Factors influencing family member perspectives on safety in the intensive care unit: a systematic review.

PURPOSE: Patient safety has developed as a strong marker for healthcare quality. Safety matters are important in the intensive care unit (ICU) where complex clinical decisions are made, intensive technology is used, and families hold a unique role. The aim of this review was to identify and describe factors that influence family member's perceptions of safety in the adult ICU. DATA SOURCES: Searches were conducted between September and November 2018 and repeated in July 2020 using CINAHL, MEDLINE (EBSCO), PubMed and PsycINFO databases. STUDY SELECTION: Published primary studies undertaken in adult ICUs and involving adult family member participants exploring safety or feeling safe. No date restrictions were applied. DATA EXTRACTION: A data extraction form collected information about sample, study design, data collection methods and results from each paper. Methodological quality was assessed using the QualSyst tools for qualitative and quantitative studies. Narrative synthesis was undertaken. RESULTS OF DATA SYNTHESIS: Twenty papers were included with 11 papers published since 2010. The majority of papers reported on qualitative studies (n = 16). Four factors were identified that influenced whether family members felt that the patient was safe in ICU: family visiting, information and communication, caring and professional competence. CONCLUSION: In detailing specific practices that make families feel safe and unsafe in ICU, these review findings provide a structure for clinicians, educators and researchers to inform future work and gives opportunity for the family role in patient safety to be reconsidered.

Anticancer Activities of Natural and Synthetic Peptides.

Anticancer peptides (ACPs) are cationic amphipathic peptides that bind to and kill cancer cells either by a direct- or indirect-acting mechanism. ACPs provide a novel treatment strategy, and selected ACPs are currently in phase I clinical trials to examine their safety and overall benefit in cancer patients. Increasing the selectivity of ACPs is important so that these peptides kill cancer cells without harming normal cells. Peptide sequence modifications may help to improve ACP selectivity. ACPs also have immune-modulatory effects, including the release of danger signals from dying cancer cells, induction of chemokine genes, increasing T-cell immune responses, and inhibiting T regulatory cells. These effects ultimately increase the potential for an effective anticancer immune response that may contribute to long-term benefits and increased patient survival. Packaging ACPs in nanoparticles or fusogenic liposomes may be beneficial for increasing ACP half-life and enhancing the delivery of ACPs to tumor target cells. Additionally, engineering ACP-producing oncolytic viruses may be an effective future treatment strategy. Overall research in this area has been slow to progress, but with ongoing ACP-based clinical trials, the potential for ACPs in cancer treatments is closer to being realized. The integration of basic research with computer modeling of ACPs is predicted to substantially advance this field of research.

A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of women.

Temporomandibular disorder (TMD) incidences are believed to be related to parafunctional behaviours like teeth clenching. This pilot study aimed to (i) develop an automated clench-detection algorithm, and (ii) apply the algorithm to test for differences in nocturnal clenching in women with and without TMD. Subjects gave informed consent to participate. Adult women were categorised using Diagnostic Criteria for TMD according to presence/absence (+/-) of both TM joint disc placement (DD) and chronic pain (P) into two groups (+DD+P, -DD-P) with 12 subjects each. Surface temporalis electromyography was recorded during oral tasks performed by subjects at two laboratory sessions. The data were used to characterise muscle activity per N of bite force (µV/N) for each subject, develop the clench-detection algorithm and test its accuracy. Ambulatory surface temporalis electromyography was self-recorded by each subject over three nights and analysed using the algorithm and bite force (N) versus muscle activity µV/N calibrations. Bonferroni-adjusted homoscedastic t-tests assessed for significant between-group differences in clenching (P < 0·05). Sensitivity, specificity and accuracy of algorithm-detected laboratory clenches were all ≥96%. During self-recordings 95% of clenches had durations of <4 s and peak forces of <10 N in both groups. Mean clench durations were significantly longer (P = 0·042) in +DD+P (1·9 ± 0·8 s) than -DD-P subjects (1·4 ± 0·4 s). Mean temporalis duty factors (%clench time/total recording time) were significantly larger (P = 0·041) in +DD+P (0·47 ± 0·34%) than -DD-P (0·26 ±0·22%) subjects. Nocturnal temporalis muscle activities detected by a validated algorithm were longer per clench and recording time in +DD+P compared to -DD-P women.

Post-release evaluation of Eretmocerus hayati Zolnerowich and Rose in Australia.

Bemisia tabaci biotype B is a significant pest of agriculture world-wide. It was first detected in Australia in 1994. Assessments of the potential of parasitoids already present in Australia to control this pest indicated that two species of Eretmocerus and 11 species of Encarsia were present, but they did not exert sufficient control with a combined average of 5.0+/-0.3% apparent parasitism of 4th instars. Further, only 25% of samples containing biotype B had parasitised individuals present. The surveys also identified that fewer B biotype were being parasitised compared with the Australian indigenous biotype. Overall, Er. mundus was the most abundant parasitoid prior to the introduction. Previous research indicated that Er. hayati offered the best prospects for Australia and, in October 2004, the first releases were made. Since then, levels of apparent parasitism have averaged 29.3+/-0.1% of 4th instars with only 24% of collections having no parasitism present. Eretmocerus hayati contributed 85% of the overall apparent parasitism. In addition, host plants of the whitefly with low or no parasitism prior to the release have had an order of magnitude increase in levels of parasitism. This study covers the establishment of the case to introduce Er. hayati and the post-release establishment period November 2004-March 2008.

Effect of Sustained Joint Loading on TMJ Disc Nutrient Environment.

The temporomandibular joint (TMJ) disc nutrient environment profoundly affects cell energy metabolism, proliferation, and biosynthesis. Due to technical challenges of in vivo measurements, the human TMJ disc extracellular nutrient environment under load, which depends on metabolic rates, solute diffusion, and disc morphometry, remains unknown. Therefore, the study objective was to predict the TMJ disc nutrient environment under loading conditions using combined experimental and computational modeling approaches. Specifically, glucose consumption and lactate production rates of porcine TMJ discs were measured under varying tissue culture conditions (n = 40 discs), and mechanical strain-dependent glucose and lactate diffusivities were measured using a custom diffusion chamber (n = 6 discs). TMJ anatomy and loading area were obtained from magnetic resonance imaging of healthy human volunteers (n = 11, male, 30 ± 9 y). Using experimentally determined nutrient metabolic rates, solute diffusivities, TMJ anatomy, and loading areas, subject-specific finite element (FE) models were developed to predict the 3-dimensional nutrient profiles in unloaded and loaded TMJ discs (unloaded, 0% strain, 20% strain). From the FE models, glucose, lactate, and oxygen concentration ranges for unloaded healthy human TMJ discs were 0.6 to 4.0 mM, 0.9 to 5.0 mM, and 0% to 6%, respectively, with steep gradients in the anterior and posterior bands. Sustained mechanical loading significantly reduced nutrient levels (P < 0.001), with a critical zone in which cells may die representing approximately 13.5% of the total disc volume. In conclusion, this study experimentally determined TMJ disc metabolic rates, solute diffusivities, and disc morphometry, and through subject-specific FE modeling, revealed critical interactions between mechanical loading and nutrient supply and metabolism for the in vivo human TMJ disc. The results suggest that TMJ disc homeostasis may be vulnerable to pathological loading (e.g., clenching, bruxism), which impedes nutrient supply. Given difficulties associated with direct in vivo measurements, this study provides a new approach to systematically investigate homeostatic and degenerative mechanisms associated with the TMJ disc.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

Structure-Function Relationships of Temporomandibular Retrodiscal Tissue.

It is estimated that 2% to 4% of the US population will seek treatment for temporomandibular joint (TMJ) symptoms, typically occurring with anterior disc displacement. The temporomandibular retrodiscal tissue (RDT) has been postulated to restrict pathologic disc displacement. To elucidate RDT function, understanding regional RDT biomechanics and ultrastructure is required. No prior biomechanical analysis has determined regional variations in RDT properties or associated biomechanical outcomes with regional variations in collagen and elastin organization. The purpose of this study was to determine direction- and region-dependent tensile biomechanical characteristics and regional fibrillar arrangement of porcine RDT. Incremental stress relaxation experiments were performed on 20 porcine RDT specimens, with strain increments from 5% to 50%, a ramp-strain rate of 2% per second, and relaxation periods of 2.5 min. Tensile characteristics were determined between temporal and condylar regions and anteroposterior and mediolateral directions. RDT preparations were imaged using second-harmonic generation (SHG) microscopy for both collagen and elastin. Young's modulus showed significant differences by region ( P < 0.001) and strain ( P < 0.001). Young's modulus was <1 MPa from 5% to 20% strain, before increasing from 20% to 50% strain to a maximum of 2.9 MPa. Young's modulus trended higher in the temporal region and mediolateral direction. Instantaneous and relaxed moduli showed no significant difference by region or direction. Collagen arrangement was most organized near the disc boundary, with disorganization increasing posteriorly. Elastin was present at the disc boundary and RDT mid-body. Porcine RDT demonstrated region- and strain-dependent variations in tensile moduli, associated with regional differences in collagen and elastin. The small tensile moduli suggest that the RDT is not resistive to pathologic disc displacement. Further biomechanical analysis of the RDT is required to fully define RDT functional roles. Understanding regional variations in tissue stiffness and ultrastructure for TMJ components is critical to understanding joint function and for the long-term goal of improving TMJ disorder treatment strategies.

Newborn screening for sickle cell disease in Jamaica: logistics and experience with umbilical cord samples.

The study aims to describe the logistics and results of a programme for newborn screening for sickle cell disease based on samples from the umbilical cord. Samples were dried on Guthrie cards and analysed by high pressure liquid chromatography. All suspected clinically significant abnormal genotypes were confirmed by age 4-6 weeks with family studies and then recruited to local sickle cell clinics. The programme has screened 66,833 samples with the sickle cell trait in 9.8 % and the HbC trait in 3.8 %. Sickle cell syndromes occurred in 407 babies (204 SS, 148 SC, 35 Sbeta+ thalassaemia, 6 Sbetao thalassaemia, 6 sickle cell-variants, 8 sickle cell-hereditary persistence of fetal haemoglobin) and HbC syndromes in 42 (22 CC, 14 Cbeta+ thalassaemia, 1 Cbetao thalassaemia, 5 HbC- hereditary persistence of fetal haemoglobin). Focusing on the year 2015, screening was performed in 15,408, compliance with sample collection was 98.1 %, and maternal contamination occurred in 335 (2.6 %) but in only 0.05 % did diagnostic confusion require patient recall and further tests. This model of newborn screening for sickle cell disease is accurate, robust and economic. It is hoped that it may be helpful for other societies with high prevalence of abnormal haemoglobins and limited resources, who are planning to embark on newborn screening for sickle cell disease.

Evaluation of the mutagenicity of compounds of known carcinogenicity, belonging to the benz[a]anthracene, chrysene, and cyclopenta[a]phenanthrene series, using Ames's test.

Fifty-four polycyclic compounds, 29 of the cyclopenta[a]phenanthrene series, 11 chrysenes, and 14 benz[a]anthracenes, have been tested for mutagenicity by Ames's method, using Salmonella typhimurium TA100. Without exception all 37 carcinogens and a known initiator were mutagens. Of the 16 noncarcinogens 7 were mutagenic, but none of these has yet been tested for initiating, as opposed to carcinogenic, activity. There appeared to be little quantitative correspondence between carcinogenic and mutagenic potency, however, and possible reasons for this are discussed. The aryl hydrocarbon hydroxylase inhibitor 7,8-benzoflavone strongly inhibited the mutagenicity of certain compounds when it was added to the incubations.

An investigation into the binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to DNA in vitro.

After metabolic activation the carcinogen 15,16-dihydro-11-[3H]methylcyclopenta[a]phenanthren-17-one binds to DNA in vitro, and this binding is prevented by 7,8-benzoflavone. Radioactivity cannot be removed from the DNA with organic solvents or by chromatography on Sephadex G-50, even after heat denaturation of the DNA. Enzymatic hydrolysis yields radioactive fractions, which elute from a column of Sephadex LH-20 immediately after the natural nucleosides. At least two species of reactive metabolites are involved in this bending, those with a half-life of a few hr and others with greater stability. After extraction from the aqueous incubation mixture, they could be detected in discrete polar fractions from separations of the complex metabolite mixture by high-pressure liquid chromatography. Their ability to bind to DNA decreased with time at ambient temperature, and they were rapidly deactivated by acid. 7,8-Benzolflavone acted by suppressing the formation of polar metabolites derived from enzymatic oxidation of the aromatic double bonds. The inhibitor had no effect on the enzymes hydroxylating saturated carbon; hence it is unlikely that metabolism of the methyl group is important in conversion of this carcinogen to its proximate form, although the presence of the 11-methyl group is essential for carcinogenic activity in this series.

Mutagenesis in Chinese hamster cells by cyclopenta(a)phenanthrenes activated by a human hepatoma cell line.

The cyclopenta(a)phenanthrene, 15,16-dihydro-11-methyl-cyclopenta(a)phenanthren-17-one, had potent mutagenic activity in cell-mediated mutation assays with V79 Chinese hamster cells as targets, and cells of the human hepatoma line HepG2 as mediators of activation. The compound was inactive when low-passage hamster embryo cells were used as activators. When the mutagenic activity of a series of cyclopenta(a)phenanthrenes was compared in mutation assays with HepG2 cells as activators, there was a good correlation between mutagenic activity in this system and carcinogenic activity in mouse skin in vivo. One exception was a noncarcinogenic compound, which is mutagenic in the Ames' test, and was also mutagenic in the mammalian cell assay.

The relationship between metabolism, DNA binding, and carcinogenicity of 15,16-dihydro-11-methylcyclopenta(alpha)phenanthren-17-one in the presence of a microsomal enzyme inhibitor.

The mean latent period for skin tumor production by the carcinogen 15, 16-dihydro-11-methylcyclopenta [alpha] phenanthren-17-one (Compound IVb) in the mouse was 30 weeks for a dose of 60 mug/week and about 45 weeks for 60 mug/week, while at 0.6 mug/week, no tumors were observed during 100 weeks. Simultaneous administration of the closely related noncarcinogen (IVa) (54 mug/week) together with the carcinogen at 60 mug/week had no effect on the mean latent period. Simultaneous administration of a threefold quantity of the microsomal enzyme inhibitor 7, 8-benzoflavone (I) with the carcinogen at the highest dose increased the mean latent period to 38 weeks, while at the intermediate dose it completely suppressed tumor formation. Neither ketone IVa nor IVb bound covalently to calf thymus DNA in vitro without prior metabolic activation. After incubation with rat liver microsomes and NADPH in the presence of air, both ketones bound covalently to added DNA in vitro, the noncarcinogen (IVa) about four times more extensively than the carcinogen (IVb), roughly in proportion to the overall extents to which these ketones were metabolized. In contrast, overall metabolism of the carcinogen (IVb) was somewhat increased by the addition of a threefold quantity of the inhibitor (I) to the incubation mixture, but binding to added DNA was almost completely prevented. These results are discussed in connection with the hypothesis that cellular DNA is the target of the carcinogen (IVb) for tumor initiation.

Mutagenic and carcinogenic metabolites of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one.

Microsomal metabolites of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one (Structure I) were separated by high-pressure liquid chromatography, and their structures were established on the basis of their ultraviolet and mass spectra, together with considerations of their general chemical properties. This was assisted by comparisons with metabolites formed in the same way from the synthetic 15-hydroxy (Structure III), 16-hydroxy (Structure II), and 11-hydroxymethyl (Structure IV) derivatives, which themselves occur as metabolites of Structural I. Products derived from attack at the two benzo-ring double bonds occurred, but no K-region products were found. Only metabolites having a non-bay region 3,4-dihydrodiol system were mutagenic and bound to DNA after in vitro microsomal activation, and it was concluded that the 3,4-dihydro-3,4-diol (Metabolite e) was the main form and that the 3,4-diols of the monools (Structure II to IV) were minor proximate forms of this carcinogen. In a two-stage experiment, the synthetic 16-ol (Structure II) was shown to be almost as carcinogenic as was Structure I itself in mice; the 15-ol (Structure III) and 11-hydroxymethyl derivative (Structure IV) were much less active. The same order was also observed in the mutagenicity of these compounds in the Ames test.

Bay region distortions in cyclopenta[a]phenanthrenes.

Two newly synthesized cyclopenta[a]phenanthrenes, namely the 1-methyl (VIII) and 7,11-dimethyl (VII) derivatives of the parent ketone 15,16-dihydrocyclopenta[a]phenanthren-17-one (I), have been tested for their capacity to produce skin tumors in mice. The former (VIII) is essentially inactive, whereas the latter (VII) is very potent in both repeated application and two-stage tests. X-ray crystallographic structure analyses have been carried out on seven derivatives of (I), namely its 11-methyl (II), 11,12-dimethyl (III), 11-methoxy (V), 11-ethyl (VI) and 7,11-dimethyl (VII) analogues (carcinogens), the 1-methyl derivative (VIII), and 11,12,15,16-tetrahydro-11-methyl-17-oxocyclopenta[a]phenanthrene (IV) (both non-carcinogens). The detailed molecular structures resulting from these studies have shown the effects of steric interactions and substitutions on the bay-region geometry. The methyl group on C(11) causes distortions of the molecule in the bay region. Out-of-plane distortions in the bay regions of the 11-methyl derivatives (II, III, VII) are greater than for the 11-methoxy or the 11-ethyl derivatives (V, VI). Molecules (except for III and IV) are packed in the crystals with interactions that include C = O...H interactions; this packing is in layers that are nearly parallel to each other. A hydrogen atom of the 11-methyl group appears, from computer modeling, to interact sterically with the hydrogen atom of the bay-region expoxide group in the activated diol-epoxide; this steric interaction may force one conformer of the diol-epoxide to be the predominant form, thereby accounting for the importance of a bay-region methyl group. Further computer modeling has been used to analyze possible modes of interaction of the diol-epoxides of cyclopenta[a]phenanthrenes with DNA.

Mechanism of mouse skin tumor promotion by chrysarobin.

The skin tumor-promoting ability of 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) was compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1,8-dihydroxy-9-anthrone (anthralin) in SENCAR mice. Although dose-response comparisons indicated that chrysarobin was several orders of magnitude less potent than TPA for promoting papilloma formation, this anthrone was 1.5 to 2 times more potent than anthralin. Maximal papilloma responses were achieved by 15 weeks of promotion with TPA whereas at least 25 weeks of promotion were necessary to achieve maximal papilloma responses with chrysarobin or anthralin indicating marked differences in tumor latency between the two classes of compounds. Interestingly, at optimal promoting doses, chrysarobin gave a carcinoma response (22% with 0.3 carcinomas per mouse at 45 weeks) similar to that of TPA suggesting that this compound may be more efficient at promoting carcinomas than papillomas. In two-stage promotion experiments, chrysarobin was incapable of functioning independently as a Stage I or II promoter despite its complete promoting activity. Chrysarobin and TPA were compared at optimal promoting doses for their ability to induce: (a) skin edema, (b) epidermal hyperplasia, and (c) epidermal ornithine decarboxylase. In each case, distinct differences were noted between the two compounds. When taken together, the data support the hypothesis that anthracene-derived skin tumor promoters work at least in part by a mechanism different from the phorbol esters.

Characteristics and dying trajectories of adult hospital patients from acute care wards who die following review by the rapid response team.

A third of patients reviewed by rapid response teams (RRT) require end-of-life care. However, little is known about the characteristics and management of these patients following RRT review. This paper presents results of a retrospective, descriptive audit that explored the dying trajectory of adult ward inpatients who died outside of intensive care following RRT review. The study setting was a 430-bed tertiary New Zealand hospital during 2013. RRT, inpatient databases and hospital notes were used to identify 100 consecutive adult inpatients who died subsequent to RRT review. Outcome measures included time from RRT review to death, place of death, pre-existing co-morbidities and frequency of medical review. Results demonstrated that patients were old (median 77 years, IQR 63-85years), emergency admissions (n=100) and admitted under a medical specialty (n=71). All but one of the cohort had pre-existing co-morbidities (mean 3.2, SD 1.7), almost a third (n=31) had cancer and 51% had 1-4 previous inpatient admissions within the previous 12 months. The mean length of stay prior to RRT review was 4.9 days (SD 5.5) during which patients were frequently reviewed by senior medical staff (mean 6.8 times, SD 6.9, range 0-44). Twenty per cent of patients died after their first RRT review with a further 40% receiving treatment limitation/palliation. Fifty-two per cent of patients had a pre-existing DNAR. Eighty per cent of patients died in hospital. Whilst the RRT fulfils an unmet need in decision-making at end of life, there is a need to understand what RRT, instead of ward-based or palliative care teams, offers dying patients.

A mixed methods epidemiological investigation of preventable deaths among U.S. Army soldiers assigned to a rehabilitative warrior transition unit.

BACKGROUND: The prevalence of medical risk factors for suicide (e.g., mental disorders, severe disability, social disruption) may be higher among WTs compared to traditional Army units. Likewise, the extent to which traditional factors that protect soldiers from developing serious mental disorders (e.g., social support, unit cohesion, leadership) are present among soldiers assigned to the WTU is unclear. OBJECTIVES: An epidemiological consultation (EPICON) was conducted in 2010 to assess potential causes for a perceived high rate of suicides and preventable deaths in U.S. Army Warrior Transition Units (WTUs) and to identify potential improvements to the system of care. METHODS OF STUDY: The EPICON focused on: (1) risk factors for suicide/preventable deaths; (2) chronic pain management; (3) utilization of and access to WTU medical and behavioral health (BH) services; and (4) the impact of the WTU environment on mission focus and warrior disposition. BH history was examined for soldiers who died by suicide or preventable death while assigned to the WTU (index cases) and a representative comparison group of non-index case soldiers. Surveys and focus groups were conducted at four WTUs with Warriors in Transition (WTs) and key support staff. RESULTS: The use of psychotropic and/or CNS depressant medications, prevalence of BH diagnoses and substance use disorders, polypharmacy, alcohol use, and a high cumulative number of stressors were identified as important risk factors for preventable deaths in the WTC. Areas of potential improvement to the system of care included addressing negative perceptions of the WTU environment, lack of social support, barriers to accessing BH services and issues related to coordination of care. CONCLUSIONS: There was no one single risk factor found to be associated with an increased likelihood of preventable deaths within the WTU. The unique design and operation of the WTUs as environments focused on treatment and rehabilitation provide both benefits and challenges to recovery and risk mitigation.

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.