A normally developed placenta is integral to a successful pregnancy. Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two common pregnancy related complications that maybe a result of ...abnormal placental development. Placental microRNAs (miRNAs) have been investigated as potential biomarkers for these complications, as they may play a role in placental development and pathophysiology by influencing gene expression. The purpose of this study is to utilize next-generation sequencing to determine miRNA and gene expression in human placental (chorionic villous) samples from three distinct patient groups with early-onset (EO) PE, IUGR, or PE + IUGR.
Placental tissues were collected from four patient groups (control N = 21, EO-PE N = 20, EO-IUGR N = 18, and EO-PE + IUGR N = 20), and total RNA was used for miRNA and RNA sequencing on the Illumina Hiseq2000 platform. For stringent differential expression analysis multiple analysis programs were used to analyze both expression datasets in each patient group compared to gestational age-matched controls.
Analysis revealed miRNAs and genes that are disease-specific, as well as others that were common between disease groups, which suggests common underlying placental pathologies in EO-PE and EO-IUGR. More specifically, 6 miRNAs and 22 genes were identified to be differentially expressed in all three patient groups. In addition, integrative analysis between the miRNA and gene expression datasets revealed candidate gene targets for miRNAs of interest.
Integration of miRNA and RNA profiling in the same three subgroups of pregnancy complications, provides an alternate level of molecular information, in addition it can be used to better understand both unique and common molecular mechanisms involved in the pathophysiology of these diseases.
Objective
Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in ...systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population.
Methods
Systemic lupus erythematosus patients (n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio (n = 105,080).
Results
During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327–1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk.
Conclusions
Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We present the first large-scale methylome-wide association studies (MWAS) for major depressive disorder (MDD) to identify sites of potential importance for MDD etiology. Using a sequencing-based ...approach that provides near-complete coverage of all 28 million common CpGs in the human genome, we assay methylation in MDD cases and controls from both blood (N = 1132) and postmortem brain tissues (N = 61 samples from Brodmann Area 10, BA10). The MWAS for blood identified several loci with P ranging from 1.91 × 10
to 4.39 × 10
and a resampling approach showed that the cumulative association was significant (P = 4.03 × 10
) with the signal coming from the top 25,000 MWAS markers. Furthermore, a permutation-based analysis showed significant overlap (P = 5.4 × 10
) between the MWAS findings in blood and brain (BA10). This overlap was significantly enriched for a number of features including being in eQTLs in blood and the frontal cortex, CpG islands and shores, and exons. The overlapping sites were also enriched for active chromatin states in brain including genic enhancers and active transcription start sites. Furthermore, three loci located in GABBR2, RUFY3, and in an intergenic region on chromosome 2 replicated with the same direction of effect in the second brain tissue (BA25, N = 60) from the same individuals and in two independent brain collections (BA10, N = 81 and 64). GABBR2 inhibits neuronal activity through G protein-coupled second-messenger systems and RUFY3 is implicated in the establishment of neuronal polarity and axon elongation. In conclusion, we identified and replicated methylated loci associated with MDD that are involved in biological functions of likely importance to MDD etiology.
Making evidence-based decisions often requires comparison of two or more options. Research-based evidence may exist which quantifies how likely the outcomes are for each option. Understanding these ...numeric estimates improves patients' risk perception and leads to better informed decision making. This paper summarises current "best practices" in communication of evidence-based numeric outcomes for developers of patient decision aids (PtDAs) and other health communication tools.
An expert consensus group of fourteen researchers from North America, Europe, and Australasia identified eleven main issues in risk communication. Two experts for each issue wrote a "state of the art" summary of best evidence, drawing on the PtDA, health, psychological, and broader scientific literature. In addition, commonly used terms were defined and a set of guiding principles and key messages derived from the results.
The eleven key components of risk communication were: 1) Presenting the chance an event will occur; 2) Presenting changes in numeric outcomes; 3) Outcome estimates for test and screening decisions; 4) Numeric estimates in context and with evaluative labels; 5) Conveying uncertainty; 6) Visual formats; 7) Tailoring estimates; 8) Formats for understanding outcomes over time; 9) Narrative methods for conveying the chance of an event; 10) Important skills for understanding numerical estimates; and 11) Interactive web-based formats. Guiding principles from the evidence summaries advise that risk communication formats should reflect the task required of the user, should always define a relevant reference class (i.e., denominator) over time, should aim to use a consistent format throughout documents, should avoid "1 in x" formats and variable denominators, consider the magnitude of numbers used and the possibility of format bias, and should take into account the numeracy and graph literacy of the audience.
A substantial and rapidly expanding evidence base exists for risk communication. Developers of tools to facilitate evidence-based decision making should apply these principles to improve the quality of risk communication in practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Brain metastases (BrMs) are a common occurrence in lung cancer with a dismal outcome. To understand the mechanism of metastasis to inform prognosis and treatment, here we analyze primary and ...metastasized tumor specimens from 44 non-small cell lung cancer patients by spatial RNA sequencing, affording a whole transcriptome map of metastasis resolved with morphological markers for the tumor core, tumor immune microenvironment (TIME), and tumor brain microenvironment (TBME). Our data indicate that the tumor microenvironment (TME) in the brain, including the TIME and TBME, undergoes extensive remodeling to create an immunosuppressive and fibrogenic niche for the BrMs. Specifically, the brain TME is characterized with reduced antigen presentation and B/T cell function, increased neutrophils and M2-type macrophages, immature microglia, and reactive astrocytes. Differential gene expression and network analysis identify fibrosis and immune regulation as the major functional modules disrupted in both the lung and brain TME. Besides providing systems-level insights into the mechanism of lung cancer brain metastasis, our study uncovers potential prognostic biomarkers and suggests that therapeutic strategies should be tailored to the immune and fibrosis status of the BrMs.
Objectives/Hypothesis
There are variants of chronic rhinosinusitis (CRS). Therefore, the objectives of this study were to phenotype the subclasses of CRS as well as characterize their polyps with ...histology and cellular–intracellular biomarkers.
Study Design
Prospective case‐control study.
Methods
Demographic data, quality‐of‐life (QoL) questionnaires, nasal endoscopy (NE), and computed tomography (CT) scores were obtained. CRS was divided into seven subclasses: aspirin‐exacerbated respiratory disease (AERD), asthmatic sinusitis with and without allergy, nonasthmatic sinusitis with and without allergy, allergic fungal sinusitis (AFS), and cystic fibrosis (CF). Histopathologic and immunohistochemistry of nasal polyps were recorded. CD3, CD4, CD8, CD19, CD45, and CD56 data were collected. Interleukin (IL)4, IL5, IL13, IL17, and interferon (IFN)‐γ were measured.
Results
Eight‐four subjects were in this study. Two QoL questionnaires were inadequate at distinguishing the control group from CRS. NE and CT were able to differentiate between the control group and all CRS subclasses (P<.01). Asthmatic sinusitis, AERD, and AFS had high NE and CT scores, nasal polyps, eosinophils, mast cell, and hypercellularity. Asthmatic sinusitis, nonasthmatic sinusitis, and AERD had higher CD4 cells than control group (P<.05). Even though asthmatic sinusitis and AFS are mediated by Th2, AFS had differing levels of Th2 cytokines. Each nonasthmatic sinusitis had purulence and low CT score. Each nonasthmatic sinusitis had higher CD4 cells and IFN‐γ than control (P<.05). CF is associated with purulence, high CT score, high polymorphonuclear leukocytes, high plasma cells, and high mast cells.
Conclusions
Well‐characterized and distinct groups of CRS have been defined for targeted treatment and research studies.
Level of Evidence
2b Laryngoscope, 123:S15–S27, 2013
Anthropometric Changes in Spaceflight Young, Karen S.; Kim, K. Han; Rajulu, Sudhakar
Human factors,
09/2023, Letnik:
65, Številka:
6
Journal Article
Recenzirano
Objective
This study aims to identify the change in anthropometric measurements during spaceflight due to microgravity exposure.
Background
Comprehensive and accurate anthropometric measurements are ...crucial to assess body shape and size changes in microgravity. However, only limited anthropometric data have been available from the astronauts in spaceflight.
Methods
A new photogrammetry-based technique in combination with a tape-measure method was used for anthropometric measurements from nine crewmembers on the International Space Station. Measurements included circumference and height for body segments (chest, waist, bicep, thigh, calf). The time-dependent variations were also assessed across pre-, in-, and postflight conditions.
Results
Stature showed a biphasic change with up to 3% increase at the early flight phase, followed by a steady phase during the remaining flight. Postflight measurements returned to a similar level of the preflight. Other linear measurements, including acromion height, showed similar trends. The chest, hip, thigh, and calf circumferences show overall decrease during the flight up to 11%, then returned close to the preflight measurement at postflight.
Conclusion
The measurements from this study provide critical information for the spacesuit and hardware design. The ground-based assessments for spacesuit fit needs to be revalidated and adjusted for in-flight extravehicular activities from this data.
Application
These data can be useful for space suit design as well as habitat, vehicle, and additional microgravity activities such as exercise, where the body shape changes can affect fit, performance, and human factors of the overall design.
Recommendations regarding key aspects related to the diagnosis and pharmacological treatment of lymphangioleiomyomatosis (LAM) were recently published. We now provide additional recommendations ...regarding four specific questions related to the diagnosis of LAM and management of pneumothoraces in patients with LAM.
Systematic reviews were performed and then discussed by a multidisciplinary panel. For each intervention, the panel considered its confidence in the estimated effects, the balance of desirable (i.e., benefits) and undesirable (i.e., harms and burdens) consequences, patient values and preferences, cost, and feasibility. Evidence-based recommendations were then formulated, written, and graded using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.
For women who have cystic changes on high-resolution computed tomography of the chest characteristic of LAM, but who have no additional confirmatory features of LAM (i.e., clinical, radiologic, or serologic), the guideline panel made conditional recommendations against making a clinical diagnosis of LAM on the basis of the high-resolution computed tomography findings alone and for considering transbronchial lung biopsy as a diagnostic tool. The guideline panel also made conditional recommendations for offering pleurodesis after an initial pneumothorax rather than postponing the procedure until the first recurrence and against pleurodesis being used as a reason to exclude patients from lung transplantation.
Evidence-based recommendations for the diagnosis and treatment of patients with LAM are provided. Frequent reassessment and updating will be needed.
Summary Objective The aim of this study was to investigate the site-dependent changes in the structure and function of articular cartilage in the lapine knee joint at a very early stage of ...osteoarthritis (OA), created experimentally by anterior cruciate ligament transection (ACLT). Methods Unilateral ACLT was performed in eight mature New Zealand white rabbits. ACL transected and contralateral (C-L) joints were prepared for analysis at 4 weeks after ACLT. Three rabbits with intact joints were used as a control group (CNTRL). Femoral groove, medial and lateral femoral condyles, and tibial plateaus were harvested and used in the analysis. Biomechanical tests, microscopy and spectroscopy were used to determine the biomechanical properties, composition and structure of the samples. A linear mixed model was chosen for statistical comparisons between the groups. Results As a result of ACLT, the equilibrium and dynamic moduli were decreased primarily in the femoral condyle cartilage. Up to three times lower moduli ( P < 0.05) were observed in the ACLT group compared to the control group. Significant ( P < 0.05) proteoglycan (PG) loss in the ACLT joint cartilage was observed up to a depth of 20–30% from the cartilage surface in femoral condyles, while significant PG loss was confined to more superficial regions in tibial plateaus and femoral groove. The collagen orientation angle was increased ( P < 0.05) up to a cartilage depth of 60% by ACLT in the lateral femoral condyle, while smaller effects, but still significant, were observed at other locations. The collagen content was increased ( P < 0.05) in the middle and deep zones of the ACLT group compared to the control group samples, especially in the lateral femoral condyle. Conclusion Femoral condyle cartilage experienced the greatest structural and mechanical alterations in very early OA, as produced by ACLT. Degenerative alterations were observed especially in the superficial collagen fiber organization and PG content, while the collagen content was increased in the deep tissue of femoral condyle cartilage. The current findings provide novel information of the early stages of OA in different locations of the knee joint.
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