The effects of losartan or angiotensin II receptor antagonists on cartilage: a systematic review.

OBJECTIVE: The aim of this study is to analyze the latest evidence on the effects of losartan or Ang II receptor antagonists on cartilage repair, with a focus on their clinical relevance. DESIGN: The PubMed, Embase, and Cochrane Library databases were searched up to November 12th 2021 to evaluate the effects of losartan or Ang II receptor antagonists on cartilage repair in in vitro studies and in vivo animal studies. Study design, sample characteristics, treatment type, duration, and outcomes were analyzed. The risk of bias and the quality of the eligible studies were assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias assessment tool and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES). RESULTS: A total of 12 studies were included in this systematic review. Of the 12 eligible studies, two studies were in vitro human studies, three studies were in vitro animal studies, one study was an in vitro human and animal study, and six studies were in vivo animal studies. The risk bias and quality assessments were predominantly classified as moderate. Since meta-analysis was difficult due to differences in treatment type, dosage, route of administration, and method of outcome assessment among the eligible studies, qualitative evaluation was conducted for each study. CONCLUSIONS: Both in vitro and in vivo studies provide evidence to demonstrate beneficial effects of Ang II receptor antagonists on osteoarthritis and cartilage defect models across animal species.

Proof-of-principle experiment for laser-driven cold neutron source.

The scientific and technical advances continue to support novel discoveries by allowing scientists to acquire new insights into the structure and properties of matter using new tools and sources. Notably, neutrons are among the most valuable sources in providing such a capability. At the Institute of Laser Engineering, Osaka, the first steps are taken towards the development of a table-top laser-driven neutron source, capable of producing a wide range of energies with high brightness and temporal resolution. By employing a pure hydrogen moderator, maintained at cryogenic temperature, a cold neutron ([Formula: see text]) flux of [Formula: see text]/pulse was measured at the proximity of the moderator exit surface. The beam duration of hundreds of ns to tens of [Formula: see text] is evaluated for neutron energies ranging from 100s keV down to meV via Monte-Carlo techniques. Presently, with the upcoming J-EPoCH high repetition rate laser at Osaka University, a cold neutron flux in orders of [Formula: see text] is expected to be delivered at the moderator in a compact beamline.

Demonstration of Machine Learning-Based Model-Independent Stabilization of Source Properties in Synchrotron Light Sources.

Synchrotron light sources, arguably among the most powerful tools of modern scientific discovery, are presently undergoing a major transformation to provide orders of magnitude higher brightness and transverse coherence enabling the most demanding experiments. In these experiments, overall source stability will soon be limited by achievable levels of electron beam size stability, presently on the order of several microns, which is still 1-2 orders of magnitude larger than already demonstrated stability of source position and current. Until now source size stabilization has been achieved through corrections based on a combination of static predetermined physics models and lengthy calibration measurements, periodically repeated to counteract drift in the accelerator and instrumentation. We now demonstrate for the first time how the application of machine learning allows for a physics- and model-independent stabilization of source size relying only on previously existing instrumentation. Such feed-forward correction based on a neural network that can be continuously online retrained achieves source size stability as low as 0.2 µm (0.4%) rms, which results in overall source stability approaching the subpercent noise floor of the most sensitive experiments.

Enhancing laser beam performance by interfering intense laser beamlets.

Increasing the laser energy absorption into energetic particle beams represents a longstanding quest in intense laser-plasma physics. During the interaction with matter, part of the laser energy is converted into relativistic electron beams, which are the origin of secondary sources of energetic ions, γ-rays and neutrons. Here we experimentally demonstrate that using multiple coherent laser beamlets spatially and temporally overlapped, thus producing an interference pattern in the laser focus, significantly improves the laser energy conversion efficiency into hot electrons, compared to one beam with the same energy and nominal intensity as the four beamlets combined. Two-dimensional particle-in-cell simulations support the experimental results, suggesting that beamlet interference pattern induces a periodical shaping of the critical density, ultimately playing a key-role in enhancing the laser-to-electron energy conversion efficiency. This method is rather insensitive to laser pulse contrast and duration, making this approach robust and suitable to many existing facilities.

A multichannel gated neutron detector with reduced afterpulse for low-yield neutron measurements in intense hard X-ray backgrounds.

A design of multichannel gated photomultiplier tube (PMT) is presented for the 960-channel neutron time-of-flight detector at the Institute of Laser Engineering of Osaka University. This is important for the fusion science and the nuclear photonics where intense hard X-rays are generated from the interaction of ultra-short laser pulse of petawatt power density with matter. The hard X-rays often overload PMTs and cause signal-induced background noises called afterpulses, making the detection of subsequent neutrons impossible. For this reason, the PMTs are coupled with an electrical time-gating (ETG) system to avoid overloading. The ETG system disables the PMT by modulating the dynode potential during the primary X-ray flash. An after-pulsing suppression technique is demonstrated by applying a reverse bias voltage between the photocathode and the first dynode. The presented multichannel scheme provides a gate response time of 80 ns, a signal cutoff ratio of 2.5 × 102, and requires reasonably low power consumption.

A large-aperture high-sensitivity avalanche image intensifier panel.

A large-aperture high-sensitivity image intensifier panel that consists of an avalanche photodiode array and a light-emitting diode array is presented. The device has 40% quantum efficiency, over 104 optical gain, and 80-ns time resolution. The aperture size of the device is 20 cm, and with the current manufacturing process, it can be scaled to arbitrarily larger sizes. The device can intensify the light from a single particle scintillation emission to an eye-visible bright flash. The image resolution of the device is currently limited by the size of the avalanche photodiode that is 2 mm, although it can be scaled to smaller sizes in the near future. The image intensifier is operated at a small voltage, typically +57 V. The device can be applied to various applications, such as scintillation imaging, night vision cameras, and an image converter from non-visible light (such as infrared or ultraviolet) to visible light.

Living Kidney Donor With Small Lymphocytic Lymphoma at the Time of Donation: A Case Report.

Living kidney donor guidelines recommend that donors in whom a malignancy is diagnosed should be excluded. Although preoperative screening for malignancies was performed, we experienced a case of living donor with small lymphocytic lymphoma (SLL) at the time of donation. A 53-year-old woman was referred to our hospital for a kidney donation to her son. She had no past medical history of malignancy. We screened the patient using medical examinations, but there was no obvious presence of malignancy. Although preoperative computed tomography showed a small lymph node swelling at the left renal hilum, we diagnosed it as an insignificant lymph node. When a laparoscopic donor nephrectomy was performed, however, we recognized the small lymph node during the surgery and performed a lymphadenectomy. Postoperatively, pathologic examination showed that the small node was lymphocytic lymphoma, known as a low malignant potential disease. Currently, there is no presence of malignancy transmission with the recipient. To the best of our knowledge, this is the first case report of living kidney donor with SLL. Although SLL is considered a low-grade malignancy, it is crucial to follow it carefully in both the donor and the recipient.

Massage therapy for home care patients using the health insurance system in Japan.

OBJECTIVES: To clarify the status of home care massage services provided to patients. This will help in understanding how many patients utilize this service and the circumstances under which treatment is provided. DESIGN: A retrospective study. SETTING: Fifty-four acupuncture, moxibustion, and massage clinics. Participants were patients who had received home care massage for six months or more. We collected a total of 1587 responses from these 54 massage clinics; of these, 1415 responses (mean age = 79.1 ±â€¯11.5 years) were valid (valid response rate 89.2%). MAIN OUTCOME MEASURES: Actual patients and actual care services. RESULTS: The most common disorder observed among patients who utilized home care massage services was cerebrovascular disease (at approximately 36%), while the second most common were arthropathy-related disorders (16.3%). Although most patients received massage, approximately 30% received manual therapy (e.g. manual correction) and hot fomentation as part of thermotherapy. Notably, only around 10% of patients received massage alone; the majority received treatment in combination with range of motion and muscle-strengthening exercises. CONCLUSIONS: This study helped to clarify the actual state of patients receiving home care massage and the details of the massage services provided. This study clearly showed the treatment effectiveness of massage, which can be used by home medical care stakeholders to develop more effective interventions.

Boosting laser-ion acceleration with multi-picosecond pulses.

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 1018 W cm-2, the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines.

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail.

Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8-10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for 'fetal programming,' which appears to have evolved phylogenetically early.

Analysis of morphological changes after facial massage by a novel approach using three-dimensional computed tomography.

BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation of facial morphological changes. Here, we describe a three-dimensional computed tomography (3D-CT) method for objective analysis of facial and intra-facial (subcutaneous) changes. The effects of facial massage were examined using both methods. METHODS: Subjects were 12 healthy female volunteers without facial scars or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of massage-induced morphological changes was done at the nasolabial folds, upper, lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA-skin surface distances (VSDs) were measured. Massage-induced changes of VSD were calculated (facial massage-induced change rate, FMCR). Intra-facial (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring revealed marked morphological changes of the nasolabial folds after facial massage, and changes of the lower, upper and lateral cheeks and lower eyelid were also observed in more than half of the subjects. FMCR values were significantly changed in the paranasal area, nasolabial fold area and cranial part of the mandibular area. Photograph-based scores at the lower cheek and lower eyelid were well correlated with FMCR in the inferior part of the nasolabial fold and the mandibular area, respectively. Massage-induced changes of subcutaneous fat tissues and facial expression muscles were also apparent on CT images. CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of facial massage, including anatomical changes in subcutaneous structures.

Relationship among cervical, thoracic, and lumbopelvic sagittal alignment in healthy adults.

PURPOSE: To evaluate the association between cervical sagittal alignment and thoracic/lumbopelvic sagittal alignment in healthy Japanese adults. METHODS: 30 male and 22 female healthy adults aged 22 to 50 years were recruited. Spinal parameters were measured on radiographs, including the cervical sagittal vertical axis, sagittal vertical axis, C7 tilt angle, Ishihara index for cervical lordosis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. RESULTS: The C7 tilt angle positively correlated with the Ishihara index (r=0.52, p<0.0001) and thoracic kyphosis (r=0.53, p<0.0001). The Ishihara index positively correlated with thoracic kyphosis (r=0.34, p=0.01) and C7 tilt angle (r=0.52, p<0.0001). Pelvic incidence positively correlated with sacral slope (r=0.45, p=0.001), lumbar lordosis (r=0.26, p=0.07), and pelvic tilt (r=0.29, p=0.03). Compared with men, women had a smaller Ishihara index (0.07 vs. 0.001, p=0.03), thoracic kyphosis (30.5º vs 24.1º, p=0.02), and C7 tilt angle (23.1º vs. 16.8º, p=0.02). Women had less cervical lordosis and thoracic kyphosis, that is, a straighter cervico-thoracic sagittal alignment. CONCLUSION: In healthy Japanese adults, cervical sagittal alignment is associated with thoracic sagittal alignment but not with lumbopelvic alignment.

The validity of the classification for lateral hinge fractures in open wedge high tibial osteotomy.

The objective of this study was to validate the efficacy of Takeuchi classification for lateral hinge fractures (LHFs) in open wedge high tibial osteotomy (OWHTO). In all 74 osteoarthritic knees (58 females, 16 males; mean age 62.9 years, standard deviation 7.5, 42 to 77) were treated with OWHTO using a TomoFix plate. The knees were divided into non-fracture (59 knees) and LHF (15 knees) groups, and the LHF group was further divided into Takeuchi types I, II, and III (seven, two, and six knees, respectively). The outcomes were assessed pre-operatively and one year after OWHTO. Pre-operative characteristics (age, gender and body mass index) showed no significant difference between the two groups. The mean Japanese Orthopaedic Association score was significantly improved one year after operation regardless of the presence or absence of LHF (p = 0.0015, p < 0.001, respectively). However, six of seven type I cases had no LHF-related complications; both type II cases had delayed union; and of six type III cases, two had delayed union with correction loss and one had overcorrection. These results suggest that Takeuchi type II and III LHFs are structurally unstable compared with type I. Cite this article: Bone Joint J 2015;97-B:1226-31.

CCN2/CTGF expression via cellular uptake of BMP-1 is associated with reparative dentinogenesis.

OBJECTIVE: CCN family member 2/connective tissue growth factor (CCN2/CTGF) is known as an osteogenesis-related molecule and is thought to be implicated in tooth growth. Bone morphogenetic protein-1 (BMP-1) contributes to tooth development by the degradation of dentin-specific substrates as a metalloprotease. In this study, we demonstrated the correlations between CCN2/CTGF and BMP-1 in human carious teeth and the subcellular dynamics of BMP-1 in human dental pulp cells. MATERIALS AND METHODS: Expression of CCN2/CTGF and BMP-1 in human carious teeth was analyzed by immunohistochemistry. BMP-1-induced CCN2/CTGF protein expression in primary cultures of human dental pulp cells was observed by immunoblotting. Intracellular dynamics of exogenously administered fluorescence-labeled BMP-1 were observed using confocal microscope. RESULTS: Immunoreactivities for CCN2/CTGF and BMP-1 were increased in odontoblast-like cells and reparative dentin-subjacent dental caries. BMP-1 induced the expression of CCN2/CTGF independently of protease activity in the cells but not that of dentin sialophosphoprotein (DSPP) or dentin matrix protein-1 (DMP-1). Exogenously added BMP-1 was internalized into the cytoplasm, and the potent dynamin inhibitor dynasore clearly suppressed the BMP-1-induced CCN2/CTGF expression in the cells. CONCLUSION: CCN2/CTGF and BMP-1 coexist beneath caries lesion and CCN2/CTGF expression is regulated by dynamin-related cellular uptake of BMP-1, which suggests a novel property of metalloprotease in reparative dentinogenesis.

Bone augmentation using a highly porous PLGA/ß-TCP scaffold containing fibroblast growth factor-2.

BACKGROUND AND OBJECTIVE: Beta-tricalcium phosphate (ß-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using ß-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/ß-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. MATERIAL AND METHODS: The ß-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/ß-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The ß-TCP scaffold, PLGA-coated scaffold, and ß-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. RESULTS: SEM and TEM observations showed a thin PLGA layer on the ß-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/ß-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/ß-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/ß-TCP scaffold loaded with FGF-2 showed significant bone augmentation. CONCLUSION: The PLGA coating improved the mechanical strength of ß-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/ß-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation.

Photonuclear reaction based high-energy x-ray spectrometer to cover from 2 MeV to 20 MeV.

A photonuclear-reaction-based hard x-ray spectrometer is developed to measure the number and energy spectrum of fast electrons generated by interactions between plasma and intense laser light. In this spectrometer, x-rays are converted to neutrons through photonuclear reactions, and the neutrons are counted with a bubble detector that is insensitive to x-rays. The spectrometer consists of a bundle of hard x-ray detectors that respond to different photon-energy ranges. Proof-of-principle experiment was performed on a linear accelerator facility. A quasi-monoenergetic electron bunch (Ne = 1.0 × 10(-6) C, Ee = 16 ± 0.32 MeV) was injected into a 5-mm-thick lead plate. Bremsstrahlung x-rays, which emanate from the lead plate, were measured with the spectrometer. The measured spectral shape and intensity agree fairly well with those computed with a Monte Carlo simulation code. The result shows that high-energy x-rays can be measured absolutely with a photon-counting accuracy of 50%-70% in the energy range from 2 MeV to 20 MeV with a spectral resolution (Δhν/hν) of about 15%. Quantum efficiency of this spectrometer was designed to be 10(-7), 10(-4), 10(-5), respectively, for 2-10, 11-15, and 15-25 MeV of photon energy ranges.

Abrogation of renal allograft tolerance in MGH miniature swine: the role of intra-graft and peripheral factors in long-term tolerance.

We have previously demonstrated that long-term tolerance (LTT) of an MHC class-I mismatched renal allograft can be achieved with a short course of cyclosporine. In order to examine regulatory mechanisms underlying tolerance in this model, we assessed the contributions of factors within the graft and in the peripheral blood for their relative roles in the maintenance of stable tolerance. Twelve LTT recipients of MHC class-I mismatched primary kidneys were subjected to a treatment consisting of donor-specific transfusion followed by leukapheresis, in order to remove peripheral leukocytes, including putative regulatory T cells (Tregs). Following treatment, 2 controls were followed clinically and 10 animals had the primary graft removed and received a second, donor-MHC-matched kidney. Neither control animal showed evidence of rejection, while 8 of 10 retransplanted animals developed either rejection crisis or full rejection of the second transplant. In vitro assays confirmed that the removed leukocytes were suppressive and that CD4(+) Foxp3(+) Treg reconstitution in blood and kidney grafts correlated with return to normal renal function in animals experiencing transient rejection crises. These data indicate that components of accepted kidney grafts as well as peripheral regulatory components both contribute to the tolerogenic environment required for tolerance of MHC class-I mismatched allotransplants.

Global methylation levels in peripheral blood leukocyte DNA by LUMA and breast cancer: a case-control study in Japanese women.

BACKGROUND: Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women. METHODS: We conducted a hospital-based case-control study of 384 patients aged 20-74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model. RESULTS: Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20-2.91) and 2.86 (95% CI=1.85-4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05). INTERPRETATION: These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk.

A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013.

Six influenza A(H1N1)pdm09 viruses were detected in Sapporo, Japan, between November and December 2013. All six viruses possessed an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir. No epidemiological link among the six cases could be identified; none of them had received neuraminidase inhibitors before specimen collection. The haemagglutinin and neuraminidase genes of the six viruses were closely related to one another, suggesting clonal spread of a single resistant virus.