Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Modeling principles of protective thyroid blocking.

PURPOSE: In the case of a nuclear incident, the release of radioiodine must be expected. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of stable (non-radioactive) iodine may inhibit radioiodine accumulation and protect the thyroid ('thyroid blocking'). Protection is based on a competition at the active carrier site in the cellular membrane and an additional temporary inhibition of the organification of iodide (Wolff-Chaikoff effect). Alternatively, other agents like e.g. perchlorate that compete with iodide for the uptake into the thyrocytes may also confer thyroidal protection against radioiodine exposure.Biokinetic models for radioiodine mostly describe exchanges between compartments by first order kinetics. This leads to correct predictions only for low (radio)iodide concentrations. These models are not suited to describe the kinetics of iodine if administered at the dosages recommended for thyroid blocking and moreover does not permit to simulate either the protective competition mechanism at the membrane or the Wolff-Chaikoff effect. Models adapted for this purpose must be used. Such models may use a mathematical relation between the serum iodide concentration and a relative uptake suppression or a dependent rate constant determining total thyroidal radioiodine accumulation. Alternatively, the thyroidal uptake rate constant may be modeled as a function of the total iodine content of the gland relative to a saturation amount. Newer models integrate a carrier-mechanism described by Michalis-Menten kinetics in the membrane and in analogy to enzyme kinetics apply the rate law for monomolecular irreversible enzyme reactions with competing substrates to model the competition mechanism. An additional total iodide uptake block, independent on competition but limited in time, is used to simulate the Wolff-Chaikoff effect. CONCLUSION: The selection of the best model depends on the issue to be studied. Most models cannot quantify the relative contributions of the competition mechanism at the membrane and the Wolff-Chaikoff effect. This makes it impossible or exceedingly difficult to simulate prolonged radioiodine exposure and the effect of repetitive administrations of stable iodine. The newer thyroid blocking models with a separate modeling of competition and Wolff-Chaikoff effect allow better quantitative mechanistic insights and offer the possibility to simulate complex radioiodine exposure scenarios and various protective dosage schemes of stable iodine relatively easily. Moreover, they permit to study the protective effects of other competitors at the membrane carrier site, like e.g. perchlorate, and to draw conclusions on their protective efficacy in comparison to stable iodine.

Ascorbic acid-2 glucoside mitigates intestinal damage during pelvic radiotherapy in a rat bladder tumor model.

PURPOSE: Ascorbic acid is a strong antioxidant and has potent radioprotective effects on radiation injuries. Ascorbic acid 2-glucoside (AA2G) is a stabilized derivative of ascorbic acid and rapidly hydrolyzed into ascorbic acid and glucose. Since there is the possibility that AA2G treatment interferes with the antitumor activity of radiotherapy, we investigated the effect of AA2G treatment during radiotherapy on acute radiation enteritis and antitumor activity of radiotherapy in rats. MATERIALS AND METHODS: AY-27 rat bladder tumor cells were used to induce bladder tumors in rats. Two weeks after inoculation rats received fractionated pelvic radiotherapy in eight fractions for 4 weeks totaling 40 Gy. During radiotherapy, one group of rats received per os AA2G (ascorbic acid: 250 mg/kg/day) and its bolus engulfment (ascorbic acid: 250 mg/kg) 8 h before each X-irradiation fraction. Seven days after the last X-irradiation, we studied histology, DNA double strand break (DSB) damage (by 53BP1 foci staining), and the M1/M2 macrophage response by immunohistochemistry of paraffin-fixed bladder and intestinal tissues. RESULTS: AA2G treatment reduced the intestinal damage (shortening of villi) but did not reduce antitumor effectiveness of radiotherapy against bladder tumors. Like the controls, AA2G-treated rats showed no residual tumor lesions in the bladder after X-irradiation. Both AA2G-treated and control groups showed similar persistent DSB damage (53BP1 foci) both in bladders and ilea seven days after radiotherapy. Radiotherapy tended to reduce CD163+ M2 macrophages, which are considered as an anti-inflammatory subtype favoring tissue repair, in the bladders. X-irradiation also reduced the occurrence of M2 macrophages in the ilea. AA2G treatment significantly increased CD163+/CD68+ macrophage ratio in the ilea of rats after pelvic irradiation in comparison to the sham irradiated control rats. AA2G treatment increased, albeit not significantly, the CD163+/CD68+ macrophage ratio in the irradiated bladders relative to the control irradiated rats. On the other hand, bladders and ilea of the irradiated rats with and without AA2G treatment showed similar frequencies of CD68+ macrophages. CONCLUSIONS: AA2G treatment mitigated radiation-induced intestinal damage without reducing antitumor activity after fractionated pelvic radiotherapy against bladder tumors in rats. The beneficial effect of AA2G treatment seems to promote a restoration of the M2 answer as well as tissue remodeling and wound healing. Similar residual DNA damage in bladders and ilea seven days post-irradiation is consistent with tumor control in both groups.

Effects of the chelating agent DTPA on naturally accumulating metals in the body.

Diethylenetriaminepentaacetate (DTPA) is the most widely used chelating agent for Pu and Am. Volunteers were assigned to receive intravenous injections or aerosol inhalations of 1 g of DTPA on days 1-4; volunteers received once daily injections of CaDTPA or ZnDTPA, CaDTPA inhalation as an aerosol, or CaDTPA injection on day 1 and ZnDTPA on days 2-4. CaDTPA injection or inhalation increased the excretion rates of Zn in urine with concomitantly reduced levels of serum Zn. Injection of CaDTPA reduced activities of serum alkaline phosphatase (AP) in parallel with the kinetics of Zn, whereas CaDTPA and ZnDTPA injection reduced activities of lactate dehydrogenase (LDH), and reduced activities of creatinine kinase (CK) were observed upon CaDTPA injection and its inhalation. Intravenous administration of CaDTPA and ZnDTPA enhanced excretion rates of Mn in urine, whereas transient reduction of Mn levels in serum was detected only via CaDTPA injection. Both CaDTPA and ZnDTPA transiently reduced levels of Mg in serum without affecting the excretion rates. On the other hand, both DTPAs increased excretion rates of toxic metals such as Pb and Cd, and CaDTPA also increased the rates of Hg. These results suggest that DTPA, and especially CaDTPA, removes essential metals and that the activities of these metalloenzymes are good indicators for the imbalance of essential metals during the DTPA administration. Our results also show that CaDTPA injection is more potent for removing these metals than ZnDTPA and inhalation of CaDTPA, and DTPA may be useful for the treatment of acute heavy metal poisoning with Pb, Cd, or Hg.

Axonal damage and behavioral deficits in rats with repetitive exposure of the brain to laser-induced shock waves: Effects of inter-exposure time.

Much attention has been given to effects of repeated exposure to a shock wave as a possible factor causing severe higher brain dysfunction and post-traumatic stress disorder (PTSD)-like symptoms in patients with mild to moderate blast-induced traumatic brain injury (bTBI). However, it is unclear how the repeated exposure and the inter-exposure time affect the brain. In this study, we topically applied low-impulse (∼54 Pa·s) laser-induced shock waves (LISWs; peak pressure, ∼75.7 MPa) to the rat brain once or twice with the different inter-exposure times (15 min, 1 h, 3 h, 24 h and 7 days) and examined anxiety-related behavior and motor dysfunction in the rats as well as expression of ß-amyloid precursor protein (APP) as an axonal damage marker in the brains of the rats. The averaged APP expression scores for the rat brains doubly-exposed to LISWs with inter-exposure times from 15 min to 24 h were significantly higher than those for rats with a single exposure (P < 0.0001). The rats with double exposure to LISWs showed significantly more frequent anxiety-related behavior (P < 0.05) and poorer motor function (P < 0.01) than those of rats with a single exposure. When the inter-exposure time was extended to 7 days, however, the rats showed no significant differences either in axonal damage score or level of motor dysfunction. The results suggest that the cumulative effects of shock wave-related brain injury can be avoided with an appropriate inter-exposure time. However, clinical bTBI occurs in much more complex environments than those in our model. Further study considering other factors, such as the effects of acceleration, is needed to know the clinically-relevant, necessary inter-exposure time.

Identification of the infrasound signals emitted by explosive eruption of Mt. Shinmoedake by three-dimensional ray tracing.

Mt. Shinmoedake, a part of the Mt. Kirishima cluster of volcanoes in Kyushu, Japan, erupted on 10 March 2018. Our infrasound sensor network located at a distance of more than 200 km from the source detected signals emitted by an explosive eruption of Mt. Shinmoedake. The arrival time of the signals is divided into three time intervals. To reveal how the observed infrasound signals propagated from the source to the sensors, we carry out three-dimensional ray tracing on the basis of the Hamilton equations including the vertical profiles of the temperature and wind around the ray path. We present formulas for calculating travel time and distance of infrasound from a source to an observation site and its turning altitude in the atmosphere. We have identified four kinds of signals, namely, the waves propagated in the troposphere undergoing multiple refraction and those refracting from the stratosphere, the mesosphere, and the lower thermosphere. Brief discussion is devoted to some of the unidentified signals.

A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure.

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff-Chaikoff effect, the latter being, however, only transient (24-48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic-dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its ED50. A dose of 100 mg stable iodine has roughly the same protective efficacy as 1000 mg perchlorate. For prolonged exposures, single doses of protective agents, whether stable iodine or perchlorate, offer substantially lower protection than after acute radioiodine exposure, and thus repetitive administrations seem necessary. In case of prolonged exposure, the higher affinity of perchlorate for the carrier in combination with the fading Wolff-Chaikoff effect of iodine confers perchlorate a higher protective efficacy compared to stable iodine. Taking into account the frequency and seriousness of adverse effects, iodine and perchlorate at equieffective dosages seem to be alternatives in case of short-term acute radioiodine exposure, whereas preference should be given to perchlorate in view of its higher protective efficacy in the case of longer lasting radioiodine exposures.

Development of New Biokinetic-Dosimetric Models for the Simulation of Iodine Blockade in the Case of Radioiodine Exposure in Man.

In the case of nuclear incidents, radioiodine may be liberated. After incorporation it accumulates in the thyroid and by internal irradiation enhances the risk of cancer occurrence. By administering a large dose of non-radioactive iodine the uptake of radioiodine into the gland can be inhibited ("iodine blockade"). Biokinetic models using first order kinetics are not suited to simulate iodine blockade, as the uptake into the gland is mediated by a saturable active transport. Therefore, we integrated an uptake mechanism described by a Michaelis-Menten kinetic into a simple ICRP biokinetic model. We moreover added a total uptake blocking mechanism representing the Wolff-Chaikoff effect becoming active when the gland is saturated with iodine. The validity of the model was ascertained by comparison with IMBA software. The competition of radioiodine and stable iodine at the membrane carrier site was modeled according to the rate law for monomolecular reactions for competing substrates. Our simulations show that competition for the uptake at the membrane carrier site accounts for about 60% and the saturation of the gland with iodine for over 35% of the total protective efficacy that exceeds 95%. Following acute radioiodine exposure, it is preferable to administer a single large dose of stable iodine. In the case of continuous radioiodine exposure, a single dose of stable iodine is less effective than after an acute exposure and splitting the total available dose and shortening the dosage intervals enhance efficacy. Model-based simulations may be a useful tool to develop antidote dosage schemes for uncommon emergencies.

Hypervelocity collision and water-rock interaction in space preserved in the Chelyabinsk ordinary chondrite.

A comprehensive geochemical study of the Chelyabinsk meteorite reveals further details regarding its history of impact-related fragmentation and melting, and later aqueous alteration, during its transit toward Earth. We support an ∼30 Ma age obtained by Ar-Ar method (Beard et al., 2014) for the impact-related melting, based on Rb-Sr isotope analyses of a melt domain. An irregularly shaped olivine with a distinct O isotope composition in a melt domain appears to be a fragment of a silicate-rich impactor. Hydrogen and Li concentrations and isotopic compositions, textures of Fe oxyhydroxides, and the presence of organic materials located in fractures, are together consistent with aqueous alteration, and this alteration could have pre-dated interaction with the Earth's atmosphere. As one model, we suggest that hypervelocity capture of the impact-related debris by a comet nucleus could have led to shock-wave-induced supercritical aqueous fluids dissolving the silicate, metallic, and organic matter, with later ice sublimation yielding a rocky rubble pile sampled by the meteorite.

Molecular Hydrogen Prevents Social Deficits and Depression-Like Behaviors Induced by Low-Intensity Blast in Mice.

Detonation of explosive devices creates blast waves, which can injure brains even in the absence of external injuries. Among these, blast-induced mild traumatic brain injury (bmTBI) is increasing in military populations, such as in the wars in Afghanistan, Iraq, and Syria. Although the clinical presentation of bmTBI is not precisely defined, it is frequently associated with psycho-neurological deficits and usually manifests in the form of poly-trauma including psychiatric morbidity and cognitive disruption. Although the underlying mechanisms of bmTBI are largely unknown, some studies suggested that bmTBI is associated with blood-brain barrier disruption, oxidative stress, and edema in the brain. The present study investigated the effects of novel antioxidant, molecular hydrogen gas, on bmTBI using a laboratory-scale shock tube model in mice. Hydrogen gas has a strong prospect for clinical use due to easy preparation, low-cost, and no side effects. The administration of hydrogen gas significantly attenuated the behavioral deficits observed in our bmTBI model, suggesting that hydrogen application might be a strong therapeutic method for treatment of bmTBI.

Clinical benefit of component-resolved diagnosis in Japanese birch-allergic patients with a convincing history of apple or peach allergy.

OBJECTIVE: In northern Japan, birch pollen is the major allergen in pollinosis, while oral allergy syndrome (OAS) is caused primarily by apple and peach, and is almost exclusively related to birch pollinosis. To clarify the clinical benefit of allergen-based component-resolved diagnosis (CRD) in Japanese birch-allergic patients with OAS, we present an analysis of IgE profiles in response to crude extracts and recombinant component-resolved allergen to birch pollen and Rosaceae fruits allergens. METHODS: The sera of 30 patients with birch pollen-related OAS to apple or peach were analyzed for specific IgE reactivity to pathogenesis-related class 10 (PR-10) family (birch: rBet v 1, apple: rMal d 1, and peach: rPru p 1), profilin (birch: rBet v 2 and peach: rPru p 4), and lipid transfer protein (LTP) (apple: rMal d 3 and peach: rPru p 3) allergens, as well as to conventional crude, unfractionated extracts (birch: T3, apple: f49, and peach: f95) using the ImmunoCAP System™. Allergen-specific IgE values <0.35kUA/L were considered negative. RESULTS: Of the 30 sera CAP-positive for natural birch pollen extract, 28 (93.3%) exhibited specific IgE against Bet v1, and two (6.7%) contained specific IgE against Bet v2. Of the 26 sera of OAS to apple patients, only 17 were positive for specific IgE against f49 extract (65.4%); however, 24 were positive for specific IgE against rMal d 1 (92.3%). Similarly, only 17 of the 23 sera of OAS to peach patients contained specific IgE against the f95 extract (73.9%); however, 22 were positive for specific IgE against rPru p 1 (95.7%). CONCLUSION: Our data suggest that CRD constitutes a reliable tool for the diagnosis of birch pollen-related OAS.

[Oral Allergy Syndrome Following Soy Milk Ingestion in Patients with Birch Pollen Allergy].

BACKGROUND: Persons allergic to birch pollen often report oral and pharyngeal hypersensitivity to fruit and vegetables, due to immunological cross-reactivity between pollen and foods. This phenomenon is referred to as the oral allergy syndrome (GAS). Such cross-reactive antigen reactions mainly involve Bet v 1, which is the major birch-pollen allergen, and partially involve birch-pollen profilin Bet v 2. Soybean contains Bet v 1-related antigen (Gly m 4), and soy milk often causes the OAS with severe symptoms such as precordial and abdominal burning sensation because soy milk undergoes little denaturation, and this water-soluble liquid is consumed by most people rather quickly. We evaluated the frequency of the oAS after ingestion of soymilk and examined IgE antibodies to various allergens. METHODS: A total of 167 patients [122 women, 45 men; age range, 4-72 years (mean age, 32 years)], who had experienced GAS episodes and had IgE birch--pollen antibodies, were interviewed. Using the CAP system, we examined IgE antibodies to birch pollen and other allergens. Of 167 patients, 161 were examined for IgE antibodies to Bet v 1, Bet v 2, Gly m 4, and soybean. We evaluated the frequency of the GAS after soy milk ingestion based on reports by GAS patients with birch pollen allergy, and evaluated the positive rates of some of the IgE antibodies. RESULTS: Among the 167 patients with birch-pollen allergy and GAS on ingestion of any of the foods, there were 16 cases (10%) with OAS following soy milk ingestion. In addition, the foods that caused OAS most often were apples (123 cases, 74%), peaches (67%), and cherries (55%), followed by pears (37%) and kiwi (37%). A higher CAP class for birch pollen, Bet v 1, Gly m 4, and soybean was associated with a higher prevalence of OAS to soy milk. Of 15 patients who had GAS on ingestion of soy milk and had birch-pollen allergy, 47% (7cases) were CAP class 1 for soybean and only 7% (case) was CAP class c2, whereas 93% (14cases) were CAP class 1 for Gly m 4, and 87% (3cases) were CAP class ≥ 2 for Gly m 4. CONCLUSION: Among the birch-pollen allergic OAS patients, 10% had the OAS on ingestion of soy milk, and among these with birch-pollen allergy and the OAS on ingestion of soy milk, the positive rate for soy milk CAP was low, whereas that for Gly m 4 CAP was high.

Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

Prospective cohort study comparing the effects of different artificial nutrition methods on long-term survival in the elderly: Japan Assessment Study on Procedures and Outcomes of Artificial Nutrition (JAPOAN).

BACKGROUND: The effects of various artificial nutrition methods on the long-term outcomes of elderly patients are still not well known. We aimed to compare the long-term survival of the elderly newly administered with parenteral nutrition (PN) or enteral nutrition. MATERIALS AND METHODS: This multicenter, prospective, observational cohort study was conducted on 546 elderly patients who were administered artificial nutrition. The main outcome was the survival ratio at 180 and 360 days after initiation of 3 different nutrition methods and estimated mean survival time: PN, nasal tube feeding (EN_N), and percutaneous endoscopic gastrostomy (PEG) feeding (EN_G). The incidence of systemic infection was also compared among different cohorts. RESULTS: At 180 and 360 days after initiation of artificial nutrition, the mortality rates in the PN, EN_N, and EN_G cohorts were 52% and 63%, 32% and 41%, and 22% and 33%, respectively. Multivariate logistic regression analysis showed that, whereas PN nutrition had significant associations with a higher death rate at 180 and 360 days in all samples, there is no significant difference on the main outcome among the 3 cohorts with neurological diseases. A subgroup analysis with neurological diseases showed that the proportional hazard ratios of the PN and EN_N cohorts in comparison with the EN_G cohort were 1.13 (95% confidence interval [CI], 0.66-1.92) and 1.22 (95% CI, 0.82-1.81). CONCLUSION: There is no significant superiority of PEG feeding compared with nasal tube feeding or PN. Clinicians should consider the choice of nutrition support method, taking into consideration the limitation of the patient's interest.

[A relationship between birch pollen counts and meteorological factors in Sapporo].

Occurrence of airborne pollen in Sapporo has been studied for 19 years during the period between 1995 and 2013. There are wide year-to-year variations in the quantities of birch pollens. A simple linear regression with the least squares method was used for studying correlations between the annual quantities of birch pollens and the meteorological factors. A significant positive correlation was found between the hours of sunlight in June of the preceding year and the annual birch pollen concentrations with the correlation coefficient, R = 0.667. Also, we found the significant positive correlation between the hours of sunlight in March and the annual birch pollen concentrations with the correlation coefficient, R = 0.684. These results suggest that the atmospheric birch pollen counts can be predicted from meteorological factors.

Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF) during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

A combination of pre- and post-exposure ascorbic acid rescues mice from radiation-induced lethal gastrointestinal damage.

The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage.

[Questionnaire about the intake of and hypersensitivity to fruits, vegetables and nuts including birch pollen related foods].

BACKGROUND: In Hokkaido and Scandinavia, birch pollen allergic persons are common and they often report oral and pharyngeal hypersensitivity to fruits and vegetables (oral allergy syndrome, OAS), because of immunological cross-reactivity. In Scandinavia, nuts as well as Rosaceae fruits such as apples were the foods most often reported to elicit symptoms. On the other hand, nuts are minor foods causing hypersensitivity in Japan. Even in Japan, regional differences of foods causing hypersensitivity have been reported, which may be related to the regional differences of elementary habit and pollen dispersion. In the present study, we evaluated the intake history of the foods and the frequency of food hypersensitivity in adults from the general population. METHODS: Three hundreds and thirty nine subjects (20-67 years old) took part in the study. With a questionnaire survey, we asked them about their intake history and hypersensitive symptoms for 33 kinds of fruit, vegetables, and nuts. RESULTS: 30% of subjects had eaten Brazil nuts, 80% had eaten pomegranates, and 81% had eaten hazelnuts. And over 95% of subjects had eaten the other 30 foods. Those who had lived in Hokkaido for more than 20 years had a higher frequency of plum consumption than the others. Those who had lived in Hokkaido for more than 20 years had a lower frequency of loquat, fig and pomegranate consumption than the others. Food hypersensitivity was found in 52 subjects (15.3%). The most common symptom was OAS (46 subjects, 13.6%), and foods most frequently causing OAS were peach (21 subjects, 6.2%), cherry (19 subjects, 5.6%) and apple (17 subjects, 5.0%). 26 subjects (7.7%) reported OAS to Rosaceae fruits. The ratio of having OAS to consuming Rosaceae fruits was 11.0% in the group who had lived in Hokkaido for more than 20 years, which was higher than the group who has lived in Hokkaido for less than 20 years. The intake history of hazelnuts and Brazil nuts was very low, with a correspondingly low frequency of food hypersensitivity associated with these nuts. CONCLUSION: The frequency of intake and hypersensitivity of some foods differ among different regions.

Quality of gastric cancer care in designated cancer care hospitals in Japan.

OBJECTIVE: To develop a set of process-of-care quality indicators (QIs) that would cover a wide range of gastric cancer care modalities and to examine the current state of the quality of care provided by designated cancer care hospitals in Japan. DESIGN: A retrospective medical record review. SETTING: Eighteen designated cancer care hospitals throughout Japan. PARTICIPANTS: A total of 1685 patients diagnosed with gastric cancer in 2007. MAIN OUTCOME MEASURES: Provision of care to eligible patients as described in the 29 QIs, which were developed using an adaptation of the RAND/UCLA (University of California, Los Angeles) appropriateness method by a panel of nationally recognized experts in Japan. RESULTS: Overall, the patients received 68.3% of the care processes recommended by the QIs. While 'deep venous thrombosis prophylaxis before major surgery' was performed for 99% of the cases, 'documentation before endoscopic resection' was completed for only 12% of the cases. The chemotherapy care was less likely to meet the QI standards (61%) than pre-therapeutic care (76%), surgical treatment (66%) and endoscopic resection (71%; overall difference: P < 0.001). A comparison based on the types of care showed that documentation and patient explanation were performed less frequently (60 and 53%, respectively) than were diagnostic and therapeutic processes as recommended in the QIs (85%; overall P < 0.001). CONCLUSIONS: Although many required care processes were provided, some areas with room for improvement were revealed, especially with respect to chemotherapy, documentation and patient explanation. Continuous efforts to improve the quality and develop a system to monitor this progress would be beneficial in Japan.

Correlation between serum thymus and activation-regulated chemokine levels and stratum corneum barrier function in healthy individuals and patients with mild atopic dermatitis.

BACKGROUND: Serum thymus and activation-regulated chemokine (TARC) levels closely reflect the disease activity of atopic dermatitis (AD). AD is characterized by impaired epidermal barrier function and atopic dry skin. However, dry skin is also a very common problem in healthy individuals. OBJECTIVE: To investigate the relationship between serum TARC levels and epidermal barrier function in healthy subjects and patients with mild AD. METHODS: This study included 2 groups, 121 healthy subjects (healthy group) and 66 patients with mild AD (mild AD group). Barrier function was assessed by transepidermal water loss (TEWL) and stratum corneum hydration (SCH). RESULTS: Significantly elevated serum TARC levels and TEWL values and significantly decreased SCH values were detected in the mild AD group compared to those in the healthy group. In the mild AD group, serum TARC levels were significantly correlated with TEWL values and were inversely correlated with SCH values. Importantly, serum TARC levels were also inversely correlated with SCH values in the healthy controls. TEWL values in the healthy group tended to be correlated with TARC levels but did not reach statistical significance. CONCLUSION: Together with TEWL and SCH, serum TARC level is a useful biomarker, reflecting impairment of epidermal function in AD patients as well as healthy subjects.