Asymptotic Self-Similar Blow-Up Profile for Three-Dimensional Axisymmetric Euler Equations Using Neural Networks.

Whether there exist finite-time blow-up solutions for the 2D Boussinesq and the 3D Euler equations are of fundamental importance to the field of fluid mechanics. We develop a new numerical framework, employing physics-informed neural networks, that discover, for the first time, a smooth self-similar blow-up profile for both equations. The solution itself could form the basis of a future computer-assisted proof of blow-up for both equations. In addition, we demonstrate physics-informed neural networks could be successfully applied to find unstable self-similar solutions to fluid equations by constructing the first example of an unstable self-similar solution to the Córdoba-Córdoba-Fontelos equation. We show that our numerical framework is both robust and adaptable to various other equations.

Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

[A study on alterations in mitochondrial biological characteristics during cellular senescence of human embryonic lung fibroblasts].

Objective: To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs). Methods: The premature senescence was induced by 400 µmol/L H(2)O(2) once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups. Results: The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05). Conclusion: During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.

Relative survival of Bacillus subtilis spores loaded on filtering facepiece respirators after five decontamination methods.

This study determines the relative survival (RS) of Bacillus subtilis spores loaded on an N95 filtering facepiece respirator (FFR) after decontamination by five methods under worst-case conditions. Relative survival was obtained by testing after decontamination and after storing the FFRs at 37°C and 95% relative humidity for 24 hours. The decontamination methods involved ethanol, bleach, ultraviolet irradiation (UVA 365 nm, UVC 254 nm), an autoclave, and a traditional electric rice cooker (TERC) that was made in Taiwan. Without decontamination, 59 ± 8% of the loaded spores survived for 24 hours. When 70% ethanol was added to the N95 FFR at a packing density of 0.23, the RS was 73 ± 5% initially and decayed to 22 ± 8% in 24 hours. Relative survival remained above 20% after 20 minutes of UVA irradiation. The other four decontamination measures achieved 99%-100% biocidal efficacy, as measured immediately after the methods were applied to the test FFRs. Relative survival is a useful parameter for measuring sterilization or degree of disinfection. Bleach, UVC, an autoclave, and a TERC provide better biocidal efficacy than ethanol and UVA. Not only a higher filter quality but also a lower value of RS produced the most decontaminated FFR.

Utilization of Western medicine and traditional Chinese medicine among patients with Alzheimer's disease in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: Large-scale studies of utilization of medical services among patients with Alzheimer's disease (AD) are lacking. We aimed to investigate the usage of Western medicine and traditional Chinese medicine (TCM) among these patients in Taiwan. METHODS: We analyzed one million samples from the National Health Insurance Research Database in Taiwan. Patients (n = 1814) newly diagnosed with AD in 2001-2010 were divided into TCM users (n = 528) and non-TCM users (n = 1286). RESULTS: Compared with non-TCM users, TCM users were younger, had a higher female:male ratio and higher utilization rate of Western medicine. The median interval between diagnosis and the first TCM consultation was 7.92 months. Donepezil and rivastigmine were commonly prescribed medications. Chinese herbal medicine was the most popular treatment among TCM users. CONCLUSIONS: This study revealed the specific usage patterns of TCM and non-TCM medical services among patients with AD. The information could be used for improving the healthcare of patients with AD.

Expanded newborn metabolic screening programme in Hong Kong: a three-year journey.

INTRODUCTION: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. METHODS: We retrieved the demographics of the screened newborns and the screening results from July 2013 to July 2016. These data were used to calculate quality metrics such as call-back rate and false-positive rate. Clinical details of true-positive and false-negative cases and their outcomes were described. Finally, the call-back logistics for newborns with positive screening results were reviewed. RESULTS: During the study period, 30 448 newborns referred from 13 private and public units were screened. Of the samples, 98.3% were collected within 7 days of life. The overall call-back rate was 0.128% (39/30 448) and the false-positive rate was 0.105% (32/30 448). Six neonates were confirmed to have inborn errors of metabolism, including two cases of medium-chain acyl-coenzyme A dehydrogenase deficiency, one case of carnitine-acylcarnitine translocase deficiency, and three milder conditions. One case of maternal carnitine uptake defect was diagnosed. All patients remained asymptomatic at their last follow-up. CONCLUSION: The Centre of Inborn Errors of Metabolism has established a comprehensive expanded newborn screening programme for selected inborn errors of metabolism. It sets a standard against which the performance of other private newborn screening tests can be compared. Our experience can also serve as a reference for policymakers when they contemplate establishing a government-funded universal expanded newborn screening programme in the future.

NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia.

A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.

Helicobacter pylori infection and the risk of acute coronary syndrome: a nationwide retrospective cohort study.

Helicobacter pylori infection (HPI) imposes substantial social costs and is of major etiological importance in peptic ulcer disease, gastric cancer, and accelerated cardiovascular diseases. This study determined the risk of acute coronary syndrome (ACS) associated with HPI in a nationwide retrospective cohort study. By using the Taiwan National Health Insurance Research Database (NHIRD), we identified patients diagnosed with HPI from 1998 to 2010. In addition, we randomly selected non-HPI controls frequency-matched by age, sex, and index year from the general population free of HPI. The risk of ACS was analyzed using Cox proportional hazards regression models in which sex, age, and comorbidities were included as variables. We identified 17,075 participants for the HPI group and selected 68,300 participants for the comparison group. The incidence rates were increased in the patients in the HPI group compared with those in the comparison group. Overall, the HPI patients exhibited a 1.93-fold high crude hazard ratio for ACS, and a 1.48-fold adjusted hazard ratio after age, sex, and comorbidities were adjusted. However, the overall adjusted hazard ratio of ACS increased with increasing age with a 3.11 to 8.24 adjusted hazard ratio among the various age groups. Several comorbidities, such as diabetes, hyperlipidemia, and COPD exhibited synergistic effects for ACS risk. We determined a significant association between ACS and comorbidities and provide evidence to encourage clinicians to observe ACS-related comorbidities.

Genetic characterization and in vivo image analysis of novel zebrafish Danio rerio pigment mutants.

This study reports the isolation and characterization of a new type of transparent zebrafish Danio rerio mutant called pinky (pk), which has been visually isolated from a spontaneous mutation in a D. rerio colony. The pk larvae possess complex mutations affecting pigmentation because of missing pigment cells or a dramatic reduction in the chromatophore number. The pk displays a totally colourless phenotype and adult body transplant with no other obvious external morphological abnormalities, except for a red retina. The molecular analysis results in several candidate genes, hps1, ap3m2 and rabggta, implicated in the Hermansky-Pudlak syndrome (HPS) genes associated with HPS in pk. To demonstrate its applications of deep-tissue imaging, this study examines green fluorescent protein alone or with other fluorescent proteins to investigate their capability for using multilabelling purposes in live adult pk. In this study, pk is particularly valuable for tissue cell labelling and internal organogenesis studies because of its optical clarity in the adult body.

Effects of Auditory Training in Older Adults.

PURPOSE: This study examines the effects of an auditory training program on the auditory and cognitive abilities of older adults. Auditory rehabilitation programs are generally designed for hearing aid users, and studies have demonstrated benefits for them. In this study, we seek to understand whether such a training program can also benefit older adults who do not wear hearing aids. We also examined if cognitive benefits can indeed be observed as a result of the training. METHOD: Sixty-four older adults were recruited and assigned into three groups: the experimental group (n = 20), the active control group (n = 21), and the no-training control group (n = 23). The experimental group underwent an auditory training program (Listening and Communication Enhancement [LACE]) during the training phase. Meanwhile, the active control group listened to short audio clips and the no-training control group did not participate in any program. An auditory test (Quick Speech-in-Noise [QuickSIN]) and a battery of cognitive tests were conducted before and after the training to examine the participants' performance on auditory ability, short-term memory, and attention. RESULTS: The results showed improvements in auditory and cognitive abilities during the training period. When assessing the training effects by comparing the pre- and the posttraining performances, a significant improvement on the QuickSIN task was found in the training group but not in the other two groups. However, other cognitive tests did not show any significant improvement. That is, the LACE training did not benefit short-term memory and attention. The improved performance on short-term memory during the training was not maintained in the posttraining session. CONCLUSION: Overall, the study has extended the auditory benefit from the LACE training to the typical aging population in terms of improved communication ability, but the effect of training on auditory abilities did not transfer to gains in cognitive abilities.

Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Amino acid sequence of rabbit muscle aldolase and the structure of the active center.

Elucidation of the amino acid sequence of fructose-1,6-bis-phosphate aldolase from rabbit muscle has made it possible to assign the positions of the functional groups known to play specific roles in the catalytic activity, and also to locate the buried, exposed, and active site cysteine residues. The results indicate that the middle portion of the polypeptide chain, including Cys-134, Cys-149, Cys-177, and Cys-l99, is buried in the native structure, with regions containing Cys-72, Lys-107, Lys-227, Cys-336, His-359, and the COOH-terminal residue (Tyr-361) folded into the active center of the enzyme, at or near the surface of the enzyme molecule.

Central venous catheter use increases ischemic stroke risk: a nationwide population-based study.

BACKGROUND: Central venous catheter (CVC) placement is a common procedure used for the treatment of critically ill patients. However, ischemic stroke is a complication after CVC placement. AIM: This study investigated the association between CVC placement and ischemic stroke risk in an Asian population. DESIGN: Population-based retrospective study. METHODS: We enrolled 37 623 patients who ever-received CVC placement over 2000-10 and propensity score-matched individuals without CVC placement as the comparison cohort from the Taiwan National Health Insurance Research Database. We determined the cumulative incidence rates and adjusted hazard ratios (aHRs) for ischemic stroke. RESULTS: We finally identified and enrolled 34 164 propensity score-matched pairs of individuals. Compared with the comparison group, CVC placement increased the average annual ischemic stroke incidence [19.5 vs. 11.6 per 10 000 person-years; crude HR=1.28, 95%, confidence interval (CI)=1.21-1.35; adjusted subhazard ratio (aSHR)=1.4, 95% CI = 1.33-1.47; P<0.001). In addition, compared with those aged >35 years, stroke risk was significantly higher in <35-year-old patients with CVC placement (aSHR=14.3, 95% CI=6.11-33.4; P<0.001). After <1-year follow-up, the ischemic stroke incidence rate in the CVC placement group was ∼3.25-fold higher than that in the comparison group (aHR=3.25, 95% CI=2.9-3.63; P<0.0001). CONCLUSION: CVC placement increases ischemic stroke risk, particularly in those aged ≤35 years; this trend warrants further investigation.

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study.

OBJECTIVES: Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva. METHODS: This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated. RESULTS: Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776-0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%-96.2%) and 100% (97.3%-100%), respectively, for saliva, and were 96.1% (88.9%-99.2%) and 98.5% (94.7%-99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA. CONCLUSIONS: Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.

The role of a nuclear protein, histone H1, on signalling pathways for the maturation of dendritic cells.

We have demonstrated previously that liver allograft tolerance is associated with the immunosuppressive activity of anti-histone H1 autoreactive antibodies induced in the serum of liver transplantation. Furthermore, we and others have shown that nuclear proteins such as histone H1 and high mobility group box 1 play an important role in maturation of dendritic cells (DCs), although the precise mechanisms are still unknown. In the present study, we focus upon the significance of histone H1 on DCs in terms of the intracellular signalling pathway of DCs. Our immunostaining and immunoblot studies demonstrated that histone H1 was detected in cytoplasm and culture supernatants upon the activation of DCs. Histone H1 blockage by anti-histone H1 antibody down-regulated the intracellular activation of mitogen-activated protein kinases (MAPKs) (p38) and IkappaBalpha of DCs, and inhibited DC activity in the proliferation of CD4+ T cells. On the other hand, the addition of histone H1 without endotoxin stimulation up-regulated major histocompatibility complex class II, the CD80 and CD86 surface markers of DCs and the activation of MAPKs (p38 and extracellular-regulated kinase 1/2) and IkappaBalpha. These results suggest that the translocation of histone H1 from nuclei to cytoplasm and the release of their own histone H1 are necessary for the maturation of DCs and the activation for T lymphocytes.

Significance of portosystemic shunt on graft survival in liver transplantation: a rat model.

AIMS: Distal splenorenal shunt effectively controls bleeding from esophageal and gastric varices but has a different effect on liver transplantation. This study sought to develop an animal model in rats to mimic the recipient with a portosystemic shunt and to investigate its hemodynamic consequences on liver transplantation. METHODS: We prepared 5 groups of allogeneic or syngeneic rat liver transplantation models with versus without portosystemic shunt, to investigate its effects on graft survival and portal flow. To explore the effects of excessive portal flow on graft survival in small-for-size liver transplantation, we transplanted partial liver grafts into syngeneic recipients. RESULTS: In allogeneic combinations, graft survival among the shunt group was shortened compared with their control counterparts. The graft survival of the large shunt group was significantly lower than that of a small shunt or without shunt group in a syngeneic liver transplantation model. Portal blood pressure of the large shunt group was significantly lower than that of the small shunt group. In contrast, excessive portal flow resulted in dysfunction of liver graft in small-for-size liver transplantation. CONCLUSIONS: These results suggested that reduction in portal flow by portosystemic shunt lead to an acceleration of acute rejection and subsequent liver graft dysfunction, but it may be applicable to regulate the excessive portal flow in small-for-size transplantations. This study showed a valuable model mimicking the recipient with a portosystemic shunt.

High-mobility group box 1 protein activates hepatic stellate cells in vitro.

OBJECTIVES: Our previous study noticed remarkably elevated titers of anti-high-mobility group box 1 (HMGB1) antibodies in sera during the tolerance induction phase of a rat tolerogenic orthotopic liver transplantation (OLT) as well as in sera of clinically drug-free patients. We hypothesized that the release of nonhistone nuclear protein HMGB1 during rejection may play a pathogenic role in deteriorating post-OLT graft functions, such as inducing liver fibrosis. This study sought to investigate whether HMGB1 can directly activate hepatic stellate cells (HSCs) and drive them toward fibrogenesis. METHODS: The cultured HSCs were treated with recombinant HMGB1. RT-PCR and Western blotting analysis were used to measure alpha-smooth muscle actin (alpha-SMA) expression. Conditioned media were collected for gelatin zymography to monitor the activities of collagen-degrading matrix metalloproteinases (MMPs). RESULTS: HMGB1 at concentrations > 1 ng/mL significantly stimulated HSC growth as revealed by proliferation and BrdU assays. alpha-SMA gene and protein expression were significantly up-regulated by HMGB1, whereas the MMP-2, but not MMP-9, activity was suppressed by HMGB1 treatment. CONCLUSION: Our data suggested that HMGB1 protein, once released during the rejection phase of OLT, activated HSCs and exhibited profibrogenic effects on liver grafts either by increasing the HSC population and extracellular matrix content in liver grafts, or by transforming HSCs into myofibroblasts. Neutralization with anti-HMGB1 antibody was suggested to be a therapeutic modality applicable to prevent fibrogenesis in post-OLT liver grafts.

Induction of indoleamine 2,3-dioxygenase in livers following hepatectomy prolongs survival of allogeneic hepatocytes after transplantation.

OBJECTIVES: Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of tryptophan into kyneurenine, has immunologic significance for the induction of maternal tolerance and liver allograft tolerance by inhibiting T-cell activation. In the present study, we compared survival of syngeneic or allogeneic hepatocytes in livers with or without hepatectomy. Subsequently, we investigated gene expression and localization of IDO in the recipient liver. METHODS: DA and Fisher 344 rats were used in the following experimental groups: group 1, DA hepatocytes transplanted into hepatectomized Fisher 344 rats; group 2, Fisher 344 hepatocytes transplanted into hepatectomized Fisher 344 rats; group 3, DA hepatocytes transplanted into nonhepatectomized Fisher 344 rats; and group 4, Fisher 344 hepatocytes transplanted into nonhepatectomized Fisher 344 rats. After transplantation, the surviving cells were evaluated on day 5. The IDO signal of the recipient liver was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: In the hepatectomized groups subjected to allogeneic or syngeneic hepatocyte transplantation, the number of surviving hepatocytes was greater than in the nonhepatectomized group after transplantation. The IDO signals (RT-PCR) in the hepatectomized groups were stronger than those in the nonhepatectomized groups. Immunohistochemistry demonstrated that the IDO signal is located in liver antigen-presenting cells, such as Kupffer cells or dendritic cells, and not expressed in hepatocytes. CONCLUSIONS: Our results demonstrated that IDO is induced in antigen-presenting cells of hepatectomized livers by which subsequently transplanted cells may be protected from rejection by inhibiting indirect or direct recognition of donor antigen and further T-cell activation.

The reaction of posttransplant denervated liver on the hemorrhagic shock in rats.

OBJECTIVE: The aims of the study were to determine the effects of denervation on the function of the liver transplantation as a blood reservoir and to define its vulnerability to ischemic-reperfusion (I/R) injury after hemorrhagic shock. MATERIALS AND METHODS: Hemorrhagic shock with a mean arterial blood pressure (MAP) of 40 to 50 mm Hg was induced by withdrawing blood at a rate of approximately 1 mL/min among 10 posttransplant denervated rats and 10 sham rats for 1 hour. The rats were then resuscitated by retransfusing the drawn blood with sacrifice under deep anesthesia at 1 hour after resuscitation. The total amount of blood required to achieve hemorrhagic shock was compared between groups as well as the vulnerability and reactions of the posttransplant denervated liver to I/R injury after hemorrhagic shock as assessed by gene expressions of c-jun, c-fos, tumor necrosis factor (TNF)-alpha, interleukin (IL)6, IL-10, and heat-shock protein 70 (HSP70). RESULTS: The volume of blood that had to be drawn to reach a MAP of 40 to 50 mm Hg was not significantly different between the groups. One hour of hemorrhagic shock followed by resuscitation resulted in significant increases in the genes expression of c-fos, TNF-alpha, IL-6, IL-10, and HSP70 in comparison to the control values, but no difference was observed between experimental and sham groups. CONCLUSION: We suggest that the function of the liver as a blood reservoir and the gene expressions of c-fos and pro- and anti-inflammatory cytokines, as well as the protective protein HSP70 in response to I/R injury, were not altered by liver transplantation.

Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae has a limited life-span, which is measured by the number of divisions that individual cells complete. Among the many changes that occur as yeasts age are alterations in chromatin-dependent transcriptional silencing. We have genetically manipulated histone deacetylases to modify chromatin, and we have examined the effect on yeast longevity. Deletion of the histone deacetylase gene RPD3 extended life-span. Its effects on chromatin functional state were evidenced by enhanced silencing at the three known heterochromatic regions of the genome, the silent mating type (HM), subtelomeric, and rDNA loci, which occurred even in the absence of SIR3. Similarly, the effect of the rpd3Delta on life-span did not depend on an intact Sir silencing complex. In fact, deletion of SIR3 itself had little effect on life-span, although it markedly accelerated the increase in cell generation time that is observed during yeast aging. Deletion of HDA1, another histone deacetylase gene, did not result in life-span extension, unless it was combined with deletion of SIR3. The hda1Delta sir3Delta resulted in an increase in silencing, but only at the rDNA locus. Deletion of RPD3 suppressed the loss of silencing in rDNA in a sir2 mutant; however, the silencing did not reach the level found in the rpd3Delta single mutant, and RPD3 deletion did not overcome the life-span shortening seen in the sir2 mutant. Deletion of both RPD3 and HDA1 caused a decrease in life-span, which resulted from a substantial increase in initial mortality of the population. The expression of both of these genes declines with age, providing one possible explanation for the increase in mortality during the life-span. Our results are consistent with the loss of rDNA silencing leading to aging in yeast. The functions of RPD3 and HDA1 do not overlap entirely. RPD3 exerts its effect on chromatin at additional sites in the genome, raising the possibility that events at loci other than rDNA play a role in the aging process.