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Epigenetics is an innovative discipline that aims to provide biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. The identification of therapeutic targets is of particular interest in cancer therapy for selecting groups of patients who may benefit most from an intervention. Understanding the relationships between the immune system and tumor cells has led to new immunotherapy-based therapies that provide a promising alternative to conventional cancer therapies. The aim of this study was to conduct an early assessment of a novel epigenetic signature (EPIMMUNE) that could predict response to programmed cell death protein 1 (PD-1) inhibitor immunotherapy in patients with non-small cell lung cancer (NSCLC).
We identified the novel epigenetic signature EPIMMUNE through the Early Awareness and Alert System, “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). A literature search of PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, The Cochrane Library, and the Centre for Reviews and Dissemination databases was conducted. Clinical studies on EPIMMUNE published in English or Spanish up to August 2019 were reviewed.
Only one retrospective study was found. Identification of EPIMMUNE was accomplished through interrogation of the DNA methylation status of CpG sites in 142 samples from adult patients with NSCLC who were treated with PD-1 inhibitors. EPIMMUNE was defined by 301 CpG sites whose methylation status was significantly associated with clinical response (progression-free and overall survival). No studies assessing the long-term clinical utility, impact on therapeutic decision making, or economic implications of EPIMMUNE were found.
The EPIMMUNE signature could provide an accurate and valid biomarker for identifying patients with NSCLC who may benefit from treatment with PD-1 inhibitors. However, the technology is under development, and there is only a single study on detecting the EPIMMUNE epigenetic profile and identifying the DNA methylation profiles associated with increased survival after PD-1 inhibitor therapy. More diagnostic accuracy studies and prospective, long-term trials are needed to evaluate the clinical impact this technology may have on therapeutic decision making. Given the limited evidence available, further research is needed before the technology can be disseminated.
Pulses such as peas, beans or lentils are one of the most complete foods at the nutritional level; however, they are one of the most often neglected foods in the diets of university students. Entrance to university translates into a major lifestyle change for many young people, and the habits acquired or cemented at this time will remain into adulthood. The objective of this study is to analyse the association between personal/sociodemographic factors, dietary intake of other food groups and the consumption of pulses in first-year university students. This cross-sectional study is part of the UniHcos project, a multicentre study of multipurpose prospective cohorts in eleven Spanish universities. Data from 9862 university students were collected through an online self-questionnaire completed by all students who met the selection criteria and agreed to participate in the project during the 2011–2018 academic years. Of students, 75·8 % presented an inadequate (≤2 times/week) consumption of pulses. Living outside the family home in either a student residence (OR 0·76; 95 % CI 0·69, 0·84) or rental (OR 0·81; 95 % CI 0·70, 0·95) decreased the compliance with recommendations on the consumption of pulses. Low consumption of pulses is seemingly not restricted to a specific profile or dietary pattern among university students, and no specific focus group for intervention can be identified. Policies promoting the consumption of pulses among the university population as a whole are necessary to increase compliance rates with the dietary recommendations.
Non-communicable chronic diseases (NCCDs) are the main cause of morbidity and mortality globally. Demographic aging has resulted in older populations with more complex healthcare needs. This necessitates a multilevel rethinking of healthcare policies, health education and community support systems with digitalization of technologies playing a central role. The European Innovation Partnership on Active and Healthy Aging (A3) working group focuses on well-being for older adults, with an emphasis on quality of life and healthy aging. A subgroup of A3, including multidisciplinary stakeholders in health care across Europe, focuses on the palliative care (PC) model as a paradigm to be modified to meet the needs of older persons with NCCDs. This development paper delineates the key parameters we identified as critical in creating a public health model of PC directed to the needs of persons with NCCDs. This paradigm shift should affect horizontal components of public health models. Furthermore, our model includes vertical components often neglected, such as nutrition, resilience, well-being and leisure activities. The main enablers identified are information and communication technologies, education and training programs, communities of compassion, twinning activities, promoting research and increasing awareness amongst policymakers. We also identified key ‘bottlenecks’: inequity of access, insufficient research, inadequate development of advance care planning and a lack of co-creation of relevant technologies and shared decision-making. Rethinking PC within a public health context must focus on developing policies, training and technologies to enhance person-centered quality life for those with NCCD, while ensuring that they and those important to them experience death with dignity.
The present study evaluated the effect of binder of sperm protein 1 (BSP1) and/or heparin on in vitro bovine capacitation and fertilization rates using epididymal and ejaculated bovine sperm. Frozen–thawed sperm were selected and used in the following treatments. Control group: Fert-TALP medium without heparin; heparin (HEP) group: Fert-TALP with heparin (10 UI/ml); BSP1 group: Fert-TALP medium with BSP1 (10 µg/ml for ejaculated sperm; 40 µg/ml for epididymal sperm); HEP + BSP1 group: Fert-TALP medium with heparin (5 UI/ml) and BSP1 (5 µg/ml for ejaculated sperm; 20 µg/ml for epididymal sperm) and determined in vitro capacitation rates in different interval times (0, 15, 30 and 60 min) using the chlortetracycline ﬂuorescence (CTC) method. Also, we evaluated the development rates of oocytes fertilized with ejaculated or epididymal sperm into the same treatments. Capacitation was greater and faster when ejaculated sperm were treated for 60 min with heparin compared with other treatments. However, developmental rates were similar in all treatments. For epididymal sperm, the treatments with BSP1 presented higher capacitation and fertilization rates compared with heparin (P < 0.05). The effects of heparin + BSP1 on capacitation and developmental rates did not cause any increase in capacitation or blastocyst rates compared with other groups for ejaculated or epididymal sperm. In conclusion, this study confirmed that either BSP1 and heparin can be used as capacitator agents for bovine ejaculated sperm during IVF. However, BSP1 seems to be more efficient compared with heparin for epididymal sperm. Furthermore, BSP1 and heparin have no synergic effects on sperm capacitation.
During menopause, women undergo a series of physiological changes that include a redistribution of fat tissue. This study was designed to investigate the effect of adding 10 g of cocoa-rich chocolate to the habitual diet of postmenopausal women daily on body composition. We conducted a 6-month, two-arm randomised, controlled trial. Postmenopausal women (57·2 (sd 3·6) years, n 132) were recruited in primary care clinics. Participants in the control group (CG) did not receive any intervention. Those of the intervention group (IG) received 10 g daily of 99 % cocoa chocolate in addition to their habitual diet for 6 months. This quantity comprises 247 kJ (59 kcal) and 65·4 mg of polyphenols. The primary outcomes were the between-group differences in body composition variables, measured by impendancemetry at the end of the study. The main effect of the intervention showed a favourable reduction in the IG with respect to the CG in body fat mass (–0·63 kg (95 % CI –1·15, –0·11), P = 0·019; Cohen’s d = –0·450) and body fat percentage (–0·79 % (95 % CI –1·31, –0·26), P = 0·004; Cohen’s d = –0·539). A non-significant decrease was also observed in BMI (–0·20 kg/m2 (95 % CI –0·44, 0·03), P = 0·092; Cohen’s d = –0·345). Both the body fat mass and the body fat percentage showed a decrease in the IG for the three body segments analysed (trunk, arms and legs). Daily addition of 10 g of cocoa-rich chocolate to the habitual diet of postmenopausal women reduces their body fat mass and body fat percentage without modifying their weight.
Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
How can societies restrain their coercive institutions and transition to a more humane criminal justice system? We argue that two main factors explain why torture can persist as a generalized practice even in democratic societies: weak procedural protections and the militarization of policing, which introduces strategies, equipment, and mentality that treats criminal suspects as though they were enemies in wartime. Using a large survey of the Mexican prison population and leveraging the date and place of arrest, this paper provides causal evidence about how these two explanatory variables shape police brutality. Our paper offers a grim picture of the survival of authoritarian policing practices in democracies. It also provides novel evidence of the extent to which the abolition of inquisitorial criminal justice institutions—a remnant of colonial legacies and a common trend in the region—has worked to restrain police brutality.
Fire and grazing are large-scale disturbances that shape the structure and function of open habitats. In temperate grasslands of southern South America, fire is used as a management tool to control tussock grasses and improve forage quality. In this study, we examined if fire and two of its components (heat and smoke) affect germination from the soil seed bank of a temperate grassland in Uruguay. Soil samples were extracted from a recently burned site and from an adjacent area that had not been burned for at least 4 years. The latter was subjected to four treatments: (1) heat shock, (2) smoke, (3) heat shock and smoke and (4) control. The samples were placed in a germination chamber and germination was recorded for 140 days. Field burn was the treatment that differed most from the control. This treatment produced a significant increase in density and richness of germinants and the germination peak preceded those of the remaining treatments. The three treatments involving fire-related cues did not affect the seedling richness and density, but the germination of some individual species was enhanced by some of them, mainly those in which the seeds were smoked. Our results show that fire and its components stimulate the germination of some species of the Río de la Plata grasslands, contrary to what had been observed previously in the region. We also suggest that, unlike Mediterranean-type systems, other fire cues, alone or in combination with heat and smoke, may promote germination after a fire event.
OBJECTIVES/GOALS: To determine the relationship among serum concentration of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and mortality in community-acquired pneumonia (CAP) patients. METHODS/STUDY POPULATION: This is a multicenter 2-year cohort study in Spain, designed to better understand the role of sTWEAK concentrations in CAP patients. CAP patients were prospectively enrolled in two University hospitals and sTWEAK was measured within the first 24 hours of ICU admission. Samples were collected and stored for laboratory analyses. To detect sTWEAK in human samples, we used a commercially available ELISA kit following manufacturer’s instructions. Demographic patients’ characteristics and ICU mortality were prospectively collected. Descriptive statistics and logistical regressions were used to assess the proposed aims. RESULTS/ANTICIPATED RESULTS: A total of forty-three patients were included in the study (10 healthy users, 10 uninfected controls and 23 CAP patients). In comparison to healthy volunteers, patients admitted to the hospital (both, infected and non-infected) had lower level of sTWEAK. During hospital admission, 7 (17%) patients died. Patients whom died during ICU stay due to CAP, had significantly lower levels of sTWEAK when comparing with patients whom survived (Median [IQR]; 509.35 [357.49, 953.92] Vs 1103.03 [716.93, 1663.16]; p = 0.015). In contrast, patients that developed shock did not have different concentrations of sTWEAK (Median [IQR]; 1008.04 [531.87, 1390.80] Vs 1062.29 [575.24, 1598.83], p = 0.84). DISCUSSION/SIGNIFICANCE OF IMPACT: Community-acquired pneumonia (CAP) is the first cause of death in underdeveloped countries. CAP is a pulmonary infection that creates a proinflammatory environment not just locally but also systemically, secondary to upregulation of molecular cascades with a wide variety of proteins being released perpetuating this inflammation and tissue damage. Several of these molecules have been described and linked to a greater risk of inhospital complications, longer length of hospital stay and mortality. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF-alpha superfamily, involved in immune response, cell growth, angiogenesis, NF-kB activation and apoptosis induction in tumor cells. It is known that serum-TWEAK plays a role in inflammatory processes, however, its behavior is unknown in patients with CAP. Therefore, this study aims to identify whether there is a relationship between serum concentration of TWEAK and prognosis in CAP patients. To our knowledge, this is the first study to shown that concentration of sTWEAK within the first 24 hours of ICU admission is lower in patients with CAP. Moreover, patients whom died during ICU admission due to CAP, have lower sTWEAK levels. This biomarker may identify patients at higher risk of dying due to CAP and may represent severe CAP. However, further studies are needed to confirm these findings.
Maternal obesity (MO) during pregnancy and lactation leads to maternal and offspring metabolic dysfunction. Recent research has suggested that probiotics might be a novel approach to counteract these unwanted MO effects. The aim of this research was to analyze the impact of Leuconostoc SD23, a probiotic isolated from aguamiel (traditional Mexican drink), on MO metabolism in rats at the end of lactation (21 days). From weaning through lactation, control female Wistar rats (C) ate chow (5% fat) or high-energy obesogenic diet (MO; 25% fat). Half the C and MO mothers received a daily dose (1 × 1010 CFU/ml) of probiotic orally, control with probiotic (CP) and MO with probiotic (MOP), 1 month before mating and through pregnancy and lactation. Histological analyses of the liver, white adipose tissue and small intestine, body composition, glucose, insulin, triglycerides, and leptin were determined in mothers at the end of lactation. Maternal weight during pregnancy was greater in MO than C mothers, but similar at the end of lactation. Probiotic intervention had no effect on maternal weight. However, at the end of lactation, percentage of body fat was higher in MO than C, CP, and MOP. Serum glucose, homeostasis model assessment of insulin resistance, and triglycerides were higher in MO versus C, CP, and MOP. MO small intestine villus height was higher versus MOP, C, and CP. Leuconostoc SD23 did not present adverse effects in C. Conclusions: maternal administration of Leuconostoc SD23 has beneficial effects on maternal metabolism, which holds possibilities for preventing adverse offspring metabolic programming.
Costa Rica is near malaria elimination. This achievement has followed shifts in malaria health policy. Here, we evaluate the impacts that different health policies have had on malaria transmission in Costa Rica from 1913 to 2018. We identified regime shifts and used regression models to measure the impact of different health policies on malaria transmission in Costa Rica using annual case records. We found that vector control and prophylactic treatments were associated with a 50% malaria case reduction in 1929–1931 compared with 1913–1928. DDT introduction in 1946 was associated with an increase in annual malaria case reduction from 7.6% (1942–1946) to 26.4% (1947–1952). The 2006 introduction of 7-day supervised chloroquine and primaquine treatments was the most effective health policy between 1957 and 2018, reducing annual malaria cases by 98% (2009–2018) when compared with 1957–1968. We also found that effective malaria reduction policies have been sensitive to natural catastrophes and extreme climatic events, both of which have increased malaria transmission in Costa Rica. Currently, outbreaks follow malaria importation into vulnerable areas of Costa Rica. This highlights the need to timely diagnose and treat malaria, while improving living standards, in the affected areas.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
The aim of the present study is to see if the changes in the regional cerebral blood flow (rCBF) experienced by restrictive anorexia nervosa (AR) and bulimia nervosa (BN) patients, following the exposure to their own body image, persist at follow-up.
Three single photon emission computed tomography (SPECT) were performed on nine patients with a DSM-IV diagnosis of AR, 13 with BP, and 12 controls: at rest, following a neutral stimulus, and after exposure to their previously filmed whole body image. Body dissatisfaction was measured by means of the Body Dissatisfaction Questionnaire (BSQ). One year later the same assessment was repeated.
Following the exposure to their own body image, BN showed an increase in body dissatisfaction, which was associated with the increase in the rCBF of the Right Temporal Area. Those changes persisted at follow-up.
More specific long term therapies are needed for the treatment of the averse response showed by ED patients to their own body image exposure that is associated with the hyperactivation of the right temporal area when they are confronted with their whole body image.
Although the epidemiology of Eating Disorders (ED) has been highly developed in Spain, further research considering false negatives and also the prevalence of these disorders in males are needed. They were the aims of the present study.
One thousand and seventy six adolescents (500 males and 576 females) participated in a two-stage survey. At the age of 13, apart from exploring numerous clinical and psychosocial variables, they were assessed by means of self-administered screening instruments, the eating attitude test (EAT), bulimic investigatory test Edinburgh (BITE), and body shape questionnaire (BSQ). The subjects were interviewed again 2 years later. Afterwards, 159 probable cases and 150 controls were interviewed by means of the structured interview SCAN.
Prevalence of ED in adolescents was 3.71% (95% CI 2.58–4.83; 6.4% of females, 0.6% of males): anorexia nervosa 0.1%, bulimia nervosa 0.75%, eating disorder not otherwise specified (EDNOS) = 2.88%. The rate of false negative was 2.6% of the control group and most of them were EDNOS.
The prevalence of ED obtained in our study, higher than others found in previous Spanish research, and a relatively high percentage of false negatives both indicate that up to now the prevalence of ED in Spanish adolescents could be underestimated.
To assess antipsychotic medication in the treatment of schizophrenia, based on trial drop-out rates.
The studies included were randomised controlled trials that compared any of the four clinically best-established atypical antipsychotics (quetiapine, olanzapine, risperidone or clozapine) against either of two typical antipsychotics regarded as the gold standard (haloperidol or chlorpromazine).
Meta-analysis indicated less risk of all-cause patient withdrawal from atypical medication trials where dosage was flexible, in both the short, relative risk (RR) 0.70 (95% CI 0.64–0.76), P < 0.00001, and long term, RR 0.72 (0.65–0.80), P < 0.00001. Similar results were observed for withdrawal due to adverse events, RR: 0.54 (0.41–0.72), P < 0.0001. Nevertheless, the favourable effects of atypical medication disappeared in trials relying on fixed dosage.
We detected a significant positive effect in terms of the outcome of treatment discontinuation for atypical versus typical medication, though only where the use of flexible rather than fixed doses (closer to an experimental control situation) was possible.