ABSTRACT
BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.
Subject(s)
Hypertension , Sodium, Dietary , Humans , Sodium/urine , Potassium/urine , Cross-Sectional Studies , Hypertension/diagnosis , Hypertension/genetics , Blood Pressure/genetics , Electrolytes , Sodium, Dietary/adverse effectsABSTRACT
OBJECTIVE: To examine the association of anesthesiologist sex on postoperative outcomes. BACKGROUND: Differences in patient postoperative outcomes exist, depending on whether the primary surgeon is male or female, with better outcomes seen among patients treated by female surgeons. Whether the intraoperative anesthesiologist's sex is associated with differential postoperative patient outcomes is unknown. METHODS: We performed a population-based, retrospective cohort study among adult patients undergoing one of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between the sex of the intraoperative anesthesiologist and the primary end point of the adverse postoperative outcome, defined as death, readmission, or complication within 30 days after surgery, using generalized estimating equations. RESULTS: Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 311,822 (26.7%) received care from a female anesthesiologist and 853,889 (73.3%) from a male anesthesiologist. Overall, 10.8% of patients experienced one or more adverse postoperative outcomes, of whom 1.1% died. Multivariable adjusted rates of the composite primary end point were higher among patients treated by male anesthesiologists (10.6%) compared with female anesthesiologists (10.4%; adjusted odds ratio 1.02, 95% CI: 1.00-1.05, P =0.048). CONCLUSIONS: We demonstrated a significant association between sex of the intraoperative anesthesiologist and patient short-term outcomes after surgery in a large cohort study. This study supports the growing literature of improved patient outcomes among female practitioners. The underlying mechanisms of why outcomes differ between male and female physicians remain elusive and require further in-depth study.
Subject(s)
Anesthesiologists , Postoperative Complications , Adult , Humans , Male , Female , Cohort Studies , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Ontario/epidemiologyABSTRACT
BACKGROUND: Socioeconomic disparities exist in pediatric patients with hematologic malignancies, leading to suboptimal survival rates. Social determinants of health impact health outcomes, and in children, they may not only lead to worse survival outcomes but carry over into late effects in adult life. The social deprivation index (SDI) is a composite score using geographic county data to measure social determinants of health. Using the SDI, the purpose of the present study is to stratify survival outcomes in pediatric patients with hematologic malignancies based on area deprivation. METHODS: A retrospective cohort study was performed using the national Surveillance, Epidemiology, and End Results oncology registry in the USA from 1975 to 2016 based on county-level data. Pediatric patients (≤18 y old) with a diagnosis of leukemia or lymphoma based on the International Classification for Oncology, third edition (ICD-O-3) were used for inclusion criteria. Patients were grouped by cancer subtype for leukemia into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia while for lymphoma into non-Hodgkin's lymphoma and Hodgkin's lymphoma. SDI scores were calculated for each patient and divided into quartiles, with Q1 being the lowest area of deprivation and Q4 being the highest, respectively. RESULTS: A total of 38,318 leukemia and lymphoma patients were included. Quartile data demonstrated stratification in survival based on area deprivation for ALL, with no survival differences in the other cancer subtypes. Patients with ALL from the most deprived area had a roughly 3% difference in both overall and cancer-specific morality at 5 years compared with the least deprived area. CONCLUSION: Disparities in pediatric patients with ALL represent a significant area for quality improvement. Social programs may have value in improving survival outcomes and could rely on metrics such as SDI.
Subject(s)
Hematologic Neoplasms , Hodgkin Disease , Leukemia, Myeloid, Acute , Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Child , Survival Rate , Retrospective Studies , Hematologic Neoplasms/epidemiology , Lymphoma, Non-Hodgkin/epidemiologyABSTRACT
Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without a clinical diagnosis, where a previously unreported ARID1B missense variant was classified as a variant of uncertain significance. The pathogenicity of this variant was refined through combined methodologies including genome-wide methylation signature analysis (EpiSign), Machine Learning (ML) facial phenotyping, and LIRICAL. Trio exome sequencing and EpiSign were performed. ML facial phenotyping compared facial images using FaceMatch and GestaltMatcher to syndrome-specific libraries to prioritize the trio exome bioinformatic pipeline gene list output. Phenotype-driven variant prioritization was performed with LIRICAL. A de novo heterozygous missense variant, ARID1B p.(Tyr1268His), was reported as a variant of uncertain significance. The ACMG classification was refined to likely pathogenic by a supportive methylation signature, ML facial phenotyping, and prioritization through LIRICAL. The ARID1B genotype-phenotype has been expanded through an extended analysis of missense variation through genome-wide methylation signatures, ML facial phenotyping, and likelihood-ratio gene prioritization.
Subject(s)
Abnormalities, Multiple , Hand Deformities, Congenital , Intellectual Disability , Micrognathism , Male , Humans , DNA-Binding Proteins/genetics , Muscle Hypotonia/pathology , Transcription Factors/genetics , Face/pathology , Abnormalities, Multiple/diagnosis , Micrognathism/genetics , Intellectual Disability/pathology , Hand Deformities, Congenital/genetics , Neck/pathologyABSTRACT
OBJECTIVES: To synthesise available data regarding the disease-free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with renal cell carcinoma (RCC) and evaluate the overall safety profile of ICIs in this setting. MATERIALS AND METHODS: We utilised PubMed, Embase, and relevant conference proceedings to identify phase III randomised controlled trials comparing adjuvant ICIs vs placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were programmed death-ligand 1 (PD-L1) expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included Grade ≥3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. All outcomes were analysed using random-effects models owing to inter-study heterogeneity. RESULTS: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2 = 64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.69-1.04) there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) and sarcomatoid features (HR 0.59, 95% CI 0.38-0.91). CONCLUSION: The evidence base to date regarding ICIs as adjuvant therapy in RCC is mixed - conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , B7-H1 Antigen , Disease-Free Survival , Immunotherapy/methods , Adjuvants, Immunologic/therapeutic use , Kidney Neoplasms/drug therapyABSTRACT
AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort. METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th percentile), normal (5-95th percentile) and high eGFR (>95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest. RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]). CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.
Subject(s)
Renal Insufficiency, Chronic , Venous Thromboembolism , Adult , Male , Female , Humans , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Postoperative Complications/etiology , Risk Factors , Cohort Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/complications , Retrospective StudiesABSTRACT
PURPOSE: We examined if malnutrition, as defined by the Geriatric Nutritional Risk Index (GNRI), is independently associated with 30-day postoperative complications in patients undergoing nephrectomy for the treatment of renal cancer. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database from 2006-2019, we identified patients ≥65 years old who underwent nephrectomy for renal cancer. The following formula for GNRI was used to define preoperative nutritional status: 1.489 x serum albumin (g/L) + 41.7 x (current body weight [kg]/ ideal body weight [kg]). Based on the GNRI, patients were classified as having no (> 98), moderate (92-98), or severe malnutrition (< 92). After adjusting for potential confounders, multivariable logistic regression analyses were performed to assess the association between GNRI and 30-day postoperative complications. Odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS: A total of 7,683 patients were identified, of which 1,241 (16.2%) and 872 (11.3%) had moderate and severe malnutrition, respectively. Compared to normal nutrition, moderate and severe malnutrition were significantly associated with a greater odds of superficial surgical site infection, progressive renal insufficiency, readmission, extended length of stay, and non-home discharge. Severe malnutrition was also associated with urinary tract infection (OR 2.10, 95% CI 1.31-3.35) and septic shock (OR 2.93, 95% CI 1.21-7.07). CONCLUSION: Malnutrition, as defined by a GNRI ≤ 98, is an independent predictor of 30-day complications following nephrectomy. The GNRI could be used to counsel elderly patients with renal cancer prior to nephrectomy.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Malnutrition , Humans , Aged , Nutrition Assessment , Geriatric Assessment , Malnutrition/complications , Nephrectomy/adverse effects , Postoperative Complications/etiology , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/complications , Kidney Neoplasms/surgery , Kidney Neoplasms/complications , Risk FactorsABSTRACT
Changes in cell phenotype are thought to occur through the expression of groups of co-regulated genes within topologically associated domains (TADs). In this paper, we allocate genes expressed within the myometrium of the human uterus during the onset of term labour into TADs. Transformation of the myometrial cells of the uterus into a contractile phenotype during term human labour is the result of a complex interaction of different epigenomic and genomic layers. Recent work suggests that the transcription factor (TF) RELA lies at the top of this regulatory network. Using deep RNA sequencing (RNAseq) analysis of myometrial samples (n = 16) obtained at term from women undergoing caesarean section prior to or after the onset of labour, we have identified evidence for how other gene expression regulatory elements interact with TFs in the labour phenotype transition. Gene set enrichment analysis of our RNAseq data identified three modules of enriched genes (M1, M2 and M3), which in gene ontology studies are linked to matrix degradation, smooth muscle and immune gene signatures, respectively. These genes were predominantly located within chromosomal TADs suggesting co-regulation of expression. Our transcriptomic analysis also identified significant differences in the expression of long non-coding RNAs (lncRNA), microRNAs (miRNA) and TFs that were predicted to target genes within the TADs. Additionally, network analysis revealed 15 new lncRNA (MCM3AP-AS1, TUG1, MIR29B2CHG, HCG18, LINC00963, KCNQ1OT1, NEAT1, HELLPAR, SNHG16, NUTM2B-AS1, MALAT1, PSMA3-AS1, GABPB1-AS1, NORAD and NKILA) and 4 miRNA (mir-145, mir-223, mir-let-7a and mir-132) as top gene hubs with three TFs (NFKB1, RELA and ESR1) as master regulators. Together, these factors are likely to be involved in co-regulatory networks driving a myometrial transformation to generate an estrogen-sensitive phenotype. We conclude that lncRNA and miRNA targeting the estrogen receptor 1 and nuclear factor kappa B pathways play a key role in the initiation of human labour. For the first time, we perform an integrative analysis to present a multi-level genomic signature made of mRNA, non-coding RNA and TFs in the myometrium for spontaneous term labour.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Acetyltransferases/genetics , Acetyltransferases/metabolism , Cesarean Section , Female , Gene Regulatory Networks , Humans , Intracellular Signaling Peptides and Proteins/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Myometrium/metabolism , Pregnancy , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , TranscriptomeABSTRACT
PURPOSE: The Geriatric Nutritional Risk Index (GNRI) is a simple screening tool to predict nutrition-related risk of morbidity and mortality in older patients. We assessed whether preoperative GNRI was associated with 30-day complications after radical cystectomy (RC). MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified patients 65 years or older who underwent RC for the treatment of bladder cancer between 2007 and 2019. Patients were dichotomized into at-risk (GNRI ≤98) or no-risk (GNRI >98) groups. Using propensity score matching, the 2 groups were compared for baseline differences and 30-day outcomes. We evaluated GNRI as an independent predictor of postoperative complications using multivariable logistic regression analysis. RESULTS: We identified 2,926 patients eligible for analysis. After propensity score matching, patients in the at-risk GNRI group had higher rates of any complication (p=0.017), blood transfusion (p=0.002), extended length of stay (p=0.004) and nonhome discharge (p <0.001). Multivariable logistic regression analysis revealed that a decreasing GNRI is an independent prognostic factor for mortality (OR 1.05, 95% CI 1.01-1.08, p=0.009), blood transfusion (OR 1.03, 95% CI 1.02-1.04, p <0.001), pneumonia (OR 1.04, 95% CI 1.01-1.07, p=0.013), extended length of stay (OR 1.03, 95% CI 1.02-1.05, p <0.001) and nonhome discharge (OR 1.04, 95% CI 1.03-1.06, p <0.001). CONCLUSIONS: We demonstrate that nutritional status evaluated by GNRI predicts 30-day complications after RC.
Subject(s)
Cystectomy/adverse effects , Geriatric Assessment , Nutrition Assessment , Urinary Bladder Neoplasms/surgery , Aged , Aged, 80 and over , Blood Transfusion , Female , Humans , Length of Stay , Male , Malnutrition/diagnosis , Nutritional Status , Patient Discharge , Pneumonia/etiology , Postoperative Complications/therapy , Propensity Score , Risk FactorsABSTRACT
State-average calculations based on a mixture of states are increasingly being exploited across chemistry and physics as versatile procedures for addressing excitations of quantum many-body systems. If not too many states should need to be addressed, calculations performed on individual states are also a common option. Here we show how the two approaches can be merged into one method, dealing with a generalized yet single pure state. Implications in electronic structure calculations are discussed and for quantum computations are pointed out.
ABSTRACT
BACKGROUND: Neutrophilic asthma (NA) is a clinically important asthma phenotype, the cellular and molecular basis of which is not completely understood. Airway macrophages are long-lived immune cells that exert important homeostatic and inflammatory functions which are dysregulated in asthma. Unique transcriptomic programmes reflect varied macrophage phenotypes in vitro. We aimed to determine whether airway macrophages are transcriptomically altered in NA. METHODS: We performed RNASeq analysis on flow cytometry-isolated sputum macrophages comparing NA (n = 7) and non-neutrophilic asthma (NNA, n = 13). qPCR validation of RNASeq results was performed (NA n = 13, NNA n = 23). Pathway analysis (PANTHER, STRING) of differentially expressed genes (DEGs) was performed. Gene set variation analysis (GSVA) was used to test for enrichment of NA macrophage transcriptomic signatures in whole sputum microarray (cohort 1 - controls n = 16, NA n = 29, NNA n = 37; cohort 2 U-BIOPRED - controls n = 16, NA n = 47, NNA n = 57). RESULTS: Flow cytometry-sorting significantly enriched sputum macrophages (99.4% post-sort, 44.9% pre-sort, p < .05). RNASeq analysis confirmed macrophage purity and identified DEGs in NA macrophages. Selected DEGs (SLAMF7, DYSF, GPR183, CSF3, PI3, CCR7, all p < .05 NA vs. NNA) were confirmed by qPCR. Pathway analysis of NA macrophage DEGs was consistent with responses to bacteria, contribution to neutrophil recruitment and increased expression of phagocytosis and efferocytosis factors. GSVA demonstrated neutrophilic macrophage gene signatures were significantly enriched in whole sputum microarray in NA vs. NNA and controls in both cohorts. CONCLUSIONS: We demonstrate a pathophysiologically relevant sputum macrophage transcriptomic programme in NA. The finding that there is transcriptional activation of inflammatory programmes in cell types other than neutrophils supports the concept of NA as a specific endotype.
Subject(s)
Asthma , Transcriptome , Asthma/diagnosis , Asthma/genetics , Humans , Macrophages , Neutrophils , SputumABSTRACT
BACKGROUND: The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. OBJECTIVE: This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. STUDY DESIGN: Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n=31), term labor (n=13), preterm not in labor (n=21), preterm labor with acute clinical chorioamnionitis (n=6), preterm labor with no acute clinical chorioamnionitis (n=9), twin preterm not in labor (n=8), and twin preterm labor with no acute clinical chorioamnionitis (n=5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis. RESULTS: Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term not-in-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. CONCLUSION: The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.
Subject(s)
Labor, Obstetric/metabolism , Myometrium/metabolism , Obstetric Labor, Premature/metabolism , Pregnancy, Twin , Uterine Contraction/metabolism , Adult , Computer Simulation , Female , Gene Expression , Gestational Age , Humans , PregnancyABSTRACT
BACKGROUND AND PURPOSE: Long periods of daily sedentary time, particularly accumulated in long uninterrupted bouts, are a risk factor for cardiovascular disease. People with stroke are at high risk of recurrent events and prolonged sedentary time may increase this risk. We aimed to explore how people with stroke distribute their periods of sedentary behavior, which factors influence this distribution, and whether sedentary behavior clusters can be distinguished? METHODS: This was a secondary analysis of original accelerometry data from adults with stroke living in the community. We conducted data-driven clustering analyses to identify unique accumulation patterns of sedentary time across participants, followed by multinomial logistical regression to determine the association between the clusters, and the total amount of sedentary time, age, gender, body mass index (BMI), walking speed, and wake time. RESULTS: Participants in the highest quartile of total sedentary time accumulated a significantly higher proportion of their sedentary time in prolonged bouts (P < 0.001). Six unique accumulation patterns were identified, all of which were characterized by high sedentary time. Total sedentary time, age, gender, BMI, and walking speed were significantly associated with the probability of a person being in a specific accumulation pattern cluster, P < 0.001 - P = 0.002. DISCUSSION AND CONCLUSIONS: Although unique accumulation patterns were identified, there is not just one accumulation pattern for high sedentary time. This suggests that interventions to reduce sedentary time must be individually tailored.Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A343).
Subject(s)
Sedentary Behavior , Stroke , Accelerometry , Adult , Cluster Analysis , Humans , Independent LivingABSTRACT
Based on a generalization of Hohenberg-Kohn's theorem, we propose a ground state theory for bosonic quantum systems. Since it involves the one-particle reduced density matrix γ as a variable but still recovers quantum correlations in an exact way it is particularly well suited for the accurate description of Bose-Einstein condensates. As a proof of principle we study the building block of optical lattices. The solution of the underlying v-representability problem is found and its peculiar form identifies the constrained search formalism as the ideal starting point for constructing accurate functional approximations: The exact functionals F[γ] for this N-boson Hubbard dimer and general Bogoliubov-approximated systems are determined. For Bose-Einstein condensates with N_{BEC}≈N condensed bosons, the respective gradient forces are found to diverge, ∇_{γ}Fâ1/sqrt[1-N_{BEC}/N], providing a comprehensive explanation for the absence of complete condensation in nature.
ABSTRACT
In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.
Subject(s)
Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , Vaccinia virus , Vaccinia/epidemiology , Vaccinia/virology , Zoonoses/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Agriculture , Animals , Child , Colombia/epidemiology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Orthopoxvirus/immunology , Risk Factors , Seroepidemiologic Studies , Vaccinia virus/immunology , Young AdultABSTRACT
BACKGROUND AND AIMS: Myelodysplasia (MDS) is characterised by abnormal haematopoiesis and increased risk of bleeding. Microvesicles (MV) play a key role in coagulation and their impact in MDS is unknown. METHODS: Platelet free plasma from 35 red-cell transfusion-dependent MDS patients and 15 controls were analysed. Pro-coagulant function was assessed by the XaCT assay and by thrombin generation (ETP). Total MV were enumerated by nano-tracking analysis. MV subsets were quantified by flow cytometry after staining with specific antibodies for various endovascular cell types. Small RNA was quantitated and sequenced. The MV measurements were correlated with MDS clinical risk scores and level of transfusion dependence. RESULTS: The pro-coagulant function of MV was significantly lower in MDS. All the MV subtypes, as measured by flow cytometric markers, were also significantly lower. The small RNA and miRNA cargo were significantly higher in MDS. The miRNA profile showed that mir-28 and mir-LETD7 were under expressed whilst mir-584J and mir-4485 were over expressed in MV from MDS. CONCLUSIONS: Circulating MV in MDS show reduced pro-coagulant functional activity, reduced subtypes by flow cytometry and significantly different miRNA content. However, the levels or subtypes of MV did not predict the clinical phenotype or level of transfusion dependence.
Subject(s)
Cell-Derived Microparticles/physiology , MicroRNAs/analysis , Myelodysplastic Syndromes/pathology , Thrombophilia/etiology , Blood Coagulation Tests , Case-Control Studies , Cell-Derived Microparticles/genetics , Flow Cytometry , HumansABSTRACT
We derive an approximate equation for the time evolution of the natural occupation numbers for fermionic systems. The evolution of such numbers is connected with the symmetry-adapted generalized Pauli exclusion principle, as well as with the evolution of the natural orbitals and a set of many-body relative phases. We then relate the evolution of these phases to a geometrical and a dynamical term attached to some of the Slater determinants appearing in the configuration-interaction expansion of the wave function. Our approach becomes exact for highly symmetric systems whenever the wave function possesses as many Slater determinants as independent occupation numbers.
ABSTRACT
BACKGROUND: Variations in an individual's electronic health (eHealth) literacy may influence the degree to which health consumers can benefit from eHealth. The eHealth Literacy Scale (eHEALS) is a common measure of eHealth literacy. However, the lack of guidelines for the standardized interpretation of eHEALS scores limits its research and clinical utility. Cut points are often arbitrarily applied at the eHEALS item or global level, which assumes a dichotomy of high and low eHealth literacy. This approach disregards scale constructs and results in inaccurate and inconsistent conclusions. Cluster analysis is an exploratory technique, which can be used to overcome these issues, by identifying classes of patients reporting similar eHealth literacy without imposing data cut points. OBJECTIVE: The aim of this cross-sectional study was to identify classes of patients reporting similar eHealth literacy and assess characteristics associated with class membership. METHODS: Medical imaging outpatients were recruited consecutively in the waiting room of one major public hospital in New South Wales, Australia. Participants completed a self-report questionnaire assessing their sociodemographic characteristics and eHealth literacy, using the eHEALS. Latent class analysis was used to explore eHealth literacy clusters identified by a distance-based cluster analysis, and to identify characteristics associated with class membership. RESULTS: Of the 268 eligible and consenting participants, 256 (95.5%) completed the eHEALS. Consistent with distance-based findings, 4 latent classes were identified, which were labeled as low (21.1%, 54/256), moderate (26.2%, 67/256), high (32.8%, 84/256), and very high (19.9%, 51/256) eHealth literacy. Compared with the low class, participants who preferred to receive a lot of health information reported significantly higher odds of moderate eHealth literacy (odds ratio 16.67, 95% CI 1.67-100.00; P=.02), and those who used the internet at least daily reported significantly higher odds of high eHealth literacy (odds ratio 4.76, 95% CI 1.59-14.29; P=.007). CONCLUSIONS: The identification of multiple classes of eHealth literacy, using both distance-based and latent class analyses, highlights the limitations of using the eHEALS global score as a dichotomous measurement tool. The findings suggest that eHealth literacy support needs vary in this population. The identification of low and moderate eHealth literacy classes indicate that the design of eHealth resources should be tailored to patients' varying levels of eHealth literacy. eHealth literacy improvement interventions are needed, and these should be targeted based on individuals' internet use frequency and health information amount preferences.
Subject(s)
Computed Tomography Angiography/methods , Electronics/methods , Health Literacy/methods , Magnetic Resonance Imaging/methods , Telemedicine/methods , Cluster Analysis , Cross-Sectional Studies , Female , Humans , Internet , Male , Middle Aged , Outpatients , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Sentinel lymph node biopsy (SLNB) was designed as a minimally invasive method for evaluation of nodal involvement in patients with penile cancer and nonpalpable lymph nodes. Nevertheless, SLNB is not used in a regular basis due to the lack of studies that adequately characterize the performance of this procedure. The purpose of this study was to evaluate the diagnostic performance of SLNB in patients with infiltrative penile carcinoma without palpable inguinal lymph nodes in a Colombian population. MATERIALS AND METHODS: This is a retrospective observational study of 89 patients diagnosed with infiltrative penile squamous cell carcinoma with nonpalpable inguinal lymph nodes. These patients underwent partial or complete penectomy, along with SLNB, between 2008 and 2017. Those individuals with a positive SLNB underwent inguinal lymphadenectomy, while those with a negative SLNB were followed on a quarterly basis with a physical examination and imaging to assess relapse. Statistical analysis was done using the STATA 14 software. A contingency table was made to calculate sensitivity, specificity, positive predictive value, negative predictive value, and exactitude, each one with its own confidence interval (CI) of 95%. RESULTS: There was an average follow-up of 31.4 months, and all 89 patients were evaluated; most primary tumors were T2 (55%), followed by T1 (37%), all of which were subclassified as T1b and T3 (8%). Tumours were most frequently located in the glans (43%). All patients were classified as cN0 and underwent SLNB. Sixty-one patients (69%) tested negative in the SLNB, four of whom (6%) presented with lymph node relapse. On the other hand, 28 patients (31%) tested positive in the SLNB and consequently underwent inguinal lymphadenectomy, seven of whom had negative lymph nodeinvolvement (25% false positives). According to the results, the sensitivity was 84% (95% CI, 65.3-93.6) and the specificity was 89% (95% CI, 79.4-94.7), with a false-negative rate of 6.5%. CONCLUSIONS: The SLNB using radiotracer can be a useful method for lymph node staging in patients with penile cancer and nonpalpable lymph nodes when performed in experienced centers.
ABSTRACT
BACKGROUND: Massively parallel genetic sequencing allows rapid testing of known intellectual disability (ID) genes. However, the discovery of novel syndromic ID genes requires molecular confirmation in at least a second or a cluster of individuals with an overlapping phenotype or similar facial gestalt. Using computer face-matching technology we report an automated approach to matching the faces of non-identical individuals with the same genetic syndrome within a database of 3681 images [1600 images of one of 10 genetic syndrome subgroups together with 2081 control images]. Using the leave-one-out method, two research questions were specified: 1) Using two-dimensional (2D) photographs of individuals with one of 10 genetic syndromes within a database of images, did the technology correctly identify more than expected by chance: i) a top match? ii) at least one match within the top five matches? or iii) at least one in the top 10 with an individual from the same syndrome subgroup? 2) Was there concordance between correct technology-based matches and whether two out of three clinical geneticists would have considered the diagnosis based on the image alone? RESULTS: The computer face-matching technology correctly identifies a top match, at least one correct match in the top five and at least one in the top 10 more than expected by chance (P < 0.00001). There was low agreement between the technology and clinicians, with higher accuracy of the technology when results were discordant (P < 0.01) for all syndromes except Kabuki syndrome. CONCLUSIONS: Although the accuracy of the computer face-matching technology was tested on images of individuals with known syndromic forms of intellectual disability, the results of this pilot study illustrate the potential utility of face-matching technology within deep phenotyping platforms to facilitate the interpretation of DNA sequencing data for individuals who remain undiagnosed despite testing the known developmental disorder genes.