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Guttate psoriasis (GP) is a variant of psoriasis characterized by scattered "drop-like" papules and plaques, accounting for up to a quarter of psoriasis cases. Although GP can clear within 3 to 4 months, up to 39% of cases may progress to chronic plaque psoriasis. Currently, there is a paucity of literature investigating the efficacy of different treatment modalities. This systematic review aims to synthesize all available data on GP treatment efficacy. A literature search was conducted using Medline, Embase, Web of Science, and CINAHL with no date limits. A total of 75 studies satisfied eligibility criteria and were analyzed. Most studies were case reports, series, or retrospective studies. Only 5 randomized controlled trials (RCTs) were identified. For topical treatments, corticosteroids and calcipotriol creams had the most evidence for efficacy. Four categories of systemic therapies were identified: traditional immunosuppressants, antibiotics, retinoids, and biologics. Evidence regarding antibiotic therapy suggests minimal connection between underlying infection resolution and GP lesion remission. Phototherapy had the most robust evidence, with narrowband ultraviolet B (UVB) being the most effective. Our findings are limited by high heterogeneity in study design and high risk of bias. Based on our review, we propose the following treatment algorithm. As first-line therapy, we recommend topical corticosteroids and calcipotriol cream, in combination with phototherapy. As supportive therapy, we recommend antibiotics if applicable. For second-line therapy, we recommend methotrexate or cyclosporine. For severe and refractory GP, biologics can be used as third-line treatment. RCTs are needed to provide higher quality evidence to create standardized treatment recommendations.
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BACKGROUND: Cosmetic breast surgeries, such as augmentation, mastopexy, and reduction, are common aesthetic medical procedures for enhancing physical appearance. Despite their popularity, the influence of these surgeries on subsequent breast reconstruction for cancer patients remains underexplored. OBJECTIVES: This study seeks to investigate the effects of previous cosmetic breast surgeries on the outcomes of breast reconstruction. METHODS: A retrospective chart review was conducted from January 2011 to May 2023. This analysis compared patients with histories of implant augmentation, breast reduction, mastopexy, and augmentation-mastopexy against those receiving reconstruction without any cosmetic surgery history. Demographics, comorbidities, complications, revisions, and BREAST-Q surveys were collected. Statistical analysis was performed using SPSS, with significance set at p<0.05. RESULTS: The study included 124 patients (50 autologous, 74 implant) with a history of cosmetic breast surgery (102 implant augmentations, 17 breast reductions, five mastopexies, and nine augmentation mastopexies). They were analyzed against 1307 patients (683 autologous, 624 implant) without prior cosmetic breast surgery. Patients with prior cosmetic surgeries showed a higher incidence of hematoma with tissue expander placement. A preference for implant-based reconstruction was more common among patients with augmentation history (p<0.001), whereas autologous reconstruction was more common in those with history of breast reduction (p=0.047). Patients with history of breast augmentation had on average significantly more breast revisions (p <0.05). CONCLUSIONS: This study demonstrates a significantly higher hematoma rate and number of revisions compared to patients without a history of cosmetic surgery. Furthermore, it suggests that types of cosmetic breast surgery influence the decision-making process regarding implant versus autologous reconstruction.
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OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.
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Estatura/efectos de los fármacos , Hipoparatiroidismo/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Adolescente , Calcinosis , Calcio/sangre , Calcio/orina , Niño , Creatinina/orina , Análisis Mutacional de ADN , Femenino , Homeostasis , Terapia de Reemplazo de Hormonas , Humanos , Pruebas de Función Renal , Modelos Lineales , Masculino , Nefrocalcinosis/metabolismo , Hormona Paratiroidea/administración & dosificación , Fósforo/sangre , Fósforo/orina , Poliendocrinopatías Autoinmunes/genética , Receptores Sensibles al Calcio/genética , Resultado del Tratamiento , Vitamina D/sangreRESUMEN
OBJECTIVES: To use magnetic resonance imaging (MRI) and computed tomography (CT) to define abdominal involvement in Erdheim-Chester disease (ECD), and to investigate the association between these findings and the BRAFV600E mutation. METHODS: This prospective study was performed on 61 ECD patients (46 men). The MRI and CT imaging studies were reviewed independently by two experienced radiologists. The association between BRAFV600E mutation and imaging findings was analysed using Fisher's exact test, and odds ratios with 95% confidence intervals. RESULTS: Perinephric infiltration was the most common finding (67%), followed by involvement of proximal ureters (61%). In 56% of cases, infiltration extended to the renal sinuses, and in 38% caused hydronephrosis. Adrenal gland infiltration was present in 48% of patients. Infiltration of renal artery (49%) and aorta (43%) were the most common vascular findings, followed by sheathing of celiac, superior mesenteric artery (SMA) or inferior mesenteric artery (IMA) (23%). The BRAFV600E mutation was positive in 53% of patients with interpretable BRAF sequencing. There was a statistically significant association between this mutation and perinephric infiltration (p = 0.003), renal sinus involvement (p < 0.001), infiltration of proximal ureters (p < 0.001), hydronephrosis (p < 0.001), adrenal gland involvement (p < 0.001), periaortic infiltration (p = 0.03), sheathing or stenosis of renal artery (p < 0.001) and sheathing of other aortic branches (p = 0.04). CONCLUSIONS: Renal and vascular structures are the most commonly affected abdominal organs in ECD patients. Some of these findings have significant positive association with the BRAFV600E mutation. KEY POINTS: ⢠Abdominal imaging plays a crucial role in management of Erdheim-Chester disease. ⢠Significant associations exist between BRAF V600E mutation and several abdominal imaging findings. ⢠Considering several associations, evaluating BRAFV600E mutation status is recommended in ECD patients.
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Abdomen/patología , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Enfermedad de Erdheim-Chester/genética , Imagen por Resonancia Magnética/métodos , Proteínas Proto-Oncogénicas B-raf/genética , Tomografía Computarizada por Rayos X/métodos , Abdomen/diagnóstico por imagen , Adulto , Anciano , Enfermedad de Erdheim-Chester/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Estudios Prospectivos , Proto-Oncogenes Mas , Adulto JovenRESUMEN
Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (â¼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (nâ=â880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and â¼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
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Hígado Graso/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Estudios de Casos y Controles , Proteoglicanos Tipo Condroitín Sulfato/genética , Estudios de Cohortes , Hígado Graso/diagnóstico por imagen , Hígado Graso/metabolismo , Estudio de Asociación del Genoma Completo , Humanos , Insulina/sangre , Lectinas Tipo C/genética , Lipasa/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación Missense , Proteínas del Tejido Nervioso/genética , Neurocano , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Tomografía Computarizada por Rayos XRESUMEN
Materials in crystalline form possess translational symmetry (TS) when the unit cell is repeated in real space with long- and short-range orders. The periodic potential in the crystal regulates the electron wave function and results in unique band structures, which further define the physical properties of the materials. Amorphous materials lack TS due to the randomization of distances and arrangements between atoms, causing the electron wave function to lack a well-defined momentum. High entropy materials provide another way to break the TS by randomizing the potential strength at periodic atomic sites. The local elemental distribution has a great impact on physical properties in high entropy materials. It is critical to distinguish elements at the sub-nanometer scale to uncover the correlations between the elemental distribution and the material properties. Here, the use of synchrotron X-ray scanning tunneling microscopy (SX-STM) with sub-nm scale resolution in identifying elements on a high entropy alloy (HEA) surface is demonstrated. By examining the elementally sensitive X-ray absorption spectra with an STM tip to enhance the spatial resolution, the elemental distribution on an HEA's surface at a sub-nm scale is extracted. These results open a pathway towards quantitatively understanding high entropy materials and their material properties.
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Cross-cultural studies of the meaning of facial expressions have largely focused on judgments of small sets of stereotypical images by small numbers of people. Here, we used large-scale data collection and machine learning to map what facial expressions convey in six countries. Using a mimicry paradigm, 5,833 participants formed facial expressions found in 4,659 naturalistic images, resulting in 423,193 participant-generated facial expressions. In their own language, participants also rated each expression in terms of 48 emotions and mental states. A deep neural network tasked with predicting the culture-specific meanings people attributed to facial movements while ignoring physical appearance and context discovered 28 distinct dimensions of facial expression, with 21 dimensions showing strong evidence of universality and the remainder showing varying degrees of cultural specificity. These results capture the underlying dimensions of the meanings of facial expressions within and across cultures in unprecedented detail.
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Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.
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Hígado Graso , Resistencia a la Insulina , Interferón gamma , Interleucina-12 , Hígado , Macrófagos , Ratones Noqueados , Obesidad , Transducción de Señal , Animales , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Masculino , Obesidad/metabolismo , Ratones , Hígado Graso/metabolismo , Hígado Graso/patología , Macrófagos/metabolismo , Hígado/metabolismo , Hígado/patología , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Receptores de Interferón/metabolismo , Receptores de Interferón/genética , Receptor de Interferón gamma , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/genéticaRESUMEN
BACKGROUND: The distal GI microbiota of hospitalized preterm neonates has been established to be unique from that of healthy full-term infants; the proximal GI, more specifically gastroesophageal colonization has not been systematically addressed. We prospectively evaluated early colonization of gastroesophageal portion of the GI tract of VLBW infants. METHODS: This study involved 12 infants admitted to a level III NICU with gestational age (GA) 27 +/- 0.5 weeks and birth weight 1105 +/- 77 grams. The gastroesophageal microbial flora was evaluated using 16S rDNA analysis of aspirates collected in a sterile manner during the first 28 days of life. RESULTS: Bacteria were detected in 9 of the 12 neonates. Ureaplasma was the dominant species in the first week of life, however, staphylococci were the predominant bacteria overall. By the fourth week, Gram (-) bacteria increased in abundance to account for 50% of the total organisms. Firmicutes were present in the majority of the neonates and persisted throughout the 4 weeks comprising nearly half of the sequenced clones. Noticeably, only two distinct species of Staphylococcus epidermidis were found, suggesting acquisition from the environment. CONCLUSIONS: In our neonates, the esophagus and stomach environment changed from being relatively sterile at birth to becoming colonized by a phylogenetically diverse microbiota of low individual complexity. By the fourth week, we found predominance of Firmicutes and Proteobacteria. Bacteria from both phyla (CONS and Gram (-) organisms) are strongly implicated as causes of hospital-acquired infections (HAI). Evaluation of the measures preventing colonization with potentially pathogenic and pathogenic microorganisms from the hospital environment may be warranted and may suggest novel approaches to improving quality in neonatal care.
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Esófago/microbiología , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Metagenoma , Estómago/microbiología , ADN Bacteriano/análisis , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Filogenia , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , ARN Ribosómico 16SRESUMEN
Parents' intentions to vaccinate their children is an important area of investigation in light of the COVID-19 pandemic. There is a growing body of research examining factors that influence parents' vaccine intentions. The current study investigated factors that would influence maternal intent to vaccinate their children for COVID-19, shortly before the CDC approved vaccines for children 11 and younger. We had a sample of n = 176 mothers (Mchildage = 71.63 months, 52% White) from California fill out an online survey during February-April 2021. Our results suggest that perceived COVID-19 threat predicts mothers' intention to vaccinate their children (b = 0.370, p < 0.001), controlling for mothers' age, socioeconomic status, race, and child age. Child age (b = 0.027, p = 0.008), SES (b = 0.396, p = 0.018), and child previous flu shot (b = 0.725, p < 0.001) also positively predicted mothers' intention to vaccinate their children. Results are discussed in light of prior research on maternal vaccine intentions and hesitancy.
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Human social life is rich with sighs, chuckles, shrieks and other emotional vocalizations, called 'vocal bursts'. Nevertheless, the meaning of vocal bursts across cultures is only beginning to be understood. Here, we combined large-scale experimental data collection with deep learning to reveal the shared and culture-specific meanings of vocal bursts. A total of n = 4,031 participants in China, India, South Africa, the USA and Venezuela mimicked vocal bursts drawn from 2,756 seed recordings. Participants also judged the emotional meaning of each vocal burst. A deep neural network tasked with predicting the culture-specific meanings people attributed to vocal bursts while disregarding context and speaker identity discovered 24 acoustic dimensions, or kinds, of vocal expression with distinct emotion-related meanings. The meanings attributed to these complex vocal modulations were 79% preserved across the five countries and three languages. These results reveal the underlying dimensions of human emotional vocalization in remarkable detail.
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Aprendizaje Profundo , Voz , Humanos , Emociones , Lenguaje , AcústicaRESUMEN
RATIONALE AND OBJECTIVES: Metastatic epidural masses are an important radiological finding. The purpose of this study is to determine factors associated with non-reporting of thoracolumbar epidural metastases on body CT. MATERIALS AND METHODS: In a study population of 166 patients from a single institution over a 12-year period, 293 body CT examinations were identified which were performed within 30 days before or after a spine MRI diagnosis of epidural metastasis. Associations were sought between patient diagnosis, CT examination characteristics, reporting radiologist (n = 17), and lesion characteristics with respect to whether an epidural metastasis was reported on CT. RESULTS: In retrospective consensus review comprised of 3 radiologists, epidural metastases reported on spine MRI were clearly visible in 80.5% (236/293) of body CT examinations, however 65.3% (154/236) of the body CT reports omitted reporting their presence, even in cases where there was a preceding MRI diagnosis within 30 days (65.4%, 74/113). The identity of the reporting radiologist was statistically significantly associated with the accurate diagnostic reporting of epidural metastasis on body CT (p = 0.04). The only lesion features which were statistically significantly associated with CT reporting were lesion volume (p = 0.03) on noncontrast CT, and lesion volume (p = 0.006) and percentage of spinal canal stenosis (p = 0.001) on intravenous contrast-enhanced CT. The presence or absence of intravenous contrast was not significantly associated with CT reporting (p = 1.0). CONCLUSION: Using spine MRI as the reference standard for the presence of epidural tumor, the majority of body CT reports omit describing thoracolumbar epidural metastases which are clearly visible in retrospect.
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Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodosRESUMEN
The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a need to develop more sophisticated approaches to regulate BMP signaling and promote bone regeneration. Here, we present a novel complementary strategy that targets both BMP antagonist noggin and agonist Trb3 to enhance bone defect repair without the application of exogenous BMP-2. In vitro studies showed that overexpression of Trb3 with simultaneous noggin suppression significantly promotes osteogenic differentiation of mesenchymal stem cells. This was accompanied by increased BMP/Smad signaling. We also developed sterosome nanocarriers, a non-phospholipid liposomal system, to achieve non-viral mediated noggin suppression and Trb3 overexpression. The gene-loaded sterosomes were integrated onto an apatite-coated polymer scaffold for in vivo calvarial defect implantation, resulting in robust bone healing compared to BMP-2 treatments. Our work provides a promising alternative for high-quality bone formation by regulating expression of BMP agonists and antagonists.
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Células Madre Mesenquimatosas , Osteogénesis , Diferenciación Celular , Regeneración Ósea , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/metabolismo , Transducción de SeñalRESUMEN
Duplication cysts are rare benign congenital malformations typically identified in children by the age of 2 years. We report a rare case of colonic duplication cyst with dysplasia in an adult. A 32-year-old male was diagnosed with non-specific abdominal symptoms. Abdominopelvic computed tomography scan demonstrated a submucosal cystic lesion in the right colon. He underwent laparoscopic right hemicolectomy. Histopathology showed colonic duplication cyst with low grade dysplasia. He is due for a surveillance colonoscopy in 3 years. Duplication cyst in an adult colon with dysplasia is extremely rare. They are usually present in the terminal ileum. They have non-specific abdominal symptoms or can be asymptomatic. They are often identified incidentally or intraoperatively. Imaging may demonstrate a cystic lesion. Histopathology is required for definitive diagnosis. There are no guidelines or consensus on managing duplication cysts in adults. We recommend an oncological resection of the involved colon. Surveillance with routine colonoscopy is advisable.
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The association between myasthenia gravis (MG) and thymomas is well-documented. Thymomas are rare epithelial cell tumors that arise from the thymus gland and occur in the mediastinum. Myasthenia gravis is a neuromuscular disorder that causes skeletal muscle weakness due to the presence of anti-acetylcholinesterase antibodies. Roughly 60% of thymomas are associated with MG, while only 10% of MG patients have thymomas. We present an atypical presentation of myasthenia gravis with an associated unusual metastatic thymoma. This case is of a young, previously healthy 26-year-old male with no previous medical history who presented with non-specific symptoms of fatigue, diarrhea, abdominal pain, back pain, blurry vision, and unintended weight loss. He underwent treatment with intravenous immunoglobulins (IVIG), had two surgical resections of the thymoma, and ultimately received radiotherapy. Based on our experience with this case, diagnosing myasthenia gravis by testing for specific muscle antibodies for patients with ptosis in the setting of non-specific complaints, including fatigue, vomiting, diarrhea, and abdominal or back pain, should be considered. Routine imaging should follow with a chest computed tomography to screen for thymomas if the specific anti-titin and anti-ryanodine receptor (anti-RyR) muscle antibodies are positive and myasthenia gravis is suspected. If a thymoma is confirmed, it is best to confirm; and mass characterizes with chest magnetic resonance imaging. A treatment approach of IVIG followed by surgical resection and possible debulking if the lesion is deemed metastatic could also be considered thereafter, especially in young patients with few comorbidities. Treatment with Pyridostigmine 30 mg twice daily for 25 days post-surgically and radiation for treatment of any remaining unresectable tumor should also be considered.
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BACKGROUND: Although there is evidence linking smoking and heart failure (HF), the association between lifetime smoking exposure and HF in older adults and the strength of this association among current and past smokers is not well known. METHODS: We examined the association between smoking status, pack-years of exposure, and incident HF risk in 2,125 participants of the Health, Aging, and Body Composition Study (age 73.6 ± 2.9 years, 69.7% women, 54.2% whites) using proportional hazard models. RESULTS: At inception, 54.8% of participants were nonsmokers, 34.8% were past smokers, and 10.4% were current smokers. During follow-up (median 9.4 years), HF incidence was 11.4 per 1,000 person-years in nonsmokers, 15.2 in past smokers (hazard ratio [HR] vs nonsmokers 1.33, 95% CI 1.01-1.76, P = .045), and 21.9 in current smokers (HR 1.93, 95% CI 1.30-2.84, P = .001). After adjusting for HF risk factors, incident coronary events, and competing risk for death, a dose-effect association between pack-years of exposure and HF risk was observed (HR 1.09, 95% CI 1.05-1.14, P < .001 per 10 pack-years). Heart failure risk was not modulated by pack-years of exposure in current smokers. In past smokers, HR for HF was 1.05 (95% CI 0.64-1.72) for 1 to 11 pack-years, 1.23 (95% CI 0.82-1.83) for 12 to 35 pack-years, and 1.64 (95% CI 1.11-2.42) for >35 pack-years of exposure in fully adjusted models (P < .001 for trend) compared with nonsmokers. CONCLUSIONS: In older adults, both current and past cigarette smoking increase HF risk. In current smokers, this risk is high irrespective of pack-years of exposure, whereas in past smokers, there was a dose-effect association.
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Insuficiencia Cardíaca/epidemiología , Fumar/epidemiología , Anciano , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Incidencia , Masculino , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
Emergency Use Authorization (EUA) allows the US Food and Drug Administration (FDA) to expedite the availability of therapeutics in the context of a public health emergency. To date, an evidentiary standard for clinical efficacy to support an EUA has not yet been established. This review examines the clinical data submitted in support of EUA for antiviral and anti-inflammatory therapeutics for coronavirus disease 2019 (COVID-19) through December of 2021 and the resilience of the authorization as new clinical data arose subsequent to the authorization. In the vast majority of cases, EUA was supported by at least one well-powered randomized controlled trial (RCT) where statistically significant efficacy was demonstrated. This included branded medications already approved for use outside of the context of COVID-19. When used, the standard of a single RCT seemed to provide adequate evidence of clinical efficacy, such that subsequent clinical studies generally supported or expanded the EUA of the therapeutic in question. The lone generic agent that was granted EUA (chloroquine/hydroxychloroquine) was not supported by a well-controlled RCT, and the EUA was withdrawn within 3 months time. This highlighted not only the ambiguity of the EUA standard, but also the need to provide avenues through which high quality clinical evidence for the efficacy of a generic medication could be obtained. Therefore, maintaining the clinical trial networks assembled during the COVID-19 pandemic could be a critical component of our preparation for future pandemics. Consideration could also be given to establishing a single successful RCT as regulatory guidance for obtaining an EUA.
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Tratamiento Farmacológico de COVID-19 , Pandemias , Humanos , Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , SARS-CoV-2 , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Zn(II), Cu(II), and Ni(II) 5,10,15,20-tetrakis(4-fluoro-2,6-dimethylphenyl)porphyrins (TFPs) have been synthesized and characterized. The electronic spectroscopy and cyclic voltammetry of these compounds, along with the free-base macrocycle (2H-TFP), have been determined; 2H-TFP was also structurally characterized by X-ray crystallography. The Cu(II)TFP exhibits catalytic activity for the hydrogen evolution reaction (HER). The analysis of linear sweep voltammograms shows that the HER reaction of Cu(II)TFP with benzoic acid is first-order in proton concentration with an average apparent rate constant for HER catalysis of k app = 5.79 ± 0.47 × 103 M-1 s-1.
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Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.