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Cube arrays are one of the most extensively studied types of surface roughness, and there has been much research on cubical roughness with low-to-moderate surface coverage densities. In order to help populate the literature of flow over cube arrays with high surface coverage densities, we conduct direct numerical simulations (DNSs) of flow over aligned cube arrays with coverage densities $\lambda =0.25$ (for validation and comparison purposes), $0.5$, $0.6$, $0.7$, $0.8$ and $0.9$. The roughness are in the d-type roughness regime. Essential flow quantities, including the mean velocity profiles, Reynolds stresses, dispersive stresses and roughness properties, are reported. Special attention is given to secondary turbulent motions in the roughness sublayer. The spanwise-alternating pattern of the thin slots between two neighbouring cubes gives rise to spanwise-alternating regions of low- and high-momentum pathways above the cube crests. We show that the strength and spanwise location of these low- and high-momentum pathways depend on the surface coverage density, and that the high-momentum pathways are not necessarily located directly above the roughness elements. In order to determine the physical processes responsible for the generation and the destruction of these secondary turbulent motions, we analyse the dispersive kinetic energy (DKE) budget. The data shows that the secondary motions get their energy from the DKE-specific production term and the wake production term, and lose energy to the DKE-specific dissipation term.
Separating and reattaching turbulent flows induced by a forward-facing step subjected to an incoming fully developed turbulent channel flow are studied using direct numerical simulation. The step height is one quarter of the channel height, and the Reynolds number based on friction velocity and half-channel height at the inlet is 180. The three-dimensional spatio-temporal characteristics of separation bubbles upstream and downstream of the step are analysed with particular attention to the effects of impinging hairpin structures and the topology of principal stretching. Immediately upstream of the step, the fluctuating vorticity parallel to the mean streamlines is significant. On the frontal surface of the step, strong spanwise skin friction appears in the form of alternating positive and negative values in vertical strips. Over the step, the principal stretching switches orientation along a curve emanating from the leading edge, which is termed the principal stretching line (PSL). The reverse flows upstream and downstream of the step possess dominant and harmonic frequencies that mirror those of the incoming flow. As a hairpin structure leans over the step, the associated vorticity is deformed by the principal stretching. Specifically, PSL marks the lower bound of the deformed hairpin legs, and an opposite-signed pair of counter-rotating quasi-streamwise vortices are induced near the top surface of the step. Consequently, the separation bubbles upstream of and over the step are enlarged and suppressed, respectively. For a sufficiently strong hairpin structure interacting with the step, an open-type separation occurs upstream of the step, while dual separation bubbles appear over the step.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
Toxoplasma gondii infections are common in humans and animals worldwide. Domestic free-range chickens (Gallus domesticus) are excellent sentinels of environmental contamination with T. gondii oocysts because they feed on the ground. Chickens can be easily infected with T. gondii; however, clinical toxoplasmosis is rare in these hosts. Chickens are comparatively inexpensive and thus are good sentinel animals for T. gondii infections on the farms. Here, the authors reviewed prevalence, the persistence of infection, clinical disease, epidemiology and genetic diversity of T. gondii strains isolated from chickens worldwide for the past decade. Data on phenotypic and molecular characteristics of 794 viable T. gondii strains from chickens are discussed, including new data on T. gondii isolates from chickens in Brazil. This paper will be of interest to biologists, epidemiologists, veterinarians and parasitologists.
Introduction: Canada is in the midst of an opioid crisis. The number of apparent opioid-related deaths between January and March 2018 increased by 44% compared to the same period in 2016. The increasing use of prescription opioids and higher doses of opioids can lead to opioid addiction, toxicity and even death. Opioids are commonly prescribed for low back pain management in the ED, but the variability in opioid-prescribing patterns suggested an opportunity for improvement. Our centre implemented Clinician Performance Indicators (CPI) in 2015. CPIs were reported to each ED physician every 3 months and included the percentage of patients who were prescribed opioids. The intent was to raise awareness of opioid-prescribing patterns at our institution. Therefore, we evaluated opioid-prescribing patterns for patients with low back pain (LBP) before and after the CPI implementation. Methods: Data were obtained retrospectively for patients discharged from the ED from July 2015 to December 2018 with LBP-associated ICD 10 codes. We excluded admitted patients, those with specialist consultations, and patients who left without being seen. The primary outcome was opioid prescribing patterns for patients with LBP before and after CPI implementation. We performed a descriptive analysis of the data and compared the prescribing rates pre-implementation (July-Dec 2015) to post-implementation (July-Dec 2016) following a 6-month wash-out period. Moreover, we analyzed opioid-prescribing patterns over an extended period until December 2018. Results: After the exclusion criteria were applied, 8993 patients were included in the analysis. 53.5% were female and the mean (SD) age was 48.3 (19.78). During the three years of the study period, the percentage of LBP patients who received opioids showed a decreasing trend. Comparison of the pre and post CPI implementation periods showed a decrease in opioid prescriptions (42.0% vs 35.5%, 95%CI 2.9% to 10.2%). There was variation in opioids prescribed at our institution, the most common being hydromorphone (29.9%), followed by acetaminophen-oxycodone (24.2%) and acetaminophen-tramadol (20.0%). Conclusion: The implementation of CPIs positively impacted physicians' opioid-prescribing patterns for patients presenting with LBPs at our institution. Future studies are required to further improve the effectiveness of CPIs in influencing opioid-prescribing patterns.
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
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)
Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
Chinese men who have sex with men (MSM) are at high risk for depression, anxiety and suicide. The estimated prevalence of these problems is essential to guide public health policy, but published results vary. This meta-analysis aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and suicide among Chinese MSM.
Systematic searches of EMBASE, MEDLINE, PsycINFO, PubMed, CNKI and Wanfang databases with languages restricted to Chinese and English for studies published before 10 September 2019 on the prevalence of depressive symptoms, anxiety symptoms, suicidal ideation, suicide plans and suicide attempts among Chinese MSM. Studies that were published in the peer-reviewed journals and used validated instruments to assess depression and anxiety were included. The characteristics of studies and the prevalence of depression and anxiety symptoms, suicidal ideation, suicide plans and suicide attempts were independently extracted by authors. Random-effects modelling was used to estimate the pooled rates. Subgroup analysis and univariate meta-regression were conducted to explore potential sources of heterogeneity. This study followed the PRISMA and MOOSE.
Sixty-seven studies were included. Fifty-two studies reported the prevalence of depressive symptoms, with a combined sample of 37 376 people, of whom 12 887 [43.2%; 95% confidence interval (CI), 38.9–47.5] reported depressive symptoms. Twenty-seven studies reported the prevalence of anxiety symptoms, with a combined sample of 10 531 people, of whom 3187 (32.2%; 95% CI, 28.3–36.6) reported anxiety symptoms. Twenty-three studies reported the prevalence of suicidal ideation, with a combined sample of 15 034 people, of whom 3416 (21.2%; 95% CI, 18.3–24.5) had suicidal ideation. Nine studies reported the prevalence of suicide plans, with a combined sample of 5271 people, of whom 401 (6.2%; 95% CI, 3.9–8.6) had suicide plans. Finally, 19 studies reported the prevalence of suicide attempts, with a combined sample of 27 936 people, of whom 1829 (7.3%; 95% CI, 5.6–9.0) had attempted suicide.
The mental health of Chinese MSM is poor compared with the general population. Efforts are warranted to develop interventions to prevent and alleviate mental health problems among this vulnerable population.
Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-β-catenin/β-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/β-catenin signalling.
Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick’s age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and −336 CpG site in HSP60 promoter and −1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around −389 and −336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around −1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.
Structure and optical properties have been successfully determined for a series of niobium- and tantalum-containing layered alkaline-earth silicate compounds, Ba3(Nb6−xTax)Si4O26 (x = 0.6, 1.8, 3.0, 4.2, 5.4). The structure of this solid solution was found to be hexagonal P-62m (No. 189), with Z = 1. With x increases from 0.6 to 5.4, the lattice parameter a increases from 8.98804(8) to 9.00565(9) Å and c decreases from 7.83721(10) to 7.75212(12) Å. As a result, the volume decreases from 548.304(11) to 544.479(14) Å3. The (Nb/Ta)O6 distorted octahedra form continuous chains along the c-axis. These (Nb/Ta)O6 chains are in turn linked with the Si2O7 groups to form distorted pentagonal channels in which Ba ions were found. These Ba2+ ions have full occupancy and a 13-fold coordination environment with neighboring oxygen sites. Another salient feature of the structure is the linear Si–O–Si chains. When x in Ba3(Nb6−xTax)Si4O26 increases, the bond valence sum (BVS) values of the Ba sites increase slightly (2.09–2.20), indicating the size of the cage becoming progressively smaller (over-bonding). While SiO cages are also slightly smaller than ideal (BVS range from 4.16 to 4.19), the (Nb/Ta)O6 octahedral cages are slightly larger than ideal (BVS range from 4.87 to 4.90), giving rise to an under-bonding situation. The bandgaps of the solid solution members were measured between 3.39 and 3.59 eV, and the x = 3.0 member was modeled by density functional theory techniques to be 3.07 eV. The bandgaps of these materials indicate that they are potential candidates for ultraviolet photocatalyst.
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
The gut is composed of a single layer of intestinal epithelial cells and plays important roles in the digestion and absorption of nutrients, immune and barrier functions and amino acid metabolism. Weaning stress impairs piglet intestinal epithelium structural and functional integrities, which results in reduced feed intake, growth rates and increased morbidity and mortality. Several measures are needed to maintain swine gut development and growth performance after weaning stress. A large body of evidence indicates that, in weaning piglets, glutamine, a functional amino acid, may improve growth performance and intestinal morphology, reduce oxidative damage, stimulate enterocyte proliferation, modulate cell survival and death and enhance intestinal paracellular permeability. This review focuses on the effects of glutamine on intestinal health in piglets. The aim is to provide evidentiary support for using glutamine as a feed additive to alleviate weaning stress.
We present a new method to combine cold gas kinematics with the stellar kinematics modelled with the Schwarzschild orbit-superposition technique, and its application to the lenticular galaxy NGC 2974. The combination of stellar and cold gas kinematics significantly improves the constraints on the measured dark matter profile: assuming a generalised NFW halo profile, we find a cuspy inner halo slope for NGC 2974.
Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.
In this paper, a novel single-cavity triangular substrate-integrated waveguide (TSIW) dual-band filter loading a complementary triangular split ring resonator (CTSRR) is proposed, which has three transmission zeros (TZs) in the stopband in total. The dual-band response is achieved by the CTSRR and the degenerate modes of the TSIW cavity. In order to control the TZs, we propose two adjustment techniques, shift feeding technique and adding via perturbation. In addition, the CTSRR etched on the surface can produce a new TZ in the upper first-passband. Finally, a dual-band filter with three TZs is simulated, fabricated, and measured. There is a good agreement between the simulated results and measured ones.
Hypoimmunity and numerous stresses are two major challenges in broiler industry. Nutrient intervention at the specific time of embryonic stage is a feasible way to improve animal performance. This study was conducted to investigate the possible effects of in ovo feeding (IOF) of vitamin C at embryonic age 15th day (E15) on growth performance, antioxidation and immune function of broilers. A total of 240 broiler fertile eggs were randomly divided into two groups (0 and 3 mg injected dose of vitamin C at E15), and new-hatched chicks from each treatment were randomly allocated into six replicates with 10 chicks per replicate after incubation. The results indicated that in ovo vitamin C injection improved the hatchability (P < 0.05) and increased immunoglobulin M (IgM) (at the broiler’s age 1st day, D1), IgG and IgM concentrations (D21), as well as lysozyme activity (D21, P < 0.05) and total antioxidant capacity (D42, P < 0.01) in plasma of broilers. On D21, the splenic expression level of DNA methyltransferase 1 (DNMT1) was up-regulated in vitamin C (VC) group, whereas interleukin (IL)-6, interferon-γ, ten-eleven translocation protein 1 and thymine-DNA glycosylase were down-regulated (P < 0.05). On D42, in ovo vitamin C injection up-regulated splenic expression levels of DNMT1, DNA methyltransferase 3B (DNMT3B) and growth arrest and DNA-damage-inducible protein beta (P < 0.05), whereas down-regulated splenic expression levels of IL-6, tumour necrosis factor-α and methyl-CpG-binding domain protein 4 (P < 0.05). Our findings suggested that IOF of 3 mg vitamin C at E15 could improve, to some extent, the antioxidant activity and immune function in plasma, corresponding with the lower expression of pro-inflammatory cytokines in spleen. However, IOF of vitamin C leading to the changes in the expression of DNA methyltransferases and demethylases may suggest an increased trend of DNA methylation level in spleen and whether DNA methylation variation is associated with the lower expression of pro-inflammatory cytokines in spleen warrants future study.
Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom.
A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements.
The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test.
Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.