Aging is Associated With an Earlier Arrival of Reflected Waves Without a Distal Shift in Reflection Sites

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Background-—Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (TINF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a “distal-shift” of reflection sites. TINF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results-—We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTTWSA) and partially distributed tube-load (TL) modeling (RWTTTL). Consistent with previous reports, TINF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population 15.0 ms/decade, P<0.001; clinical population 9.07 ms/decade, P=0.003) and RWTTTL (general 15.8 ms/ decade, P<0.001; clinical 11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions-—RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with agingNIH/ R56 HL-124073-01A1, 5-R21-AG-043802-02, PPG/1P01-1HL09430

Computer-aided rational design of the phosphotransferase system for enhanced glucose uptake in Escherichia coli

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided design (CAD) system and verified the simulated results with biological experiments. CAD supports construction of a biochemical map, mathematical modeling, simulation, and system analysis. Assuming that the PTS aims at controlling the glucose uptake rate, the PTS was decomposed into hierarchical modules, functional and flux modules, and the effect of changes in gene expression on the glucose uptake rate was simulated to make a rational strategy of how the gene regulatory network is engineered. Such design and analysis predicted that the mlc knockout mutant with ptsI gene overexpression would greatly increase the specific glucose uptake rate. By using biological experiments, we validated the prediction and the presented strategy, thereby enhancing the specific glucose uptake rate

Is dietary pattern of schizophrenia patients different from healthy subjects?

<p>Abstract</p> <p>Background</p> <p>There are limited findings about dietary patterns and food preferences among patients suffering from schizophrenia. The main objective of this study was therefore to compare the nutritional pattern of schizophrenia patients with that of matched healthy subjects.</p> <p>Methods</p> <p>The dietary pattern of 30 hospitalized 16–67 years old schizophrenic patients (11 female) was compared with that of 30 healthy age and sex matched individuals as control group. Subjects' anthropometric measurements including weight, height and body mass index (BMI), semi-quantitative food frequency (FFQ), medical and food history questionnaires were also collected and FFQs were then scored using Food Guide Pyramid to obtain the dietary scores. Percent body fat (%BF) was measured using bioelectrical impedance analysis (BIA) method.</p> <p>Results</p> <p>Female patients had more %BF and lower dietary pattern scores than that of their controls (32 ± 3.6 vs 27.7 ± 4.6 percent and 43.2 ± 11.9 vs 54.5 ± 10.7 points; respectively, p < 0.05 for both). They also consumed less milk and dairy products, fresh vegetables, fruits, chicken, and nuts compared with the female controls (p < 0.03). However, these patients used to eat more full-fat cream and carbonated drinks (p < 0.05). Male patients had lower BMI (22 ± 4.7 vs 25.6 ± 4.4; p < 0.05) than their counterpart controls but there was no significant difference between their %BFs. Moreover, they used to have more full-fat cream, hydrogenated fats, less red meat and nuts compared with the male controls (p < 0.05).</p> <p>Conclusion</p> <p>Schizophrenia patients have poor nutritional patterns. In particular, female patients have more percent body fat and lower dietary pattern scores compared with their healthy controls. All patients used to consume more fats and sweet drinks frequently. The findings of this study suggest that schizophrenia patients need specific medical nutrition therapies through limiting dietary fats and sugars intakes and weight control. Whether obesity is the consequence of disease, dietary preference or medications used remains to be cleared.</p

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11-13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11-13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19

Tetralogy of Fallot with rheumatic mitral stenosis: A case report

<p>Abstract</p> <p>Introduction</p> <p>Rheumatic and congenital heart diseases account for the majority of hospital admissions for cardiac patients in India. Tetralogy of Fallot is the most common congenital heart disease with survival to adulthood. Infective endocarditis accounts for 4% of admissions to a specialized unit for adult patients with a congenital heart lesion. This report is unique in that a severe stenotic lesion of the mitral valve, probably of rheumatic aetiology, was noted in an adult male with Tetralogy of Fallot.</p> <p>Case presentation</p> <p>An unusual association of rheumatic mitral stenosis in an adult Indian male patient aged 35 years with Tetralogy of Fallot and subacute bacterial endocarditis of the aortic valve is presented.</p> <p>Conclusion</p> <p>In this case report the diagnostic implications, hemodynamic and therapeutic consequences of mitral stenosis in Tetralogy of Fallot are discussed. In addition, the morbidity and mortality of infective endocarditis in adult patients with congenital heart disease are summarized. The risk of a coincident rheumatic process in patients with congenital heart disease is highlighted and the need for careful attention to this possibility during primary and follow-up evaluation of such patients emphasized.</p

A Rapid Assessment of the Quality of Neonatal Healthcare in Kilimanjaro Region, Northeast Tanzania.

While child mortality is declining in Africa there has been no evidence of a comparable reduction in neonatal mortality. The quality of inpatient neonatal care is likely a contributing factor but data from resource limited settings are few. The objective of this study was to assess the quality of neonatal care in the district hospitals of the Kilimanjaro region of Tanzania. Clinical records were reviewed for ill or premature neonates admitted to 13 inpatient health facilities in the Kilimanjaro region; staffing and equipment levels were also assessed. Among the 82 neonates reviewed, key health information was missing from a substantial proportion of records: on maternal antenatal cards, blood group was recorded for 52 (63.4%) mothers, Rhesus (Rh) factor for 39 (47.6%), VDRL for 59 (71.9%) and HIV status for 77 (93.1%). From neonatal clinical records, heart rate was recorded for3 (3.7%) neonates, respiratory rate in 14, (17.1%) and temperature in 33 (40.2%). None of 13 facilities had a functioning premature unit despite calculated gestational age <36 weeks in 45.6% of evaluated neonates. Intravenous fluids and oxygen were available in 9 out of 13 of facilities, while antibiotics and essential basic equipment were available in more than two thirds. Medication dosing errors were common; under-dosage for ampicillin, gentamicin and cloxacillin was found in 44.0%, 37.9% and 50% of cases, respectively, while over-dosage was found in 20.0%, 24.2% and 19.9%, respectively. Physician or assistant physician staffing levels by the WHO indicator levels (WISN) were generally low. Key aspects of neonatal care were found to be poorly documented or incorrectly implemented in this appraisal of neonatal care in Kilimanjaro. Efforts towards quality assurance and enhanced motivation of staff may improve outcomes for this vulnerable group

Peroxisome proliferator-activated receptor α (PPARα) mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer.</p> <p>Methods</p> <p>The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system.</p> <p>Results</p> <p>The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.</p> <p>Conclusion</p> <p>The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.</p

Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients

BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF) but national samples are rarely large, and case-selection may be biased due to enrolment in academic centres. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, healthcare resource utilization (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from four high-income countries (USA, UK, Taiwan, Japan) on three continents. METHODS AND RESULTS: We used EHR to identify unplanned HFH between 2012-2014. We identified 231,512, 10,991, 36,900 and 133,982 patients with a primary HFH from USA, UK, Taiwan and Japan, respectively. HFH per 100,000 population was highest in USA and lowest in Taiwan. Patients in Taiwan and Japan were older but fewer were obese or had chronic kidney disease. LOHS was shortest in USA (median 4 days) and longer in UK, Taiwan and Japan (medians 7, 9 and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in USA (direct standardized rates: 1.8 [95%CI:1.7-1.9]%)and progressively higher in Taiwan (direct standardized rates: 3.9 [95%CI:3.8-4.1]%), UK (direct standardized rates: 6.4 [95%CI:6.1-6.7]%) and Japan (direct standardized rates: 6.7 [95%CI:6.6-6.8]%). 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in USA and lowest in Japan (11.9% and 5.1% respectively). CONCLUSION: Marked international variations in patient characteristics, HRU and clinical outcome exist; understanding them might inform health care policy and international trial design

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)