The Tokyo 2020 and Beijing 2022 Olympic Games held during the COVID-19 pandemic: planning, outcomes, and lessons learnt.

The COVID-19 pandemic profoundly affected all mass gatherings for sporting and religious events, causing cancellation, postponement, or downsizing. On March 24, 2020, the Japanese Government, the Tokyo Organising Committee of the Olympic and Paralympic Games, and the International Olympic Committee decided to postpone the Tokyo 2020 Olympic and Paralympic Games until the summer of 2021. With the emergence of SARS-CoV-2, the potential creation of a superspreading event that would overwhelm the Tokyo health system was perceived as a risk. Even with a delayed start date, an extensive scale of resources, planning, risk assessment, communication, and SARS-CoV-2 testing were required for the Games to be held during the COVID-19 pandemic. The effectiveness of various mitigation and control measures, including the availability of vaccines and the expansion of effective testing options, allowed event organisers and the Japanese Government to successfully host the rescheduled 2020 Tokyo Olympic Games from July 23 to Aug 8, 2021 with robust safety plans in place. In February and March, 2022, Beijing hosted the 2022 Winter Olympic Games as scheduled, built on the lessons learnt from the Tokyo Games, and developed specific COVID-19 countermeasure plans in the context of China's national framework for the plan called Zero COVID. Results from the testing programmes at both the Tokyo and Beijing Games show that the measures put in place were effective at preventing the spread of COVID-19 within the Games, and ensured that neither event became a COVID-19-spreading event. The extensive experience from the Tokyo and Beijing Olympic Games highlights that it is possible to organise mass gatherings during a pandemic, provided that appropriate risk assessment, risk mitigation, and risk communication arrangements are in place, leaving legacies for future mass gatherings, public health, epidemic preparedness, and wider pandemic response.

Efficacy, safety, and tissue penetration of solithromycin in Japanese patients with otorhinolaryngological infections.

OBJECTIVE: To assess the efficacy, safety, and tissue penetration of solithromycin for the treatment of otorhinolaryngological infections, we conducted three studies: a tissue penetration study with patients scheduled to undergo otorhinolaryngological tissue removal, an open-label study comprising patients with otitis media, pharyngitis, laryngitis, and tonsillitis, and a non-inferiority study compared with high-dose cefcapene-pivoxil (CFPN-PI). METHODS: Tissue penetration study; 17 patients with chronic rhinosinusitis, chronic otitis media, chronic tonsillitis, or palatine tonsillar hypertrophy, who required resection or removal of their tissue, were enrolled. Solithromycin was administered orally, and otorhinolaryngological tissues were collected 3.5-6 h after drug administration; blood was collected within 15 min before and after drug administration. The collected tissues and blood concentrations were measured at a central laboratory. Open-label study; 55 patients who were diagnosed with acute otitis media, laryngopharyngitis, or tonsillitis were enrolled. Solithromycin was administered orally 800 mg on Day 1, while on days 2-7, 400 mg of the drug was administered once daily. The primary endpoint is the clinical response at Test-of-Cure (TOC: 5-10 days after completion) Non-inferiority study; 283 patients with acute rhinosinusitis or acute exacerbation of chronic rhinosinusitis were randomized into either the solithromycin group or CFPN-PI group. Solithromycin was administered 800 mg once daily on Day 1 and 400 mg once daily while on Days 2-7 in solithromycin group, and CFPN-PI was administered 150 mg three times a day while on Days 1-7 in CFPN-PI group. The primary endpoint is the clinical response at TOC. RESULTS: In the tissue penetration study, the tissue concentration ratios (tissue concentration/plasma concentration) of solithromycin were 4.19 in the sinonasal mucosa, 1.33 in the middle ear mucosa, and 6.12 in the palatine tonsil tissue. In the open-label study, the efficacy rates at the TOC were 97.0 % for acute otitis media, 100 % for laryngopharyngitis, and 81.8 % for tonsillitis. In the non-inferiority study comprising patients with rhinosinusitis, the efficacy rate at the TOC was 87.7 % for solithromycin and 89.7 % for CFPN-PI. The difference in the efficacy rate (95 % confidence interval) was -2.0 % (-9.4 % to 5.4 %), verifying the non-inferiority of solithromycin to CFPN-PI. The most common adverse events in patients administered solithromycin were diarrhea (20.7 %), nausea and nasopharyngitis (3.6 %,), pharyngitis and elevated hepatic function test results (3.1 %), and abnormal hepatic function (2.1 %). CONCLUSION: Based on the findings, it is suggested that solithromycin is useful for the treatment of otorhinolaryngological infections.

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake.

In this study, novel methods were developed, which allowed continuous (24/7) measurement of arterial blood pressure and renal blood flow in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O2 and metabolites. Specifically, the study determined the effects of a high salt (HS; 4.0% NaCl) diet upon whole kidney O2 consumption and arterial and renal venous plasma metabolomic profiles of normal Sprague-Dawley rats. A separate group of rats was studied to determine changes in the cortex and outer medulla tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to 4.0% NaCl diet. In addition, targeted mRNA expression analysis of cortical segments was performed. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. A novel finding was the increased expression of glycolysis-related genes in Cx and isolated proximal tubular segments in response to an HS diet, consistent with increased release of pyruvate and lactate from the kidney to the renal venous blood. Data suggests that aerobic glycolysis (eg, Warburg effect) may contribute to energy production under these circumstances. The study provides evidence that kidney metabolism responds to an HS diet enabling enhanced energy production while protecting from oxidative stress and injury. Metabolomic and transcriptomic analysis of kidneys of Sprague-Dawley rats fed a high salt diet.

Metabolic responses of normal rat kidneys to a high salt intake.

In the present study, novel methods were developed which allowed continuous (24/7) measurement of blood pressure (BP) and renal blood flow (RBF) in freely moving rats and the intermittent collection of arterial and renal venous blood to estimate kidney metabolic fluxes of O 2 and metabolites. The study determined the effects of a high salt (HS) diet upon whole kidney O 2 consumption and the metabolomic profiles of normal Sprague Dawley (SD) rats. A separate group of rats was studied to determine changes in the cortex (Cx) and outer medulla (OM) tissue metabolomic and mRNAseq profiles before and following the switch from a 0.4% to a 4.0% NaCl diet. Significant changes in the metabolomic and transcriptomic profiles occurred with feeding of the HS diet. A progressive increase of kidney O 2 consumption was found despite a reduction in expression of most of the mRNA encoding enzymes of TCA cycle. Increased glycolysis was evident with the elevation of mRNA expression encoding key glycolytic enzymes and release of pyruvate and lactate from the kidney in the renal venous blood. Glycolytic production of NADH is used in either the production of lactate or oxidized via the malate aspartate shuttle. Aerobic glycolysis (e.g., Warburg-effect) may account for the needed increase in cellular energy. The study provides evidence that kidney metabolism responds to a HS diet enabling enhanced energy production while protecting from oxidate stress and injury.

A model for generating differences in microtubules between axonal branches depending on the distance from terminals.

In the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry.

Faster algorithms to measure visual field using the variational Bayes linear regression model in glaucoma: comparison with SITA-Fast.

AIMS: To compare the visual field (VF) test results measured with the Swedish Interactive Threshold Algorithm Fast (SITA-Fast) and newly developed variational Bayes linear regression visual field (VBLR-VF) Fast or VBLR-VF Fast+. METHOD: Of 65 patients with glaucoma, 31 eyes of 31 patients performed VBLR-VF Fast and SITA-Fast, and 34 eyes of 34 patients performed VBLR-VF Fast+ and SITA-Fast on the same day and iterated the same procedures within 6 months using the 24-2 test grid in the current prospective study. Global index (mean deviation and pattern SD), pointwise retinal sensitivity, test duration and reliability index (fixation loss, false positive and false negative) were compared between SITA-Fast and VBLR-VF Fast or VBLR-VF Fast+. RESULTS: Global indices were not significantly different between SITA-Fast and VBLR-VF Fast or VBLR-VF Fast+. There was no significant difference in the pointwise retinal sensitivity between the SITA-Fast and VBLR-VF Fast algorithms at the first visit, while the VBLR-VF Fast algorithm was approximately 1 dB higher compared to the SITA-Fast algorithm at the second visit. Test duration was reduced by approximately 30 s (10%) with VBLR-VF Fast and by approximately 80 s (30%) with VBLR-VF Fast+ compared with to SITA-Fast (p<0.05). Most cases showed good reliability index values; however, a marginal but significant difference was observed between the VBLR-VF and SITA-Fast algorithms. CONCLUSION: Both VBLR-VF Fast and VBLR-VF Fast+ considerably reduced the test durations. Although there was a marginal difference in the pointwise retinal sensitivities, global indices were almost interchangeable between the VBLR-VF Fast and SITA-Fast.

Inhibition of platelet-derived growth factor pathway suppresses tubulointerstitial injury in renal congestion.

OBJECTIVE: Increased central venous pressure in congestive heart failure is responsible for renal dysfunction, which is mediated by renal venous congestion. Pericyte detachment from capillaries after renal congestion might trigger renal fibrogenesis via pericyte-myofibroblast transition (PMT). Platelet-derived growth factor receptors (PDGFRs), which are PMT indicators, were upregulated in our recently established renal congestion model. This study was designed to determine whether inhibition of the PDGFR pathway could suppress tubulointerstitial injury after renal congestion. METHODS: The inferior vena cava between the renal veins was ligated in male Sprague-Dawley rats, inducing congestion only in the left kidney. Imatinib mesylate or vehicle were injected intraperitoneally daily from 1 day before the operation. Three days after the surgery, the effect of imatinib was assessed by physiological, morphological and molecular methods. The inhibition of PDGFRs against transforming growth factor-ß1 (TGFB1)-induced fibrosis was also tested in human pericyte cell culture. RESULTS: Increased kidney weight and renal fibrosis were observed in the congested kidneys. Upstream inferior vena cava (IVC) pressure immediately increased to around 20 mmHg after IVC ligation in both the imatinib and saline groups. Although vasa recta dilatation and pericyte detachment under renal congestion were maintained, imatinib ameliorated the increased kidney weight and suppressed renal fibrosis around the vasa recta. TGFB1-induced elevation of fibrosis markers in human pericytes was suppressed by PDGFR inhibitors at the transcriptional level. CONCLUSION: The activation of the PDGFR pathway after renal congestion was responsible for renal congestion-induced fibrosis. This mechanism could be a candidate therapeutic target for renoprotection against renal congestion-induced tubulointerstitial injury.

Acute Increase of Renal Perfusion Pressure Causes Rapid Activation of mTORC1 (Mechanistic Target Of Rapamycin Complex 1) and Leukocyte Infiltration.

BACKGROUND: The present study in Sprague-Dawley rats determined the effects of a rapid rise of renal perfusion pressure (RPP) upon the activation of mTOR (mechanistic target of rapamycin), and the effects upon the infiltration of CD68-positive macrophages/monocytes and CD3-positive T lymphocytes into the kidneys. METHODS: RPP was elevated by 40 mm Hg for 30 minutes in male Sprague-Dawley rats while measuring renal blood flow and urine flow rate. Sham rats were studied in the same way, but RPP was not changed. Since initial studies found that the acute increase of RPP resulted in activation of mTORC1 (phosphorylation of S6S235/236), the effects of inhibition of mTORC1 with rapamycin pretreatment were then determined. RESULTS: It was found that a 30-minute increase of RPP (≈40 mm Hg) resulted in an 8-fold increase of renal sodium excretion which was blunted by rapamycin treatment. Renal blood flow was not affected by the elevation of RPP. Activation of mTORC1 was observed. Significant increases in CD68-positive macrophages were found in both the cortex (intraglomerular and periglomerular regions) and in the outer medullary interstitial regions of the kidney and prevented by rapamycin treatment. Increases in CD3-positive T lymphocytes were observed exclusively in the periglomerular regions and prevented by rapamycin treatment. Upregulation of several proinflammatory markers was observed. CONCLUSIONS: We conclude that elevation of RPP rapidly activates mTORC1 resulting in infiltration of immune cells into the kidney.

Divergent roles of angiotensin II upon the immediate and sustained increases of renal blood flow following unilateral nephrectomy.

Although the molecular and functional responses related to renal compensatory hypertrophy after unilateral nephrectomy (UNX) has been well described, many aspects of these events remain unclear. One question is how the remaining kidney senses the absence of the contralateral organ, and another is what the role of the renin-angiotensin system is in these responses. Both acute anesthetized and chronic unanesthetized experiments were performed using the angiotensin II type 1 receptor blocker losartan and the renin inhibitor aliskiren to determine the contribution of the renin-angiotensin system to immediate changes and losartan for chronic changes of renal blood flow (RBF) and the associated hypertrophic events in male Sprague-Dawley rats. Chronic experiments used implanted RBF probes and arterial catheters for continuous data collection, and the glomerular filtration rate was determined by noninvasive transcutaneous FITC-sinistrin measurements. The results of the acute experiments found that RBF increased nearly 25% (4.6 ± 0.5 to 5.6 ± 0.6 mL/min/g kidney wt) during the first 15 min following UNX and that this response was abolished by losartan (6.7 ± 0.7 to 7.0 ± 0.7 mL/min/g kidney wt) or aliskiren (5.8 ± 0.4 to 6.0 ± 0.4 mL/min/g kidney wt) treatment. Thereafter, RBF increased progressively over 7 days, and kidney weight increased by 19% of pre-UNX values. When normalized to kidney weight determined at day 7 after UNX, RBF was not significantly different from pre-UNX levels. Semiquantification of CD31-positive capillaries revealed increases of the glomeruli and peritubular capillaries that paralleled the kidney hypertrophy. None of these chronic changes was inhibited by losartan treatment, indicating that neither the compensatory structural nor the RBF changes were angiotensin II type 1 receptor dependent.NEW & NOTEWORTHY This study found that the immediate increases of renal blood flow (RBF) following unilateral nephrectomy (UNX) are a consequence of reduced angiotensin II type 1 (AT1) receptor stimulation. The continuous monitoring of RBF and intermittent measurement of glomerular filtration rate (GFR) in conscious rats during the 1-wk period of rapid hypertrophy following UNX provided unique insights into the regulation of RBF and GFR when faced with increased metabolic loads. It was found that neither kidney hypertrophy nor the associated increase of capillaries was an AT1-dependent phenomenon.

Long-Term Continuous Measurement of Renal Blood Flow in Conscious Rats.

The kidneys play a crucial role in maintaining the homeostasis of body fluids. The regulation of renal blood flow (RBF) is essential to the vital functions of filtration and metabolism in kidney function. Many acute studies have been carried out in anesthetized animals to measure RBF under various conditions to determine mechanisms responsible for the regulation of kidney perfusion. However, for technical reasons, it has not been possible to measure RBF continuously (24 h/day) in unrestrained unanesthetized rats over prolonged periods. These methods allow the continuous determination of RBF over many weeks while also simultaneously recording blood pressure (BP) with implanted catheters (fluid-filled or by telemetry). RBF monitoring is carried out with rats placed in a circular servo-controlled rat cage that enables the unrestrained movement of the rat throughout the study. At the same time, the tangling of cables from the flow probe and arterial catheters is prevented. Rats are first instrumented with an ultrasonic flow probe placement on the left renal artery and an arterial catheter implanted in the right femoral artery. These are routed subcutaneously to the nape of the neck, and connected to the flowmeter and pressure transducer, respectively, to measure RBF and BP. Following surgical implantation, rats are immediately placed in the cage to recover for at least one week and stabilize the ultrasonic probe recordings. Urine collection is also feasible in this system. The surgical and post-surgical procedures for continuous monitoring are demonstrated in this protocol.

Phylogeography of a canopy-forming kelp, Eisenia bicyclis (Laminariales, Phaeophyceae), based on a genome-wide sequencing analysis.

Analyses of phylogeographic patterns and genetic diversity provide fundamental information for the management and conservation of species. However, little is published about these patterns in Japanese kelp species. In this study, we conducted phylogeographic analyses of a canopy-forming kelp, Eisenia bicyclis, based on genome-wide SNPs identified by ddRAD-seq. We obtained 1,299 SNPs for 76 samples from nine localities across the distribution. STRUCTURE, NeighborNet, and discriminant analysis of principal components consistently showed high genetic differentiation among the Eastern Pacific, Central Pacific, and Sea of Japan coastal regions. Relatively strong gene flow was detected only within populations in the Eastern Pacific and in the Sea of Japan. Genetic diversity and genetic uniqueness were high in the Central Pacific and low in the Sea of Japan. These results suggest that there were at least three independent refugia corresponding to the three regions during the Last Glacial Maximum (LGM). Furthermore, relatively larger populations in the Central Pacific and smaller populations in the Sea of Japan have been maintained in the demographic history from before the LGM to the present. These phylogeographic histories were supported by an Approximate Bayesian Computation analysis. From a conservation genetics perspective, the loss of southern populations in the Central Pacific would greatly reduce the total genetic diversity of the species. Southern populations in the Sea of Japan, which have relatively low genetic diversity, may be highly vulnerable to environmental change, such as heat waves and increased feeding. Therefore, careful monitoring and conservation are needed in the two regions.

Comparing the usefulness of a new algorithm to measure visual field using the variational Bayes linear regression in glaucoma patients, in comparison to the Swedish interactive thresholding algorithm.

BACKGROUND/AIMS: We previously reported that the visual field (VF) prediction model using the variational Bayes linear regression (VBLR) is useful for accurately predicting VF progression in glaucoma (Invest Ophthalmol Vis Sci. 2014, 2018). We constructed a VF measurement algorithm using VBLR, and the purpose of this study was to investigate its usefulness. METHOD: 122 eyes of 73 patients with open-angle glaucoma were included in the current study. VF measurement was performed using the currently proposed VBLR programme with AP-7700 perimetry (KOWA). VF measurements were also conducted using the Swedish interactive thresholding algorithm (SITA) standard programme with Humphrey field analyser. VF measurements were performed using the 24-2 test grid. Visual sensitivities, test-retest reproducibility and measurement duration were compared between the two algorithms. RESULT: Mean mean deviation (MD) values with SITA standard were -7.9 and -8.7 dB (first and second measurements), whereas those with VBLR-VF were -8.2 and -8.0 dB, respectively. There were no significant differences across these values. The correlation coefficient of MD values between the 2 algorithms was 0.97 or 0.98. Test-retest reproducibility did not differ between the two algorithms. Mean measurement duration with SITA standard was 6 min and 02 s or 6 min and 00 s (first or second measurement), whereas a significantly shorter duration was associated with VBLR-VF (5 min and 23 s or 5 min and 30 s). CONCLUSION: VBLR-VF reduced test duration while maintaining the same accuracy as the SITA-standard.

Heat-Stress Responses Differ among Species from Different 'Bangia' Clades of Bangiales (Rhodophyta).

The red alga 'Bangia' sp. ESS1, a 'Bangia' 2 clade member, responds to heat stress via accelerated asexual reproduction and acquires thermotolerance based on heat-stress memory. However, whether these strategies are specific to 'Bangia' 2, especially 'Bangia' sp. ESS1, or whether they are employed by all 'Bangia' species is currently unknown. Here, we examined the heat-stress responses of 'Bangia' sp. ESS2, a newly identified 'Bangia' clade 3 member, and Bangia atropurpurea. Intrinsic thermotolerance differed among species: Whereas 'Bangia' sp. ESS1 survived at 30 °C for 7 days, 'Bangia' sp. ESS2 and B. atropurpurea did not, with B. atropurpurea showing the highest heat sensitivity. Under sublethal heat stress, the release of asexual spores was highly repressed in 'Bangia' sp. ESS2 and completely repressed in B. atropurpurea, whereas it was enhanced in 'Bangia' sp. ESS1. 'Bangia' sp. ESS2 failed to acquire heat-stress tolerance under sublethal heat-stress conditions, whereas the acquisition of heat tolerance by priming with sublethal high temperatures was observed in both B. atropurpurea and 'Bangia' sp. ESS1. Finally, unlike 'Bangia' sp. ESS1, neither 'Bangia' sp. ESS2 nor B. atropurpurea acquired heat-stress memory. These findings provide insights into the diverse heat-stress response strategies among species from different clades of 'Bangia'.

Effects of Temperature and Position Change on Neonatal Brain Regional Oxygen Saturation in Tub Bathing: A Prospective Study.

INTRODUCTION: A major goal in neonatal medicine is to reduce stress as much as possible in routine care. Bathing is one of the important routine cares for neonates, but it makes a big environmental change for them. We aimed to examine whether water temperature, room temperature, and position changes in tub bathing serve as noxious stimuli to neonates. METHODS: This prospective trial was performed in full-term and non-low-birth-weight neonates admitted to the hospital between July 2020 and March 2021. Those with underlying diseases, fetal distress, infection, and other medical conditions were excluded. Measurements were taken during the neonates' first tub bath since birth, which was performed by a trained nurse. Changes in regional oxygen saturation (rSO2), determined using near-infrared spectroscopy, and water and room temperature, were examined at five different time points: upon entering the bath, head washing, position change, exiting the bath, and during the 3 min after bathing. RESULTS: In total, 17 neonates were analyzed. No changes in rSO2 due to head washing or position change were observed; however, rSO2 significantly decreased upon entering (78.5 ± 4.1% vs. 75.7 ± 4.1%, p < 0.001) and exiting the bath (75.8 ± 5.7% vs. 74.4 ± 5.4%, p < 0.04). The rate change in rSO2 upon entering the bath showed a significant inverse correlation with water temperature (r = - 0.53, p < 0.03), and there were no significant correlations between rSO2 and water or room temperature upon exiting the bath. There was no change in body skin temperature before and after bathing, but rSO2 gradually decreased during the 3 min after bathing. CONCLUSIONS: Neonates may perceive certain temperatures during bathing as noxious stimuli. Therefore, methods to minimize stress associated with bathing should be implemented to reduce the difference between water temperature and room temperature during bathing. TRIAL REGISTRATION: This trial has been registered at UMIN repository with the trial number UMIN000041045 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046500 ). The date of the final dataset was April 01, 2021.

Renal Perfusion Pressure Determines Infiltration of Leukocytes in the Kidney of Rats With Angiotensin II-Induced Hypertension.

The present study examined the extent to which leukocyte infiltration into the kidneys in Ang II (angiotensin II)-induced hypertension is determined by elevation of renal perfusion pressure (RPP). Male Sprague-Dawley rats were instrumented with carotid and femoral arterial catheters for continuous monitoring of blood pressure and a femoral venous catheter for infusion. An inflatable aortic occluder cuff placed between the renal arteries with computer-driven servo-controller maintained RPP to the left kidney at control levels during 7 days of intravenous Ang II (50 ng/kg per minute) or vehicle (saline) infusion. Rats were fed a 0.4% NaCl diet throughout the study. Ang II-infused rats exhibited nearly a 50 mm Hg increase of RPP (carotid catheter) to the right kidney while RPP to the left kidney (femoral catheter) was controlled at baseline pressure throughout the study. As determined at the end of the studies by flow cytometry, right kidneys exhibited significantly greater numbers of T cells, B cells, and monocytes/macrophages compared with the servo-controlled left kidneys and compared with vehicle treated rats. No difference was found between Ang II servo-controlled left kidneys and vehicle treated kidneys. Immunostaining found that the density of glomeruli, cortical, and outer medullary capillaries were significantly reduced in the right kidney of Ang II-infused rats compared with servo-controlled left kidney. We conclude that in this model of hypertension the elevation of RPP, not Ang II nor dietary salt, leads to leukocyte infiltration in the kidney and to capillary rarefaction.

The early effects of uninephrectomy on rat kidney metabolic state using optical imaging.

Uninephrectomy (UNX) is known to result in structural and metabolic changes to the remaining kidney, although it is uncertain if this alters the mitochondrial redox state and how soon such changes may occur. A custom-designed fluorescence cryo-imaging technique was used to quantitatively assess the effect of UNX by measuring the levels of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the remaining kidney. Kidneys were snap-frozen 3 days following UNX, and the intrinsic fluorescence of NADH and FAD were optically acquired. The 3D images were created to characterize the NADH/FAD redox ratios (RR) of the right kidneys, which underwent UNX and the remaining kidneys 3 days following UNX. Both the NADPH-oxidases (Nox2 and Nox4) and the mitochondria are the main sources of reactive oxygen species (ROS) production in tubular epithelial cells. Responses to the UNX were obtained in kidneys of normal Sprague Dawley (SD) rats, Dahl salt-sensitive (SS) rats and SS rats in which NADPH-oxidase isoform 4 (Nox4) was knocked out (SSNox4-/- ). The results found that each of the strains exhibited similar increase in kidney weights averaging 17% after 3 days of UNX. SD and SSNox4-/- rats both exhibited global reductions of the RR (P < .05) with a similar tendency observed in SS rats (P < .08), indicating increased ROS production. The unexpected reduction of the RR in the remnant kidneys of SSNox4-/- rats indicates that mechanisms independent of H2 O2 produced from Nox4 may be responsible for this global increase of ROS. We propose that the reduced RR was largely a consequence of enhanced mitochondrial bioenergetics due to increased tubular workload of the remaining kidney. The data indicate that mitochondria become the dominant source of increased ROS following UNX and could represent an important hypertrophic signaling mechanism.

Detection of viral RNA in diverse body fluids in an SFTS patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed.