ABSTRACT
This review delves into the critical role of automation and sensor technologies in optimizing parameters for thermal treatments within electrical power generation. The demand for efficient and sustainable power generation has led to a significant reliance on thermal treatments in power plants. However, ensuring precise control over these treatments remains challenging, necessitating the integration of advanced automation and sensor systems. This paper evaluates the pivotal aspects of automation, emphasizing its capacity to streamline operations, enhance safety, and optimize energy efficiency in thermal treatment processes. Additionally, it highlights the indispensable role of sensors in monitoring and regulating crucial parameters, such as temperature, pressure, and flow rates. These sensors enable real-time data acquisition, facilitating immediate adjustments to maintain optimal operating conditions and prevent system failures. It explores the recent technological advancements, including machine learning algorithms and IoT integration, which have revolutionized automation and sensor capabilities in thermal treatment control. Incorporating these innovations has significantly improved the precision and adaptability of control systems, resulting in heightened performance and reduced environmental impact. This review underscores the imperative nature of automation and sensor technologies in thermal treatments for electrical power generation, emphasizing their pivotal role in enhancing operational efficiency, ensuring reliability, and advancing sustainability in power generation processes.
ABSTRACT
BACKGROUND: Cancer pain is one of the main causes of human suffering, which can generate disabilities and compromise quality of life, giving rise to several psychosocial and economic consequences. AIMS: This quantitative study sought to perform a cost-effectiveness pharmacoeconomic analysis to assess the impact of implanting epidural morphine associated with ropivacaine treatment in gastrointestinal cancer patients with pain that is difficult clinical control, compared with conventional oral treatment. MATERIALS AND METHODS: The study population consisted of 24 patients with gastrointestinal neoplasia who underwent treatment for cancer pain that was difficult to clinically control. 12 patients each were recruited into the control and intervention groups, respectively. While patients in the control group were administered drug treatment orally, patients in the intervention group underwent a surgical procedure for subcutaneous implantation of a catheter that allowed epidural administration of morphine and ropivacaine. For pain assessment, the Visual Analogue Scale was applied. Data analysis had a descriptive character of costs, taking into account the costs for the year 2021. The study perspective was the Brazilian public healthcare provider, referred to as the Unified Health System (Sistema Único de-SUS in Portuguese). Costs were computed over the time horizon corresponding to the duration of treatment, from the first medical consultation (when the treatment was defined) to the end (end of treatment, disease progression, or death). Treatment duration was divided into three phases (first 60 days, support with palliative care, and end-of-life care). To assess the robustness of the economic analysis, sensitivity analyses were performed, considering the effectiveness of pain reduction on the Visual Analogue Scale, and a comparison of results using the median prices of pharmaceutical components used in the study. RESULTS: The mean age of patients was 59.3 years. The results from the cost-effectiveness analysis showed the epidural morphine/ropivacaine treatment to be more effective with regard to pain reduction on the pain scale, particularly for end-of-life care, when compared to the conventional oral treatment, however, at a significantly higher cost. DISCUSSION: From the accomplishment of this research, it was observed that the application of the pain assessment scale is a way to better interpret and understand the patient's pain, facilitating care planning and decision-making by health professionals, as well as monitoring the effectiveness of the proposed new treatment. CONCLUSION: To present a better cost-effectiveness ratio, a reduction in the cost of the new epidural technology or an increase in the value of the existing oral intervention would be required. However, the latter is not feasible and unlikely to occur. A value judgement to decide whether the incremental benefit associated with the use of the new intervention is worth the extra cost will have to be made by the healthcare provider. Interventions that can relieve cancer pain symptoms should be investigated continuously, in search of evidence to support clinical practice and promote better quality of life for patients.
Subject(s)
Cancer Pain , Neoplasms , Humans , Middle Aged , Morphine , Ropivacaine , Cost-Effectiveness Analysis , Quality of Life , Cancer Pain/drug therapy , Cancer Pain/etiology , Cost-Benefit Analysis , Neoplasms/drug therapyABSTRACT
Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever-increasing relevance. Opioid-sparing strategies, such as multimodal analgesia, are trends in this scenario. Pregabalin is a well-established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double-blind, placebo-controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty-five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy.
Subject(s)
Analgesia , Analgesics, Opioid , Humans , Female , Pregabalin/therapeutic use , Prospective Studies , Analgesics/therapeutic use , Hysterectomy/adverse effects , Hysterectomy/methods , Pain, Postoperative/etiology , Pain, Postoperative/chemically induced , Double-Blind MethodABSTRACT
The genetic influence in obesity prevalence is well described, but the role of genetic markers related to athletic strength/ endurance performance remains controversial. We investigated associations between obesity and the genetic polymorphisms alpha-actinin-3 (ACTN3) R577X and angiotensin-converting enzyme (ACE) I/D in schoolchildren aged 4-13 years from Southern Brazil. We collected sociodemographic data from parents through a questionnaire and conducted an anthropometric assessment. DNA was extracted from buccal cells and genotyping was performed by PCR. We found that 1.9% of the individuals were classified as low weight-for-age, 57.6% as normal weight and 40.5% as overweight/ obesity. Regarding allelic distribution, we found that 52.5% of individuals were DD, 30.8% ID, and 16.7% II for ACE; and 38.8% of individuals were RR, 40.2% RX and 21.0% XX for ACTN3. When both polymorphisms were combined, we observed a clear association between the composed genetic profile of these alleles and severe obesity in schoolchildren. Our data suggest that the combined analysis of ACTN3 R577X and ACE I/D polymorphisms may serve as a predictor for the risk of severe obesity in children. These data can contribute to a better understanding of the relationship between these polymorphisms and the body weight development of school-age children.
Subject(s)
Actinin/genetics , Pediatric Obesity/genetics , Peptidyl-Dipeptidase A/genetics , Adolescent , Brazil/epidemiology , Child , Child, Preschool , Female , Genotype , Humans , Male , Polymorphism, Genetic , Risk FactorsABSTRACT
This study aims to analyze the behaviour of cardiac autonomic modulation in adolescents with a family history of hypertension along with polymorphism of the ACE gene (rs1799752). The study involved 141 adolescents, with a mean age of 14.89, divided into the following six groups: offspring of normotensive parents (ONP): DD, DI and II; and offspring of hypertensive parents (OHP): DD, DI and II. Blood pressure, body composition, family history of hypertension, sleep disorder, and sexual maturation were assessed for the groups' characterization. Afterwards, an electrocardiogram was performed, and oral mucosal cells were collected to analyze heart rate variability and genotypic research of angiotensin-converting enzyme. The main finding of this study was the decrease of vagal action in group OHP (genotype DD) relative to group ONP (genotype II): LF (%), 54.25 ± 3.14 vs 39.33 ± 3.80; HF (%), 45.74 ± 3.14 vs 60.66 ± 3.80; LF/HF, 1.48 ± 0.23 vs 0.68 ± 0.19. The results also showed changes in the variable diastolic blood pressure (DBP) in OHP (genotype DI) to ONP (genotype II) groups: 72.99 ± 2.33 vs 63.27 ± 1.72; and OHP (genotype DI) to ONP (genotype DD) groups. Adolescents with genotype DD and a family history of arterial hypertension present chances in cardiac autonomic modulation, the cardiac parasympathetic modulation is lower in these adolescents in comparison to participants of ONP + II group.
Subject(s)
Peptidyl-Dipeptidase A , Adolescent , Humans , Hypertension , Male , Middle Aged , Polymorphism, GeneticABSTRACT
BACKGROUND: Immune haemolysis in liver transplant (LT) can occur due to autoantibodies and alloantibodies. The aim of this study was to evaluate the prevalence and risk factors for immune haemolysis in LT. METHODS: A total of 175 consecutive patients were included. Multiorgan recipients were excluded. Samples, from before LT, seven consecutive days and weekly for 4 weeks, were evaluated for haemolysis and immunohaematological tests. SPSS 24 was used for statistical analysis. RESULTS: Nine patients (5·1%) presented positive antibody screen (AS) before LT, (2·3% clinically significant), more frequent in RhD-negative (P = 0·017). Positive DAT occurred in 53 (30·3%) and was related to high MELD score (P = 0·048), HCV (P = 0·005) and furosemide use (P = 0·001). Positive AS after LT occurred in 22 patients (12·5%), with nine (5·7%) clinically significant antibodies. Positive AS occurred more frequently in RhD negative (P = 0·021) and in those transfused (P = 0·022). Post-transplant positive DAT was associated with piperacillin-tazobactam use (P = 0·021) and minor ABO incompatibility (P = 0·0038). Five patients presented passenger lymphocyte syndrome (PLS), all received liver-graft O, four presented haemolysis, and three were transfused due to PLS. CONCLUSION: Auto- and alloantibodies against red blood cell antigens are frequent in LT, but the frequency of immune haemolysis was only 2·8%. The only risk factor for PLS was minor ABO mismatch.
Subject(s)
Anemia, Hemolytic/etiology , Hemolysis , Liver Transplantation/adverse effects , ABO Blood-Group System , Adolescent , Adult , Autoantibodies , Female , Humans , Isoantibodies , Male , Middle Aged , Prospective Studies , Young AdultABSTRACT
The aim of this study was to investigate the effect of calorie restriction (CR) during pregnancy in mice on metabolism and ovarian function in the offspring. Pregnant female mice were divided into two groups, a control group and a CR group (n=7 in each). Mice in the CR group were fed 50% of the amount consumed by control females from Day 10 of gestation until delivery. After weaning, the offspring received diet ad libitum until 3 months of age, when ovaries were collected. Ovaries were serially cut and every sixth section was used for follicle counting. Female offspring from CR dams tended to have increased bodyweight compared with offspring from control females (P=0.08). Interestingly, fewer primordial follicles (60% reduction; P=0.001), transitional follicles (P=0.0006) and total follicles (P=0.006) were observed in offspring from CR mothers. The number of primary, secondary and tertiary follicles did not differ between the groups (P>0.05). The CR offspring had fewer DNA double-strand breaks in primary follicle oocytes (P=0.03). In summary, CR during the second half of gestation decreased primordial ovarian follicle reserve in female offspring. These findings suggest that undernutrition during the second half of gestation may decrease the reproductive lifespan of female offspring.
Subject(s)
Caloric Restriction/adverse effects , Ovarian Reserve/physiology , Prenatal Nutritional Physiological Phenomena/physiology , Animals , Animals, Newborn , Female , Glucose/metabolism , Male , Malnutrition/complications , Malnutrition/metabolism , Malnutrition/physiopathology , Mice , Mice, Inbred C57BL , Phenotype , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Reproduction/physiologyABSTRACT
ß-hydroxy-ß-methyl butyrate (HMB) is a bioactive metabolite derived from the amino acid leucine, usually applied for muscle mass increase during physical training, as well as for muscle mass maintenance in debilitating chronic diseases. The hypothesis of the present study is that HMB is a safe supplement for muscle mass gain by strength training. Based on this, the objective was to measure changes in body composition, glucose homeostasis and hepatic metabolism of HMB supplemented mice during strength training. Two of four groups of male mice (n = 6/group) underwent an 8-week training period session (climbing stairs) with or without HMB supplementation (190 mg/kgBW per day). We observed lower body mass gain (4.9 ± 0.43% versus 1.2 ± 0.43, p < 0.001) and increased liver mass (40.9 ± 0.9 mg/gBW versus 44.8 ± 1.3, p < 0.001) in the supplemented trained group compared with the non-supplemented groups. The supplemented trained group had an increase in relative adipose tissue mass (12.4 ± 0.63 mg/gBW versus 16.1 ± 0.88, P < 0.01) compared to the non-supplemented untrained group, and an increase in fasting blood glucose (111 ± 4.58 mg/dL versus 122 ± 3.70, P < 0.05) and insulin resistance (3.79 ± 0.19 % glucose decay/min versus 2.45 ± 0.28, P < 0.05) comparing with non-supplemented trained group. Adaptive heart hypertrophy was observed only in the non-supplemented trained group (4.82 ± 0.05 mg/gBW versus 5.12 ± 0.13, P < 0.05). There was a higher hepatic insulin-like growth factor-1 expression (P = 0.002) in supplemented untrained comparing with non-supplemented untrained group. Gene expression of gluconeogenesis regulatory factors was increased by training and reduced by HMB supplementation. These results confirm that HMB supplementation associated with intensive training protocol drives changes in glucose homeostasis and liver metabolism in mice.
Subject(s)
Dietary Supplements , Glucose/metabolism , Homeostasis/drug effects , Muscle, Skeletal , Valerates/metabolism , Animals , Glucose/chemistry , Humans , Liver , Male , Mice , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Valerates/chemistryABSTRACT
We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients treated with interferon-free direct-acting antiviral agent-based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%-93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12-2.41), a baseline cluster of differentiation 4-positive (CD4+) T-cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. CONCLUSION: In this large real-world study, direct-acting antiviral agent-based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus-related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct-acting antiviral agent-based regimens. (Hepatology 2018;68:32-47).
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C/drug therapy , Registries , Administration, Oral , Coinfection , Female , Hepacivirus/genetics , Hepatitis C/complications , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Treatment FailureABSTRACT
Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention.
Subject(s)
Heart Rate , Heart/innervation , INDEL Mutation , Peptidyl-Dipeptidase A/genetics , Renal Dialysis , Renal Insufficiency, Chronic/therapy , Sympathetic Nervous System/physiopathology , Adult , Aged , Body Composition , Cross-Sectional Studies , Female , Gene Frequency , Heterozygote , Homozygote , Humans , Male , Middle Aged , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/enzymology , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/physiopathology , Time Factors , Treatment Outcome , Water-Electrolyte BalanceABSTRACT
We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Coinfection/drug therapy , Hepatitis C, Chronic/epidemiology , Interferon-alpha/therapeutic use , Ribavirin/therapeutic use , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/epidemiology , Adult , Cohort Studies , Coinfection/physiopathology , Comorbidity , Databases, Factual , Drug Therapy, Combination , Female , Follow-Up Studies , HIV/drug effects , HIV/isolation & purification , Hepacivirus/drug effects , Hepacivirus/isolation & purification , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Humans , Incidence , Male , Middle Aged , Regression Analysis , Retrospective Studies , Risk Assessment , Spain/epidemiology , Survival Analysis , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: Fructose intake is directly related to vascular dysfunction and it is a risk factor for the development of metabolic and cardiovascular diseases, such as obesity, diabetes, and hypertension. Selenium, a component of antioxidant enzymes, improves hyperglycemia and vascular function in diabetic animals. The aim of this study was to evaluate the effects of dietary selenium supplementation on microcirculatory and metabolic parameters of fructose-fed hamsters. METHODS AND RESULTS: Male hamsters (Mesocricetus auratus) had their drinking water substituted or not by 10% fructose solution for 60 days, during which their microcirculatory function was evaluated in the cheek pouch preparation. Blood glucose and serum insulin levels were also tested. Microcirculatory responses to acetylcholine (an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator), and macromolecular permeability increase induced by a 30-min ischemia/reperfusion (I/R) procedure, showed that endothelium-dependent and independent vasodilatation was significantly increased in animals that had high selenium supplementation, in both the control and fructose-fed groups. Selenium supplementation protected against plasma leakage induced by I/R in all control and fructose-fed groups. CONCLUSION: Our results indicate that dietary selenium supplementation reduces microvascular dysfunction by increasing endothelial-dependent and independent dilatation and reducing macromolecular permeability increase in fructose-fed animals.
Subject(s)
Fructose/administration & dosage , Microcirculation/drug effects , Selenium/administration & dosage , Acetylcholine/pharmacology , Animals , Blood Glucose/analysis , Capillary Permeability/drug effects , Cheek/blood supply , Cricetinae , Dietary Supplements , Drinking , Endothelium, Vascular/physiology , Fructose/adverse effects , Insulin/blood , Male , Mesocricetus , Microcirculation/physiology , Nitroprusside/pharmacology , Reperfusion Injury , Vasodilation/drug effects , Vasodilator Agents/pharmacologyABSTRACT
Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four ß-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc.
Subject(s)
Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cell Membrane/drug effects , DNA-Binding Proteins/pharmacology , Humans , K562 Cells , Peptides, Cyclic/pharmacologyABSTRACT
The aim of this study was to compare serum lipid profiles and ovarian gene expression between aged and younger female mice fed a control or a high-fat diet for 2 months. For this 16 female mice (C57BL/6) of 4 months (Young, n = 8) or 13 months (Old, n = 8) of age were used. The females were divided into four groups: (i) young females fed a normal diet; (ii) young females fed a high-fat diet; (iii) old females fed a normal diet; and (iv) old females fed a high-fat diet. Food intake was reduced (P < 0.05) in mice fed with a high-fat (2.9 ± 0.1 g) diet in comparison with control mice (3.9 ± 0.1 g). Body weight was higher for old females on the high-fat diet (35.1 ± 0.3 g) than for young females on the same diet (23.3 ± 0.4 g; P < 0.05). PON1 activity was lower in the high-fat than control diet group (114.3 ± 5.8 vs. 78.1 ± 6.0 kU/L, respectively) and was higher in older than younger females (85.9 ± 6.4 vs. 106.5 ± 5.3; P < 0.05, respectively). Females fed a high-fat diet had lower expression of Igf1 mRNA (P = 0.04). There was an interaction between age and diet for the expression of Gdf9 and Survivin, with lower expression in older females in both diets and young females that received the high-fat diet (P < 0.05). Concluding, the high-fat diet reduced the expression of ovarian Igf1 mRNA, and Gdf9 and Survivin mRNA in younger females, which can indicate lower fertility rates. High-density lipoprotein concentration and PON1 activity were higher in aged female mice.
Subject(s)
Diet, High-Fat/adverse effects , Gene Expression Regulation , Lipids/blood , Ovary/physiology , Aging/physiology , Animals , Aryldialkylphosphatase/blood , Cholesterol/blood , Eating , Female , Growth Differentiation Factor 9/genetics , Inhibitor of Apoptosis Proteins/genetics , Insulin-Like Growth Factor I/genetics , Mice, Inbred C57BL , Ovary/drug effects , Repressor Proteins/genetics , SurvivinABSTRACT
Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.
Subject(s)
HIV Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/prevention & control , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/prevention & control , Antiretroviral Therapy, Highly Active , Bacterial Infections/drug therapy , Coinfection , Humans , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/prevention & control , Mycobacterium Infections/drug therapy , Mycobacterium Infections/prevention & control , Mycoses/drug therapy , Mycoses/prevention & control , Opportunistic Infections/etiology , Parasitic Diseases/drug therapy , Parasitic Diseases/prevention & control , Virus Diseases/drug therapy , Virus Diseases/prevention & controlABSTRACT
Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
Subject(s)
HIV Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/prevention & control , AIDS-Related Opportunistic Infections/prevention & control , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Coinfection/drug therapy , Coinfection/prevention & control , Humans , Immune Reconstitution Inflammatory Syndrome/diagnosis , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/prevention & control , Mycoses/drug therapy , Mycoses/prevention & control , Parasitic Diseases/drug therapy , Parasitic Diseases/prevention & control , Virus Diseases/drug therapy , Virus Diseases/prevention & controlABSTRACT
After three decades of reform, the medical care system in China has experienced significant changes. However, the present research has not made a tentative evaluation of it to justify further reform. This paper analyses the cost efficiency of Chinese hospitals in 31 provinces during the period from 2002 to 2011 and adopts a Bayesian stochastic frontier model taking account of the identified heterogeneity according to the background of Chinese medical system reform, including the coastal location, 3A class hospital proportion, public subsidies and medical insurance reforms. It finds that the public subsidies and medical insurance reforms have improved the cost efficiency of Chinese hospitals, while the coastal location and 3A class hospital proportion have decreased the cost efficiency of Chinese hospitals. Therefore, these results imply that it will be beneficial for Chinese medical system to optimize the fiscal subsidies of public hospitals, encourage the entrance of private hospitals, improve the medical insurance coverage and set up the pre-triage system.
ABSTRACT
The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity.
Subject(s)
Gluconeogenesis/physiology , Glucose Intolerance/enzymology , Insulin Resistance/physiology , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Adipose Tissue/physiology , Animals , Blood Glucose/metabolism , Blood Pressure/physiology , Genotype , Gluconeogenesis/genetics , Glucose Intolerance/genetics , Insulin Resistance/genetics , Liver/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Fibers, Fast-Twitch/physiology , Muscle, Skeletal/physiology , Phenotype , Physical Conditioning, Animal/physiology , Pyruvic Acid/metabolismABSTRACT
BACKGROUND: We compared the prognostic value of liver biopsy (LB) and FIB-4 index in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. METHODS: We studied patients from the Grupo de Estudio del SIDA 3603 study cohort, in whom fibrosis was evaluated at baseline using both LB (Metavir score) and FIB-4 index. We assessed overall death (OD) and liver-related events (LREs), defined as decompensation or hepatocellular carcinoma, whichever occurred first. We used receiver operating characteristic (ROC) curves to determine the ability of LB and FIB-4 to predict outcomes. We also assessed the association between advanced fibrosis-LB (F3 or greater) or FIB-4 (≥3.25)-and outcomes using multivariate Cox regression analysis. RESULTS: The study sample comprised 903 patients (328 with sustained virologic response [SVR]). Baseline fibrosis by LB was as follows: F0, n = 71; F1, n = 242; F2, n = 236; F3, n = 236; F4, n = 118. Fibrosis by FIB-4 was as follows: ≤1, n = 148; >1 to <3.25, n = 597; ≥3.25, n = 158. After a median follow-up of 62 months, there were 46 deaths and 71 LREs. The area under the ROC curves for OD/LREs was 0.648 and 0.742 for LB and FIB-4, respectively (P = .006). Similar results were found for patients without SVR and for OD and LREs separately. The adjusted hazard ratios of OD or LRE were 1.740 (95% confidence interval [CI], 1.119-2.7.06; P = .014) for advanced fibrosis assessed by LB and 3.896 (95% CI, 2.463-6.160; P < .001) assessed by FIB-4. CONCLUSIONS: FIB-4 outperformed LB as a predictor of OD and LRE. These findings are of relevance for clinical practice and research and call into question the role of LB as a gold standard for assessing prognosis in HIV/HCV coinfection.
Subject(s)
Coinfection , HIV Infections/complications , Hepatitis C, Chronic/complications , Liver Cirrhosis/diagnosis , Liver/pathology , Adult , Biopsy , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cohort Studies , Female , Follow-Up Studies , HIV Infections/diagnosis , HIV Infections/therapy , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/therapy , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Prognosis , ROC CurveABSTRACT
There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(â¢)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(â¢) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(â¢)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(â¢) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(â¢)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(â¢)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(â¢) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling.