HUNCHEST-II contributes to a shift to earlier-stage lung cancer detection: final results of a nationwide screening program.

OBJECTIVES: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases. METHODS: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients. RESULTS: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001). CONCLUSIONS: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary. CLINICAL RELEVANCE STATEMENT: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region. KEY POINTS: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary.

Identification of ascorbate- and salicylate-responsive miRNAs and verification of the spectral control of miR395 in Arabidopsis.

We assumed that miRNAs might regulate the physiological and biochemical processes in plants through their effects on the redox system and phytohormones. To check this hypothesis, the transcriptome profile of wild-type Arabidopsis and lines with decreased ascorbate (Asc), glutathione (GSH), or salicylate (Sal) levels were compared. GSH deficiency did not influence the miRNA expression, whereas lower levels of Asc and Sal reduced the accumulation of 9 and 44 miRNAs, respectively, but only four miRNAs were upregulated. Bioinformatics analysis revealed that their over-represented target genes are associated with the synthesis of nitrogen-containing and aromatic compounds, nucleic acids, and sulphate assimilation. Among them, the sulphate reduction-related miR395 - ATP-sulfurylase couple was selected to check the assumed modulating role of the light spectrum. A greater induction of the Asc- and Sal-responsive miR395 was observed under sulphur starvation in far-red light compared to white and blue light in wild-type and GSH-deficient Arabidopsis lines. Sal deficiency inhibited the induction of miR395 by sulphur starvation in blue light, whereas Asc deficiency greatly reduced it independently of the spectrum. Interestingly, sulphur starvation decreased only the level of ATP sulfurylase 4 among the miR395 target genes in far-red light. The expression level of ATP sulfurylase 3 was higher in far-red light than in blue light in wild-type and Asc-deficient lines. The results indicate the coordinated control of miRNAs by the redox and hormonal system since 11 miRNAs were affected by both Asc and Sal deficiency. This process can be modulated by light spectrum, as shown for miR395.

Light-Dependent Regulatory Interactions between the Redox System and miRNAs and Their Biochemical and Physiological Effects in Plants.

Light intensity and spectrum play a major role in the regulation of the growth, development, and stress response of plants. Changes in the light conditions affect the formation of reactive oxygen species, the activity of the antioxidants, and, consequently, the redox environment in the plant tissues. Many metabolic processes, thus the biogenesis and function of miRNAs, are redox-responsive. The miRNAs, in turn, can modulate various components of the redox system, and this process is also associated with the alteration in the intensity and spectrum of the light. In this review, we would like to summarise the possible regulatory mechanisms by which the alterations in the light conditions can influence miRNAs in a redox-dependent manner. Daily and seasonal fluctuations in the intensity and spectral composition of the light can affect the expression of miRNAs, which can fine-tune the various physiological and biochemical processes due to their effect on their target genes. The interactions between the redox system and miRNAs may be modulated by light conditions, and the proposed function of this regulatory network and its effect on the various biochemical and physiological processes will be introduced in plants.

A cross-national study on gender differences in suicide intent.

BACKGROUND: Suicide accounts for over 58,000 deaths in Europe per annum, where suicide attempts are estimated to be 20 times higher. Males have been found to have a disproportionately lower rate of suicide attempts and an excessively higher rate of suicides compared to females. The gender difference in suicide intent is postulated to contribute towards this gender imbalance. The aim of this study is to explore gender differences in suicide intent in a cross-national study of suicide attempts. The secondary aims are to investigate the gender differences in suicide attempt across age and country. METHODS: Data on suicide attempts (acquired from the EU-funded OSPI-Europe project) was obtained from eight regions in Germany, Hungary, Ireland and Portugal. Suicide intent data was categorized into 'Non-habitual Deliberate Self-Harm' (DSH), 'Parasuicidal Pause' (SP), 'Parasuicidal Gesture' (SG), and 'Serious Suicide Attempt' (SSA), applying the Feuerlein scale. Gender differences in intent were explored for significance by using χ2-tests, odds ratios, and regression analyses. RESULTS: Suicide intent data from 5212 participants was included in the analysis. A significant association between suicide intent and gender was found, where 'Serious Suicide Attempts' (SSA) were rated significantly more frequently in males than females (p < .001). There was a statistically significant gender difference in intent and age groups (p < .001) and between countries (p < .001). Furthermore, within the most utilised method, intentional drug overdose, 'Serious Suicide Attempt' (SSA) was rated significantly more often for males than females (p < .005). CONCLUSIONS: Considering the differences in suicidal intent between males and females highlighted by the current study, gender targeted prevention and intervention strategies would be recommended.

Circadian and Light Regulated Expression of CBFs and their Upstream Signalling Genes in Barley.

CBF (C-repeat binding factor) transcription factors show high expression levels in response to cold; moreover, they play a key regulatory role in cold acclimation processes. Recently, however, more and more information has led to the conclusion that, apart from cold, light-including its spectra-also has a crucial role in regulating CBF expression. Earlier, studies established that the expression patterns of some of these regulatory genes follow circadian rhythms. To understand more of this complex acclimation process, we studied the expression patterns of the signal transducing pathways, including signal perception, the circadian clock and phospholipid signalling pathways, upstream of the CBF gene regulatory hub. To exclude the confounding effect of cold, experiments were carried out at 22 °C. Our results show that the expression of genes implicated in the phospholipid signalling pathway follow a circadian rhythm. We demonstrated that, from among the tested CBF genes expressed in Hordeumvulgare (Hv) under our conditions, only the members of the HvCBF4-phylogenetic subgroup showed a circadian pattern. We found that the HvCBF4-subgroup genes were expressed late in the afternoon or early in the night. We also determined the expression changes under supplemental far-red illumination and established that the transcript accumulation had appeared four hours earlier and more intensely in several cases. Based on our results, we propose a model to illustrate the effect of the circadian clock and the quality of the light on the elements of signalling pathways upstream of the HvCBFs, thus integrating the complex regulation of the early cellular responses, which finally lead to an elevated abiotic stress tolerance.

Exploring synergistic interactions and catalysts in complex interventions: longitudinal, mixed methods case studies of an optimised multi-level suicide prevention intervention in four european countries (Ospi-Europe).

BACKGROUND: The Medical Research Council (MRC) Framework for complex interventions highlights the need to explore interactions between components of complex interventions, but this has not yet been fully explored within complex, non-pharmacological interventions. This paper draws on the process evaluation data of a suicide prevention programme implemented in four European countries to illustrate the synergistic interactions between intervention levels in a complex programme, and to present our method for exploring these. METHODS: A realist evaluation approach informed the process evaluation, which drew on mixed methods, longitudinal case studies. Data collection consisted of 47 semi-structured interviews, 12 focus groups, one workshop, fieldnoted observations of six programme meetings and 20 questionnaires (delivered at six month intervals to each of the four intervention sites). Analysis drew on the framework approach, facilitated by the use of QSR NVivo (v10). Our qualitative approach to exploring synergistic interactions (QuaSIC) also developed a matrix of hypothesised synergies that were explored within one workshop and two waves of data collection. RESULTS: All four implementation countries provided examples of synergistic interactions that added value beyond the sum of individual intervention levels or components in isolation. For instance, the launch ceremony of the public health campaign (a level 3 intervention) in Ireland had an impact on the community-based professional training, increasing uptake and visibility of training for journalists in particular. In turn, this led to increased media reporting of OSPI activities (monitored as part of the public health campaign) and also led to wider dissemination of editorial guidelines for responsible reporting of suicidal acts. Analysis of the total process evaluation dataset also revealed the new phenomenon of the OSPI programme acting as a catalyst for externally generated (and funded) activity that shared the goals of suicide prevention. CONCLUSIONS: The QuaSIC approach enabled us to develop and refine our definition of synergistic interactions and add the innovative concept of catalytic effects. This represents a novel approach to the evaluation of complex interventions. By exploring synergies and catalytic interactions related to a complex intervention or programme, we reveal the added value to planned activities and how they might be maximised.

Developing social capital in implementing a complex intervention: a process evaluation of the early implementation of a suicide prevention intervention in four European countries.

BACKGROUND: Variation in the implementation of complex multilevel interventions can impact on their delivery and outcomes. Few suicide prevention interventions, especially multilevel interventions, have included evaluation of both the process of implementation as well as outcomes. Such evaluation is essential for the replication of interventions, for interpreting and understanding outcomes, and for improving implementation science. This paper reports on a process evaluation of the early implementation stage of an optimised suicide prevention programme (OSPI-Europe) implemented in four European countries. METHODS: The process analysis was conducted within the framework of a realist evaluation methodology, and involved case studies of the process of implementation in four European countries. Datasets include: repeated questionnaires to track progress of implementation including delivery of individual activities and their intensity; serial interviews and focus groups with stakeholder groups; and detailed observations at OSPI implementation team meetings. RESULTS: Analysis of local contexts in each of the four countries revealed that the advisory group was a key mechanism that had a substantial impact on the ease of implementation of OSPI interventions, particularly on their ability to recruit to training interventions. However, simply recruiting representatives of key organisations into an advisory group is not sufficient to achieve impact on the delivery of interventions. In order to maximise the potential of high level 'gatekeepers', it is necessary to first transform them into OSPI stakeholders. Motivations for OSPI participation as a stakeholder included: personal affinity with the shared goals and target groups within OSPI; the complementary and participatory nature of OSPI that adds value to pre-existing suicide prevention initiatives; and reciprocal reward for participants through access to the extended network capacity that organisations could accrue for themselves and their organisations from participation in OSPI. CONCLUSIONS: Exploring the role of advisory groups and the meaning of participation for these participants revealed some key areas for best practice in implementation: careful planning of the composition of the advisory group to access target groups; the importance of establishing common goals; the importance of acknowledging and complementing existing experience and activity; and facilitating an equivalence of benefit from network participation.

Relationship between religiosity and health: evidence from a post-communist country.

BACKGROUND: The relationship between religiosity and health has been investigated in the western world for decades. However, very little data are available from the post-communist region of Europe, where religion was suppressed for a long time. PURPOSE: The aim of the present study was to lessen this gap. METHODS: In 2002, 13 years after the regime change, 12,643 persons (mean age = 47.6 ± 17.9 years; 44.8 % male) were interviewed in a Hungarian representative survey. The relationship of mental and physical health indicators with religious worship and personal importance of religion-controlling for several psychological and lifestyle characteristics-were analyzed using the general linear model procedure. RESULTS: Our results showed that practicing religion was largely associated with better mental health and more favorable physical health status. However, persons being religious in their own way tended to show more unfavourable results across several variables when compared to those practicing religion regularly in a religious community or even to those considering themselves as non-religious. The personal importance of religion showed a mixed pattern, since it was positively associated not only with well-being but depression and anxiety as well. CONCLUSIONS: We can conclude that even after an anti-religious totalitarian political system practicing religion still remained a health protecting factor.

[Role of pulse oximetric monitoring during gastrointestinal endoscopy. Prospective multicenter study of the Gastroenterology Working Group of the Veszprém Regional Committee of the Hungarian Academy of Sciences (VEAB)]. / Az endoszkópos vizsgálatok pulzoximetriás monitorozásának jelentosége. Az MTA VEAB Gasztroenterológiai Munkabizottságának prospektív multicentrikus vizsgálata.

INTRODUCTION: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units. AIMS: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy. METHOD: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation. RESULTS: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors. CONCLUSION: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia.

Early ERCP and biliary sphincterotomy with or without small-caliber pancreatic stent insertion in patients with acute biliary pancreatitis: better overall outcome with adequate pancreatic drainage.

OBJECTIVE: To analyze the efficacy of pancreatic duct (PD) stenting following endoscopic sphincterotomy (EST) compared with EST alone in reducing complication rate and improving overall outcome in acute biliary pancreatitis (ABP). METHODS: Between 1 January 2009 and 1 July 2010, 141 nonalcoholic patients with clinical, laboratory and imaging evidence of ABP were enrolled. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was performed within 72 h from the onset of pain. Seventy patients underwent successful ERCP, EST, and stone extraction (control group); 71 patients (PD stent group) had EST, stone extraction and small-caliber (5 Fr, 3-5 cm) pancreatic stent insertion. All patients were hospitalized for medical therapy and jejunal feeding and were followed up. RESULTS: The mean age, Glasgow score, symptom to ERCP time, mean amylase and CRP levels at initial presentation were not significantly different in the PD stent group compared to the control group: 60.6 vs. 64.3, 3.21 vs. 3.27, 34.4 vs. 40.2, 2446.9 vs. 2114.3, 121.1 vs. 152.4, respectively. Complications (admission to intensive care unit, pancreatic necrosis with septicemia, large (>6 cm) pseudocyst formation, need for surgical necrosectomy) were less frequent in the PD stent group resulting in a significantly lower overall complication rate (9.86% vs. 31.43%, p < 0.002). Mortality rates (0% vs. 4.28%) were comparable, reasonably low and without any significant differences. CONCLUSIONS: Temporary small-caliber PD stent placement may offer sufficient drainage to reverse the process of ABP. Combined with EST the process results in a significantly less complication rate and better clinical outcome compared with EST alone during the early course of ABP.

Competency-Based Training and Assessment of Listening Skills: A Waitlist-Controlled Study in European Telephone Emergency Services.

Background: Telephone emergency services (TES) provide an essential part of suicide prevention and emotional support services across different health care settings. TES are usually provided by paraprofessional counselors, who need specific training in listening skills to meet the demands of callers. Method: This project developed a competency-based training for listening skills which was then evaluated in a randomized controlled waitlist study across four EU countries (Germany, Hungary, Italy, and the Netherlands). Each country provided one training group and one waitlist group. Across countries, a total of 71 (trained: n = 36, waiting: n = 35) counselor trainees were assessed in a standardized, simulated emergency call with an actor client either before or after training participation. Calls were audiotaped and competencies in listening skills were evaluated by external raters using a standardized rating form. Results: Trained counselors showed significantly better listening skills than participants from the waitlist condition. Conclusion: Results provide support for the efficacy of a competency-based training for listening skills in the field of TES across Europe. Furthermore, results demonstrated that a standardized competency-based assessment with an actor client is suitable to assess listening skills.

Drug suicide: a sex-equal cause of death in 16 European countries.

BACKGROUND: There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). METHODS: Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. RESULTS: No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. CONCLUSIONS: Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.

An intra-abdominal desmoid tumor.

Desmoid tumor is a very rare neoplasm which develops from fibroblasts. These tumors do not have the ability to metastasize, but they can cause significant morbidity and mortality by local invasion and they are prone to local recurrence. We present a case of an aggressive fibromatosis in a 28-year-old male patient with no previous medical history. The tumor was in the retroperitoneum and eventually caused perforation of the coecum. During the operation, no metastasis was found; however, local lymphadenopathy was seen. After the surgical resection, no adjuvant therapy (radio or chemotherapy) was given to the patient and on follow-up (after three years), no recurrence was observed.

Feasibility and safety of emergency ERCP and small-caliber pancreatic stenting as a bridging procedure in patients with acute biliary pancreatitis but difficult sphincterotomy.

BACKGROUND: The aims of the present study were: (1) to assess the feasibility and safety of emergency endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic duct (PD) stenting with small-caliber stents as a bridging procedure in acute biliary pancreatitis (ABP) patients in whom biliary endoscopic sphincterotomy (EST) proved difficult, failed or was contraindicated, and (2) to compare the clinical outcome of those patients having emergency ERCP with and without pancreatic stent. METHOD: Eighty-seven consecutive patients with ABP were referred for emergency ERCP. In 60 of these ABP patients, ERCP, EST, and stone extraction (if necessary) were performed without PD stenting. In the remaining 27 patients, small-caliber (3-5 F, 4 cm) pancreatic stent insertion was initially applied. All patients were hospitalized for medical therapy and were followed up. RESULTS: The mean ages, the initial symptom-to-ERCP times, the Glasgow severity scores, and the peak amylase and CRP levels at initial presentation were not significantly different in the ERCP + EST with PD stent group versus the ERCP + EST without PD stent group. More importantly, the complication rate was significantly lower in the ERCP + EST with PD stent group versus the ERCP + EST without PD stent group (7.4% vs. 25%); while the mortality rates (0% vs. 6.7%) were comparable, reasonably low, and demonstrated no statistically significant differences. CONCLUSIONS: Temporary PD stenting with small-caliber stents is a safe and effective procedure that may afford sufficient PD decompression to reverse the process of ABP and serve as a bridging procedure in severe ABP in patients with failed, complicated, or contraindicated biliary EST.

Rescue ERCP and insertion of a small-caliber pancreatic stent to prevent the evolution of severe post-ERCP pancreatitis: a case-controlled series.

INTRODUCTION: Recently prophylactic placement of a trans-sphincteric pancreatic stent has successfully been applied to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Rescue ERCP and emergency application of small-caliber pancreatic stents during the early course of post-ERCP pancreatitis as a possible endoscopic therapy has not been reported yet. METHODS: All patients who underwent ERCP were hospitalized for at least 24 h, with routine laboratory testing of amylase levels. Out of 1,225 ERCPs, evolution of severe post-ERCP pancreatitis was anticipated in six consecutive patients, based on severe pancreatic pain attack, more than tenfold elevation of serum amylase levels at 8 and 24 h, and moderate rise of white blood cell (WBC) and C-reactive protein (CRP) levels. Rescue ERCP and emergency application of small-caliber (4-5F, 4-cm, Geenen stent) pancreatic stents were successfully performed in all patients within 8-20 h after the initial ERCP. RESULTS: Moderate to severe papillary oedema was observed in all patients during the rescue ERCP. Pancreatic pain was promptly reduced after the rescue pancreatic drainage procedure and completely diminished within 24 h after pancreatic stenting. Serum amylase levels were exponentially reduced and normalized within 72 h in all patients; no pancreatic necrosis or any other late complications were observed. Pancreatic stents could be safely removed a few days later. CONCLUSION: Rescue pancreatic stenting with small-caliber prophylactic pancreatic stents seems to be a safe and effective procedure that might be feasible to stop the evolution of severe post-ERCP pancreatitis, but prospective controlled studies are clearly demanded to support this innovative approach.

Prophylactic pancreas stenting followed by needle-knife fistulotomy in patients with sphincter of Oddi dysfunction and difficult cannulation: new method to prevent post-ERCP pancreatitis.

INTRODUCTION: The aim of the present study was to reduce post-endoscopic retrograde cholangiopancreatography (ERCP) complications with a combination of early needle-knife access fistulotomy and prophylactic pancreatic stenting in selected high-risk sphincter of Oddi dysfunction (SOD) patients with difficult cannulation. METHODS: Prophylactic pancreatic stent insertion was attempted in 22 consecutive patients with definite SOD and difficult cannulation. After 10 min of failed selective common bile duct cannulation, but repeated (>5x) pancreatic duct contrast filling, a prophylactic small calibre (3-5 Fr) pancreatic stent was inserted, followed by fistulotomy with a standard needle-knife, then a standard complete biliary sphincterotomy followed. The success and complication rates were compared retrospectively with a cohort of 35 patients, in which we persisted with the application of standard methods of cannulation without pre-cutting methods. RESULTS: Prophylactic pancreatic stenting followed by needle-knife fistulotomy was successfully carried out in all 22 consecutive patients, and selective biliary cannulation and complete endoscopic sphincterotomy were achieved in all but two cases. In this group, not a single case of post-ERCP pancreatitis was observed, in contrast with a control group of three mild, 10 moderate and two severe post-ERCP pancreatitis cases. The frequency of post-ERCP pancreatitis was significantly different: 0% versus 43%, as were the post-procedure (24 h mean) amylase levels: 206 U/L versus 1959 U/L, respectively. CONCLUSIONS: In selected, high-risk, SOD patients, early, prophylactic pancreas stent insertion followed by needle-knife fistulotomy seems a safe and effective procedure with no or only minimal risk of post-ERCP pancreatitis. However, prospective, randomized studies are awaited to lend to support to our approach.

Light intensity and spectrum affect metabolism of glutathione and amino acids at transcriptional level.

The effects of various light intensities and spectral compositions on glutathione and amino acid metabolism were compared in wheat. Increase of light intensity (low-normal-high) was accompanied by a simultaneous increase in the shoot fresh weight, photosynthetic activity and glutathione content. These parameters were also affected by the modification of the ratios of blue, red and far-red components (referred to as blue, pink and far-red lights) compared to normal white light. The photosynthetic activity and the glutathione content decreased to 50% and the percentage of glutathione disulfide (characterising the redox state of the tissues) in the total glutathione pool doubled in far-red light. The alterations in the level and redox state of the antioxidant glutathione resulted from the effect of light on its synthesis as it could be concluded from the changes in the transcription of the related genes. Modification of the light conditions also greatly affected both the amount and the ratio of free amino acids. The total free amino acid content was greatly induced by the increase of light intensity and was greatly reduced in pink light compared to the normal intensity white light. The concentrations of most amino acids were similarly affected by the light conditions as described for the total free amino acid content but Pro, Met, Thr, ornithine and cystathionine showed unique response to light. As observed for the amino acid levels, the expression of several genes involved in their metabolism also enhanced due to increased light intensity. Interestingly, the modification of the spectrum greatly inhibited the expression of most of these genes. Correlation analysis of the investigated parameters indicates that changes in the light conditions may affect growth through the adjustment of photosynthesis and the glutathione-dependent redox state of the tissues. This process modifies the metabolism of glutathione and amino acids at transcriptional level.

Prevention of suicidal behaviour: Results of a controlled community-based intervention study in four European countries.

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.

Somatosensory hypersensitivity in the referred pain area in patients with chronic biliary pain and a sphincter of Oddi dysfunction: new aspects of an almost forgotten pathogenetic mechanism.

BACKGROUND AND AIMS: Somatosensory hyperalgesia in the referred pain area (RPA) in patients with acute or chronic abdominal pain syndromes may result from the convergence of nerve fibers from visceral and somatic tissues at the spinal and supraspinal levels. Chronic biliary pain in patients with the postcholecystectomy syndrome (i.e., biliary hypersensitivity) may be explained by persistent hyperexcitability of neurons in the central nervous system (CNS). The aim of this study was to evaluate the cutaneous neural sensory perception in the RPA in patients with chronic postcholecystectomy biliary pain and a sphincter of Oddi (SO) dysfunction (SOD). METHODS: Forty-two patients with persistent biliary pain and suspected SOD, 27 age-matched healthy volunteers, and 18 age-matched asymptomatic cholecystectomized controls were prospectively investigated by quantitative sensory testing (Neurometer CPT). The biliary symptoms and the severity of pain were classified on a visual analog pain severity scale system via a previously validated and standardized questionnaire. The patients helped the doctors locate the RPA in the right upper quadrant. The sensory detection threshold was determined noninvasively (Neurometer CPT) with transcutaneous electrical stimulation at 5, 250, and 2,000 Hz, and different current intensities (range from 0.01 to 9.99 mA) applied in a single (patient) blinded method. These three frequencies selectively excite small unmyelinated (C fibers), small myelinated (A-delta), and large myelinated (A-beta) fibers, which transmit dull pain, sharp pain, and touch, respectively. The contralateral region of the abdomen left upper quadrant served as the control area. The sensory current perception threshold ratio (SCPTR) of the data measured in the contralateral area and the RPA was calculated. RESULTS: The SCPTRs in the definite SOD patients with biliary pain, healthy volunteers, the asymptomatic cholecystectomized controls, and the symptomatic cholecystectomized patients but without SOD were 2.32 +/- 1.4 versus 1.06 +/- 0.24 versus 0.97 +/- 0.16 versus 0.83 +/- 0.35 at 2,000 Hz; 2.19 +/- 1.0 versus 1.01 +/- 0.26 versus 1.02 +/- 0.25 versus 0.88 +/- 0.35 at 250 Hz; and 2.19 +/- 1.1 versus 1.12 +/- 0.26 versus 0.99 +/- 0.37 versus 0.84 +/- 0.32 at 5 Hz, respectively. Significant hypersensitivity was detected in the RPA at different stimulation frequencies in the SOD patients with biliary pain versus the cholecystectomized controls: at 5 Hz: P = 0.00001; at 250 Hz: P = 0.00001; and at 2,000 Hz: P = 0.0001, respectively. CONCLUSION: Continuous visceral pain (biliary pain) caused by local inflammatory/sensitizing processes or a CNS malfunction could lead to significant hypersensitivity of the peripheral nociceptive nerve fibers in SOD patients. Postcholecystectomy pain may be explained by persistent hyperexcitability of the nociceptive neurons in the CNS with or without objective motility disorders of the SO.

Effectiveness of General Practitioner training to improve suicide awareness and knowledge and skills towards depression.

BACKGROUND: General Practitioners (GPs) are well placed as gatekeepers for managing depression and suicidal ideation but not always well prepared. Capacity building has therefore been recommended as a useful strategy for suicide prevention. This study aimed to examine whether GPs' knowledge and attitudes towards and confidence to deal with depression and suicide improve after following a training program. METHODS: As part of the OSPI-Europe multilevel intervention, a standardized training on depression and suicide was provided to 208 GPs in three European countries. Core outcomes were assessed using the Depression Attitude Questionnaire, the Attitude towards Suicide Prevention Scale, and the Morriss Confidence Scale. Data were collected before and after training, and at three to six months follow-up. RESULTS: At baseline, GPs demonstrated various stigmatizing attitudes towards depression and low optimism about the therapeutic treatment of depression. They showed moderately positive attitudes towards suicide prevention but felt little confident in dealing with depression and suicide in daily practice. The training resulted in improved knowledge, attitudes and confidence regarding depression and suicide and their prevention and treatment. At follow-up, only the increase in confidence to deal with depression and suicide was sustained. LIMITATIONS: The Depression Attitude Questionnaire has rather weak psychometric properties. Other external factors may have contributed to the observed training effects as the study included no control group. CONCLUSIONS: The OSPI-Europe training program was able to improve the GPs' attitudes towards suicide prevention, several attitudes towards depression and its treatment as well as the GPs' confidence to deal with depression and suicide in everyday practice. At follow, only the GPs' confidence to deal with depression and suicide was preserved.