Limosilactobacillus fermentum Limits Candida glabrata Growth by Ergosterol Depletion.

Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Δerg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum. IMPORTANCE The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. Lactobacillus species, belonging to the healthy human microbiome, are thought to prevent C. glabrata infections. We investigated the antifungal effect of Limosilactobacillus fermentum on C. glabrata strains quantitively in vitro. The interaction between C. glabrata and L. fermentum evokes an upregulation of genes required for the synthesis of ergosterol, a sterol constituent of the fungal plasma membrane. We found a dramatic reduction of ergosterol in C. glabrata when it was exposed to L. fermentum. This effect extended to other Candida species and other Lactobacillus species. Furthermore, fungal growth was efficiently suppressed by a combination of L. fermentum and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by L. fermentum.

Modification in the Motor Skills of Seniors in Care Homes Using Serious Games and the Impact of COVID-19: Field Study.

BACKGROUND: The pandemic has highlighted the importance of low-threshold opportunities for exercise and physical activity. At the beginning of 2020, the COVID-19 pandemic led to many restrictions, which affected seniors in care facilities in the form of severe isolation. The isolation led, among other things, to a lack of exercise, which has led to a multitude of negative effects for this target group. Serious games can potentially help by being used anywhere at any time to strengthen skills with few resources. OBJECTIVE: The aim of this study is to evaluate the effectiveness of a serious game to strengthen motor skills (study 1) and the influence of pandemic restrictions (study 2) on seniors in care facilities. METHODS: The data on motor skills (measured by the Tinetti test) originated from an intervention study with repeated measurements that was interrupted by the pandemic conditions. Data were collected 4 times every 3 months with an intervention group (IG, training 3 times for 1 hour per week) and a control group (CG, no intervention). There were 2 substudies. The first considered the first 6 months until the pandemic restrictions, while the second considered the influence of the restrictions on motor skills. RESULTS: The sample size was 70. The IG comprised 31 (44%) participants, with 22 (71%) female and 9 (29%) male seniors with an average age of 85 years. The CG comprised 39 (56%) participants, with 31 (79%) female and 8 (21%) male seniors with an average age of 87 years. In study 1, mixed-design ANOVA showed no significant interaction between measurement times and group membership for the first measurements (F2.136=1.414, P<.25, partial η2=.044), but there was a significant difference between the CG (mean 16.23, SD 1.1) and the IG (mean 19.81, SD 1.2) at the third time of measurement (P=.02). In study 2 the mixed-design ANOVA (used to investigate motor skills before and after the pandemic conditions between the 2 groups) couldn't reveal any significant interaction between measurement times and group membership: F1.67=2.997, P<.09, partial η2=.043. However, there was a significant main effect of the time of measurement: F1.67=5.44, P<.02, partial η²=.075. CONCLUSIONS: During the first 6 months, the IG showed increased motor skills, whereas the motor skills of the CG slightly deteriorated and showed a statistically significant difference after 6 months. The pandemic restrictions leveled the difference and showed a significant negative effect on motor skills over 3 months. As our results show, digital games have the potential to break down access barriers and promote necessary maintenance for important skills. The pandemic has highlighted the importance of low-threshold opportunities for exercise and physical activity. This potentially great benefit for the challenges of tomorrow shows the relevance of the topic and demonstrates the urgent need for action and research. TRIAL REGISTRATION: Deutsches Register klinischer Studien DRKS00016633; https://tinyurl.com/yckmj4px.

The Effectiveness of a Serious Game (MemoreBox) for Cognitive Functioning Among Seniors in Care Facilities: Field Study.

BACKGROUND: Serious games have been found to have enhancing and preventative effects on cognitive abilities in healthy older adults. Yet, there are few results on the effects in older seniors with age-related low cognitive impairments. Their special needs were considered when designing and using innovate technology in the area of prevention, which is especially relevant owing to the continuously aging population. OBJECTIVE: The objective of this study was to evaluate the impact of a serious game on the cognitive abilities of seniors in order to potentially implement innovative resource-oriented technological interventions that can help to meet future challenges. METHODS: In this controlled trial, we tested the serious game MemoreBox, which features modules specifically designed for seniors in nursing homes. Over a period of 1 year, we tested the cognitive abilities of 1000 seniors at 4 time points using the Mini-Mental Status Test. Only half of the participating seniors engaged with the serious game. RESULTS: The study included an intervention group (n=56) and a control group (did not play; n=55). Based on the in-game data collection, a second intervention group (n=38) was identified within the original intervention group, which exactly followed the planned protocol. There were no noteworthy differences between the demographic and main variables of the overall sample. The large reduction in the sample size was due to the effects of the COVID-19 pandemic (drop-out rate: 88.9%). The CI was set at 5%. Mixed analysis of variance (ANOVA) between the cognitive abilities of the intervention and control groups did not show a statistically significant difference between time and group (F2.710,295.379=1.942; P=.13; partial η²=0.018). We noted approximately the same findings for mixed ANOVA between the cognitive abilities of the second intervention and control groups (F3,273=2.574; P=.054; partial η²=0.028). However, we did observe clear tendencies and a statistically significant difference between the 2 groups after 9 months of the intervention (t88.1=-2.394; P=.02). CONCLUSIONS: The results of this study show similarities with the current research situation. Moreover, the data indicate that the intervention can have an effect on the cognitive abilities of seniors, provided that they regularly play the serious game of MemoreBox. The small sample size means that the tendency toward improvement cannot be proven as statistically significant. However, the tendency shown warrants further research. Establishing an effective prevention tool as part of standard care in nursing homes by means of an easy-to-use serious game would be a considerable contribution to the weakened health care system in Germany as it would offer a means of activating senior citizens in partially and fully inpatient care facilities. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016633; https://tinyurl.com/2e4765nj.

Narrow mutational signatures drive acquisition of multidrug resistance in the fungal pathogen Candida glabrata.

Fungal infections are a growing medical concern, in part due to increased resistance to one or multiple antifungal drugs. However, the evolutionary processes underpinning the acquisition of antifungal drug resistance are poorly understood. Here, we used experimental microevolution to study the adaptation of the yeast pathogen Candida glabrata to fluconazole and anidulafungin, two widely used antifungal drugs with different modes of action. Our results show widespread ability of rapid adaptation to one or both drugs. Resistance, including multidrug resistance, is often acquired at moderate fitness costs and mediated by mutations in a limited set of genes that are recurrently and specifically mutated in strains adapted to each of the drugs. Importantly, we uncover a dual role of ERG3 mutations in resistance to anidulafungin and cross-resistance to fluconazole in a subset of anidulafungin-adapted strains. Our results shed light on the mutational paths leading to resistance and cross-resistance to antifungal drugs.

A phosphatase-centric mechanism drives stress signaling response.

Changing environmental cues lead to the adjustment of cellular physiology by phosphorylation signaling networks that typically center around kinases as active effectors and phosphatases as antagonistic elements. Here, we report a signaling mechanism that reverses this principle. Using the hyperosmotic stress response in Saccharomyces cerevisiae as a model system, we find that a phosphatase-driven mechanism causes induction of phosphorylation. The key activating step that triggers this phospho-proteomic response is the Endosulfine-mediated inhibition of protein phosphatase 2A-Cdc55 (PP2ACdc55 ), while we do not observe concurrent kinase activation. In fact, many of the stress-induced phosphorylation sites appear to be direct substrates of the phosphatase, rendering PP2ACdc55 the main downstream effector of a signaling response that operates in parallel and independent of the well-established kinase-centric stress signaling pathways. This response affects multiple cellular processes and is required for stress survival. Our results demonstrate how a phosphatase can assume the role of active downstream effectors during signaling and allow re-evaluating the impact of phosphatases on shaping the phosphorylome.

Human Pathogenic Candida Species Respond Distinctively to Lactic Acid Stress.

Several Candida species are opportunistic human fungal pathogens and thrive in various environmental niches in and on the human body. In this study we focus on the conditions of the vaginal tract, which is acidic, hypoxic, glucose-deprived, and contains lactic acid. We quantitatively analyze the lactic acid tolerance in glucose-rich and glucose-deprived environment of five Candida species: Candidaalbicans, Candida glabrata, Candida parapsilosis, Candida krusei and Candida tropicalis. To characterize the phenotypic space, we analyzed 40-100 clinical isolates of each species. Each Candida species had a very distinct response pattern to lactic acid stress and characteristic phenotypic variability. C. glabrata and C. parapsilosis were best to withstand high concentrations of lactic acid with glucose as carbon source. A glucose-deprived environment induced lactic acid stress tolerance in all species. With lactate as carbon source the growth rate of C. krusei is even higher compared to glucose, whereas the other species grow slower. C. krusei may use lactic acid as carbon source in the vaginal tract. Stress resistance variability was highest among C. parapsilosis strains. In conclusion, each Candida spp. is adapted differently to cope with lactic acid stress and resistant to physiological concentrations.

High Throughput Screening for New Fungal Polyester Hydrolyzing Enzymes.

There is a strong need for novel and more efficient polyester hydrolyzing enzymes in order to enable the development of more environmentally friendly plastics recycling processes allowing the closure of the carbon cycle. In this work, a high throughput system on microplate scale was used to screen a high number of fungi for their ability to produce polyester-hydrolyzing enzymes. For induction of responsible enzymes, the fungi were cultivated in presence of aliphatic and aromatic polyesters [poly(1,4-butylene adipate co terephthalate) (PBAT), poly(lactic acid) (PLA) and poly(1,4-butylene succinate) (PBS)], and the esterase activity in the culture supernatants was compared to the culture supernatants of fungi grown without polymers. The results indicate that the esterase activity of the culture supernatants was induced in about 10% of the tested fungi when grown with polyesters in the medium, as indicated by increased activity (to >50 mU/mL) toward the small model substrate para-nitrophenylbutyrate (pNPB). Incubation of these 50 active culture supernatants with different polyesters (PBAT, PLA, PBS) led to hydrolysis of at least one of the polymers according to liquid chromatography-based quantification of the hydrolysis products terephthalic acid, lactic acid and succinic acid, respectively. Interestingly, the specificities for the investigated polyesters varied among the supernatants of the different fungi.

Antifungal susceptibility of yeast bloodstream isolates collected during a 10-year period in Austria.

BACKGROUND: Candida-associated infections put a significant burden on western healthcare systems. Development of (multi-)resistant fungi can become untreatable and threaten especially vulnerable target groups, such as the immunocompromised. OBJECTIVES: We assessed antifungal susceptibility and explored possible influence factors of clinical Candida isolates collected from Austrian hospitals between 2007 and 2016. METHODS: Thousand three hundred and sixty clinical Candida spp. isolated from blood cultures were subjected to antifungal susceptibility testing (AFST) in a liquid-handling aided continuous microdilution assay. We tested against fluconazole, voriconazole, posaconazole, itraconazole, isavuconazole, anidulafungin, caspofungin and micafungin according to EUCAST with additional recording of growth curves. We performed rigid quality control on each assay via growth curve assessment and included two standard reference strains. Minimal inhibitory concentrations (MIC) were quantified according to EUCAST guideline E.DEF 7.3.1, and susceptibility was evaluated using EUCAST clinical breakpoints. RESULTS: The isolate collection consisted of Candida albicans (59%), C. glabrata (19%), C. parapsilosis (9%), C. tropicalis (5%) and C. krusei (3%) and few other Candida species and fungi (5%). During the observed time period, species abundance and antifungal resistance rates remained constant. Multi-resistance was rare and we found no single isolate which was resistant to both azoles and echinocandins. Within the antifungal resistance profile of our strain collection, we observed clusters along species boundaries. CONCLUSIONS: Over the last decade, the distribution of Candida species and its level of antifungal resistance remained constant in Austria. Our data compare well with other European countries. Principal component analysis of the susceptibility profile of this collection revealed species-specific clusters and substantial intra-species variation, especially for C. glabrata.

Competition of Candida glabrata against Lactobacillus is Hog1 dependent.

Candida glabrata is a common human fungal commensal and opportunistic pathogen. This fungus shows remarkable resilience as it can form recalcitrant biofilms on indwelling catheters, has intrinsic resistance against azole antifungals, and is causing vulvovaginal candidiasis. As a nosocomial pathogen, it can cause life-threatening bloodstream infections in immune-compromised patients. Here, we investigate the potential role of the high osmolarity glycerol response (HOG) MAP kinase pathway for C. glabrata virulence. The C. glabrata MAP kinase CgHog1 becomes activated by a variety of environmental stress conditions such as osmotic stress, low pH, and carboxylic acids and subsequently accumulates in the nucleus. We found that CgHog1 allows C. glabrata to persist within murine macrophages, but it is not required for systemic infection in a mouse model. C. glabrata and Lactobacilli co-colonise mucosal surfaces. Lactic acid at a concentration produced by vaginal Lactobacillus spp. causes CgHog1 phosphorylation and accumulation in the nucleus. In addition, CgHog1 enables C. glabrata to tolerate different Lactobacillus spp. and their metabolites when grown in co-culture. Using a phenotypic diverse set of clinical C. glabrata isolates, we find that the HOG pathway is likely the main quantitative determinant of lactic acid stress resistance. Taken together, our data indicate that CgHog1 has an important role in the confrontation of C. glabrata with the common vaginal flora.

Characteristics of adapted hydrogenotrophic community during biomethanation.

The results presented in this study were carried out as concomitant experiments during the start-up and operation of a biomethanation unit to evaluate the effect of process parameters on carbon conversion, product formation (methane and acetate) and community composition. For that, two different samples were withdrawn from a trickle-bed reactor with immobilized enrichment culture of hydrogenotrophic methanogens adapted from sewage sludge. One sample was taken from the recirculation liquid during start-up phase while the other was withdrawn directly from the carrier material in the reactor. Elevated acid levels especially during start-up were shown to affect the overall carbon conversion. This effect was also seen during the acid tolerance testing reported here. Final acid concentrations of 1.6±0.3g/L resulted in a reduced conversion ratio of only 46%. Without acid addition complete conversion of CO2 in the headspace was achieved. However, maximum methane production of 0.55±0.02mmol after 4days of incubation was monitored at moderate initial acetate concentration of 0.4g/L. In both analyzed inoculation materials Methanobacterium species were by far the most dominant Archaea with 21.8% in the recirculation liquid during start-up and 84.8% in the enrichment culture immobilized on the carrier material. The microbial composition of the two analyzed samples is in accordance with the results obtained for the carbon conversion and product formation. With approximately 50% of Bacteroidetes and Firmicutes present during reactor start-up the acetic acid production significantly contributed to the overall carbon conversion. In contrast, methane was produced almost exclusively in trials representing continuous operation where acetogenic bacteria accounted only up to 17.5%. In summary, the acid accumulation monitored during reactor start-up of a biomethanation unit is most likely to result from the microbial composition present. Nevertheless, complete adaptation to hydrogenotrophic conditions was proven to alter the consortium and yield methane as main product alongside high carbon conversion of up to 70.5±1.8%.

Ribosome quality control is a central protection mechanism for yeast exposed to deoxynivalenol and trichothecin.

BACKGROUND: The trichothecene mycotoxins deoxynivalenol (DON) and trichothecin (TTC) are inhibitors of eukaryotic protein synthesis. Their effect on cellular homeostasis is poorly understood. We report a systematic functional investigation of the effect of DON and TTC on the yeast Saccharomyces cerevisiae using genetic array, network and microarray analysis. To focus the genetic analysis on intracellular consequences of toxin action we eliminated the PDR5 gene coding for a potent pleiotropic drug efflux protein potentially confounding results. We therefore used a knockout library with a pdr5Δ strain background. RESULTS: DON or TTC treatment creates a fitness bottleneck connected to ribosome efficiency. Genes isolated by systematic genetic array analysis as contributing to toxin resistance function in ribosome quality control, translation fidelity, and in transcription. Mutants in the E3 ligase Hel2, involved in ribosome quality control, and several members of the Rpd3 histone deacetylase complex were highly sensitive to DON. DON and TTC have similar genetic profiles despite their different toxic potency. Network analysis shows a coherent and tight network of genetic interactions among the DON and TTC resistance conferring gene products. The networks exhibited topological properties commonly associated with efficient processing of information. Many sensitive mutants have a "slow growth" gene expression signature. DON-exposed yeast cells increase transcripts of ribosomal protein and histone genes indicating an internal signal for growth enhancement. CONCLUSIONS: The combination of gene expression profiling and analysis of mutants reveals cellular pathways which become bottlenecks under DON and TTC stress. These are generally directly or indirectly connected to ribosome biosynthesis such as the general secretory pathway, cytoskeleton, cell cycle delay, ribosome synthesis and translation quality control. Gene expression profiling points to an increased demand of ribosomal components and does not reveal activation of stress pathways. Our analysis highlights ribosome quality control and a contribution of a histone deacetylase complex as main sources of resistance against DON and TTC.

Affective set-shifting deficits in patients with major depression in remission.

While numerous studies have focused on neuropsychological deficits during acute depressive episodes, results have been inconsistent for patients in remission. This case-control study aimed to explore whether remitted patients show deficits in an affective shifting task that has proven sensitive to assess emotional-cognitive deficits in acute depression. 69 fully remitted depressed patients were compared with 76 matched healthy subjects in their performance of a picture-based affective shifting task. Compared to healthy subjects, remitted patients show impaired go/no-go performance during shift, but not during non-shift conditions, reflecting a specific deficit in affective set-shifting. Impaired performance concerns omissions rather than false alarms or response times and is correlated with the duration of illness, but not the number of depressive episodes, time since remission or age. Our findings suggest that affective set-shifting deficits are also present during remission of depressive symptoms. These deficits may particularly concern enhanced inhibitory control and seem to develop over the course of the illness independent of acute episodes.

Impact of phonological processing skills on written language acquisition in illiterate adults.

Illiteracy remains a world-wide problem not only for children but also for adults. Phonological processing has been defined as a crucial factor for the acquisition of written language, which usually occurs in childhood. However, it is unclear to what extent phonological processing is necessary in order for adults to acquire written language skills. We tested 47 illiterate adults before and after a one-year alphabetization course in several cognitive domains relevant to phonological processing and compared their results to 41 matched controls who did not take part in the alphabetization course. Phonological awareness in the narrower sense (e.g., phoneme association) was a stronger predictor of alphabetization outcome than demographic variables such as years of education. In addition, despite improvement of illiterate individuals in phonological awareness, short-term memory, and visual attention from before to after the alphabetization course, they did not reach the phonological processing level of literate controls. Our results confirm that the alphabetization of adults requires and enhances phonological processes similar to those of children. Nevertheless, specific aspects, such as improvements in short-term memory or visual attention, need to be considered in order to improve and optimize alphabetization programs for adults.

Resource allocation and fluid intelligence: insights from pupillometry.

Thinking is biological work and involves the allocation of cognitive resources. The aim of this study was to investigate the impact of fluid intelligence on the allocation of cognitive resources while one is processing low-level and high-level cognitive tasks. Individuals with high versus average fluid intelligence performed low-level choice reaction time tasks and high-level geometric analogy tasks. We combined behavioral measures to examine speed and accuracy of processing with pupillary measures that indicate resource allocation. Individuals with high fluid intelligence processed the low-level choice reaction time tasks faster than normal controls. The task-evoked pupillary responses did not differ between groups. Furthermore, individuals with high fluid intelligence processed the high-level geometric analogies faster, more accurately, and showed greater pupil dilations than normal controls. This was only true, however, for the most difficult analogy tasks. In addition, individuals with high fluid intelligence showed greater preexperimental pupil baseline diameters than normal controls. These results indicate that individuals with high fluid intelligence have more resources available and thus can solve more demanding tasks. Moreover, high fluid intelligence appears to be accompanied by more task-free exploration.

[Women with a history of pregnancy loss or abortion in a behavioural medicine hospital--an exploratory field study]. / Frauen mit belasteter geburtshilflicher Anamnese in der stationären psychosomatischen Versorgung--eine hypothesengenerierende Feldexploration.

OBJECTIVE: Gaining insights into the frequencies of negative obstetric histories in inpatients of a behavioural medicine hospital and the extent of their current psychological burdens. METHOD: We acquired sociodemographic, obstetric and psychological (psychopathology, coping patterns, and attribution styles) data of 117 inpatients by means of standardized questionnaires and interviews. RESULTS: Eighteen percent of the women exhibited a negative obstetric history (spontaneous, medically indicated or voluntary abortion) that dated back an average of 16 years. These women suffered more often from somatoform disorders and showed higher depression scores as well as other distinctive problems regarding their psychological wellbeing and their attributional and coping styles. Women who had undergone voluntary abortions showed a particular pattern of psychological distress. Those women who still felt psychological burden of pregnancy loss or abortion were younger and had fewer children. CONCLUSIONS: Almost one fifth of this inpatient sample in a behavioural medicine hospital exhibited a negative obstetric history and one third of these women still were affected psychologically. Clinicians therefore need to include obstetric data when taking a woman's psychiatric history, in particular with regard to depression, in order to be able to include this issue in their treatment plan, even if the pregnancy loss or abortion dates back many years.

Levels and effects of different forms of anxiety during pregnancy after a prior miscarriage.

OBJECTIVES: The aim of the study was to assess the current level of pregnancy-related fear and state anxiety in pregnant women who experienced prior miscarriages and to explore the impact of higher levels of anxiety during the first trimester on the following course and outcome of the pregnancy. STUDY DESIGN: One hundred forty-three pregnant women who had experienced prior miscarriage (sporadic or recurrent) were measured during each trimester and postpartum. Three independent control groups consisting of pregnant women without a history of miscarriage were recruited. For assessment, a battery of questionnaires including the STAI-state scale and various instruments were administered to record pregnancy-related fear, complications during pregnancy, the course of delivery and the health status of the neonate. Correlations, univariate logistic regression modelling, and ANOVA statistics including post hoc tests were conducted. RESULTS: Compared to women without miscarriages, women with prior miscarriage had higher levels of pregnancy-related fear and state anxiety during the first trimester. The level of anxiety differed between pregnant women with a single as compared to those with recurrent miscarriage. Early pregnancy-related fear significantly correlated with complications during pregnancy and delivery. This effect was not found for state anxiety. CONCLUSIONS: This study suggests that miscarriages may lead to higher levels of pregnancy-related fear and state anxiety. In particular, pregnancy-related fear may have a negative impact on the course of pregnancy and delivery. Thus, interventions to reduce pregnancy-related fear are highly recommended.

[Mourning, coping and subjective attribution after early miscarriage]. / Trauer, Bewältigung und subjektive Ursachenzuschreibungen nach Frühaborten: Adaptivität von Verarbeitungsmustern untersucht in einer Längsschnittstudie.

A few weeks after miscarriage 232 women were questioned with standardized questionnaires and symptom scales about the way in which they coped with an early miscarriage (up to the 16th week of gestation) about mourning processes and subjective attribution as well as anamnestic and psychosocial characteristics. Seven and fourteen months after pregnancy loss and if necessary in the first trimester of a following pregnancy the psychological symptoms of the women (fear and depressive symptoms) were evaluated. A few weeks after miscarriage we found with main component analysis three patterns of coping. The pattern of "depressive coping" could be diagnosed as a predictor of increased depression seven months after the miscarriage and in a new pregnancy. Depressive pathology in a new pregnancy of the women with early pregnancy loss can be predicted also over the pattern of "anxious grieving". On the other hand, the pattern of "active coping" is associated with lower state anxiety in a new pregnancy. Lack of perceived partner support and past divorces or separations are risk factors for increased fears in a new pregnancy. These results suggest that women who have had an early miscarriage especially if they have maladaptive coping patterns and psychosocial risk factor for maladjustment need prevention of psychological disturbances with an integrated psychosomatic concept.

Pregnancy after early pregnancy loss: a prospective study of anxiety, depressive symptomatology and coping.

Miscarriages can have lasting psychological effects on those concerned. In a prospective longitudinal study, 342 women were questioned about the way in which they coped after an early miscarriage (up to the 16th week of gestation), a few weeks after the pregnancy loss. There are data available from the first trimester of a subsequent pregnancy for 108 of these women. Standardized symptom scales were used to explore the pregnancy-specific anxiety, state and trait anxiety (STAI) and depressive symptoms in pregnant women and these were compared with the symptoms of 69 pregnant women with no history of miscarriages. Women with a history of miscarriages suffer more from pregnancy-specific anxieties in the first trimester of a new pregnancy than pregnant women with no history of miscarriages. Patterns of "depressive coping" and "anxious grieving" after the losses are predictive of more marked anxiety and depression symptoms in the first trimester of a subsequent pregnancy. These results suggest that women who have had an early miscarriage are particularly at risk of disturbances in their psychological adaptation in a new pregnancy. It is possible to determine risk factors which can be used to recognize those women who are particularly at risk directly after the miscarriage.

Temporal order relations in language comprehension.

The role of temporal orientation (chronological or reverse) and chronological distance (close, intermediate, or distant) in general event knowledge on language comprehension was examined. Experiment 1 used a relation-recognition paradigm in which the comprehension of a target event could be facilitated or disrupted by the temporal orientation implied by the prior information. Experiments 2 and 3 used a sentence-probe-recognition paradigm in which the temporal orientation, the stimulus onset asynchrony, and the chronological distance between the sentence event and the probe event were manipulated. The results demonstrated that readers used temporal information conveyed by their knowledge to construct situation models while comprehending sentences. The internal temporal dimension appeared to be directional and reflected the chronological distance between everyday events.