Hair Mineral and Trace Element Contents as Reliable Markers of Nutritional Status Compared to Serum Levels of These Elements in Children Newly Diagnosed with Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) are at high risk for nutritional deficiencies because of long-term inflammation in the gut mucosa and decreased oral intake. Because inflammation responses affect serum micronutrient concentrations, serum levels are limited in reflecting body nutrient status in acute and chronic illness. We investigated the usefulness of measuring trace elements in hair as reliable markers of nutritional status compared to serum levels in children with IBD. We retrospectively analyzed pediatric patients newly diagnosed with Crohn’s disease (n?=?49) and ulcerative colitis (n?=?16) and controls (n?=?29) from 2012 to 2016. Serum micronutrient levels, inflammatory markers, and hair trace element content were evaluated and compared at the time of diagnosis and before initiating treatment. Serum calcium (p?<?0.001), iron (p?<?0.001), zinc (p?=?0.013), selenium (p?=?0.008), albumin (p?<?0.001), prealbumin (p?<?0.001), hemoglobin and hematocrit (p?<?0.001), and WBC (p?=?0.001) and lymphocytes (p?<?0.001) differed significantly between the groups. After adjustment for the erythrocyte sedimentation rate, serum zinc and selenium levels were no longer significantly different between the groups (p?<?0.062 and p?<?0.057, respectively). Following hair analysis for mineral and trace elements, iron (p?=?0.033), selenium (p?=?0.017), and manganese (p?=?0.009) differed significantly between the groups. Serum micronutrient levels need cautious interpretation in conjunction with inflammatory markers. Hair mineral and trace element measurement may support understanding micronutrient status in children with IBD.     

Genetic associations between ADHD and dopaminergic genes (<Emphasis Type="Italic">DAT1</Emphasis> and <Emphasis Type="Italic">DRD4</Emphasis>) VNTRs in Korean children

It is well known that dopaminergic genes affect the development of attention deficit hyperactivity disorder (ADHD) in various populations. Many studies have shown that variable number tandem repeats (VNTRs) located within the 3′-untranslated region of DAT1 and in exon 3 of DRD4 are associated with ADHD development; however, these results were inconsistent. Therefore, we investigated the genetic association between two VNTRs and ADHD in Korean children. We determined the VNTRs using PCR. We examined genotype and allele frequency differences between the experimental and control groups, along with the odds ratios, using Chi square and exact tests. We observed a significant association between the children with ADHD and the control group in the 10R/10R genotype of DAT1 VNTRs (p?=?0.025). In addition, the 11R allele of DAT1 VNTRs showed a higher frequency in the control group than in the ADHD group (p?=?0.023). Also, the short repeat (without 11R) and long repeat alleles (including 11R) were associated with ADHD (p?<?0.05). The analysis of DRD4 VNTRs revealed that the 2R allele is associated with ADHD (p?=?0.025). A significant result was also observed in long and short repeats (p?<?0.05). Additionally, ADHD subtypes showed that the DRD4 VNTRs are associated with combined and hyperactive-impulsive subtype groups (p?<?0.05). Therefore, our results suggest that DAT1 VNTRs and DRD4 VNTRs play a role in the genetic etiology of ADHD in Korean children.     

Interleukin-6 and C-reactive protein,successful aging,and mortality: the PolSenior study

Background

In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.

Results

IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n?=?3496 individuals, p?<?0.001 and CRP: n?=?3632, p?=?0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n?=?1258, p?<?0.001 and CRP: n?=?1312, p?<?0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n?=?2238, p?<?0.001 and CRP: n?=?2320, p?=?0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p?<?0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p?<?0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR?=?1.063 per each pg/mL, 95 % CI: 1.052-1.074, p?<?0.001 and HR?=?1.020 per each mg/L, 95 % CI: 1.015-1.025, p?<?0.001, respectively) but also in the successfully aging subgroup (HR?=?1.163 per each pg/mL, 95 % CI: 1.128-1.199, p?<?0.001 and HR?=?1.074 per each mg/L, 95 % CI: 1.047-1.100, p?<?0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p?<?0.001).

Conclusions

Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

     

Effect of Percent Relative Humidity,Moisture Content,and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

The effect of percent relative humidity (16–84% RH), moisture content (4.2–6.5% w/w MC), and compression force (4.9–44.1 kN CF) on the light-induced fluorescence (LIF) response of 10% w/w active pharmaceutical ingredient (API) compacts is reported. The fluorescent response was evaluated using two separate central composite designs of experiments. The effect of % RH and CF on the LIF signal was highly significant with an adjusted R ² ?=?0.9436 and p?<?0.0001. Percent relative humidity (p?=?0.0022), CF (p?<?0.0001), and % RH² (p?=?0.0237) were statistically significant factors affecting the LIF response. The effects of MC and CF on LIF response were also statistically significant with a p value <0.0001 and adjusted R ² value of 0.9874. The LIF response was highly impacted by MC (p?<?0.0001), CF (p?<?0.0001), and MC² (p?=?0022). At 10% w/w API, increased % RH, MC, and CF led to a nonlinear decrease in LIF response. The derived quadratic model equations explained more than 94% of the data. Awareness of these effects on LIF response is critical when implementing LIF as a process analytical tool.     

<Emphasis Type="Italic">Agaricus bisporus</Emphasis> supplementation reduces high-fat diet-induced body weight gain and fatty liver development

Obesity is a global epidemic characterized not only by excessive fat deposition but also by important complications such as nonalcoholic liver steatosis. Beneficial antiobesogenic effects have been described for some mushrooms. The current study aimed to demonstrate the protective effect of Agaricus bisporus (AB) supplementation against the metabolic alterations induced by high-fat-diet (HFD) feeding. Eight-week-old C57BL/6J mice were fed for 10 weeks with one of the following diets: (1) control diet (n?=?7), (2) HFD (n?=?7), (3) HFD supplemented with 5% AB (n?=?9), and (4) HFD supplemented with 10% AB (n?=?9). A pair-fed group was also included for the 10% AB group (n?=?6). The impact of AB supplementation on food intake, body weight gain, and liver and fat pad weights was examined. Biochemical, histological, and molecular parameters were also analyzed. Dietary supplementation with 10% AB reduced the HFD-induced increase in body, epididymal, and mesenteric fat weights (p?<?0.01, p?<?0.05, and p?<?0.05, respectively). Supplementation with AB also reduced liver damage in a dose-dependent manner (p?<?0.01 and p?<?0.001). This effect was confirmed by histological analysis that showed that liver steatosis was markedly reduced in mice fed with AB. The beneficial properties of 10% AB supplementation appear to be mediated through a decrease in food intake and via stimulation of mesenteric and hepatic free-fatty acid beta-oxidation, along with a decrease in epidydimal and hepatic expression of CD36. In conclusion, supplementation with AB prevents excessive body weight gain and liver steatosis induced by HFD consumption.     

Protein malnutrition during fetal programming induces fatty liver in adult male offspring rats

We evaluated the effects of protein malnutrition on liver morphology and physiology in rats subjected to different malnutrition schemes. Pregnant rats were fed with a control diet or a low protein diet (LPD). Male offspring rats received a LPD during gestation, lactation, and until they were 60 days old (MM group), a late LPD that began after weaning (CM), or a LPD administrated only during the gestation-lactation period followed by a control diet (MC). On day 60, blood was collected and the liver was dissected out. We found a decrease in MM rats’ total body (p < 0.001) and liver (p < 0.05) weight. These and CM rats showed obvious liver dysfunction reflected by the increase in serum glutamic pyruvic transaminase (SGOT) (MM p < 0.001) and serum glutamic pyruvic transaminase (SGPT) (MM and CM p < 0.001) enzymes, and liver content of cholesterol (MM and CM p < 0.001) and triglycerides (MM p < 0.01; CM p < 0.001), in addition to what we saw by histology. Liver dysfunction was also shown by the increase in gamma glutamyl transferase (GGT) (MM, MC, and CM p < 0.001) and GST-pi1 (MM and CM p < 0.001, MC p < 0.05) expression levels. MC rats showed the lowest increment in GST-pi1 expression (MC vs. MM; p < 0.001, MC vs. CM; p < 0.01). ROS production (MM, CM, and MC: p < 0.001), lipid peroxidation (MM, CM, and MC p < 0.001), content of carbonyl groups in liver proteins (MM and CM p < 0.001, MC p < 0.01), and total antioxidant capacity (MM, CM, and MC p < 0.001) were increased in the liver of all groups of malnourished animals. However, MM rats showed the highest increment. We found higher TNF-α (MM and CM p < 0.001), and IL-6 (MM and CM p < 0.001) serum levels and TGF-β liver content (MM p < 0.01; CM p < 0.05), in MM and CM groups, while MC rats reverted the values to normal levels. Pro-survival signaling pathways mediated by tyrosine or serine/threonine kinases (pAKT) (MM and CM p < 0.001; MC p < 0.01) and extrasellular signal-regulated kinase (pERKs) (MM p < 0.01; CM p < 0.05) appeared to be activated in the liver of all groups of malnourished rats, suggesting the presence of cells resistant to apoptosis which would become cancerous. In conclusion, a LPD induced liver damage whose magnitude was related to the developmental stage at which malnutrition occurs and to its length.     

Effects of VEGF levels on anti-VEGF therapy for patients with idiopathic choroidal neovascularization

The objective of this study is to investigate the levels of vascular endothelial growth factor (VEGF) and other cytokines in aqueous humor of patients with idiopathic choroidal neovascularization (CNV) and their effects together with central retinal thickness (CRT) on the response to intravitreal injection of anti-VEGF antibody ranibizumab. This clinical study recruited 32 eyes from 32 patients with CNV under or besides fovea. VEGF, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 levels were detected in aqueous humor (0.1 ml) sampled during intravitreal injection. Aqueous humor controls were from nine cataract patients without any systemic disorders. The VEGF levels in aqueous humor were negatively related (r = ?0.373, p = 0.035) to CRT, which was positively related (r = 0.743, p < 0.001) to the number of injections. The VEGF levels before treatment and during the third injection in four patients with three or more injections were 13.42 ± 8.50 and 5.75 ± 3.68 (p = 0.055), respectively. The average best corrected visual acuity (BCVA) before and 12 months after treatment were 57.03 ± 16.15 and 75.16 ± 11.78 (p < 0.001), and the average CRT before and 12 months after treatment were 352.09 ± 84.15 and 251.13 ± 63.96 (p < 0.001), respectively. The visual improvement was negatively related (r = ?0.815, p < 0.001) to the visual baseline, and the vision 12 months after treatment was positively related (r = 0.581, p < 0.001) to that before treatment. No severe ocular or systemic complication appeared during treatment and follow-ups for all the patients. Intravitreal injection of anti-VEGF antibody ranibizumab is safe and effective for the treatment of idiopathic CNV through decreasing CRT. The patients with larger CRT baseline need more injections of ranibizumab.     

Association Between Chronic Exposure to Tobacco Smoke and Accumulation of Toxic Metals in Hair Among Pregnant Women

Tobacco smoke contains various toxic heavy metals that individuals are exposed to when they smoke. Despite the presence of heavy metals in tobacco smoke, the relationship between smoking and the accumulation of toxic metals in pregnant women after long-term exposure remains under discussion. We examined the association between long-term exposure to tobacco smoke and the accumulation of toxic metals in the hair of female participants. Our study recruited 252 women from the Shanxi and Hebei provinces of Northern China; these participants were self-reported non-active smokers, and had previously delivered healthy babies without birth defects. Scalp hair was collected and analyzed for nicotine and cotinine and five potentially toxic metals (specifically, silver, chromium, cadmium, mercury, and lead). Our results showed significant positive correlations between cotinine and four metals, including silver (r?=?0.369, p?<?0.001), cadmium (r?=?0.185, p?<?0.01), mercury (r?=?0.161, p?<?0.05), and lead (r?=?0.243, p?<?0.001). Significant positive correlations were also found between nicotine and three metals—specifically silver (r?=?0.331, p?<?0.001), cadmium (r?=?0.176, p?<?0.01), and lead (r?=?0.316, p?<?0.001). A logistic regression model showed significant associations between cotinine and potentially toxic metals including mercury, silver, and lead (with or without adjusting for potential confounders). We thus conclude that long-term passive smoking could potentially increase the exposure level of toxic metals including lead, silver, and mercury in our study, which are especially harmful for pregnant women and their unborn fetus.     

Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet

The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5–9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B₁₂ and a significantly higher intake of vitamin C (p < 0.05) compared with non-vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p < 0.01) lower in vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p < 0.05) but sTfR concentrations significantly higher (p < 0.001) compared with omnivorous children. In the multivariate regression model, we observed associations between hepcidin level and ferritin concentration (β = 0.241, p = 0.05) in the whole group of children as well as between hepcidin concentration and CRP level (β = 0.419, p = 0.047) in vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.     

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia

Background

The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD).

Methods

Adult (≥18?years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density. CT-density scores were calculated using fixed and adapted thresholds based on various combinations of histogram characteristics, such as mean lung density (MLD), skewness, and standard deviation (SD). Additionally, visual scoring using the Bhalla score was performed by 2 independent radiologists. Correlations between CT scores, forced expiratory volume in 1?s (FEV₁) and forced vital capacity (FVC) were evaluated.

Results

Sixty-two adult patients with PCD were included. Of all histogram characteristics, those showing good positive or negative correlations to both FEV₁ and FVC were SD (R?=???0.63 and???0.67; p?<?0.001) and Skewness (R?=?0.67 and 0.67; p?<?0.001). Among all evaluated thresholds, the CT-density score based on MLD?+?1SD provided the best negative correlation with both FEV₁ (R?=???0.68; p?<?0.001) and FVC (R?=???0.71; p?<?0.001), close to the correlations of the visual score (R?=???0.60; p?<?0.001 for FEV₁ and R?=???0.62; p?<?0.001, for FVC).

Conclusions

Automated CT scoring of lung structural abnormalities lung in primary ciliary dyskinesia is feasible and may prove useful for evaluation of disease severity in the clinic and in clinical trials.

     

Factors Influencing Non-<Emphasis Type="Italic">albicans</Emphasis> Candidemia: A Case–Case–Control Study

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case–case–control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.     

Heat acclimation increases mitochondrial respiration capacity of C2C12 myotubes and protects against LPS-mediated energy deficit

This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer. HA stimulated mitochondrial biogenesis and increased indicators of mitochondrial content [SIRT1 (+?62%); PGC-1α (+?57%); NRF-1 (+?40%); TFAM (+?141%); CS (+?25%); CytC (+?38%); all p?<?0.05]. Altered lipid biosynthesis enzymes [p-ACCa:ACC (+?59%; p?=?0.04) and FAS (??86%; p?<?0.01)] suggest fatty acid generation may have been downregulated, whereas increased GLUT4 (+?69%; p?<?0.01) and LDH-B (+?366%; p?<?0.01) suggest aerobic glycolytic capacity may have been improved. Mitochondrial biogenesis signaling in HA myotubes was suppressed by 500 ng/ml LPS (PGC-1α, NRF-1, TFAM; all p?> 0.05) but increased LDH-B (+?30%; p?=?0.02) and CPT-1 (+?55%; p?<?0.01) suggesting improved catabolic function. Basal respiration was increased in HA myotubes (+?8%; p?<?0.01) and HA myotubes maintained elevated basal respiration during LPS challenge (+?8%; p?<?0.01). LPS reduced peak respiration in C myotubes (??6%; p?<?0.01) but did not impair peak respiration in HA myotubes (p?>?0.05). Oxidative reliance was elevated in HA over that in control (+?25%; p?<?0.01) and in HA?+?LPS over C?+?LPS (+?30%; p?<?0.01). In summary, HA stimulated mitochondrial biogenesis in C2C12 myotubes. HA myotubes exhibited (1) elevated basal/peak mitochondrial respiration capacities; (2) greater oxidative reliance; and (3) protection against LPS-mediated respiration impairment. Collectively, these data suggest HA may improve aerobic metabolism in skeletal muscle and protect against LPS-mediated energy deficit.     

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5–8 years), whereas in the case of ASD—in the younger group (3–4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.     

Association between circulating levels of heat-shock protein 27 and aggressive periodontitis

Heat-shock protein (Hsp) 27 is a major intracellular molecular chaperone and controller of intracellular responses to inflammatory signals. In the extracellular space, recombinant Hsp27 has been described to exert anti-inflammatory activities. The aim of this study was to assess the association between circulating levels of Hsp27 and different types of periodontitis. Pro- and anti-inflammatory cytokines and the stress proteins Hsp27 and Hsp60 with proposed anti- and pro-inflammatory properties, respectively, were measured by two-site ELISA in the serum of patients with aggressive periodontitis (AgP, n?=?30), chronic periodontitis (CP, n?=?29) and periodontally healthy controls (H, n?=?28). Furthermore, Hsp27 and Hsp60 levels were also measured longitudinally in 12 AgP patients at 6 time points up to 3 months after treatment. AgP patients had lower levels of Hsp27 compared to CP patients and healthy subjects (adjusted one-way ANOVA, p?<?0.001, followed by post hoc Tukey HSD comparisons), while no differences in levels of Hsp60 or cytokines between the three groups were detected. In CP patients and H subjects, the systemic Hsp27 levels correlated with Hsp60 (r?=?0.43, p?<?0.001; r?=?0.59, p?<?0.001, respectively) and with pro-inflammatory cytokines TNF-α (r?=?0.48, p?<?0.001; r?=?0.55, p?<?0.001, respectively) and IL-6 (r?=?0.44, p?<?0.01). However, no such correlations were detected in AgP cases. No consistent temporal patterns of changes of Hsp27 concentration were detected across AgP patients following periodontal treatment. This study provides the first evidence that Hsp27 may be differentially expressed and regulated in AgP patients as compared with CP patients and healthy individuals.     

Comparative Hair Trace Element Profile in the Population of Sakhalin and Taiwan Pacific Islands

The objective of the current study is to perform a comparative analysis of hair trace element content in 393 apparently healthy adults living in Taipei, Taiwan, Republic of China (94 women and 46 men) and Yuzhno-Sakhalinsk, Sakhalin, Russia (186 women and 67 men). The obtained data indicate that Yuzhno-Sakhalinsk inhabitants were characterized by significantly higher hair Co, Cr, Mn, and V levels, exceeding the respective Taipei values by a factor of 3, 2, 7, and 5, respectively (all p?<?0.001). Hair Cu, Fe, and Si levels were also higher in examinees from Yuzhno-Sakhalinsk than those from Taipei by 10% (p?=?0.001), 61% (p?<?0.001), and 68% (p?<?0.001), respectively. It is notable that the only essential element, being significantly higher (+?30%; p?<?0.001) in Taipei inhabitants, is selenium. Yuzhno-Sakhalinsk inhabitants were characterized by 60% higher levels of hair Sn, and nearly two- and threefold higher scalp hair content of Be and Cd in comparison to Taipei values, respectively (all p?<?0.001). Oppositely, the examinees from Taipei had 14% (p?=?0.040) and 47% (p?=?0.001) higher levels of hair As and Hg as compared to Yuzhno-Sakhalinsk inhabitants. Further analysis demonstrated that men from both Yuzhno-Sakhalinsk and Taipei were characterized by significantly higher hair Mn, As, and Pb levels in comparison to women. The intensive development of heavy industry in Yuzhno-Sakhalinsk may result in increased metal emissions, whereas fish consumption may result in elevation of hair Hg, As, and Se levels in Taiwan inhabitants.     

The role of visual information in maintaining postural stability after the maximum exercise for the upper and lower limb muscles

The postural stability on a seesaw generating anterior–posterior instability with the eyes open (EO) and then the eyes closed (EC) in young healthy subjects (n = 28) before and 6 min after the maximum bicycle exercise (Wingate test) performed using lower limbs (“leg exercise”) or upper limbs (“hand exercise”) was investigated. It was found that “hand exercise” caused the same increase in average velocity (V, mm/s) and in the average range of sway of the centre of pressure (Qy, mm) as “leg exercise.” However, the duration of V recovery (EC: 2 min 30 s and 50 s; EO: 60 s and 40 s after “leg exercise” and “hand exercise,” respectively) and Qy (EC: 1 min 10 s and 30 s after “leg exercise” and “hand exercise,” respectively; EO: no changes from baseline) was shorter after “hand exercise.” In the presence of visual information, the increment in V decreased more than 2 times after “leg exercise” (+100.5% and + 40.5%, p < 0.01 for EC and EO, respectively) and after “hand exercise” (+73.0% and +30.3%, p < 0.01 for EC and EO, respectively). Moreover, Qy after both exercises remained at the initial level under EO conditions but significantly increased under EC conditions (+42.8%, p < 0.01 after “leg exercise” and +40.3%, p < 0.01 after “hand exercise”). Thus, the maximum exercise for the muscles of the upper limbs causes the same reduction in postural stability as analogous exercise for the muscles of the lower limbs, but the recovery period after “hand” exercise was shorter. The presence of visual information allows the baseline maintenance of postural stability and significantly reduces the strain of postural regulation while standing on a movable support after the maximum “leg exercise” and “hand exercise.”     

Heterogeneity in Colorectal Primary Tumor and Synchronous Liver Metastases

The expression profile of the ZEB1, ZEB2, VIM, CDH1, SFRP2, FOXQ1, TNC, MACC1, PLS3, CFTR, FLNA, MUC2, TFF3, and RARRES3 genes, as well as the mutational status of the KRAS, NRAS, BRAF, and PIK3CA genes, were investigated in 40 patients with colorectal cancer and liver metastases. A comparative analysis of changes in gene expression in primary tumor cells and liver metastases was performed. Statistically significant differences were found between the expression levels of the ZEB2 (p = 0.004), VIM (p < 0.001), FLNA (p = 0.04), and MUC2 (p < 0.001) genes. It was demonstrated that the overall frequency of mutations of the KRAS gene was 18/40 (45%) and the PIK3CA gene was 9/40 (23%). Mutations in the NRAS and BRAF genes were not found. The concordance between the primary tumor and metastases in the liver by mutation status was 100%.     

Bovine tuberculosis visible lesions in cattle culled during herd breakdowns: the effects of individual characteristics,trade movement and co-infection

Background

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a significant problem for livestock industries in many countries worldwide including Northern Ireland, where a test and slaughter regime has utilised the Single Intradermal Comparative Cervical Tuberculin (SICCT) test since 1959.We investigated the variation in post-mortem confirmation based on bTB visible lesion (VL) presence during herd breakdowns using two model suites. We investigated animal-level characteristics, while controlling for herd-level factors and clustering. We were interested in potential impacts of concurrent infection, and therefore we assessed whether animals with evidence of liver fluke infection (Fasciola hepatica; post-mortem inspection), M. avium reactors (animals with negative M. bovis-avium (b-a) tuberculin reactions) or Bovine Viral Diarrhoea Virus (BVDV; RT-PCR tested) were associated with bTB confirmation.

Results

The dataset included 6242 animals removed during the 14 month study period (2013–2015). bTB-VL presence was significantly increased in animals with greater b-a reaction size at the disclosing SICCT test (e.g. b-a?=?5-9 mm vs. b-a?= 0 mm, adjusted Odds ratio (aOR): 14.57; p?<?0.001). M. avium reactor animals (b-a?<?0) were also significantly more likely to disclose VL than non-reactor animals (b-a?= 0; aOR: 2.29; p?=?0.023). Animals had a greater probability of exhibiting lesions with the increasing number of herds it had resided within (movement; log-herds: aOR: 2.27–2.42; p?<?0.001), if it had an inconclusive penultimate test result (aOR: 2.84–3.89; p?<?0.001), and with increasing time between tests (log-time; aOR: 1.23; p?=?0.003). Animals were less likely to have VL if they were a dairy breed (aOR: 0.79; p?=?0.015) or in an older age-class (e.g. age-quartile 2 vs. 4; aOR: 0.65; p?<?0.001). Liver fluke or BVDV variables were not retained in either multivariable model as they were non-significantly associated with bTB-VL status (p?>?0.1).

Conclusions

Our results suggest that neither co-infection of liver fluke nor BVDV had a significant effect on the presence of VLs in this high-risk cohort. M. avium tuberculin reactors had a significantly increased risk of disclosing with a bTB lesion, which could be related to the impact of co-infection with M. avium subsp. paratuberculosis (MAP) affecting the performance of the SICCT however further research in this area is required. Movements, test history, breed and age were important factors influencing confirmation in high-risk animals.

     

Robot-assisted therapy using the MOTOmed letto 2 for the integrated early rehabilitation of stroke patients admitted to the intensive care unit

In this study, we aimed to assess the effects of early robot-assisted rehabilitation using the MOTOmed letto 2 on neurological recovery, disease severity, the rate and severity of multiple organ dysfunction syndrome, and the rate of venous thromboembolism in acute stroke patients in the intensive care unit (ICU), including patients requiring mechanical ventilation. This case-control study included 66 patients (49 men and 17 women; median age, 59 years) with acute ischemic stroke and cerebral hemorrhage admitted to the ICU. Patients were divided into two comparable groups, the intervention group (n = 33) and the control group (n = 33), and monitored from admission to day 21. After admission, both groups received standard rehabilitation, and patients in the intervention group also received robot-assisted arm and leg therapy. The groups had similar median Glasgow coma scale (GCS), National Institutes of Health Stroke Scale (NIHSS), APACHE II, and multiple organ dysfunction scale (MODS) scores on admission. There were no significant differences in neurological and medical outcomes on day 21 between the intervention and control groups (median GCS: 15 vs. 15, p = 0.32; median NIHSS 11 vs. 15, p > 0.05; median APACHE II: 6 vs. 9, p > 0.05; median MODS: 0 vs. 1, p > 0.05). The prevalence of multiple organ dysfunction syndrome and deep venous thrombosis (DVT) on day 21 was also similar in the intervention and control groups (60% vs. 67%, p > 0.05, and 58% vs. 45%, p > 0.05, respectively). However, the prevalence of severe multiple organ dysfunction syndrome, the incidence of pulmonary embolism, and the mortality rate were lower in the intervention group compared with the control group (14% vs. 41%, p < 0.05; 12% vs. 33%; p < 0.05; 12% vs. 39%, p < 0.05, respectively). Our results indicate that early robot-assisted therapy in patients with severe stroke admitted to the ICU reduces the rate of pulmonary embolism, the incidence of severe multiple organ dysfunction, and mortality on day 21, but does not influence neurological outcomes or the rate of deep vein thrombosis.