There is widespread acceptance that cationic antimicrobial peptides, apart from their membrane-permeabilizing/disrupting properties, also operate through interactions with intracellular targets, or ...disruption of key cellular processes. Examples of intracellular activity include inhibition of DNA and protein synthesis, inhibition of chaperone-assisted protein folding and enzymatic activity, and inhibition of cytoplasmic membrane septum formation and cell wall synthesis. The purpose of this minireview is to question some widely held views about intracellular-targeting antimicrobial peptides. In particular, I focus on the relative contributions of intracellular targeting and membrane disruption to the overall killing strategy of antimicrobial peptides, as well as on mechanisms whereby some peptides are able to translocate spontaneously across the plasma membrane. Currently, there are no more than three peptides that have been convincingly demonstrated to enter microbial cells without the involvement of stereospecific interactions with a receptor/docking molecule and, once in the cell, to interfere with cellular functions. From the limited data currently available, it seems unlikely that this property, which is isolated in particular peptide families, is also shared by the hundreds of naturally occurring antimicrobial peptides that differ in length, amino acid composition, sequence, hydrophobicity, amphipathicity, and membrane-bound conformation. Microbial cell entry and/or membrane damage associated with membrane phase/transient pore or long-lived transitions could be a feature common to intracellular-targeting antimicrobial peptides and mammalian cell-penetrating peptides that have an overrepresentation of one or two amino acids, i.e. Trp and Pro, His, or Arg. Differences in membrane lipid composition, as well as differential lipid recruitment by peptides, may provide a basis for microbial cell killing on one hand, and mammalian cell passage on the other.
Objective
We aimed to clarify the definition, epidemiology, and pathophysiology of excited delirium syndrome (ExDS) and to summarize evidence‐based treatment recommendations.
Methods
We conducted a ...systematic literature search of MEDLINE, Ovid, Web of Knowledge, and Cochrane Library for articles published to March 18, 2017. We also searched the gray literature (Google Scholar) and official police or medical expert reports to complete specific epidemiologic data. Search results and full‐text articles were independently assessed by two investigators and agreements between reviewers assessed with K statistics. We classified articles by study type, setting, and evidence level.
Results
After reviewing the title and of 3,604 references, we fully reviewed 284 potentially relevant references, from which 66 were selected for final review. Six contributed to the definition of ExDS, 24 to its epidemiology, 38 to its pathophysiology, and 27 to its management. The incidence of ExDS varies widely with medical or medicolegal context. Mortality is estimated to be as much as 8.3% to 16.5%. Patients are predominantly male. Male sex, young age, African‐American race, and being overweight are independent risk factors. Pathophysiology hypotheses mostly implicate dopaminergic pathways. Most cases occur with psychostimulant use or among psychiatric patients or both. Proposed treatments are symptomatic, often with rapid sedation with benzodiazepines or antipsychotic agents. Ketamine is suggested as an alternative.
Conclusion
The overall quality of studies was poor. A universally recognized definition is lacking, remaining mostly syndromic and based on clinical subjective criteria. High mortality rate may be due to definition inconsistency and reporting bias. Our results suggest that ExDS is a real clinical entity that still kills people and that has probably specific mechanisms and risk factors. No comparative study has been performed to conclude whether one treatment approach is preferable to another in the case of ExDS.
Currently, the decision to initiate extracorporeal life support for patients who suffer cardiac arrest due to accidental hypothermia is essentially based on serum potassium level. Our goal was to ...build a prediction score in order to determine the probability of survival following rewarming of hypothermic arrested patients based on several covariates available at admission.
We included consecutive hypothermic arrested patients who underwent rewarming with extracorporeal life support. The sample comprised 237 patients identified through the literature from 18 studies, and 49 additional patients obtained from hospital data collection. We considered nine potential predictors of survival: age; sex; core temperature; serum potassium level; mechanism of hypothermia; cardiac rhythm at admission; witnessed cardiac arrest, rewarming method and cardiopulmonary resuscitation duration prior to the initiation of extracorporeal life support. The primary outcome parameter was survival to hospital discharge.
Overall, 106 of the 286 included patients survived (37%; 95% CI: 32–43%), most (84%) with a good neurological outcome. The final score included the following variables: age, sex, core temperature at admission, serum potassium level, mechanism of cooling, and cardiopulmonary resuscitation duration. The corresponding area under the receiver operating characteristic curve was 0.895 (95% CI: 0.859–0.931) compared to 0.774 (95% CI: 0.720–0.828) when based on serum potassium level alone.
In this large retrospective study we found that our score was superior to dichotomous triage based on serum potassium level in assessing which hypothermic patients in cardiac arrest would benefit from extracorporeal life support. External validation of our findings is required.
BACKGROUND
Identifying vulnerable older patients admitted to an emergency department (ED) who are at increased risk for adverse events and require a comprehensive geriatric assessment remains a major ...challenge. The interRAI Emergency Department Screener (EDS) was developed for this specific purpose, but data regarding its validity are scarce.
OBJECTIVES
To determine (1) convergent validity of the EDS with results of a geriatricianʼs assessment in defining the need for prompt versus delayed/no further geriatric assessment and (2) predictive validity of the EDS for hospital admission, prolonged hospital length of stay (LOS), and 30‐day readmission.
DESIGN
Prospective observational study.
SETTING
ED of an academic hospital in Switzerland.
PARTICIPANTS
Older patients, aged 75 years or older (N = 202), who visited the ED over a 4‐month period. Patients with life‐threatening conditions were excluded.
MEASUREMENTS
Data for EDS were collected by two clinical nurses. A brief geriatric assessment was performed separately and interpreted by a geriatrician blinded to the EDS results. Orientation after ED discharge, hospital LOS, and 30‐day readmission were retrieved from the administrative database.
RESULTS
Participants were aged 83.2 ± 5.4 years, 56.9% were female, and 43.6% lived alone. Frequent findings at geriatric assessment were impairment in gait/balance (69.3%), polypharmacy (64.9%), cognitive impairment/delirium (48.2%), risk of malnutrition (46.0%), and mood impairment (38.1%). The proportions of participants who required prompt, delayed, and no further geriatric assessment, according to the EDS, were 27.2%, 29.2%, and 43.6%, respectively. The EDS had low sensitivity in predicting hospital admission (28.8%), prolonged LOS (26.3%), and 30‐day readmission (26.1%), with the Area Under the Receiver Operating Characteristics (AUROC) being 51.8%, 48.1%, and 49.4%, respectively.
CONCLUSION
The EDS performed poorly in both convergent and predictive validity analyses, precluding its use as a screening tool in this ED environment. Further efforts should be undertaken to better target interventions to reduce adverse health trajectories in the older ED population.
A genetic assay permits simultaneous quantification of two interacting proteins and their bound fraction at the single‐cell level using flow cytometry. Apparent in‐cellula affinities of ...protein‐protein interactions can be extracted from the acquired data through a titration‐like analysis. The applicability of this approach is demonstrated on a diverse set of interactions with proteins from different families and organisms and with in‐vitro dissociation constants ranging from picomolar to micromolar.
Using fluorescent probes, we estimate at the cellular level the fraction of Bait molecules bound by Prey molecules in a quantitative yeast‐two hybrid assay. A titration‐like analysis of flow cytometer data permits the extraction of the apparent in‐cellula dissociation constant.
Background: Chronic job insecurity seems to be a prominent feature within elite sport, where coaches work under pressure of dismissals if failing to meet performance expectations of stakeholders. The ...aim of the current study was to get a deeper understanding of elite football coaches’ experiences of getting fired and how they made sense of that process. Method: A qualitative design using semi-structured interviews was conducted with six elite football coaches who were fired within the same season. Interpretative phenomenological analysis was chosen as framework to analyze the data. Results: The results reflected five emerging themes: Acceptance of having an insecure job, working for an unprofessional organization and management, micro-politics in the organization, unrealistic and changing performance expectation, and emotional responses. Conclusion: All coaches expressed awareness and acceptance regarding the risk of being fired. However, they experienced a lack of transparency and clear feedback regarding the causes of dismissal. This led to negative emotional reactions as the coaches experienced being evaluated by poorly defined expectations and by anonymous stakeholders. Sports organizations as employers should strive to be transparent during dismissal. In addition, job insecurity is a permanent stressor for coaches and should be acknowledged and targeted within coach education.
Abstract
Background
Tropical infectious diseases and vaccine-preventable emergencies are the mainstay of pre-travel consultations. However, non-communicable diseases, injuries and accidents that ...occur during travel are not emphasized enough in these settings.
Methods
We performed a narrative review based on a literature search of PubMed, Google Scholar, UpToDate, DynaMed and LiSSa and on reference textbooks and medical journals dedicated to travel, emergency and wilderness medicine. Relevant secondary references were extracted. We also aimed to discuss newer or neglected issues, such as medical tourism, Coronavirus Disease 2019, exacerbations of co-morbidities associated with international travel, insurance coverage, health care seeking abroad, medical evacuation or repatriation and tips for different types of travellers’ emergency medical kits (personal, group, physician handled).
Results
All sources reviewed led to the selection of >170 references. Among epidemiological data on morbidity and deaths while abroad, only retrospective data are available. Deaths are estimated to occur in 1 in 100 000 travellers, with 40% caused by trauma and 60% by diseases, and <3% linked to infectious diseases. Trauma and other injuries acquired during travel, such as traffic accidents and drowning, can be reduced by up to 85% with simple preventive recommendations such as avoiding simultaneous alcohol intake. In-flight emergencies occur on 1 in 604 flights on average. Thrombosis risk is two to three times greater for travellers than for non-travellers. Fever during or after travel can occur in 2–4% of travellers, but in up to 25–30% in tertiary centres. Traveller’s diarrhoea, although rarely severe, is the most common disease associated with travel. Autochthonous emergencies (acute appendicitis, ectopic pregnancy, dental abscess) can also occur.
Conclusions
Pre-travel medicine encounters must include the topic of injuries and medical emergencies, such as the risk-taking behaviours and foster better planning in a comprehensive approach along with vaccines and infectious diseases advices.
Bacillus subtilis possesses three essential enzymes thought to be involved in mRNA decay to varying degrees, namely RNase Y, RNase J1, and RNase III. Using recently developed high-resolution tiling ...arrays, we examined the effect of depletion of each of these enzymes on RNA abundance over the whole genome. The data are consistent with a model in which the degradation of a significant number of transcripts is dependent on endonucleolytic cleavage by RNase Y, followed by degradation of the downstream fragment by the 5'-3' exoribonuclease RNase J1. However, many full-size transcripts also accumulate under conditions of RNase J1 insufficiency, compatible with a model whereby RNase J1 degrades transcripts either directly from the 5' end or very close to it. Although the abundance of a large number of transcripts was altered by depletion of RNase III, this appears to result primarily from indirect transcriptional effects. Lastly, RNase depletion led to the stabilization of many low-abundance potential regulatory RNAs, both in intergenic regions and in the antisense orientation to known transcripts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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