[Studies on the distribution of working people, subject to continuous noise levels equivalent to 85-90 dB (AI) and over 90 dB (AI)].
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Environmental Exposure↗
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Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris.
ApoAI Milano (AI(M)) and apoAI Paris (AI(P)) are mutant forms of apoAI in which cysteine is substituted for arginine at residues 173 and 151 respectively leading to the formation of homodimers and heterodimers with apoAII. Heterozygous subjects with these mutants are characterized by low levels of plasma HDL cholesterol and apoAI. The present study analyzed the metabolism of the different complexes of apoAI in three subjects, two AI(M) and one AI(P), using a primed-constant infusion of trideuterated leucine. In AI(M) carriers, the mutant form was almost equally distributed in AI(M) dimer, AI(M):AII heterodimer and the monomer, whereas, in the AI(P) subject, the mutant apoAI was essentially in the apoAI(P):AII complex. Normal apoAI was low in the AI(M) subjects (20 and 16 mg/dl) but very low in the AI(P) subject (0.3 mg/dl). In the AI(M) subjects, the low levels of apoAI were due to a rapid catabolism with a normal synthetic rate. However, the apoAI kinetics were heterogeneous with a rapid catabolism of the AI(M):AII complex (FCR of 0.430 and 0.401 day(-1)) and the AI(M) monomer (FCR of 0.570 and 0.406 day(-1)) whereas the AI(M) dimer was catabolized slowly (FCR of 0.114 and 0. 118 day(-1)). In contrast, AI(P) was catabolized relatively slowly with a FCR of 0.263, 0.182 and 0.258 day(-1) for AI(P) homodimer, apoAI(P):AII heterodimer and AI(P) monomer. In the three subjects, normal apoAI was catabolized quickly, with an FCR of 0.805 and 0.601 day(-1) in AI(M) carriers and 0.526 day(-1) in the AI(P) carrier. Therefore, the low level of apoAI in the AI(P) carrier is caused by a low production rate of apoAI, particularly of normal apoAI. In conclusion, apoAI is kinetically heterogeneous in AI(M) and in AI(P) subjects. Moreover, the two mutations lead to significant differences in the kinetic behavior of mutant apoAI depending on its inclusion in its complexes.
Adult↗
Deceleration energy and change in velocity on impact: key factors in fatal versus potentially survivable motor vehicle crash (mvc) aortic injuries (AI): the role of associated injuries as determinants of outcome.
OBJECTIVE: To examine the difference in force mechanisms between fatal and potentially survivable MVC aortic injuries (AI) compared to non-AI severe thoracic injuries (ST). METHODS: Of 324 autopsied MVC driver or front seat passenger fatalities (1997-2000), there were 43 fatal AI (36 scene deaths, 7 hospital deaths) and 5 additional AI survivors. RESULTS: Of the 48 AI, there was only a 42% survival for those reaching hospital alive. 80% of AI survivors had isthmus lesions and all had no or minimal brain injury (GCS >= 13), no cardiac injury and only 20% ribs 1-4 fx or shock; of AI non-survivors reaching hospital alive, 67% had GCS <= 12, 50% cardiac injury, 83% ribs 1-4 fx and 83% shock; AI scene deaths had 78% severe brain injury, 56% cardiac injury, 69% lung injury and 78% ribs 1-4 fx. Quantifying forces in AI scene mortality: the Instantaneous Velocity on Impact of the subject vehicle (delta V1) and the Impact Energy Dissipated (IE) on the subject vehicle (V1) in joules demonstrated a linear regression in fatal car MVC AIs: Energy dissipated (joules) = -56.65 x (delta V1)(2) + 15972 x delta V1 - 454661, r(2) = 0.83. However, for 27 patients with non-AI but severe thoracic (ST) injury (AIS>=3), the relationship of IE to delta V1 had a linear regression of Energy dissipated (joules) = -5.0787 x (delta V1)(2) + 4282.1 x delta V1 - 57182 1, r(2) = 0.84, with the slope difference between the regression for AI scene deaths and that of ST and AI survivors being significant (p<0.05). Based on these relationships, a Critical Zone limited by MVC Impact Energy level of 336000 joules and a delta V1 of 64 kph appears to be the limit of potential survivability in MVCs producing aortic injuries. All AI above these thresholds died. In contrast, ST had greater use of seatbelts (AI 10% vs all ST 60%) and airbags (AI 50% vs all ST 72%), and an 83% survival. CONCLUSION: The data suggest different mechanisms of force delivery and injury patterns in fatal vs potentially survivable AI, and vs ST MVCs. They suggest that an approach to improving vehicle safety measures for AI may involve better safety devices and mechanisms for reducing that fraction of Impact Energy dissipated on V1 for a given delta V1 which is focused on the upper portion of the subject's thoracic cage between the levels of ribs1-8.
Acceleration↗
[Over-expression in Escherichia coli and characterization of apolipoprotein AI].
Apolipoprotein AI (apo AI), the major protein component of human high-density lipoprotein (HDL), is a single-chain polypeptide of 243 amino acids. Several epidemiological studies have shown that the plasma concentrations of HDL has the role of reverse cholesterol transport (RCT) and inversely correlated with the incidence of coronary artery disease. Because apo AI lacks post-translational modifications, it is convenient to express human apo AI in Escherichia coli expression system. However, there is a poor stability of the mRNA and the apo AI protein in E. coli, it is difficult to express mature apo AI in recombinant bacteria, moreover, even as a fusion protein, apo AI is still sensitive to degradation and can not be cleaved efficiently from the fusion tags. In contrast, proapolipoprotein AI (proapo AI, having an additional polypeptide containing the amino acids Arg-His-Phe-Trp-Gln-Gln at the amino-teminal of the mature protein) proved stable and undegraded in Escherichia coli, and therefore, in this research, an expression system of E. coli including a plasmid of P(R)P(L) tandem promoter was adapted to produce proapo AI. Furthermore, site-directed mutagenesis of the proapo AI cDNA was performed to generate a Clu8Asp mutation in the amino-terminal sequence of proapo AI which created an acid labile Asp-Pro peptide bond between amino acid 8 and 9, and permitted specific chemical cleavage to remove pro-peptide. After inducing with a shift of temperature, yields of recombinant proapo AI achieved about 40% of total cell protein and the recombinant proapo AI expressed proved as a form of inclusion body in cells, so protein need to renature. First of all, the protein was dissolved in buffer with denaturant, and renaturation was carried out on a hydrophobic interaction column (Phenyl Sepharose), ion-exchange chromatography and gel-filtration chromatography were then used to further purify the protein. The purified recombinant apo AI was detected by a set of tests including Western-blotting, Circular dichroism spectra and lipid-binding test, the results shown that recombinant apo AI has similar structural and lipid-binding properties identical to those of native plasma apo AI, which facilitates further research and application.
Apolipoprotein A-I↗
Assessing AI literacy and attitudes among medical students: implications for integration into healthcare practice.
PURPOSE: This study aims to assess AI literacy and attitudes among medical students and explore their implications for integrating AI into healthcare practice. DESIGN/METHODOLOGY/APPROACH: A quantitative research design was employed to comprehensively evaluate AI literacy and attitudes among 374 Lusaka Apex Medical University medical students. Data were collected from April 3, 2024, to April 30, 2024, using a closed-ended questionnaire. The questionnaire covered various aspects of AI literacy, perceived benefits of AI in healthcare, strategies for staying informed about AI, relevant AI applications for future practice, concerns related to AI algorithm training and AI-based chatbots in healthcare. FINDINGS: The study revealed varying levels of AI literacy among medical students with a basic understanding of AI principles. Perceptions regarding AI's role in healthcare varied, with recognition of key benefits such as improved diagnosis accuracy and enhanced treatment planning. Students relied predominantly on online resources to stay informed about AI. Concerns included bias reinforcement, data privacy and over-reliance on technology. ORIGINALITY/VALUE: This study contributes original insights into medical students' AI literacy and attitudes, highlighting the need for targeted educational interventions and ethical considerations in AI integration within medical education and practice.
Students, Medical↗
Thyroid hormone modulates apolipoprotein-AI gene expression at the post-transcriptional level in Hep G2 cells.
Hyperthyroidism is associated with elevated plasma levels of apolipoprotein AI (apo AI). We have examined the effects of 3,3',-5-triiodothyronine on apo AI mRNA, transcription run-on activity, apo AI mRNA half-life, and the rate of protein synthesis in Hep G2 cells, to understand the molecular mechanism by which thyroid hormone regulates apo AI gene expression. Incubation with thyroid hormone increased the apo AI and apo AII mRNA concentrations twofold. Cycloheximide alone caused a significant increase in apo AI mRNA. Nuclear run-on assays indicate that thyroid hormone did not change the rate of the apo AI gene transcription at 6, 12 or 24 h, showing that thyroid hormone did not modulate apo AI gene transcription. Kinetic studies performed in the presence of actinomycin D showed that the half-life of apo AI mRNA was increased 2-3-fold by thyroid hormone over control cells. Thyroid hormone did not change the incorporation of [35S]methionine into immunoprecipitable apo AI. Pulse-chase experiments demonstrated that there was no change in the secretion and degradation rates of labeled apo AI in response to T3. This suggests that thyroid hormone does not affect the catabolism of apo AI (degradation or/and uptake) and that translation control strongly influences the regulation of apo AI gene expression. The stabilization of apo AI mRNA by thyroid hormone and its role in translation remain to be elucidated.
Apolipoprotein A-I↗
Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol.
Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (</=40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7+/-4.0% (P=0.033) and 24.0+/-4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of (125)I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [(3)H]cholesterol ester was approximately 75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.
Apolipoprotein A-I↗
From fear to empowerment: the impact of employees AI awareness on workplace well-being - a new insight from the JD-R model.
PURPOSE: The primary purpose of the study was to explore the impact of health workers' awareness of artificial intelligence (AI) on their workplace well-being, addressing a critical gap in the literature. By examining this relationship through the lens of the Job demands-resources (JD-R) model, the study aimed to provide insights into how health workers' perceptions of AI integration in their jobs and careers could influence their informal learning behaviour and, consequently, their overall well-being in the workplace. The study's findings could inform strategies for supporting healthcare workers during technological transformations. DESIGN/METHODOLOGY/APPROACH: The study employed a quantitative research design using a survey methodology to collect data from 420 health workers across 10 hospitals in Ghana that have adopted AI technologies. The study was analysed using OLS and structural equation modelling. FINDINGS: The study findings revealed that health workers' AI awareness positively impacts their informal learning behaviour at the workplace. Again, informal learning behaviour positively impacts health workers' workplace well-being. Moreover, informal learning behaviour mediates the relationship between health workers' AI awareness and workplace wellbeing. Furthermore, employee learning orientation was found to strengthen the effect of AI awareness on informal learning behaviour. RESEARCH LIMITATIONS/IMPLICATIONS: While the study provides valuable insights, it is important to acknowledge its limitations. The study was conducted in a specific context (Ghanaian hospitals adopting AI), which may limit the generalizability of the findings to other healthcare settings or industries. Self-reported data from the questionnaires may be subject to response biases, and the study did not account for potential confounding factors that could influence the relationships between the variables. PRACTICAL IMPLICATIONS: The study offers practical implications for healthcare organizations navigating the digital transformation era. By understanding the positive impact of health workers' AI awareness on their informal learning behaviour and well-being, organizations can prioritize initiatives that foster a learning-oriented culture and provide opportunities for informal learning. This could include implementing mentorship programs, encouraging knowledge-sharing among employees and offering training and development resources to help workers adapt to AI-driven changes. Additionally, the findings highlight the importance of promoting employee learning orientation, which can enhance the effectiveness of such initiatives. ORIGINALITY/VALUE: The study contributes to the existing literature by addressing a relatively unexplored area - the impact of AI awareness on healthcare workers' well-being. While previous research has focused on the potential job displacement effects of AI, this study takes a unique perspective by examining how health workers' perceptions of AI integration can shape their informal learning behaviour and, subsequently, their workplace well-being. By drawing on the JD-R model and incorporating employee learning orientation as a moderator, the study offers a novel theoretical framework for understanding the implications of AI adoption in healthcare organizations.
Humans↗
Commissural neurons in layer III of cat primary auditory cortex (AI): pyramidal and non-pyramidal cell input.
The types of layer III neurons in cat primary auditory cortex (AI) projecting to the contralateral AI were studied with horseradish peroxidase or horseradish peroxidase conjugated to wheat germ agglutinin. Injections between the anterior and posterior ectosylvian sulci retrogradely labeled both pyramidal and non-pyramidal somata in contralateral cortical layers III, V, and VI in AI, and in the ventral nucleus of the ipsilateral medial geniculate body. Three-quarters (72%) of the retrogradely labeled cells were found in layer III and one-quarter (28%) lay in layers V and VI. Every part of AI was innervated by commissural neurons. The topographical distribution of the labeled cells varied systematically. Injections in the caudal part of AI labeled cells in the caudal part of the opposite AI, while more rostral injections labeled cells in the contralateral, rostral AI. Injections covering the rostro-caudal extent of AI labeled cells throughout the opposite AI. Each part of AI thus projects most strongly to a contralateral, homotypic area, and less strongly to other, adjacent sectors of AI. The types of labeled cells were distinguished from one another on the basis of size, somatic and dendritic morphology, laminar distribution, and nuclear membrane morphology. Their somatodendritic profiles were compared to, and correlated with, those in Golgi-impregnated material from adult animals. Among the pyramidal cells of origin were small, medium-sized, and large neurons, and star pyramidal cells. The non-pyramidal cells of origin included bipolar and multipolar cells. Thus, at least six of the 12 kinds of neurons, as defined by morphological methods, participate in the interhemispheric pathway. Pyramidal cells comprised 65% of the cells of origin, 14% of the labeled cells in layer III were non-pyramidal, and 21% of the neurons could not be classified. It is unknown if these different types of commissural neurons have the same laminar or cytological targets in AI, or if they represent more than one functional or parallel pathway within AI. In any case, cytologically diverse layer III neurons contribute to the commissural system.
Animals↗
Quantitative and qualitative changes of apolipoprotein AI-containing lipoproteins in patients on continuous ambulatory peritoneal dialysis.
Using immunoaffinity chromatography, two species of apo-AI containing lipoproteins (AILp); lipoprotein containing apo-AI and apo-AII (Lp-AI/AII), and lipoprotein containing apo-AI, but no apo-AII (Lp-AI) were isolated from 13 female patients on continuous ambulatory peritoneal dialysis (CAPD), then characterized. The results were compared with findings obtained in agematched normolipidemic (control I) and mild hypertriglyceridemic (control II) female subjects. In comparison with control I: In AILp, the levels of total cholesterol (TC), cholesteryl ester (CE) and phospholipid (PL), and the levels of apoE were significantly lower in the CAPD patients while the levels of triglyceride (TG) and apo-CIII were significantly higher in these patients. The levels of apo-AI and apo-AII did not differ between the CAPD and control subjects. In Lp-AI/AII, changes of TC, CE, PL, TG, and apolipoproteins were similar to those of AILp, except for the ratio of apo-AI/apo-AII and the level of apo-CII, which was higher in the CAPD patients. In Lp-AI, changes of TC, CE, PL, and TG were also similar to those of AILp and Lp-AI/AII, but the apo-AI level was significantly lower in the CAPD patients. In comparison with control II: In AILp, the levels of PL, apo-AI, apo-AII, and apo-E were significantly lower in CAPD patients, but the apo-CIII levels were significantly higher. In Lp-AI/AII, the levels of PL and apo-E were significantly lower in CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Inhibition of apolipoprotein AI gene expression by 1, 25-dihydroxyvitamin D3.
Members of the steroid receptor superfamily are known to alter the transcription of apolipoprotein AI (apo AI), the major apoprotein of high-density lipoprotein (HDL). To assess the role of vitamin D receptor (VDR) in apo AI gene expression, we investigated the effect of 1alpha, 25-dihydroxycholecalciferol (1, 25-(OH)2 D3) as well as the vitamin D antagonist ZK-191784 (ZK), on apo AI gene expression and promoter activity in the human hepatoma cell line HepG2. Apo AI secretion and mRNA levels were both suppressed in a dose-dependent manner in HepG2 cells treated 1, 25-(OH)2 D3. This was accompanied by a similar decrease in apo AI promoter activity. Mapping of the vitamin D response element showed that suppression required a region of the apo AI gene promoter identified previously to contain site A. However, vitamin D treatment had no effect on nuclear factor binding to site A of the apo AI promoter. Treatment with vitamin D receptor antagonist ZK inhibited the ability of 1, 25-(OH)2 D3 to repress apo AI promoter activity, while higher doses of ZK increased apo AI promoter activity. ZK did not alter estradiol stimulated apo AI promoter activity. The VDR antisense ODN had no effect on apo AI promoter activity in control cells, however, it reversed the repression normally seen in cells treated with 1, 25-(OH)2D3. It is concluded that 1, 25-(OH)2 D3 suppresses apo A1 gene expression at the transcriptional level, possibly by altering coactivators or corepressors. This effect requires the VDR as well as a vitamin D response element in the apo AI promoter.
Acetyltransferases↗
Transient expression of wild type and mutant human apolipoprotein AI in COS cells.
A human apolipoprotein AI (apo AI) minigene and two mutants were cloned into the vector pUHD10-1 for expression studies in COS cells under the control of the strong CMV (cytomegalovirus) enhancer and the own apo AI promoter. In the mutated apo AI minigene (mutant M1) the positions of the triplets of Gln(-2)-Gln-1 at the C-terminus of the prosequence were exchanged against Gln(-8)-Ala-7, the recognition site of the signal peptidase of the wild type human apo AI. The prosequence has been deleted in mutant M2 and the presequence linked directly to the N-terminus of the mature apo AI form. We report here on expression studies in COS cells, a cell line, which does not express apo AI. They were transfected by electroporation with pUHD10-1 constructs, which contain a) the wild type apo AI minigene and b) the two mutant apo AI minigenes with mutations described above. The following results were obtained: a) the wild type and mutant apo AI constructs were efficiently transcribed and translated in COS cells, b) the expression of the wild type preproapo AI minigene in COS cells led to the secretion of proapo AI (29 kDa), that of the mutant (M2) gene, devoid of the prosequence of mature apo AI (28.4 kDa), whereas the product of mutant gene M1 (31 kDa) with the recognition site of the signal peptides transposed to the C-terminus of the prosequence remained uncleaved within the COS cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Manual, digital, and AI tumour-infiltrating lymphocyte scoring: a secondary analysis of the APHINITY randomised trial.
BACKGROUND: Stromal tumour-infiltrating lymphocytes (sTILs) are prognostic in early-stage HER2-positive breast cancer, but their role in the context of dual HER2 blockade remains undefined. We evaluated manual, digital, and artificial intelligence (AI)-based sTIL quantification, together with AI-derived spatial metrics, for prognostic and treatment-benefit stratification using tumour samples from the phase 3 APHINITY trial. METHODS: In the APHINITY trial, 4805 patients were randomly assigned to receive chemotherapy plus trastuzumab with pertuzumab or chemotherapy plus trastuzumab with placebo. Median follow-up was 74·1 months (IQR 68·3-75·4). We analysed 4262 haematoxylin and eosin-stained images using manual assessment, an automated digital approach, AI-based lymphocyte quantification (AI percentage lymphocytes), and two AI-derived spatial features (AI-TIL and immune hotspot). Interobserver reproducibility was assessed in 262 randomly chosen tumour samples scored independently by five pathologists. Multivariable Cox models were used to assess associations between TIL levels and invasive disease-free survival (primary outcome in APHINITY), distant recurrence-free interval, and overall survival. The heterogeneity of pertuzumab benefit was evaluated using subgroup analyses, subpopulation treatment effect pattern plot analyses, and nested Cox models with treatment-by-biomarker interaction terms. FINDINGS: Manual scoring showed high interobserver reproducibility (intraclass correlation coefficient 0·84 [95% CI 0·79-0·88]). Concordance between manual and automated methods was modest. AI-based scoring (AI percentage lymphocytes) reclassified 120 (11·6%) of 1035 node-positive tumours from immune-low (by manual scoring) to immune-high; this subgroup of patients showed greater separation of 5-year invasive disease-free survival curves between pertuzumab and placebo groups compared with patients whose tumours were concordantly classified as immune-low by both manual and AI-based approaches. Higher levels of TILs were associated with improved invasive disease-free survival for all sTIL measurement approaches and spatial measurements (hazard ratios [HRs] 0·41-0·93). Pertuzumab was associated with improved invasive disease-free survival at higher sTIL levels across all measurement approaches (HRs 0·36-0·48), but was not associated with higher values of spatial measures. The largest 6-year absolute improvements with pertuzumab were observed in patients with node-positive disease whose tumours scored in the highest level of immune infiltration of manual sTIL scoring (≥70·0%; mean absolute improvement 12·1 percentage points [SD 2·8]). In nested prognostic and predictive models, AI-based immune hotspot scores provided the most consistent additional information when combined with any sTIL measurement (all p<0·010). INTERPRETATION: Standardised manual sTIL scoring was reproducible, and digital and AI-based methods showed consistent prognostic stratification and potential for treatment-benefit stratification despite only modest correlation between platforms. AI spatial metrics provided complementary information beyond sTIL density and could support more scalable immune assessment. Future studies are needed to validate these approaches in independent cohorts and to clarify their clinical utility for stratifying contemporary HER2-directed therapies. FUNDING: None.
Humans↗
Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.
Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats.
Animals↗
The effects of fat feeding on apolipoprotein AI secretion from rat small intestinal epithelium.
The small intestine is known to be an important synthetic site for certain apolipoproteins, which are subsequently secreted from the enterocyte into the mesenteric lymph. We have studied apolipoprotein AI and CIII content of the enterocyte during the course of fat feeding in order to determine their relative synthetic and secretory rates. Rat intestinal enterocytes were isolated from the entire jejunal villus after fat feeding in vivo. The apo AI content fell 50% as determined by RIA one and two hours after fat feeding. By four hours, the intracellular cellular levels had returned to prefeeding levels. These changes in apolipoprotein AI levels were not seen in the terminal ileum. Apolipoprotein CIII levels remained unchanged afer fat feeding. To determine the effect of free fatty acids on apolipoprotein AI secretion, organ culture explants were incubated for four hours in the presence and absence of 360 microM oleic acid bound to albumin. Apolipoprotein AI detected in the incubation media reflected release from the lamina propria (which was not colchicine sensitive), and secretion from the enterocyte (which was inhibited by colchicine). In the absence of oleic acid, enterocyte secretion of apolipoprotein AI accounted for about half of the apo AI recovered in the medium. In the presence of oleic acid, the total apolipoprotein AI content of the tissue increased by 50 percent. A similar increase in colchicine sensitive secretion was observed. The secretion of apolipoprotein AI from explants was more rapid in the presence of oleic acid and began without the half hour lag noted when oleic acid was absent. The mid intestine was most active in the secretion of apolipoprotein AI. These data are consistent with the hypothesis that in the first few hours after feeding the rate of secretion of apolipoprotein AI exceeds the synthetic capacity of the small intestinal epithelium.
Animals↗
A Sentiment-Based Comparison of AI- and Physician-Generated Empathic Statements in Palliative Care.
CONTEXT: Empathic communication promotes trust in patient-provider relationships. As healthcare integrates artificial intelligence (AI) into patient communication, we have yet to understand how these models' communication compares to that of physicians. OBJECTIVES: Our primary objectives were to examine patient preferences for AI-generated vs. palliative care physician-generated empathic statements addressing fear and anxiety around cancer treatment, and to analyze associations between linguistic features and patient preferences. METHODS: We conducted a secondary analysis of the PALL-AI trial, a randomized controlled survey comparing cancer patients' preferences of AI- to physician-generated empathic statements. Physicians and AI were provided the same prompt with a maximum sentence length. Patient preferences for each statement were measured in blinded surveys. We analyzed sentiment of the statements using the Valence Aware Dictionary and Sentiment Reasoner (VADER) and the National Research Council Canada (NRC) Emotion Lexicon. We evaluated associations between sentiment scores and patient preferences using Spearman's correlation coefficients. RESULTS: A total of 105 patients completed blinded surveys, preferring the AI-generated statement 72.4% of the time. VADER sentiment analysis showed all three AI statements displayed positive sentiment, while all three physician statements displayed negative sentiment. Controlling for statement length, AI statements used twice as many positive words as human statements. However, they contained a similar number of negative words. Of the eight NRC emotions, "trust" and "joy" demonstrated the strongest correlations with patient preference. CONCLUSION: Patients preferred AI-generated statements around cancer care over those from palliative care physicians when standardized for prompt and statement length. Analysis shows AI-generated statements contain more positive language which may be the factor driving patient preference toward AI.
Humans↗
AI-3 synthesis is not dependent on luxS in Escherichia coli.
The quorum-sensing (QS) signal autoinducer-2 (AI-2) has been proposed to promote interspecies signaling in a broad range of bacterial species. AI-2 is spontaneously derived from 4,5-dihydroxy-2,3-pentanedione that, along with homocysteine, is produced by cleavage of S-adenosylhomocysteine (SAH) and S-ribosylhomocysteine by the Pfs and LuxS enzymes. Numerous phenotypes have been attributed to AI-2 QS signaling using luxS mutants. We have previously reported that the luxS mutation also affects the synthesis of the AI-3 autoinducer that activates enterohemorrhagic Escherichia coli virulence genes. Here we show that several species of bacteria synthesize AI-3, suggesting a possible role in interspecies bacterial communication. The luxS mutation leaves the cell with only one pathway, involving oxaloacetate and l-glutamate, for de novo synthesis of homocysteine. The exclusive use of this pathway for homocysteine production appears to alter metabolism in the luxS mutant, leading to decreased levels of AI-3. The addition of aspartate and expression of an aromatic amino acid transporter, as well as a tyrosine-specific transporter, restored AI-3-dependent phenotypes in an luxS mutant. The defect in AI-3 production, but not in AI-2 production, in the luxS mutant was restored by expressing the Pseudomonas aeruginosa S-adenosylhomocysteine hydrolase that synthesizes homocysteine directly from SAH. Furthermore, phenotype microarrays revealed that the luxS mutation caused numerous metabolic deficiencies, while AI-3 signaling had little effect on metabolism. This study examines how AI-3 production is affected by the luxS mutation and explores the roles of the LuxS/AI-2 system in metabolism and QS.
Amino Acid Transport Systems↗
Cyclosporin A inhibits apolipoprotein AI gene expression.
Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo AI) is a major protein component of HDL particles and reduction of apo AI results in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression contributing to its lipid effects. Therefore, we first measured the serum apo AI protein levels in rats with or without CsA treatment, and found that both serum apo AI protein and liver apo AI mRNA levels were significantly reduced in response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI-474-CAT reporter gene, we found that intracellular calcium mobilization by A23187 a calcium ionophore stimulated apo AI gene expression and the calcineurin inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we conclude that activation of the calcineurin pathway by intracellular calcium mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA results in reduced apo AI gene expression.
Animals↗