Development and multi-institutional evaluation of a new phantom for verifying beam-positioning errors at off-isocenter positions.

PURPOSE: Single-isocenter stereotactic radiotherapy for multiple brain metastases requires highly accurate treatment delivery at off-isocenter positions (off-iso). This study aimed to verify the beam-positioning errors at off-iso using a newly developed phantom tested at multiple institutions. METHODS: The off-iso phantom comprised five stainless-steel balls with a 3-mm diameter placed at the center and at four peripheral positions on a diagonal line. Each ball was placed 3.5 cm apart along each of the three axes. Two patterns of the phantom setup were defined as 0° and 90° phantom rotations to evaluate the beam-positioning error, which is the distance between the center of the ball and the irradiated field on the electronic portal imaging device. Furthermore, the reproducibility of the beam-positioning errors was verified by evaluating their standard deviation (SD) at a single institution, which included five measurements for two treatment machines. The errors were evaluated at multiple institutions using eight treatment machines. RESULTS: The measurement time from setup to image acquisition was approximately 20 min for two patterns. The SD of the beam-positioning errors in the reproducibility tests was 0.41 mm. In the multi-institutional evaluation, the beam-positioning error at the isocenter position was within 1.00 mm of the AAPM-RSS tolerance, with the exception of two linacs. The largest beam-positioning error (1.36 mm) was observed 7.5 cm away from the isocenter in three directions at a gantry angle of 180°. CONCLUSIONS: The developed phantom can be applied as a new tool for establishing beam-positioning errors in single-isocenter stereotactic radiotherapy at off-isocenter positions.

Neutralizing Antibody Levels and Epidemiological Characteristics of Patients with Breakthrough COVID-19 Infection in Toyama, Japan.

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has increased owing to the emergence of novel SARS-CoV-2 variants. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses. Analysis of 44 specimens from patients diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many patients without neutralizing activity or BI were immunosuppressed. The results of this study show that contact with an infected person can result in BI, even when there are sufficient neutralizing antibodies in the blood. Thus, sufficient precautions must be taken to prevent infection even after vaccination.

Molecular epidemiological and pharmaceutical studies of methicillin-resistant Staphylococcus aureus isolated at hospitals in Kure City, Japan.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens of nosocomial infections throughout the world. In the medical field, it is extremely important to this pathogen's trends when considering infection control. Hypothesis/Gap Statement: We hypothesized that clarifying the characteristics of clinically isolated MRSA would contribute to infection control and proper use of antimicrobial agents against MRSA. Aim: The purpose of this study is to elucidate the genetic and biological characteristics of the MRSA isolates found at our hospital and to reveal changes in the spread of this pathogen in the local area where we live. Methodology: Pulse-field gel electrophoresis (PFGE) and polymerase chain reaction were used for the genetic analyses of MRSA isolates. Toxin production by each isolate was examined using toxin-specific detection systems. Results: During the 3 years from 2017 through 2019, over 1000 MRSA strains were isolated at our hospital. Genomic analysis of 237 of these clinical isolates by PFGE revealed 12 PFGE types (types A to L), each consisting of five or more MRSA clinical strains with over 80% genetic similarity. Examination of the SCCmec genotypes found that 219 of 237 isolated MRSA strains (approximately 92%) were SCCmec genotype II or IV and that only four of the isolates carried the Panton-Valentine leukocidin (PVL) gene. Examination of the toxin production of the isolates using staphylococcal enterotoxin detection kits found that most isolates carrying the SCCmec genotype II produced enterotoxin B and/or C, and that most isolates carrying the SCCmec genotype IV produced enterotoxin A. Conclusion: The present results revealed that MRSA isolates with common properties were isolated at certain rates throughout the 3 year study period, suggesting that relatively specific MRSA clones may have settled in the local area around our hospital. We also examine the relationship between antimicrobial usage over time and changes in MRSA isolation rates.

Viral isolation analysis of SARS-CoV-2 from clinical specimens of COVID-19 patients.

Genetic testing using reverse transcriptase real-time polymerase chain reaction (rRT-PCR) is the mainstay of diagnosis of COVID-19. However, it has not been fully investigated whether infectious viruses are contained in SARS-CoV-2 genome-positive specimens examined using the rRT-PCR test. In this study, we examined the correlation between the threshold Cycle (Ct) value obtained from the rRT-PCR test and virus isolation in cultured cells, using 533 consecutive clinical specimens of COVID-19 patients. The virus was isolated from specimens with a Ct value of less than 30 cycles, and the lower the Ct value, the more efficient the isolation rate. A cytopathic effect due to herpes simplex virus type 1 contamination was observed in one sample with a Ct value of 35 cycles. In a comparison of VeroE6/TMPRSS2 cells and VeroE6 cells used for virus isolation, VeroE6/TMPRSS2 cells isolated the virus 1.7 times more efficiently than VeroE6 cells. There was no significant difference between the two cells in the mean Ct value of the detectable sample. In conclusion, Lower Ct values in the PCR test were associated with higher virus isolation rates, and VeroE6/TMPRSS2 cells were able to isolate viruses more efficiently than VeroE6 cells.

Resection and reconstruction of pancreatic artery aneurysms caused by the compression of the celiac trunk by the median arcuate ligament: a report of two cases.

BACKGROUND: Some patients with the compression of the celiac trunk by the median arcuate ligament (MAL) suffer pancreatic artery aneurysms (PAAs) due to excessive blood flow from the superior mesenteric artery. These aneurysms are in peril because they are prone to rupture irrespective of size. Here, we present two cases of resection and reconstruction of PAAs caused by the compression of the celiac trunk by the MAL. CASE PRESENTATION: Patient 1 was a 44-year-old man who was first diagnosed to have a visceral artery aneurysm with a diameter of 4 cm accidentally found by ultrasound examination at a regular medical check-up. Contrast-enhanced CT revealed the compression of the celiac trunk by the MAL and a PAA originating from the first jejunal artery. First, laparoscopic excision of the MAL followed by a stent placement into the celiac trunk was performed. Although the stent was patent, the PAA still grew. The patient underwent resection and reconstruction of the PAA. Reconstruction of the pancreatic arterial arcade was needed because clamping of the inferior pancreaticoduodenal artery (IPDA) resulted in disappearance of the hepatic arterial blood flow. The follow-up CT 2 years and 9 months after the operation revealed no recurrence of aneurysms and the patent anastomosis. Patient 2 was a 68-year-old man who presented with an epigastric pain. Contrast-enhanced CT revealed the compression of the celiac trunk by the MAL and a PAA approximately 6 cm in diameter originating from the IPDA. The PAA was surrounded by a relatively low-intensity area, suggesting impending rupture of the PAA. The patient underwent resection and reconstruction of the PAA under an emergency situation. Reconstruction of the pancreatic arterial arcade was needed because clamping of the inflow IPDA resulted in disappearance of the hepatic blood flow. The follow-up CT 1 year and 8 months after the operation revealed no recurrence of aneurysms and the patent anastomosis. CONCLUSIONS: Although long-term follow-up is needed, resection and reconstruction is one of the therapeutic choices for PAAs caused by the compression of the celiac trunk by the MAL in order to prevent catastrophic aneurysm rupture.

Combined Effect of Arginine, Valine, and Serine on Exercise-Induced Fatigue in Healthy Volunteers: A Randomized, Double-Blinded, Placebo-Controlled Crossover Study.

Although several kinds of amino acids (AAs) are known to affect physiological actions during exercise, little is known about the combined effects of a mixture of several AAs on fatigue during exercise. The aim of the present study was to investigate the effect of an AA mixture supplement containing arginine, valine, and serine on exercise-induced fatigue in healthy volunteers. These AAs were selected because they were expected to reduce fatigue during exercise by acting the positive effects synergistically. A randomized, double-blinded, placebo-controlled crossover trial was conducted. Thirty-nine males ingested an AA mixture containing 3600 mg of arginine, 2200 mg of valine, and 200 mg of serine or a placebo each day for 14 days. On the 14th day, the participants completed an exercise trial on a cycle ergometer at 50% of VO2max for 120 min. After the two-week washout period, the participants repeated the same trial with the other test sample. The participant's feeling of fatigue based on a visual analog scale (VAS) and a rating of perceived exertion (RPE), as well as blood and physical parameters were evaluated. The feeling of fatigue based on VAS and RPE were significantly improved in AA compared to those in placebo. In the blood analysis, the increase in serum total ketone bodies during exercise and plasma tryptophan/branched-chain amino acids were significantly lower in AA than those in placebo. The present study demonstrated that supplementation with an AA mixture containing arginine, valine, and serine reduced the feeling of fatigue during exercise. The AA mixture also changed several blood parameters, which may contribute to the anti-fatigue effect.

Age-related and seasonal changes in covalently bound ceramide content in forearm stratum corneum of Japanese subjects: determination of molecular species of ceramides.

The stratum corneum (SC) consists of corneocytes surrounded by a neutral lipid-enriched intercellular matrix. Ceramides represent approximately 50% of intercellular lipids, and play important roles in retaining epidermal water. The SC also contains covalently bound ceramides, which are thought to play a crucial role in the formation of lamellar structures, and are involved in maintaining skin barrier function. A previous report showed that levels of free ceramides in human SC changed with the seasons and age, although whether the content of different species of covalently bound ceramides also underwent such temporal changes was unclear. Here, SC samples were taken from 99 healthy individuals of different ages (24-64 years) and during different seasons. The content of different molecular species of covalently bound ceramides in the samples was quantified using HPLC-MS/MS. The levels of total covalently bound ceramides (Total-Cers) significantly decreased approximately 50% in autumn and winter, compared with that of spring and summer. The levels of covalently bound ceramides containing saturated fatty acids (SFA-Cers) in the spring and summer were approximately 2.3-fold higher than that seen in autumn and winter, whereas the level of covalently bound ceramides containing unsaturated fatty acids (USFA-Cers) in spring and summer were approximately 1.6-fold higher than that in autumn and winter. Furthermore, the ratio between SFA-Cers and USFA-Cers was significantly lower in spring and summer than in autumn and winter. The levels of SFA-Cers, but not USFA-Cers, were significantly lower in individuals ≥ 50 years old compared to those who are 30- and 40-years old in the spring. Our study showed for the first time that, similar to free ceramides, the level of covalently bound ceramides changed with the seasons. However, age-related changes in covalently bound ceramide content were limited in that only the amount of SFA-Cers in the spring was lower in older individuals.

Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults.

A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida⁻Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida⁻Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.

Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers.

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67-2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25-1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23-1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84-4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63-0.67)]. CONCLUSIONS: We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients.

Post-Exercise Muscle Protein Synthesis in Rats after Ingestion of Acidified Bovine Milk Compared with Skim Milk.

Bovine milk proteins have a low absorption rate due to gastric acid-induced coagulation. Acidified milk remains liquid under acidic conditions; therefore, the absorption rate of its protein may differ from that of untreated milk. To investigate how this would affect muscle protein synthesis (MPS), we compared MPS after ingestion of acidified versus skim milk in rats. Male Sprague-Dawley rats swam for 2 h and were immediately administered acidified or skim milk, then euthanized at 30, 60, 90, and 120 min afterwards. Triceps muscle samples were excised for assessing fractional synthetic rate (FSR), plasma components, intramuscular free amino acids and mTOR signaling. The FSR in the acidified milk group was significantly higher than in the skim milk group throughout the post-ingestive period. Plasma essential amino acids, leucine, and insulin levels were significantly increased in the acidified milk group at 30 min after administration compared to the skim milk group. In addition, acidified milk ingestion was associated with greater phosphorylation of protein kinase B (Akt) and ribosomal protein S6 kinase (S6K1), and sustained phosphorylation of 4E-binding protein 1 (4E-BP1). These results indicate that compared with untreated milk, acidified milk ingestion is associated with greater stimulation of post-exercise MPS.

Effects of Whey, Caseinate, or Milk Protein Ingestion on Muscle Protein Synthesis after Exercise.

Whey protein (WP) is characterized as a "fast" protein and caseinate (CA) as a "slow" protein according to their digestion and absorption rates. We hypothesized that co-ingestion of milk proteins (WP and CA) may be effective for prolonging the muscle protein synthesis response compared to either protein alone. We therefore compared the effect of ingesting milk protein (MP) to either WP or CA alone on muscle protein synthesis after exercise in rats. We also compared the effects of these milk-derived proteins to a control, soy protein (SP). Male Sprague-Dawley rats swam for two hours. Immediately after exercise, one of the following four solutions was administered: WP, CA, MP, or SP. Individual rats were euthanized at designated postprandial time points and triceps muscle samples collected for measurement of the protein fractional synthesis rate (FSR). FSR tended to increase in all groups post-ingestion, although the initial peaks of FSR occurred at different times (WP, peak time = 60 min, FSR = 7.76%/day; MP, peak time = 90 min, FSR = 8.34%/day; CA, peak time = 120 min, FSR = 7.85%/day). Milk-derived proteins caused significantly greater increases (p < 0.05) in FSR compared with SP at different times (WP, 60 min; MP, 90 and 120 min; CA, 120 min). Although statistical analysis could not be performed, the calculated the area under the curve (AUC) values for FSR following this trend were: MP, 534.61; CA, 498.22; WP, 473.46; and SP, 406.18. We conclude that ingestion of MP, CA or WP causes the initial peak time in muscle protein synthesis to occur at different times (WP, fast; MP, intermediate; CA, slow) and the dairy proteins have a superior effect on muscle protein synthesis after exercise compared with SP.

Whey protein hydrolysates enhance water absorption in the perfused small intestine of anesthetized rats.

We evaluated the effect of whey protein hydrolysates (WPH) on the water absorption rate in the small intestine using a rat small intestine perfusion model. The rate was significantly higher with 5 g/L WPH than with 5 g/L soy protein hydrolysates or physiological saline (p < 0.05). WPH dose-dependently increased the water absorption rate in the range of 1.25-10.0 g/L. WPH showed a significantly higher rate than an amino acid mixture whose composition was equal to that of WPH (p < 0.05). The addition of 4-aminomethylbenzoic acid, an inhibitor of PepT1, significantly suppressed WPH's enhancement of water absorption (p < 0.05). The rate of water absorption was significantly correlated with that of peptides/amino acids absorption in WPH (r = 0.82, p < 0.01). These data suggest that WPH have a high water absorption-promoting effect, to which PepT1 contributes.

Increased Milk Protein Concentration in a Rehydration Drink Enhances Fluid Retention Caused by Water Reabsorption in Rats.

A fluid-retention effect is required for beverages that are designed to prevent dehydration. That is, fluid absorbed from the intestines should not be excreted quickly; long-term retention is desirable. Here, we focused on the effect of milk protein on fluid retention, and propose a new effective oral rehydration method that can be used daily for preventing dehydration. We first evaluated the effects of different concentrations of milk protein on fluid retention by measuring the urinary volumes of rats fed fluid containing milk protein at concentrations of 1, 5, and 10%. We next compared the fluid-retention effect of milk protein-enriched drink (MPD) with those of distilled water (DW) and a sports drink (SD) by the same method. Third, to investigate the mechanism of fluid retention, we measured plasma insulin changes in rats after ingesting these three drinks. We found that the addition of milk protein at 5 or 10% reduced urinary volume in a dose-dependent manner. Ingestion of the MPD containing 4.6% milk protein resulted in lower urinary volumes than DW and SD. MPD also showed a higher water reabsorption rate in the kidneys and higher concentrations of plasma insulin than DW and SD. These results suggest that increasing milk protein concentration in a beverage enhances fluid retention, which may allow the possibility to develop rehydration beverages that are more effective than SDs. In addition, insulin-modifying renal water reabsorption may contribute to the fluid-retention effect of MPD.

Milk Phospholipids Enhance Lymphatic Absorption of Dietary Sphingomyelin in Lymph-Cannulated Rats.

Supplementation with sphingomyelin has been reported to have beneficial effects on disease prevention and health maintenance. However, compared with glycerolipids, intact sphingomyelin and ceramides are poorly absorbed. Therefore, if the bioavailability of dietary sphingomyelin is increased, then the dose administered can be reduced. This study was designed to identify molecular species of ceramide in rat lymph after the ingestion of milk sphingomyelin, and to compare the effect of purified sphingomyelin with milk phospholipids concentrate (MPL, 185 mg sphingomyelin/g) on lymphatic absorption of milk sphingomyelin. Lymph was collected hourly for 6 h from lymph-cannulated rats (n = 8/group) after the administration of a control emulsion (triolein, bovine serum albumin, and sodium taurocholate), a sphingomyelin emulsion (control + purified sphingomyelin), or a MPL emulsion (control + MPL). Molecular species of ceramide in lymph were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Molecular species of ceramide, containing not only d18:1, but also d17:1 and d16:1 sphingosine with 16:0, 22:0, 23:0, and 24:0 fatty acids (specific to milk sphingomyelin), were increased in rat lymph after the administration of milk sphingomyelin. Their molecular species were similar to those of dietary milk sphingomyelin. Recovery of ceramide moieties from dietary sphingomyelin was 1.28- to 1.80-fold significantly higher in the MPL group than in the sphingomyelin group. Our results demonstrated that dietary sphingomyelin from milk was transported to lymph as molecular species of ceramide hydrolyzed from milk sphingomyelin and co-ingestion of sphingomyelin with glycerophospholipids enhanced the bioavailability of dietary sphingomyelin.

A novel mechanism for improvement of dry skin by dietary milk phospholipids: Effect on epidermal covalently bound ceramides and skin inflammation in hairless mice.

BACKGROUND: Dietary milk phospholipids (MPLs) increase hydration of the stratum corneum and reduced transepidermal water loss (TEWL) in hairless mice fed a standard diet. However, the mechanism by which MPLs improve skin barrier functions has yet to be established. OBJECTIVE: This study was designed to examine the mechanism by which MPLs may affect covalently bound ceramides and markers of skin inflammation and improve the skin barrier defect in hairless mice fed a magnesium-deficient (HR-AD) diet. METHODS: Four-week-old female hairless mice were randomized into four groups (n=10/group), and fed a standard (control) diet, the HR-AD diet, the HR-AD diet supplemented with either 7.0 g/kg MPLs (low [L]-MPL) or 41.0 g/kg MPLs (high [H]-MPL). RESULTS: Dietary MPLs improved the dry skin condition of hairless mice fed the HR-AD diet. MPLs significantly increased the percentage of covalently bound ω-hydroxy ceramides in the epidermis, and significantly decreased both thymus and activation-regulated chemokine (TARC) mRNA and thymic stromal lymphopoietin (TSLP) mRNA levels in skin, compared with the HR-AD diet. Furthermore, the MPL diets significantly decreased serum concentrations of immunoglobulin-E, TARC, TSLP, and soluble P-selectin versus the HR-AD diet. CONCLUSION: Our study showed for the first time that dietary MPLs may modulate epidermal covalently bound ceramides associated with formation of lamellar structures and suppress skin inflammation, resulting in improved skin barrier function.

Midterm outcomes of endovascular repair for abdominal aortic aneurysms with the on-label use compared with the off-label use of an endoprosthesis.

PURPOSE: Endovascular repair of an abdominal aortic aneurysm (EVAR) is sometimes not performed in accordance with the instructions for use (IFU) of the endoprosthesis ("off-label use"). We investigated whether the off-label use of the endograft affected the outcomes of EVAR. METHODS: Demographic, anatomical, intraoperative and follow-up data on 100 patients in whom the endograft was used on-label in EVAR were compared retrospectively with the corresponding data of 50 patients with off-label endograft use. RESULTS: The endograft IFU were most often not followed in patients with challenging aortic neck anatomy or iliac access or fixation, steep neck angulation or bilateral hypogastric artery embolization. Compared with patients in whom the device was used on-label, patients with off-label use had significantly higher rates of intraoperative type I or III endoleaks and proximal aortic cuff placement or other adjunctive procedures. However, there were no midterm differences between the two groups in the rates of type 1b or II endoleaks, sac enlargement, device-limb occlusion or patient survival. CONCLUSIONS: Most midterm outcomes of EVAR in which the endografts were used off-label were similar to those associated with on-label use of the devices. Off-label use of EVAR endoprostheses is feasible, but requires the use of special techniques in patients with challenging anatomical features.

[Resveratrol did not prevent sevoflurane-induced neuroapoptosis in the neonatal mice brain].

BACKGROUND: In an animal model, neonatal exposure to sevoflurane induces neuroapoptosis, leading to memory deficits in adulthood. A recent study showed that resveratrol (20 mg x kg(-1)) prevent alcohol-induced cognitive deficits and neural apotosis in rat pups postnatally exposed to ethanol. We investigated if resveratorol prevent sevoflurane induced neuroapotosis. METHODS: Six-day-old mice were divided into two groups: resveratorol and control groups. Pups were given resveratrol orally 24h and 1h before sevoflurane anesthesia. Anesthesia was maintained for 6h. After anesthesia, apotosis was evaluated by immunohistochemical staining for activated caspase-3. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apotosis. RESULTS: Neonatal exposure to sevoflurane induced severe neuroapotosis. There were no differences between control groups and resveratrol groups with regards to immunohistochemical staining and western blot analysis. CONCLUSIONS: Resveratrol did not prevent sevoflurane-induced neuroapoptosis in the neonatal mice brain.

Effects of Lactobacillus gasseri OLL2809 and α-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial.

Strenuous exercise reduces immune cell function and increases the risk of respiratory and gastrointestinal infections. In addition, it affects mood state and causes physical fatigue. Athletes require both mental and physical conditioning to execute good performance. In this study, we conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the immunopotentiation and fatigue-alleviation effects of Lactobacillus gasseri OLL2809 (LG2809) and α-lactalbumin (αLA) in university-student athletes after strenuous exercise. A total of 44 university students who performed strenuous exercise daily were separated into 3 groups to receive a 4-week course of placebo, 100 mg LG2809, or 100 mg LG2809 in combination with 900 mg αLA, respectively. Before and after each dietary treatment, the subjects performed strenuous cycle ergometer exercise for 1 h. Before and after each exercise session, blood samples and visual analogue scale scores for fatigue were obtained. In addition, the mood of each subject before and after the dietary treatment was evaluated using the Profile of Mood States (POMS) questionnaire. LG2809 ingestion was effective in preventing reduced natural killer cell activity due to strenuous exercise and elevating mood from a depressed state. In addition, LG2809 + αLA was found to alleviate minor resting fatigue, which was supported objectively by the significant reduction in the serum reactive oxygen metabolites and transforming growth factor ß1 levels. These effects could be helpful for athletes to maintain mental and physical condition.

Neuroleptic malignant syndrome in a patient with tongue cancer: a report of a rare case.

Background. Neuroleptic malignant syndrome (NMS) is a rare but life-threatening complication of neuroleptic drugs, which are used widely in head and neck cancer (HANC) patients who develop delirium. Methods and Results. Postoperative delirium in a 39-year-old man with tongue cancer was treated with haloperidol and chlorpromazine. Three days after the first administration of antipsychotics, the patient exhibited elevated body temperature, autonomic and extrapyramidal symptoms, and impaired consciousness. A definitive diagnosis was made using the research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were immediately discontinued. The patient was given dantrolene and bromocriptine to treat the NMS. The patient's hyperthermia, elevated creatinin kinase (CK), and muscle rigidity improved gradually, with all symptoms of NMS resolving completely by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for early signs of NMS and use antipsychotics conservatively to avoid NMS and its potentially fatal outcome.

Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis.

The oral intake of Lactobacillus spp. can provide beneficial effects to the host by modulating the immune response. Atopic dermatitis (AD) is an allergic inflammatory disease mediated by various immune responses. In this study, we examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD that was developed by the topical application of mite antigen in NC/Nga mice. The oral intake of heat-killed OLL1073R-1 cells inhibited both the development of dermatitis and the elevation of an acute inflammation marker, serum amyloid A. Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also attenuated secretion of IL-6 from lymph node cells in response to mite antigen and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN-γ or IL-4 was not influenced by OLL1073R-1 intake. We also found that inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1) markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in BALB/c mice. These results indicate that IL-6 plays an essential role in the development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1 inhibits dermatitis, at least in part, by suppressing the IL-6 response.