Development of an Inhibition Enzyme-Linked Immunosorbent Assay (ELISA) Prototype for Detecting Cytotoxic Three-Finger Toxins (3FTxs) in African Spitting Cobra Venoms.

The administration of toxin-specific therapy in snake envenoming is predicated on improved diagnostic techniques capable of detecting specific venom toxins. Various serological tests have been used in detecting snakebite envenoming. Comparatively, enzyme-linked immunosorbent assay (ELISA) has been shown to offer a wider practical application. We report an inhibition ELISA for detecting three-finger toxin (3FTx) proteins in venoms of African spitting cobras. The optimized assay detected 3FTxs in N. ashei (including other Naja sp.) venoms, spiked samples, and venom-challenged mice samples. In venoms of Naja sp., the assay showed inhibition, implying the detection of 3FTxs, but showed little or no inhibition in non-Naja sp. In mice-spiked samples, one-way ANOVA results showed that the observed inhibition was not statistically significant between spiked samples and negative control (p-value = 0.164). Similarly, the observed differences in inhibition between venom-challenged and negative control samples were not statistically significant (p-value = 0.9109). At an LOD of 0.01 µg/mL, the assay was able to confirm the presence of 3FTxs in the samples. Our results show a proof of concept for the use of an inhibition ELISA model as a tool for detecting 3FTxs in the venoms of African spitting cobra snakes.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Antimicrobial Activity of Protein Fraction from Naja ashei Venom Against Staphylococcus epidermidis.

One of the key problems of modern infectious disease medicine is the growing number of drug-resistant and multi-drug-resistant bacterial strains. For this reason, many studies are devoted to the search for highly active antimicrobial substances that could be used in therapy against bacterial infections. As it turns out, snake venoms are a rich source of proteins that exert a strong antibacterial effect, and therefore they have become an interesting research material. We analyzed Naja ashei venom for such antibacterial properties, and we found that a specific composition of proteins can act to eliminate individual bacterial cells, as well as the entire biofilm of Staphylococcus epidermidis. In general, we used ion exchange chromatography (IEX) to obtain 10 protein fractions with different levels of complexity, which were then tested against certified and clinical strains of S. epidermidis. One of the fractions (F2) showed exceptional antimicrobial effects both alone and in combination with antibiotics. The protein composition of the obtained fractions was determined using mass spectrometry techniques, indicating a high proportion of phospholipases A2, three-finger toxins, and L-amino acids oxidases in F2 fraction, which are most likely responsible for the unique properties of this fraction. Moreover, we were able to identify a new group of low abundant proteins containing the Ig-like domain that have not been previously described in snake venoms.

Snake venoms promote stress-induced senescence in human fibroblasts.

Snake venoms are widely studied in terms of their systemic toxicity and proteolytic, hemotoxic, neurotoxic, and cytotoxic activities. However, little is known about snake-venom-mediated effects when used at low, noncytotoxic concentrations. In the current study, two human fibroblast cell lines of different origin, namely WI-38 fetal lung fibroblasts and BJ foreskin fibroblasts were used to investigate snake-venom-induced adaptive response at a relatively noncytotoxic concentration (0.01 µg/ml). The venoms of Indochinese spitting cobra ( Naja siamensis), western green mamba ( Dendroaspis viridis), forest cobra ( Naja melanoleuca), and southern copperhead ( Agkistrodon contortrix) were considered. Snake venoms promoted FOXO3a-mediated oxidative stress response and to a lesser extent DNA damage response, which lead to changes in cell cycle regulators both at messenger RNA and protein levels, limited cell proliferation and migration, and induced cellular senescence. Taken together, we have shown for the first time that selected snake venoms may also exert adverse effects when used at relatively noncytotoxic concentrations.

[Mental health of teenage mothers: impact on the next generation]. / Psychische Gesundheit von Teenagermüttern: Auswirkungen auf die nächste Generation.

BACKGROUND: Motherhood in adolescence is associated with risks for both the young mother and the children. OBJECTIVE: Presentation of the current state of research on the mental health of adolescent mothers and its effects on the development of their children. MATERIAL AND METHODS: Electronic database search in PubMed using various combined key terms such as "teenage pregnancy", "adolescent pregnancy", "teenage mother", "child development", "mother-child interaction". Review of the literature of the sources found and discussion of current publications and databases of public institutions. RESULTS: In addition to psychosocial risks such as fewer education years due to family formation and lower incomes, young mothers also suffer more frequently from mental disorders, both before pregnancy and due to the additional burden of motherhood in their own developmental phase of youth. These can have unfavorable effects on the mother-child interaction and on the psychosocial and cognitive development of the children, thereby leading to the transgenerational transmission of risk factors. CONCLUSION: In addition to primary prevention by avoiding teenage pregnancies, early identification of adolescent mothers and children at risk for early treatment and intervention is necessary.

Spatio-temporal Aspects of Ca2+ Signalling: Lessons from Guard Cells and Pollen Tubes.

Changes in cytosolic Ca2+ concentration ([Ca2+]cyt) serve to transmit information in eukaryotic cells. The involvement of this second messenger in plant cell growth as well as osmotic- and water relations is well established. After almost 40 years of intense research on the coding and decoding of plant Ca2+ signals, numerous proteins involved in Ca2+ action have been identified. However, we are still far from understanding the complexity of Ca2+ networks. New in vivo Ca2+ imaging techniques combined with molecular genetics allow visualisation of spatio-temporal aspects of Ca2+ signalling. In parallel, cell biology together with protein biochemistry and electrophysiology are able to dissect information processing by this second messenger in space and time. Here we focus on the time-resolved changes in cellular events upon Ca2+ signals, concentrating on the two best-studied cell types, pollen tubes and guard cells. We put their signalling networks side by side, compare them with those of other cell types and discuss rapid signalling in the context of Ca2+ transients and oscillations to regulate ion homeostasis.

Altered brain network integrity after childhood maltreatment: A structural connectomic DTI-study.

Childhood maltreatment is associated with alterations in neural architecture that potentially put these children at increased risk for psychopathology. Alterations in white matter (WM) tracts have been reported, however no study to date has investigated WM connectivity in brain networks in maltreated children to quantify global and local abnormalities through graph theoretical analyses of DTI data. We aimed for a multilevel investigation examining the DTI-based structural connectome and its associations with basal cortisol levels of 25 children with documented maltreatment experiences before age 3, and 24 matched controls (age: 10.6 ± 1.75 years). On the global and lobar level, maltreated children showed significant reductions in global connectivity strength, local connectivity and increased path length, suggesting deviations from the small-world network architecture previously associated with psychopathology. Reductions in global connectivity were associated with placement instability, attenuated cortisol secretion and higher levels of internalizing and externalizing behaviours. Regional measures revealed lower connectivity strength especially in regions within the ventromedial prefrontal cortex (vMPFC) in maltreated children. These findings show that childhood maltreatment is associated with systemic global neurodevelopmental alterations in WM networks next to regional alterations in areas involved in the regulation of affect. These alterations in WM organization could underlie global functional deficits and multi-symptom patterns frequently observed in children with maltreatment experiences. Hum Brain Mapp 38:855-868, 2017. © 2016 Wiley Periodicals, Inc.

Look into my eyes: Investigating joint attention using interactive eye-tracking and fMRI in a developmental sample.

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects.

Serotonergic modulation of resting state default mode network connectivity in healthy women.

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.

Brain morphological changes in adolescent and adult patients with anorexia nervosa.

Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains.

Current practice of diabetes education in children and adolescents with type 1 diabetes in Germany and Austria: analysis based on the German/Austrian DPV database.

BACKGROUND: Diabetes education of patients and/or parents is an essential part of diabetes care with effects on diabetes outcome. The objective of our study was to describe the current practice of diabetes education in Germany and Austria with regard to training frequency, patient age, migration background and diabetes therapy in a large cohort of pediatric patients with diabetes mellitus type 1 (T1DM). METHODS: We analyzed data from pediatric T1DM patients with diabetes training in 2013 and complete data available for treatment year in the multicenter Diabetes Patienten Verlaufsdokumentation (DPV) registry using sas 9.4. RESULTS: In 2013 21 871 pediatric patients with T1DM were documented [52.4% male, age: 12.70 (9.35-15.30) yr (median (interquartile range)], diabetes duration: 3.80 (1.45-7.00) yr, migration background: 21.4%, twice daily injections: 5.5%, multiple daily injections: 52.5%, insulin-pump therapy: 42%. Of these 32.31% were trained in 2013. Younger patients and their parents were trained more intensely and more frequently as inpatients compared with older patients (0-6 vs. 6-12 and 12-18 yr: teaching units: 13.07 vs. 12.05 and 9.79; inpatient: 79% vs. 72% and 70%). There was also a difference in training frequency with regard to migration background. Severe hypoglycemia or ketoacidosis resulted in intensification of training (4.0 vs. 2.0%; 7.8 vs. 3.1%). Centre-specific education tools were used frequently alone or in combination with published, standardized education programs. CONCLUSION: Training frequency was highest in younger patients and during the first year of diabetes. Acute complications resulted in more frequent diabetes training, indicating that currently many education sessions take place in consequence to these complications.

Diabetes in Patients with ß-thalassemia or other Hemoglobinopathies - Analysis from the DPV Database.

Background: Diabetes mellitus is a common endocrinopathy in patients with thalassemia major, but the occurrence of hemoglobinopathies is rare in Germany and Western Europe. The longitudinal German-Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry allows a comprehensive characterization of this group of patients. Patients/methods: Patients from the DPV-registry aged<30 years with thalassemia major or other hemoglobinopathies were compared to patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) using the statistical software SAS 9.4. Results: 94 patients (0.13% of patients) with hemoglobinopathies are registered in DPV. 82.4% of 17 patients with thalassemia major, 100% of 12 patients with sickle cell disease (SCD) and >90% of 65 patients with other hemoglobinopathies receive insulin treatment. In the majority of patients with thalassemia major, hemosiderosis is documented. Patients with thalassemia major developed diabetes at a median age of 14.6 [IQR 8.4-18.0] years (9.0 years [5.3-12.5] in T1D; 18.7 years [14.2-25.6] in TD2; both p<0.01). They show high HbA1c/fructosamine levels and frequent hypoglycemia, reflecting poor metabolic control. Conclusion: Diabetes in thalassemia major is probably caused by hemosiderosis due to polytransfusion, while patients with SCD/thalassemia minor are most likely affected by T1D. The high rate of hypoglycemia in patients with ß-thalassemia major may be caused by liver fibrosis and a lack of hepatic glycogen stores.

Treatment of young patients with HNF1A mutations (HNF1A-MODY).

AIM: Children and adolescents with a molecular diagnosis of HNF1A-MODY should be treated with oral sulfonylurea according to current International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines. METHODS: We surveyed the German-Austrian DPV database of 50 043 people and included 114 patients with a confirmed molecular-genetic diagnosis of HNF1A mutation and diabetes onset at below age 18 years. We analysed hypoglycaemic episodes, metabolic control (HbA1c ) and other clinical variables according to treatment groups. RESULTS: People with HNF1A-MODY were included and analysed according to treatment with insulin alone (n = 34), sulfonylurea (n = 30), meglitinides (n = 22) or lifestyle (n = 28). In those receiving any drug treatment (n = 86), severe hypoglycaemia did not occur with meglitinide and was highest (at 3.6 events per 100 patient-years) with insulin. HbA1c was highest with insulin treatment (insulin = 58 mmol/mol, 7.5%; sulfonylurea = 55 mmol/mol, 7.2%; meglitinides = 52 mmol/mol, 6.9%; P = 0.008), whereas weight (BMI SD score), serum lipids and blood pressure were not different. CONCLUSIONS: Of note, 40% of people with HNF1A-MODY and medical treatment were receiving insulin alone and thus were not being treated in line with up-to-date International Society for Pediatric and Adolescent Diabetes/International Diabetes Federation guidelines, despite insulin treatment being associated with worse metabolic control and the risk of hypoglycaemia. The unlicensed use of oral drugs in patients below age 18 years and adherence by both doctors and patients to the initial insulin treatment might contribute to this finding.

Venom diversity in Naja mossambica: Insights from proteomic and immunochemical analyses reveal intraspecific differences.

BACKGROUND: Intraspecific variations in snake venom composition have been extensively documented, contributing to the diverse clinical effects observed in envenomed patients. Understanding these variations is essential for developing effective snakebite management strategies and targeted antivenom therapies. We aimed to comprehensively investigate venoms from three distinct populations of N. mossambica from Eswatini, Limpopo, and KwaZulu-Natal regions in Africa in terms of their protein composition and reactivity with three commercial antivenoms (SAIMR polyvalent, EchiTAb+ICP, and Antivipmyn Africa). METHODOLOGY/PRINCIPAL FINDINGS: Naja mossambica venoms from Eswatini region exhibited the highest content of neurotoxic proteins, constituting 20.70% of all venom proteins, compared to Limpopo (13.91%) and KwaZulu-Natal (12.80%), and was characterized by the highest diversity of neurotoxic proteins, including neurotoxic 3FTxs, Kunitz-type inhibitors, vespryns, and mamba intestinal toxin 1. KwaZulu-Natal population exhibited considerably lower cytotoxic 3FTx, higher PLA2 content, and significant diversity in low-abundant proteins. Conversely, Limpopo venoms demonstrated the least diversity as demonstrated by electrophoretic and mass spectrometry analyses. Immunochemical assessments unveiled differences in venom-antivenom reactivity, particularly concerning low-abundance proteins. EchiTAb+ICP antivenom demonstrated superior reactivity in serial dilution ELISA assays compared to SAIMR polyvalent. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a substantial presence of neurotoxic proteins in N. mossambica venoms, challenging previous understandings of their composition. Additionally, the detection of numerous peptides aligning to uncharacterized proteins or proteins with unknown functions underscores a critical issue with existing venom protein databases, emphasizing the substantial gaps in our knowledge of snake venom protein components. This underscores the need for enhanced research in this domain. Moreover, our in vitro immunological assays suggest EchiTAb+ICP's potential as an alternative to SAIMR antivenom, requiring confirmation through prospective in vivo neutralization studies.

Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females.

Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed.

Bipolar disorder risk alleles in children with ADHD.

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of α = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.

Development and Characterization of Anti-Naja ashei Three-Finger Toxins (3FTxs)-Specific Monoclonal Antibodies and Evaluation of Their In Vitro Inhibition Activity.

Antivenom immunotherapy is the mainstay of treatment for snakebite envenoming. Most parts of the world affected by snakebite envenoming depend on broad-spectrum polyspecific antivenoms that are known to contain a low content of case-specific efficacious immunoglobulins. Thus, advances in toxin-specific antibodies production hold much promise in future therapeutic strategies of snakebite envenoming. We report anti-3FTxs monoclonal antibodies developed against N. ashei venom in mice. All the three test mAbs (P4G6a, P6D9a, and P6D9b) were found to be IgG antibodies, isotyped as IgG1. SDS-PAGE analysis of the test mAbs showed two major bands at approximately 55 and 29 kDa, suggestive of immunoglobulin heavy and light chain composition, respectively. The immunoaffinity-purified test mAbs demonstrated higher binding efficacy to the target antigen compared to negative control. Similarly, a cocktail of the test mAbs was found to induce a significantly higher inhibition (p-value < 0.0001) compared to two leading commercial brands of antivenoms on the Kenyan market, implying a higher specificity for the target antigen. Both the test mAbs and 3FTxs polyclonal antibodies induced comparable inhibition (p-value = 0.9029). The inhibition induced by the 3FTxs polyclonal antibodies was significantly different from the two antivenoms (p-value < 0.0001). Our results demonstrate the prospects of developing toxin-specific monoclonal-based antivenoms for snakebite immunotherapy.

Development of neural correlates of empathy from childhood to early adulthood: an fMRI study in boys and adult men.

Although empathy is rooted early in life, the ability to understand and share the emotions of others continues to develop after childhood. Here, we aimed at exploring developmental changes in the neural mechanisms underlying empathy from childhood to early adulthood. Using functional magnetic resonance imaging, 47 healthy male subjects aged 8-27 years were investigated during an explicit empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). A perceptual decision on the width of faces was used as a control condition. Age-related activity increases were observed in the fusiform gyrus and inferior frontal gyrus, depending on whether subjects attributed emotions to self or other. During the self-task, activity in the right precuneus and right intraparietal sulcus decreased as a function of age. No age-related differences were observed in behavioral performance measures. Increased activity in the fusiform gyrus and in the frontal component of the human mirror neuron system with increasing age may be explained by greater experience and expertise accumulated during socio-emotional interactions. Greater recruitment of right parietal structures in younger as compared to older subjects might reflect developmental differences in the cognitive strategies to infer one's own emotional response. This study is the first to show developmental changes in the neural mechanisms supporting empathy. Our findings may have important implications for the development of novel therapeutic interventions in clinical conditions characterized by empathy deficits, such as autism spectrum disorder.

[Development of antisocial disorders--impact of the autonomic stress system]. / Entwicklungsfaktoren dissozialer Störungen--die Bedeutung des autonomen Stresssystems.

The current selective review emphasizes the heterogeneity of antisocial behaviour in children and adolescents. It focuses on the development of children of the early-starter subtype of conduct disorder who are at high risk for the development of an antisocial personality disorder. Especially the autonomic stress system seems to have an important impact on symptoms and the prognosis of antisocial individuals. While autonomic hypoarousal and a reduced autonomic reagibility seem to be associated with more proactive aggressiveness and a negative outcome, increased autonomic arousal and reagibility might be related to reactive aggressiveness and constitutes possibly a protective trait. Data of the current psychophysiological and neuroendocrinological literature are summarized. Moreover, the impact of comorbid attention deficit hyperactivity disorder and anxiety disorders on dissocial development is illustrated. Particularly early diagnostic assessment of the individual's extent of trait anxiety might help to specify therapeutic opportunities and could thereby improve therapeutic efficiency.

Evaluation of Antifungal Activity of Naja pallida and Naja mossambica Venoms against Three Candida Species.

In contrast to comprehensively investigated antibacterial activity of snake venoms, namely crude venoms and their selected components, little is known about antifungal properties of elapid snake venoms. In the present study, the proteome of two venoms of red spitting cobra Naja pallida (NPV) and Mozambique spitting cobra Naja mossambica (NMV) was characterized using LC-MS/MS approach, and the antifungal activity of crude venoms against three Candida species was established. A complex response to venom treatment was revealed. NPV and NMV, when used at relatively high concentrations, decreased cell viability of C. albicans and C. tropicalis, affected cell cycle of C. albicans, inhibited C. tropicalis-based biofilm formation and promoted oxidative stress in C. albicans, C. glabrata and C. tropicalis cells. NPV and NMV also modulated ammonia pulses during colony development and aging in three Candida species. All these observations provide evidence that NPV and NMV may diminish selected pathogenic features of Candida species. However, NPV and NMV also promoted the secretion of extracellular phospholipases that may facilitate Candida pathogenicity and limit their usefulness as anti-candidal agents. In conclusion, antifungal activity of snake venoms should be studied with great caution and a plethora of pathogenic biomarkers should be considered in the future experiments.