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The 'European Alliance Against Depression' community-based intervention approach simultaneously targets depression and suicidal behaviour by a multifaceted community based intervention and has been implemented in more than 115 regions worldwide. The two main aims of the European Union funded project "Optimizing Suicide Prevention Programmes and Their Implementation in Europe" were to optimise this approach and to evaluate its implementation and impact. This paper reports on the primary outcome of the intervention (the number of completed and attempted suicides combined as 'suicidal acts') and on results concerning process evaluation analysis. Interventions were implemented in four European cities in Germany, Hungary, Portugal and Ireland, with matched control sites. The intervention comprised activities with predefined minimal intensity at four levels: training of primary care providers, a public awareness campaign, training of community facilitators, support for patients and their relatives. Changes in frequency of suicidal acts with respect to a one-year baseline in the four intervention regions were compared to those in the four control regions (chi-square tests). The decrease in suicidal acts compared to baseline in the intervention regions (-58 cases, -3.26%) did not differ significantly (χ2 = 0.13; p = 0.72) from the decrease in the control regions (-18 cases, -1.40%). However, intervention effects differed between countries (χ2 = 8.59; p = 0.04), with significant effects on suicidal acts in Portugal (χ2 = 4.82; p = 0.03). The interviews and observations explored local circumstances in each site throughout the study. Hypothesised mechanisms of action for successful implementation were observed and drivers for 'added-value' were identified: local partnership working and 'in-kind' contributions; an approach which valued existing partnership strengths; and synergies operating across intervention levels. It can be assumed that significant events during the implementation phase had a certain impact on the observed outcomes. However, this impact was, of course, not proven., Competing Interests: UH reports personal fees from Takeda, personal fees from Lilly, personal fees from Lundbeck, personal fees from Otsuka, personal fees from Bristol Myers Squibb, outside the submitted work. RM reports personal fees from Nycomed, a Takeda company, outside the submitted work. DMcD reports grants from the European Commission Seventh Framework Research Programme during the conduct of the study; moreover, he had received honorariums from Johnson & Johnson, the Otsuka-Lundbeck Alliance and Bristol Myers Squibb for lectures. None of these are related to the work in this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Information on factors associated with suicide among young individuals in Ireland is limited. The aim of this study was to identify socio-demographic characteristics and circumstances of death associated with age among individuals who died by suicide., Methods: The study examined 121 consecutive suicides (2007-2012) occurring in the southern eastern part of Ireland (Cork city and county). Data were obtained from coroners, family informants, and health care professionals. A comparison was made between 15-24-year-old and 25-34-year-old individuals. Socio-demographic characteristics of the deceased, methods of suicide, history of alcohol and drug abuse, and findings from toxicological analysis of blood and urine samples taken at post mortem were included. Pearson's χ2 tests and binary logistic regression analysis were performed., Results: Alcohol and/or drugs were detected through toxicological analysis for the majority of the total sample (79.5%), which did not differentiate between 15-24-year-old and 25-34-year-old individuals (74.1% and 86.2% respectively). Compared to 25-34-year-old individuals, 15-24-year-old individuals were more likely to engage in suicide by hanging (88.5%). Younger individuals were less likely to die by intentional drug overdose and carbon monoxide poisoning compared to older individuals. Younger individuals who died between Saturday and Monday were more likely to have had alcohol before dying. Substance abuse histories were similar in the two age groups., Conclusion: Based on this research it is recommended that strategies to reduce substance abuse be applied among 25-34-year-old individuals at risk of suicide. The wide use of hanging in young people should be taken into consideration for future means restriction strategies., Competing Interests: The authors have declared that no competing interests exist.

More than 60% of suicides globally are estimated to take place in low- and middle-income nations. Prior research on suicide has indicated that over 50% of those who die by suicide do so on their first attempt. Nevertheless, there is a dearth of knowledge on the attributes of individuals who die on their first attempt and the factors that can predict mortality on the first attempt in these regions. The objective of this study was to create an individual-level risk-prediction model for mortality on the first suicide attempt. We analyzed records of individuals' first suicide attempts that occurred between May 1, 2017, and April 30, 2018, from the national suicide surveillance system, which includes all of the provinces of Thailand. Subsequently, a risk-prediction model for mortality on the first suicide attempt was constructed utilizing multivariable logistic regression and presented through a web-based application. The model's performance was assessed by calculating the area under the receiver operating curve (AUC), as well as measuring its sensitivity, specificity, and accuracy. Out of the 3,324 individuals who made their first suicide attempt, 50.5% of them died as a result of that effort. Nine out of the 21 potential predictors demonstrated the greatest predictive capability. These included male sex, age over 50 years old, unemployment, having a depressive disorder, having a psychotic illness, experiencing interpersonal problems such as being aggressively criticized or desiring plentiful attention, having suicidal intent, and displaying suicidal warning signals. The model demonstrated a good predictive capability, with an AUC of 0.902, a sensitivity of 84.65%, a specificity of 82.66%, and an accuracy of 83.63%. The implementation of this predictive model can assist physicians in conducting comprehensive evaluations of suicide risk in clinical settings and devising treatment plans for preventive intervention. [ABSTRACT FROM AUTHOR]

The emergence of the covid-19 health crisis, in this advanced technological era where connections between markets, nations, and economies have grown stronger than ever before, the shock of the COVID-19 pandemic quickly had an impact on both physical and digital financial assets. The Chinese financial market experienced the first consequences of the covid-19 pandemic, then spilled over to other financial markets, including those for cryptocurrencies and the precious metals. This study examines the impact of the covid-19 pandemic on the volatilities of the dynamics of bitcoin and gold. Both assets share some characteristics, such as online trading platforms, however, gold is a tangible financial asset unlike bitcoin, which is digitally generated without any physical form. This study argues that the similarities and differences between bitcoin and gold play major roles in how the covid-19 crisis affected their respective dynamics. Using daily data ranging from 9/22/2014 to 1/31/2023 and employing ARMA as the mean equation for GARCH model, the impact of the health crisis (covid-19) is examined on the volatilities of the prices and volumes of bitcoin and gold. Empirical evidence points out that, the pandemic has a symmetric impact on the volatilities of bitcoin and gold price returns, causing them to be more volatile. The impact of the covid-19 observed on the volume returns of the assets, however, is asymmetrical. The empirical results give evidence to the role that the vital differences existing between these assets played during the covid-19 pandemic. [ABSTRACT FROM AUTHOR]

Effectively addressing public health crises like the COVID-19 pandemic requires persuading the mass public to change their behavior in significant ways. Many efforts to encourage behavior change–such as public service announcements, social media posts, and billboards–involve short, persuasive appeals, yet the effectiveness of these messages is unclear. Early in the COVID-19 pandemic, we tested whether short messages could increase intentions to comply with public health guidelines. To identify promising messages, we conducted two pretests (n = 1,596) in which participants rated the persuasiveness of 56 unique messages: 31 based on the persuasion and social influence literatures and 25 drawn from a pool of crowdsourced messages generated by online respondents. The four top-rated messages emphasized: (1) civic responsibility to reciprocate the sacrifices of health care workers, (2) caring for the elderly and vulnerable, (3) a specific, sympathetic victim, and (4) limited health care system capacity. We then conducted three well-powered, pre-registered experiments (total n = 3,719) testing whether these four top-rated messages, and a standard public health message based on language from the CDC, increased intentions to comply with public health guidelines, such as masking in public spaces. In Study 1, we found the four messages and the standard public health message significantly outperformed a null control. In Studies 2 and 3, we compared the effects of persuasive messages to the standard public health message, finding that none consistently out-performed the standard message. This is in line with other research showing minimal persuasive effects of short messages after the very early stages of the pandemic. Across our studies, we found that (1) short messages can increase intentions to comply with public health guidelines, but (2) short messages featuring persuasive techniques from the social science literature did not substantially outperform standard public health messages. [ABSTRACT FROM AUTHOR]

Background: Adolescent girls and young women (AGYW) in Nigeria are especially at risk of HIV in Nigeria. Their vulnerability to HIV is linked to multiple concurrent sexual relationships, transgenerational sex, and transactional sex, amongst other factors. These factors have sociocultural contexts that vary across a multi-cultural country like Nigeria. The aim of this study was to use an innovative collaborative approach to develop a minimum HIV prevention package for AGYW which is responsive to sociocultural settings and based on combination HIV prevention. Methods: We conducted action research to develop and implement actionable HIV prevention intervention models that address AGYW's vulnerabilities to HIV in three Nigerian States and the Federal Capital Territory (FCT) Abuja. The action research adopted the breakthrough series (BTS) collaborative, which accelerates improvement through mutual learning. The BTS implementation involved rapid Plan-Do-Study-Act (PDSA) cycles: an iterative process to plan and implement a basket of interventions. Problems or problematic situations, termed change topics, for which interventions could be carried out were identified in each study location. Using participatory approaches during a series of meetings called learning sessions, specific and innovative interventions, termed change ideas, were developed. These learning sessions were conducted with young women groups and other stakeholders. The change ideas were tested, studied, adapted, adopted, or discarded at each participating site. Exposure to and uptake of the implemented interventions was assessed in the study areas using a household survey with 4308 respondents, 53 focus group discussions, and 40 one-on-one interviews in intervention and control study sites. Results: Five categories of interventions were collaboratively developed, namely: Parental communication; Peer to peer interventions; Facilitator-led interventions; Non-traditional outlets for condoms, and Social media-based interventions. A good reach of the interventions was demonstrated as 77.5% of respondents reported exposure to at least one type of intervention. Nearly half of the respondents reported being exposed to the parental communication interventions, while 45.1% reported being exposed to the youth facilitator-driven interventions. Social media interventions had the lowest penetration. Also, there was between 15 to 20 positive percentage point difference between intervention and control for the uptake of HIV testing, and between 5 to 9 positive percentage point difference for uptake of male condoms. These differences were statistically significant at p<0.001. Conclusions: Interventions developed through participatory approaches with young people and well-tailored to local realities can improve the acceptability and accessibility of programs that are able to reduce the risk of HIV infection among AGYW. [ABSTRACT FROM AUTHOR]

Interactions between stock and cryptocurrency markets have experienced shifts and changes in their dynamics. In this paper, we study the connection between S&P500 and Bitcoin in higher-order moments, specifically up to the fourth conditional moment, utilizing the time-scale perspective of the wavelet coherence analysis. Using data from 19 August 2011 to 14 January 2022, the results show that the co-movement between Bitcoin and S&P500 is moment-dependent and varies across time and frequency. There is very weak or even non-existent connection between the two markets before 2018. Starting 2018, but mostly 2019 onwards, the interconnections emerge. The co-movements between the volatility of Bitcoin and S&P500 intensified around the COVID-19 outbreak, especially at mid-term scales. For skewness and kurtosis, the co-movement is stronger and more significant at mid- and long-term scales. A partial-wavelet coherence analysis underlines the intermediating role of economic policy uncertainty (EPU) in provoking the Bitcoin-S&P500 nexus. These results reflect the co-movement between US stock and Bitcoin markets beyond the second moment of return distribution and across time scales, suggesting the relevance and importance of considering fat tails and return asymmetry when jointly considering US equity-Bitcoin trading or investments and the policy formulation for the sake of US market stability. [ABSTRACT FROM AUTHOR]

Exploring the coupling coordination mechanism between higher education and environmental governance is conducive to understanding the mutual interactions between them and thus enhancing mutual development. This study constructs the coupling coordination mechanism and the aggregated evaluation index system to measure the mutual coordination relations between them, assesses the performances and the coupling coordination degrees between them in the case of western provincial regions in China, and proposes countermeasures based on the prediction results. It is found that the performances of higher education are relatively more stable than those of environmental governance, and the distributions of the average performance grades exist noticeable geographical differences. Besides, the coupling coordination degrees increase with mild fluctuations with relatively small spatial variations, demonstrating the balanced and similar coordinated development status among regions; furthermore, in the future, the gaps in the coordination status among regions will gradually decline. This study highlights the mutual coordination mechanism between the two subsystems, compares the coupling coordination status among regions both temporally and spatially, and proposes specific, generalizable development suggestions that contribute to the academic sector, policymakers, ecology, and sustainability. [ABSTRACT FROM AUTHOR]

Reproductive health program managers seek information about existing and potential clients' motivations, behaviors, and barriers to services. Using sequence and cluster analysis of contraceptive calendar data from the 2016–17 Burundi Demographic and Health Survey, we identified discrete clusters characterizing patterns in women's contraceptive and pregnancy behaviors over the previous 5 years. This study pairs these clusters with data on factors typically targeted in social behavior change interventions: knowledge, attitudes, and women's interactions with media and health services, to create composite profiles of women in these clusters. Of six clusters, three are characterized by contraceptive use and three are characterized by its absence. Media exposure and attitudes regarding sex preference, wife beating, and self-efficacy largely do not explain cluster membership. Contraceptive knowledge is positively associated with two clusters (Family Builder 1 and Traditional Mother) and negatively associated with a third (Quiet Calendar). Clusters also differ in their members' fertility desires, contraceptive intentions, and interactions with health services. Two "Family Builder" clusters are both characterized by the presence (but not timing) of multiple pregnancies in their calendar histories, but differ in that women with high contraceptive knowledge, intentions to use contraception, and well-articulated family size ideals are characteristic of one cluster (Family Builder 1), and low contraceptive knowledge, no use of contraception, and vague family size preferences are characteristic of the other (Family Builder 2). These results can guide reproductive health programs as they target social and behavioral change and other interventions to the unique subpopulations they seek to serve. [ABSTRACT FROM AUTHOR]

As information about COVID-19 safety behavior changed, people had to judge how likely others were to protect themselves through mask-wearing and vaccination seeking. In a large, campus-wide survey, we assessed whether University of Kansas students viewed others' protective behaviors as different from their own, how much students assumed others shared their beliefs and behaviors, and which individual differences were associated with those estimations. Participants in our survey (N = 1, 704; 81.04% white, 64.08% female) estimated how likely they and others were to have worn masks on the University of Kansas campus, have worn masks off-campus, and to seek a vaccine. They also completed measures of political preference, numeracy, and preferences for risk in various contexts. We found that participants estimated that others were less likely to engage in health safety behaviors than themselves, but that their estimations of others were widely shared. While, in general, participants saw themselves as more unique in terms of practicing COVID-19 preventative behaviors, more liberal participants saw themselves as more unique, while those that were more conservative saw their own behavior as more similar to others. At least for masking, this uniqueness was false—estimates of others' health behavior were lower than their actual rates. Understanding this relationship could allow for more accurate norm-setting and normalization of mask-wearing and vaccination. [ABSTRACT FROM AUTHOR]

This study aims to explore the effects of COVID-19 indicators and the oil price crash on the Saudi Exchange (Tadawul) Trading Volume and Tadawul Index (TASI) for the period from January 1, 2020, to December 2, 2020. The independent variable is oil price, and the COVID-19 indicators are lockdown, first and second decreases of Repo and Reverse Repo rates, Saudi government response, and cumulative deceased cases. The study adopts two phases. In the first phase, linear regression is used to identify the most influential variables affecting Trading volume and TASI. According to the results, the trading volume model is significant with an adjusted R2 of 65.5% and a standard error of 81. The findings of this model indicate a positive effect of cumulative deceased cases and first decrease of Repo and Reverse Repo rates and a negative effect of oil prices on Trading Volume. The TASI model is significant with an adjusted R2 of 86% and a standard error of 270. The results of this model indicate that lockdown and first decrease of Repo and Reverse Repo rates have a significant negative effect on TASI while the cumulative decrease in cases and oil prices have a positive effect on TASI. In the second phase, linear regression, and neural network predictors (with and without validation) are applied to predict the future TASI values. The neural network model indicates that the neural networks can achieve the best results if all independent variables are used together. By combining the collected results, the study finds that oil price has the most substantial effect on the changes in TASI as compared to the COVID-19 indicators. The results indicate that TASI rapidly follows the changes in oil prices. [ABSTRACT FROM AUTHOR]

As an emerging digital asset, Bitcoin has been traded for more than a decade, reaching an impressively high market capitalization and continuing to expand its volume of trading at a rapid pace. Many countries have legalized or are considering legalizing a trading platform for this asset, and a set of companies worldwide accept it as a medium of exchange. As a result of this expansion, many studies in finance literature have focused on studying the efficiency of this cryptocurrency. In line with this literature, this paper investigates, using the abnormal returns and abnormal trading volumes methodologies, the dynamics of investors' reaction to the arrival of unexpected favorable and unfavorable information regarding the Bitcoin market in the context of the three famous hypotheses: the overreaction, the uncertain information, and the efficient market hypotheses. Overall, we find evidence confirming that the Bitcoin market tends to mature over time. More precisely, over the entire analyzed period, investors behave in accordance with the predictions of the uncertain information hypothesis when positive and negative events occur. However, splitting the timespan into sub-periods provides interesting insights. Remarkably in this respect is the fact that starting with the second sub-period, the response of investors in the Bitcoin market supports, in a moderate manner, the postulate of the efficient market hypothesis when favorable events are addressed. Moreover, our findings reveal that during the pandemic period, the efficiency of Bitcoin has increased, thus turning this stressful period into an advantage for this cryptocurrency. This improved market efficiency is also supported by the abnormal trading volume analysis. [ABSTRACT FROM AUTHOR]

The purpose of our study is to figure out the transitions of the cryptocurrency market due to the outbreak of COVID-19 through network analysis, and we studied the complexity of the market from different perspectives. To construct a cryptocurrency network, we first apply a mutual information method to the daily log return values of 102 digital currencies from January 1, 2019, to December 31, 2020, and also apply a correlation coefficient method for comparison. Based on these two methods, we construct networks by applying the minimum spanning tree and the planar maximally filtered graph. Furthermore, we study the statistical and topological properties of these networks. Numerical results demonstrate that the degree distribution follows the power-law and the graphs after the COVID-19 outbreak have noticeable differences in network measurements compared to before. Moreover, the results of graphs constructed by each method are different in topological and statistical properties and the network's behavior. In particular, during the post-COVID-19 period, it can be seen that Ethereum and Qtum are the most influential cryptocurrencies in both methods. Our results provide insight and expectations for investors in terms of sharing information about cryptocurrencies amid the uncertainty posed by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

This study investigates the reaction of stock markets to the Covid-19 pandemic and the Global Financial Crisis of 2008 (GFC) and compares their influence in terms of risk exposures. The empirical investigation is conducted using the modified ICSS test, DCC-GARCH, and Diebold-Yilmaz connectedness analysis to examine financial contagion and volatility spillovers. To further reveal the impact of these two crises, the statistical features of tranquil and crisis periods under different time intervals are also compared. The test results show that although the outbreak's origin was in China, the US stock market is the source of financial contagion and volatility spillovers during the pandemic, just as it was during the GFC. The propagation of shocks is considerably higher between developed economies compared to emerging markets. Additionally, the results show that the COVID-19 pandemic induced a more severe contagious effect and risk transmission than the GFC. The study provides an extensive examination of the COVID-19 pandemic and the GFC in terms of financial contagion and volatility spillovers. The results suggest the presence of strong co-movements of world stock markets with the US equity market, especially in periods of financial turmoil. [ABSTRACT FROM AUTHOR]

Introduction: On psychiatric wards, aggressive behaviour displayed by patients is common and problematic. Understanding factors associated with the development of aggression offers possibilities for prevention and targeted interventions. This review discusses factors that contribute to the development of aggression on psychiatric wards. Method: In Pubmed and Embase, a search was performed aimed at: prevalence data, ward characteristics, patient and staff factors that are associated with aggressive behaviour and from this search 146 studies were included. Results: The prevalence of aggressive behaviour on psychiatric wards varied (8–76%). Explanatory factors of aggressive behaviour were subdivided into patient, staff and ward factors. Patient risk factors were diagnosis of psychotic disorder or bipolar disorder, substance abuse, a history of aggression, younger age. Staff risk factors included male gender, unqualified or temporary staff, job strain, dissatisfaction with the job or management, burn-out and quality of the interaction between patients and staff. Staff protective factors were a good functioning team, good leadership and being involved in treatment decisions. Significant ward risk factors were a higher bed occupancy, busy places on the ward, walking rounds, an unsafe environment, a restrictive environment, lack of structure in the day, smoking and lack of privacy. Conclusion: Despite a lack of prospective quantitative data, results did show that aggression arises from a combination of patient factors, staff factors and ward factors. Patient factors were studied most often, however, besides treatment, offering the least possibilities in prevention of aggression development. Future studies should focus more on the earlier stages of aggression such as agitation and on factors that are better suited for preventing aggression such as ward and staff factors. Management and clinicians could adapt staffing and ward in line with these results. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains a major cause of morbidity and disability worldwide and a healthcare burden. TBI is an important risk factor for neurodegenerative diseases hallmarked by exacerbated neuroinflammation. Neuroinflammation in the cerebral cortex plays a critical role in secondary injury progression following TBI. The NOD-like receptors (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is a key player in initiating the inflammatory response in various central nervous system disorders entailing TBI. This current study aims to investigate the role of NLRP3 in repetitive mild traumatic brain injury (rmTBI) and identify the potential neuroprotective effect of saffron extract in regulating the NLRP3 inflammasome. 24 hours following the final injury, rmTBI causes an upregulation in mRNA levels of NLRP3, caspase-1, the apoptosis-associated speck-like protein containing a CARD (ASC), nuclear factor kappa B (NF-κB), interleukin-1Beta (IL-1β), interleukin 18 (IL-18), nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase 1 (HMOX1). Protein levels of NLRP3, sirtuin 1 (SIRT1), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), and neuronal nuclei (Neu N) also increased after rmTBI. Administration of saffron alleviated the degree of TBI, as evidenced by reducing the neuronal damage, astrocyte, and microglial activation. Pretreatment with saffron inhibited the activation of NLRP3, caspase-1, and ASC concurrent to reduced production of the inflammatory cytokines IL-1β and IL-18. Additionally, saffron extract enhanced SIRT1 expression, NRF2, and HMOX1 upregulation. These results suggest that NLRP3 inflammasome activation and the subsequent inflammatory response in the mice cortex are involved in the process of rmTBI. Saffron blocked the inflammatory response and relieved TBI by activating detoxifying genes and inhibiting NLRP3 activation. The effect of saffron on the NLRP3 inflammasome may be SIRT1 and NF-κB dependent in the rmTBI model. Thus, brain injury biomarkers will help in identifying a potential therapeutic target in treating TBI-induced neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objectives: There is limited insight into gender differences in suicide-related communication (SRC) in youths. SRC is defined as "the act of conveying one's own suicide ideation, intent or behaviours to another person". Increasing our understanding of SRC in youths will enable us to recognize and specify needs of female versus male youths. The current study explores SRC in a sample of Dutch suicide victims aged under 20 and examines gender differences. Methods: Interview data from a psychological autopsy study of 35 youths who died by suicide in the Netherlands in 2017 were analysed. Qualitative analyses were performed to examine explicit SRC throughout the youths' lives and implicit SRC during the last months prior to suicide. We employed the Constant Comparative Method to explore patterns in the debut, form, frequency, medium, content, type of recipient, and SRC in the last months prior to suicide death. Results: We identified commonalities in the SRC of youths, including the content of suicide notes and an emphasis on suicide method and preparation in the last months. Girls, however, had an earlier debut of SRC, a higher frequency of explicit SRC, and more often directed SRC towards varied types of recipients compared to boys. Moreover, SRC of girls seemed focused on coping and achieving support from others more than SRC of boys. The SRC of boys in comparison to girls was often ambiguous or diluted by "humorous" connotations. Conclusion: Unique patterns in SRC of boys and girls posed corresponding challenges for next of kin to interpret communications and respond adequately to SRC. The early debut of girls' SRC highlights the importance of early screening and prevention efforts in girls, while the late debut and ambiguity in boys' SRC implores professionals and next of kin to encourage young males to be unequivocal about suicide ideation or intent. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic seems to be the most important phenomenon observed from March 2020 in virtually all countries of the world. The necessity to prevent the spread of COVID-19 and keep health care systems efficient resulted in the forced, drastic limitation of economic activity. Many service sectors were hit particularly hard with this but industry and agriculture were also affected. In particular, the pandemic substantially influenced financial markets and we can observe that some markets or instruments vary in stability since they have been affected in the different degree. In the paper, we present the problem of stability of stock markets during the COVID-19 pandemic. Due to the low number of works related to CEE countries during the pandemic, we analyze the Warsaw Stock Exchange, which is one of the most important markets in the CEE. Our main goal was to find how various industries represented by stock market indices have reacted to the COVID-19 shock and consequently which sectors turned out to keep stability and remained resistant to the pandemic. In our investigation, we use two clustering methods: the K-means and the Ward techniques with the criterion of maximizing the silhouette coefficient and six indicators describing stability in terms of profitability, volume, overbought/oversold conditions and volatility. The results of the research present that during the pandemic it was possible to identify 5 clusters of sector indices in the short term and 4 in the medium term. We found that the composition of the clusters is quite stable over time and that none of the obtained clusters can be univocally considered the most or the least stable taking into account all the analyzed indicators. However, we showed that the obtained clusters have different stability origins, i.e. they vary from each other in terms of the investigated indicators of stability. [ABSTRACT FROM AUTHOR]

This paper examines the sentiment spillovers among oil, gold, and Bitcoin markets by employing spillovers index methods in a time-frequency framework. We find that the total sentiment spillover among crude oil, gold and Bitcoin markets is time-varying and is greatly affected by major market events. The directional sentiment spillovers are also time-varying. On average, the Bitcoin market is the major transmitter of directional sentiment spillovers, whereas the crude oil and gold markets are the major receivers. In particular, the sentiment spillover effects are major created at high-frequency components, implying that the markets rapidly process the sentiment spillover effects and the shock is transmitted over the short-term. Moreover, we also find that the sentiment spillover effects differ significantly in term of intensity and direction when compared with return and volatility spillover effects. The present study has certain applications for investors and policymakers. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) rates in England are among the highest in high-income countries. Poverty and historic and current immigration from high TB incidence parts of the world are two major drivers of tuberculosis in England. However, little has been done in recent years to examine socio-economic trends in TB rates in England, and to disentangle the role of deprivation from that of place of birth in the current TB epidemiology. Objectives: To assess the association between England's 2008–2012 TB notification rates and small area-level deprivation, together and separately in the UK-born and foreign-born populations. Methods: Ecological analysis of the association between quintiles of England's 2010 Index of Multiple Deprivation (IMD) and TB rates at the Lower-layer Super Output Area (LSOA; average population ~1500) level, using negative binomial and zero-inflated negative binomial regression models, adjusting for age, sex, urban/rural area classification, and area-level percentage of non-White residents. Results: There was a log-linear gradient between area-deprivation levels and TB rates, with overall TB rates in the most deprived quintile areas three times higher than the least deprived quintile after adjustment for age and sex (IRR = 3.35; 95%CI: 3.16 to 3.55). The association and gradient were stronger in the UK-born than the foreign-born population, with UK-born TB rates in the most deprived quintiles about two-and-a-half times higher than the least deprived quintile (IRR = 2.39; 95%CI: 2.19 to 2.61) after controlling for age, sex, urban/rural classification and percentage of non-White residents; whereas the comparable figure for foreign-born persons was 80% higher (IRR = 1.78; 95%CI: 1.66 to 1.91). Conclusions: Socio-economic deprivation continues to play a substantial role in sustaining the TB epidemic in England, especially in the UK-born population. This supports the case for further investigations of the underlying social- determinants of TB. [ABSTRACT FROM AUTHOR]

High-risk cancer resection surgeries are increasingly being performed at fewer, more specialised, and higher-volume institutions across Canada. The resulting increase in travel time for patients to obtain treatment may be exacerbated by socioeconomic barriers to access. Focussing on five high-risk surgery types (oesophageal, ovarian/fallopian, liver, lung, and pancreatic cancers), this study examines socioeconomic trends in age-adjusted resection rates and travel time to surgery location for urban, suburban, and rural populations across Canada, excluding Québec, from 2004 to 2012. Significant differences in age-adjusted resection rates were observed between urban (14.9 per 100 000 person-years [95% CI: 12.2, 17.6]), suburban (40.7 [40.1, 41.2]), and rural (32.7 [29.6, 35.9]) populations, with higher rates in suburban and rural areas throughout the study period for all cancer types. Resection rates did not differ between the highest (Q1) and lowest (Q5) socioeconomic strata (Q1: 13.3 [12.2, 14.4]; Q5: 12.0 [10.7, 13.4]), with significantly higher rates among middle-SES patients (Q2: 27.3 [25.6, 29.0]; Q3: 39.6 [37.4, 41.8]; Q4: 37.5 [35.3, 39.7]). Travel times to treatment were consistently higher among the most socioeconomically deprived patients, most notably in suburban and rural areas. The results suggest that the conventional inclusion of suburbs with urban areas in health research may obfuscate important trends for public health policy and programmes. [ABSTRACT FROM AUTHOR]

Objectives: In the Netherlands, there was a sharp increase in the number of suicides among 10- to 19-year-olds in 2017. A multi-method psychological autopsy study (PA) was conducted to assess feasibility, identify related factors, and study the interplay of these factors to inform suicide prevention strategies. Methods: Coroners identified youth suicides in 2017 in their records and then general practitioners (GPs) contacted the parents of these youths. Over a period of 7 months, 66 qualitative interviews were held with the parents, peers, and teachers, providing information on precipitating factors and five topics involving 35 cases (17 boys and 18 girls, mean age 17 years). Furthermore, 43 parents and care professionals filled in questionnaires to examine risk and care–related factors. Qualitative and quantitative analyses were performed. Results: Although registration problems faced by coroners and resistance to contacting bereaved families by GPs hampered the recruitment, most parents highly appreciated being interviewed. Several adverse childhood experiences played a role at an individual level, such as (cyber) bullying, parental divorce, sexual abuse, as well as complex mental disorders, and previous suicide attempts. Two specific patterns stood out: (1) girls characterized by insecurity and a perfectionist attitude, who developed psychopathology and dropped out of school, and (2) boys with a developmental disorder, such as autism, who were transferred to special needs education and therefore felt rejected. In addition, adolescents with complex problems had difficulty finding appropriate formal care. Regarding potential new trends, contagion effects of social media use in a clinical setting and internet use for searching lethal methods were found. Conclusion: This first national PA study showed that, as expected, a variety of mostly complex clusters of problems played a role in youth suicides. An infrastructure is needed to continuously monitor, evaluate, and support families after each youth suicide and thereby improve prevention strategies. [ABSTRACT FROM AUTHOR]

Site-specific conjugation of ubiquitin onto a range of DNA repair proteins regulates their critical functions in the DNA damage response. Biochemical and structural characterization of these functions are limited by an absence of tools for the purification of DNA repair proteins in purely the ubiquitinated form. To overcome this barrier, we designed a ubiquitin fusion protein that is N-terminally biotinylated and can be conjugated by E3 RING ligases onto various substrates. Biotin affinity purification of modified proteins, followed by cleavage of the affinity tag leads to release of natively-mono-ubiquitinated substrates. As proof-of-principle, we applied this method to several substrates of mono-ubiquitination in the Fanconi anemia (FA)-BRCA pathway of DNA interstrand crosslink repair. These include the FANCI:FANCD2 complex, the PCNA trimer and BRCA1 modified nucleosomes. This method provides a simple approach to study the role of mono-ubiquitination in DNA repair or any other mono-ubiquitination signaling pathways. [ABSTRACT FROM AUTHOR]

Aim: Intestinal metaplasia (IM) and gastric atrophy (GA) are precancerous lesions in the stomach. There is a large debate on natural course of these lesions and surveillance strategy in these patients. This meta-analysis was aimed to find the most appropriate follow up and the rate of progression from IM and GA to GC. Methods: This meta-analysis is followed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases including EMBASE, PubMed, Web of Science databases, Scopus, and the Cochrane Library were searched until July 2018. Cochran’s Q test and I-square (I2) test were used to examine heterogeneity across included studies. We pooled data using random-effect or fixed effect models indicated as incidence rate or proportion with 95% confidence intervals (CI). The variables of study included demographic data, endoscopy interval, follow up interval and time, GA and IM type and GC stage. Moreover, incidence rate of GC and progress rate, regress and persistence proportion in both GA and IM patients were assessed. Results: Overall, 68 original articles out of 32981 citations were included in our meta-analysis. The pooled GC incidence rate in patients with GA was 1.24 (95% CI, 0.80, 1.76; I2: 83.6%) cases per 1,000 person-years. The rates of later diagnosis of IM and gastric dysplasia in patients with GA were estimated as 41.42 (95% CI, 3.11, 64.45; I2: 95.6%) and 6.23 (95% CI, 2.34, 11.46; I2: 83.0%) cases per 1,000 person-years, respectively. The pooled regressed proportion was 32.23 (95% CI, 18.07–48.02; I2: 94.0%) and the persistence proportion was 38.83 (95% CI, 20.20–59.13; I2: 97.0%) per 100 observations in GA patients. In IM studies, the pooled incidence rate of GC was 3.38 (95% CI, 2.13, 4.85; I2: 93.4%) cases per 1,000 person-years. The progressed rate to dysplasia in IM patient was estimated to be 12.51 (95% CI, 5.45, 22.03; I2: 95.1%) cases per 1,000 person-years. The pooled regressed proportion was 31.83 (95% CI, 25.48–38.51; I2: 91.0%) and the persistence proportion was 43.46 (95% CI, 32.52–54.71; I2: 96.0%) per 100 observations in IM patients. Conclusion: Overall, the incidence of GC in patients with IM and GA are low but there is heterogeneity in data with the highest rate in Asian, males with those with incomplete IM. There is probability of regression or persistence without progression in patients with IM and GA who receive appropriate management. [ABSTRACT FROM AUTHOR]

Introduction: Repetition of deliberate self-harm is an important predictor of subsequent suicide. Repetition rates in Asian countries appear to be significantly lower than in western high-income countries. Methodological differences in studies, and the impact of access to means of self-harm with comparatively higher lethality have been suggested as reasons for these reported differences. This prospective study determines the rates and demographic patterns of deliberate self-poisoning (DSP), suicide and repeated deliberate self-harm resulting non-fatal and fatal outcomes in rural Sri Lanka. Methods: Details of DSP admission in all hospitals (n = 46) and suicides reported to all police stations (n = 28) in a rural district were collected for the years 2011, 2012 and 2013. Demographic details of the cohort of patients admitted to all hospitals in 2011 due to deliberate self-poisoning (N = 4022), were screened to link with patient records and police reports of the successive two years with high sensitivity using a computer program. Then high specificity manual matching of all screened links was performed to identify repetition within 2 years of initial presentation. Life time repetition was assessed in a randomly selected subset of DSP patients (n = 433). Results: There were 15,639 DSP admissions, aged more than 9 years, and 1078 suicides during the study period. The incidence of deliberate self-poisoning and suicide in the population within the study area were 248.3/100,000 and 20.7/100,000 respectively, in 2012. Repetition rates at four weeks, one-year and two-years were 1.9% (95% CI 1.5–2.3%), 5.7% (95% CI 5.0–6.4) and 7.9% (95% CI 7.1–8.8) respectively. The median interval between two attempts were 92 (IQR 10–238) and 191 (IQR 29–419.5) days for the one and two-year repetition groups. The majority of patients used the same poison in the repeat attempt. The age and duration of hospital stay of individuals with repetitive events were not significantly different from those who had no repetitive events. The rate of suicide at two years following DSP was 0.7% (95% CI 0.4–0.9%). The reported life time history of deliberate self-harm attempts was 9.5% (95% CI 6.7–12.2%). Conclusions: The comparatively low rates of repetition in rural Sri Lanka was not explained by higher rates of suicide, access to more lethal means or differences in study methodology. [ABSTRACT FROM AUTHOR]

Drinking water can be exposed to different biological contaminants from the source, through the pipelines, until reaching the final consumer or industry. Some of these are pathogenic bacteria and viruses which may cause important gastrointestinal or systemic diseases. The microbiological quality of drinking water relies mainly in monitoring three indicator bacteria of faecal origin, Escherichia coli, Enterococcus faecalis and Clostridium perfringens, which serve as early sentinels of potential health hazards for the population. Here we describe the analysis of three chimeric fluorescent protein bullets as biosensor candidates for fast detection of E. coli in drinking water. Two of the chimeric proteins (based on GFP-hadrurin and GFP-pb5 chimera proteins) failed with respect to specificity and/or sensitivity, but the GFP-colS4 chimera protein was able to carry out specific detection of E. coli in drinking water samples in a procedure encompassing about 8 min for final result and this biosensor protein was able to detect in a linear way between 20 and 103 CFU of this bacterium. Below 20 CFU, the system cannot differentiate presence or absence of the target bacterium. The fluorescence in this biosensor system is provided by the GFP subunit of the chimeric protein, which, in the case of the better performing sensor bullet, GFP-colS4 chimera, is covalently bound to a flexible peptide bridge and to a bacteriocin binding specifically to E. coli cells. Once bound to the target bacteria, the excitation step with 395 nm LED light causes emission of fluorescence from the GFP domain, which is amplified in a photomultiplier tube, and finally this signal is converted into an output voltage which can be associated with a CFU value and these data distributed along mobile phone networks, for example. This method, and the portable fluorimeter which has been developed for it, may contribute to reduce the analysis time for detecting E. coli presence in drinking water. [ABSTRACT FROM AUTHOR]

Background: Individuals with schizophrenia who are involuntarily admitted may have poorer prognosis, including higher readmission rates, than those voluntarily admitted. However, little is known about the risk factors for readmission in those schizophrenia patients who are involuntarily admitted. Aims: We aim to explore the risk factors for readmission in this population. Method: We enrolled 138 schizophrenia patients with involuntary admission from July 2008 to June 2013 and followed those patients for readmission outcomes at 3 months and at 1 year. Results: The one-year and 3-months readmission rates were 33.3% and 15.2%, respectively. Unmarried status (adjusted odds ratio (aOR) = 6.28, 95% CI: 1.48–26.62), previous history of involuntary admission (aOR = 4.08, 95% CI: 1.19–14.02), longer involuntary admission days (aOR = 1.04, 95% CI: 1.01–1.07) and shorter total admission days (aOR = 1.03, 95% CI: 1.01–1.05) were associated with increased risk for 1-year readmission. Younger age (aOR = 1.10, 95% CI 1.02–1.18) was associated with increased risk for 3-months readmission. Conclusions: Unmarried status, prior history of involuntary admission, longer involuntary admission days and shorter total admission days were associated with increased risk for 1-year readmission. Healthcare providers may need to focus on patients with these risk factors to reduce subsequent readmissions. [ABSTRACT FROM AUTHOR]

Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency. Notch signaling promotes the expansion of Pax7+MyoD- mouse muscle stem-like cells and inhibits differentiation even after passage in vitro. Treatment with Notch ligands induced the Notch target genes and generated PAX7+MYOD- stem-like cells from human myoblasts previously cultured on conventional culture plates. However, cells treated with Notch ligands exhibit a stem cell-like state in culture, yet their regenerative ability was less than that of freshly isolated cells in vivo and was comparable to that of the control. These unexpected findings suggest that artificial maintenance of Notch signaling alone is insufficient for improving regenerative capacity of mouse and human donor-muscle cells and suggest that combinatorial events are critical to achieve muscle stem cell and myoblast engraftment potential. [ABSTRACT FROM AUTHOR]

Postural dysfunctions are prevalent in patients with schizophrenia and affect their daily life and ability to work. In addition, sensory functions and sensory integration that are crucial for postural control are also compromised. This study intended to examine how patients with schizophrenia coordinate multiple sensory systems to maintain postural stability in dynamic sensory conditions. Twenty-nine patients with schizophrenia and 32 control subjects were recruited. Postural stability of the participants was examined in six sensory conditions of different level of congruency of multiple sensory information, which was based on combinations of correct, removed, or conflicting sensory inputs from visual, somatosensory, and vestibular systems. The excursion of the center of pressure was measured by posturography. Equilibrium scores were derived to indicate the range of anterior-posterior (AP) postural sway, and sensory ratios were calculated to explore ability to use sensory information to maintain balance. The overall AP postural sway was significantly larger for patients with schizophrenia compared to the controls [patients (69.62±8.99); controls (76.53±7.47); t1,59 = -3.28, p<0.001]. The results of mixed-model ANOVAs showed a significant interaction between the group and sensory conditions [F5,295 = 5.55, p<0.001]. Further analysis indicated that AP postural sway was significantly larger for patients compared to the controls in conditions containing unreliable somatosensory information either with visual deprivation or with conflicting visual information. Sensory ratios were not significantly different between groups, although small and non-significant difference in inefficiency to utilize vestibular information was also noted. No significant correlations were found between postural stability and clinical characteristics. To sum up, patients with schizophrenia showed increased postural sway and a higher rate of falls during challenging sensory conditions, which was independent of clinical characteristics. Patients further demonstrated similar pattern and level of utilizing sensory information to maintain balance compared to the controls. [ABSTRACT FROM AUTHOR]

Studies in high-income countries have shown an association between heatwaves and hospital admissions for mental disorders. It is unknown whether such associations exist in subtropical nations like Vietnam. The study aim was to investigate whether hospital admissions for mental disorders may be triggered, or exacerbated, by heat exposure and heatwaves, in a low- and middle-income country, Vietnam. For this, we used data from the Hanoi Mental Hospital over five years (2008–2012) to estimate the effect of heatwaves on admissions for mental disorders. A zero-inflated negative binomial regression model accounting for seasonality, time trend, days of week, and mean humidity was used to analyse the relationship. Heatwave events were mainly studied as periods of three or seven consecutive days above the threshold of 35°C daily maximum temperature (90th percentile). The study result showed heatwaves increased the risk for admission in the whole group of mental disorders (F00-79) for more persistent heatwaves of at least 3 days when compared with non-heatwave periods. The relative risks were estimated at 1.04 (0.95–1.13), 1.15 (1.005–1.31), and 1.36 (1–1.90) for a one-, three- and seven-day heatwave, respectively. Admissions for mental disorders increased among men, residents in rural communities, and the elderly population during heatwaves. The groups of organic mental disorders, including symptomatic illnesses (F0-9) and mental retardation (F70-79), had increased admissions during heatwaves. The findings are novel in their focus on heatwave impact on mental diseases in a population habituating in a subtropical low- and middle-income country characterized by rapid epidemiological transitions and environmental changes. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines have recommended psychosocial assessment of self-harm patients for years, yet estimates of its impact on the risk of repeat self-harm vary. Assessing the association of psychosocial assessment with risk of repeat self-harm is challenging due to the effects of confounding by indication. Methods: We analysed data from a cohort study of 15,113 patients presenting to the emergency departments of three UK hospitals to investigate the association of psychosocial assessment with risk of repeat hospital presentation for self-harm. Time of day of hospital presentation was used as an instrument for psychosocial assessment, attempting to control for confounding by indication. Results: Conventional regression analysis suggested psychosocial assessment was not associated with risk of repeat self-harm within 12 months (Risk Difference (RD) 0.00 95% confidence interval (95%CI) -0.01 to 0.02). In contrast, IV analysis suggested risk of repeat self-harm was reduced by 18% (RD -0.18, 95%CI -0.32 to -0.03) in those patients receiving a psychosocial assessment. However, the instrument of time of day did not remove all potential effects of confounding by indication, suggesting the IV effect estimate may be biased. Conclusions: We found that psychosocial assessments reduce risk of repeat self-harm. This is in-line with other non-randomised studies based on populations in which allocation to assessment was less subject to confounding by indication. However, as our instrument did not fully balance important confounders across time of day, the IV effect estimate should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states. Objectives: To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients. Methods: Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011. Results: A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome. Conclusions: The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment. [ABSTRACT FROM AUTHOR]

Background: Childhood abuse has been associated with significant increases in non-suicidal self-injury (NSSI) behaviors in adolescents; however, only general definitions of this risk indicator have been examined. This study identified relationships between specific forms of childhood abuse and NSSI in mainland Chinese adolescents. Method: A total of 14,221 cases were retained from an epidemiological study involving adolescents from junior and senior middle schools. Information relating to the perpetrator, perceived harm, timing of exposure to different types of childhood abuse, and NSSI were obtained. Logistic regression was used to analyze relationships between each form of childhood abuse and NSSI. Results: Approximately 51.0% of the students reported at least one abusive childhood experience. Nearly one in four students (24.9%) reported that they had engaged in NSSI in the past 12 months. Each type of childhood abuse, occurring at any time within the first 16 years of life, especially in situations of continuous exposure, was significantly associated with NSSI. A significant graded relationship was found between number of abusive childhood experiences and NSSI. Students maltreated by parents or others were at high risk of engaging in NSSI, the risk was greater in students maltreated by both; students who had been exposed to childhood abuse with no perceived harm still demonstrated an elevated risk for NSSI. The pattern of associations did not vary by gender. Conclusions: These findings suggest that experiencing any of various forms of childhood abuse should be considered a risk factor for NSSI during adolescence. Further research should focus upon psychosocial, neural, and genetic factors that might moderate or mediate the onset of NSSI in adolescents who have experienced childhood abuse. [ABSTRACT FROM AUTHOR]

Background: Violence in acute psychiatric wards affects the safety of other patients and the effectiveness of treatment. However, there is a wide variation in reported rates of violence in acute psychiatric wards. Objectives: To use meta-analysis to estimate the pooled rate of violence in published studies, and examine the characteristics of the participants, and aspects of the studies themselves that might explain the variation in the reported rates of violence (moderators). Method: Systematic meta-analysis of studies published between January 1995 and December 2014, which reported rates of violence in acute psychiatric wards of general or psychiatric hospitals in high-income countries. Results: Of the 23,972 inpatients described in 35 studies, the pooled proportion of patients who committed at least one act of violence was 17% (95% confidence interval (CI) 14–20%). Studies with higher proportions of male patients, involuntary patients, patients with schizophrenia and patients with alcohol use disorder reported higher rates of inpatient violence. Conclusion: The findings of this study suggest that almost 1 in 5 patients admitted to acute psychiatric units may commit an act of violence. Factors associated with levels of violence in psychiatric units are similar to factors that are associated with violence among individual patients (male gender, diagnosis of schizophrenia, substance use and lifetime history of violence). [ABSTRACT FROM AUTHOR]

Introduction: Minor physical anomalies (MPA) are dysmorphic features that reflect deviations in early development, are morphological variants that appear during the first trimester of pregnancy and could be used as a marker of disease risk in susceptible people. The literature agrees that the number of MPA is higher in patients with schizophrenia compared with their relatives and healthy subjects. The purpose of this study is to compare the MPA, assessed using the Gourion Scale, in complete nuclear families (families with a member with schizophrenia and control families) by determining the MPA mean, concordance and heritability for the total score on the MPA Gourion Scale for each anomaly. Method: The sample consisted of 60 families with at least one schizophrenic patient (284 members) and 61 control families (249 members). Results: The mean total score for the scale was 5.72 ± 2.3 MPA in the case of families with at least one schizophrenic patient and 1.8 ± 4.46 MPA for control families. The average for families of patients without considering the patient in the analysis was 5.59 ± 2.3 MPA; for patients, the mean was 6.14 ± 2.4 MPA. In the analysis by anomaly differences were found only in eleven anomalies found no evidence of heritability or concordance. Conclusions: MPA occur more frequently in patients, but a pattern of low consistency between them persists. It is concluded that MPA could be a marker of neurodevelopmental problems, but it is not suitable to consider them a Gourion scale as endophenotype. [ABSTRACT FROM AUTHOR]

To facilitate the detection of Salmonella and to be able to rapidly and conveniently determine the species/subspecies present, we developed and tested a generic and differential FRET-PCR targeting their tetrathionate reductase response regulator gene. The differential pan-Salmonella FRET-PCR we developed successfully detected seven plasmids that contained partial sequences of S. bongori and the six S. enterica subspecies. The detection limit varied from ∼5 copies of target gene/per PCR reaction for S. enterica enterica to ∼200 for S. bongori. Melting curve analysis demonstrated a Tm of ∼68°C for S. enterica enterica, ∼62.5°C for S. enterica houtenae and S. enterica diarizonae, ∼57°C for S. enterica indica, and ∼54°C for S. bongori, S. enterica salamae and S. enterica arizonae. The differential pan-Salmonella FRET-PCR also detected and determined the subspecies of 4 reference strains and 47 Salmonella isolated from clinically ill birds or pigs. Finally, we found it could directly detect and differentiate Salmonella in feline (5/50 positive; 10%; one S. enterica salamae and 4 S. enterica enterica) and canine feces (15/114 positive; 13.2%; all S. enterica enterica). The differential pan-Salmonella FRET-PCR failed to react with 96 non-Salmonella bacterial strains. Our experiments show the differential pan-Salmonella FRET-PCR we developed is a rapid, sensitive and specific method to detect and differentiate Salmonella. [ABSTRACT FROM AUTHOR]

Objective: The pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings. Method: High resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS). Results: The TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = −0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = −0.399, p<0.001), and PANSS general score (r = −0.338, p<0.05). Limitations: The cross-section design can’t separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype. Conclusions: The schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively. [ABSTRACT FROM AUTHOR]

The highly pathogenic avian influenza (HPAI) H5N1 viruses, especially the laboratory-generated H5N1 mutants, have demonstrated the potential to cross the species barrier and infect mammals and humans. Consequently, the design of an effective and safe anti-H5N1 vaccine is essential. We previously demonstrated that the full-length hemagglutinin 1 (HA1) could induce significant neutralizing antibody response and protection. Here, we intended to identify the critical neutralizing domain (CND) in an optimal conformation that can elicit strong cross-neutralizing antibodies and protection against divergent H5N1 strains. We thus constructed six recombinant proteins covering different regions of HA1 of A/Anhui/ 1/2005(H5N1), each of which was fused with foldon (Fd) and Fc of human IgG. We found that the critical fragment fused with Fd/Fc (HA-13-263-Fdc, H5 numbering) that could elicit the strongest neutralizing antibody response is located in the N-terminal region of HA1 (residues 13-263), which covers the receptor-binding domain (RBD, residues 112-263). We then constructed three additional recombinants fused with Fd plus His tag (HA-13-263-Fd-His), Fc only (HA-13-263-Fc), and His tag only (HA-13-263-His), respectively. We found that the HA-13-263-Fdc, which formed an oligomeric conformation, induced the strongest neutralizing antibody response and cross-protection against challenges of two tested H5N1 virus strains covering clade 1: A/VietNam/1194/2004 (VN/1194) or clade 2.3.4: A/Shenzhen/406H/06 (SZ/406H), while HA-13-263-Fc dimer and HA-13-263-Fd-His trimer elicited higher neutralizing antibody response and protection than HA-13-263-His monomer. These results suggest that the oligomeric form of the CND containing the RBD can be further developed as an effective and safe vaccine for cross-protection against divergent strains of H5N1 viruses. [ABSTRACT FROM AUTHOR]

Endogenous microbiota play essential roles in the host's immune system, physiology, reproduction and nutrient metabolism. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's development. Thus, we treated zebrafish from birth to sexual maturation (2-months treatment) with Lactobacillus rhamnosus, a probiotic species intended for human use. We monitored for the presence of L. rhamnosus during the entire treatment. Zebrafish at 6 days post fertilization (dpf) exhibited elevated gene expression levels for Insulin-like growth factors -I and -II, Peroxisome proliferator activated receptors -α and -Β, VDR-α and RAR-γ when compared to untreated-10 days old zebrafish. Using a gonadotropin-releasing hormone 3 GFP transgenic zebrafish (GnRH3-GFP), higher GnRH3 expression was found at 6, 8 and 10 dpf upon L. rhamnosus treatment. The same larvae exhibited earlier backbone calcification and gonad maturation. Noteworthy in the gonad development was the presence of first testes differentiation at 3 weeks post fertilization in the treated zebrafish population -which normally occurs at 8 weeks- and a dramatic sex ratio modulation (93% females, 7% males in control vs. 55% females, 45% males in the treated group). We infer that administration of L. rhamnosus stimulated the IGF system, leading to a faster backbone calcification. Moreover we hypothesize a role for administration of L. rhamnosus on GnRH3 modulation during early larval development, which in turn affects gonadal development and sex differentiation. These findings suggest a significant role of the microbiota composition on the host organism development profile and open new perspectives in the study of probiotics usage and application. [ABSTRACT FROM AUTHOR]

Recently, a new class of broadly neutralizing anti-influenza virus antibodies that target the stalk domain of the viral hemagglutinin was discovered. As such, induction, isolation, characterization, and quantification of these novel antibodies has become an area of intense research and great interest. Since most of these antibodies bind to conformational epitopes, the structural integrity of hemagglutinin substrates for the detection and quantification of these antibodies is of high importance. Here we evaluate the binding of these antibodies to soluble, secreted hemagglutinins with or without a carboxy-terminal trimerization domain based on the natural trimerization domain of T4 phage fibritin. The lack of such a domain completely abolishes binding to group 1 hemagglutinins and also affects binding to group 2 hemagglutinins. Additionally, the presence of a trimerization domain positively influences soluble hemagglutinin stability during expression and purification. Our findings suggest that a carboxy-terminal trimerization domain is a necessary requirement for the structural integrity of stalk epitopes on recombinant soluble influenza virus hemagglutinin. [ABSTRACT FROM AUTHOR]

Background: Assessing neighborhood environment in access to mammography remains a challenge when investigating its contextual effect on breast cancer- related outcomes. Studies using different Geographic Information Systems (GIS)- based measures reported inconsistent findings. Methods: We compared GIS-based measures (travel time, service density, and a two-Step Floating Catchment Area method [2SFCA]) of access to FDA-accredited mammography facilities in terms of their Spearman correlation, agreement (Kappa) and spatial patterns. As an indicator of predictive validity, we examined their association with the odds of late-stage breast cancer using cancer registry data. Results: The accessibility measures indicated considerable variation in correlation, Kappa and spatial pattern. Measures using shortest travel time (or average) and service density showed low correlations, no agreement, and different spatial patterns. Both types of measures showed low correlations and little agreement with the 2SFCA measures. Of all measures, only the two measures using 6-timezone-weighted 2SFCA method were associated with increased odds of late-stage breast cancer (quick- distance-decay: odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.01- 1.32; slow-distance-decay: OR = 1.19, 95% CI = 1.03-1.37) after controlling for demographics and neighborhood socioeconomic deprivation. Conclusions: Various GIS-based measures of access to mammography facilities exist and are not identical in principle and their association with late-stage breast cancer risk. Only the two measures using the 2SFCA method with 6-timezone weighting were associated with increased odds of late-stage breast cancer. These measures incorporate both travel barriers and service competition. Studies may observe different results depending on the measure of accessibility used. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice. Our aim was to replicate and extend these promising findings. Methodology/Principal Findings: Isolation and maintenance of human muscle derived cells (mdcs) was performed as published for human pericytes. Mdscs were characterized by immunostaining, flow cytometry and RT-PCR; also, their ability to differentiate into myotubes in vitro and into muscle fibres in vivo was assayed. Despite minor differences between human mdcs and pericytes, mdscs contributed to muscle regeneration after intra-muscular injection in mdx nu/nu mice, the CD56+ sub-population being especially myogenic. However, in contrast to human pericytes delivered intra-arterially in mdx SCID hosts, mdscs did not contribute to muscle regeneration after systemic delivery in mdx nu/nu hosts. Conclusions/Significance: Our data complement and extend previous findings on human skeletal muscle-derived stem cells, and clearly indicate that further work is necessary to prepare pure cell populations from skeletal muscle that maintain their phenotype in culture and make a robust contribution to skeletal muscle regeneration after systemic delivery in dystrophic mouse models. Small differences in protocols, animal models or outcome measurements may be the reason for differences between our findings and previous data, but nonetheless underline the need for more detailed studies on muscle-derived stem cells and independent replication of results before use of such cells in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Prior infection with one strain TB has been linked with diminished likelihood of re-infection by a new strain. This paper attempts to determine the role of declining prevalence of drug-susceptible TB in enabling future epidemics of MDR-TB. Methods: A computer simulation of MDR-TB epidemics was developed using an agent-based model platform programmed in NetLogo (See http://mdr.tbtools.org/). Eighty-one scenarios were created, varying levels of treatment quality, diagnostic accuracy, microbial fitness cost, and the degree of immunogenicity elicited by drug-susceptible TB. Outcome measures were the number of independent MDR-TB cases per trial and the proportion of trials resulting in MDR-TB epidemics for a 500 year period after drug therapy for TB is introduced. Results: MDR-TB epidemics propagated more extensively after TB prevalence had fallen. At a case detection rate of 75%, improving therapeutic compliance from 50% to 75% can reduce the probability of an epidemic from 45% to 15%. Paradoxically, improving the case-detection rate from 50% to 75% when compliance with DOT is constant at 75% increases the probability of MDR-TB epidemics from 3% to 45%. Conclusions: The ability of MDR-TB to spread depends on the prevalence of drug-susceptible TB. Immunologic protection conferred by exposure to drug-susceptible TB can be a crucial factor that prevents MDR-TB epidemics when TB treatment is poor. Any single population that successfully reduces its burden of drug-susceptible TB will have reduced herd immunity to externally or internally introduced strains of MDR-TB and can experience heightened vulnerability to an epidemic. Since countries with good TB control may be more vulnerable, their self interest dictates greater promotion of case detection and DOTS implementation in countries with poor control to control their risk of MDR-TB. [ABSTRACT FROM AUTHOR]

Background:Mortality among TB/HIV co-infected patients is still high particularly in developing countries. This study aimed to determine the predictors of death in TB/HIV co-infected patients during TB treatment. Methods:We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all newly registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in the Klang Valley between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes and survival. We analysed using Kaplan-Meier and conducted multivariate Cox proportional hazards analysis to identify predictors of death during TB treatment in TB/HIV co-infected patients. Results:Of the 227 patients studied, 53 (23.3%) had died at the end of the study with 40% of deaths within two months of TB diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were 90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73-11.64), CD4 T-lymphocytes count < 200 cells/µl (aHR 3.89; 95% CI 1.20-12.63), three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per 103 total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20) Conclusion:TB/HIV co-infected patients had a high case fatality rate during TB treatment. Initiation of antiretroviral therapy in these patients can improve survival by restoring immune function and preventing opportunistic infections. [ABSTRACT FROM AUTHOR]