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Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator
rather than the local time-rate operator
, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
Impairments of attention and memory are evident in early psychosis, and often lead to severe, longstanding functional disability. Effective non-pharmacological interventions are needed due to the unsuccessful results of pharmacological interventions.
To determine whether yoga is effective for cognitive impairments, and the neural mechanism underlying these effects.
It was a randomized controlled study of 12-week of yoga and aerobic exercise (walking and cycling) intervention vs wait-list control for female early psychotic patients. Memory was measured with Hong Kong List Learning Test and Digit Span test, and attention was measured with Letter Cancellation test. Cognitive data analysis was based on the Intention-to-Treat method using a mixed-model analysis. Seed based functional connectivity was applied using posterior cingulate cortex (PCC) as seed with AFNI. Cortical thickness analyses were performed using FreeSurfer. Results from yoga and control groups were presented.
A total of 140 women were recruited and randomized into three groups. 95 completed the study, and 115 were included for cognitive data analysis. For imaging data, 42 participants were used for cortical thickness analyses; and 60 were included for neural connectivity analyses. Yoga group demonstrated significant improvements in working memory, verbal acquisition and attention (P=.01). Cortical thickness increased in the postcentral gyrus (P<.01); connectivity between PCC and bilateral inferior parietal gyrus increased after yoga intervention (P<.005).
Yoga has been found to be effective for memory and attention in early psychotic patients. The increases of thickness and neural connectivity indicate the possible neural mechanisms underlying the improvements of cognition.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Precise bone cut is fundamental in total knee arthroplasty. However, notching of anterior femoral is not uncommon in clinical practice. Reviewing the article, notching and its complication may reach up to 30% and 2.5%, and there is scanty study of notching on the femoral strength. We therefore conduct the finite element analysis to elucidate the effect of notching on femoral mechanical strength. The computerized tomography images were used as the basis to develop the knee model, which was assumed mainly to consist of cortical and cancellous bones. For the implant joint, Zimmer data was considered partly as the basis to develop the model. This study investigated the femoral improper cut effect on the surgery with a static standing condition. The results show that the anterior femoral cut should be undercut 2 mm to overcut 1 mm during the surgery, in order to prevent bone materials from yielding. The exposure of the cancellous bone may cause bone materials to yield when the femur overcut was 2 mm; the cancellous bone may load too much and result in a fracture when the undercut was 3 mm. The effect of undercut, which was rarely discussed, was particularly addressed in our study. Precise femoral cut is crucial for the longevity of total knee arthroplasty.
We prove some congruences on sums involving fourth powers of central q-binomial coefficients. As a conclusion, we confirm the following supercongruence observed by Long [Pacific J. Math. 249 (2011), 405–418]:
Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body’s metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group. Pigs in the SB group were intravenously infused with 10 ml SB (200 mmol/l) for 7 days, whereas pigs in the CO group were treated with the same amount of saline. The livers of pigs were collected for gene expression and metabolome analyses. The RNA sequencing (RNA-Seq) analysis showed that the mRNA expression of Acyl-CoA synthetase long-chain family member 1 (ACSL1), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA acyltransferase 2 (ACAA2) and phosphoenolpyruvate carboxykinase 1 (PCK1) were downregulated (Q<0.05), whereas fatty acid binding protein 1 (FABP1) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) were upregulated (P<0.05) by SB treatment, indicating a decrease in fatty acid oxidation and gluconeogenesis and an increase in fatty acid transportation and cholesterol metabolism. Gas chromatography-mass spectrometry analysis showed that raffinose was enriched in the SB group compared with the CO group, indicating a decrease in metabolism of galactose. Moreover, SB treatment significantly decreased the concentration of blood cholesterol. The results suggest that a short-term intravenous infusion of SB could modulate hepatic lipid metabolism by decreasing fatty acid oxidation and increasing fatty acid transportation and cholesterol metabolism.
Monolithic large-aperture diffraction grating tiling is desired to increase the output capability of multi-kilojoule petawatt laser facilities. However, the wavefront errors of input pulse and gratings will degrade the focal spot quality and the compressibility of the output pulse. In this work, the effects of wavefront error of input pulse, deformation and wave aberration of the grating for the large-aperture tiled-grating compressor are investigated theoretically. A series of numerical simulations are presented to discuss the changing trends of focal spot energy caused by wavefront error of input pulse and obtain the error tolerance for specific goals. The influences of coating stress and the wave aberration of holographic exposure gratings on the diffraction wavefront are also discussed. Some advice is proposed for improving the performance of large-aperture tiled-grating. This work paves the way for the design of practical large-aperture tiled-grating compressor for ultrahigh intensity laser facilities in the future.
To characterise multi-level obstruction in terms of prevalence, obstructive sleep apnoea severity and predictive factors, and to collect epidemiological data on upper airway morphology in obstructive sleep apnoea patients.
Retrospective review of 250 obstructive sleep apnoea patients.
On clinical examination, 171 patients (68.4 per cent) had multi-level obstruction, 49 (19.6 per cent) had single-level obstruction and 30 (12 per cent) showed no obstruction. Within each category of obstructive sleep apnoea severity, multi-level obstruction was more prevalent. Multi-level obstruction was associated with severe obstructive sleep apnoea (more than 30 events per hour) (p = 0.001). Obstructive sleep apnoea severity increased with the number of obstruction sites (correlation coefficient = 0.303, p < 0.001). Multi-level obstruction was more likely in younger (p = 0.042), male (p = 0.045) patients, with high body mass index (more than 30 kg/m2) (p < 0.001). Palatal (p = 0.004), tongue (p = 0.026) and lateral pharyngeal wall obstructions (p = 0.006) were associated with severe obstructive sleep apnoea.
Multi-level obstruction is more prevalent in obstructive sleep apnoea and is associated with increased severity. Obstruction at certain anatomical levels contributes more towards obstructive sleep apnoea severity.
Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.
Over the past 8 years, human enteroviruses (HEVs) have caused 27 227 cases of hand, foot and mouth disease (HFMD) in Xiamen, including 99 severe cases and six deaths. We aimed to explore the molecular epidemiology of HFMD in Xiamen to inform the development of diagnostic assays, vaccines and other interventions. From January 2009 to September 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription PCR that targeted the HEV 5′ untranslated region and viral protein 1 region. Of these samples, 4290 were tested positive for HEV and the amplicons were sequenced and genotyped. Twenty-two genotypes were identified. Enterovirus 71 (EV71) and coxsackieviruses A16, A6 and A10 (CA16, CA6 and CA10) were the most common genotypes, and there were no changes in the predominant lineages of these genotypes. EV71 became the most predominant genotype every 2 years. From 2013, CA6 replaced CA16 as one of the two most common genotypes. The results demonstrate the vast diversity of HFMD pathogens, and that minor genotypes are able to replace major genotypes. We recommend carrying-out long-term monitoring of the full spectrum of HFMD pathogens, which could facilitate epidemic prediction and the development of diagnostic assays and vaccines.
Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.
Elderly individuals with tuberculosis (TB) are more likely to have a non-specific clinical presentation of TB and high mortality. However, factors associated with mortality in elderly TB patients have not been extensively studied. This retrospective cohort study aimed to identify factors associated with death among elderly Taiwanese with TB. All elderly patients with TB from 2006 to 2014 in Taipei, Taiwan, were included in a study. Multiple logistic regression was used to identify the factors associated with death in elderly TB patients. The mean age of the 5011 patients was 79·7 years; 74·1% were men; 32·7% had mortality during the study follow-up period. After controlling for potential confounders, age ⩾75 years (reference: 65–74 years), male sex, end-stage renal disease (ESRD), malignancy, acid-fast bacilli-smear positivity, TB-culture positivity, pleural effusion on chest radiograph and notification by an ordinary ward or intensive care unit were associated with a higher risk of all-cause death; while high school, and university or higher education, cavity on chest radiograph and directly observed therapy were associated with a lower risk of all-cause death. This study found that the proportion of death among elderly patients with TB in Taipei, Taiwan, was high. To improve TB treatment outcomes, future control programmes should particularly target individuals with comorbidities (e.g. ESRD and malignancy) and those with a lower socio-economic status (e.g. not educated).
Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB).
A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation. Freesurfer was used to segment the total hippocampus and delineate its subfields. The hippocampal segmentations were co-registered to the mean diffusivity (MD) and fractional anisotropy (FA) maps obtained from the DTI images.
Both AD and MCI groups showed significantly smaller hippocampal volumes compared to DLB and controls, predominantly in the CA1 and subiculum subfields. Compared to controls, hippocampal MD was elevated in AD, but not in MCI. DLB was characterized by both volumetric and microstructural preservation of the hippocampus. In MCI, higher hippocampal MD was associated with greater atrophy of the hippocampus and CA1 region. Hippocampal volume was a stronger predictor of memory scores compared to MD within the MCI group.
Through a multi-modal integration, we report novel evidence that the hippocampus in DLB is characterized by both macrostructural and microstructural preservation. Contrary to recent suggestions, our findings do not support the view that DTI measurements of the hippocampus are superior to volumetric changes in characterizing group differences, particularly between MCI and controls.
We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope (E) gene sequences of 67 DENV-1 strains isolated in Guangzhou, together with 58 representative sequences downloaded from NCBI, have shown shifts in viral genotypes. The genotype changed several times, from genotype I to IV in 2002, from IV to I in 2005, and from I to V in 2014. These genotype shifts may be the cause of DENV outbreaks. The diversity of genotypes and clades demonstrates a high risk of future outbreaks in Guangzhou. The mean rate of virus nucleotide substitution in Guangzhou was determined to be 7·77 × 10−4 per site per year, which represents a medium substitution rate compared to two other countries. Our research can point to different ancestors of the isolated strains, which may further reveal the different origins and transmission of DENV-1 strains in Guangzhou.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10−13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).
We previously reported that patients with early-stage bipolar disorder,
but not healthy comparison controls, had body mass index (BMI)-related
volume reductions in limbic brain areas, suggesting that the structural
brain changes characteristic of bipolar disorder were more pronounced
with increased weight.
To determine whether the most consistently reported neurochemical
abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was
also more prominent with higher BMI.
We used single-voxel proton magnetic resonance spectroscopy to measure
hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1)
and 28 healthy controls (mean BMI = 23.3).
In patients, but not healthy controls, linear regression demonstrated
that higher BMI predicted greater Glx. Factorial ANCOVA showed a
significant BMI×diagnosis interaction, confirming a distinct effect of
weight on Glx in patients.
Together with our volumetric studies, these results suggest that higher
BMI is associated with more pronounced structural and neurochemical
limbic brain changes in bipolar disorder, even in early-stage patients
with low obesity rates.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.