Hepatitis B Virus-related Membranous Nephropathy with Crescentic Formation in an Inactive Carrier of Positive Hepatitis B Surface Antigen with Undetectable DNA under Anti-viral Treatment.

A man who was an inactive hepatitis B virus (HBV) carrier with positive hepatitis B surface antigen (HBs antigen) and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and HBs antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.

Histopathology of fused triplet placenta in rat.

A fused triplet placenta was observed in a Wistar Hannover rat on gestation day 15. Each placenta (referred to as PL-A, PL-B, and PL-C) of this fused placenta was attached to one fetus each, but their fetal weights were lower than that of the fetus attached to the only normal placenta (referred to as PL-N) in this dam. Histopathologically, thinning of the trophoblastic septa and dilatation of the maternal sinusoid in the labyrinth zone were observed in PL-B and PL-C, but not in PL-A or PL-N. The points of placental fusion were at the junctional zone derived from each side of the placenta without connective tissues, and the septum was composed of trophoblastic giant cells. Although PL-A had a solitary metrial gland, PL-B and PL-C shared one metrial gland with one spiral artery terminus branching towards each labyrinth zone.

Nonadditivities of the Particle Sizes Hidden in Model Pair Potentials and Their Effects on Physical Adsorptions.

It is important to understand the mechanism of colloidal particle assembly near a substrate for development of drug delivery systems, micro-/nanorobots, batteries, heterogeneous catalysts, paints, and cosmetics. Understanding the mechanism is also important for crystallization of the colloidal particles and proteins. In this study, we calculated the physical adsorption of colloidal particles on a flat wall mainly using the integral equation theory, wherein small and large colloidal particles were employed. In the calculation system, like-charged electric double-layer potentials were used as pair potentials. In some cases, it was found that the small particles are more easily adsorbed. This result is unusual from the viewpoint of the Asakura-Oosawa theory, and we call it a "reversal phenomenon". Theoretical analysis revealed that the reversal phenomenon originates from the nonadditivities of the particle sizes. Using the knowledge obtained from this study, we invented a method to analyze the size nonadditivity hidden in model pair potentials. The method will be useful for confirmation of various simulation results regarding the adsorption and development of force fields for colloidal particles, proteins, and solutes.

Effects of cyclophosphamide on rat placental development.

We examined the morphological effects of cyclophosphamide (CPA) on placental development in pregnant rats. CPA was administered as a single dose to pregnant rats intraperitoneally at 0 mg/kg (the control group), 25 mg/kg on gestation day (GD) 12 (the CPA GD 12-treated group), and 25 mg/kg on GD 14 (the CPA GD 14-treated group). The fetal and placental weight decreased in the CPA-treated groups, complete fetal resorption from GD 17 onwards in the CPA GD 12-treated group, and external malformations in the CPA GD 14-treated group. Histopathologically, CPA induced apoptosis and/or cell proliferation inhibition in each part of the placenta. In the labyrinth zone, syncytiotrophoblasts were selectively reduced, resulting in a small placenta. In the basal zone, the number of spongiotrophoblasts was reduced, resulting in hypoplasia of glycogen cell islands. In addition, a small number of interstitial trophoblasts invaded the metrial gland from the basal zone on GD 15. The severity of these lesions was higher in the CPA GD 12-treated group than in the CPA GD 14-treated group. In the metrial gland, although the number of uterine natural killer cells was reduced, metrial gland development was not affected.

Methods for assessing change in brain plasticity at night and psychological resilience during daytime between repeated long-duration space missions.

This study was designed to examine the feasibility of analyzing heart rate variability (HRV) data from repeat-flier astronauts at matching days on two separate missions to assess any effect of repeated missions on brain plasticity and psychological resilience, as conjectured by Demertzi. As an example, on the second mission of a healthy astronaut studied about 20 days after launch, sleep duration lengthened, sleep quality improved, and spectral power (ms2) co-varying with activity of the salience network (SN) increased at night. HF-component (0.15-0.50 Hz) increased by 61.55%, and HF-band (0.30-0.40 Hz) by 92.60%. Spectral power of HRV indices during daytime, which correlate negatively with psychological resilience, decreased, HF-component by 22.18% and HF-band by 37.26%. LF-component and LF-band, reflecting activity of the default mode network, did not change significantly. During the second mission, 24-h acrophases of HRV endpoints did not change but the 12-h acrophase of TF-HRV did (P < 0.0001), perhaps consolidating the circadian system to help adapt to space by taking advantage of brain plasticity at night and psychological resilience during daytime. While this N-of-1 study prevents drawing definitive conclusions, the methodology used herein to monitor markers of brain plasticity could pave the way for further studies that could add to the present results.

Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight.

The intrinsic cardiovascular regulatory system (ß, 0.00013-0.02 Hz) did not adapt to microgravity after a 6-month spaceflight. The infraslow oscillation (ISO, 0.01-0.10 Hz) coordinating brain dynamics via thalamic astrocytes plays a key role in the adaptation to novel environments. We investigate the adaptive process of a healthy astronaut during a 12-month-long spaceflight by analyzing heart rate variability (HRV) in the LF (0.01-0.05 Hz) and MF1 (0.05-0.10 Hz) bands for two consecutive days on four occasions: before launch, at 1-month (ISS01) and 11-month (ISS02) in space, and after return to Earth. Alteration of ß during ISS01 improved during ISS02 (P = 0.0167). During ISS01, LF and MF1 bands, reflecting default mode network (DMN) activity, started to increase at night (by 43.1% and 32.0%, respectively), when suprachiasmatic astrocytes are most active, followed by a 25.9% increase in MF1-band throughout the entire day during ISS02, larger at night (47.4%) than during daytime. Magnetic declination correlated positively with ß during ISS01 (r = 0.6706, P < 0.0001) and ISS02 (r = 0.3958, P = 0.0095). Magnetic fluctuations may affect suprachiasmatic astrocytes, and the DMN involving ISOs and thalamic astrocytes may then be activated, first at night, then during the entire day, a mechanism that could perhaps promote an anti-aging effect noted in other investigations.

Failure to gulp surface air induces swim bladder adenomas in Japanese medaka (Oryzias latipes).

In order to elucidate the effects of swim bladder inflation failure on swim bladder carcinogenesis, we investigated the sequential histopathological changes of swim bladders at 13, 24, 35, and 53 days post-hatch (dph) in medakas with an uninflated swim bladder, which was experimentally induced by denying access to the air-water interface between 0 and 6 dph. The reactive oxygen species (ROS) levels were measured at 24 dph. An uninflated swim bladder was induced in 47.3% of the fish denied access to the air-water interface (the denied group). The total incidence of swim bladder adenoma was 54.1% in the denied group; however, these tumors were observed in all fish with an uninflated swim bladder. In fact, these tumors were observed from 13 dph and onwards. The TBARS levels of the juveniles showed a 2.6-fold increase in fish with an uninflated swim bladder in the denied group compared to that in the control group. It is speculated that swim bladder inflation failure has some effects on the gas gland to produce ROS, leading to DNA damage in the gas glandular epithelium, which develops into swim bladder adenomas. Consequently, it is concluded that denying access to the air-water interface between 0 and 6 dph in medaka is an easy method of inducing swim bladder tumors in a short-term period, and is a useful method for producing tumor-bearing fish.

Muscle synergies of multidirectional postural control in astronauts on Earth after a long-term stay in space.

Movements of the human biological system have adapted to the physical environment under the 1-g gravitational force on Earth. However, the effects of microgravity in space on the underlying functional neuromuscular control behaviors remain poorly understood. Here, we aimed to elucidate the effects of prolonged exposure to a microgravity environment on the functional coordination of multiple muscle activities. The activities of 16 lower limb muscles of 5 astronauts who stayed in space for at least 3 mo were recorded while they maintained multidirectional postural control during bipedal standing. The coordinated activation patterns of groups of muscles, i.e., muscle synergies, were estimated from the muscle activation datasets using a factorization algorithm. The experiments were repeated a total of five times for each astronaut, once before and four times after spaceflight. The compositions of muscle synergies were altered, with a constant number of synergies, after long-term exposure to microgravity, and the extent of the changes was correlated with the increased velocity of postural sway. Furthermore, the muscle synergies extracted 3 mo after the return were similar in their activation profile but not in their muscle composition compared with those extracted in the preflight condition. These results suggest that the modularity in the neuromuscular system became reorganized to adapt to the microgravity environment and then possibly reoptimized to the new sensorimotor environment after the astronauts were reexposed to a gravitational force. It is expected that muscle synergies can be used as physiological markers of the status of astronauts with gravity-dependent change.NEW & NOTEWORTHY The human neuromuscular system has adapted to the gravitational environment on Earth. Here, we demonstrated that prolonged exposure to a microgravity environment in space changes the functional coordination of multiple muscle activities regarding multidirectional standing postural control. Furthermore, the amount of change led to a greater regulatory balancing activity needed for postural control immediately after returning to Earth and differences in muscular coordination before space flight and 3 mo after the return to Earth.

Effects of testosterone on rat placental development.

We investigated the morphological effects of testosterone on placental development in a rat model of polycystic ovarian syndrome (PCOS). Testosterone propionate (TP), which was subcutaneously administered to pregnant rats with 5 mg/animal from gestation day (GD) 14 to GD 18, induced a maternal weight reduction without mortality or clinical signs from GD 19 onwards. A decrease in fetal and placental weight, an increase in intrauterine growth retardation (IUGR) rates, and histological changes in the placenta were observed on GD 21 but not on GD15 or 17. Histopathologically, on GD 21, the trophoblast septa thickened, and the maternal sinusoids were narrowed in the labyrinth zone, resulting in a small placenta. Additionally, the placental weight, thickness, and histological morphology in the labyrinth zone on GD 21 in the TP-treated group were nearly identical to those on GD 17 in the control and TP-treated groups. Therefore, it was assumed that the testosterone-induced small placenta was induced in association with the developmental inhibition of the fetal part of the placentas from GD 17 onwards.

Spontaneous seminoma in medaka (Oryzias latipes).

Although spontaneous development of seminoma is rare in medaka, we encountered spontaneous testicular tumors located within the abdominal cavity in two adult medakas. The growth patterns of the tumors were a combination of solid and cord arrangements in one of the two cases (Case I) and lobular in the other case (Case II). The tumor cells resembled the cells at different stages of spermatogenesis, and a small number of oocyte-like cells were also scattered within the tumor. The tumor with solid and cord patterns showed loss of normal testicular architecture, and the tumor cells had partly invaded the dorsal muscular tissue and metastasized to the liver, kidney, and eye. The tumor with a lobular pattern did not exhibit local invasion or metastasis. The tumors were diagnosed as seminomas based on their histopathological characteristics, and the tumor in Case I was observed to be more malignant than that in Case II.

Effects of microgravity exposure and fructo-oligosaccharide ingestion on the proteome of soleus and extensor digitorum longus muscles in developing mice.

Short-chain fatty acids produced by the gut bacterial fermentation of non-digestible carbohydrates, e.g., fructo-oligosaccharide (FOS), contribute to the maintenance of skeletal muscle mass and oxidative metabolic capacity. We evaluated the effect of FOS ingestion on protein expression of soleus (Sol) and extensor digitorum longus muscles in mice exposed to microgravity (µ-g). Twelve 9-week-old male C57BL/6J mice were raised individually on the International Space Station under µ-g or artificial 1-g and fed a diet with or without FOS (n = 3/group). Regardless of FOS ingestion, the absolute wet weights of both muscles tended to decrease, and the fiber phenotype in Sol muscles shifted toward fast-twitch type following µ-g exposure. However, FOS ingestion tended to mitigate the µ-g-exposure-related decrease in oxidative metabolism and enhance glutathione redox detoxification in Sol muscles. These results indicate that FOS ingestion mildly suppresses metabolic changes and oxidative stress in antigravity Sol muscles during spaceflight.

Astronauts well-being and possibly anti-aging improved during long-duration spaceflight.

This study assesses how circadian rhythms of heart rate (HR), HR variability (HRV) and activity change during long-term missions in space and how they relate to sleep quality. Ambulatory 48-h ECG and 96-h actigraphy were performed four times on ten healthy astronauts (44.7 ± 6.9 years; 9 men): 120.4 ± 43.7 days (Before) launch; 21.1 ± 2.5 days (ISS01) and 143.0 ± 27.1 days (ISS02) after launch; and 86.6 ± 40.6 days (After) return to Earth. Sleep quality was determined by sleep-related changes in activity, RR-intervals, HRV HF- and VLF-components and LF-band. The circadian amplitude of HR (HR-A) was larger in space (ISS01: 12.54, P = 0.0099; ISS02: 12.77, P = 0.0364) than on Earth (Before: 10.90; After: 10.55 bpm). Sleep duration in space (ISS01/ISS02) increased in 3 (Group A, from 370.7 to 388.0/413.0 min) and decreased in 7 (Group B, from 454.0 to 408.9/381.6 min) astronauts. Sleep quality improved in Group B from 7.07 to 8.36 (ISS01) and 9.36 (ISS02, P = 0.0001). Sleep-related parasympathetic activity increased from 55.2% to 74.8% (pNN50, P = 0.0010) (ISS02). HR-A correlated with the 24-h (r = 0.8110, P = 0.0044), 12-h (r = 0.6963, P = 0.0253), and 48-h (r = 0.6921, P = 0.0266) amplitudes of the magnetic declination index. These findings suggest associations of mission duration with increased well-being and anti-aging benefitting from magnetic fluctuations.

A case report of RccHanTM: WIST rat with multiple neoplastic and non-neoplastic proliferative lesions.

It is extremely rare to have multiple spontaneous proliferative lesions in young adult rats. Here, we report the occurrence of different proliferative lesions in multiple tissues of a 7-week-old female rat in a 1-week repeated toxicity study. Grossly, multiple white patches and nodules in the bilateral kidneys, femoral and subcutaneous masses, and a nodule in the liver were observed. Renal lesions were diagnosed as renal mesenchymal tumors. One of the femoral subcutaneous masses was diagnosed as an adenolipoma consisting of mammary epithelial cells and mature adipocytes. The other femoral and abdominal subcutaneous masses were diagnosed as lipomas consisting of mature adipocytes. The liver nodule was diagnosed as non-regenerative hepatocellular hyperplasia, which was characterized by the proliferation of slightly hypertrophic hepatocytes. In the cauda equina, the growth of enlarged Schwann cells around the axon was observed, and this lesion was diagnosed as a neuroma.

Comparison of acute inhalation toxicity of sulfuric acid by the inhalation and intratracheal instillation methods.

Recently, intratracheal instillation has been focused on as a simple, low-cost alternative to the inhalation method. In this study, intratracheal instillation of sulfuric acid, a typical acidic compound, was performed to compare the acute toxicity of acidic compounds that could cause damage to the respiratory system between intratracheal instillation and inhalation. Sulfuric acid was administered to male rats at doses of 0.7, 2, 7, 20, and 60 mg/kg by dividing the total dose into four doses. General condition and body weight were examined up to 14 days after administration, and macropathological and histopathological examinations were performed. The half-lethal dose was then estimated. All animals administered 20 and 60 mg/kg sulfuric acid and one animal administered 2 mg/kg sulfuric acid died within 4 h after administration. No abnormalities were observed in other animals. At 20 and 60 mg/kg, multiple red foci or diffuse red areas were macroscopically observed in the lungs. In these lesions, histopathologically, clefts between the mucosal epithelium and basement membrane and necrosis of the alveolar epithelium were observed. Deaths in these groups may have resulted from lung injury. No notable changes were observed in other animals. Therefore, the half-lethal dose of sulfuric acid by intratracheal instillation was estimated as 7-20 mg/kg. The acute toxicity by intratracheal instillation was evaluated with two-fold sensitivity since the exposure at the half-lethal sulfuric acid concentration in inhalation studies was calculated as 43.2 mg/kg.

Findings from recent studies by the Japan Aerospace Exploration Agency examining musculoskeletal atrophy in space and on Earth.

The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly.

Swim bladder tumor in the young adult scoliotic medaka (Oryzias latipes).

A swim bladder tumor was detected in one scoliotic medaka aged 22 weeks. The tumor was located in the dorsal abdominal cavity, with maximum dimension of 1,850 × 1,500 µm. No swim bladder lumen was identified, and the region where the swim bladder lumen would have been located, was replaced with adipose tissues. The tumor was a non-invasive, expansile, and encapsulated solid mass with a few cysts, and comprised a homogenous population of well-differentiated, densely packed, gas glandular epithelium-like cells. The tumor mass was connected to a rete mirabile that showed a hyperplastic capillary plexus; however, the tumor cells did not invade the rete mirabile, thereby revealing that the tumor was an adenoma originating from the gas glandular epithelium of the swim bladder. Since proliferative lesions in the swim bladder have been reported in some teleosts with skeletal deformations, including medaka, the occurrence of a spontaneous swim bladder tumor in teleosts is considered to be closely associated with various types of skeletal deformation, and spinal curvature in particular.

Swim bladder tumors in the wavy medaka (Oryzias latipes).

Swim bladder tumors were detected in three out of 28 wavy medakas aged about 2 years old, all of which displayed abnormal swimming patterns caused by their spinal curvature. The tumors were located in the dorsal abdominal cavity. The swim bladder lumen was not detected in the region where it was originally assumed to be located, and that region was replaced with adipose tissue. The tumors were non-invasive, expansile, and encapsulated solid masses composed of a homogenous population of well-differentiated, densely packed, gas glandular epithelium-like cells. The tumor masses were connected to the rete mirabile, but the tumor cells did not infiltrate into them. Histopathologically, these tumors were diagnosed as adenomas originating from the gas glandular epithelium of the swim bladder. Spontaneous swim bladder tumors are rare in medaka, with an incidence of 0.02%; however, in the present study of wavy medaka, the incidence was much higher (10.7%). The long-term physical effects on the gas gland caused by swim bladder deformation considered to be a secondary effect of the spinal curvature may be an important factor in the proliferation of the gas glandular epithelium in the wavy medaka, resulting in the higher incidence of swim bladder tumors.

Effect of sampling time on somatic and germ cell mutations induced by acrylamide in gpt delta mice.

BACKGROUND: Acrylamide (AA) is a rodent carcinogen and classified by the IARC into Group 2A (probable human carcinogen). AA has been reported to induce mutations in transgenic rodent gene mutation assays (TGR assays), the extent of which is presumed to depend on exposure length and the duration of expression after exposure. In particular, it is not clear in germ cells. To investigate mutagenicity with AA in somatic and germ cells at different sampling times, we conducted TGR assays using gpt delta transgenic mice. RESULTS: The male gpt delta mice at 8 weeks of age were treated with AA at 7.5, 15 and 30 mg/kg/day by gavage for 28 days. Peripheral blood was sampled on the last day of the treatment for micronucleus tests and tissues were sampled for gene mutation assays at day 31 and day 77, those being 3 and 49 days after the final treatment (28 + 3d and 28 + 49d), respectively. Another group of mice was treated with N-Ethyl-N-nitrosourea (ENU) at 50 mg/kg/day by intraperitoneal administration for 5 consecutive days and tissues were sampled at the day 31 and day 77 (5 + 26d and 5 + 72d). Frequencies of micronucleated erythrocytes in the peripheral blood significantly increased at AA doses of 15 and 30 mg/kg/day. Two- to three-fold increases in gpt mutation frequencies (MFs) compared to vehicle control were observed in the testes and lung treated with 30 mg/kg/day of AA at both sampling time. In the sperm, the gpt MFs and G:C to T:A transversions were significantly increased at 28 + 3d, but not at 28 + 49d. ENU induced gpt mutations in these tissues were examined at both 5 + 26d and 5 + 72d. A higher mutant frequency in the ENU-treated sperm was observed at 5 + 72d than that at 5 + 26d. CONCLUSIONS: The gpt MFs in the testes, sperm and lung of the AA-treated mice were determined and compared between different sampling times (3 days or 49 days following 28 day-treatment). These results suggest that spermatogonial stem cells are less sensitive to AA mutagenicity under the experimental condition. Prolonged expression time after exposure to AA to detect mutagenicity may be effective in somatic cells but not in germ cells.

Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva.

As part of a series of studies regarding the microbiota in manned space environments, we isolated the fungal strains from nasal and pharyngeal smears and saliva of 21 astronauts preflight, in-flight, and postflight. On the ground, 120 strains from 43 genera of environmental fungi were isolated from the astronauts. The dominant fungal genera were Cladosporium, Penicillium, and Aspergillus. Only 18 strains from four genera were isolated from the astronauts inside the International Space Station. These fungi are currently thought to be harmless, but regular screening and cleaning are necessary to prevent fungus-related health disorders.

The skin mycobiome of an astronaut during a 1-year stay on the International Space Station.

Analysis of the skin mycobiome of an astronaut during a 1-year stay on the International Space Station (ISS) revealed an increased relative abundance of Malassezia restricta and level of Malassezia colonization, and the presence of Cyberlindnera jadinii and Candida boidinii, uncommon skin mycobiome taxa. Similar observations were made in astronauts during a 6-month stay on the ISS (Med Mycol. 2016; 54: 232-239). Future plans for extended space travel should consider the effect of high levels of Malassezia colonization over long periods on astronauts' skin, and the abnormal proliferation of uncommon microorganisms that may occur in closed environments such as the ISS.