of FADS1 in cancer survival, especially in kidney cancers. We explored the underlying mechanism in this study. We found that pharmacological inhibition or knockdown of the expression of FADS1 effectively inhibits renal cancer cell proliferation and induces cell cycle arrest. The stable knockdown of FADS1 also significantly inhibits tumor formation in vivo. Mechanistically, we show that while FADS1 inhibition induces ER stress, its expression is also augmented by ER-stress inducers. Notably, FADS1-inhibition sensitized cellular response to ER stress inducers, providing evidence of FADS1's role in modulating the ER stress response in cancer cells. We show that, while FADS1 inhibition-induced ER stress leads to activation of ATF3, ATF3-knockdown rescues the FADS1 inhibition-induced ER stress and cell growth suppression. In addition, FADS1 inhibition results in the impaired biosynthesis of nucleotides and decreases the level of UPD-N-Acetylglucosamine, a critical mediator of the unfolded protein response. Our findings suggest that PUFA desaturation is crucial for rescuing cancer cells from persistent ER stress, supporting FADS1 as a new therapeutic target.
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Guyana is an English-speaking country in South America and, culturally, it is part of the Caribbean. Objective of this study was to determine the community prevalence and true burden and economic impact of acute gastroenteritis (AGE) and foodborne diseases (FBDs) in Guyana. A cross-sectional population-based survey was conducted in 7 of the 10 regions in Guyana during August and November 2009 to capture the high- and low-AGE season respectively. Overall, 1,254 individual surveys were administered at a response rate of 96.5%. The overall monthly prevalence of self-reported cases of AGE was 7.7% (97 cases) (95% CI 6.3-9.3), and the yearly incidence was 1.0 episodes per person-year. The highest monthly prevalence of AGE was observed in region 4 (8.9%) and in children aged 1-4 year(s) (12.7%). Of the 97 AGE cases, 23% sought medical care; 65% reported spending time at home due to their illness [range 1-20 day(s), mean 2.7 days], of whom 51% required other individuals to look after them while ill. The maximum number of stools per 24 hours ranged from 3 to 9 (mean 4.5), and number of days an individual suffered from AGE ranged from 1 to 21 day(s) (mean 2.7 days). The burden of syndromic AGE cases in the population for 2009 was estimated to be 131,012 cases compared to the reported 30,468 cases (76.7% underreporting), which implies that, for every syndromic case of AGE reported, there were additional 4.3 cases occurring in the community. For every laboratory-confirmed case of FBD/AGE pathogen reported, it was estimated that approximately 2,881 more cases were occurring in the population. Giardia was the most common foodborne pathogen isolated. The minimum estimated annual cost associated with the treatment for AGE was US$ 2,358,233.2, showing that AGE and FBD pose a huge economic burden on Guyana. Underreporting of AGE and foodbome pathogens, stool collection, and laboratory capacity were major gaps, affecting the surveillance of AGE in Guyana.
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Efeitos Psicossociais da Doença , Doenças Transmitidas por Alimentos/economia , Doenças Transmitidas por Alimentos/epidemiologia , Gastroenterite/economia , Gastroenterite/epidemiologia , Vigilância da População/métodos , Características de Residência/estatística & dados numéricos , Doença Aguda , Adolescente , Adulto , Distribuição por Idade , Idoso , Causalidade , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Diarreia/economia , Diarreia/epidemiologia , Feminino , Guiana/epidemiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença , Distribuição por Sexo , Adulto JovemAssuntos
Benchmarking/normas , Procedimentos Endovasculares/normas , Neurologia/normas , Acidente Vascular Cerebral/terapia , Fluxo de Trabalho , Procedimentos Endovasculares/métodos , Humanos , Neurologia/organização & administração , Terapia Trombolítica/métodos , Terapia Trombolítica/normas , Fatores de TempoAssuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Acidente Vascular Cerebral/terapia , Humanos , Recursos Humanos de Enfermagem Hospitalar/provisão & distribuição , UrbanizaçãoRESUMO
Bone is a frequent site of metastasis from several organs and a host for cancer cells that have originated from the bone marrow itself. Skeletal malignancies are extremely difficult to treat. This is largely due to the complex, heterogenous nature of the bone marrow microenvironment and the dynamic interplay between the tumor cells and multiple cell types within the marrow niche. One cell type whose dominant role in supporting tumor progression and therapy evasion is being increasingly recognized are bone marrow adipocytes (BMAs). BMAs are metabolically active endocrine cells that supply lipids, hormones and adipocytokines to the neighboring cells. Their numbers in bone marrow increase with age, obesity and in response to certain treatments and metabolic conditions. BMAs have been shown to directly promote tumor growth through a transfer of lipids, upregulation of lipid transporters, modulation of tumor metabolism and activation of adaptive stress mechanisms in the cancer cells to promote survival. Less is known, however, regarding how adipocyte interactions with other cell types in the bone tumor microenvironment support malignant progression. This review summarizes recent findings on the crosstalk between BMAs and immune cells in bone. We focus specifically on how adipocyte-mediated changes in the immune milieu impact the tumor cell survival and therapy response. We also discuss how adipocyte-immune cell interactions alter bone homeostasis to support malignant progression in a context of current therapeutic strategies for skeletal malignancies.
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Adipócitos , Neoplasias Ósseas , Adipócitos/metabolismo , Adipócitos/patologia , Adipocinas/metabolismo , Neoplasias Ósseas/metabolismo , Hormônios/metabolismo , Humanos , Lipídeos , Microambiente TumoralRESUMO
BACKGROUND AND OBJECTIVES: Small iatrogenic brain infarcts are often seen on diffusion-weighted MRI (DWI) following surgical or endovascular procedures, but there are few data on their clinical effects. We examined the association of iatrogenic infarcts with outcomes in the ENACT (Evaluating Neuroprotection in Aneurysm Coiling Therapy) randomized controlled trial of nerinetide in patients undergoing endovascular repair of intracranial aneurysms. METHODS: In this post hoc analysis, we used multivariable models to evaluate the association of the presence and number of iatrogenic infarcts on DWI with neurologic impairment (NIH Stroke Scale [NIHSS]), functional status (modified Rankin Scale [mRS]), and cognitive and neuropsychiatric outcomes (30-minute test battery) at 1-4 days and 30 days postprocedure. We also related infarct number to a z score-derived composite outcome score using quantile regression. RESULTS: Among 184 patients (median age 56 years [interquartile range (IQR) 50-64]), 124 (67.4%) had postprocedural DWI lesions (median 4, IQR 2-10.5). Nerinetide treatment was associated with fewer iatrogenic infarcts but no overall significant clinical treatment effects. Patients with infarcts had lower Mini-Mental State Examination (MMSE) scores at 2-4 days (median 28 vs 29, adjusted coefficient [acoef] -1.11, 95% CI -1.88 to -0.34, p = 0.005). Higher lesion counts were associated with worse day 1 NIHSS (adjusted odds ratio for NIHSS ≥1: 1.07, 1.02-1.12, p = 0.009), day 2-4 mRS (adjusted common odds ratio [acOR] 1.05, 1.01-1.09, p = 0.005), and day 2-4 MMSE (acoef -0.07, -0.13 to -0.003, p = 0.040) scores. At 30 days, infarct number remained associated with worse mRS (acOR 1.04, 1.01-1.07, p = 0.016) and Hopkins Verbal Learning Test (HVLT) delayed recall scores (acoef -0.21, -0.39 to -0.03, p = 0.020). Patients with infarcts trended towards lower 30-day Digit Symbol Substitution Test (DSST) scores (acoef -3.73, -7.36 to -0.10, p = 0.044). Higher lesion count was associated with worse composite outcome scores at both 1-4 days and 30 days (30-day acoef -0.12, 95% CI -0.21 to -0.03, p = 0.008). Among those with infarcts, day 1 NIHSS and day 2-4 mRS correlated with 30-day NIHSS, DSST, HVLT, and mRS scores, whereas day 2-4 MMSE correlated with 30-day NIHSS and DSST scores (Spearman ρ 0.47, p = 0.001). DISCUSSION: Iatrogenic brain infarcts were associated with subtle differences in postprocedural (1-4 days) and 30-day outcomes on different measures in this middle-aged cohort, with earlier dysfunction correlating with later differences. TRIAL REGISTRATION INFORMATION: Clinical trials registration NCT00728182.
Assuntos
Isquemia Encefálica , Aneurisma Intracraniano , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Cognição , Humanos , Doença Iatrogênica/prevenção & controle , Infarto/complicações , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Pessoa de Meia-Idade , Neuroproteção , Acidente Vascular Cerebral/complicações , Resultado do TratamentoRESUMO
The hyperdense sign is a marker of thrombus in non-contrast computed tomography (NCCT) datasets. The aim of this work was to determine optimal Hounsfield unit (HU) thresholds for thrombus segmentation in thin-slice non-contrast CT (NCCT) and use these thresholds to generate 3D thrombus models. Patients with thin-slice baseline NCCT (≤2.5 mm) and MCA-M1 occlusions were included. CTA was registered to NCCT, and three regions of interest (ROIs) were placed in the NCCT, including: the thrombus, contralateral brain tissue, and contralateral patent MCA-M1 artery. Optimal HU thresholds differentiating the thrombus from non-thrombus tissue voxels were calculated using receiver operating characteristic analysis. Linear regression analysis was used to predict the optimal HU threshold for discriminating the clot only based on the average contralateral vessel HU or contralateral parenchyma HU. Three-dimensional models from 70 participants using standard (45 HU) and patient-specific thresholds were generated and compared to CTA clot characteristics. The optimal HU threshold discriminating thrombus in NCCT from other structures varied with a median of 51 (IQR: 49-55). Experts chose 3D models derived using patient-specific HU models as corresponding better to the thrombus seen in CTA in 83.8% (31/37) of cases. Patient-specific HU thresholds for segmenting the thrombus in NCCT can be derived using normal parenchyma. Thrombus segmentation using patient-specific HU thresholds is superior to conventional 45 HU thresholds.
RESUMO
BACKGROUND: Evidence for efficacy and safety in stroke patients ≥80 years is limited, since they were underrepresented in randomized thrombectomy trials. This study sought to explore how physicians approach endovascular therapy (EVT) decision making in octogenarians and nonagenarians under their current local resources under assumed ideal conditions, i.e. without external (monetary or infrastructural) limitations. METHODS: In an international multidisciplinary survey, 607 physicians involved in acute stroke care were randomly assigned 10 out of a pool of 22 case scenarios with different evidence levels for EVT, 4 of which involved octogenarians and 2 nonagenarians, and asked how they would treat the patient in the given scenario A) under their current local resources and B) under assumed ideal conditions, i.e. with no external restraints. Decision rates were calculated and clustered multivariable regression analysis performed to determine adjusted measures of effect size for patient age. RESULTS: In octogenarians, physicians decided in favor of EVT in 76.7% (all of which were level 2B evidence scenarios) under current local resources and in 80.2% under assumed ideal conditions. In nonagenarians, 74.0% decided in favor of EVT under current local resources (level 1A scenarios: 87.7%, level 2B scenarios: 60.3%) and 79.2% would offer EVT under assumed ideal conditions (level 1A scenarios: 91.3%, level 2B scenarios: 67.2%). Age was not a significant predictor for treatment decision under current local resources (adjusted odds ratio, OR: 0.99, confidence interval, CI: 0.96-1.02 per decile increase) and under assumed ideal conditions (adjusted OR: 1.00, CI 0.97-1.03 per decile increase). CONCLUSION: The vast majority of physicians participating in this survey would offer EVT to acute ischemic stroke patients above 80 years.