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There are several injuries potentially related to high-G exposure, including neck and back pain, spinal fractures, and pneumomediastinum. We present a young military pilot diagnosed with isolated fractures of the right 9th and 10th ribs via X-ray after high-G exposure (maximum G level: 9G). This patient presented with progressive and localized pain in the right anterior chest and flank region. After conservative treatment with rest and pain management, he recovered from the rib fractures and completed all profile challenges in the advanced high-G training program. A review of the annual health examination of the pilot did not show any rib lesions or other related illnesses. He was qualified for flying class II and considered fit for flight training. His medication history was unremarkable, and he did not have a family history of malignancy, osteoporosis, or osteopenia. He also denied having previously experienced trauma of the rib cage or participated in any strenuous military training program or exercise before centrifuge training. The potential explanations for the multiple rib fractures are repetitive stress from the anti-G straining maneuver and anti-G suit compression of the abdominal bladder. To our knowledge, consecutive rib fractures related to high-G exposure have never been documented. This report may increase the awareness of flight surgeons and training units regarding the risk of chest wall injuries during high-G exposure and encourage them to use multiple diagnostic tools to determine the correct diagnosis.

Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09–3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19–7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65–2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable.

In the past decade, the high morbidity and mortality of atherosclerotic disease have been prevalent worldwide. High-fat food consumption has been suggested to be an overarching factor for atherosclerosis incidence. This study aims to investigate the effects of kefir peptides on high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout (ApoE−/−) mice. 7-week old male ApoE−/− and normal C57BL/6 mice were randomly divided into five groups (n = 8). Atherosclerotic lesion development in ApoE−/− mice was established after fed the HFD for 12 weeks compared to standard chow diet (SCD)-fed C57BL/6 and ApoE−/− control groups. Kefir peptides oral administration significantly improved atherosclerotic lesion development by protecting against endothelial dysfunction, decreasing oxidative stress, reducing aortic lipid deposition, attenuating macrophage accumulation, and suppressing the inflammatory immune response compared with the HFD/ApoE−/− mock group. Moreover, the high dose of kefir peptides substantially inhibited aortic fibrosis and restored the fibrosis in the aorta root close to that observed in the C57BL/6 normal control group. Our findings show, for the first time, anti-atherosclerotic progression via kefir peptides consumption in HFD-fed ApoE−/− mice. The profitable effects of kefir peptides provide new perspectives for its use as an anti-atherosclerotic agent in the preventive medicine.

This study investigated the effects of yelling intervention on symptoms and autonomic responses in motion sickness. Forty-two healthy participants were recruited, and they participated in Coriolis stimulation, a technique for inducing motion sickness. The experimental procedure comprised five 1-min rotating stimuli with 1-min rest after each stimulus. Then, the symptom severity was assessed using the Motion Sickness Symptom Rating (MSSR). The d2 Test of Attention scores and cardiovascular responses were recorded before and after Coriolis stimulation. The electrocardiogram results were documented to analyze heart rate variability (HRV). During Coriolis stimulus, the participants were required to yell 5–8 times in the experimental trial, and to keep quiet for each minute of rotation in the control trial. The yelling intervention significantly reduced the MSSR score (p < 0.001). Nevertheless, it did not significantly affect the d2 Test of Attention scores. Yelling while rotating did not significantly affect the heart rate nor blood pressure. However, it decreased the normalized low frequency of HRV (p = 0.036). Moreover, it improved motion sickness, but its effect on attention was not evident. Motion sickness could significantly affect cardiovascular responses and HRV. However, yelling did not affect cardiovascular response, and it reduced sympathetic nervous system activity.

Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture.Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment.The results demonstrated that KPs treatment improved the progression of the fracture healing process (p 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1, Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21).This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing.

All aircrews are required to undertake the altitude hypoxia training and be familiarized with the hypobaric effect on their physiological regulation. Due to the characteristics of the helicopter aircrafts, few researches have reported in-flight hypoxia events among the helicopter aircrews. The main goal of this study was designed to compare the hypoxia symptoms of helicopter aircrews between the altitude hypoxia training and during flight. We developed a questionnaire to collect the details of chamber flights and in-flight hypoxia events in 2019. All data were managed by the SPSS software and two-tailed 0.05 alpha level was considered as a significant level. Of the 213 study participants, there were eight (3.8%) cases that experienced hypoxia symptoms during the flight. The top five symptoms that appeared both in the last and current altitude hypoxia trainings were visual impairment (20.7%), difficulty concentrating (12.7%), tiredness (12.2%), cognitive impairment (8.0%), and air hunger (5.2%). Meanwhile, the frequency of those symptoms above was not significantly different from the last or current training compared with those in-flight hypoxia events. The survey unveiled a series of consistency correlations of hypoxia symptoms between the chamber flights and in-flight environment for the helicopter aircrew group.

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (−509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (−509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (−509 C/T) genotype in all subjects and TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (−509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

Background A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. Some genetic studies have demonstrated that the NF-κB genetic mutation could cause kidney injury and kidney disease progression. However, the association of a gene polymorphism in the transcription factor binding site of NF-κB with kidney disease is not clear. Methods We used the Taiwan Biobank database, the University of California, Santa Cruz, reference genome, and a chromatin immunoprecipitation sequencing database to find single nucleotide polymorphisms (SNPs) at potential binding sites of NF-κB. In addition, we performed a case–control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service General Hospital from 2015 to 2016. Furthermore, we used the ChIP assay to identify the binding activity of different genotypes and used Luciferase reporter assay to examine the function of the rs9395890 polymorphism. Result The results of biometric screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.049). The ChIP assay revealed an approximately 1.49-fold enrichment of NF-κB of the variant type TT when compared to that of the wild-type GG in rs9395890 (P = 0.027; TT = 3.20 ± 0.16, GT = 2.81 ± 0.20, GG = 1.71 ± 0.18). The luciferase reporter assay showed that the NF-κB binding site activity in T allele was slightly higher than that in G allele, though it is not significant. Conclusions Our findings indicate that rs9395890 is associated with susceptibility to ESRD in Taiwan population. Electronic supplementary material The online version of this article (10.1186/s12882-019-1471-2) contains supplementary material, which is available to authorized users.

Extracellular superoxide dismutase 3 (SOD3), one member of the antioxidant defense system and a superoxide scavenger, has been noted to be downregulated in the kidneys of diabetic mice and is characterized by a heparin-binding domain that can anchor the protein to the endothelium and extracellular matrix. The association of the serum and urinary SOD3 levels with diabetic nephropathy in different stages has never been evaluated. It remains unclear how urinary SOD3 changes in different renal diseases. We recruited 98 Taiwanese patients with type 2 diabetes and 10 patients with early chronic kidney disease (CKD) into this study. Biochemical analyses were performed, including evaluation of the serum SOD3, urinary SOD3, urinary albumin, urinary vascular endothelial growth factor (VEGF), and urinary angiotensinogen (ANG). The Kruskal-Wallis rank sum test was used to compare various parameters among the three groups of patients: early CKD, diabetes alone, and diabetes with CKD. Results showed that lower serum and urinary SOD3 levels were observed in the group of patients with diabetes alone. Higher serum and urinary SOD3 levels were observed in the group of patients with diabetes and CKD, which had higher albuminuria and serum creatinine levels. The serum SOD3 levels were significantly positively correlated with renal function, according to the serum creatinine level. The urinary levels of SOD3 were significantly correlated with other urinary biomarkers such as urinary ANG and VEGF. Furthermore, albuminuria can positively predict the serum SOD3 level for the ratio of urinary albumin to urinary creatinine (ACR) >1,190.769 mg/g and the urinary SOD3 level for ACR ≥300 mg/g.

BACKGROUND Military aircrew are occupationally exposed to a high-G environment. G force causes blood to flow to the lower body region and challenges their cardiac function and anti-G straining maneuver effectiveness. A tolerance test is necessary for every military aircrew member before undergoing flight training. A novel cardiac force index (CFI) has been developed and used to assess long-distance running by mobile health (mHealth) technology. There is still no study to monitor the CFI by wearable devices during the G tolerance test. OBJECTIVE We added the cardiac function parameter CFI to the G tolerance test and elucidated the relationship between cardiac function and G tolerance among military aircrew. METHODS A noninvasive device, BioHarness 3.0, was used to measure heart rate (HR) and activity while resting and walking on the ground. The mathematical formula for cardiac function calculation is CFI = weight × activity/HR. The cardiac force ratio (CFR) is calculated by walking CFI (WCFI)/resting CFI (RCFI). G tolerance includes relaxed G tolerance (RGT) and straining G tolerance (SGT) tested by a human centrifuge under the gradual-onset-rate profile. RESULTS In total, 92 male participants voluntarily completed this study. The average values of RCFI, WCFI, and CFR were 0.02 [SD 0.04], 0.15 [SD 0.04], and 10.77 [SD 4.11], respectively. The mean RGT and SGT were 5.1G [SD 0.9] and 7.8G [SD 1.1], respectively, in the centrifuge. The percentages of participants with RGT greater than 5G or SGT greater than 8G were equally noted as 54.3%. Each 100-unit increase in WCFI increased RGT by 0.14G [SE 0.02, 95% CI 0.09 to 0.19] and by 0.17G [SE 0.03, 95% CI 0.11 to 0.22], corresponding to SGT. In addition, there was an increased chance of RGT values higher than 5G and SGT values higher than 8G according to the increase in WCFI. CONCLUSIONS Our results suggested that WCFI is positively correlated with G tolerance in the centrifuge and has the potential to be used for military aircrew selection.

Hypoxia remains a flight-safety issue in terms of aviation medicine. Hypoxia-awareness training has been used to help aircrew members recognize personal hypoxia symptoms. There is still no study, as yet, to establish the association of within-subject data between inflight hypoxia events and the altitude chamber. The main purpose of our study was to use paired subjects’ data on inflight hypoxia symptoms compared with those experienced during training. A questionnaire was developed to obtain information on military aircrew members in 2018. Among 341 subjects, 46 (13.49%) suffered from inflight hypoxia. The majority of the subjects detected ongoing inflight hypoxia on the basis of their previous experience with personal hypoxia symptoms or sensations in previous chamber flights. Of the top five hypoxia symptoms, the data revealed that hot flashes, poor concentration, and impaired cognitive function appeared both during the inflight events and during the hypoxia-awareness training. The occurrence rate of hypoxia symptoms was found to not be significantly different between the in-flight events and the past chamber flights through an analysis of within-subject data. Because the individual memory had faded away over time, fresher hypoxia awareness training is still mandatory and valuable to recall personal hypoxia experience for military aircrew members.

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor-phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use.

BackgroundExacerbation of chronic obstructive pulmonary disease (COPD) severely impacts the quality of life and causes high mortality and morbidity. COPD is involved with systemic and pulmonary inflammation, which may be attenuated with antidiabetic agents exerting anti-inflammatory effects. Real-world evidence is scant regarding the effects of antidiabetic agents on COPD exacerbation. Accordingly, we conducted a disease risk score (DRS)-matched nested case–control study to systemically assess the association between each class of oral hypoglycemic agents (OHAs) and risk of severe COPD exacerbation in a nationwide COPD population co-diagnosed with diabetes mellitus (DM).MethodsWe enrolled 23,875 COPD patients receiving at least one OHA for management of DM by analyzing the Taiwan National Health Insurance claims database between January 1, 2000, and December 31, 2015. Cases of severe exacerbation were defined as those who had the first hospital admission for COPD. Each case was individually matched with four randomly-selected controls by cohort entry date, DRS (the estimated probability of encountering a severe COPD exacerbation), and COPD medication regimens using the incidence density sampling approach. Conditional logistic regressions were performed to estimate odds ratios (OR) of severe COPD exacerbation for each type of OHAs.ResultsWe analyzed 2700 cases of severe COPD exacerbation and 9272 corresponding controls after DRS matching. Current use of metformin versus other OHAs was associated with a 15% (adjusted OR [aOR], 0.85; 95% confidence interval [CI] 0.75–0.95) reduced risk of severe COPD exacerbation, whereas the reduced risk was not observed with other types of antidiabetic agents. When considering the duration of antidiabetic medication therapy, current use of metformin for 91–180 and 181–365 days was associated with a 28% (aOR, 0.72; 95% CI 0.58–0.89) and 37% (aOR, 0.63; 95% CI 0.51–0.77) reduced risk of severe COPD exacerbation, respectively. Similarly, 91–180 days of sulfonylureas therapy led to a 28% (aOR, 0.72; 95% CI 0.58–0.90) lower risk, and longer treatments consistently yielded 24–30% lower risks. Current use of thiazolidinediones for more than 181 days yielded an approximately 40% decreased risk.ConclusionsDuration-dependent beneficial effects of current metformin, sulfonylurea, and thiazolidinedione use on severe COPD exacerbation were observed in patients with COPD and DM.

Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1&ndash, 5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio: 9.91, 95% confidence interval: 4.11&ndash, 23.88). The chances of failure were inversely related to the HR increase percentage (p for trend &lt, 0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.

The increased prevalence of renal dysfunction and chronic kidney disease (CKD) and the high costs and poor outcomes of treatment are a significant health issue. The consequence of chronic high blood pressure is the increased prevalence of target organ end-stage renal disease, which has been proven to be a strong independent risk factor for adverse cardiovascular disease. A previous study showed that kefir products have anti-inflammatory and anti-hypertensive activities and immunological modulation functions. However, no data regarding the beneficial effects of kefir peptides (KPs) on salt-induced renal damage or related kidney diseases are available. In this study, KPs were orally administered to aged salt-induced stroke-prone spontaneously hypertensive (SHRSP) rats, and the effects of KPs against inflammation and oxidative stress and their ability to protect against renal dysfunction were evaluated. Fifty-five-week-old SHRSP rats under induction with 1% NaCl in drinking water for 4 weeks showed multiple renal injuries with increased renal inflammation, fibrosis, oxidative stress, tubular atrophy, and glomerulosclerosis. In contrast, oral gavage with KPs reduced the urine protein to creatinine (UPC) ratio, the fractional excretion of electrolytes (FeNa and FeCl), extracellular matrix deposition, and the interstitial fibrotic &alpha, smooth muscle actin (&alpha, SMA) levels in salt-induced SHRSP rats. The renal infiltration of inflammatory cells, the release of monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and the cytokine nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and transforming growth factor-&beta, (TGF-&beta, ), the reactive oxygen species (ROS) levels, and histopathological lesions were also decreased in salt-induced SHRSP rats. Furthermore, KP treatment significantly increased the renal superoxide dismutase (SOD) activity and the glomerular filtration rate (GFR), which exerted potent protection against salt-induced chronic kidney disease in SHRSP rats. The results of this study suggest that KPs ameliorate salt-induced renal damage, tubular atrophy, and glomerular dysfunction through anti-inflammatory, antioxidative stress, and antifibrotic activities, and might be a promising protective agent against high salt-induced renovascular-related diseases.

BackgroundAircrew members are required to attend hypoxia awareness training regularly to strengthen their memory of their personal hypoxia symptoms by undergoing training inside a hypobaric chamber. The aim of this study was to examine the association between hypoxia symptoms experienced during two training sessions that were 4 years apart.MethodsThis was a crossover study to compare hypoxia symptoms and self-reported physiological effects of trapped gas between a previous training session and a current training session in an altitude chamber. The subjects were military crew members who undertook a 25,000-feet refresher training course in 2018. We used a structured questionnaire to obtain the target information before and during hypoxia exposure. Data were analyzed using SPSS software.ResultsA total of 341 trainees participated in this survey and completely filled out the questionnaire. Gastrointestinal tract discomfort caused by the expansion of trapped gas was the main physiological reaction during the previous and current training sessions. Frequently reported symptoms were poor concentration (30.5%), impaired cognitive function (20.5%), visual disturbances (16.4%), hot flashes (15.8%), and paresthesia (12.6%) during both exposures. However, the proportions of participants reporting poor concentration (P = 0.378) and visual disturbances (P = 0.594) were not significantly different between the recalled and current training sessions. The five most common symptoms among the subjects with less than 1,000 flight hours were poor concentration (29.8%), visual disturbance (27.3%), impaired cognitive function (14.9%), dizziness/lightheadedness (11.6%), and hot flashes (9.9%), which overlapped substantially with the symptoms reported by other subjects. The occurrence of those five most common symptoms in the group with more than 1,000 flight hours did not significantly differ between the recalled training session and the current training session.ConclusionsThe most common hypoxia symptoms reported were similar between the recalled and current training sessions in an environment with a low oxygen concentration. This finding was also clearly affected by the duration of flight experience. Moreover, GI effects of the expansion of trapped gas were commonly observed at low atmospheric pressure.

Scope Kefir is an acidic and alcoholic fermented milk product with multiple health-promoting benefits. Our previous study demonstrated that kefir enhanced calcium absorption in intestinal Caco-2 cells. In this study, kefir-fermented peptide-1 (KFP-1) was isolated from the kefir peptide fraction, and its function as a calcium-binding peptide was characterized. Methods and results KFP-1 was identified as a 17-residue peptide with a sequence identical to that of κ-casein (residues 138-154) in milk protein. KFP-1 was demonstrated to promote calcium influx in Caco-2 and IEC-6 small intestinal cells in a concentration-dependent manner. TRPV6, but not L-type voltage-gated calcium channels, was associated with the calcium influx induced by KFP-1. An in vitro calcium binding assay indicated that the full-length KFP-1 peptide has a higher calcium-binding capacity than the two truncated KFP-1 peptides, KFP-1∆C5 and KFP-1C5. Alexa Fluor 594 labeling showed that KFP-1 is taken up by Caco-2 cells and interacts with calcium ions and TRPV6 protein. Moreover, KFP-1 was found moderately resistant to pepsin and pancreatin digestions and enhanced calcium uptake by intestinal enterocytes in vivo. Conclusion These data suggest that KFP-1, a novel calcium-binding peptide, binds extracellular calcium ions and enters Caco-2 and IEC-6 cells, and promotes calcium uptake through TRPV6 calcium channels. The present study is of great importance for developing kefir-derived metal ion-binding peptides as functional nutraceutical additives. This article is protected by copyright. All rights reserved.

Military aircrew are occupationally exposed to a high-G environment. A tolerance test and surveillance is necessary for military aircrew before flight training. A cardiac force index (CFI) has been developed to assess long-distance running by health technology. We added the parameter CFI to the G tolerance test and elucidated the relationship between the CFI and G tolerance. A noninvasive device, BioHarness 3.0, was used to measure heart rate (HR) and activity while resting and walking on the ground. The formula for calculating cardiac function was CFI = weight × activity/HR. Cardiac force ratio (CFR) was calculated by walking CFI (WCFI)/resting CFI (RCFI). G tolerance included relaxed G tolerance (RGT) and straining G tolerance (SGT) tested in the centrifuge. Among 92 male participants, the average of RCFI, WCFI, and CFR were 0.02 ± 0.04, 0.15 ± 0.04, and 10.77 ± 4.11, respectively. Each 100-unit increase in the WCFI increased the RGT by 0.14 G and the SGT by 0.17 G. There was an increased chance of RGT values higher than 5 G and SGT values higher than 8 G according to the WCFI increase. Results suggested that WCFI is positively correlated with G tolerance and has the potential for G tolerance surveillance and programs of G tolerance improvement among male military aircrew.

Background: In-flight spatial disorientation (SD) is a predominant threat to flight safety in aviation. This study was conducted to understand the prevalence, severity, and frequency of in-flight SD among military pilots in Taiwan. Methods: A survey was conducted to collect tri-service pilots' experiences of SD during flight. Participants completed anonymous SD questionnaires during refresher physiology training. There were 486 questionnaires delivered to trainees and the completion rate was 97.1% (n = 472). All data were processed using SPSS version 24 software (IBM, Armonk, NY, USA). Results: Of the 472 participants, the average age of the pilots was 36.7 so 7.3 years and 97.7% were male. About 80% of participants experienced in-flight SD events. There was a significant difference between prevalence of SD in fighter (87.0%), trainer (89.8%), transporter (70.6%), and helicopter (66.7%) pilots (P < 0.001). Less than 10% of the events were severe, and there was no obvious variation between aircraft types (P = 0.126). Pilots were sensitive to SD in clouds and under low visibility. Over 70% of pilots experienced visual illusions, especially loss of horizon during bad weather (45.1%), followed by leans (44.5%), false horizon (44.1%), false sense in clouds (39.6%), Coriolis illusion (25.0%), and confusion on entry to instrument meteorological conditions (25.0%). Conclusions: Our survey showed that SD is a common physiological problem among military pilots, who were easily disoriented by in-flight SD without visual cues. Visual illusion was relatively more frequent, especially for trainer and fighter pilots.

Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. &alpha, Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of Alloprevotella, Anaerostipes, Parasutterella, Romboutsia, Ruminococcus_1 and Streptococcus genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.

Spinal epidural abscess is rare in patients following dental extraction. Only seven cases have been described in the literature. We report the first case of an epidural abscess in the lumbar spine following dental extraction, and present a review of the relevant literature. A 53-year-old man presented with low back pain 1 week following dental extraction, and imaging revealed the presence of a lumbar epidural abscess. He underwent surgical drainage by decompressive laminectomy with evacuation of pus and debridement of the infected bone, and he was treated with a prolonged course of intravenous antibiotics. The patient demonstrated no neurologic sequelae at the 6-month follow-up examination. A search of the relevant literature showed that, of the seven epidural abscesses that occurred following dental extractions, five were cervical and two were intracranial. An epidural abscess in the lumbar spine following dental extraction had not been reported. Thus, this is the first report of an epidural abscess in the lumbar spine following dental extraction. It is also the first case of epidural abscess following dental extraction that was determined to be caused by Streptococcus suis . Our findings indicate that epidural abscess must be considered as a diagnosis for all patients presenting with intractable low back pain, with or without fever and neurologic impairment, after a recent dental extraction. We conclude that appropriate imaging must be conducted for early diagnosis.

// Cheng-Wei Lai 1,2,* , Hsiao-Ling Chen 3,* , Min-Yu Tu 1,4,5 , Wei-Yu Lin 1,2 , Theresa Rohrig 1,2 , Shang-Hsun Yang 6 , Ying-Wei Lan 1,7 , Kowit-Yu Chong 7,8 and Chuan-Mu Chen 1,2,9 1 Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan 2 Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan 3 Department of Bioresources, Da-Yeh University, Changhua, Taiwan 4 Department of Orthopaedic Surgery, Taichung Armed Forces General Hospital, Taichung, Taiwan and National Defense Medical Center, Taipei, Taiwan 5 Department of Biomedical Engineering, Hungkuang University, Taichung, Taiwan 6 Department of Physiology and Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan 7 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan 8 Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan 9 Rong-Hsing Translational Medicine Center, and iEGG Center, National Chung Hsing University, Taichung, Taiwan * These authors have contributed equally to this study Correspondence to: Chuan-Mu Chen, email: // Kowit-Yu Chong, email: // Keywords : osteoporosis; Akr1A1 gene; ascorbic acid; knockout mice; micro-CT imaging; trabecular bone; cortical bone; Pathology Section Received : August 13, 2016 Accepted : December 07, 2016 Published : January 02, 2017 Abstract The AKR1A1 protein is a member of the aldo-keto reductase superfamily that is responsible for the conversion of D-glucuronate to L-gulonate in the ascorbic acid (vitamin C) synthesis pathway. In a pCAG-eGFP transgenic mouse line that was produced by pronuclear microinjection, the integration of the transgene resulted in a 30-kb genomic DNA deletion, including the Akr1A1 gene, and thus caused the knockout (KO) of the Akr1A1 gene and targeting of the eGFP gene. The Akr1A1 KO mice ( Akr1A1 eGFP/eGFP ) exhibited insufficient serum ascorbic acid levels, abnormal bone development and osteoporosis. Using micro-CT analysis, the results showed that the microarchitecture of the 12-week-old Akr1A1 eGFP/eGFP mouse femur was shorter in length and exhibited less cortical bone thickness, enlargement of the bone marrow cavity and a complete loss of the trabecular bone in the distal femur. The femoral head and neck of the proximal femur also showed a severe loss of bone mass. Based on the decreased levels of serum osteocalcin and osteoblast activity in the Akr1A1 eGFP/eGFP mice, the osteoporosis might be caused by impaired bone formation. In addition, administration of ascorbic acid to the Akr1A1 eGFP/eGFP mice significantly prevented the condition of osteoporotic femurs and increased bone formation. Therefore, through ascorbic acid administration, the Akr1A1 KO mice exhibited controllable osteoporosis and may serve as a novel model for osteoporotic research.

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02361372","term_id":"NCT02361372"}}NCT02361372

Study design Retrospective review. Objective To assess the effectiveness of posterior correction and fixation without anterior fusion for pseudarthrosis with kyphosis in patients with ankylosing spondylitis. Summary of background data Anterior fusion is the current surgical treatment for pseudarthrosis with kyphosis in ankylosing spondylitis. The unique characteristic in ankylosing spondylitis is the superior ability to bridge and fuse the large anterior opening-wedge gap created by posterior osteotomy to correct the kyphosis without anterior fusion after the osteotomy site is adequately fixed. This ability may persist even if pseudarthrosis is present. Methods A total of 30 consecutive patients with ankylosing spondylitis (mean age 41.7 years, range 29-55) underwent posterior correction and fixation without anterior fusion to treat pseudarthrosis with kyphosis. Mean follow-up was 4.7 years (range 2.2-9.1). Radiographic and clinical results and complications were assessed. Results Local kyphosis was substantially corrected from 45.5 degrees (range 37 degrees-68 degrees) to 7.5 degrees (0 degrees-14 degrees), with a mean correction of 38 degrees. All patients had no evidence of nonunion on x-ray at the level of the pseudarthrosis at final follow-up. None had a notable loss of correction. No major complication occurred. There were 3 patients with neurologic deficits who had postoperative improvement. Conclusion Posterior correction and fixation is effective for treating pseudarthrosis with kyphosis in ankylosing spondylitis. No anterior fusion procedure was necessary.

Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.

In this study, the bone structures, nanomechanical properties and fracture behaviors in different groups of female C57BL/6 mice (control, sham operated, ovariectomized, casein supplemented, and fermented milk supplemented) were examined by micro-computed tomography, scanning and transmission electron microscopy, and nanoindentation. The control and sham operated mice showed dense bone structures with high cortical bone mineral densities of 544 mg/cm(3) (average) and high hardness of 0.9-1.1 GPa; resistance to bone fracture was conferred by microcracking, crack deflections and ligament bridging attributed to aligned collagen fibers and densely packed hydroxyapatite crystals. Bone mineral density, hardness and fracture resistance in ovariectomized mice markedly dropped due to loose bone structure with randomly distributed collagens and hydroxyapatites. The acidic casein supplemented mice with blood acidosis exhibited poor mineral absorption and loose bone structure, whereas the neutralized casein or fermented milk supplemented mice were resistant to osteoporosis and had high bone mechanical properties.