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On Coronavirus Disease 2019 (COVID-19) wards, severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid was frequently detected on high-touch surfaces, floors, and socks inside patient rooms. Contamination of floors and shoes was common outside patient rooms on the COVID-19 wards but decreased after improvements in floor cleaning and disinfection.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
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.
The pandemic of coronavirus disease 2019 (COVID-19) has posed serious challenges. It is vitally important to further clarify the epidemiological characteristics of the COVID-19 outbreak for future study and prevention and control measures. Epidemiological characteristics and spatial−temporal analysis were performed based on COVID-19 cases from 21 January 2020 to 1 March 2020 in Shandong Province, and close contacts were traced to construct transmission chains. A total of 758 laboratory-confirmed cases were reported in Shandong. The sex ratio was 1.27: 1 (M: F) and the median age was 42 (interquartile range: 32–55). The high-risk clusters were identified in the central, eastern and southern regions of Shandong from 25 January 2020 to 10 February 2020. We rebuilt 54 transmission chains involving 209 cases, of which 52.2% were family clusters, and three widespread infection chains were elaborated, occurring in Jining, Zaozhuang and Liaocheng, respectively. The geographical and temporal disparity may alert public health agencies to implement specific measures in regions with different risk, and should attach importance on how to avoid household and community transmission.
Microvascular health is a main determinant of coronary blood flow reserve and myocardial vascular resistance. Extracardiac capillary abnormality has been reported in subjects at increased coronary heart disease risk, such as prehypertension, hypertension, diabetes, hyperlipidemia, and atherosclerosis. We have reported cardiovascular dysfunction in a cohort of maternal nutrient reduction (MNR)-induced intrauterine growth restriction (IUGR) baboon offspring. Here we test the hypothesis that there is oral capillary rarefaction associated with MNR-induced IUGR. Capillary density was quantified using in vivo high-power capillaroscopy on seven middle-aged (~10.7 yr; human equivalent ~40 yr) male IUGR baboons and seven male age-matched controls in the lateral buccal and inferior labial mucosa. While no difference was found between groups in either area by fraction area or optical density for these vascular beds derived from fetal preductal vessels, further studies are needed on post-ductal vascular beds, retina, and function.
This paper examines whether green Official Development Aid (ODA) has a significant role in mitigating carbon emissions in recipient countries, and if institutional quality matters for the effectiveness of green ODA. For 86 green ODA recipient countries over the period 2003–2014, we explore the nexus between green ODA, institutions and carbon emissions. By using a two-step system generalized method of moment (GMM), we find that green ODA overall has no direct association with the mitigation of carbon emissions. However, when institutional quality indices are included, we found a significant effect of institutional quality on the effectiveness of green ODA. In general, green ODA is associated with higher carbon emissions in countries with poor institutions. In particular, green ODA is effective in mitigating carbon emissions when channeled to countries that enjoy higher economic freedom as well as more freedom from corruption. Results are mixed for the rule of law.
Few studies have evaluated the association between a healthful plant-based diet and health-related quality of life (HRQoL). We followed 50 290 women in the Nurses’ Health Study (NHS; 1992–2000) and 51 784 women in NHSII (1993–2001) for 8 years to investigate changes in plant-based diet quality in relation to changes in physical and mental HRQoL. Plant-based diet quality was assessed by three plant-based diet indices: overall plant-based diet index (PDI), healthful PDI (hPDI) and unhealthful PDI (uPDI). Physical and mental HRQoL were measured by physical component score (PCS) and mental component score (MCS) of the 36-Item Short Form Health Survey. Diet was assessed 2 years before the HRQoL measurements and both were updated every 4 years. The associations between 4-year changes in PDIs and HRQoL were evaluated. Each 10-point increase in PDI was associated with an improvement of 0·07 (95 % CI 0·01, 0·13) in PCS and 0·11 (95 % CI 0·05, 0·16) in MCS. A 10-point increase in hPDI was associated with an increment of 0·13 (95 % CI 0·08, 0·19) in PCS and 0·09 (95 % CI 0·03, 0·15) in MCS. Conversely, a 10-point increase in uPDI was associated with decreases in PCS and MCS (−0·07 (95 % CI −0·12, −0·02) and −0·10 (95 % CI −0·16, −0·05), respectively). Compared with a stable diet, an increase in hPDI was significantly associated with improvements in physical HRQoL in older women and with mental HRQoL in younger women. In conclusion, adherence to a healthful plant-based diet was modestly associated with improvements in both physical and mental dimensions of HRQoL.
Soybean meal is rich in soybean isoflavones, which exhibit antioxidant, anti-inflammatory, antiviral and anticancer functions in humans and animals. This study was conducted to investigate the effects of soybean isoflavones on the growth performance, intestinal morphology and antioxidative properties in pigs. A total of 72 weaned piglets (7.45 ± 0.13 kg; 36 males and 36 females) were allocated into three treatments and fed corn-soybean meal (C-SBM), corn-soy protein concentrate (C-SPC) or C-SPC supplemented with equal levels of the isoflavones found in the C-SBM diet (C-SPC + ISF) for a 72-day trial. Each treatment had six replicates and four piglets per replicate, half male and half female. On day 42, one male pig from each replicate was selected and euthanized to collect intestinal samples. The results showed that compared to pigs fed the C-SPC diet, pigs fed the C-SBM and C-SPC + ISF diets had higher BW on day 72 (P < 0.05); pigs fed the C-SBM diet had significantly higher average daily gain (ADG) during days 14 to 28 (P < 0.05), with C-SPC + ISF being intermediate; pigs fed the C-SBM diet tended to have higher ADG during days 42 to 72 (P = 0.063), while pigs fed the C-SPC + ISF diet had significantly higher ADG during days 42 to 72 (P < 0.05). Moreover, compared to pigs fed the C-SPC diet, pigs fed the C-SBM diet tended to have greater villus height (P = 0.092), while pigs fed the C-SPC + ISF diet had significantly greater villus height (P < 0.05); pigs fed the C-SBM and C-SPC + ISF diets had significantly increased villus height-to-crypt depth ratio (P < 0.05). Compared with the C-SPC diet, dietary C-SPC + ISF tended to increase plasma superoxide dismutase activity on days 28 (P = 0.085) and 42 (P = 0.075) and reduce plasma malondialdehyde (MDA) content on day 42 (P = 0.089), as well as significantly decreased jejunal mucosa MDA content on day 42 (P < 0.05). However, no significant difference in the expression of tight junction genes among the three groups was found (P > 0.05). In conclusion, our results suggest that a long-term exposure to soybean isoflavones enhances the growth performance, protects the intestinal morphology and improves the antioxidative properties in pigs.
Changed spatial configurations at sowing have been investigated as a strategy to minimize interspecific competition and improve the establishment and persistence of multi-species plantings in pastures, but the impact of this practice on the soil microbiome has received almost no previous research attention. Differences in populations of bacteria and fungi in the surface 10 cm of soil in the third year following pasture establishment were quantified using quantitative polymerase chain reaction and terminal restriction fragment length polymorphism methods. Populations were compared on, and between, drill rows sown to either the perennial grass phalaris (Phalaris aquatica L.), perennial legume lucerne (alfalfa; Medicago sativa L.) or the annual legume subterranean clover (Trifolium subterraneum L.). Results showed that soil microbial abundance and diversity were related to plant distribution across the field at the time of sampling and to soil chemical parameters including total carbon (C), mineral nitrogen (N), pH, and available phosphorus (P), potassium (K) and sulfur (S). Despite the 27-month lag since sowing, pasture species remained concentrated around the original drill row with very little colonization of the inter-row area. The abundance and diversity of bacterial and fungal populations were consistently greater under drill rows associated with higher total C concentrations in the surface soil compared with the inter-row areas. Our results showed that the pH and available nutrients were similar between the subterranean clover drill row and the inter-row, suggesting that soil microbial populations were not impacted directly by these soil fertility parameters, but rather were related to the presence or absence of plants. The abundance of bacteria and fungi were numerically lower under phalaris rows compared to rows sown to legumes. The richness and diversity of fungal populations were lowest between rows where lucerne was planted. Possible explanations for this observation include a lower C:N ratio of lucerne roots and/or a lack of fibrous roots at the soil surface compared to the other species, illustrating the influence of contrasting plant types on the soil microflora community. This study highlights the enduring legacy of the drill row on the spatial distribution of plants well into the pasture phase of a cropping rotation and discusses the opportunity to enhance the microbiome of cropping soils on a large scale during the pasture phase by increasing plant distribution across the landscape.
OBJECTIVES/GOALS: The current proposal seeks to investigate the effect of early life antibiotic use in the development of functional gastrointestinal (GI) disorders. We propose that infants exposed to antibiotics will present with gut microbial dysbiosis, changes in fecal bile acid concentrations and develop more GI symptoms compared to unexposed children. METHODS/STUDY POPULATION: We analyzed fecal samples from 174 subjects at 12 months of age, of whom 52 were exposed to antibiotics in their first year of life. Of these, 33 subjects were sampled again at 24 months of age. DNA from 200mg of frozen stool (−80C) was isolated with the Qiagen DNeasy PowerSoil kit. Shotgun libraries were generated using the NexteraXT kit and sequenced on the Illumina HiSeq 2500 using 2x125 bp chemistry. Sequence data were analyzed using the Sunbeam metagenomics pipeline. The abundance of bacteria was estimated using Kraken version 2.0.8. Fecal bile acids will be quantified by liquid chromatography–mass spectrometry (LC-MS). RESULTS/ANTICIPATED RESULTS: Overall bacterial community composition at 12 or 24 months was not associated with antibiotic exposure (PERMANOVA test, Bray-Curtis distance). An increase in Enterobacteriaceae, in particular Escherichia coli, is a signature of antibiotic-induced dysbiosis, but also of early infant gut. Children with antibiotic exposure had slightly higher abundance of Escherichia coli compared to those with no exposure (p = 0.03). At 24 months, the abundance of Bacteroides caccae, a commensal gut species, was decreased for children exposed to antibiotics in the first year of life (fdr = 0.02). We will perform further analysis of bile acid modifying bacteria, fecal bile acid concentrations and correlate to GI symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest a significant but nuanced impact of early life antibiotic use on the composition of the gut microbiota. The association of antibiotic exposure with B. caccae and E. coli warrant further attention in the context of the rapidly developing early-life microbiome. CONFLICT OF INTEREST DESCRIPTION: The authors declare no conflicts of interest relevant to this work.
For patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, a traditional fist-bump greeting did not significantly reduce MRSA transfer in comparison to a handshake. However, transfer was reduced with a modified fist bump that minimized the surface area of contact and when hand hygiene was performed before the handshake.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
Cariprazine is a potent D3/D2 partial agonist with preferential binding to D3 receptors.
To evaluate the efficacy and safety of cariprazine versus placebo in acute exacerbation of schizophrenia.
A multinational, multicenter, double-blind, randomized, placebo- and active-controlled, fixed-dose trial in patients aged 18–60 years with DSM-IV-TR-defined schizophrenia, current psychotic episode < 2 weeks, and PANSS total score between 80 and 120. After 1-week washout, patients received 6-weeks treatment (cariprazine 1.5, 3.0, or 4.5 mg/d, risperidone 4.0 mg/d, or placebo) and 2-week safety follow-up. Risperidone was used to assess assay sensitivity. Primary and secondary efficacy: baseline to Week 6 change (LOCF) in PANSS total and CGI-S scores, respectively. Safety: adverse events (AEs), vital signs, laboratory measures, extrapyramidal symptom (EPS) scales.
Of 732 randomized patients, 64% completed the study. Mean baseline PANSS (98) and CGI-S scores (4.8) were similar across groups. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (placebo-adjusted improvements: −7.5, −8.9, −10.4, respectively; P < .001; LOCF) and risperidone (−15.0, P < .001, LOCF); significant improvement on CGI-S was demonstrated for all active treatments (P < .05). The most common cariprazine AEs were insomnia, EPS, akathisia, sedation, nausea, dizziness, and constipation. AE discontinuation rates were 15% for placebo, 10%, 5% and 8% for cariprazine 1.5, 3.0, and 4.5 mg/d, respectively, and 9% for risperidone 4.0 mg/d.
Cariprazine significantly improved PANSS and CGI-S scores versus placebo in acute exacerbation of schizophrenia and was generally well tolerated.
Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.
This is a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. 210 treatment-seekers with DSM-IV diagnosis of cocaine dependence consented and enrolled. 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants attended the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy once per week. The primary outcome was the increase in weekly percentage of non-use days. Secondary outcomes included: decrease in the weekly median log of urine benzoylecgonine, subgroup analyses of balancing factors and co-morbid conditions, self-report of alcohol use, addiction severity, craving, and risk behaviors for HIV.
125 participants completed 12 weeks of treatment (60%). The GEE regression analysis showed that for the total sample, the difference between modafinil groups and placebo in the weekly percentage of cocaine non-use days over the 12-week treatment period was not statistically significant (p=0.95). A post-hoc analysis showed a significant effect for modafinil, only in the subgroup of cocaine patients without alcohol dependence. Modafinil 200mg also showed significant effects of an increase in the total number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04).
These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing craving.
Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Bioinformatic investigations indicate that has-mir-206 (microRNA-206, miRNA-206) could regulate BDNF protein synthesis by interfering with BDNF mRNA translation, which is disrupted in bipolar disorder (BPD).
This study is to investigate whether miRNA-206 gene variants were associated with BPD susceptibility in a Han Chinese population.
342 patients who met DSM-IV criteria for bipolar disorder type I (BPD-I) or type II (BPD-II) and 386 matched health controls were enrolled into this study. the miRNA-206 gene and +/-500bp were selected for gene sequencing. for the case-control genetic comparisons, differences in the genotype and allele distributions between patients and controls were examined using Pearson's χ2 test.
Gene sequencing showed that there are two polymorphisms rs16882131(C/T) and rs62408583 (A/C) located at the upstream of miRNA-206 gene, which are complete linkage disequilibrium. the association analysis showed that there was no significant difference for genotype frequencies (χ2 = 2.075, df = 2, P = 0.354) or for allele frequencies (χ2 = 0.041, df = 1, P = 0.839) between BPD patients and controls. Similarly, no significant difference was found between BPD-I patients and controls (genotype χ2 = 1.411, df = 2, P = 0.494; allele χ2 = 0.380, df = 1, P = 0.538). However, there was significant difference between BPD-II patients and controls (genotype χ2 = 7.933, df = 2, P = 0.019; allele χ2 = 5.403, df = 1, P = 0.020).
Our findings do not support that BPD susceptibility was associated with miRNA-206 gene polymorphisms in the studied Han Chinese population. the association between miRNA-206 gene polymorphisms and bipolar disorder type II is needed to be carefully interpreted. Further studies are necessary to elucidate the involvement miRNA-206 in the pathophysiology of BPD.
Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.
The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.
CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.
The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.
Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.