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Anorexia nervosa (AN) is a complex mental disorder mainly characterized by a voluntary food restriction and excessive physical activity resulting in dramatic weight loss. Changes in the brain-derived neurotropic factor (BDNF) have been reported in AN patients compared to controls. According to meta-analysis, functional variant rs6265 Val66Met of the BDNF gene has been found genetically associated to AN. We also reported an association of this functional variant and electrodermal response to images of thinness suggesting an association between rs6265 and a reward effect of weight loss in AN. In animal models, BDNF modulates negatively the central control of food intake and its injection in rodents induces weight loss and anorexia. Thus, besides its function on neuronal survival, synaptic plasticity and mood, BDNF was also reported to have a metabolic effect via both central nervous system and peripheral organs, which makes BDNF a good candidate for AN diagnosis biomarker.
Our study investigates the levels of expression of Bdnf, gene and protein, taking advantage of the mouse AN-like model by measuring Bdnf levels in specific brain areas and blood in food-restricted and refeed animals.
We used a mouse AN-like model combining a phase of chronic food restriction (50%) during 15 days followed by an ad libitum refeeding period of one week. Female mice have or not access to a running with wheel to create a similar metabolic environment that those patients suffering from AN during restriction and recovery once hospitalised. The Bdnf mRNA and protein levels were measured in samples of blood and brain regions (prefrontal cortex, hippocampus, hypothalamus, dorsal striatum, nucleus Accumbens, ventral tegmental area and amygdala) using quantitative PCR and ELISA methods in the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel). Statistical analysis will compare the measures for different samples by one-way or two-way ANOVAs depending the group of animals or brain regions and blood.
To date, no difference of the level of transcription for Bdnf was observed between the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel) in the prefrontal cortex, hippocampus and hypothalamus. We expect significant differences of Bdnf expression in the other brain regions of interest for the food restricted animals with or without the wheel compared to ad libitum animals. We expect also differences in the level of expression of Bdnf in fasted animals compared to the refeed animals.
The BDNF could represent a potential biomarker of AN for the diagnostic and the prognosis in the evolution to the remission when weight recover and thus will allow a better understanding of the aetiology of AN. This study is supported by Fédération pour la Recherche sur le Cerveau.
Systemic inflammation has been increasingly related to bipolar disorder -BD- (Tanaka et al. Neurosci Res 2017;115 59-63). Intestinal bacterial translocation has been postulated as one of the causes of this inflammation (Nguyen et al. J Psychiatr Res 2018;99 50-61). A possible pathway is through the lipopolysaccharide, which is presented to CD14 through lipopolysaccharide binding protein (LBP) leading to a release of systemic inflammatory markers like C-reactive protein (CPR) (Funda et al. Infect Immun 2001;69 3772-81).
1) Describe gut permeability in patients with BD through the determination of intestinal inflammatory markers (LBP, sCD14) in plasma; 2) Analyze variables associated with intestinal inflammation.
Cross-sectional study of 38 patients with BD [mean age=45.50 (SD=10.93; range 23-68); males=15 (39.5%)], recruited from mental health outpatient clinics in Oviedo (Spain).
Assessment: Pro-inflammation biomarkers [CRP (mg/dL), Erythrocyte Sedimentation Rate (ESR) (mm/h), Neutrophil/Lymphocyte, Monocyte/Lymphocyte, Platelet/Lymphocyte and Systemic Immune Inflammation Indexes]. Indirect markers of intestinal bacterial translocation [LBP, soluble CD14 (sCD14)]. Dichotomous variables were created for LBP, considering LBP ≥15 μg/dL as increased gut permeability; and for CPR, considering CRP≥0.3 as systemic inflammation. Metabolic syndrome [ATPIII criteria: glucose, HDL, triglycerides (mg/dl), arterial pressure (mmHg), abdominal circumference (cm)], body mass index (BMI) (kg/m2), smoking, cannabis or alcohol use.
Statistical analyses: t-Student test, multiple linear regression analyses.
Average LBP was 14.60 μg/dL (SD=6.4) and 15 patients (39.5%) had increased gut permeability. Moreover, average CPR was 0.40 mg/dL (SD=0.58) and 16 patients (47.1%) showed systemic inflammation. There were no patients with increased levels of sCD14.
Associations were found between LBP and CPR (r=0.357; p=0.032), cannabis use in the last month (t=-2.293; p=0.029), BMI (r=0.433; p=0.008) and abdominal obesity (t=3.006; p=0.005); but no with age or sex.
Subsequently, a multiple linear regression model for LBP was calculated with variables previously mentioned, and age (based on expert criteria). The overall regression was statistically significant (R2=0.49, F=9.273, p<0.001). It was found that CPR, abdominal obesity, and cannabis use in the last month significantly predicted LBP levels (table 1).Table 1.
Multiple linear regression analyses to LBP
More than one third of patients with BD had increased gut permeability. Almost 50% had systemic inflammation. Intestinal permeability was directly related to abdominal obesity and systemic inflammation, but inversely related to cannabis use.
Anorexia nervosa (AN) is a complex psychiatric disorder characterized by a persistant decrease in food intake leading to dramatic weight loss and energy deficit. The ghrelin system is a key regulator of appetite and food intake across species. LEAP-2, a recently discovered ghrelin antagonist, appears to be up-regulated in obesity and opposes to the orexigenic drive of ghrelin. The evolution of LEAP-2 levels could be an interesting insight to reflect the regulation of appetite in eating disorders such as anorexia nervosa (AN).
We tested this hypothesis and here provide the first study exploring the ghrelin and LEAP-2 regulation in long-term food restriction followed by refeeding in both mice and patients suffering from AN.
Using a translational strategy, we compared the regulation of ghrelin and LEAP-2 concentrations in blood during food restriction and after refeeding i/ in female mice exposed to a 14 days protocol combining quantitative food restriction and running wheel activity followed by 10 days of progressive refeeding; ii/ in an ongoing longitudinal study of patients with AN evaluated before and after refeeding (n=30) as well as 6 months after hospital discharge to evaluate if the weight gain was stable (n=7) or unstable (n=10). Plasma concentrations of ghrelin and LEAP-2 were measured with selective immunoassays.
Long-term food restriction in mice was associated with increased ghrelin (p<0.001) and decreased LEAP-2 concentrations (p=0.006) compared to ad libitum fed controls. Refeeding led to a decrease in ghrelin (p<0.01) and increase in LEAP-2 concentrations (p<0.01). Patients with AN displayed increased ghrelin levels (p<0.01) but also higher LEAP-2 concentrations on admission than after refeeding (p=0.04). LEAP-2 decreased with refeeding. On 17 patients re-evaluated 6 months after discharge, patients with unstable weight gain exhibited a greater decrease of LEAP-2 concentrations during refeeding compared to patient with stable weight gain (p=0.02). Decreasing LEAP-2 concentrations was able to predict a negative outcome (i.e. unstable weight gain) in 80% of the cases.
We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN as it is in the case of a physiological adaptation to food restriction. Results from an ongoing longitudinal study exploring remission in AN suggest that the evolution of LEAP-2 concentrations during refeeding is opposed to data from preclinical model and could give new insights on the outcome of weight gain in AN.
Since 2018, the radiocarbon laboratory of Lanzhou University has been equipped with a compact accelerator mass spectrometer—a 200-KV mini carbon dating system (MICADAS), together with an auto graphitization equipment (AGE III). The laboratory has for a long time prepared graphite targets for 14C dating of plant fossils, charcoal, bones, and bulk organic matter. Herein, we give an overview of the operating status and performance of the dating facility. The long-term measurements of the standard and blank samples indicated that the results for MICADAS in Lanzhou University were accurate and stable and of high sensitivity. Fifteen sets of organic materials collected from archaeological sites in northwest China were selected for an inter-comparison study involving the participation of four specialist laboratories. The 14C dating results for the homogenized archaeological samples from several of the laboratories showed a high degree of consensus. The long-term performance and inter-comparison data for MICADAS confirmed that the radiocarbon laboratory of Lanzhou University could provide stable and accurate 14C dating results. In this context, the 14C dating results for a number of key archaeological/environmental samples were validated.
This study aimed to explore the utility of the eosinophil percentage in peripheral blood for guiding post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
Forty-four patients with chronic rhinosinusitis with nasal polyps underwent functional endoscopic sinus surgery and were randomly divided into two groups. Patients in the standard treatment group used oral and nasal spray glucocorticoids. In the biomarker treatment group, patients with peripheral blood eosinophil percentage values less than 3.05 per cent did not receive glucocorticoid treatment, whereas patients with values 3.05 per cent or above were part of the standard treatment group. Visual Analogue Scale, Sino-Nasal Outcome Test-22 scores, endoscopic Lund–Kennedy scores, eosinophils, interleukin-5 and eosinophil cationic protein in peripheral blood, and nasal secretions were measured.
After functional endoscopic sinus surgery, the Visual Analogue Scale, Sino-Nasal Outcome Test-22 and Lund–Kennedy scores were significantly reduced in both groups; there were no significant differences in those indicators between the groups during the three follow-up visits.
Peripheral blood eosinophil percentage offers a potential biomarker to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
Sleep and circadian disturbances have been widely studied in patients with bipolar disorder (BD) (Duarte Faria et al., 2015; Gonzalez, 2014). However, there is no clear evidence about the role of peripheral biomarkers of circadian cycle in this population.
This systematic review aims to identify potential endocrine biomarkers of circadian rhythm in blood and study their relationship with sleep problems in BD.
An electronic search of Pubmed and PsycoInfo databases were performed. It includes articles about the topic from 1991 to 2021. The search strategy was: (“Peripheral biomarkers” OR “biological markers” OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR “circadian rhythm” OR sleep OR insomnia) AND “bipolar”.
92 records were obtained after excluding duplicates. Only five studies met the inclusion criteria (n = 499; BD = 125; unipolar depression = 148; schizophrenia = 80; controls = 146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study) and orexin-A (1 study). Overall, no significant associations between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures, were detected.
This systematic review highlights the lack of studies that explores the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in BD.
Bipolar disorder (BD) is a chronic deteriorating illness which has a strong impact on functionality. In the past few years, orexins have gained importance as possible biomarkers of circadian rhythms, affected in BD. Up to this date, we have not found any bibliographical review evaluating the association of orexins and BD.
To review published literature in relation to the associaton of orexins and BD.
A bibliographical search was conducted in PubMed. Inclusion criteria were a) the study evaluated orexins in plasma or cerebrospinal fluid, and b) patients with BD were included within the subjects of study.
Reference lists of the articles that met inclusion criteria were also examined.
Ten articles were retrieved from the initial search. Only three met inclusion criteria and another one was selected from the reference list examination. One study observed significantly higher levels of orexin A in plasma of BD patients versus depression and controls. Other found higher concentration of orexin A of unipolar and bipolar depression versus controls, but this result was not statistically significant. Another one did not find differences in orexin A concentration between mania, depression and controls. The remaining study detected significantly lower concentration of orexin A in BD versus depression, schizophrenia and controls.
Despite being heterogenous, the results point out there are differences in orexin levels in BD when compared to other diagnostic groups or controls. This sets a starting point to focus research on this subject and continue analyzing the role of orexins as biomarkers in BD.
Extracts of mulberry have been shown to reduce post-prandial glucose (PPG) and insulin (PPI) responses, but reliability of these effects and required doses and specifications are unclear. We previously found that 1·5 g of a specified mulberry fruit extract (MFE) significantly reduced PPG and PPI responses to 50 g carbohydrate as rice porridge, with no indications of intolerance. The trials reported here aimed to replicate that work and assess the efficacy of lower MFE doses, using boiled rice as the carbohydrate source. Two separate randomised controlled intervention studies were carried out with healthy Indian males and females aged 20–50 years (n 84 per trial), with PPG area under the curve over 2 h as the primary outcome. Trial 1 used doses of 0, 0·37, 0·75, 1·12 and 1·5 g MFE in boiled rice and 0 or 1·5 g MFE in rice porridge. Trial 2 used doses of 0, 0·04, 0·12, 0·37 g MFE in boiled rice. In trial 1, relative to control, all MFE doses significantly decreased PPG (–27·2 to −22·9 %; all P ≤ 0·02) and PPI (–34·6 to −14·0 %, all P < 0·01). Breath hydrogen was significantly increased only at 1·5 g MFE (in rice porridge), and self-reported gastrointestinal symptoms were uniformly low. In trial 2, only 0·37 g MFE significantly affected PPG (–20·4 %, P = 0·002) and PPI (–17·0 %, P < 0·001). Together, these trials show that MFE in doses as low as 0·37 g can reliably reduce PPG and PPI responses to a carbohydrate-rich meal, with no apparent adverse effects.
South-east Asia's diverse coastal wetlands, which span natural mudflats and mangroves to man-made salt pans, offer critical habitat for many migratory waterbird species in the East Asian–Australasian Flyway. Species dependent on these wetlands include nearly the entire population of the Critically Endangered spoon-billed sandpiper Calidris pygmaea and the Endangered spotted greenshank Tringa guttifer, and significant populations of several other globally threatened and declining species. Presently, more than 50 coastal Important Bird and Biodiversity Areas (IBAs) in the region (7.4% of all South-east Asian IBAs) support at least one threatened migratory species. However, recent studies continue to reveal major knowledge gaps on the distribution of migratory waterbirds and important wetland sites along South-east Asia's vast coastline, including undiscovered and potential IBAs. Alongside this, there are critical gaps in the representation of coastal wetlands across the protected area networks of many countries in this region (e.g. Viet Nam, Indonesia, Malaysia), hindering effective conservation. Although a better understanding of the value of coastal wetlands to people and their importance to migratory species is necessary, governments and other stakeholders need to do more to strengthen the conservation of these ecosystems by improving protected area coverage, habitat restoration, and coastal governance and management. This must be underpinned by the judicious use of evidence-based approaches, including satellite-tracking of migratory birds, ecological research and ground surveys.
This study investigated the characteristics and prognosis of the feeling of ear fullness in patients with unilateral all-frequency sudden sensorineural hearing loss.
Our study included 56 patients with a diagnosis of unilateral all-frequency sudden sensorineural hearing loss accompanied by a feeling of ear fullness and 48 patients without a feeling of ear fullness. The condition of these patients was prospectively observed.
Positive correlations were observed between grading of feeling of ear fullness and hearing loss in patients with a feeling of ear fullness (r = 0.599, p < 0.001). No significant differences were observed in the total effective rate of hearing recovery between patients with and without a feeling of ear fullness after one month of treatment (Z = −0.641, p = 0.521). Eighty-six per cent of patients (48 out of 56) showed complete recovery from the feeling of ear fullness. There was no correlation between feeling of ear fullness recovery and hearing recovery (r = 0.040, p = 0.769).
The prognosis of feeling of ear fullness is good. There was no correlation between feeling of ear fullness recovery and hearing recovery for all-frequency sudden sensorineural hearing loss patients.
Schizophrenia is one of the most disabling diseases affecting the patient’s ability to live independently, to be socially active and to work or study1,2. Therefore, identifying predictors of functioning in the first stages of the disease is important to prevent a negative progression of functional outcome in these patients3.
To identify the factors associated with real-world functioning in patients with recent onset of the disease.
Secondary analysis of a cross-sectional, naturalistic study. 84 patients with Schizophrenia (F20), aged 18-71 in their first five years of the disorder under maintenance treatment. Assessments: PANSS, CDS, CGI-S, CAINS; functioning: PSP, cognition: MATRICS. Statistical analysis: student-t test, ANOVA, Pearson correlation and lineal regression.
Mean age (SD): 31.30 (10.08); men: 62.8%. Statistical significant differences (p<0.05) were found in work status, benzodiazepines and antidepressants use. Furthermore, significant correlations (p<0.05) were found with depressive, positive and negative symptoms (avolition, anhedonia, alogia and affective flattening) and cognition. A significant predictive model was obtained that explains the 72.1% of the variance [F(5,74)= 20.952; p< 0.001]. This model included depressive symptoms (B= -0.940; p= 0.001), negative symptoms (B= -1.696; p< 0.001), avolition and anhedonia (B= -0.643; p= 0.001), affective flattening and alogia (B= 1.197; p= 0.003), and visual learning (B= 0.202 p= 0.039).
Negative and depressive symptoms are the main determinants of real-world functioning in patients with recent onset of schizophrenia. Visual learning also contributes to this outcome. On the other hand, the positive relationship between expressive domain and functioning needs furthermore investigation.
Worse sleep quality and increased inflammatory markers in women with schizophrenia (Sch) have been reported (Lee et al. 2019). However, the physiological mechanisms underlying the interplay between sleep and the inflammatory pathways are not yet well understood (Fang et al. 2016).
Analyze the relationship between Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR) and Platelet/Lymphocyte (PLR) ratios, and insomnia in Sch stratified by sex.
Final sample included 176 Sch patients (ICD-10 criteria) [mean age: 38.9±13.39; males: 111(63.1%)]. Assessment: PANSS, Calgary Depression Scale (CDSS), and Oviedo Sleep Questionnaire (OSQ) to identify a comorbid diagnosis of insomnia based on ICD-10. Fasting counting blood cell were performed to calculate ratios. Statistics: U Mann-Whitney, logistic regression.
Insomnia as comorbid diagnosis was present in 22 Sch (12.5%) with no differences between sex [14 males (12.6%), 8 females (12.3%)], neither in their age. Female patients with insomnia showed increased NLR [2.44±0.69 vs. 1.88±0.80, U=122.00 (p=0.034)]. However, no differences in PLR and MLR were found, neither in any ratio in males. Regression models using insomnia as dependent variable and covariates (age, PANSS-positive, PANSS-negative, CDSS) were estimated. Females: presence of insomnia was associated with NLR [OR=3.564 (p=0.032)], PANSS-positive [OR=1.263 (p=0.013)] and CDSS [OR=1.198 (p=0.092)]. Males: only PANSS-positive [OR=1.123 (p=0.027)] and CDSS scores [OR=1.220 (p=0.005)] were associated with insomnia.
NLR represent an inflammatory marker of insomnia in Sch but only in female patients. Improving sleep quality in these patients could help to decrease their inflammatory response.
Depressed patients with early traumatic experiences may represent a clinically distinct subtype with worse clinical outcome. Since early traumatic experiences alter the development of systems that regulate the stress response, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behaviour.
To determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behaviour in patients with major depressive disorder (MDD).
The sample included 190 patients [mean age (SD)=53.71 (10.37); females: 66.3%], with current MDD. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity. We developed mediation models by bootstrap sampling methods.
81 (42.6%) patients had previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b=0.007, 95% CI=0.001, 0.015), after controlling for sex, HDRS-Total, and LTE-Total.
Impulsivity could mediate the influence of childhood trauma on suicidal behaviour. This will help understand the role of risk factors in suicidal behaviour and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.
Suicidal behavior has a great impact on world public health. The literature describes the possible existence of an association between neurobiological, clinical and cognitive factors in suicidal behavior.
To determine the possible relationship between clinical variables (history of abuse/maltreatment in childhood), psychopathology (impulsivity traits) and cognitive (decision-making) with a history of suicide attempt and/or current suicidal idea in patients with major depressive disorder.
Cross-sectional study in a sample of adult patients with major depressive disorder in which two types of comparisons are made. In the first case, two groups were compared based on the presence or absence of history of suicide attempt. In the second case, two groups were compared based on the presence or absence of suicidal ideation in the same sample of patients. Finally, sociodemographic, clinical and cognitive variables were evaluated in that population sample.
When the joint influence of sociodemographic, clinical and cognitive characteristics are present, it can be said that being single/divorced/separated, a history of sexual abuse in childhood and an alteration in decision-making, specifically a lower number of choices of deck D in the IGT test, are associated with a higher probability of a personal history of suicide attempt. While a higher score on the Barrat impulsivity scale is associated with a greater probability of presenting current suicidal ideation once the influence of sociodemographic, clinical and cognitive variables has been taken into account.
Different sociodemographic, clinical and cognitive factors are associated with the presence of a history of suicide attempt and/or current suicidal ideation.
COVID-19 pandemic and lockdown have provoked a considerable psychological impact in Spain. Some studies have reported greater psychological impact in the younger population. To date, no previous study has focused on depressive disorder (DD) patients based on their age.
To describe the psychological impact on DD according to age.
Cross-sectional study of an online survey available from 19 to 26 March 2020. Out of a total of 21207 respondents, 608 (2.9%) reported suffering from DD (mean age ±SD = 41.2 years±14.07 [18-82], 80.6% women). The subsample (608) was divided according to age, “youngsters” <45 (57.4%)/ “elders” ≥45. DASS-21 and IES scales were employed. Statistical analyses: Chi-square, t-Student test.
Both groups did not differ (p>0.05) in sex, having COVID-19 symptoms, having family/friends infected, or income changes. While youngsters were single more frequently (68.8% vs 14.3%, χ² = 179.7, p<0.001), elders had somatic illness more frequently (64.8% vs 39.7% χ² =30.401, p<0.001). Youngsters obtained higher scores in depression (4.69 vs 4.1, T=5.413, p<0.001), anxiety (2.86 vs 1.97, T=5.249, p<0.001) and stress (4.48 vs 3.17, T=6.355, p<0.001) DASS-21 subscales, as in intrusive (3.42 vs 3.05, T=1.984, p=0.048) and avoidant (4.64 vs 4.11, T=3.056, p=0.002) IES scores.
Despite the group of elders with depression being more vulnerable to severe COVID-19 disease and presenting more frequently somatic comorbidities, younger depressive patients suffered more from depressive, anxiety, stress and avoidant symptoms and intrusive thoughts, in line with previous reports in the general population.
This study reports on the changes in stress, anxiety, and depressive symptoms of subscribers after 3 months using Text4Hope, a supportive text messaging program designed to provide support during the pandemic.
Standardized self-report measures were used to evaluate perceived stress (measured with the Perceived Stress Scale-10 [PSS-10]), anxiety (measured with the General Anxiety Disorder Scale 7 [GAD-7]), and depressive symptoms (measured with the Patient Health Questionnaire [PHQ-9]), at baseline and 3rd month (n = 373).
After 3 months of using Text4Hope, subscribers’ self-reports revealed significant (p< 0.001) mean score reductions compared with baseline on: the GAD-7 by 22.7%, PHQ-9 by 10.3%, and PSS-10 scores by 5.7%. Reductions in inferred prevalence rates for moderate to high symptoms were also observed, with anxiety demonstrating the largest reduction (15.7%).
Observed Text4Hope-related reductions in psychological distress during COVID-19 indicate that Text4Hope is an effective, convenient, and accessible means of implementing a population-level psychological intervention.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
This study assessed the relationships between different perpetrator-victim roles in intimate partner violence (IPV), emotion regulation (ER) and mental health problems among men who have sex with men (MSM) in China.
From April to June 2019, 1233 participants were approached via gay-friendly non-governmental organisations in 15 cities across mainland China.
Of the total, 578 eligible participants completed an anonymous online survey. All participants provided informed consent and information about their violent perpetrator-victim role and mental health status. The results revealed a high prevalence of IPV in this study sample, with 32.7% of participants reporting IPV victimisation and 32.5% of participants reporting IPV perpetration during their lifetime. A total of 81 (14.0%) participants were suicidal, 309 (53.5%) participants reported poor general mental health and 208 (36.0%) had significant depressive symptoms. Adjusted logistic regression models revealed that both physical victimisation (adjusted odds ratio [ORa] = 3.22, 95% confidence interval [CI] = 1.11–9.32) and sexual victimisation (ORa = 2.90, 95% CI = 1.39–6.05) had positive associations with suicidality, and unidirectional and bidirectional psychological perpetration were associated with poor general mental health and significant depressive symptoms. Although high cognitive reappraisal showed a negative association with poor general mental health (ORa = 0.89，95% CI = 0.86–0.92), the correlation with victims of IPV was weaker than it was with non-victims.
This study revealed that different perpetrator-victim roles in different IPV situations should be considered comprehensively in research, prevention and intervention. ER is not enough to buffer the effects of IPV on the mental health of MSM victims.
OBJECTIVES/GOALS: Non-alcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in the world for which no anti-fibrotic therapies exist. We hypothesized that BMS-22 and maraviroc (MVC), chemokine receptor 2 (CCR2) and 5 (CCR5) antagonists, respectively, would diminish the fibrogenic activity of "fat-exposed" murine pHSCs. METHODS/STUDY POPULATION: pHSCs were isolated from livers of 6 week old male mice following 4 weeks on a NASH-inducing choline-deficient high fat diet (CDAHFD, “fat-exposed”) or standard diet (SD) and passaged in vitro. Early passage (6-12) pHSCs were plate-adhered and TGF-b-treated (10ng/mL) to maximally activate their pro-fibrogenic genes, collagen 1α1 (Col1A1), tissue inhibitor of metalloproteinase 1 (TIMP1), or α-smooth muscle actin (ACTA2). CDAHFD and SD pHSCs were then treated for 48 hours with increasing doses of BMS-22 or MVC (range: 0.3-120ng/mL) to determine (1) the degree of attenuation of the pro-fibrogenic response as measured by qPCR of fibrogenic genes (Col1A1, TIMP1,ACTA2); (2) enhancement of a fibrolytic response as measured by qPCR of matrix metalloproteinases (MMP) 2, 9 and 13 genes; and (3) pHSC migration using the scratch assay. Cell viability and CCR2 and CCR5 gene expression in response to escalating doses of antagonists were also measured. RESULTS/ANTICIPATED RESULTS: Plate- and TGF-b activated CDAHFD pHSCs had a 2-fold greater, dose-dependent attenuation of their pro-fibrogenic activity in response to BMS-CCR2-22 and MVC, when compared with plate- and TGF-b activated SD pHSCs, as measured by reductions in collagen 1α1 (Col1A1) and α-smooth muscle actin (ACTA2) gene expression. TIMP1 gene expression was unaffected by drug treatment for 48 hours. Cell viability was not affected up to doses of 30ng/mL of each drug. pHSCs also demonstrated a dose-dependent increase in CCR2, CCR5 and MMP-9 gene expression in response to surface receptor antagonism. Migration assays comparing CDAHFD and SD pHSCs in response to escalating doses of MVC and BMS-22 are ongoing and expected to demonstrate a significantly decreased migratory capacity of CDAHFD pHSCs than SD pHSCs in response to therapy, reflecting the increased susceptibility of the “fat-exposed” pHSCs to anti-fibrotic therapy than normal pHSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-fibrotic drugs that dampen pro-fibrogenic activities of “fat-exposed” pHSCs are urgently needed. CCR2 and CCR5 antagonists, BMS-22 and MVC, respectively, can selectively dampen the pro-fibrogenic response of fat-exposed pHSCs, and must be considered for future trials in human NASH. CONFLICT OF INTEREST DESCRIPTION: Dr. Jill Smith has a patent licensing agreement with Immune Therapeutics, Inc.
Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-ﬂight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.