Genetics

Is Gcn4-induced autophagy the ultimate downstream mechanism by which hormesis extends yeast replicative lifespan? Abstract The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is still little understanding of the underlying molecular mechanisms involved. One unifying theme is that most, if not all, interventions that extend replicative lifespan induce "hormesis", where a little inflicted damage makes cells more able to resist similar challenges in the future. One of the many cellular changes that occur during hormesis is a global reduction in protein synthesis, which has been linked to enhanced longevity in many organisms. Our recent study in budding yeast found that it was not the reduction in protein synthesis per se, but rather the subsequent induction of the conserved Gcn4 transcriptional regulator and its ability to induce autophagy that was responsible for extending replicative lifespan. We propose that Gcn4-dependent induction of autophagy occurring downstream of reduced global protein synthesis may be a unifying molecular mechanism for many interventions that extend replicative lifespan.

More than just a phase: the search for membraneless organelles in the bacterial cytoplasm Abstract The bacterial cytoplasm, once thought to be a relatively undifferentiated reaction medium, has now been recognized to have extensive microstructure. This microstructure includes bacterial microcompartments, inclusion bodies, granules, and even some membrane-bound vesicles. Several recent papers suggest that bacteria may also organize their cytoplasm using an additional mechanism: phase-separated membraneless organelles, a strategy commonly used by eukaryotes. Phase-separated membraneless organelles such as Cajal bodies, the nucleolus, and stress granules allow proteins to become concentrated in sub-compartments of eukaryotic cells without being surrounded by a barrier to diffusion. In this review, we summarize the known structural organization of the bacterial cytoplasm and discuss the recent evidence that phase-separated membraneless organelles might also play a role in bacterial systems. We specifically focus on bacterial ribonucleoprotein complexes and two different protein components of the bacterial nucleoid that may have the ability to form subcellular partitions within bacteria cells.

Linking the organization of DNA replication with genome maintenance Abstract The spatial and temporal organization of genome duplication, also referred to as the replication program, is defined by the distribution and the activities of the sites of replication initiation across the genome. Alterations to the replication profile are associated with cell fate changes during development and in pathologies, but the importance of undergoing S phase with distinct and specific programs remains largely unexplored. We have recently addressed this question, focusing on the interplay between the replication program and genome maintenance. In particular, we demonstrated that when cells encounter challenges to DNA synthesis, the organization of DNA replication drives the response to replication stress that is mediated by the ATR/Rad3 checkpoint pathway, thus shaping the pattern of genome instability along the chromosomes. In this review, we present the major findings of our study and discuss how they may bring new perspectives to our understanding of the biological importance of the replication program.

Role of Mediator in virulence and antifungal drug resistance in pathogenic fungi Abstract Mediator complex has recently emerged as an important regulator of gene expression in pathogenic fungi. Mediator is a multi-subunit complex of polypeptides involved in transcriptional activation in eukaryotes, with roles including preinitiation complex (PIC) assembly and chromatin remodeling. Within the last decade, Mediator has been shown to play an integral role in regulating virulence gene expression and drug resistance in human fungal pathogens. In some fungi, specific Mediator subunits have been shown to be required for virulence. In Candida species, duplication and expansion of Mediator subunit encoding genes has occurred on at least three occasions (CgMED15 in C. glabrata and MED2/TLO in C. albicans and C. dubliniensis) suggesting important roles for Mediator in the evolution of these pathogens. This review summarises recent developments in our understanding of Mediator in fungal pathogens and the potential for the development of therapeutic drugs to target Mediator functions.

Disturbance in biosynthesis of arachidonic acid impairs the sexual development of the onion blight pathogen Stemphylium eturmiunum Abstract The formation of sexual fruiting bodies for plant pathogenic fungi is a key strategy to propagate their progenies upon environmental stresses. Stemphylium eturmiunum is an opportunistic plant pathogen fungus causing blight in onion. This self-fertilizing filamentous ascomycete persists in the soil by forming pseudothecia, the sexual fruiting body which helps the fungus survive in harsh environments. However, the regulatory mechanism of pseudothecial formation remains unknown. To uncover the mechanism for pseudothecial formation so as to find a practical measure to control the propagation of this onion pathogen, we tentatively used DNA methyltransferase inhibitor 5-azacytidine (5-AC) to treat S. eturmiunum. 5-AC treatment silenced the gene-encoding monoacylglycerol lipase (magl) concomitant with the presence of the inheritable fluffy phenotype and defectiveness in pseudothecial development. Moreover, the silence of magl also resulted in a reduction of arachidonic acid (AA) formation from 27 ± 3.1 µg/g to 9.5 ± 1.5 µg/g. To correlate the biosynthesis of AA and pseudothecial formation, we created magl knockdown and overexpression strains. Knockdown of magl reduced AA to 11 ± 2.4 µg/g, which subsequently disabled pseudothecial formation. In parallel, overexpression of maglincreased AA to 37 ± 3.4 µg/g, which also impaired pseudothecial formation. Furthermore, exogenous addition of AA to the culture of magl-silenced or magl knockdown strains rescued the pseudothecial formation but failed in the gpr1 knockdown strain of S. eturmiunum, which implicates the involvement of AA in signal transduction via a putative G protein-coupled receptor 1. Thus, AA at a cellular level of 27 ± 3.1 µg/g is essential for sexual development of S. eturmiunum. Disturbance in the biosynthesis of AA by up- and down-regulating the expression of magl disables the pseudothecial development. The specific requirement for AA in pseudothecial development by S. eturmiunum provides a hint to curb this onion pathogen: to impede pseudothecial formation by application of AA.

Synergy of Hir1, Ssn6, and Snf2 global regulators is the functional determinant of a Mac1 transcriptional switch in S. cerevisiae copper homeostasis Abstract To gain insights on the transcriptional switches that modulate proper copper homeostasis in yeast, we have examined in detail functional interactions of the relevant transcriptional activator Mac1. We identified Hir1 transcriptional repressor and histone chaperone as a Mac1-interacting protein. This association directly recruits Hir1 on a Mac1 target, CTR1 promoter, quantitatively under induction conditions. We also found Hir1 interacting directly with a previously unknown partner, the Ssn6 (Cyc8) co-regulator. On the non-induced CTR1 promoter, a Hir1 transcriptional activation function was revealed, in the absence of Ssn6, which was dependent on the presence of Snf2 (Swi2) nucleosome remodeler. Moreover, Ssn6 was identified as a Mac1-dependent prominent repressor of CTR1 transcription, antagonizing Snf2 occupancy. Transcriptional induction by copper depletion was effected by the quantitative recruitment of Snf2 directed mainly by Mac1 and redundantly by the quantitatively accumulated Hir1 and Ssn6 pair. Our analysis showed that the activation-effecting chromatin remodeling of CTR1 was due to Snf2 and not to the Hir1 histone chaperone activity or ability to regulate histone levels and stoichiometry. Following initiation, Hir1 and Snf2, but not Ssn6, were found to associate also with the actively transcribing CTR1 coding region, where Hir1 followed the pattern of the elongating RNA polymerase II. Therefore, we have shown that, at the CTR1 gene, in association with Mac1 DNA-binding transcriptional activator, the distinct and alternate genetic and physical collaboration of three global regulators modulates the transcriptional state of a switch involved in copper homeostasis.

Versatility of the Mec1 ATM/ATR signaling network in mediating resistance to replication, genotoxic, and proteotoxic stresses Abstract The ataxia-telangiectasia mutated/ATM and Rad3-related (ATM/ATR) family proteins are evolutionarily conserved serine/threonine kinases best known for their roles in mediating the DNA damage response. Upon activation, ATM/ATR phosphorylate numerous targets to stabilize stalled replication forks, repair damaged DNA, and inhibit cell cycle progression to ensure survival of the cell and safeguard integrity of the genome. Intriguingly, separation of function alleles of the human ATM and MEC1, the budding yeast ATM/ATR, were shown to confer widespread protein aggregation and acute sensitivity to different types of proteotoxic agents including heavy metal, amino acid analogue, and an aggregation-prone peptide derived from the Huntington's disease protein. Further analyses unveiled that ATM and Mec1 promote resistance to perturbation in protein homeostasis via a mechanism distinct from the DNA damage response. In this minireview, we summarize the key findings and discuss ATM/ATR as a multifaceted signalling protein capable of mediating cellular response to both DNA and protein damage.

On the duration of the microbial lag phase Abstract When faced with environmental changes, microbes enter a lag phase during which cell growth is arrested, allowing cells to adapt to the new situation. The discovery of the lag phase started the field of gene regulation and led to the unraveling of underlying mechanisms. However, the factors determining the exact duration and dynamics of the lag phase remain largely elusive. Naively, one would expect that cells adapt as quickly as possible, so they can resume growth and compete with other organisms. However, recent studies show that the lag phase can last from several hours up to several days. Moreover, some cells within the same population take much longer than others, despite being genetically identical. In addition, the lag phase duration is also influenced by the past, with recent exposure to a given environment leading to a quicker adaptation when that environment returns. Genome-wide screens in Saccharomyces cerevisiae on carbon source shifts now suggest that the length of the lag phase, the heterogeneity in lag times of individual cells, and the history-dependent behavior are not determined by the time it takes to induce a few specific genes related to uptake and metabolism of a new carbon source. Instead, a major shift in general metabolism, and in particular a switch between fermentation and respiration, is the major bottleneck that determines lag duration. This suggests that there may be a fitness trade-off between complete adaptation of a cell's metabolism to a given environment, and a short lag phase when the environment changes.

SET domains and stress: uncovering new functions for yeast Set4 Abstract Chromatin dynamics are central to the regulation of gene expression and genome stability, particularly in the presence of environmental signals or stresses that prompt rapid reprogramming of the genome to promote survival or differentiation. While numerous chromatin regulators have been implicated in modulating cellular responses to stress, gaps in our mechanistic understanding of chromatin-based changes during stress suggest that additional proteins are likely critical to these responses and the molecular details underlying their activities are unclear in many cases. We recently identified a role for the relatively uncharacterized SET domain protein Set4 in promoting cell survival during oxidative stress in Saccharomyces cerevisiae. Set4 is a member of the Set3 subfamily of SET domain proteins which are defined by the presence of a PHD finger and divergent SET domain sequences. Here, we integrate our new observations on the function of Set4 with known roles for other related family members, including yeast Set3, fly UpSET and mammalian proteins MLL5 and SETD5. We discuss outstanding questions regarding the molecular mechanisms by which these proteins control gene expression and their potential contributions to cellular responses to environmental stress.

Quiescence, an individual journey Abstract Quiescence is operationally characterized as a temporary and reversible proliferation arrest. There are many preconceived ideas about quiescence, quiescent cells being generally viewed as insignificant sleeping G1 cells. In fact, quiescence is central for organism physiology and its dysregulation involved in many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. This diversity challenges not only quiescence uniformity but also the universality of the molecular mechanisms beyond quiescence regulation. In this mini-perspective, we discuss recent advances in the concept of quiescence, and illustrate that this multifaceted cellular state is gaining increasing attention in many fields of biology.

Police and Criminal Psychology

The Eyes Really Do Have It: Attribution of Character in the Eyes of Killers Abstract "The eyes are the window of the soul" is a staple cliché in many cultures, but is there any truth to this concept, of any potential importance in the forensic realm? The present study addressed this question in two experiments. It was shown that observation of the eyes and ocular regions of normal control individuals, and of serial killers, enabled average respondents to distinguish these individuals clearly in terms of trustworthiness, likability, and general "goodness." In both experiments, and based on nothing but this observation, serial killers were consistently rated lower on all three indices. No sex or individual differences were observed in this pattern of results. These findings are consistent with current evolutionary and cognitive theory, and may highlight the importance of the perception of defendants by witnesses and jurors in criminal proceedings.

An Interview Study of the Experiences of Police Officers in Regard to Psychological Contract and Wellbeing Abstract In this paper, it is argued that the psychological contract (PC) could provide rich insights into the understanding of employee and employer relations within the police and the stress and wellbeing of officers. Eighteen semi-structured interviews were conducted with active, full-time police officers and these were analysed using framework analysis. More than 100 base-units of meaning were identified which were categorised into six main themes namely 'Motivation', 'Mutual obligations', 'Stressors', 'Negative consequences', 'Mediators' and 'Positive impact of the job'. From the interviews, it was apparent that some officers are experiencing PC breach and that this was having a negative impact on their wellbeing. These findings are considered and avenues for improving the situation are discussed.

An Examination of Mock Jurors' Judgments in Familiar Identification Cases Abstract The present studies examined jurors' perceptions of "familiar" identifications—that is, identifications where an eyewitness espouses prior exposure to the perpetrator. In two studies, undergraduate mock jurors (total N = 760) read a criminal case vignette that manipulated whether the eyewitness claimed to have prior exposure to the perpetrator (and how much). Study 1 additionally manipulated the eyewitness' subsequent lineup identification confidence level, finding that confidence (but not familiarity) increased participants' beliefs in guilt and identification accuracy. Study 2 employed a stronger familiarity manipulation while additionally manipulating how long before the crime the prior exposure occurred and the viewing conditions during the crime. Results indicated that this stronger familiar identification was perceived as more accurate and indicative of guilt than the stranger identification, but only in cases of minimal prior exposure. And while viewing conditions independently affected legal judgments, it rarely moderated these familiarity effects. Theoretical and applied implications are discussed.

Memory for Cars Among a Female Population: Is the Cognitive Interview Beneficial in Reducing Stereotype Threat? Abstract The first aim of the present study was to assess the effect of stereotype threat on recall of a visual event involving cars by female witnesses. It was expected that stereotyped women (by the interviewer) would provide a poorer description of the cars involved than non-stereotyped women. The second aim was to test if a modified cognitive interview (MCI) could reduce this negative effect. We expected that MCI reduce the harmful effect of stereotype threat on women's recall in comparison with a control interview (CI). Sixty-nine women watched a videotape of a criminal event involving cars. Two days later, they had to recall the to-be-remembered event and were given either a neutral or a threatening (= stereotyping) instruction. They were then interviewed using a CI or an MCI. Results showed that threatened women were less accurate and made more errors and confabulations than non-threatened women. They also produced more incorrect details about the cars involved. Moreover, the MCI elicited more correct details but without impairing accuracy for both threatened and non-threatened women. Our study supports the existing evidence that women's testimony may be affected by the social context and highlights the need to use the MCI during judicial interviews.

Exploring the Validity of Behavioral Cues Predictive of Physically Resisting Arrest Abstract Police officers are sometimes trained that certain behavioral cues predict impending violent behavior. Additionally, surveys revealed many hold perceptions that these behavioral predictors of violence are valid, yet empirical evidence of validity is sparse and contradictory. The present study used frame-by-frame analysis of videotaped police arrest encounters to explore the validity of nine behavioral cues in predicting whether the arrestee violently resisted arrest. The results revealed that four of the nine behaviors were predictive of violence, yet notable variation occurred across racial groups. The validity of the remaining behavioral cues remains equivocal at this time.

Predictors of Mental Health Stigma among Police Officers: the Role of Trauma and PTSD Abstract Police officers are both at risk of exposure to trauma and experiencing PTSD and are more likely to come into contact with people with mental illness than community members. As a result, the extent and predictors of mental health stigma is an issue of concern among police officers; however, little prior research on stigma has focused on police officers. The present study examined the predictors of mental health stigma among police officers, including the experience of trauma and PTSD symptoms. Active duty police officers (N = 296) were recruited through an online survey and completed measures of trauma exposure, PTSD symptoms, and a number of dimensions of stigma (negative stereotypes, attributions, intended behavior, and attitudes toward seeking help). Findings supported that police officers experience high rates of trauma exposure and higher rates of current PTSD than the general population. Endorsement of negative stereotypes about people with mental illness was higher among police officers than the general population. Contrary to what was expected, officers meeting criteria for current PTSD endorsed more stigma about mental illness, even when controlling for common demographic predictors of stigma, including gender and knowing someone with a mental illness. Findings have important implications for the training of police officers regarding mental illness.

Challenges for Police Leadership: Identity, Experience, Legitimacy and Direct Entry Abstract The police service in England and Wales has developed a new approach to police leadership where individuals from outside of the police service can now enter directly to leadership ranks. Previous research identified that officers place great value on being led by someone who has experience of being a police officer. Adopting a social identity perspective, the current paper reports on quantitative and qualitative data about police officer views on direct entry and existing police leadership captured as part of a wider national survey (N = 12,549) of police officers in England and Wales. The paper identifies the importance that shared identity and credibility play in police follower/leadership relationships. It argues that direct-entry police leaders face credibility issues linked to their lack of shared police identity but also that serving officers perceive existing leaders to be poor because they believe they have forgotten what it is like to be a police officer. This paper develops a new theoretical and empirical approach to police leadership utilizing social and organizational psychology theory and research. The paper suggests that if police leaders understand police identity, then they can create propitious conditions within which police officers will follow their leaders.

Effectiveness of Emotional Fitness Training in Police Abstract This paper reports the effectiveness of Emotional Fitness Training launched by the Hong Kong Police Force (HKPF) in enhancing four aspects of emotional fitness in police officers, namely resilience, positive emotions, cognitive flexibility, and emotional well-being. The Emotional Fitness Training workshops evaluated were conducted in three phases. Phase 1 workshops were offered to junior police officers and frontline commanders for voluntary participation. Phase 2 workshops were offered to supervisory staff with train-the-trainer purposes. Phase 3 workshops were also offered to supervisory staff, but as a regular training-day activity to let the staff learn to deliver training packages. A total of 300 respondents participated in the program evaluation exercises, and these were assessed before the workshop (pretest), immediately after the workshop (posttest), and 10 weeks after the workshop took place (10 weeks posttest). Most of the seven measures registered statistically significant improvements compared to pretest in all three training phases. We noted varying effectiveness in the three phases of training that could be attributed to the amount of out-of-class practice engaged in by the participants. We measured professional pride and organizational commitment 1 year after the workshop and found that workshop participants reported greater pride and commitment compared with nonparticipants of the same rank. Among workshop participants, those with better emotional fitness also reported greater pride and commitment. The findings provide strong evidence supporting the effectiveness of emotional fitness training to enhance resilience, positive emotions, cognitive flexibility, and emotional well-being, and more importantly, they strengthen professional pride and organizational commitment even 1 year after training.

Secondary Traumatic Stress: Prevalence and Symptomology Amongst Detective Officers Investigating Child Protection Cases Abstract It has been increasingly recognised that individuals exposed to the trauma of others within their professional roles can be affected by secondary traumatic stress (STS). Despite this recognition, there is a dearth of literature examining the prevalence of secondary traumatic stress amongst police officers in the UK. This study aims to meet this gap. Sixty-three Detective Officers from Family Protection Units (FPU(s)), primarily engaged in child protection/abuse investigations, self-reported their experiences and symptoms associated with STS through a questionnaire. Findings indicate that over half of the respondents experienced STS symptoms with 11% reporting levels of symptoms that were in the high or severe range. This study is significant in that it provides empirical evidence of issues that have so far been little documented in the UK and considers the implications for policing policy and practice in terms of the health and well-being of serving police officers.

The Impact of Childhood Abuse on Adult Male Prisoners: a Systematic Review Abstract Childhood abuse has been associated with a broad range of adverse cognitive, emotional, behavioural and social outcomes. Research specific to adult male prisoners indicates an association between childhood abuse experiences and crime recidivism, mental health issues, substance abuse and interpersonal difficulties. The purpose of this review was to conduct a systematic investigation of databases, using predetermined search strategies and key terms, in order to collate and describe the current literature examining the impact childhood abuse has on the functioning of adult males incarcerated for criminal offences. The investigation yielded 217 studies, which, through further analysis, was reduced to a total of 17 peer-reviewed articles. A narrative synthesis summary of findings was subsequently carried out. The findings identified four main themes, revealing the means by which childhood abuse impacts the functioning of adult male prisoners: mental health difficulties, crime and recidivism, substance use and behaviour/personality issues. In addition, less robust themes of revictimisation and adult life functional difficulties were revealed. Lastly, the noteworthy limitations of the collated research and the clinical implications for the findings were discussed.

Functional Foods

Insulin resistance accelerated the clearance of resveratrol: A note of caution Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Zhixia Qiu, Qiuyan Liu, Jiaojiao Yu, Yu Dai, Xiaonan Li, Fang Huang, Ning Li Abstract Trans-resveratrol (RES), a well-known polyphenol exerts various health-promoting benefits, including glucose homeostasis maintenance. Here, we have investigated the impact of insulin resistance (IR) on RES disposition. Rats were fed with 10%-fructose-water for 8 weeks for developing IR. The systemic exposure to RES significantly decreased (IR vs normal, AUC0-24h, 1.73, 3.79, 9.27 vs 2.50, 6.12, 12.6 μM∙h, 20, 50, 100 mg/kg, p < 0.05). Tissue exposures to RES and conjugates were significantly decreased. The accumulated amount of RES in urine of IR rats was significantly increased (IR vs normal, 44.1 vs 21.5 μmol). The expression of UDP-glucuronosyltransferases (UGT1a1, 1a6) was significantly up-regulated, whereas that of sulfotransferases (SULT1a1, 1a2, 1a3) was down-regulated in specific tissues. Down-regulation of specific transporters (MRP2, BCRP, OATP1b2, OAT1, OAT3) might alter RES pharmacokinetics. The altered pharmacokinetic behavior of RES was largely attributed to its higher urinary excretion in IR rats. Specific strategies are required for compensating these metabolic alterations. Graphical abstract

Anti-pancreatic-cancer effect of a newly bred cabbage line, Amtak-ssamchae, is mediated by a reduction in regulatory-T-cell recruitment Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Sunggun Kim, Soo Jeong Kim, Eun-Sang Jo, Kicheol Gil, Na-Yeon Kim, Ji Sung Park, Dongbok Park, So-Young Park, Kwang Woo Hwang Abstract We aimed to investigate possible anticancer effects of Amtak-ssamchae (a newly bred cabbage line containing more carotenoids) in an in vitro pancreatic-tumor cell model and an in vivo model (Panc02 cells). In an in vitroassay, Amtak-ssamchae significantly reduced the viability of Panc02 cells relative to normal ssamchae. Furthermore, an Amtak-ssamchae extract significantly reduced the tumor size in mice inoculated with Panc02 cells, and this effect was accompanied by changes in the cell population in/near the tumor and spleen. Treatment with the extract of the new cabbage line blocked regulatory-T-cell recruitment, which is known as the main pathological mechanism of action of pancreatic cancer to avoid host immunity. Additionally, Amtak-ssamchae (not the normal line) contained β-carotene (at 27.9 ± 2.1 μg/g). Thus, we suggest that the Amtak-ssamchae extract could be a resource for natural supplements and functional foods for combating pancreatic cancer. Graphical abstract

Enterococcus faecalis milk fermentates display antioxidant properties and inhibitory activity towards key enzymes linked to hypertension and hyperglycaemia Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Ken Graham, Rosemary Rea, Paul Simpson, Helena Stack Abstract In this study, Enterococcus faecalis milk fermentates were assayed for total phenolic content, related antioxidant activity and the inhibition of key enzymes linked to hypertension and hyperglycaemia. Of the 25 isolates, milk fermented with E. faecalis DPC5154 had the highest level of total phenolic compounds (739.06 µg GAE/ml) and demonstrated the highest level of Trolox Equivalent Antioxidant Activity (TEAA) based on DPPH radical scavenging activity and ferric reducing antioxidant power (271.27 TEAA (µM) and 272.75 TEAA (µM), respectively). Inhibition of Angiotensin Converting Enzyme (ACE) and α-glucosidase is considered a useful therapeutic approach in the management of hypertension and hyperglycaemia, respectively. Milk fermented with DPC5154 completely inhibited ACE and displayed the highest level of α-glucosidase inhibitory activity (33.41%). These studies provide in vitro evidence for the beneficial use of DPC5154 and other E. faecalis isolates for the generation of bioactive milk products with antioxidant, antihypertensive and anti-hyperglycaemic activity. Graphical abstract

Extruded sorghum (Sorghum bicolor L.) improves gut microbiota, reduces inflammation, and oxidative stress in obese rats fed a high-fat diet Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Andressa Rodrigues de Sousa, Maria Eliza de Castro Moreira, Mariana Grancieri, Renata Celi Lopes Toledo, Fernanda de Oliveira Araújo, Hilário Cuquetto Mantovani, Valéria Aparecida Vieira Queiroz, Hercia Stampini Duarte Martino Abstract The aim of this study was to investigate the effects of extruded sorghum flour (ESF) on rats fed with a high-fat diet (HFD) on gut microbiota modulation, inflammation, and oxidative stress. Male Wistar rats were fed a normal diet (AIN-93 M, n = 8), HFD (n = 8), or HFD plus ESF replacing 50% cellulose and 100% corn starch (HFDS50, n = 8) or HFD plus ESF replacing 100% cellulose and 100% corn starch (HFDS100, n = 8) for eight weeks. ESF improved the composition of intestinal microbiota by increasing the proportion of the Bacteroidetes phylum instead of the Firmicutes phylum. Furthermore, ESF reduced the concentrations of p65 NF-κB in liver, seric resistin, lipids peroxidation and increase the total antioxidant capacity of plasma, the expression of superoxide dismutase, and the heat shock protein 72. In conclusion, ESF improves the intestinal dysbiosis, inflammation and oxidative stress in obese rats fed a hyperlipid diet. Graphical abstract

Enhanced bioavailability of iron from spray dried whey protein concentrate-iron (WPC-Fe) complex in anaemic and weaning conditions Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Kamal Gandhi, Savita Devi, Priyae Brath Gautam, Rajan Sharma, Bimlesh Mann, Suvartan Ranvir, Khushbu Sao, Vanita Pandey Abstract The lower bioavailability of iron from the diet has led to iron deficiency and several ill-effects on health. The objective of this study was to assess the bioavailability of iron from spray dried whey protein concentrate-iron (WPC-Fe) complex in weaning and anaemic rats. Blood hemoglobin level, bioavailability, lipid profile, antioxidant status and concentration of iron delivery molecules were analysed under in vivo conditions. Hemoglobin level, % apparent digestibility coefficient and % retention/intake were increased in weaning and anaemic rats on 7th and 28th days. Additionally, WPC-Fe supplementation reduced nitric oxide (NO) production, maintained serum triglycerides, total cholesterol, LDL, VLDL and HDL-cholesterol. Simultaneously, it decreased the superoxide level and lipid peroxidation and increased the catalase activity. The level of iron delivery/transport molecules including liver and serum ferritin and transferrin concentration was enhanced. Thus, WPC-Fe complex could be a better and innovative organic iron fortificant with enhanced bioavailability of iron. Graphical abstract

Metabolic profiling and investigations on crude extract of Olea europaea L. leaves as a potential therapeutic agent against skin cancer Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Debabrata Majumder, Mousumi Debnath, K.V. Libin Kumar, Priyatosh Nath, Rahul Debnath, Chaitali Sarkar, G.B.K.S. Prasad, Yogesh Kumar Verma, Debasish Maiti Abstract Olive (Olea europaea L.) leaf extract (OLE) have shown therapeutic activity against different types of cancer. However, it is less known that olive leaf extract has anti myeloma activity. The in vitro cytotoxic activity of OLE was evaluated against mouse metastatic melanoma B16F10 cell lines. The extracts were analyzed for their antioxidant activity by DPPH radical scavenging activity and the presence of bioactive compounds by liquid chromatography-electrospray ionization-tandem mass spectrometry respectively. The aqueous OLE induced apoptosis of B16F10 cells through ERK 1/2 and p53 mediated pathway. The metabolic profiling of OLE showed 23 metabolites notably oleuropein aglycone, apigenin, luteolin, tyrosol, oleuropein and hydroxytyrosol. Oleuropein present in OLE may be responsible for disrupting the activation of ERK1/2 receptor in melanoma B16F10 cell lines. These findings pave path for further investigations of the structure and function at the molecular level to establish the anticancer activity of oleuropein in melanoma skin cancer. Graphical abstract

Modulation of Akt-p38-MAPK/Nrf2/SIRT1 and NF-κB pathways by wine pomace product in hyperglycemic endothelial cell line Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Gisela Gerardi, Mónica Cavia-Saiz, María D. Rivero-Pérez, María L. González-SanJosé, Pilar Muñiz Abstract Wine by-products show great potential as source of bioactive compounds that protect the vascular endothelial function by the modulation of both Nrf2 and Nf-κB pathways. This study investigates the pathways involved in the effects of a red wine pomace product (rWPP) against inflammatory and oxidative damage in hyperglycemic EA.hy926 endothelial cells. rWPP-digested fractions showed an inhibitory effect on IKK/IκBα/NF-κB pathway and a stimulatory effect on Akt-p38-MAPK/Nrf2 pathway with an impact on their antioxidant and anti-inflammatory downstream targets. In addition, the pathways regulation was also accompanied by downregulation of the gene expression of superoxide dismutase 2, cyclooxygenase 2 and NADPH oxidase 4. These results suggest the expression of SOD2 as an early adaptive response to the inflammatory effect mediated by NF-κB in hyperglycemic cells, and the treatment with the rWPP-digested fractions regulate this inflammatory process by Nrf2 pathway increased expression of antioxidant enzymes. Graphical abstract

Polyphenols from Morchella angusticepes Peck attenuate D-galactosamine/lipopolysaccharide-induced acute hepatic failture in mice Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Qiming Wang, Keke Lu, Fuhua Li, Lin Lei, Jichun Zhao, Surui Wu, Ran Yin, Jian Ming Abstract We investigated the effect of polyphenols extracted from M. angusticepes Peck (PMP) on D-galactosamine/lipopolysaccharide (D-GalN/LPS) induced acute hepatic failure (AHF) in mice. Results indicated that administration of PMP relieved the leakage of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The level of serum ALT was reduced in groups of P-H (800 mg PMP/kg BW) and P-L (400 mg PMP/kg BW) by 44.6% and 31.8%, respectively. RT-PCR and Western blot analyses showed that NF-E2-related factor 2 (Nrf2), PPARα, PPARγ gene and protein were up-regulated after injection D-GalN/LPS. In contrast, PMP pretreatment noticeably prevented D-GalN/LPS-induced hepatocyte apoptosis and steatosis. It suggested that PMP attenuated D-GalN/LPS-induced AHF in mice, which was likely attributed to the co-activation of Nrf2, PPARα, PPARγ and alleviating the oxidative stress reaction, reducing the body inflammatory response and regulating the lipid metabolism. Graphical abstract

Thelenota ananas saponin extracts attenuate the atherosclerosis in apoE−/− mice by modulating lipid metabolism Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Qi-An Han, Shiliang Jia, Kaifeng Li, Yinqiang Sui, Hui Hong, Xiuping Dong, Yongkang Luo, Beiwei Zhu Abstract As one of the most nutrient-rich marine species, Thelenota ananas has various effects, but its antiatherosclerosis activity has yet to be plumbed in depths. In this work, T. ananas saponin extracts were used to assess the effect on atherosclerosis development in the apoE−/− mice. In detail, the saponin treated groups clearly showed an inhibitory effect on the size of aortic atheromatous plaque, and the levels of serum lipid and inflammatory cytokines compared with the atherosclerosis model mice. Interestingly, the saponin extracts decreased the lipid profiles and oxidation in the visceral fat, and markedly altered the expressions of key proteins related to lipid synthesis and inflammation in the liver. Furthermore, saponin extracts promoted the diversity of the fecal bacterial colonies which has a close correlation with lipid metabolism. The results above revealed that T. ananassaponin extracts may be a beneficial natural resource for the prevention of atherosclerosis by modulating lipid metabolism. Graphical abstract

l-histidine and l-carnosine accelerate wound healing via regulation of corticosterone and PI3K/Akt phosphorylation in d-galactose-induced aging models in vitro and in vivo Publication date: July 2019 Source: Journal of Functional Foods, Volume 58 Author(s): Yerin Kim, Eunju Kim, Yuri Kim Abstract Impaired skin wound healing in the elderly can lead to medical issues and increased mortality. Although l-histidine and l-carnosine are potent anti-aging amino acids, the wound healing effects of these amino acids in aging remain to be elucidated. Here, we investigated the regenerative potential of l-histidine and l-carnosine in in vitro and in vivo aging models. l-histidine (1 mM), l-carnosine (10 mM), or a combination improved proliferation, migration, senescence, and epithelial-mesenchymal transition (EMT) in d-galactose-induced aged keratinocytes. An in vivo mouse aging model was established with injection of d-galactose (s.c. 500 mg/kg) daily for eight weeks. Supplementation with l-histidine (2 g/L), l-carnosine (2 g/L), or a combination improved collagen and wound healing with EMT markers, E-cadherin, N-cadherin, and MMP-2. These effects were concomitant with reduced circulating levels of corticosterone and increased PI3K/Akt phosphorylation. These results suggest that l-histidine and l-carnosine have the potential to facilitate wound healing in aging skin. Graphical abstract

Otorhinolaryngology, Head and Neck Diseases

Paradoxes of the French health care system Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): E. Babin, G. Grandazzi

Ileal migration of a salivary bypass tube in a dysphagic patient with bipolar disorder Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): S.D. Le Bon, A. Rodriguez Ruiz

Endoscopic lateralization of the vocal fold Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): C. Fabre, C.A. Righini, P.F. Castellanos, I. Atallah Abstract Vocal fold paralysis in adduction can result in significant breathing difficulties. Techniques such as vocal fold lateralization and/or arytenoidopexy help to improve respiratory function in this setting. These techniques require open approach or specific instruments. The authors describe an original vocal fold lateralization technique performed exclusively via an endoscopic approach. This technique helps to enlarge the glottic aperture, while preserving laryngeal architecture, and permanently improves respiratory function in patients with vocal fold paralysis in adduction.

Persistent stapedial artery in PHACE syndrome Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): R. Quatre, P. Manipoud, S. Schmerber Abstract Introduction PHACE syndrome is characterized by posterior fossa malformations, haemangioma, arterial anomalies, coarctation of the aorta, and eye abnormalities. Case report We present the case of a 6-year-old girl followed since birth for PHACE syndrome and left hemifacial haemangioma, who presented with left hearing loss. Computed tomography scan showed left persistent stapedial artery (PSA). Discussion Two types of arterial anomalies may be observed in PHACE syndrome: persistence of embryonic arteries and anomalies of cerebral arteries. PSA can be observed in the context of PHACE syndrome. Children with PHACE syndrome require regular audiometric follow-up to detect hearing loss and avoid its consequences on speech and language development.

Schwannoma of the external auditory canal: An exceptional site Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): A. Sbai, A. Lachkar, F. Elayoubi, R. Ghailan Abstract Introduction Schwannomas are benign solitary neural tumours that are only exceptional located in the external auditory canal, as only a few cases have been reported in the literature. Case report We report a case of schwannoma of the external auditory canal in an 18-year-old man admitted for an isolated mass of the initial segment of the right external auditory canal visible to the naked eye, obstructing all of the external auditory meatus. Computed tomography of the temporal bone showed an isolated mass of the external auditory canal. Management of this patient consisted of biopsy-excision of the mass, histological examination of which confirmed a schwannoma of the external auditory canal. Discussion Although rare, the possibility of a nerve tumour of the external auditory canal should always be considered. These tumours may be isolated or may occur in the context of von Recklinghausen's disease. The clinical presentation in the external auditory canal may correspond to recurrent otitis externa secondary to obstruction of the canal by the tumour, as in the case reported here. The definitive diagnosis must be based on the results of histological and immunohistochemical examination.

Desmoid tumours of the head and neck: A case report Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): R. Bouatay, R. Jabnoun, N. Kolsi, J. Koubaa Abstract Introduction Desmoid tumours of the head and neck, also known as fibromatosis, are rare, locally invasive benign tumours with high recurrence rate, causing considerable morbidity. Complete surgical excision of desmoid tumours is considered to be the only effective treatment. Case report We present a case of fibromatosis of the right posterolateral region of the neck in a 56-year-old woman who presented with right neck mass. The patient underwent complete excision of the tumour with no adjuvant therapy. No recurrence or neurological deficit was observed 2 years after surgery. Conclusion Although desmoid tumour is a benign neoplasm with no metastatic potential, treatment is challenging due to its aggressive, infiltrative behaviour with a tendency to recur.

Laryngeal lesion associated with epidermolysis bullosa secondary to congenital plectin deficiency Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): T. Bourhis, S. Buche, S. Fraitag, P. Fayoux Abstract Introduction Epidermolysis bullosa (EB) is a congenital disease characterized by fragility of epithelial structures. The skin is the organ primarily affected, resulting in the formation of skin blisters. Some forms of EB may also present mucosal lesions. Case report We report the case of a girl with epidermolysis bullosa simplex (EBS) associated with muscular dystrophy secondary to congenital plectin deficiency. She presented severe respiratory tract lesions extending from the oral cavity to the larynx. In particular, we describe our medical and surgical management of the laryngeal lesions, responsible for several episodes of respiratory distress and feeding difficulties. Discussion Epidermolysis bullosa simplex associated with muscular dystrophy is a rare hereditary form of EB, as fewer than 50 cases have been reported in the literature. This form is characterized by mucosal lesions involving the upper aerodigestive tract, with consequences for feeding, phonation and breathing. Special care must be taken when performing diagnostic and therapeutic procedures to avoid worsening the lesions of this very fragile mucosa. Tracheotomy is a harmful procedure in these patients and should only be considered as a last resort.

Hypereosinophilic syndrome presenting with bilateral ear fullness Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): H.J. Jung, G.H. Yu, J.H. Park Abstract Introduction Hypereosinophilic syndrome is a rare disease with hypereosinophilia resulting in end-organ dysfunction. Patients present with organ-associated symptoms, and the targets frequently affected are heart, lung, skin, or the nervous system, and the middle ear involvement is rare. Case report A 30-year-old female with left ear fullness and hearing loss, which persisted for 6 months, was finally diagnosed with hypereosinophilic syndrome (HES). After high dose systemic steroids treatment, all symptoms improved. Conclusion Eosinophilic otitis media and HES involving the middle ear share many clinical manifestations. Prompt and accurate differential diagnosis is required for these diseases to ameliorate symptoms and promote recovery.

French Society of ENT (SFORL) guidelines. Indications for cochlear implantation in adults Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): R. Hermann, E. Lescanne, N. Loundon, P. Barone, J. Belmin, C. Blanchet, S. Borel, A. Charpiot, A. Coez, O. Deguine, A. Farinetti, B. Godey, D. Lazard, M. Marx, I. Mosnier, Y. Nguyen, N. Teissier, M.B. Virole, S. Roman, E. Truy Abstract The authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding indications for cochlear implantation in adults. After a literature review by a multidisciplinary workgroup, guidelines were drawn up based on retrieved articles and group-members' experience, then read over by an independent reading group to edit the final version. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence. There is no upper age limit to cochlear implantation in the absence of proven dementia and if autonomy is at least partial. Bilateral implantation may be proposed if unilateral implantation fails to provide sufficiently good spatial localization, speech perception in noise and quality of life, and should be preceded by binaural hearing assessment. Rehabilitation by acoustic and electrical stimulation may be proposed when low-frequency hearing persists. Quality of life should be assessed before and after implantation.

Head and neck carcinoma of unknown primary Publication date: June 2019 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 136, Issue 3 Author(s): T. Kennel, R. Garrel, V. Costes, P. Boisselier, L. Crampette, V. Favier Abstract In adult cervicofacial pathology, carcinoma of unknown primary is defined as lymph-node metastasis the anatomic origin of which is not known at the time of initial management. It constitutes up to 5% of head and neck cancers. Presentation may suggest benign pathology, delaying and confusing oncologic treatment. Diagnostic strategy in cervical lymph node with suspicion of neoplasia requires exhaustive work-up to diagnose malignancy and, in 45% to 80% of cases, depending on the series, to identify the primary site. Histologic types comprise squamous cell carcinoma, thyroid carcinoma, adenocarcinoma, neuroendocrine carcinoma and undifferentiated carcinoma. Association is sometimes found with human papilloma virus or Epstein Barr virus, guiding treatment. The objective of the present study was to provide clinicians with the necessary diagnostic tools, based on the current state of clinical, imaging and pathologic knowledge, and to detail treatment options.

Child Indicators Research

Locus of Hope: External Hope in Parents/Guardians as an Antecedent of Adolescents' Internal Hope and Life Satisfaction Abstract While hope has been frequently referenced as a protective factor associated with resilience, limited research exists examining hope's origins. To expand the research base on the origins of hope among adolescents, we conducted 2 studies to test Bernardo's locus of hope theory, along with Snyder's theory that hope originates from attentive caregivers. Two cross sectional studies were performed with 2 independent samples collected from adolescents residing in the South Central United States (Study 1: N′ = 556; Study 2: N′ = 578). Covariance based structural equation modeling (CB-SEM) was used to test an a priori model of external locus of hope in parents/guardians as an antecedent of life satisfaction mediated by children's internal hope. The results of both studies indicate that the proposed theoretical model provided good fit to the observed data. The study concludes with a discussion of the implications of the results, particularly the potential importance of parenting approaches that involve parents/guardians acting as external agents promoting their adolescents' goals.

Sibling Effects on Adult Earnings Among Poor and Wealthy Children Evidence from Sweden Abstract While previous research in general observes adverse effects of siblings on children, less is known about the ways in which material circumstances condition these effects. Using propensity score matching on longitudinal data, this study estimates the effects of being an only child, being born first, and having a large sibling group on adult earnings. Estimates are made for poor and wealthy children respectively in order to examine whether effects occur for both groups. The results show that being an only child, or having a large sibling group, impacts negatively on adult earnings among poor children. Having one younger sibling furthermore has a positive effect on adult earnings among poor children. No corresponding effects were observed for wealthy children. The results indicate that sibling effects are not linear and that they are dependent on family resources.

Poverty, Parental Mental Health and Child/Adolescent Mental Disorders: Findings from a National Australian Survey Abstract The purpose of this study is to examine the association between poverty and child mental disorders, and in particular, address an important knowledge gap by examining the influence of primary carer mental health in these relationships. We extend previous research by differentiating by specific child mental disorders, age group (4–11 and 12–17 year-olds) and gender using data from a 2013/14 national survey of 4–17 year-olds in Australia, Young Minds Matter (N = 6310). Mental disorders were assessed using the Diagnostic Interview Schedule for Children – Version IV. Primary carer mental health problems were determined by three self-reported measures. We calculated a poverty line according to OECD standards. The greatest risk of any mental disorders when living in poverty was among 12–17 year-old males (unadjusted OR = 2.77; 95% CIs = 1.91–4.02), a significantly higher risk than for 4–11 year-old males, and particularly strong for Attention-Deficit/Hyperactivity Disorder (ADHD). By disorder type, poverty was most strongly related to Conduct Disorder (CD) and least strongly related to Major Depressive Disorder (unrelated in adolescent females). When adjusting for primary carer mental health problems, the associations between poverty and child mental disorders were not statistically significant, except among 12–17 year-old males, and for CD and ADHD in the whole sample. Further adjustment for family structure and area-level disadvantage accounted for these associations. Our results demonstrated the importance of paying attention to parental and child mental health, and the child's developmental stage and gender when assessing the welfare, social and health service needs of families and their children living in poverty.

The Relation between Multiple Living Environment Profiles and Adolescent Self-Identity: a Person-Centered Approach Abstract Theoretical and empirical evidence illustrates that family and school are the important living environments for adolescent self-identity development. The current study aimed to use the latent profile analysis, a person-centered approach, to test the relation between multiple family and school environment profiles and adolescent self-identity. In the current study, we surveyed 1030 7th-grade students (478 girls, Mage = 12.56 ± 0.33 years) from 26 classes in one junior high school in a moderate-size inland China city. Participants completed questionnaires on 8 living environmental indicators and 6 self-identity indicators. Results showed that four environment profiles were identified: High Family/High School Living Environment (HF/HS LE) (n = 384), Moderate Family/Moderate School Living Environment (MF/MS LE) (n = 377), Moderate Family/Low School Living Environment (MF/LS LE) (n = 151), and Low Family/Low School Living Environment (LF/LS LE) (n = 118). Students in HF/HS LE reported the highest scores and students in LF/LS LE reported the lowest scores on commitment and in-depth exploration in both educational and relational domains. The present study highlighted the important compensatory impacts of school environment on students with disadvantageous family environment. Limitations and implications were discussed.

Validity of the Middle Years Development Instrument for Population Monitoring of Student Wellbeing in Australian School Children Abstract The importance of social and emotional wellbeing has long been recognised by education systems but the measurement of wellbeing still receives far less attention than the measurement of academic achievement. This paper reports on a five-year project to measure student wellbeing across an education system within the state of South Australia using the Middle Years Development Instrument (MDI). All schools (Government, Catholic, and Independent) were invited to participate in the collection at no cost and aggregated school reports provided an incentive to participate. A total of 51,574 students completed the MDI between 2013 and 2015, with higher participation rates in Government schools than Catholic or Independent schools (65%, 18 and 13% respectively in 2015). Validity and reliability analyses confirmed that the MDI scales had good psychometric properties (i.e., favourable model fit in confirmatory factor analyses, high internal consistency, and correlations between scales were consistent with theoretical expectations). Test-retest reliability (based on a sub-sample of 82 children) was acceptable for most scales except for the connectedness to adults at school (r = .50) and friendship intimacy scales (r = .40), where test-retest reliability was low. However, several of the MDI scales had ceiling effects, particularly for girls and younger students (10–11 years old), which may present challenges when using these scales for population monitoring, program and policy evaluations. Pragmatic factors for education systems and governments to consider in selecting social and emotional wellbeing tools are discussed.

Children's Use of Time and Well-Being in Italy Abstract Several studies indicate that the manner in which children spend their time affects their cognitive and social development. But, the time that a child dedicates to compulsory and extra-curricular activities depends on a set of key factors such as family demographic and economic characteristics, social and behavioral norms, and how parents allocate their time. Although these studies focus on the impact of parental investments (time and resources) on child cognitive development, minimal information regarding children's use of time is available. Our empirical approach is based on the assumption that attitudes and behavioral norms may be considered as latent factors related to how both mothers and children allocate their time. Therefore, focusing on the strict connection between time, parental and child resources and attitudes, we estimated in a Seemingly Unrelated Regression Estimation model how children and mothers spend their time. Data come from the National Time Use Survey 2008–2009 carried out by the Italian National Statistics Office. The use of a simultaneous-equation model to estimate all activities, taking into account the unobservable components included in the error terms, provides an innovative method for analyzing children's time allocation, by identifying the influence of latent variables common to mother and child's use of time. In particular, the estimated correlations between the error terms confirm that parental activities affect the children's allocation of time even through unobservable factors, such as subjective attitudes. The main results support the thesis that the mother's level of education plays an important role in the positive child outcomes. In addition, we found that the same trend that exists between Italian men and women also exists between boys and girls; and that girls spend more time in domestic activities and reading for pleasure and less time in leisure activities.

Social Exclusion and School Achievement: Children of Immigrants and Children of Natives in Three European Countries Abstract Ethnic minorities in Europe show diverging patterns of educational success, but in most national contexts, migrants and children of immigrants have lower achievements in terms of grades than their majority peers. This study asks whether social exclusion in the classroom can contribute to explaining this pattern. While limited access to social resources is often assumed to be of significance for educational success, it has rarely been measured explicitly. In this study, social exclusion is measured accurately and on a large, cross-national scale, by using social network data from 731 classrooms in England, Germany, and Sweden (CILS4EU data). Results show that social exclusion is negatively associated with school grades, but this does not contribute much to understanding grade differences between children of immigrant and children of majority background.

Stress-coping Strategies, Attachment Styles, and Resiliency of Working Children in Tehran, Iran Abstract Child labor is a bitter reality in developing countries and is necessary to be addressed in terms of its psychological aspects. Considering the limitations of the conducted studies and cultural environment in Iran, it is still unknown that how these children cope with their stresses, how the quality and type of their attachment styles are, and how resilient they are to inconveniences. In a causal-comparative study, a sample of 100 working children in Tehran using convenient sampling method and a sample of 150 non-working children using purposive sampling were selected; all the samples were asked to fill Endler and Parker Coping Inventory for Stressful Situations‌(CISS-21), Collins and Read Attachment Styles Scale, and Connor-Davidson Resilience Scale‌(CD-RISC).‌The obtained data were analyzed using ANCOVA and MANCOVA in the form of 2 × 2 factorial using SPSS-16. After adjusting for education level, the results showed that working children mostly use emotion-oriented strategy to cope with stress but the avoidance-oriented strategy is less used by these children. Regardless of group member factor, girls and boys used respectively emotion-oriented and avoidance strategies more frequently. However, in the interaction between group and gender, the results revealed that boys in working children group obtained the lowest scores in task-oriented strategy. In addition, working children‌ group (especially girls), compared to non-working children presented more insecurity in terms of attachment style. Finally, it was found that working children were less resilient than non-working children, but the main effect of gender alone and the interaction between group and gender on resilience scores was not statistically significant‌(p > 0.05). The findings emphasized the protective role of resilience and secure attachment in preventing possible psychological and behavioral disorders in working children. Moreover, the results demonstrated that risky role of emotion-oriented strategy and insecure attachment style in exacerbating the problems of these children, especially for girls.

The Daily Life and Reality Behind Child Poverty in Sweden: Children's and Adolescents' Voices Abstract Today, approximately 12% of children growing up in Sweden are living in what could be defined as child poverty. Although the number of children living in poverty has slightly decreased during recent years, social exclusion and segregation between different groups in society have increased. The present study will shed a light on the reality of how children and adolescents living in poverty experience their daily lives. Analytically, the study explores how these experiences connect to different practices concerning child poverty. The study draws from an empirical and theoretical analysis of interviews with children and adolescents published in the Swedish Save the Children's report At the margin. The daily life behind the statistics of child poverty [På marginalen. Vardagen bakom barnfattigdomsstatistiken]. The results reveal that lack of material and financial resources creates social stigmatization for this group of children and adolescents; they have fewer possibilities to spend time with peers, and this quite often also results in self-exclusion. The children's and adolescents' narratives also indicate the importance of the social role of the school, here in relation to the school providing nutritious school lunches and free packed lunch for school excursions.

Eastern and Western Children's Voices on their Well-Being Abstract Few studies are planned to 'give voice' to children from different cultural backgrounds to explore their sources of happiness. To address this gap, the present study analysed focus group discussions with 42 South Indian and 48 European children aged 8 to 17 years. During the discussions, the children were asked about what makes them happy and sad and about what helps them feel good again when they feel sad. The data were analysed based on grounded theory. Data analysis revealed the following seven themes: 'Indian and European children attach different values to school', 'interactions with biological families both support and threaten well-being', 'positive and negative effects of relationships on the self', 'Indian and European children name different exclusive well-being sources', 'cross-cultural and culture-specific coping and relaxation strategies', 'staying physically healthy is important to the children's well-being', and 'material and economic resources are clearly linked with children's well-being'. Moreover, the results suggest that the meaning of the well-being themes is shaped by a child's self-construal, which is either independent (the self is separated from others) or interdependent (the self is connected with others). How culture might influence children's viewpoints regarding their own well-being is discussed.

Biochimica et Biophysica Acta (BBA)

Achalasia and associated esophageal cancer risk: What lessons can we learn from the molecular analysis of Barrett's–associated adenocarcinoma? Publication date: Available online 4 May 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): K. Nesteruk, M.C.W. Spaander, I. Leeuwenburgh, M.P. Peppelenbosch, G.M. Fuhler Abstract Idiopathic achalasia and Barrett's esophagus (BE) are preneoplastic conditions of the esophagus. BE increases the risk of esophageal adenocarcinoma (EAC), while achalasia is associated with both EAC and esophageal squamous cell carcinoma (ESCC). However, while the molecular mechanisms underlying the transformation of esophageal epithelial cells in BE are relatively well characterized, less is known regarding these processes in achalasia. Nevertheless, both conditions are associated with chronic inflammation and BE can occur in achalasia patients, and it is likely that similar processes underlie cancer risk in both diseases. The present review will discuss possible lessons that we can learn from the molecular analysis of BE for the study of achalasia-associated cancer and contrast findings in BE with those in achalasia. First, we will describe cellular fate during development of BE, EAC, and ESCC, and consider the inflammatory status of the epithelial barrier in BE and achalasia in terms of its contribution to carcinogenesis. Next, we will summarize current data on genetic alterations and molecular pathways involved in these processes. Lastly, the plausible role of the microbiota in achalasia-associated carcinogenesis and its contribution to abnormal lower esophageal sphincter (LES) functioning, the maintenance of chronic inflammatory status and influence on the esophageal mucosa through carcinogenic by-products, will be discussed.

The role of inflammatory programmed cell death in gastrointestinal cancer and immune responses to intestinal microbial infection Publication date: Available online 3 May 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Cheng-Bei Zhou, Jing-Yuan Fang Abstract Inflammatory programmed cell death, also called pyroptosis, is mediated by multiple inflammasomes which can recognize danger signals and activate the secretion of pro-inflammatory cytokines like IL-181 and IL-1β.2 It can induce cancer cell death within the gastrointestinal tract. NLRs,3 AIM2,4 GSDM5 family play important roles in pyroptosis signaling pathways in intestinal cancer such as gastric cancer, colitis-associated colorectal cancer and esophageal cancer, etc. Furthermore, several inflammasomes are elucidated to be involved in mucosal innate immune responses and modulate specific enteric pathogens infection. Precise modulation of inflammasome activation and exploration of potential diagnostic markers can contribute to the diagnosis, prevention and treatment of intestinal tumors and inflammatory or infectious disorders in human patients in the near future.

The AP-1 transcriptional complex: Local switch or remote command? Publication date: Available online 26 April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer Author(s): Bejjani Fabienne, Evanno Emilie, Zibara Kazem, Piechaczyk Marc, Jariel-Encontre Isabelle Summary The ubiquitous family of AP-1 dimeric transcription complexes is involved in virtually all cellular and physiological functions. It is paramount for cells to reprogram gene expression in response to cues of many sorts and is involved in many tumorigenic processes. How AP-1 controls gene transcription has largely remained elusive till recently. The advent of the "omics" technologies permitting genome-wide studies of transcription factors has however changed and improved our view of AP-1 mechanistical actions. If these studies confirm that AP-1 can sometimes act as a local transcriptional switch operating in the vicinity of transcription start sites (TSS), they strikingly indicate that AP-1 principally operates as a remote command binding to distal enhancers, placing chromatin architecture dynamics at the heart of its transcriptional actions. They also unveil novel constraints operating on AP-1, as well as novel mechanisms used to regulate gene expression via transcription-pioneering-, chromatin-remodeling- and chromatin accessibility maintenance effects.

The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Sheetal Parida, Dipali Sharma Abstract Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the "forgotten organ" contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [[2], [3], [4], [5], [6], [7]]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,[7], [8], [9], [10], [11], [12], [13], [14]] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].

Targeting the mTOR regulatory network in hepatocellular carcinoma: Are we making headway? Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Xiang-Nan Yu, Hong Chen, Tao-Tao Liu, Jian Wu, Ji-Min Zhu, Xi-Zhong Shen Abstract The mechanistic target of rapamycin (mTOR) pathway coordinates organismal growth and homeostasis in response to growth factors, nutrients, and cellular energy stage. The pathway regulates several major cellular processes and is implicated in various pathological conditions, including hepatocellular carcinoma (HCC). This review summarizes recent advances of the mTOR pathway, highlights the potential of the mTOR pathway as a therapeutic target, and explores clinical trials targeting the mTOR pathway in HCC. Although the review focuses on the mTOR pathway involved in HCC, more comprehensive discussions (eg, developing a rational design for future trials targeting the mTOR pathway) are also applicable to other tumors.

Atomic force microscopy-based cancer diagnosis by detecting cancer-specific biomolecules and cells Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Taeyun Kwon, Sundaram Gunasekaran, Kilho Eom Abstract Atomic force microscopy (AFM) has recently attracted much attention due to its ability to analyze biomolecular interactions and to detect certain biomolecules, which play a crucial role in disease expression. Despite recent studies reporting AFM imaging for the analyses of biomolecules, the application of AFM-based cancer-specific biomolecule/cell detection has remained largely underexplored, especially for the early diagnosis of cancer. In this paper, we review the recent attempts, including our efforts, to analyze and detect cancer-specific biomolecules and cancer cells. We particularly focus on two AFM-based cancer diagnosis techniques: (i) AFM imaging-based biomolecular and cellular detection, (ii) AFM cantilever-based biomolecular sensing and cell analysis. It is shown that AFM-based biomolecular detection has been applied for not only early diagnosing cancer, by measuring the minute amount of cancer-specific proteins, but also monitoring of cancer progression, by correlating the amount of cancer-specific proteins with the progression of cancer. In addition, AFM-based cell imaging and detection have been employed for diagnosing cancer, by detecting cancerous cells in tissue, as well as understanding cancer progression, by characterizing the dynamics of cancer cells. This review, therefore, highlights AFM-based biomolecule/cell detection, which will pave the way for developing a fast and point-of-care diagnostic system for biomedical applications.

Targeting PI3K signaling in cancer: Challenges and advances Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Maria Chiara De Santis, Federico Gulluni, Carlo Cosimo Campa, Miriam Martini, Emilio Hirsch Abstract The key role of phosphoinositide 3-kinase (PI3K) pathway in different cellular processes and several disorders, together with the presence of targetable proteins, opened the way to promising studies for the development of small molecule inhibitors. Despite the high expectation, the shift of PI3K inhibitors to the clinic met several limitations due to the emergence of dose-limiting, on-target adverse effects. In this review, we will summarize the main issues and recent advances in PI3K inhibitors clinical trials. The effort to develop isoform-specific inhibitors, together with novel therapeutic strategies aimed at reducing the toxicity and adverse effects, opened a new promising era for PI3K inhibitors. In addition, we will focus on the recent emergence of class II and III PI3K inhibitors, which helped to define their class I non-redundant role.

Recent advances in extracellular vesicle research for urological cancers: From technology to application Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Liang Dong, Richard C. Zieren, Yanqing Wang, Theo M. de Reijke, Wei Xue, Kenneth J. Pienta Abstract Urological malignancies, including prostate cancer, bladder cancer and kidney cancer, are major causes of morbidity and mortality worldwide. Because of the high incidence, diversity in biology, and especially direct interaction with urine, urological cancers are an important resource for both scientists and clinicians for novel diagnostic and therapeutic discovery. Extracellular vesicles (EVs) are lipid bilayer encapsulated particles released by cells into the extracellular space. Since EVs work as a safe way to transport important biological information through the whole body, they are now recognized as an important mechanism of cell–cell communication and have opened a new window for us to gain a better understanding of cancer biology, novel diagnostics, and therapeutic options. In recent years, numerous evolutions in EV technologies and novel biological and clinical findings continue to be reported in the research field of urological cancers. This comprehensive review aims to give an update of recent advances in EV technologies and summarize the state-of-the-art knowledge of EVs related to prostate cancer, bladder cancer and kidney cancer, particularly focusing on the potential of EV as biomarkers and their biological roles in promoting cancer and metastasis.

Pyruvate kinase M2: A multifarious enzyme in non-canonical localization to promote cancer progression Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Sajid Amin, Peng Yang, Zhuoyu Li Abstract Rewiring glucose metabolism, termed as Warburg effect or aerobic glycolysis, is a common signature of cancer cells to meet their high energetic and biosynthetic demands of rapid growth and proliferation. Pyruvate kinase M2 isoform (PKM2) is a key player in such metabolic reshuffle, which functions as a rate-limiting glycolytic enzyme in the cytosol of highly-proliferative cancer cells. During the recent decades, PKM2 has been extensively studied in non-canonical localizations such as nucleus, mitochondria, and extracellular secretion, and pertained to novel biological functions in tumor progression. Such functions of PKM2 open a new avenue for cancer researchers. This review summarizes up-to-date functions of PKM2 at various subcellular localizations of cancer cells and draws attention to the translocation of PKM2 from cytosol into the nucleus induced by posttranslational modifications. Moreover, PKM2 in tumor cells could have an important role in resistance acquisition processes against various chemotherapeutic drugs, which have raised a concern on PKM2 as a potential therapeutic target. Finally, we summarize the current status and future perspectives to improve the potential of PKM2 as a therapeutic target for the development of anticancer therapeutic strategies.

Rethinking pulmonary toxicity in advanced non-small cell lung cancer in the era of combining anti-PD-1/PD-L1 therapy with thoracic radiotherapy Publication date: April 2019 Source: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1871, Issue 2 Author(s): Mengqian Li, Lu Gan, Andrew Song, Jianxin Xue, You Lu Abstract The combination of programmed cell death 1/programmed cell death ligand 1 blockade and thoracic radiotherapy has become the new standard of care in the treatment of locally advanced non-small-cell lung cancer. The information regarding the pulmonary safety of such therapy remains limited to mostly retrospective studies and case reports with a small portion of data from prospective clinical trials. By analyzing the underlying mechanisms of interactions between radiation and immunotherapy from preclinical data and summarizing safety data from relevant clinical studies with pulmonary toxicity, we believe that longer and rigorous follow-up is warranted, to determine if the combination of such modalities is appropriate for patients without risking undue toxicity.