Staff Turnover Intention at Long-Term Care Facilities: Implications of Resident Aggression, Burnout, and Fatigue.

OBJECTIVES: Staff shortages and the high turnover rate of nursing assistants pose great challenges to long-term care. This study examined the effects of aggression from residents of long-term care facilities, burnout, and fatigue on staff turnover intention. The findings will help managers to devise effective measures to retain their staff. DESIGN: Cross-sectional descriptive study design. SETTING AND PARTICIPANTS: A total of 800 nursing assistants were recruited from 70 long-term care facilities using convenience sampling. METHODS: The participants were individually interviewed and provided information about their turnover intention, resident aggression witnessed and experienced, self-efficacy, neuroticism, burnout, fatigue, and personal and facility characteristics. RESULTS: Hierarchical multiple regression analysis revealed that the size and organizational practices of long-term care facilities were not associated with staff turnover intention. Staff who spent less time in the industry reported witnessing resident-to-resident aggression, experienced resident-to-staff aggression, reported high levels of burnout, had acute or chronic fatigue, and had low levels of inter-shift recovery were more likely than others to report a high turnover intention. CONCLUSIONS AND IMPLICATIONS: Staff turnover poses great challenges to staff, residents, and organizations. This study identified important factors that may help support staff in long-term care facilities. Specific measures, such as person-centered care to diminish resident aggression by addressing residents' unmet needs, work-directed programs to mitigate burnout and improve staff mental health, and flexible schedules to prevent fatigue should also be advocated to prevent staff turnover.

Typology of family caregivers of older persons: A latent profile analysis using elder mistreatment risk and protective factors.

This study sought to identify subpopulations of caregivers of older persons based on their profiles of individual characteristics and caregiving contexts and aimed at examining the associations between caregiver profiles and elder mistreatment. A convenient sample of 600 adult caregivers of community-dwelling older people in Hong Kong participated. Results of latent profile analysis support a typology of 3 distinctive caregiver profiles: (a) non-vulnerable caregivers; (b) isolated, vulnerable caregivers; and (c) traumatized, vulnerable caregivers. Isolated and traumatized caregivers reported greater risk factors related to elder mistreatment: They had higher levels of caregiver stress and burden, lower levels of social support and resilience, greater neurotic personality orientation and problematic gambling behavior, and more severe childhood traumatic experiences. The two groups also display significantly higher level of abusive behaviors than non-vulnerable caregivers.

Trends in elder abuse and age discrimination during the COVID-19 pandemic in Hong Kong: Findings from a two-wave representative telephone survey study.

OBJECTIVES: Empirical evidence about the heightened risks of elder abuse and age discrimination during the COVID-19 pandemic is scarce. This study aimed to track the changes in rates of both, and investigated their associated factors in the community-dwelling older population in Hong Kong. METHODS: In this two-wave, cross-sectional telephone survey, we interviewed a population-based sample of individuals (≥55 years), and captured the situation of elder abuse and age discrimination before the COVID-19 outbreak (n = 1209, Wave 1: October-December 2019) and during the pandemic (n = 891, Wave 2: December 2020-January 2021). Participants reported their experiences of different types of abuse and discrimination, financial health, subjective well-being, satisfaction with environment, health and social services, and resilience. RESULTS: Abuse was reported by 20.2% of the sample before the outbreak and 17.8% during the pandemic; while discrimination was reported by 24.6% and 29.8% at the two time points, respectively. A drop in physical abuse was observed, but it was accompanied by a rise in discrimination in the form of harassment or refusal of services. Findings of logistic regression analysis show that abuse during the pandemic was associated with younger age, poorer subjective well-being, and lower resilience; while discrimination was associated with female gender, being married, and poorer subjective well-being. CONCLUSIONS: Elder abuse and discrimination were prevalent across time points. The pandemic has highlighted the marginalization of older persons in our communities. There is an urgent need for development of effective interventions to end abuse and discrimination.

Physical, psychological and pandemic fatigue in the fourth wave of COVID-19 outbreak in Hong Kong: population-based, cross-sectional study.

OBJECTIVES: To examine the physical, psychological and pandemic fatigue during the COVID-19 pandemic, and to explore the correlates of fatigue using a representative, population-based, community sample of Chinese adults in Hong Kong. DESIGN: Cross-sectional study. SETTING: Telephone surveys in Hong Kong from December 2020 to January 2021 (during the fourth wave of COVID-19 outbreak). PARTICIPANTS: 1255 adults living in Hong Kong aged 18 years or older sampled using a multistage approach (53% women). MAIN OUTCOME MEASURES: Physical and psychological fatigue: The Fatigue Assessment Scale (with a cut-off score of 22). Pandemic fatigue: Adherence to six disease prevention measures (DPM) recommended by the government. RESULTS: About 25.7% of the participants were feeling fatigued physically and psychologically. Physical and psychological fatigue was not directly associated with pandemic fatigue, and their association was fully mediated by self-perceived disruptions of COVID-19-related restrictions in daily life. Results from the hierarchical regression analysis showed that higher levels of fatigue were associated with economically inactive status (B=0.18, SE=0.04, p<0.001), having family or friend infected with COVID-19 before or during the study (B=0.17, SE=0.01, p<0.001), lower acceptability of DPM (B=-0.16, SE=0.03, p<0.001), greater disruptions in daily life (B=0.22, SE=0.02, p<0.001), and greater trust in authorities in ending the pandemic (B=0.11, SE=0.02, p<0.001). CONCLUSIONS: Fatigue affected many individuals during the pandemic. Disruptions of DPM in daily life may serve as a mediator in the association between pandemic fatigue and physical and psychological fatigue, reflecting the need of effective interventions to reduce self-perceived disruptions of COVID-19-related restrictions in the general population. Resources should be allocated to provide sufficient services to individuals vulnerable to fatigue during the prolonged pandemic.

Predictors of COVID-19 actual vaccine uptake in Hong Kong: A longitudinal population-based survey.

Purpose of the research: Identifying predictors of COVID-19 vaccine uptake decisions is central to the development of evidence-based strategies for promoting vaccination. This longitudinal study investigated the link between previous willingness to vaccinate and vaccine uptake decision, and examined potential predictors of vaccine uptake in Hong Kong. Methods: A longitudinal telephone survey study was conducted using a population-based sample of Chinese adult residents (≥18 years) in Hong Kong. Data were collected at two time points: T1 (December 2020-January 2021) and T2 (June-July 2021). Primary outcome was vaccine uptake status; whilst independent variables and covariates included socio-demographic factors, COVID-19 related experiences, health beliefs, and perception, as well as vaccine related perceptions. Results: Among the 1,003 participants, 23.7% had received a COVID-19 vaccine. Previous willingness to vaccinate did not predict vaccine uptake at later stage. Vaccine uptake by known others (aOR = 8.00), trust in authorities (aOR = 1.53), acceptability of non-pharmaceutical preventive measures (aOR = 2.96), and first-hand experience of COVID-19 (aOR = 1.32) were significant predictors of vaccine uptake after adjusting for confounding factors. Conclusions: Future strategies to promote vaccination may focus on building public trust in government and healthcare professional, and encouraging vaccinated individuals to share their vaccine uptake status via social networking.

Predicting Public Adherence to COVID-19 Preventive Measures: A Cross-Sectional Study in Hong Kong.

Objectives: To effectively control the spread of COVID-19, the public's adherence to relevant disease preventive measures (DPM) is critical. This study examined individuals' adherence to various DPM and identified facilitators and barriers to adherence in a community sample in Hong Kong. Methods: In this cross-sectional study, telephone surveys were conducted over December 2020 and January 2021. Participants provided responses on their adherence to DPM as well as other psychosocial and cognitive factors via the phone. Results: Of the sample of 1255 Chinese adults (aged >18 years, 53% women), 94.4% wore face masks in public areas; 88.4% avoided touching their eyes, nose, and mouth; 82.1% performed hand hygiene practices; 81.5% used alcohol-based hand rubs; 74.6% abided by social distancing; and 39.7% tested for COVID-19 on a voluntary basis. Perceived benefits, perceived barriers, self-efficacy, cues to action, perceived acceptability, and disruptions to daily life related to COVID-19 were associated with individuals' adherence to DPM. Conclusions: Adherence to DPM was strong in Hong Kong, and the adherence level could be predicted by various factors. It is vital to consider these factors in order to improve the public's adherence.

Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Neopterin is associated with plaque inflammation and destabilisation in human coronary atherosclerotic lesions.

BACKGROUND: Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages. OBJECTIVE: To elucidate the role of neopterin in coronary plaque destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). PATIENTS AND METHODS: All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n = 25) and UAP (n = 25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils and neopterin. RESULTS: In 22/25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (p<0.001) in patients with UAP than in patients with SAP. Moreover, the neopterin-positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, p<0.001; T cells, r = 0.70, p<0.001). CONCLUSIONS: Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.

Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography.

OBJECTIVE: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). METHODS: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2-4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months' follow up. Percentage increase in LV end diastolic volume (%DeltaEDV) was also calculated. RESULTS: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %DeltaEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%DeltaEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). CONCLUSION: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling.

Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan.

OBJECTIVES: To determine the clinical features of a novel heart syndrome with transient left ventricular (LV) apical ballooning, but without coronary artery stenosis, that mimics acute myocardial infarction, we performed a multicenter retrospective enrollment study. BACKGROUND: Only several case presentations have been reported with regard to this syndrome. METHODS: We analyzed 88 patients (12 men and 76 women), aged 67 +/- 13 years, who fulfilled the following criteria: 1) transient LV apical ballooning, 2) no significant angiographic stenosis, and 3) no known cardiomyopathies. RESULTS: Thirt-eight (43%) patients had preceding aggravation of underlying disorders (cerebrovascular accident [n = 3], epilepsy [n = 3], exacerbated bronchial asthma [n = 3], acute abdomen [n = 7]) and noncardiac surgery or medical procedure (n = 11) at the onset. Twenty-four (27%) patients had emotional and physical problems (sudden accident [n = 2], death/funeral of a family member [n = 7], inexperience with exercise [n = 6], quarreling or excessive alcohol consumption [n = 5] and vigorous excitation [n = 4]). Chest symptoms (67%), electrocardiographic changes (ST elevation [90%], Q-wave formation [27%] and T-wave inversion [97%]) and elevated creatine kinase (56%) were found. After treatment of pulmonary edema (22%), cardiogenic shock (15%) and ventricular tachycardia/fibrillation (9%), 85 patients had class I New York Heart Association function on discharge. The LV ejection fraction improved from 41 +/- 11% to 64 +/- 10%. Transient intraventricular pressure gradient and provocative vasospasm were documented in 13/72 (18%) and 10/48 (21%) of the patients, respectively. During follow-up for 13 +/- 14 months, two patients showed recurrence, and one died suddenly. CONCLUSIONS: A novel cardiomyopathy with transient apical ballooning was reported. Emotional or physical stress might play a key role in this cardiomyopathy, but the precise etiologic basis still remains unclear.

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.

Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

Moyamoya disease and coronary artery disease--case report.

A 26-year-old female with idiopathic moyamoya disease developed chest pain with concomitant ST depression on electrocardiography. Coronary angiography detected no stenotic lesions in the epicardial coronary arteries. The clinical diagnosis was vasospastic angina pectoris. She was medicated with calcium antagonists, which reduced the frequency of chest pain episodes. Angina pectoris is a rare occurrence in young patients with moyamoya disease. Coronary artery disease and moyamoya disease may have common etiological factors.

Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response.

The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCACG. We recently proposed that ER stress response factor (ERSF) binding to ERSE is a heterologous protein complex consisting of the constitutive component NF-Y (CBF) binding to CCAAT and an inducible component binding to CCACG and identified the basic leucine zipper-type transcription factors ATF6alpha and ATF6beta as inducible components of ERSF. ATF6alpha and ATF6beta produced by ER stress-induced proteolysis bind to CCACG only when CCAAT is bound to NF-Y, a heterotrimer consisting of NF-YA, NF-YB, and NF-YC. Interestingly, the NF-Y and ATF6 binding sites must be separated by a spacer of 9 bp. We describe here the basis for this strict requirement by demonstrating that both ATF6alpha and ATF6beta physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6alpha and ATF6beta bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6alpha and/or beta and capable of binding to ERSE is indeed formed when the cellular UPR is activated. We concluded that ATF6 homo- or heterodimers recognize and bind directly to both the DNA and adjacent protein NF-Y and that this complex formation process is essential for transcriptional induction of ER chaperones.

ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response.

Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by the cis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N(9)-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1.

[Does reperfusion therapy reduce complications in acute inferior myocardial infarction?].

Both right ventricular infarction and complete atrioventricular block were frequently seen in patients with acute inferior myocardial infarction before the introduction of reperfusion therapy (RT). However, the effect of reperfusion therapy on these 2 complications is not well known. To evaluate the effect of reperfusion therapy in them, we retrospectively studied the in-hospital outcome of 103 consecutive patients with acute inferior myocardial infarction within 72 hr after the onset, 23 with right ventricular infarction and 36 with complete atrioventricular block. Patients were divided into 2 groups: RT group (n = 63) in which Thrombolysis in Myocardial Infarction (TIMI) III flow was obtained by reperfusion therapy within 24 hr after the onset, and the non-RT group (n = 40) in which TIMI III flow was not obtained or did not receive reperfusion therapy. Patients with right ventricular infarction in the RT group had a larger proportion of proximal occlusion of the right coronary artery and the absence of preinfarction angina. There were no effects of perfusion on complete atrioventricular block. In 23 patients with right ventricular infarction and 36 patients with complete atrioventricular block, in-hospital stay, duration of using temporary pacing and Swan-Ganz catheter were shorter in the RT group than the non-RT group. Reperfusion therapy does not decrease the incidence of both complications. However, successful reperfusion therapy results in a rapid improvement in hemodynamic instability and atrioventricular conduction injury, and early hospital discharge. Preinfarction angina may be associated with a protective effect against the development of these 2 complications.

Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress.

The unfolded protein response (UPR) controls the levels of molecular chaperones and enzymes involved in protein folding in the endoplasmic reticulum (ER). We recently isolated ATF6 as a candidate for mammalian UPR-specific transcription factor. We report here that ATF6 constitutively expressed as a 90-kDa protein (p90ATF6) is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed cells. Furthermore, we showed that the most important consequence of this conversion was altered subcellular localization; p90ATF6 is embedded in the ER, whereas p50ATF6 is a nuclear protein. p90ATF6 is a type II transmembrane glycoprotein with a hydrophobic stretch in the middle of the molecule. Thus, the N-terminal half containing a basic leucine zipper motif is oriented facing the cytoplasm. Full-length ATF6 as well as its C-terminal deletion mutant carrying the transmembrane domain is localized in the ER when transfected. In contrast, mutant ATF6 representing the cytoplasmic region translocates into the nucleus and activates transcription of the endogenous GRP78/BiP gene. We propose that ER stress-induced proteolysis of membrane-bound p90ATF6 releases soluble p50ATF6, leading to induced transcription in the nucleus. Unlike yeast UPR, mammalian UPR appears to use a system similar to that reported for cholesterol homeostasis.