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Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-ﬂight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
A 2-year fertilization experiment was conducted to study the effect of different ratios of organic (pig) manure on wheat yield and nitrogen use efficiency (NUE). The four treatments were no nitrogen (N) (CK); 100% chemical fertilizer N (urea; T1); 70% chemical fertilizer N + 30% organic manure N (T2) and 50% chemical fertilizer N + 50% organic manure N (T3), with the same amount of applied nitrogen (120 kg/ha). The results showed the maximum grain yield (3049 kg/ha), crop nitrogen uptake (216 kg/ha), NUE (65.4%) and accumulated nitrate nitrogen (NO3−-N in 0–200 cm, 142 kg/ha) were observed in the T1 among all treatments in the first year. However, the largest grain yield (5074 kg/ha), crop nitrogen uptake (244 kg/ha) and NUE (82.5%) were under T2 treatment in the second year. Furthermore, T2 had the maximum NO3−-N content in 0–100 cm layer (116 kg/ha), especially 0–40 cm layer, and the lowest NO3−-N content in 100–200 cm (58.8 kg/ha). However, 50% organic manure N in T3 increased apparent nitrogen loss by 39.0% compared to that in T2. Therefore, 30% organic manure N application was more conducive for enhancing wheat yield and NUE and promoting environmental safety after 1-year fertilization time.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
We hypothesized an increase in dorsolateral prefrontal cortex (DLPFC) glutamate levels would occur after three weeks of repetitve transcranial magnetic stimulation (rTMS) treatment and a decrease in major depressive disorder (MDD) symptoms.
We report six cases (four females) 15–21 years of age with treatment-resistant MDD. Participants had a mean age of 18.7 years and a mean IQ of 102.3. Short echo proton magnetic resonance spectroscopy (H-MRS) was used to quantify glutamate levels in the left DLPFC (4.5cc) before and after rTMS treatment. rTMS was localized to the left DLPFC and applied for 15 consecutive weekdays. Treatment response was defined as a greater than 50% reduction in Hamilton Depression Rating Scale scores (Ham-D).1H-MRS data was analyzed with LCModel to determine glutamate concentration.
Following rTMS, treatment responders (N=4) showed an increase (relative to baseline) in left DLPFC glutamate levels (11%), which corresponded to an improvement in depressive symptom severity (68% Ham-D score reduction). Treatment non-responders (N=2) had elevated baseline glutamate levels compared to responders in that same region, which decreased with rTMS (−10%). Procedures were generally well tolerated with no adverse events.
rTMS is feasible and possibly efficacious in adolescents with MDD. In responders, rTMS may act by Induced elevations in elevating DFPLC glutamate levels in the left DLPFC, thereby leading to symptom improvement. Transcranial Magnetic Stimulation for Adolescent Depression (TMSAD)
Cardiovascular disease (CVD) and depressive disorders are the most two harmful problems for human health in the 21st century. The relationships between the two diseases are complicated, yet the mechanisms are not clear so far. This study addressed this issue by clarifying shared and unique factors between metabolic syndrome (MS) and mild psychiatric disorder (MPD) using the 8-year follow-up Landseed cohort.
A total of 5712 community residents were followed-up and analyzed. The point prevalence rates of MS and MPD and their comorbidity rate were estimated by each wave. Three multiple logistic regression models, with each treating MS, MPD, and comorbid condition as dependent variable, were compared to identify the shared and unique factors. Variables specifically correlate with MS or MPD are defined as unique factors; whilst those correlated with both MS and MPD or with comorbid condition as shared factors.
The point prevalence rates of MS ranged 13.83-14.26%, MPD ranged 17.17-19.60%, and comorbidity rates 2.75-3.07% in three waves. Educational level and weekly exercise frequency are shared factors of MS and MPD. Moderate personal income is a unique protective factor for MS; and male and abstaining from alcohol use are unique protective factors for MPD.
A balanced life style is beneficial for both physical and psychological health. Specifically, there are no dose-response effects between weekly exercise frequency and MS or MPD. It is important for clinicians and health educators to educate community people to engage in exercise in a proper way to improve public health.
Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD.
Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [123I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) and [99mTc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment.
SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups.
The results with regard to the midbrain SERT level suggest the heritability of MDD.
The presence of comorbid anxiety disorders (AD) and bipolar II disorders (BP-II) compounds disability complicates treatment, worsens prognosis, and has been understudied. The genes involved in metabolizing dopamine and encoding dopamine receptors, such as aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor (DRD2) genes, may be important to the pathogenesis of BP-II comorbid with AD. We aimed to clarify ALDH2 and DRD2 genes for predisposition to BP-II comorbid with and without AD. The sample consisted of 335 subjects BP-II without AD, 127 subjects BP-II with AD and 348 healthy subjects as normal control. The genotypes of the ALDH2 and DRD2 Taq-IA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a statistically significant association between DRD2 Taq-I A1/A2 genotype and BP-II with AD (OR = 2.231, P = 0.021). Moreover, a significant interaction of the DRD2 Taq-I A1/A1 and the ALDH2*1*1 genotypes in BP-II without AD was revealed (OR = 5.623, P = 0.001) compared with normal control. Our findings support the hypothesis that a unique genetic distinction between BP-II with and without AD, and suggest a novel association between DRD2 Taq-I A1/A2 genotype and BP-II with AD. Our study also provides further evidence that the ALDH2 and DRD2 genes interact in BP-II, particularly BP-II without AD.
Gastroenteritis remains a serious health condition among children under 5 years especially in Africa. We conducted a systematic review and meta-analysis to investigate the aetiologic pathogens of gastroenteritis in the region. We did a systematic search for articles with original data on the aetiology of gastroenteritis and acute diarrhoea among children younger than 5 years. Pooled results were extracted and analysed in STATA version 12.0 using random-effects for statistical test for homogeneity following the guidelines provided in the Cochrane Collaboration and Preferred reporting items for systematic reviews and meta-analyses. Overall, viruses accounted for 50.2% of the cases followed by bacteria with 31.6% of the cases. Parasites accounted for 12.1% of the case. Rotavirus was the most common cause of acute diarrhoea in all regions resulting in 29.2% of the cases followed by E. coli (15.6%) of diarrhoeal cases and Adenovirus (10.8%). The most prevalent parasite detected was Giardia lamblia (7.3%). Acute diarrhoea remains rampant with Rotavirus still being the major pathogen responsible for the disease in children less than 5 years old despite the introduction of vaccine. It is recommended that the vaccine should be promoted much more widely in the region.
There is evidence indicating that using the current UK energy feeding system to ration the present sheep flocks may underestimate their nutrient requirements. The objective of the present study was to address this issue by developing updated maintenance energy requirements for the current sheep flocks and evaluating if these requirements were influenced by a range of dietary and animal factors. Data (n = 131) used were collated from five experiments with sheep (5 to 18 months old and 29.0 to 69.8 kg BW) undertaken at the Agri-Food and Biosciences Institute of the UK from 2013 to 2017. The trials were designed to evaluate the effects of dietary type, genotype, physiological stage and sex on nutrient utilization and energetic efficiencies. Energy intake and output data were measured in individual calorimeter chambers. Energy balance (Eg) was calculated as the difference between gross energy intake and a sum of fecal energy, urine energy, methane energy and heat production. Data were analysed using the restricted maximum likelihood analysis to develop the linear relationship between Eg or heat production and metabolizable energy (ME) intake, with the effects of a range of dietary and animal factors removed. The net energy (NEm) and ME (MEm) requirements for maintenance derived from the linear relationship between Eg and ME intake were 0.358 and 0.486 MJ/kg BW0.75, respectively, which are 40% to 53% higher than those recommended in energy feeding systems currently used to ration sheep in the USA and the UK. Further analysis of the current dataset revealed that concentrate supplement, sire type or physiological stage had no significant effect on the derived NEm values. However, female lambs had a significantly higher NEm (0.352 v. 0.306 or 0.288 MJ/kg BW0.75) or MEm (0.507 v. 0.441 or 0.415 MJ/kg BW0.75) than those for male or castrated lambs. The present results indicate that using present energy feeding systems in the UK developed over 40 years ago to ration the current sheep flocks could underestimate maintenance energy requirements. There is an urgent need to update these systems to reflect the higher metabolic rates of the current sheep flocks.
The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009–2010 to 2015–2016. We carried out weighted regression among young adults (20–39 years) and adults (40–59 years) separately. In total, 5230 men and 5794 women aged 20–59 years were included in the present analyses. In total, 0.8% men and 0.2% women were tested HIV-positive. Each increasing HIV risk behaviour was associated with elevated odds of being tested HIV-positive (1.15, 95% CI 1.15–1.15) among young adults and adults (1.61, 95% CI 1.61–1.61). Multi-faceted, community-based interventions are urgently required to reduce the incidence of HIV in the USA.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.