Role of sleep and sleep-related correlates in the development of delirium: A feasibility study

Purpose of the study. The purpose was to determine if sleep deprivation in hospitalized older adults predicts the development of delirium, and if sleep is predicted by nighttime light and sound levels. ^ Method. This observational feasibility study enrolled 54 adults ≥70 years of age (mean age 79, range 70–94) who were negative for delirium. The sample was monitored for sleep via wrist actigraphy, and light and sound levels were monitored from 2200 to 0700 the first night of hospitalization. The Richards Campbell Sleep Questionnaire (RCSQ) was administered to measure subjective sleep satisfaction. Subjects were assessed for delirium daily using the Confusion Assessment Method. ^ Conclusions. Of 50 subjects completing the study, two (4%) developed delirium. Mean nighttime sleep was 225 minutes (± 137) with frequent awakenings (13 ± 6) Light levels were elevated episodically (mean intense light = 64 lux, lasting 1¾ hours); median sound levels [49.65 dB(A)] exceeded WHO recommendations [35 dB(A)]. Neither median sound (r = -.63, p = 67) nor mean light levels (r = -.104, p = .47) significantly correlated with sleep. Mean RCSQ was 50.7 ± 24 and showed a moderate correlation with nighttime sleep minutes (r = .577, p .000). Power analysis determined that 294 subjects will be required to determine if nighttime sleep minutes predict delirium, and 182 subjects will be required to determine if sound and light levels predict nighttime sleep minutes.^

Impact of hormonal therapy on survival and racial disparities in a large community-based cohort of older men with local/regional prostate cancer

Prostate cancer (CaP) is the most diagnosed non-cutaneous malignancy and the second leading cause of cancer mortality among United States males. Major racial disparities in incidence, survival, as well as treatment persist. The mortality is three times higher among African Americans (AAs) compared with Caucasians. Androgen carcinogenesis has been persistently implicated but results are inconsistent; and hormone manipulation has been the main stay of treatment for metastatic disease, supportive of the androgen carcinogenesis. The survival disadvantage of AAs has been attributed to the differences in socioeconomic factors (SES), tumor stage, and treatment. We hypostasized that HT prolongs survival in CaP and that the racial disparities in survival is influenced by variation in HT and primary therapies as well as SES. To address these overall hypothesis, we first utilized a random-effect meta-analytic design to examine evidence from randomized trials on the efficacy of androgen deprivation therapy in localized and metastatic disease, and assessed, using Cox proportional hazards models, the effectiveness of HT in prolonging survival in a large community-based cohort of older males diagnosed with local/regional CaP. Further we examined the role of HT and primary therapies on the racial disparities in CaP survival. The results indicated that adjuvant HT compared with standard care alone is efficacious in improving overall survival, whereas HT has no significant benefit in the real world experience in increasing the overall survival of older males in the community treated for local/regional disease. Further, racial differences in survival persist and were explained to some extent by the differences in the primary therapies (radical prostatectomy, radiation and watchful waiting) and largely by SES. Therefore, given the increased used of hormonal therapy and the cost-effectiveness today, more RCTs are needed to assess whether or not survival prolongation translates to improved quality of life, and to answer the research question on whether or not the decreased use of radical prostatectomy by AAs is driven by the Clinicians bias or AAs's preference of conservative therapy and to encourage AAs to seek curative therapies, thus narrowing to some degree the persistent mortality disparities between AAs and Caucasians. ^

An evaluation of sleep hypnotic and stimulant effect on human performance using a computerized psychological test battery

This study evaluated the administration-time-dependent effects of a stimulant (Dexedrine 5-mg), a sleep-inducer (Halcion 0.25-mg) and placebo (control) on human performance. The investigation was conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized sixway-crossover three-treatment, two-timepoint (0830 vs 2030) design. Performance tests were conducted hourly during sleepless 13-hour studies using a computer generated, controlled and scored multi-task cognitive performance assessment battery (PAB) developed at the Walter Reed Army Institute of Research. Specific tests were Simple and Choice Reaction Time, Serial Addition/Subtraction, Spatial Orientation, Logical Reasoning, Time Estimation, Response Timing and the Stanford Sleepiness Scale. The major index of performance was "Throughput", a combined measure of speed and accuracy.^ For the Placebo condition, Single and Group Cosinor Analysis documented circadian rhythms in cognitive performance for the majority of tests, both for individuals and for the group. Performance was best around 1830-2030 and most variable around 0530-0700 when sleepiness was greatest (0300).^ Morning Dexedrine dosing marginally enhanced performance an average of 3% with reference to the corresponding in time control level. Dexedrine AM also increased alertness by 10% over the AM control. Dexedrine PM failed to improve performance with reference to the corresponding PM control baseline. With regard to AM and PM Dexedrine administrations, AM performance was 6% better with subjects 25% more alert.^ Morning Halcion administration caused a 7% performance decrement and 16% increase in sleepiness and a 13% decrement and 10% increase in sleepiness when administered in the evening compared to corresponding in time control data. Performance was 9% worse and sleepiness 24% greater after evening versus morning Halcion administration.^ These results suggest that for evening Halcion dosing, the overnight sleep deprivation occurring in coincidence with the nadir in performance due to circadian rhythmicity together with the CNS depressant effects combine to produce performance degradation. For Dexedrine, morning administration resulted in only marginal performance enhancement; Dexedrine in the evening was less effective, suggesting the 5-mg dose level may be too low to counteract the partial sleep deprivation and nocturnal nadir in performance. ^

Regulation of Protein Degradation in the Heart by AMP-Activated Protein Kinase

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of protein degradation, and AMPK activity are increased during nutrient deprivation. Pharmacologic and genetic activation of AMPK is sufficient for the induction of MAFbx/Atrogin-1 and MuRF1 in cardiomyocytes and in the heart in vivo. Comprehensive experiments demonstrate that the molecular mechanism by which AMPK regulates MuRF1 expression is through the transcription factor myocyte enhancer factor 2 (MEF2), which is involved in stress response and cardiomyocyte remodeling. MuRF1 is required for AMPK-mediated protein degradation through the UPS in cardiomyocytes. Consequently, the absence of MuRF1 during chronic fasting preserves cardiac function, possibly by limiting degradation of critical metabolic enzymes. Furthermore, during cardiac hypertrophy, chronic activation of AMPK also leads to cardiac dysfunction, possibly through enhanced protein degradation and metabolic dysregulation. Collectively, my findings demonstrate that AMPK regulates expression of ubiquitin ligases which are required for UPS-mediated protein degradation in the heart. Based on these results, I propose that specific metabolic signals may serve as modulators of intracellular protein degradation in the heart.

Regulation of Protein Degradation in the Heart by AMP-Activated Protein Kinase

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of protein degradation, and AMPK activity are increased during nutrient deprivation. Pharmacologic and genetic activation of AMPK is sufficient for the induction of MAFbx/Atrogin-1 and MuRF1 in cardiomyocytes and in the heart in vivo. Comprehensive experiments demonstrate that the molecular mechanism by which AMPK regulates MuRF1 expression is through the transcription factor myocyte enhancer factor 2 (MEF2), which is involved in stress response and cardiomyocyte remodeling. MuRF1 is required for AMPK-mediated protein degradation through the UPS in cardiomyocytes. Consequently, the absence of MuRF1 during chronic fasting preserves cardiac function, possibly by limiting degradation of critical metabolic enzymes. Furthermore, during cardiac hypertrophy, chronic activation of AMPK also leads to cardiac dysfunction, possibly through enhanced protein degradation and metabolic dysregulation. Collectively, my findings demonstrate that AMPK regulates expression of ubiquitin ligases which are required for UPS-mediated protein degradation in the heart. Based on these results, I propose that specific metabolic signals may serve as modulators of intracellular protein degradation in the heart.

The Relationship of Provincial Economic Level and Child Injury Mortality in Thailand: A Cross-Sectional Analysis in a Middle Income Country

The objective of this cross-sectional study was to examine the relationship of provincial economic development indices with incidences of child injury mortality in Thailand from 1999 - 2001. All injury deaths among children age 1-14 years were included. The independent variables included gross provincial product per capita (GPP/c), poverty and inequality indices, material and social deprivation indices, population in rural/ urban areas, and migration. Due to multicollinearity of such variables, the 76 provinces were categorized by GPP/c quartile, and means of overall injury, drowning, and transport-related mortality rates were compared among quartile groups. Spearman’s rho correlation between GPP/c and injury mortality rates was also performed. Finally, factor analysis was employed to create a set of factors to be treated as uncorrelated variables and stepwise multiple regression was carried out for the effects of the factors on injury mortality rates. A significant direct relationship was observed between GPP/c and overall injury mortality among children age 1-4 years, and 10-14 year-olds of both genders. Drowning was the main cause of this relationship among children age 1-4 years, and transport-related injury was the principle cause among children age 10-14 years. Conversely, provinces with lower GPP/c experienced higher injury mortality rates among school-age children 5-9 years old for both genders, mostly due to drowning. Factor analysis, and multiple regression results confirmed the relationships between economic development and injury mortality rates. These findings revealed that economic development had an adverse impact on injury-related mortality among children 1 to 4 and 10 to14 in Thailand.

Influence of Crop Load on Tree Growth, Yield, and Fruit Quality of Scab Resistant Apples at Harvest

Apple scab, caused by Venturia inaequalis, is a major disease affecting apple production. Breeding programs have developed over 30 releases of scab-resistant cultivars since 1970 with recent ones having much improved quality. Redfree and GoldRush are from a cooperative breeding program involving Purdue, Rutgers, and Illinois universities while Liberty was introduced from the Cornell University breeding program. For these cultivars to gain better acceptance, more information is needed on their cropping capacities and the effect of crop load on fruit quality attributes. Our study was conducted to determine the relationship between increasing crop load on tree growth, fruit size, and fruit quality variables of the three cultivars under Iowa conditions.

Bone metabolic and hormonal characteristics of Australian Antarctic expeditioners

Summary: Serum 25(OH)D levels decline without sunlight exposure. We studied 120 expeditioners to Antarctica to determine the skeletal and hormonal responses to sunlight deprivation. With emerging vitamin D insufficiency, serum calcium decreased, PTH increased, and bone loss at the proximal femur was observed. Baseline serum 25(OH)D levels >100 nmol/L prevented vitamin D insufficiency. Introduction: Vitamin D stores deplete without adequate sunlight exposure unless supplementation is provided. We studied 120 healthy adults who spent a year in Antarctica as a model for sunlight deprivation to define the timing and magnitude of the skeletal and hormonal responses to emerging vitamin D insufficiency. Methods: Fasting blood samples were assessed at baseline, 6 and 12 months for serum 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), bone formation (P1NP) and resorption (CTx), PTH and calcium. Lumbar spine and proximal femur BMD was measured using DXA. Differences over time were determined using repeated measures ANOVA. Percent changes were expressed as (Delta value/(value A +value B)/2)x100. Relationships between outcome measures were determined using Spearman's correlations. Results: Vitamin D insufficiency (<50 nmol/L) was observed in 85% of expeditioners by 6 months when serum calcium decreased and PTH increased (p<0.01). By 12 months, OC increased by 7.4±3.0% (p<0.05), and BMD decreased by 1.0±2.0% at the total proximal femur (p<0.05). For those with vitamin D sufficiency at baseline (>50 nmol/L), sunlight deprivation produced vitamin D insufficiency within 4 months unless baseline values were >100 nmol/L. Conclusion: Supplementation may be necessary for expeditioners with limited access to UV light.

Migration and Wellbeing at the Lower Echelons of the Economy: A Study of Delhi Slums

This paper based on a primary survey of households (2004-05) in the slum clusters of Delhi examines whether migrants are likely to experience upward mobility in their place of destination or alternatively, if they merely transfer their poverty from rural areas to large cities. First, a simple bifurcation of population in terms of poor and non-poor sub-groups is examined along with the incidence of poverty across different categories of occupations and non-workers. Then, an explanation of the variations in per capita expenditure across households is provided, and a binomial logit model (poor/non-poor) is developed identifying the variables which raise (or reduce) the probability of being non-poor (or poor). Next, an estimate of the wellbeing (deprivation) index is derived from factor analysis of a large number of variables including demographic and economic aspects of households. Empirical findings suggest that while duration of migration and the wellbeing index do not have a definite relationship, migrant households who have been in the city for a very long time have a higher wellbeing index on average than those who migrated in the last ten years. This tends to support the view that migrants do not merely transfer rural poverty to urban areas, and further that population mobility yields improvement in the living standard, if only in the very long term. Implementation of "employment-cum-shelter" support schemes in the urban areas may contribute to their wellbeing.

Effect of short-term fasting prior to slaughter on welfare and meat quality or rainbow trout (Oncorhynchus mykiss)

El manejo pre-sacrificio es de vital importancia en acuicultura, ya que afecta tanto a las reacciones fisiológicas como a los procesos bioquímicos post mortem, y por tanto al bienestar y a la calidad del producto. El ayuno pre-sacrificio se lleva a cabo de forma habitual en acuicultura, ya que permite el vaciado del aparato digestivo de restos de alimento y heces, reduciendo de esta manera la carga bacteriana en el intestino y la dispersión de enzimas digestivos y potenciales patógenos a la carne. Sin embargo, la duración óptima de este ayuno sin que el pez sufra un estrés innecesario no está clara. Además, se sabe muy poco sobre la mejor hora del día para realizar el sacrificio, lo que a su vez está regido por los ritmos diarios de los parámetros fisiológicos de estrés. Finalmente, se sabe que la temperatura del agua juega un papel muy importante en la fisiología del estrés pero no se ha determinado su efecto en combinación con el ayuno. Además, las actuales recomendaciones en relación a la duración óptima del ayuno previo al sacrificio en peces no suelen considerar la temperatura del agua y se basan únicamente en días y no en grados día (ºC d). Se determinó el efecto del ayuno previo al sacrificio (1, 2 y 3 días, equivalente a 11,1-68,0 grados día) y la hora de sacrificio (08h00, 14h00 y 20h00) en trucha arco iris (Oncorhynchus mykiss) de tamaño comercial en cuatro pruebas usando diferentes temperaturas de agua (Prueba 1: 11,8 ºC; Prueba 2: 19,2 ºC; Prueba 3: 11,1 ºC; y Prueba 4: 22,7 ºC). Se midieron indicadores biométricos, hematológicos, metabólicos y de calidad de la carne. En cada prueba, los valores de los animales ayunados (n=90) se compararon con 90 animales control mantenidos bajo condiciones similares pero nos ayunados. Los resultados sugieren que el ayuno tuvo un efecto significativo sobre los indicadores biométricos. El coeficiente de condición en los animales ayunados fue menor que en los controles después de 2 días de ayuno. El vaciado del aparato digestivo se produjo durante las primeras 24 h de ayuno, encontrándose pequeñas cantidades de alimento después de 48 h. Por otra parte, este vaciado fue más rápido cuando las temperaturas fueron más altas. El peso del hígado de los animales ayunados fue menor y las diferencias entre truchas ayunadas y controles fueron más evidentes a medida que el vaciado del aparato digestivo fue más rápido. El efecto del ayuno hasta 3 días en los indicadores hematológicos no fue significativo. Los niveles de cortisol en plasma resultaron ser altos tanto en truchas ayunadas como en las alimentadas en todas las pruebas realizadas. La concentración media de glucosa varió entre pruebas pero mostró una tendencia a disminuir en animales ayunados a medida que el ayuno progresaba. En cualquier caso, parece que la temperatura del agua jugó un papel muy importante, ya que se encontraron concentraciones más altas durante los días 2 y 3 de ayuno en animales mantenidos a temperaturas más bajas previamente al sacrificio. Los altos niveles de lactato obtenidos en sangre parecen sugerir episodios de intensa actividad muscular pero no se pudo encontrar relación con el ayuno. De la misma manera, el nivel de hematocrito no mostró efecto alguno del ayuno y los leucocitos tendieron a ser más altos cuando los animales estaban menos estresados y cuando su condición corporal fue mayor. Finalmente, la disminución del peso del hígado (índice hepatosomático) en la Prueba 3 no se vio acompañada de una reducción del glucógeno hepático, lo que sugiere que las truchas emplearon una estrategia diferente para mantener constantes los niveles de glucosa durante el periodo de ayuno en esa prueba. En relación a la hora de sacrificio, se obtuvieron niveles más bajos de cortisol a las 20h00, lo que indica que las truchas estaban menos estresadas y que el manejo pre-sacrificio podría resultar menos estresante por la noche. Los niveles de hematocrito fueron también más bajos a las 20h00 pero solo con temperaturas más bajas, sugiriendo que las altas temperaturas incrementan el metabolismo. Ni el ayuno ni la hora de sacrificio tuvieron un efecto significativo sobre la evolución de la calidad de la carne durante los 3 días de almacenamiento. Por el contrario, el tiempo de almacenamiento sí que parece tener un efecto claro sobre los parámetros de calidad del producto final. Los niveles más bajos de pH se alcanzaron a las 24-48 h post mortem, con una lata variabilidad entre duraciones del ayuno (1, 2 y 3 días) en animales sacrificados a las 20h00, aunque no se pudo distinguir ningún patrón común. Por otra parte, la mayor rigidez asociada al rigor mortis se produjo a las 24 h del sacrificio. La capacidad de retención de agua se mostró muy estable durante el período de almacenamiento y parece ser independiente de los cambios en el pH. El parámetro L* de color se incrementó a medida que avanzaba el período de almacenamiento de la carne, mientras que los valores a* y b* no variaron en gran medida. En conclusión, basándose en los resultados hematológicos, el sacrificio a última hora del día parece tener un efecto menos negativo en el bienestar. De manera general, nuestros resultados sugieren que la trucha arco iris puede soportar un período de ayuno previo al sacrificio de hasta 3 días o 68 ºC d sin que su bienestar se vea seriamente comprometido. Es probable que con temperaturas más bajas las truchas pudieran ser ayunadas durante más tiempo sin ningún efecto negativo sobre su bienestar. En cualquier caso, se necesitan más estudios para determinar la relación entre la temperatura del agua y la duración óptima del ayuno en términos de pérdida de peso vivo y la disminución de los niveles de glucosa en sangre y otros indicadores metabólicos. SUMMARY Pre-slaughter handling in fish is important because it affects both physiological reactions and post mortem biochemical processes, and thus welfare and product quality. Pre-slaughter fasting is regularly carried out in aquaculture, as it empties the viscera of food and faeces, thus reducing the intestinal bacteria load and the spread of gut enzymes and potential pathogens to the flesh. However, it is unclear how long rainbow trout can be fasted before suffering unnecessary stress. In addition, very little is known about the best time of the day to slaughter fish, which may in turn be dictated by diurnal rhythms in physiological stress parameters. Water temperature is also known to play a very important role in stress physiology in fish but the combined effect with fasting is unclear. Current recommendations regarding the optimal duration of pre-slaughter fasting do not normally consider water temperature and are only based on days, not degree days (ºC d). The effects of short-term fasting prior to slaughter (1, 2 and 3 days, between 11.1 and 68.0 ºC days) and hour of slaughter (08h00, 14h00 and 20h00) were determined in commercial-sized rainbow trout (Oncorhynchus mykiss) over four trials at different water temperatures (TRIAL 1, 11.8 ºC; TRIAL 2, 19.2 ºC; TRIAL 3, 11.1 ºC; and TRIAL 4, 22.7 ºC). We measured biometric, haematological, metabolic and product quality indicators. In each trial, the values of fasted fish (n=90) were compared with 90 control fish kept under similar conditions but not fasted. Results show that fasting affected biometric indicators. The coefficient of condition in fasted trout was lower than controls 2 days after food deprivation. Gut emptying occurred within the first 24 h after the cessation of feeding, with small traces of digesta after 48 h. Gut emptying was faster at higher water temperatures. Liver weight decreased in food deprived fish and differences between fasted and fed trout were more evident when gut clearance was faster. The overall effect of fasting for up to three days on haematological indicators was small. Plasma cortisol levels were high in both fasted and fed fish in all trials. Plasma glucose response to fasting varied among trials, but it tended to be lower in fasted fish as the days of fasting increased. In any case, it seems that water temperature played a more important role, with higher concentrations at lower temperatures on days 2 and 3 after the cessation of feeding. Plasma lactate levels indicate moments of high muscular activity and were also high, but no variation related to fasting could be found. Haematocrit did not show any significant effect of fasting, but leucocytes tended to be higher when trout were less stressed and when their body condition was higher. Finally, the loss of liver weight was not accompanied by a decrease in liver glycogen (only measured in TRIAL 3), suggesting that a different strategy to maintain plasma glucose levels was used. Regarding the hour of slaughter, lower cortisol levels were found at 20h00, suggesting that trout were less stressed later in the day and that pre-slaughter handling may be less stressful at night. Haematocrit levels were also lower at 20h00 but only at lower temperatures, indicating that higher temperatures increase metabolism. Neither fasting nor the hour of slaughter had a significant effect on the evolution of meat quality during 3 days of storage. In contrast, storage time seemed to have a more important effect on meat quality parameters. The lowest pH was reached 24-48 h post mortem, with a higher variability among fasting durations at 20h00, although no clear pattern could be discerned. Maximum stiffening from rigor mortis occurred after 24 h. The water holding capacity was very stable throughout storage and seemed to be independent of pH changes. Meat lightness (L*) slightly increased during storage and a* and b*-values were relatively stable. In conclusion, based on the haematological results, slaughtering at night may have less of a negative effect on welfare than at other times of the day. Overall, our results suggest that rainbow trout can cope well with fasting up to three days or 68 ºC d prior to slaughter and that their welfare is therefore not seriously compromised. At low water temperatures, trout could probably be fasted for longer periods without negative effects on welfare but more research is needed to determine the relationship between water temperature and days of fasting in terms of loss of live weight and the decrease in plasma glucose and other metabolic indicators.

The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae

Initiation factor eIF4G is an essential protein required for initiation of mRNA translation via the 5′ cap-dependent pathway. It interacts with eIF4E (the mRNA 5′ cap-binding protein) and serves as an anchor for the assembly of further initiation factors. With treatment of Saccharomyces cerevisiae with rapamycin or with entry of cells into the diauxic phase, eIF4G is rapidly degraded, whereas initiation factors eIF4E and eIF4A remain stable. We propose that nutritional deprivation or interruption of the TOR signal transduction pathway induces eIF4G degradation.

English Language Skills and Socioeconomic Segregation of UK Immigrants

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Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells triggers the unfolded protein response (UPR), which activates transcription of several genes encoding ER chaperones and folding enzymes. This study reports that conversion of dolichol-linked Man2–5GlcNAc2 intermediates into mature Glc3Man9GlcNAc2 oligosaccharides in primary human adult dermal fibroblasts is also stimulated by the UPR. This stimulation was not evident in several immortal cell lines and did not require a cytoplasmic stress response. Inhibition of dolichol-linked Glc3Man9GlcNAc2 synthesis by glucose deprivation could be counteracted by the UPR, improving the transfer of Glc3Man9GlcNAc2 to asparagine residues on nascent polypeptides. Glycosidic processing of asparagine-linked Glc3Man9GlcNAc2 in the ER leads to the production of monoglucosylated oligosaccharides that promote interaction with the lectin chaperones calreticulin and calnexin. Thus, control of the dolichol-linked Glc3Man9GlcNAc2 supply gives the UPR the potential to maintain efficient protein folding in the ER without new synthesis of chaperones or folding enzymes.