Structure of putative epidermal sensory receptors in an acoel flatworm, Praesagittifera naikaiensis.

Acoel flatworms possess epidermal sensory-receptor cells on their body surfaces and exhibit behavioral repertoires such as geotaxis and phototaxis. Acoel epidermal sensory receptors should be mechanical and/or chemical receptors; however, the mechanisms of their sensory reception have not been elucidated. We examined the three-dimensional relationship between epidermal sensory receptors and their innervation in an acoel flatworm, Praesagittifera naikaiensis. The distribution of the sensory receptors was different between the ventral and dorsal sides of worms. The nervous system was mainly composed of a peripheral nerve net, an anterior brain, and three pairs of longitudinal nerve cords. The nerve net was located closer to the body surface than the brain and the nerve cords. The sensory receptors have neural connections with the nerve net in the entire body of worms. We identified five homologs of polycystic kidney disease (PKD): PKD1-1, PKD1-2, PKD1-3, PKD1-4, and, PKD2, from the P. naikaiensis genome. All of these PKD genes were implied to be expressed in the epidermal sensory receptors of P. naikaiensis. PKD1-1 and PKD2 were dispersed across the entire body of worms. PKD1-2, PKD1-3, and PKD1-4 were expressed in the anterior region of worms. PKD1-4 was also expressed around the mouth opening. Our results indicated that P. naikaiensis possessed several types of epidermal sensory receptors to convert various environmental stimuli into electrical signals via the PKD channels and transmit the signals to afferent nerve and/or effector cells.

Aberrant course of the petrous internal carotid artery associated with ipsilateral type 1 proatlantal artery.

PURPOSE: To describe an extremely rare case of an aberrant course of the petrous internal carotid artery (ICA) associated with an ipsilateral type 1 proatlantal artery (PA) that was diagnosed by cerebral magnetic resonance (MR) angiography. CASE REPORT: The patient was a 64-year-old man with double vision. Cerebral MR imaging and MR angiography were subsequently performed using a 1.5-T scanner. MR angiography showed an aberrant course of the petrous right ICA that was associated with right type 1 PA. The left vertebral artery (VA) and proximal right VA were absent. DISCUSSION: An aberrant course of the petrous ICA is rare but clinically significant, because it is dangerous during middle ear surgery. Type 1 PA is an extremely rare type of persistent fetal anastomosis between the carotid and vertebrobasilar systems. Type 1 PA is also clinically significant, because it is dangerous during craniovertebral junction surgery. We found no similar cases in the relevant English-language literature. CONCLUSION: Although both variations were seen ipsilaterally and were located relatively close to each other, the embryological development of these variations is quite different. In addition, no similar case has been reported previously. Thus, these may have formed incidentally.

Visualization of Airborne Particles as a Risk for Microbial Contamination in Orthopedic Surgery.

Background: The operating theater is recognized to involve a high frequency of occupational blood and body fluid contacts. Objectives: This study aimed to visualize the production of blood and body fluid airborne particles by surgical procedures and to investigate risks of microbial contamination of the conjunctival membranes of surgical staff during orthopedic operations. Methods: Two physicians simulated total knee arthroplasty (TKA) and total hip arthroplasty (THA) in a bio-clean theater using model bones. The generation and behaviors of airborne particles were filmed using a fine particle visualization system, and numbers of airborne particles per 2.83 L of air were counted at the height of the operating and instrument tables. Each action was repeated five times, and particle counts were evaluated statistically. Results: Numerous airborne particles were dispersed to higher and wider areas while "cutting bones in TKA" and "striking and driving the cup component on the pelvic bone in THA" compared to other surgical procedures. The highest particle counts were detected while "cutting bones in TKA" under unidirectional laminar air flow. Discussion: These results provide a clearer image of the dispersion and distribution of airborne particles and identified higher-risk surgical procedures for microbial contamination of the conjunctival membranes. Surgical staff including surgeons, nurses, anesthesiologists, and visitors, should pay attention to and take measures against occupational infection particularly in high-risk surgical situations.

Incidence of and risk factors for hip fracture in Nagasaki, Japan from 2005 to 2014.

The annual incidence of new hip fractures increased from 2005 to 2014 in Nagasaki and females were much more affected. High-risk factors were identified as age ≥ 80 years, winter, indoors, living room, Monday, and early morning. Seven days after admission, most patients remained hospitalized and had been treated surgically. INTRODUCTION: Hip fractures are major osteoporotic fractures that reduce quality of life. In Japan, the incidence of hip fractures increased steadily from 1986 to 2014 and the number of hip fractures could be 7.3-21.3 million by 2050. This study aimed to determine the incidence of hip fractures from 2005 to 2014 in Nagasaki Prefecture and to analyze the characteristics of and risk factors for hip fracture. METHODS: Hip fractures that occurred in Nagasaki Prefecture between 2005 and 2014 were analyzed using emergency transportation records. Fracture type, age, sex, location in which fracture occurred, and risk factors for hip fracture were clarified. RESULTS: The total number of new hip fractures among individuals ≥ 35 years old was 17,395 (mean age, 82.6 years old) and the annual incidence per 100,000 population increased from 147.9 in 2005 to 235.0 in 2014. Females (79.6%) were much more commonly affected than males (20.4%) and cervical fractures were more common than trochanteric fractures in all age groups. Hip fracture tended to be associated with age ≥ 80 years, winter rather than summer, indoors rather than outdoors, and living room rather than the bathroom or toilet. Other high-risk factors were Monday as day of the week, and early morning as the time of day. Seven days after admission, 97.3% of patients were hospitalized and 78.1% of hip fractures had been treated surgically. CONCLUSION: Information on actual situations and valid preventive measures relevant to hip fracture are urgently needed.

Estimating Joint External Evaluation Scores Using Country Data from 77 Countries, 2016-2018.

Since 2016, Joint External Evaluations (JEEs) help countries assess their health security preparedness and capacity to respond to public health risks. JEEs are 1 of 4 components of the International Health Regulations 2005 (IHR) Monitoring and Evaluation Framework. Compared with the mandatory State Party Self-Assessment Annual Reporting tool, JEEs use a transparent, rigorous, and collaborative process with international and in-country experts to evaluate IHR implementation. Because it is voluntary and not all States Parties have completed JEEs, we conducted a multiple linear regression model using publicly available JEE data to estimate global IHR implementation. We extracted JEE scores from the published JEE reports for 78 States Parties to the IHR and 12 sociodemographic, economic, and health indicator variables from 3 official reports and 3 official databases for all 194 World Health Organization Member States. Our final model consisted of 4 variables that significantly account for the variance of JEE score: total score from IHR annual reporting, lost disability-adjusted life years due to communicable diseases, gross domestic product, and health professional density (adjusted R2 = 0.833; P < .0001). We estimated only 1 in 10 countries (n = 19, 9.7%) worldwide had achieved average scores indicating demonstrated capacity or sustainable capacity across the 19 technical areas in the JEE tool. All 19 of these countries were in the high-income group, according to the World Bank classification, and were ranked very high on the Human Development Index, according to the United Nations Development Programme. These findings highlight the importance of ongoing efforts toward advancing global health security, especially in middle- to lower-income countries with limited resources.

Additive effect of heparin on the photoinactivation of Escherichia coli using tricationic P-porphyrins.

Polycationic porphyrins have received substantial attention in developing singlet oxygen-sensitizers for biological use such as in the photoinactivation of bacteria and photodynamic therapy (PDT) of tumor cells because they have strong binding affinities for DNA and proteins. However, these strong cellular interactions can retard elimination of the drug after PDT. Therefore, the studies on the interactions of porphyrins with other molecules present much interest, in order to modulate the sensitizers' activity or even remove them from the human body after PDT. Here, we studied the additive effect of heparin on the photoinactivation by polycationic porphyrins using Escherichia coli as a model cell. Tricationic P-porphyrin sensitizers substituted with an N-alkylpyridinium group (alkyl = pentyl (1a), hexyl (1b), and heptyl (1c)) or N-hexylammonium (1d) as the axial ligand were used. Additionally, dicationic Sb-porphyrin substituted with an N-hexylpyridinium group (1e) was prepared. We studied the additive effect of heparin on the photoinactivation of E. coli by 1a-1e. The bactericidal activities were evaluated using the half-life (T1/2 in min) of E. coli and the minimum effective concentrations ([P]) of the porphyrin sensitizers. In the absence of heparin, the [P] values were determined to be 0.4-0.5 µM for 1a-1c and 2.0 µM for 1d-1e. The bactericidal activity of 1a-1c was completely retarded by the addition of heparin (1.0 µM). However, the addition of heparin (1.0 µM) could not completely retard the bactericidal activity of 1d-1e whose [P] values were relatively large. It is suggested that tricationic 1a-1c adsorbed onto the anionic heparin through electrostatic interactions. The adsorption of 1 on heparin disturbs the uptake of 1 into E. coli cells. Thus, the addition of heparin was found to be a useful method for retarding photoinactivation.

Facilitatory effects of fetuin-A on atherosclerosis.

OBJECTIVE: Fetuin-A is a circulating glycoprotein that is produced by liver and adipose tissue. Fetuin-A is known to induce insulin resistance and suppress vascular calcification. There are conflicting reports that show increased or decreased serum fetuin-A levels in patients with coronary artery disease (CAD). Since the role of fetuin-A in atherosclerosis remains still controversial, we aimed to clarify it in this study. METHODS: We investigated the expression of fetuin-A in atheromatous plaques in CAD patients and restenosis lesions in balloon-injured rat carotid arteries in vivo. We also assessed in vitro effects of fetuin-A on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), oxidized low-density lipoprotein-induced foam cell formation in human monocyte-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs) in a serum-free culture system. RESULTS: Fetuin-A was abundantly expressed in cultured human monocytes, macrophages, fibroblasts, HASMCs, and human coronary artery SMCs, atheromatous plaques in human coronary arteries, and restenosis lesions in rat carotid arteries. In vitro experiments showed that fetuin-A stimulated interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, and E-selectin expression in HUVECs. Fetuin-A enhanced macrophage foam cell formation associated with scavenger receptors (CD36 and SR-A) and acyl-CoA:cholesterol acyltransferase-1 up-regulation and ATP-binding cassette transporter A1 down-regulation, and increased cell proliferation and collagen-1 and -3 expression via PI3K/AKT/c-Src/NF-κB/ERK1/2 pathways in HASMCs. CONCLUSION: Our results indicate that fetuin-A exerts the stimulatory effects on inflammatory responses in HUVECs, macrophage foam cell formation, and proliferation and collagen production in HASMCs, leading to the development of atherosclerosis.

Counteractive effects of omentin-1 against atherogenesis†.

AIMS: Omentin-1, a novel adipocytokine expressed in visceral fat tissue, is negatively correlated with obesity, insulin resistance, and stable coronary artery disease (CAD). However, there have been no previous reports regarding the effects of omentin-1 on atherogenesis. METHODS AND RESULTS: This study was performed to evaluate the atheroprotective effects of omentin-1 on human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in Apoe(-/-) mice in vivo. The histological expression of omentin-1 in coronary artery lesions and epicardial adipose tissues and its plasma levels were compared between CAD and non-CAD patients. Omentin-1 was abundantly expressed in human umbilical vein endothelial cells, macrophages, HASMCs, and human coronary artery SMCs in vitro. Omentin-1 promoted anti-inflammatory M2 phenotype during differentiation of human monocytes into macrophages. Omentin-1 suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1 and up-regulation of neutral cholesterol ester hydrolase in human macrophages. Omentin-1 suppressed angiotensin II-induced migration and platelet-derived growth factor-BB-induced proliferation, and collagen-1 and -3 expression in HASMCs. Four-week infusion of omentin-1 into Apoe(-/-) mice retarded the development of aortic atherosclerotic lesions with reduced contents of monocytes/macrophages, SMCs, and collagen fibres along with peritoneal M2-activated macrophages with inflammasome down-regulation and lowered plasma total cholesterol levels. Omentin-1 levels were markedly reduced in coronary endothelium and epicardial fat but increased in plasma and atheromatous plaques (macrophages/SMCs) in CAD patients compared with non-CAD patients. CONCLUSION: This study provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.

Atheroprotective Effects of Tumor Necrosis Factor-Stimulated Gene-6.

Tumor necrosis factor-stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported. We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs), human monocyte-derived macrophages (HMDMs), human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in apolipoprotein E-deficient mice, along with expression levels of TSG-6 in coronary lesions and plasma from patients with coronary artery disease (CAD). TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype and suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and -3 expressions. Four-week infusion of TSG-6 into apolipoprotein E-deficient mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules and lowered plasma total cholesterol levels. In patients with CAD, plasma TSG-6 levels were significantly increased, and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques. These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD.

Characterization of five cases of suspected bathtub suicide.

We reviewed five autopsy cases of suspected bathtub suicide. The immediate cause of death in all cases was determined to be drowning on the basis of macropathological findings such as frothy fluid in the airways or overinflation of the lungs as well as histological findings obtained at autopsy. We suspected that the manner of death in those cases was suicide based on comprehensive postmortem investigations of statements from witnesses, the presence of a farewell letter, the fact that clothes had been worn, additional means to ensure suicide, and results of drug tests, as well as autopsy findings. Cases of bathtub suicide should be investigated carefully to distinguish them from accidental or natural death.

Recording spatially incoherent Fourier hologram using dual channel rotational shearing interferometer.

The method to record an incoherent Fourier hologram is proposed. The interference patterns in the dual channel rotational shearing interferometer are obtained as the figure of the cosine and the sine transformation in the vertical and the horizontal polarization, respectively. The proposed optical system is simple without spatial light modulators or mechanical phase shifting devices. The experiment, in which the letter "A" displayed on a liquid crystal display with a blue LED backlight was used as an object, confirms the proposed method to obtain an incoherent Fourier hologram.

Brain fragility can be estimated by its putrefactive signs on postmortem computed tomography.

Along with time after death, postmortem computed tomography (PMCT) of the brain can reveal sequential changes. In the present study, we investigated the relationship between brain rigidity and advanced postmortem changes such as intravascular gas production, cerebral settling or cerebral liquefaction on PMCT. We then examined the findings of PMCT as an indicator of successful macroscopic examination of arbitrary brain slices at classical autopsy. The association between these advanced postmortem changes and the validity of macroscopic brain examination was investigated in 149 cases that were examined by PMCT at our department prior to autopsy in the period from September 2011 to December 2013. We found that the postmortem changes, classified into four stages, generally reflected the fragility of the brain. Thus, it is likely that PMCT findings of advanced postmortem changes are able to indicate decreased brain rigidity ahead of autopsy. These findings support the idea that PMCT could be used as a guide by forensic pathologists for suitable handling of a fragile brain, thus enhancing the quality of autopsy.

Vasoprotective effects of urocortin 1 against atherosclerosis in vitro and in vivo.

AIM: Atherosclerosis is the complex lesion that consists of endothelial inflammation, macrophage foam cell formation, vascular smooth muscle cell (VSMC) migration and proliferation, and extracellular matrix production. Human urocortin 1 (Ucn1), a 40-amino acid peptide member of the corticotrophin-releasing factor/urotensin I family, has potent cardiovascular protective effects. This peptide induces potent and long-lasting hypotension and coronary vasodilation. However, the relationship of Ucn1 with atherosclerosis remains unclear. The present study was performed to clarify the effects of Ucn1 on atherosclerosis. METHODS: We assessed the effects of Ucn1 on the inflammatory response and proliferation of human endothelial cells (ECs), human macrophage foam cell formation, migration and proliferation of human VSMCs, extracellular matrix expression in VSMCs, and the development of atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. RESULTS: Ucn1 significantly suppressed cell proliferation without inducing apoptosis, and lipopolysaccharide-induced up-regulation of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 in human ECs. Ucn1 significantly reduced oxidized low-density lipoprotein-induced foam cell formation with a significant down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase 1 in human monocyte-derived macrophages. Ucn1 significantly suppressed the migration and proliferation of human VSMCs and increased the activities of matrix metalloproteinase-2 (MMP2) and MMP9 in human VSMCs. Intraperitoneal injection of Ucn1 into Apoe-/- mice for 4 weeks significantly retarded the development of aortic atherosclerotic lesions. CONCLUSIONS: This study provided the first evidence that Ucn1 prevents the development of atherosclerosis by suppressing EC inflammatory response and proliferation, macrophage foam cell formation, and VSMC migration and proliferation. Thus, Ucn1 could serve as a novel therapeutic target for atherosclerotic cardiovascular diseases.