Recent advances in technology have enabled the noninvasive evaluation of pulsatile hemodynamics in the central aorta; namely, central pressure and flow measurements. The central blood pressure represents the true load imposed on the heart, kidney and brain, and the central blood flow influences the local flow into these vital organs. An elevation of the central blood pressure has a direct, adverse impact on the target organ and, thus, the cardiovascular prognosis in patients with hypertension. A decrease in the central blood flow can cause organ dysfunction and failure. The central pressure and flow dynamics were conventionally regarded as unidirectional from the heart to the periphery. However, current evidence suggests that it should be recognized as a bidirectional interplay between the central and peripheral arteries. Specifically, the pressure pulse wave is not only transmitted forward to the periphery but also reflected backward to the central aorta. The flow pulse wave is also composed of the forward and reverse components. Aortic stiffening and arteriolar remodeling due to hypertension not only augment the central pressure by increasing the wave reflection but also may alter the central bidirectional flow, inducing hemodynamic damage/dysfunction in susceptible organs. Therefore, central hemodynamic monitoring has the potential to provide a diagnostic and therapeutic basis for preventing systemic target organ damage and for offering personalized therapy suitable for the arterial properties in each patient with hypertension. This brief review will summarize hypothetical mechanisms for the association between the central hemodynamics and hypertensive organ damage in the heart, kidney and brain.
Acute abdominal pain is one of the most frequent causes of admission to emergency departments. However, there is a shortage of detail information showing the difference of outcomes or etiology of acute abdominal pain according to age. We therefore conducted an epidemiological analysis to reveal the difference between age on outcomes and etiology of acute abdominal pain using an administrative database associated with the Diagnosis Procedure Combination (DPC) system. We obtained discharge data relating to 12,209 patients with acute abdominal pain from 931 DPC participation hospitals between 2009 and 2011 in Japan. We compared length of hospital stay (LOS), in-hospital mortality, and etiology of acute abdominal pain between age categories. Patients were divided into five age groups as follows: < 20 (n = 1,106), 20-39 (n = 3,353), 40-59 (n = 2,925), 60-79 (n = 3,144), and ≥ 80 years (n = 1,681). Longer LOS and higher in-hospital mortality were observed in patients aged ≥ 80 years (p < 0.001). Regarding etiologies of acute abdominal pain, intestinal infection or acute appendicitis were more frequent in patients aged < 20 or 20-39 years, while ileus or cholelithiasis were more frequent in patients aged 60-79 or ≥ 80 years in both male and female patients (p < 0.001). This study demonstrated the significant differences between age with regard to the patient outcomes and etiology of acute abdominal pain. The current findings highlight the importance of improving the quality of medical care for patients with acute abdominal pain.
Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.
Prostate cancer (PCa) is the second leading cause of cancer-related death in men globally. However, there are few sensitive biomarkers for PCa, especially those which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody microarrays allow for high-throughput and high-sensitivity detection of multiple proteins simultaneously, providing a powerful tool for biomarker screening. Here, we selected 46 patients with PCa and 42 controls with BPH, and compared the serum levels of different cytokines in PCa and BPH patients using antibody microarrays. The results indicated that serum levels of macrophage colony-stimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa pathogenesis, and thus were used as positive controls in the present study. CCL-18 is a chemokine primarily involved in recruitment of the adaptive immune system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells. Serum levels of these four cytokines could distinguish PCa from BPH with high sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC) was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as new potential serum biomarkers for PCa.
Integrins, which act as an important role in the connection between cells and extra-cellular environments, are important cell surface receptors. Integrins have been demonstrated to play critical roles in many aspects of the progression of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in microRNA-binding sites of integrin genes and the susceptibility and progression of OSCC in Chinese Han Population. We recruited 167 OSCC patients and 200 cancer-free controls from three independent medical centers. Genotyping was completed successfully for the five selected integrin SNPs: rs1062484 (integrin α3), rs11902171 (integrin αv), rs17468 (integrin β1), rs3809865 (integrin β3), and rs2675 (integrin β5). The results demonstrated that the A allele of rs3809865 T/A (a T-to-A nucleotide change), a functional polymorphism in the 3′UTR of integrin β3 gene, was associated with OSCC risk (p < 0.05). In addition, the association analysis between this SNP and integrin β3 mRNA expression level in the patients’ peripheral blood mononuclear cells indicated that OSCC patients carrying the A allele would have a lower integrin β3 expression level (p = 0.047). Meanwhile, survival analysis showed that the C allele of rs2675 A/C (nucleotide change from A to C), another 3′UTR polymorphism in integrin β5 gene, was related with progression of OSCC. Overall, our results suggest that rs3809865 and rs2675 may contribute to OSCC risk and progression in Chinese Han Population. These two SNPs may be used as potential diagnostic and prognostic biomarkers for OSCC in future.
As the impacts of natural disasters have grown more severe, the importance of education for disaster medicine gains greater recognition. We launched a project to establish an international educational program for disaster medicine. In the present study, we surveyed medical personnel and medical/public health students in the Philippines (n = 45) and Indonesia (n = 67) for their awareness of the international frameworks related to disaster medicine: the Human Security (securing individual life and health), the Sphere Project (international humanitarian response), and the Hyogo Framework for Action 2005-2015 (international strategy for disaster reduction). In both countries, more than 50% responders were aware of human security, but only 2 to 12% were aware of the latter two. The survey also contained questions about the preferred subjects in prospective educational program, and risk perception on disaster and disaster-related infections. In the Philippines, significant disasters were geophysical (31.0%), hydrological (33.3%), or meteorological (24.8%), whereas in Indonesia, geophysical (63.0%) and hydrological (25.3%) were significant. Moreover, in the Philippines, leptospirosis (27.1%), dengue (18.6%), diarrhea (15.3%), and cholera (10.2%) were recognized common disaster-related infections. In Indonesia, diarrhea (22.0%) and respiratory infection (20.3%) are major disaster-related infections. Water-related infections were the major ones in both countries, but the profiles of risk perception were different (Pearson’s chi-square test, p = 1.469e-05). The responders tended to overestimate the risk of low probability and high consequence such as geophysical disaster. These results are helpful for the development of a postgraduate course for disaster medicine in Asia Pacific countries.
Eosinophils are regarded as the major effector cells that produce symptoms in allergic diseases. Activation of eosinophils induces extracellular release of a number of eosinophil granule proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin. The objective of this study was to evaluate the differences and significance of the sputum eosinophil% and expression levels of eosinophilic granule protein mRNAs in allergic airway disease. Induced sputum samples were obtained from non-smokers with 25 asthma, 54 eosinophilic bronchitis, 16 allergic rhinitis, and 19 healthy control subjects. The eosinophil granule protein mRNAs were measured with real time RT-PCR. There was no correlation between the sputum eosinophil% and the mRNA level of any of eosinophil granule proteins. However, the expression levels of MBP and ECP mRNAs were higher in subjects with each of the specified allergic diseases than those in control subjects (P < 0.05). Moreover, in the subjects with allergic sensitization, the expression levels of MBP and EPO mRNAs were significantly higher in those with airway hyperresponsiveness (13 subjects) than in those without airway hyperresponsiveness (32 subjects) (P = 0.004 and 0.010, respectively). In asthma patients, the FEV1% was negatively correlated with ECP mRNA levels (r = −0.510, P = 0.022), but showed no correlation with sputum eosinophil%. In conclusion, mRNA levels of eosinophil granule proteins, rather than sputum eosinophil%, may reflect airway hyperresponsiveness and airflow limitation. In practice, consideration for the eosinophil% as well as the eosinophil granule proteins levels in induced sputum is needed.
A cardiopulmonary exercise test (CPX) can provide objective measures of exercise capacity. Specifically, incremental ramp exercise (IRE) and constant work-rate exercise (CWE) protocols are frequently used in clinical practice and for research. The CWE endurance time has shown larger increases than other indexes assessed by IRE after rehabilitation intervention. Muscle oxygen extraction is one of the important physiological factors of exercise capacity; however, the differences in muscle oxygen kinetics between IRE and CWE remain unclear. The purpose of this study was to compare the muscle oxygen kinetics during IRE and CWE. Each of the 15 participants performed IRE and CWE to exhaustion on a cycle ergometer. Ventilatory and muscle deoxygenation responses were measured during the tests; muscle deoxygenation was determined using near-infrared spectroscopy. No differences in oxygen uptake and heart rate were observed between the two tests. A comparison of the muscle deoxygenation kinetics between the two tests indicated significantly greater deoxygenation during the CWE than during the IRE at all time points (p < 0.05). The muscle deoxygenation kinetics, as percentages of maximal oxygen uptake (VO2max), were higher during CWE than during IRE, except at 80% of VO2max (p < 0.05). These results suggest that skeletal muscle during CWE extracts oxygen at a rate comparable to that during IRE, and that exercise capacity assessed using CWE might be linked to a higher overall O2 extraction. The fact that endurance time during CWE is more sensitive to rehabilitation intervention may be due to improvements in muscle oxygen extraction.
Gastrointestinal stromal tumors (GISTs) are the most common among gastrointestinal mesenchymal tumors, but its prognosis has not been accurately predicted by the current risk stratification guidelines, National Institutes of Health classification. In this study, we evaluated the predictive factors for GIST prognosis in a retrospective analysis of 332 patients. The data collected included tumor sites, including the esophagus, stomach, duodenum, small intestine, and extragastrointestinal sites; tumor size; microscopic indicators for malignant tumor behavior, such as the number of dividing cells, cell necrosis, atypical morphology, and invasion into the muscular or mucous layer; and previously established immunohistochemical indicators, CD117, CD34, and discovered on GIST-1 (DOG-1). No single occurrence of any microscopic indicators correlated with the prognosis of GIST; however, the total number of microscopic indicators was a significant prognostic factor of GIST (P < 0.001). Regarding the tumor sites, the order of prognostic risk (from the lowest to the highest) was as follows: the esophagus, stomach, duodenum, small intestine, extragastrointestinal sites, and colorectum. The association between tumor sites and prognosis was significant (P < 0.001). On the other hand, the expression of CD117 or CD34 was not associated with the risk of GIST. Importantly, 91% of the patients (302/332) showed the expression of DOG-1, and the lack of DOG-1 expression was associated with poor prognosis (P < 0.05). In conclusion, both tumor sites and total number of microscopic indicators are independent risk factors associated with the prognosis of GIST. The lack of DOG-1 expression may be predictive of malignant outcome.