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To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.
Responding to the extreme scarcity of medical resources during the early outbreak of the coronavirus disease (COVID-19) in Wuhan, China, an emergency specialist hospital of Leishenshan started to construct on January 26, 2020, and accommodate patients on February 6, 2020. The clinical laboratory center of Leishenshan Hospital (CLCLH) was constructed at the same time within 11 days to support the treatment of inpatients in Leishenshan Hospital and the testing of suspected patients from different fever clinics in Wuhan. The CLCLH could perform a total of 320 clinic, 299 biochemistry, 31 microorganism, and 47 infection and immunity examinations per day. It could also complete an average of 239 nucleic acid tests and 118 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody examinations per day. No suspected cases were documented among the health care workers during the operation of the CLCLH. The construction and operation experiences of the CLCLH is provided in this study and might be used by other countries as reference. The content of this study is divided into 4 parts: (1) the establishment of the CLCLH, including its layout and medical resource allocation; (2) the major testing items; (3) the specific procedure of COVID-19 indicator examination; and (4) the standardized personal protection measures.
A one-dimensional steady-state model for stimulated Raman backscatter (SRS) and stimulated Brillouin backscatter (SBS) processes in laser-irradiated plasmas is presented. Based on a novel “predictor-corrector” method, the model is capable to deal with broadband scattered light and inhomogeneous plasmas, exhibiting robustness and high efficiency. Influences of the electron density and temperature on the linear gains of both SRS and SBS are investigated, which indicates that the SRS gain is more sensitive to the electron density and temperature than that of the SBS. For the low-density case, the SBS dominates the scattering process, while the SRS exhibits much higher reflectivity in the high-density case. The nonlinear saturation mechanisms and competition between SRS and SBS are included in our model by a phenomenological method. The typical anti-correlation between SRS and SBS versus electron density is reproduced in the model. Calculations of the reflectivities are qualitatively in agreement with the typical results of experiments and simulations.
Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.
OBJECTIVES/GOALS: Allopregnanolone (ALLO), a modulator of GABAA receptors, may be useful as a treatment for human and canine benzodiazepine-refractory status epilepticus (SE). Our objective was to develop a phamacokinetic-pharmacodynamic (PKPD) model relating ALLO plasma concentrations to electroencephalographic (EEG) effects in dogs. METHODS/STUDY POPULATION: Four healthy dogs and one dog with epilepsy that had implanted intracranial electrodes were utilized. ALLO doses ranging from 1-6 mg/kg were administered IV over 5 min. EEG data were collected during four IM doses (1-2 mg/kg). Blood samples were collected up to 6 hr following dosing. ALLO concentrations were measured using HPLC-MS/MS. Power density was determined in EEG bands using a custom algorithm. A two-compartment link PKPD model was developed to describe the relation between ALLO plasma concentration and change in EEG power in the alpha, beta, delta and theta bands. RESULTS/ANTICIPATED RESULTS: ALLO caused a rapid increase in absolute power density in all EEG bands measured (1-4, >4 – 8, >8 – 12, >12 – 25, and >25 – 100 Hz). The onset of effect was rapid (1-3 min) and demonstrated by frequency band and dose analysis. Concentration-EEG data were best fit by a two-compartment PK model and sigmoidal Emax PD indirect link model. The beta frequency band was most sensitive, showing increases in power at the lowest ALLO concentrations. The EC50 concentration for the beta frequency was ~270 ng/mL. The EC50 values for effects on the other frequency bands were ~500-700 ng /mL. In conclusion, IV ALLO causes a rapid effect on EEG that can be used to determine minimal plasma concentrations associated with target engagement. DISCUSSION/SIGNIFICANCE OF IMPACT: Dose selection for future clinical trials will use the effective concentrations determined here in conjunction with studies in animal status epilepticus models. Studies are planned in client owned dogs with epilepsy to evaluate clinical efficacy in dogs and as nonclinical proof-of-concept evidence supporting translational studies in people. CONFLICT OF INTEREST DESCRIPTION: Michael Rogawski and Dorota Zolkowska are named as inventors on patent applications claiming use of neuroactive steroids including allopregnanolone and ganaxolone in the treatment of status epilepticus.
Outbreaks of norovirus-associated gastroenteritis have been reported in schools in recent decades in China. For early warning and response to infectious disease outbreaks, the Shanghai Infectious Diseases Bud Event Surveillance System (IDBESS) was established in 2016. Bud event is a term used for the early sign of a potential infectious disease outbreak in public settings when the first few cases appear. This study aimed to describe the epidemiological characteristics of Norovirus-associated gastroenteritis bud events from June 2016 to December 2017 and to understand factors influencing the severity of events. Data were extracted from the IDBESS, supplemented by field investigations and school absence surveillance. In total, 189 bud events of Norovirus-associated gastroenteritis were reported in schools and kindergartens, affecting 3827 individuals and 52.38% happened in primary schools. The attack rate of Norovirus-associated gastroenteritis was 3.82% on average in students in the affected schools. In each event, case numbers varied between 5 and 148, with a median of 16. The duration of bud events lasted for 2 days on average. School absence happened in 47.93% (1797/3749) of affected students and the average duration of absence was 3.07 days. It was found that a longer delay before reporting was associated with a longer-lasting duration of bud event (OR = 2.25, 95% CI: 1.65, 3.07). In conclusion, ascribed to the sensitive threshold for alerting and the timely field investigation, the surveillance of bud events of Norovirus-associated gastroenteritis is effective in the control of Norovirus infection among preschool children and students in Shanghai.
Situated between the North China Craton to the east and the Tarim Craton to the west, the northern Alxa area in westernmost Inner Mongolia in China occupies a key location for interpreting the late-stage tectonic evolution of the southern Central Asian Orogenic Belt. New LA-ICP-MS zircon U–Pb dating results reveal 282.2 ± 3.9 Ma gabbros and 216.3 ± 3.2 Ma granites from the Yagan metamorphic core complex in northern Alxa, NW China. The gabbros are characterized by low contents of Si, Na, K, Ti and P and high contents of Mg, Ca, Al and Fe. These gabbros have arc geochemical signatures with relative enrichments in large ion lithophile elements and depletions in high field strength elements, as well as negative εNd(t) (−0.91 to −0.54) and positive εHf(t) (2.59 to 6.37) values. These features indicate that a depleted mantle magma source metasomatized by subduction fluids/melts and contaminated by crustal materials was involved in the processes of magma migration and emplacement. The granites show high-K calc-alkaline and metaluminous to weakly peraluminous affinities, similar to A-type granites. They have positive εNd(t) (1.55 to 1.99) and εHf(t) (5.03 to 7.64) values. These features suggest that the granites were derived from the mixing of mantle and crustal sources and formed in a postcollisional tectonic setting. Considering previous studies, we infer that the final closure of the Palaeo-Asian Ocean in the central part of the southern Central Asian Orogenic Belt occurred in late Permian to Early–Middle Triassic times.
Advanced Ni8W/Ni12W/Ni8W alloy composite substrates used in YBCO-coated conductors with a strong cube texture and high yield strength have been fabricated, and a CeO2 buffer layer film was successfully deposited on the composite substrates. Through in situ tensile testing coupled with electron backscattered diffraction (EBSD) analysis, the stability of the cube texture of Ni8W/Ni12W/Ni8W alloy composite substrates has been investigated. The stress–strain curve shows that the yield strength (at 0.2% strain) of the composite substrates exceeds 250 Mpa. The orientation of grains and boundaries on the surface of the substrates was almost unchanged, while the strain exceeds 0.2%, which indicated that the composite substrates are adequate for depositing buffer layers and YBCO layers by the reel-to-reel process.
To examine the Efficacy and side effects of modified electroconvulsive therapy (MECT) combined with antipsychotic medication in treatment-refractory schizophrenia(TRS).
the 39 patients with TRS who had received antipsychotic medication were assigned to receive MECT, and the Positive and Negtive Syndrome Scale (PANSS) ,Treatment Emergent Symptoms Scale (TESS) and Wechsler Memory Scale were used to measure therapeutic efficacy ,side effects and memory function.
The PANSS scores decreased significantly at 1,4,12 weeks after MECT (P<0.01), and the efficacy ratio of MECT at 1,4,12 weeks treatment was 5%,26%,23% respectively. No significant difference was found on the scores of TESS between before and after endpoint treatment of MECT. The WMS scores decreased significantly at 1 day after endpoint of MECT, but there was no significant difference between before and after 1,2 weeks of endpoint treatment of MECT.
MECT was effective in TRS case, and it had little side effects and a little effect on memory temporarily.
Schizophrenia is a chronic psychiatry disorder with high heritability. Schizophrenic patients with early age at onset trend to have more genetic component and thus may be an attractive subpopulation for genetic studies. Brain-derived neurotrophimc factor (BDNF) is considered as candidate gene for schizophrenia. A single nucleotide polymorphism (BDNF Val66Met) was reported to be associated with schizophrenia, although discrepancy remains. The aim of this study was to evaluate the association between BDNF Val66Met polymorphism and schizophrenia using an early onset sample in Chinese Han population. Our sample consisted of 353 schizophrenic patients with onset before age 18 and 394 healthy age and sex matched controls. All subjects were ethnically homogenous Han Chinese origin. No significant differences of genotype or allele distribution were identified between the patients and controls. However, the Met allele was significantly associated with an earlier age at onset in male schizophrenic patients (Kaplan-Meier log-rank test P = 0.005), but not in females (P = 0.289). The BDNF Val66Met polymorphism has an important effect on the age at onset of schizophrenia in a gender-specific manner, and this may provided a significant genetic clue for the etiology of schizophrenia. Therefore, further studies are required to uncover the exact role of BDNF in the development of schizophrenia.
To study the relationship between insulin-like growth factor 1 receptor (IGF1R)and subsyndromal symptomatic depression (SSD).
In this case-control study, real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) with TaqMan MGB was used to analyzing the differences of IGF1R gene mRNA expression in peripheral leukocytes between subsyndromal symptomatic depression group(n = 47) and healthy controls(n = 52). At the same time Hamilton Depression Rating Scale -17(HAMD17) were assessed.
IGF1R gene mRNA expression was 0.21 ± 0.11 in SSD group, 0.56 ± 0.37 in healthy group, and there was significant difference between both groups on IGF1R expression(z = 39.54, P < 0.001). the expression levels of IGF1R in SSD patients was not correlated with Hamilton score(r = −0.292, p = 0.275).
This study suggested that the decreased expression of IGF1R were related with the pathophysiology of SSD.
Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of ‘school-household-school’ transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.
In this paper, we report the recent progress on the
laser beamline of Shanghai Superintense Ultrafast Laser Facility (SULF). The SULF-1 PW laser beamline is based on the double chirped pulse amplification (CPA) scheme, which can generate laser pulses of 50.8 J at 0.1 Hz after the final amplifier; the shot-to-shot energy fluctuation of the amplified pulse is as low as 1.2% (std). After compression, the pulse duration of 29.6 fs is achieved, which can support a maximal peak power of 1 PW. The contrast ratio at
before main pulse is measured to be
. The focused peak intensity is improved by optimizing the angular dispersion in the grating compressor. The maximal focused peak intensity can reach
even with an
off-axis parabolic mirror. The horizontal and vertical angular pointing fluctuations in 1 h are measured to be 1.89 and
, respectively. The moderate repetition rate and the good stability are desirable characteristics for laser–matter interactions. The SULF-1 PW laser beamline is now in the phase of commissioning, and preliminary experiments of particle acceleration and secondary radiation under 300–400 TW/0.1 Hz laser condition have been implemented. The progress on the experiments and the daily stable operation of the laser demonstrate the availability of the SULF-1 PW beamline.
Several studies suggested a potential role of viral infection in the pathophysiology of Parkinson’s disease (PD). However, the association between herpes zoster and PD was not investigated well till now.
Using the Taiwan National Health Insurance Research Database, 13 083 patients aged ≥45 years with herpes zoster and 52 332 (1:4) age-/sex-matched controls were enrolled between 1998 and 2008 and followed to the end of 2011. Those who developed PD during the follow-up period were identified.
The Cox regression analysis with adjustment of demographic characteristics, health system utilization, and comorbidities demonstrated that patients with herpes zoster had an increased risk (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.43-2.28) of developing PD in later life compared to the control group. Sensitivity tests after excluding the first year (HR: 1.50, 95% CI: 1.16-1.93) and first 2-year (HR: 1.44, 95% CI: 1.10-1.88) observation periods showed consistent results.
Patients with herpes zoster were more likely to develop PD in later life compared to the controls. Additional studies are necessary for validating our results and to clarify the underlying pathophysiology between herpes zoster and PD.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals’ 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01–0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals’ long-term exposures.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
Civil emergencies occurring with little warning can quickly produce mass casualties. To develop an Emergency Department’s surge capacity, medical student involvement in the disaster response has been advocated. Duke-NUS Medical School in Singapore is located in proximity to Singapore General Hospital (SGH) and represents an untapped manpower resource. With appropriate training, medical students can be leveraged upon as ready and reasonably qualified manpower.
This review provides a snapshot of the conceptualization and setting up of the Disaster Volunteer Corps (DVC) program. We discuss the overall strategy and benefits to stakeholders, emphasizing the close symbiotic relationship between academia and healthcare services.
Duke-NUS medical students will be recruited to receive training from SGH emergency physicians. The frequency of training will be four times yearly, with ad hoc participation in disaster simulation exercises. A call-tree will be employed for DVC activation. The DVC curriculum includes disaster response principles, HAZMAT, crowd control, marshaling, logistics, psychological support, and basic first aid. Teaching methods include didactic lectures, case discussions, involvement in event medical cover, and participation in disaster simulation exercises and response planning.
To date, there are 10 medical students and four emergency physician faculty volunteers involved in the program. Support is provided by adjunct instructors from nursing, nuclear medicine, social work, and security, for training in decontamination, radiological disasters, psychological first aid, and crowd control measures respectively. Assessment by faculty will be conducted to ensure the quality of training and competency of skills.
The DVC provides a unique way of teaching medical students disaster medicine principles in a hands-on experiential format, while simultaneously enhancing the operational readiness of the hospital in times of disaster. This model of close collaboration between university educational and healthcare services provides a feasible model of structured volunteerism that could be replicated in other similar settings.