Critical Care: What You May Have Missed in 2023 Ajzenberg, Henry; Binhashr, Mansor Abdalaziz N; Hewitt, Mark Keith ...
Annals of internal medicine,
05/2024, Letnik:
177, Številka:
5_Supplement
Journal Article
Recenzirano
Critical care medicine is a specialty that brings together a truly wide spectrum of patient populations, disease states, and treatment methods. This article highlights 10 important pieces of research ...from 2023 (and 1 from 2022) in critical care. The literature was screened for new evidence relevant to internal medicine physicians and hospitalists whose focus of practice is not critical care but who may be taking care of seriously ill patients. The articles highlight the diverse spectrum of pathology and interplay of various specialties that go into critical care. Topics include transfusion medicine, fluid resuscitation, safe intubation practices and respiratory failure, and the management of acute ischemic stroke. Several trials are groundbreaking, forcing clinicians to reconsider preexisting dogma and likely adopt new treatment strategies.
Neonatal sepsis is a life-threatening diagnosis, with a reported incidence of 1-4 per 1,000 live births in the US. Common culprit bacteria in the neonatal ( 30 d) age group include group B ...Streptococcus, Escherichia coli and other gram-negative bacilli, thought to be acquired through vertical transmission from the maternal genitourinary tract. In Canada, missed meningitis is a common complaint to the Canadian Medical Protection Association, with most cases concerning children aged 0-4 years. Citrobacter koseri is a gram-negative bacterium that is universally resistant to penicillin; it is a rare cause of neonatal meningitis. Case-fatality rates in neonates are about 30%, with 70% of cases developing brain abscess and 50% of survivors left with longterm neurologic sequelae. Here, Hewitt et al examine the case of a 13-day-old boy with citrobacter koseri meningitis and septicemia.
DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific ...disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features.
DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12-13 y from 20 individuals from the Southampton Women's Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals.
HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue.
This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation.
While ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated ...in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.
We measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated cytosine phosphate guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR, an index for the assessment of insulin resistance, and levels of glycated hemoglobin HbA1c.
Thirty-eight dmCpGs (false discovery rate (FDR) < 0.05) were associated with HOMA2-IR, with dmCpGs enriched in genes linked with JNK, AMPK and insulin signaling. The methylation signal associated with HOMA2-IR was attenuated after the addition of either BMI (6 dmCpGs), appendicular lean mass index (ALMi) (7 dmCpGs), grip strength (15 dmCpGs) or gait speed (23 dmCpGs) as covariates in the model. There were 8 DMRs (Stouffer < 0.05) associated with HOMA2-IR, including DMRs within T-box transcription factor (TBX1) and nuclear receptor subfamily-2 group F member-2 (NR2F2); the DMRs within TBX1 and NR2F2 remained associated with HOMA2-IR after adjustment for BMI, ALMi, grip strength or gait speed. Forty-nine dmCpGs and 21 DMRs were associated with HbA1c, with cg13451048, located within exoribonuclease family member 3 (ERI3) associated with both HOMA2-IR and HbA1c. HOMA2-IR and HbA1c were not associated with accelerated epigenetic ageing.
These findings suggest that insulin resistance is associated with differential DNA methylation in human primary myoblasts with both muscle mass and body composition making a significant contribution to the methylation changes associated with IR.
Haemostatic dressings in prehospital care Smith, Adam Hewitt; Laird, Colville; Porter, Keith ...
Emergency medicine journal : EMJ,
10/2013, Letnik:
30, Številka:
10
Journal Article
Recenzirano
Massive haemorrhage still accounts for up to 40% of mortality after traumatic injury. The importance of limiting blood loss after injury in order to prevent its associated complications has led to ...rapid advances in the development of dressings for haemostatic control. Driven by recent military conflicts, there is increasing evidence to support their role in the civilian prehospital care environment. This review aims to summarise the key characteristics of the haemostatic dressings currently available on the market and provide an educational review of the published literature that supports their use. Medline and Embase were searched from start to January 2012. Other sources included both manufacturer and military publications. Agents not designed for use in prehospital care or that have been removed from the market due to significant safety concerns were excluded. The dressings reviewed have differing mechanisms of action. Mineral based dressings are potent activators of the intrinsic clotting cascade resulting in clot formation. Chitosan based dressings achieve haemostasis by adhering to damaged tissues and creating a physical barrier to further bleeding. Acetylated glucosamine dressings work via a combination of platelet and clotting cascade activation, agglutination of red blood cells and local vasoconstriction. Anecdotal reports strongly support the use of haemostatic dressings when bleeding cannot be controlled using pressure dressings alone; however, current research focuses on studies conducted using animal models. There is a paucity of published clinical literature that provides an evidence base for the use of one type of haemostatic dressing over another in humans.
Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically ...relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin‐fixed, paraffin‐embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead‐based microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in individual CpG sites were compared using a t‐test, and results were summarized by computing p‐values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1, DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA methylation profiling, plus an additional three genes identified from the literature (EPB41L3, MAL and miR‐124) were chosen for validation in an independent set of 167 liquid‐based cytology specimens using pyrosequencing and targeted, next‐generation bisulfite sequencing. Of the 15 candidate gene markers, 10 had an area under the curve (AUC) of ≥ 0.75 for discrimination of high grade squamous intraepithelial lesions or worse (HSIL+) from <HSIL cytology using at least one assay. Overall, SOX1, DCC, and EPB41L3 showed the best discrimination with AUC values of ≥0.80, irrespective of methylation detection assay. In addition to verifying candidate markers from the literature (e.g., SOX1 and EPB41L3), we identified novel markers that may be considered for detection of cervical precancer and cancer and warrant further validation in prospective studies.
What's new?
Testing for human papillomavirus (HPV) is gaining traction for cervical‐cancer screening. However, most HPV infections are transient. Additional screening tests are thus needed, to identify women with precancerous or cancerous lesions who need further testing and treatment. Certain tumor‐suppressor genes in cervical cancer cells have been found to have altered methylation. In this study, the authors used pyrosequencing and next‐generation bisulfite sequencing to identify and validate several new DNA‐methylation markers, which may lead to better screening tests.
This study provides further evidence for the impact of the aromas of plant essential oils on aspects of cognition and mood in healthy participants. One hundred and forty-four volunteers were randomly ...assigned to conditions of ylang-ylang aroma, peppermint aroma, or no aroma control. Cognitive performance was assessed using the Cognitive Drug Research computerized assessment battery, with mood scales completed before and after cognitive testing. The analysis of the data revealed significant differences between conditions on a number of the factors underpinning the tests that constitute the battery. Peppermint was found to enhance memory whereas ylang-ylang impaired it, and lengthened processing speed. In terms of subjective mood peppermint increased alertness and ylang-ylang decreased it, but significantly increased calmness. These results provide support for the contention that the aromas of essential oils can produce significant and idiosyncratic effects on both subjective and objective assessments of aspects of human behavior. They are discussed with reference to possible pharmacological and psychological modes of influence.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In previous experiments, bleached kraft chemical recovery condensates generated during softwood pulp production have been identified as a primary source of substances causing testosterone depressions ...in mummichog (Fundulus heteroclitus). Recent toxicity identification evaluations have encountered inconsistencies in the potential of condensates and fractions to reduce steroid concentrations between three repeated exposures. To assess the sources of these inconsistencies, temporal assessments of condensate extractives and analytical methodologies were evaluated. Condensates were collected during a six‐month period, extracted by solid‐phase extraction (SPE), and analyzed by gas chromatography–mass spectrometry and gas chromatography–flame photometric detection. All unique extractives were cataloged by mass spectra, peak area, and gas chromatographic retention time, and nine were confirmed and quantified against authentic standards. Confirmed components included phenolic guaiacyl–based lignin degradation products, sulfur (S8), three diterpenoids, and a dimethoxy stilbene. Concentrations of confirmed condensate extractives were consistent in all samples collected. Spiking experiments of confirmed extractives revealed substantial losses following high‐pressure liquid chromatographic fractionation and three different methods of fraction preparation. In an effort to propose chemical classes associated with biological activity, all unique condensate extractives in previously established bioactive and inactive fractions were classified based on their potential to depress testosterone in mummichog. Of 39 unique components in bioactive SPE extracts of condensates, six were associated with hormonal activity. Mass spectral interpretation indicated hydroxylated diterpenoids, sesquiterpenoids, and a lignin‐derived stilbene as classes of chemicals associated with steroid depressions.
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