Immunohistochemical Detection of Propionibacterium acnes in Granulomas for Differentiating Sarcoidosis from Other Granulomatous Diseases Utilizing an Automated System with a Commercially Available PAB Antibody

Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody

Designing isolation guidelines for COVID-19 patients with rapid antigen tests

新型コロナウイルス感染者の隔離短縮は可能か？. 京都大学プレスリリース. 2022-08-24.Appropriate isolation guidelines for COVID-19 patients are warranted. Currently, isolating for fixed time is adopted in most countries. However, given the variability in viral dynamics between patients, some patients may no longer be infectious by the end of isolation, whereas others may still be infectious. Utilizing viral test results to determine isolation length would minimize both the risk of prematurely ending isolation of infectious patients and the unnecessary individual burden of redundant isolation of noninfectious patients. In this study, we develop a data-driven computational framework to compute the population-level risk and the burden of different isolation guidelines with rapid antigen tests (i.e., lateral flow tests). Here, we show that when the detection limit is higher than the infectiousness threshold values, additional consecutive negative results are needed to ascertain infectiousness status. Further, rapid antigen tests should be designed to have lower detection limits than infectiousness threshold values to minimize the length of prolonged isolation

Detection of significant antiviral drug effects on COVID-19 with reasonable sample sizes in randomized controlled trials : a modeling study

Background Development of an effective antiviral drug for Coronavirus Disease 2019 (COVID-19) is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence from clinical studies is limited. The lack of evidence from clinical trials may stem in part from the imperfect design of the trials. We investigated how clinical trials for antivirals need to be designed, especially focusing on the sample size in randomized controlled trials. Methods and findings A modeling study was conducted to help understand the reasons behind inconsistent clinical trial findings and to design better clinical trials. We first analyzed longitudinal viral load data for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) without antiviral treatment by use of a within-host virus dynamics model. The fitted viral load was categorized into 3 different groups by a clustering approach. Comparison of the estimated parameters showed that the 3 distinct groups were characterized by different virus decay rates (p-value < 0.001). The mean decay rates were 1.17 d−1 (95% CI: 1.06 to 1.27 d−1), 0.777 d−1 (0.716 to 0.838 d−1), and 0.450 d−1 (0.378 to 0.522 d−1) for the 3 groups, respectively. Such heterogeneity in virus dynamics could be a confounding variable if it is associated with treatment allocation in compassionate use programs (i.e., observational studies). Subsequently, we mimicked randomized controlled trials of antivirals by simulation. An antiviral effect causing a 95% to 99% reduction in viral replication was added to the model. To be realistic, we assumed that randomization and treatment are initiated with some time lag after symptom onset. Using the duration of virus shedding as an outcome, the sample size to detect a statistically significant mean difference between the treatment and placebo groups (1:1 allocation) was 13,603 and 11,670 (when the antiviral effect was 95% and 99%, respectively) per group if all patients are enrolled regardless of timing of randomization. The sample size was reduced to 584 and 458 (when the antiviral effect was 95% and 99%, respectively) if only patients who are treated within 1 day of symptom onset are enrolled. We confirmed the sample size was similarly reduced when using cumulative viral load in log scale as an outcome. We used a conventional virus dynamics model, which may not fully reflect the detailed mechanisms of viral dynamics of SARS-CoV-2. The model needs to be calibrated in terms of both parameter settings and model structure, which would yield more reliable sample size calculation. Conclusions In this study, we found that estimated association in observational studies can be biased due to large heterogeneity in viral dynamics among infected individuals, and statistically significant effect in randomized controlled trials may be difficult to be detected due to small sample size. The sample size can be dramatically reduced by recruiting patients immediately after developing symptoms. We believe this is the first study investigated the study design of clinical trials for antiviral treatment using the viral dynamics model

PPAR beta/delta activation of CD300a controls intestinal immunity

Macrophages are important for maintaining intestinal immune homeostasis. Here, we show that PPAR beta/delta (peroxisome proliferator-activated receptor beta/delta) directly regulates CD300a in macrophages that express the immunoreceptor tyrosine based-inhibitory motif (ITIM)-containing receptor. In mice lacking CD300a, high-fat diet (HFD) causes chronic intestinal inflammation with low numbers of intestinal lymph capillaries and dramatically expanded mesenteric lymph nodes. As a result, these mice exhibit triglyceride malabsorption and reduced body weight gain on HFD. Peritoneal macrophages from Cd300a(-/-) mice on HFD are classically M1 activated. Activation of toll-like receptor 4 (TLR4)/MyD88 signaling by lipopolysaccharide (LPS) results in prolonged IL-6 secretion in Cd300a(-/-) macrophages. Bone marrow transplantation confirmed that the phenotype originates from CD300a deficiency in leucocytes. These results identify CD300a-mediated inhibitory signaling in macrophages as a critical regulator of intestinal immune homeostasis

Site preference and occurrence patterns of Picea jezoensis and Abies sachalinensis on decayed logs in natural coniferous forests in Hokkaido, northern Japan

The objectives of this study were to investigate differences in the site preferences of seedlings of Picea jezoensis and Abies sachalinensis on decayed logs, and to examine the occurrence patterns of seedlings and saplings of the two species and whether they occur together or separately on logs. We characterized the habitats of 1-2-year-old seedlings of the two species on logs and examined the relationship of the two species on logs by growth stages in two plots. One plot had been disturbed about 50 years ago, whereas the other had not for a long time. Although the thickness of moss and the litter layer in the habitats of 1-2-year-old seedlings were significantly different between the two species, the two species could occur together. In one study plot, seedlings and saplings of the two species occurred together. The initial occurrence pattern of the seedlings affected the occurrence patterns of the saplings on logs. The occurrence patterns of the seedlings and saplings of the two species on logs seemed to be affected by the abundance of seed trees. In the other study plot, saplings of the two species occurred separately, but one species was not always competitively superior to the other species. Disturbance history affected the occurrence patterns of the saplings of the two species on decayed logs at the two study plots. Consequently, it is concluded that seed dispersal and the abundance of available logs, which are usually affected by disturbance, are significant factors in the natural regeneration of conifers in Hokkaido

Optimization of conditions for growth of vanadium dioxide thin films on silicon by pulsed-laser deposition

We systematically examined the effects of the substrate temperature (TS) and the oxygen pressure (PO2) on the structural and optical properties polycrystalline V O2 films grown directly on Si(100) substrates by pulsed-laser deposition. A rutile-type V O2 phase was formed at a TS ≥ 450 °C at PO2 values ranging from 5 to 20 mTorr, whereas other structures of vanadium oxides were stabilized at lower temperatures or higher oxygen pressures. The surface roughness of the V O2 films significantly increased at growth temperatures of 550 °C or more due to agglomeration of V O2 on the surface of the silicon substrate. An apparent change in the refractive index across the metal–insulator transition (MIT) temperature was observed in V O2 films grown at a TS of 450 °C or more. The difference in the refractive index at a wavelength of 1550 nm above and below the MIT temperature was influenced by both the TS and PO2, and was maximal for a V O2 film grown at 450 °C under 20 mTorr. Based on the results, we derived the PO2 versus 1/TS phase diagram for the films of vanadium oxides, which will provide a guide to optimizing the conditions for growth of V O2 films on silicon platforms

Low-Dimensional Semiconducting Scintillators

In recent times, many researchers have been developing devices that exceed the conventional capabilities by constructing a low-dimensional structure and exploiting its unique and advantageous properties. These are entirely different from those of the conventional materials due to quantum confinement effects, and their applications are called "nanotechnology". This chapter shows that a demonstration of the "nanotechnology" in the development of scintillators, a kind of ionizing radiation sensor, that can simultaneously achieve both a quick response and a large signal output, which has been difficult by using conventional bulk materials.\nThe second section explains the physics of semiconducting scintillators including the thermal quenching (TQ) that prevents the operation at room temperature (RT). In the third section, a quantum confinement system (QCS) is introduced to solve this problem, and the physical effects are described. In the fourth section, low-dimensional (LD) semiconducting scintillators are demonstrated to show the possibilities of developing them with very short decay time constants and practical emission efficiency at RT. The fifth section contains the summary with a guide for the development of new LD semiconducting systems that will be an important field in the development of inorganic scintillators in the following decade