Combining skin and olfactory α-synuclein seed amplification assays (SAA)-towards biomarker-driven phenotyping in synucleinopathies.

Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson's disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.

Site-selectively generated photon emitters in monolayer MoS2 via local helium ion irradiation.

Quantum light sources in solid-state systems are of major interest as a basic ingredient for integrated quantum photonic technologies. The ability to tailor quantum emitters via site-selective defect engineering is essential for realizing scalable architectures. However, a major difficulty is that defects need to be controllably positioned within the material. Here, we overcome this challenge by controllably irradiating monolayer MoS2 using a sub-nm focused helium ion beam to deterministically create defects. Subsequent encapsulation of the ion exposed MoS2 flake with high-quality hBN reveals spectrally narrow emission lines that produce photons in the visible spectral range. Based on ab-initio calculations we interpret these emission lines as stemming from the recombination of highly localized electron-hole complexes at defect states generated by the local helium ion exposure. Our approach to deterministically write optically active defect states in a single transition metal dichalcogenide layer provides a platform for realizing exotic many-body systems, including coupled single-photon sources and interacting exciton lattices that may allow the exploration of Hubbard physics.

The impact of vaccines on heterologous adaptive immunity.

BACKGROUND: Vaccines induce antigen-specific memory in adaptive immune cells that enables long-lived protection against the target pathogen. In addition to this, several vaccines have beneficial effects greater than protection against their target pathogen. These non-specific effects are proposed to be the result of vaccine-induced immunomodulation. In the case of bacille Calmette-Guérin (BCG) vaccine, this involves induction of innate immune memory, termed 'trained immunity', in monocytes and natural killer cells. OBJECTIVES: This review discusses current evidence for vaccine-induced immunomodulation of adaptive immune cells and heterologous adaptive immune responses. CONTENT: The three vaccines that have been associated with changes in all-cause infant mortality: BCG, diphtheria-tetanus-pertussis (DTP) and measles-containing vaccines (MCV) alter T-cell and B-cell immunity. The majority of studies that investigated non-specific effects of these vaccines on the adaptive immune system report changes in numbers or proportions of adaptive immune cell populations. However, there is also evidence for effects of these vaccines on adaptive immune cell function and responses to heterologous stimuli. There is some evidence that, in addition to BCG, DTP and MCV, other vaccines (that have not been associated with changes in all-cause mortality) may alter adaptive immune responses to unrelated stimuli. IMPLICATIONS: This review concludes that vaccines alter adaptive immune cell populations and heterologous immune responses. The non-specific effects differ between various vaccines and their effects on heterologous adaptive immune responses may also involve bystander activation, cross-reactivity and other as yet undefined mechanisms. This has major implications for future vaccine design and vaccination scheduling.

Treatment strategy and long-term functional outcome of traumatic elbow dislocation in childhood: a single centre study.

PURPOSE: Traumatic elbow dislocation (TED) is the most common injury of large joints in children. There is an ongoing debate on the optimal treatment for TED. We aimed to assess the functional outcome after operative and nonoperative treatment of TED. METHODS: We analysed the medical records of patients with TED treated at the University Children's Hospital, Basel, between March 2006 and June 2015. Functional outcome was assessed using the Mayo Elbow Performance Score (MEPS) and Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) Sport and Music Module score. These scores were compared between nonoperatively and operatively treated patients. RESULTS: A total of 37 patients (mean age 10.2 years, 5.2 to 15.3) were included. Of these, 21 (56.8%) children had undergone nonoperative treatment, with 16 (43.2%) patients having had operative treatment. After a mean follow-up of 5.6 years (1.2 to 5.9), MEPS and QuickDASH Sport and Music Module scores in the nonoperative group and operative group were similar: MEPS: 97.1 points (SD 4.6) versus 97.2 points (SD 2.6); 95% confidence interval (CI)-2.56 to 2.03); p = 0.53; QuickDASH Sport and Music Module score: 3.9 points (SD 6.1) versus 3.1 points (SD 4.6); 95% CI 2.60 to 4.17; p = 0.94. We noted no significant differences regarding the long-term functional outcome between the subgroup of children treated operatively versus those treated nonoperatively for TED with accompanying fractures of the medial epicondyle and medial condyle. CONCLUSION: Functional outcome after TED was excellent, independent of the treatment strategy. If clear indications for surgery are absent, a nonoperative approach for TED should be considered. LEVEL OF EVIDENCE: Level III - therapeutic, retrospective, comparative study.

Burdens on emergency responders after a terrorist attack in Berlin.

Background: Terrorist attacks induce various responses in emergency responders. Addressing this range of responses in individual workers is of central interest. Aims: To assess the gender- and occupation-specific effects of a terrorist attack, particularly in emergency responders. Methods: This was a pilot study. Emergency responders present during the 2016 terrorist attack at Breitscheidplatz in Berlin were asked to participate. Measures for crisis management had been previously implemented. Stress (Patient Health Questionnaire [PHQ]), quality of life (The World Health Organization Quality of Life [WHOQOL-BREF]), post-traumatic stress disorder (PTSD Checklist for DSM-5 [PCL-5]) and current psychological symptoms (Brief Symptom Inventory [BSI]) were assessed. Results: Thirty-seven subjects were included, 11 female and 26 male. The occupational groups included 16 firefighters, six police officers, five psychosocial health care personnel and nine members of aid organizations. Three months after the attack, female workers showed higher scores in stress and paranoid ideation, police officers showed higher scores in hostility and firefighters scored lower quality of life in environment and physical health. Conclusions: The mental health burden identified in this study plays an important role for emergency responders after terrorist attacks. Differences between occupational groups may be attributable to differences in tasks that responders perform during acute incidents. The presence of these differences 3 months after the incident suggests that these are at least medium-term conditions. This study may inform the development of treatments and policies and it thus recommended to develop a multi-level assessment and treatment programme that is gender- and occupation-specific.

ANALYSIS OF TISSUE OXYGENATION IN CHRONIC LEG ULCERS BY COMBINATION OF A MULTI-SPECTRAL CAMERA AND A HYPER-SPECTRAL PROBE.

Objective evaluation of chronic wounds, such as leg ulcers, by the use of non-invasive techniques is of importance for diagnosis, monitoring treatment response, and probably leads to improved treatment strategies. We performed a feasibility study for the combined use of a multi-spectral camera and a hyper-spectral probe to evaluate chronic leg ulcers with a focus on tissue oxygenation. Sixty patients - 40 females and 20 males were enrolled in the study. The age range was 46 to 85 years for males (mean 65.8 years, median 73.0 years) and 51 to 91 years for females (mean 74.4 years, median 77.0 years). Measurements were performed by hyper-spectral wound (HySkinII) probe and multi-spectral (DeMuk) camera on wounds and surrounding skin. The investigation results demonstrate a high variability of oxygenation within ulcers and the surrounding tissue. The methods allow an investigator to independently assess of tissue oxygenation in superficial and deeper layers. Non-invasive multi- and hyper-spectral imaging techniques offer new opportunities of an objective assessment of chronic wounds.

Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population.

Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings. We assessed 27 combat trauma-exposed individuals by means of whole-brain voxel-based morphometry on 3 T magnetic resonance imaging scans and identified a negative association between duration of military deployment and gray matter volumes in ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (ACC). We also found a negative relationship between deployment-related gray matter volumes and psychological symptoms, but not between military deployment and psychological symptoms. To our knowledge, this is the first whole-brain analysis showing that longer military deployment is associated with smaller regional brain volumes in combat-exposed individuals without PTSD. Notably, the observed gray matter associations resemble those previously identified in PTSD populations, and concern regions involved in emotional regulation and fear extinction. These findings question the current dichotomy between clinical and subclinical populations in PTSD neuroimaging research. Instead, neural correlates of both stress exposure and PTSD symptomatology may be more meaningfully investigated at a continuous level.

Enhancement cavities for few-cycle pulses.

We address the challenge of increasing the bandwidth of high-finesse femtosecond enhancement cavities and demonstrate a broad spectrum spanning 1800 cm-1 (195 nm) at -10 dB around a central wavelength of 1050 nm in an EC with an average finesse exceeding 300. This will benefit a host of spectroscopic applications, including transient absorption spectroscopy, direct frequency comb spectroscopy, and Raman spectroscopy. The pulse circulating in the EC is composed of only 5.4 optical cycles, at a kilowatt-level average power. Together with a suitable gating technique, this paves the way to the efficient generation of multi-megahertz-repetition-rate isolated extreme ultraviolet attosecond pulses via intracavity high-order harmonic generation.

[Association of Deployment and Tobacco Dependence among Soldiers]. / Zusammenhang von Auslandseinsätzen und Tabakabhängigkeit bei Soldaten.

OBJECTIVE: Smoking is a highly preventable risk factor. The present study investigates whether military operations abroad, as compared to deployment preparation, increase the risk of starting to smoke, enhance tobacco dependence and moderator variables can be identified on smoking behavior. METHOD: The study was conducted at 2 mechanized infantry battalions with N=264 soldiers. The task force completed a deployment in Afghanistan, the control group performed a deployment training. Assessments of tobacco dependence, posttraumatic symptoms, depression and stress were done before (t1) and after (t3) deployment. In addition, one assessment was done at mid-point (t2) during deployment and during the pre-deployment training, respectively. RESULTS: The prevalence rate of smoking soldiers was 56,4%. 51,1% (n=135) of all examined soldiers smoked more than 20 cigarettes per day. The results show a significant increase of tobacco dependence in the task force from t1 to t3 (p=0,040) as compared to the control group. For both groups, there was no increase in starting to smoke during the period of investigation (χ²<1; n. s.). Moderator variables on smoking were not found, but there was a significant increase in posttraumatic stress symptoms in the deployed group (p=0,006). CONCLUSIONS: Perhaps the increase in tobacco dependence in the experimental group can be attributed to the specific burdens of deployment. If high smoking rates were to be found also in other branches of the armed services, effective smoking cessation programs should be offered more widely.

Prevalence and severity of mental disorders in military personnel: a standardised comparison with civilians.

AIMS: Provision and need for mental health services among military personnel are a major concern across nations. Two recent comparisons suggest higher rates of mental disorders in US and UK military personnel compared with civilians. However, these findings may not apply to other nations. Previous studies have focused on the overall effects of military service rather than the separate effects of military service and deployment. This study compared German military personnel with and without a history of deployment to sociodemographically matched civilians regarding prevalence and severity of 12-month DSM-IV mental disorders. METHOD: 1439 deployed soldiers (DS), 779 never deployed soldiers (NS) and 1023 civilians were assessed with an adapted version of the Munich Composite International Diagnostic interview across the same timeframe. Data were weighted using propensity score methodology to assure comparability of the three samples. RESULTS: Compared with adjusted civilians, the prevalence of any 12-month disorder was lower in NS (OR: 0.7, 95% CI: 0.5-0.99) and did not differ in DS. Significant differences between military personnel and civilians regarding prevalence and severity of individual diagnoses were only apparent for alcohol (DS: OR: 0.3, 95% CI: 0.1-0.6; NS: OR: 0.2, 95% CI: 0.1-0.6) and nicotine dependence (DS: OR: 0.5, 95% CI: 0.3-0.6; NS: OR: 0.5, 95% CI: 0.3-0.7) with lower values in both military samples. Elevated rates of panic/agoraphobia (OR: 2.7, 95% CI: 1.4-5.3) and posttraumatic stress disorder (OR: 3.2, 95% CI: 1.3-8.0) were observed in DS with high combat exposure compared with civilians. CONCLUSIONS: Rates and severity of mental disorders in the German military are comparable with civilians for internalising and lower for substance use disorders. A higher risk of some disorders is reduced to DS with high combat exposure. This finding has implications for mental health service provision and the need for targeted interventions. Differences to previous US and UK studies that suggest an overall higher prevalence in military personnel might result from divergent study methods, deployment characteristics, military structures and occupational factors. Some of these factors might yield valuable targets to improve military mental health.

Femtosecond X-ray absorption study of electron localization in photoexcited anatase TiO2.

Transition metal oxides are among the most promising solar materials, whose properties rely on the generation, transport and trapping of charge carriers (electrons and holes). Identifying the latter's dynamics at room temperature requires tools that combine elemental and structural sensitivity, with the atomic scale resolution of time (femtoseconds, fs). Here, we use fs Ti K-edge X-ray absorption spectroscopy (XAS) upon 3.49 eV (355 nm) excitation of aqueous colloidal anatase titanium dioxide nanoparticles to probe the trapping dynamics of photogenerated electrons. We find that their localization at Titanium atoms occurs in <300 fs, forming Ti(3+) centres, in or near the unit cell where the electron is created. We conclude that electron localization is due to its trapping at pentacoordinated sites, mostly present in the surface shell region. The present demonstration of fs hard X-ray absorption capabilities opens the way to a detailed description of the charge carrier dynamics in transition metal oxides.

Thrombectomy vs. Systemic Thrombolysis in Acute Embolic Stroke with High Clot Burden: A Retrospective Analysis.

PURPOSE: The efficacy of i. v. thrombolysis in acute stroke with high clot burden is limited. Successful recanalization is very unlikely if the thrombus length exceeds 7 mm. Thus this retrospective controlled study evaluated the efficacy and safety of neurothrombectomy in the treatment of acute embolic stroke in patients selected by a thrombus length of ≥ 8 mm using the stent retriever Trevo(®) device. MATERIALS AND METHODS: 40 patients with acute occlusion of the anterior intracranial arteries with a thrombus length of ≥ 8 mm were treated with neurothrombectomy. We compared the outcome with a historical cohort of 42 patients with a thrombus length of ≥ 8 mm that received i. v. thrombolysis only. Clinical outcome was assessed by modified Rankin scale in both groups at discharge and on day 90. RESULTS: Patients did not differ in age, mRS on admission, thrombus length or time from symptom onset to i. v. thrombolysis, but the thrombectomy group had higher NIHSS on admission. Successful recanalization was achieved in 33/40 patients (83 %) with neurothrombectomy. 15 patients received i. v. thrombolysis prior to neurothrombectomy. Median mRS at discharge was 3.5 (1.25 - 5) vs. 5 (4 - 6; p < 0.01) and on day 90 3 (1 - 4) vs. 5 (4 - 6; p < 0.01). Symptomatic hemorrhage occurred in 3 vs. 7 patients. 3 vs. 17 patients died within 90 days (thrombectomy vs. control each). There were only a few intervention-related complications. CONCLUSION: Thrombectomy in acute stroke with high clot burden using the Trevo(®) device has a low risk and improved clinical outcome compared to i. v. thrombolysis alone. Treatment selection by a clot length of ≥ 8 mm might be a powerful approach to improve the outcome of mechanical thrombectomy. KEY POINTS: • Clot length of ≥ 8 mm might be a valuable criterion for indicating neurothrombectomy. • Thrombolysis only in high clot burden is associated with poor clinical outcome. • Thrombectomy using the Trevo(®) stent retriever is safe and effective.

[Influence of post-traumatic stress disorder on heart rate variability as marker of the autonomic nervous system - a systematic review]. / Einfluss einer posttraumatischen Belastungsstörung auf die Herzfrequenzvariabilität als Marker des autonomen Nervensystems - eine systematische Literaturübersicht.

INTRODUCTION: PTSD is associated with comprehensive disruption of several neurobiological regulation mechanisms and with a disruption in the parasympathetic-sympathetic balance. This can be measured with the heart rate variability (HRV). METHODS: A systematic review in PubMed using the keywords "hrv" or "heart rate variability" and "PTSD" or "posttraumatic stress disorder" was performed. RESULTS: Overall 15 original studies were identified. In most cases a significant relationship of PTSD for reduction of HRV was demonstrated (9 studies) or, respectively, a reduction by trends was shown in 3 studies. Limitations were discussed. DISCUSSION: In spite of the limitations, most of the studies have shown a relationship between PTSD and HRV. However, an assessment of this potential marker as a supplement for clinical diagnosis and therapy follow-up in patients with PTSD seems to be premature on the basis of the data obtained so far. Further research is required.

Predictors of changes in daily alcohol consumption in the aftermath of military deployment.

BACKGROUND: Several studies have documented factors related to increase in alcohol consumption in the context of stressful experiences. However, little is known about predictors of different courses of alcohol use in this context. This study aims to investigate diverse predictors and correlates of increase and decrease of average daily alcohol consumption (aDAC) in the aftermath of military deployment taking into account a variety of potentially relevant factors. METHODS: N=358 soldiers were examined before (T1) and 12 months after return from deployment (T2) using standardized interviews. Change in aDAC was categorized into decreased (n=72), stable (n=215) and increased (n=71) aDAC. RESULTS: Overall, aDAC did not change significantly between T1 and T2 (median change=0.0 g, inter quartile range=11.3g). Compared to stable aDAC, increase was characterized by a lower proportion of high-educated individuals (OR: 0.3 (0.1-0.7), p=0.008), lower rank (marginally significant: OR: 2.0 (1.0-4.1), p=0.050), and less acceptance (trend: MR: 0.97 (0.93-1.00), p=0.053). Correlates of increased aDAC were less social support (MR: 0.84 (0.71-0.99), p=0.043), more sleeping problems (MR: 1.15 (1.00-1.31), p=0.045) and more negative post-event cognitions following deployment (MR: 2.32 (1.28-4.21), p=0.006). Decrease in aDAC was predicted by lower PTSD symptom severity before deployment (MR: 0.34 (0.16-0.72), p=0.005) and less childhood emotional neglect (marginally significant: MR: 0.78 (0.60-1.00), p=0.050). CONCLUSIONS: Increase and decrease in alcohol use after stressful experiences might have differential risk factors and correlates. Findings might stimulate future research that could result in improved measures to prevent increases as well as in interventions that could foster decreases in alcohol consumption in the context of stressful experiences.

Associations between lifetime PTSD symptoms and current substance use disorders using a five-factor model of PTSD.

This paper aimed to extend the existing knowledge on the association between PTSD symptoms, alcohol use disorders (AUD) and nicotine dependence (ND) by distinguishing between anxious and dysphoric arousal PTSD symptoms and by considering the putative contribution of additional comorbidity. Data stem from a cross-sectional study in a stratified, representative sample of 1483 recently deployed soldiers using standardized diagnostic interviews. All lifetime PTSD symptom clusters (occurrence of any symptom and number of symptoms) were associated with current AUD and ND in crude models except that anxious arousal was not related to AUD. Associations were reduced in magnitude when controlling for comorbidity. Current ND was related to the occurrence of any emotional numbing and to the number of re-experiencing symptoms above the contribution of other symptom clusters and comorbidity. In conclusion, associations between PTSD symptoms, AUD and ND may be partially attributable to additional comorbidity. Findings also yield further evidence for a role of emotional numbing and re-experiencing symptoms in the comorbidity between PTSD and ND and for a distinction between dysphoric and anxious arousal PTSD symptoms.

Genetic effects on information processing speed are moderated by age--converging results from three samples.

Information processing is a cognitive trait forming the basis of complex abilities like executive function. The Trail Making Test (TMT) is a well-established test of information processing with moderate to high heritability. Age of the individual also plays an important role. A number of genetic association studies with the TMT have been performed, which, however, did not consider age as a moderating factor. We report the results of genome-wide association studies (GWASs) on age-independent and age-dependent TMT performance in two population-representative community samples (Munich Antidepressant Response Signature, MARS: N1 = 540; Ludwig Maximilians University, LMU: N2 = 350). Age-dependent genome-wide findings were then evaluated in a third sample of healthy elderly subjects (Sydney Memory and Ageing Study, Sydney MAS: N3 = 448). While a meta-analysis on the GWAS findings did not reveal age-independent TMT associations withstanding correction for multiple testing, we found a genome-wide significant age-moderated effect between variants in the DSG1 gene region and TMT-A performance predominantly reflecting visual processing speed (rs2199301, P(meta-analysis) = 1.3 × 10(-7)). The direction of the interaction suggests for the minor allele a beneficial effect in younger adults turning into a detrimental effect in older adults. The detrimental effect of the missense single nucleotide polymorphism rs1426310 within the same DSG1 gene region could be replicated in Sydney MAS participants aged 70-79, but not in those aged 80 years and older, presumably a result of survivor bias. Our findings demonstrate opposing effects of DSG1 variants on information processing speed depending on age, which might be related to the complex processes that DSG1 is involved with, including cell adhesion and apoptosis.

Substance use and substance use disorders in recently deployed and never deployed soldiers.

BACKGROUND: Military studies investigating the prevalence of substance use (SU) and substance use disorders (SUD) and the relation between SU and mental disorders often lack a comprehensive assessment of SU, SUD and mental disorders and comparable groups of deployed and non-deployed personnel. There is also limited data regarding SU and SUD in the German military to date. METHODS: Cross-sectional examination of n=1483 soldiers recently deployed in Afghanistan and 889 never deployed soldiers using a fully-standardized diagnostic interview (MI-CIDI) including a comprehensive substance section. RESULTS: Across both groups, 12-months prevalence of DSM-IV alcohol use disorders was 3.1%, 36.9% reported binge drinking, 13.9% heavy drinking, 1.3% illegal drug use. 55.1% were regular smokers, 10.9% nicotine dependent. Although recently deployed soldiers revealed slightly higher rates in some measures, there were no significant differences to the never deployed regarding SU und SUD except that recently deployed soldiers smoked more cigarettes per day. The association of SU with mental mental disorders was substantially different though, revealing significant associations between SU and mental disorders only among recently deployed soldiers. CONCLUSIONS: We do not find remarkable differences in the prevalence of SU and SUD between recently deployed and never deployed soldiers. Especially binge drinking and regular smoking were prevalent across both samples indicating needs for improved interventions. The finding that SU and mental disorders are only associated in recently deployed soldiers might have implications for improved screening and prevention and suggests that deployment might promote different pathways and mechanisms involved in the evolution of SU and mental disorders.