Reliability and validity of the training satisfaction questionnaire for family members (TSQ-FM) entering the ICU during an isolation disease outbreak.

BACKGROUND: The presence of family members in an isolated ICU during an isolation disease outbreak is restricted by hospital policies because of the infectious risk. This can be overcome by conferring to family members the skill and the ability to safely don and doff the personal protective equipment (PPE) through a nurse-led training intervention and assess their satisfaction, to respond to the need to define a safe, effective and quality care pathway focused on Family-Centered Care (FCC) principles. OBJECTIVE: the study aimed to build a valid and reliable instrument for clinical practice to assess family members' satisfaction to allow ICU nurses to restore family integrity in any case of infectious disease outbreak that requires isolation. METHODS: A cross-sectional study was conducted to test the psychometric properties. The questionnaire was constructed based on a literature review on the needs of family members in the ICU. 76 family members were admitted to a COVID-ICU. Cronbach's coefficient, Geomin rotated loading, and EFA were applied to assess the reliability and validity of the instrument. RESULTS: The Kaiser-Mayer-Olkin (KMO) measure was 0.662, the Bartlett sphericity test showed a significant p-value (χ²=448.33; df=45; p < 0.01), Cronbach's alpha coefficient was.896. A further CFA analysis confirmed that all fit indices were acceptable. The results showed satisfactory validity and reliability, which could be generalized and extended to any outbreak of isolation disease. CONCLUSIONS: This study provides a valid and reliable instrument for clinical practice to maintain family integrity in the dyadic relationship between the patient and the family member, even during an emergency infectious disease outbreak that requires isolation.

Quality of life in ICU survivors and their relatives with post-intensive care syndrome: A systematic review.

BACKGROUND: Post-intensive care syndrome (PICS) is characterized by all three adverse survivorship dimensions: physical function, cognitive function and mental health status. AIM: This review aimed to describe the quality of life (QoL) of Intensive Care Unit (ICU) survivors with PICS after discharge and of their relatives with Family Post-intensive care syndrome (PICS-F) and to report anxiety, depression and Post-Traumatic Stress Disorders (PTSD) in studies investigating PICS. STUDY DESIGN: A systematic review was carried out. We searched PubMed, Scopus, Web of Science and the Cumulative Index to Nursing and Allied Health Literature. This review was registered in the PROSPERO database (CRD42022382123). RESULTS: We included 19 studies of PICS and PICS-F in this systematic review. Fourteen observational studies report the effects of PICS on depression, 12 studies on anxiety and nine on post-traumatic stress disorder and 10 on QoL. Mobility, personal care, usual activities and pain/discomfort in QoL were the domains most affected by PICS. A significant association was demonstrated between a high level of ICU survivors' anxiety and high levels of ICU relatives' burden. Strain-related symptoms and sleep disorders were problems encountered by ICU relatives with PICS-F. CONCLUSION: PICS and PICS-F were widespread experiences among ICU survivors and their ICU relatives, respectively. The results of this review showed the adverse effects of PICS and PICS-F on QoL. RELEVANCE TO CLINICAL PRACTICE: PICS and PICS-F strongly impact the rehabilitation process and are measured in terms of health costs, financial stress and potentially preventable readmission.

Nurses quality of life, sleep disturbance, and intention to leave critical care units: A cross-sectional moderated mediation analysis.

OBJECTIVES: This study aims to explore the complex relationships between personal and demographic factors, intermediary factors such as quality of life (depression, anxiety, stress, burnout), and the mediating impact of sleep disturbance on nurses' intention to leave critical care units. DESIGN: Cross-sectional quantitative survey. SETTING: Data were collected from registered nurses at a major university hospital in southern Italy. Seven inpatient critical care units were sampled. MAIN OUTCOME MEASURES: Intention to leave critical care units. RESULTS: We included 160 participants recruited over five weeks in May and June 2023. The data showed that most were female, married, and possessed a bachelor's degree in nursing. The mean quality of life score was moderate, while stress, anxiety, and burnout were mild. A significant percentage of nurses reported poor sleep quality. Logistic regression indicates that service length did not significantly impact the intention to leave. The structural equation model showed that stress positively correlated with emotional exhaustion, whereas job quality was negatively associated with emotional exhaustion and the intention to leave. Sleep disturbance did not explain the relationship between stress and emotional fatigue; however, the results revealed that male gender moderated sleep mediation. CONCLUSIONS: This study investigated factors influencing intention to leave among critical care unit nurses. The results suggest that the role of sleep disturbance should always be considered when assessing the issue. In this chain of causes, sleep disturbance explains the relationship between stress and emotional exhaustion. Furthermore, the strength of this mediation was influenced by gender, particularly by the male gender. IMPLICATIONS FOR CLINICAL PRACTICE: Stress and emotional exhaustion significantly impact nurses' working quality of life, particularly when sleep quality is taken into account. This leads to a higher intention to leave critical care units. To reduce this tendency, healthcare managers could implement specific evidence-based interventions to promote a good climate of work, which would positively affect stress, emotional exhaustion and sleep disturbance. The likelihood of intention to leave decreased with achieving personal self-fulfilment among nurses.

The lived experiences of family members who visit their relatives in Covid-19 intensive care unit for the first time: A phenomenological study.

BACKGROUND: COVID-19 patient experiences in the intensive care unit (ICU) are marked by family separation. Families understand the importance of isolation and hospital visiting policies, but they consider it necessary to visit their loved ones and use personal protective equipment. OBJECTIVE: To describe the lived experiences of family members in their first contact with a relative in a COVID-ICU. METHODS: A phenomenological study was conducted using Cohen's method. The subjects were interviewed using an open-question format to allow them full freedom of expression. Twelve family members were recruited between February and March 2021. RESULTS: Analysis of the qualitative data resulted in five major themes: (1) fear of contagion related to donning/doffing procedures, (2) positive emotions related to first contact with the hospitalized relative, (3) concern for the emotional state of the hospitalized relative, (4) impact of the COVID-ICU and comparisons between imagination and reality regarding the severity of the disease, and (5) recognition of and gratitude toward healthcare professionals. CONCLUSIONS: It has been confirmed that visits to the ICU reduce anxiety among family members. Our findings constitute an internationally relevant contribution to understanding of the needs of relatives who meet loved ones for the first time while wearing personal protective equipment.

The lived experiences of family members of Covid-19 patients admitted to intensive care unit: A phenomenological study.

INTRODUCTION: The family members of a patient admitted to a COVID Intensive Care Unit (COVID-ICU) could not communicate with and stay close to their loved one, which resulted in them becoming dependent on hospital staff for remote updates. OBJECTIVE: To describe the lived experiences of families with a member admitted to a COVID-ICU. METHODS: A phenomenological study was conducted. The subjects were interviewed with open-ended questions to allow them full freedom of expression. The researchers involved in the analysis immersed themselves in the data, independently reading and rereading the transcripts to gain a sense of the entire dataset. RESULTS: Fourteen first-degree family members were recruited. Five main themes emerged: fear, detachment, life on standby, family-related loneliness in the COVID-ICU, and an unexpected event. CONCLUSIONS: Knowing the experience of families who have a relative in the COVID-ICU is essential for recognizing and reducing the risk of developing symptoms of post-intensive care syndrome.

Statins Reduce Intratumor Cholesterol Affecting Adrenocortical Cancer Growth.

Mitotane causes hypercholesterolemia in patients with adrenocortical carcinoma (ACC). We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to estrogen receptor α (ERα) action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated their relationship with patients' survival in ACC TCGA. We then blocked cholesterol synthesis with simvastatin and determined the effects on H295R cell proliferation, estradiol production, and ERα activity in vitro and in xenograft tumors. We found that mitotane increases intratumor cholesterol content and expression of genes involved in cholesterol homeostasis, among them INSIG, whose expression affects patients' survival. Treatment of H295R cells with simvastatin to block cholesterol synthesis decreased cellular cholesterol content, and this affected cell viability. Simvastatin reduced estradiol production and decreased nuclear and mitochondrial ERα function. A mitochondrial target of ERα, the respiratory complex IV (COXIV), was reduced after simvastatin treatment, which profoundly affected mitochondrial respiration activating apoptosis. Additionally, simvastatin reduced tumor volume and weight of grafted H295R cells, intratumor cholesterol content, Ki-67 and ERα, COXIV expression and activity and increase terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Collectively, these data demonstrate that a reduction in intratumor cholesterol content prevents estradiol production and inhibits mitochondrial respiratory chain-inducing apoptosis in ACC cells. Inhibition of mitochondrial respiration by simvastatin represents a novel strategy to counteract ACC growth.

Cholesterol as an Endogenous ERRα Agonist: A New Perspective to Cancer Treatment.

The estrogen-related receptors (ERRs) are important members of nuclear receptors which contain three isoforms (α, ß, and γ). ERRα is the best-characterized isoform expressed mainly in high-energy demanding tissues where it preferentially works in association with the peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and PGC-1ß. ERRα together with its cofactors modulates cellular metabolism, supports the growth of rapidly dividing cells, directs metabolic programs required for cell differentiation and maintains cellular energy homeostasis in differentiated cells. In cancer cells, the functional association between ERRα and PGC-1s is further influenced by oncogenic signals and induces metabolic programs favoring cell growth and proliferation as well as tumor progression. Recently, cholesterol has been identified as a natural ERRα ligand using a combined biochemical strategy. This new finding highlighted some important physiological aspects related to the use of cholesterol-lowering drugs such as statins and bisphosphonates. Even more meaningful is the link between increased cholesterol levels and certain cancer phenotypes characterized by an overexpressed ERRα such as mammary, prostatic, and colorectal cancers, where the metabolic adaptation affects many cancer processes. Moreover, high-energy demanding cancer-related processes are strictly related to the cross-talk between tumor cells and some key players of tumor microenvironment, such as tumor-associated macrophage that fuels cancer progression. Some evidence suggests that high cholesterol content and ERRα activity favor the inflammatory environment by the production of different cytokines. In this review, starting from the most recent observations on the physiological role of the new signaling activated by the natural ligand of ERRα, we propose a new hypothesis on the suitability to control cholesterol levels as a chance in modulating ERRα activity in those tumors in which its expression and activity are increased.

Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment.

Cholesterol is essential for cell function and viability. It is a component of the plasma membrane and lipid rafts and is a precursor for bile acids, steroid hormones, and Vitamin D. As a ligand for estrogen-related receptor alpha (ESRRA), cholesterol becomes a signaling molecule. Furthermore, cholesterol-derived oxysterols activate liver X receptors (LXRs) or estrogen receptors (ERs). Several studies performed in cancer cells reveal that cholesterol synthesis is enhanced compared to normal cells. Additionally, high serum cholesterol levels are associated with increased risk for many cancers, but thus far, clinical trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have had mixed results. Statins inhibit cholesterol synthesis within cells through the inhibition of HMG-CoA reductase, the rate-limiting enzyme in the mevalonate and cholesterol synthetic pathway. Many downstream products of mevalonate have a role in cell proliferation, since they are required for maintenance of membrane integrity; signaling, as some proteins to be active must undergo prenylation; protein synthesis, as isopentenyladenine is an essential substrate for the modification of certain tRNAs; and cell-cycle progression. In this review starting from recent acquired findings on the role that cholesterol and its metabolites fulfill in the contest of cancer cells, we discuss the results of studies focused to investigate the use of statins in order to prevent cancer growth and metastasis.

GPER-independent inhibition of adrenocortical cancer growth by G-1 involves ROS/Egr-1/BAX pathway.

We previously demonstrated that treatment of the H295R adrenocortical cancer cell line with the non-steroidal, high-affinity GPER (G protein-coupled estrogen receptor 1) agonist G-1 reduced tumor growth in vitro and in vivo through a GPER independent action. Moreover, we observed that G-1 treatment induces cell-cycle arrest and apoptosis following a sustained ERK1/2 activation. However, the precise mechanisms causing these effects were not clarified. Starting from our preliminary published results, we performed a microarray study that clearly evidenced a strong and significative up-regulation of EGR-1 gene in H295R cells treated for 24h with micromolar concentration of G-1. The microarray findings were confirmed by RT-PCR and Western-blot analysis as well as by immunofluorescence that revealed a strong nuclear staining for EGR-1 after G-1 treatment. EGR-1 is a point of convergence of many intracellular signaling cascades that control tumor cell growth and proliferation as well as others that relate to cell death machinery. Here we found that the increased Egr-1 expression was a consequence of G-1-mediated ROS-dependent ERK activation that were promptly reversed by the presence of the antioxidant n-acetyl-cysteine. Finally, we observed that silencing EGR-1 gene expression reversed the main effects induced by G-1 in ACC cells, including upregulation of the negative regulator of cell cycle, p21Waf1/Cip1 and the positive regulator of mitochondrial apoptotic pathway, BAX, as well as the cell growth inhibition. The identified ROS/MAPK/Egr-1/BAX pathway as a potential off-target effect of the G-1 could be useful in implementing the pharmacological approach for ACC therapy.

In Vitro Inhibition of 4-Nitroquinoline-1-Oxide Genotoxicity by Probiotic Lactobacillus rhamnosus IMC501.

Inhibition of 4-nitroquinoline-1-oxide (4-NQO) genotoxicity by a probiotic strain of Lactobacillus rhamnosus (IMC501) was assessed by the prokaryotic short-term bioassay SOSChromotest, using Escherichia coli PQ37 as the target organism. Results showed the ability of strain IMC501 to rapidly and markedly counteract, in vitro, the DNA damage originated by the considered genotoxin. The inhibition was associated with a spectroscopic hypsochromic shift of the original 4-NQO profile and progressive absorbance increase of a new peak. IR-Raman and GC-MS analyses confirmed the disappearance of 4-NQO after contact with the microorganism, showing also the absence of any genotoxic molecule potentially available for metabolic activation (i.e., 4-hydroxyaminoquinoline-1-oxide and 4-nitrosoquinoline-1-oxide). Furthermore, we have shown the presence of the phenyl-quinoline and its isomers as major non-genotoxic conversion products, which led to the hypothesis of a possible pattern of molecular transformation. These findings increase knowledge on lactobacilli physiology and contribute to the further consideration of antigenotoxicity as a nonconventional functional property of particular probiotic strains.

Protective effects of probiotic Lactobacillus rhamnosus IMC501 in mice treated with PhIP.

The aim of the present study was to investigate the antigenotoxic properties of the probiotic Lactobacillus rhamnosus IMC501; DNA damage was induced by one representative food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Mice were treated orally with suspensions of lactobacilli for 10 days before administration of food mutagen. During the treatment, the abundance of lactobacilli in feces, as assessed by qPCR analysis, increased, whereas ß-glucuronidase and N-acetyl-ß-glucosaminidase activities decreased. The extent of DNA damage was measured in colon and liver cells by comet assay. In colonocytes, diet supplementation with IMC501 resulted in a significant inhibition of DNA damage induced by PhIP. The results obtained in this in vitro study suggest that Lactobacillus rhamnosus IMC501 used as a dietary supplement can provide a useful integration of antimutagen food components of the normal diet, which are generally lower than the protective level.

Food borne yeasts as DNA-bioprotective agents against model genotoxins.

Yeasts isolated from Italian beverages and foods (wine and cheeses) were identified as Saccharomyces cerevisiae and Debaryomyces hansenii by sequencing the D1/D2 domain of the 26S rRNA gene and differentiated, at strain level, by microsatellite PCR fingerprinting and RAPD-PCR. All the strains showed antioxidant activity, as demonstrated by their ability to scavenge the free radical diphenyl-1-picrylhydrazyl (DPPH). Furthermore, tested strains revealed high in vitro inhibitory activity against two model genotoxins, 4-nitroquinoline-1-oxide (4-NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), as showed by short-term methods with different target cells: SOS-Chromotest with Escherichia coli PQ37 and Comet assay with HT-29 enterocytes. High inhibitory activity towards 4-NQO was associated with cell viability, while heat-inactivated cells showed a reduced antigenotoxic capability. Surprisingly, high inhibition of MNNG genotoxicity was observed even with heat-treated cells. Moreover, the strains able to inhibit the genotoxins induced some changes in the spectroscopic properties of the original compound. This result perfectly agrees with the information obtained by the two bioassays. Interestingly, strains characterized for antioxidant and antigenotoxic properties, also presented acid-bile tolerance, indicating that food autochthonous yeasts could be expected to reach gut in viable form and thus prevent genotoxin DNA damage in situ.

Raw milk traditional Italian ewe cheeses as a source of Lactobacillus casei strains with acid-bile resistance and antigenotoxic properties.

Twenty-five Lactobacillus casei group strains isolated from ewe cheeses from Abruzzo region, central Italy, were identified by 16S rRNA gene sequencing, differentiated by RAPD-PCR analysis and characterized as in vitro for acid-bile tolerance and antigenotoxic properties. All the strains were very susceptible to simulated gastric fluid (pH 2.0) but most of them recovered viability (ca. 2-3 log-units) when transferred and maintained in simulated intestinal fluid (0.5% w/v bovine bile) for 3 h. Some strains showed potential for deactivating representative genotoxins as highlighted by the SOS-Chromotest. Twelve were active and nine moderately active against 4-nitroquinoline-1-oxide, and one active and only one moderately active against N-methyl-N'-nitro-N-nitrosoguanidine. The active strains produced evident spectroscopic modification of genotoxins after co-incubation. Most isolates with antigenotoxic activity resulted as acid-bile tolerant demonstrating that cheese autochthonous lactobacilli may reach the gut as a viable form and prevent genotoxin DNA damage.

Modulatory activity of a Lactobacillus casei strain on 1,2-dimethylhydrazine-induced genotoxicity in rats.

The present study was designed to investigate the putative antigenotoxic effects of supplementing the diet of rats treated with the colon carcinogen 1,2-dimethylhydrazine hydrochloride (DMH) with a Lactobacillus casei strain using an in vivo approach. The antigenotoxic response was evaluated in colon and liver cells using the alkaline comet assay. Since the balance between the bioactivation and detoxification metabolic pathways is crucial for the formation of toxic and genotoxic metabolites, alterations in the level of some xenobiotic metabolizing enzymes (XME) were studied in liver preparations. In the challenge group (L. casei + DMH), lactobacilli-supplemented diet, there was a decrease in the extent of DMH-induced DNA damage, especially in colon cells. Compared with control rats, there was less basal DNA damage in colon cells of rats fed on a lactobacilli-supplemented diet. These findings are the first to give clear evidence of DNA-protective effects of lactobacilli against basal DNA damage. Moreover, the chemopreventive effects were accompanied by changes in the activities of several XME. The observed decrease in the concentration of nonenzymatic antioxidants (i.e. GSH) and the reduced activity of enzymatic antioxidants (i.e., GST, GPx, and SOD) in liver could reflect an overall reduction in the level of oxidative stress in rats on a diet supplemented with the L. casei suspension compared with control rats (basal state). Thus, the concentrations of GSH and the activities of GST, GPx, and SOD could be downregulated by supplementing the diet with L. casei as a response to an improved antioxidant status.

Evidence for in vitro anti-genotoxicity of cheese non-starter lactobacilli.

The inhibition of direct acting DNA reactive agents by 63 non-starter lactobacilli isolated from raw ewes milk cheeses was examined by short-term assay (SOS-Chromotest) and compared with already characterized starter lactobacilli. The screening revealed strains active against the nitroarene 4-nitroquinoline-1-oxide (NQO) and the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in different species of the genus Lactobacillus (L. rhamnosus, L. casei, L. plantarum, L. brevis, Lactobacillus spp.). It was proved that the anti-genotoxicity was strain-dependent, and always associated with spectroscopic modification of genotoxins. The frequency of strains inhibiting nitroarene genotoxicity was comparable for non-starter and starter lactobacilli, whereas inhibition of the alkylating agent was largely predominant in non-starter isolates. Seventeen strains presented inhibitory activity against both genotoxins. DNA RAPD-PCR performed with M13, Pro-Up and RPO2 primers on the lactobacilli under examination showed genetic diversity in these strains. The non-starter isolates clustered in seven groups and the strains presenting a high degree of activity against 4-nitroquinoline-1-oxide clustered in a single group with a similarity around 75%. Interestingly, the strains with anti-genotoxic properties also showed acid-bile tolerance, indicating that the autochthonous lactobacilli which survive cheese ripening may also reach the gut as viable cells and could prevent genotoxin DNA damage to enterocytes, as is desirable for probiotic bacteria.

Inhibition of 4-nitroquinoline-1-oxide genotoxicity by Bacillus strains.

The effect of 16 Bacillus strains from pharmaceutical probiotic preparations (Bacillus spp.) and collection (B. subtilis, B. firmus, B. megaterium, B. pumilus) on genotoxicity induced by the known mutagen 4-nitroquinoline-1-oxide (4-NQO) was studied using the short-term bacterial assay SOS-chromotest. with Escherichia coli PQ37 as the tester organism. It was found that the activity of 0.1 mM 4-NQO was reduced (P < 0.01) after coincubation with Bacillus suspensions (10(8) CFU/ml for 150 min at 37 degrees C). All isolates showed potential for deactivating 4-NQO, and genotoxicity inhibition ranged from 92.9 to 100%. There were no appreciable differences in behaviour observed among probiotic and collection strains or in relation to species. The observed antigenotoxicity was associated with a clear-cut modification of 4-NQO molecular characteristics.

Lactic acid bacteria isolated from dairy products inhibit genotoxic effect of 4-nitroquinoline-1-oxide in SOS-chromotest.

Antigenotoxic activity against 4-nitroquinoline-1-oxide (4-NQO) of lactic acid bacteria isolated from commercial dairy products was studied using SOS-Chromotest. The supernatants from bacteria-genotoxin co-incubations in general exhibited a strong suppression on SOS-induction produced by 4-NQO on the tester organism Escherichia coli PQ37 (sfiA::lacZ). High genotoxicity inhibition (>75%) was found for 31/67 of the examined bacteria and the maximum values of some strains within the species were as follows: Lactobacillus casei, 99.1%; L. plantarum, 93.3%; L. rhamnosus, 93.4%; L. acidophilus, 90.9%; L. delbrueckii subsp. bulgaricus, 85.7% and Bifidobacterium bifidum, 89.6%; Strains with low antigenotoxicity (5-60%) were evidenced in both L. acidophilus and L. delbrueckii subsp. bulgaricus, whereas some inactive strains were found only in L. casei and L. delbrueckii subsp. bulgaricus. Cell exposure to 100 degrees C for 15 min prevented antigenotoxicity and no effect was evidenced for cell-free spent media. The active strains survived at 0.1 mM 4-NQO exposure and generally presented some relevant functional properties, such as tolerance to bile (0.5%) or acid environment (pH 2.0) and adherence to Caco-2 enterocytes. Antigenotoxicity was always associated with modification of the 4-NQO absorbance profile.