Evaluation of a Primary E-Health Intervention for People with Alcohol Use Disorder: Clinical Characteristics of Users and Efficacy.

In Germany, only about 10% of patients with alcohol use disorder (AUD) are treated by the professional help system. "The First 30 Days without Alcohol", an interactive e-health intervention, was developed to support people with "alcohol problems" to abstain from alcohol. The aim of this study was to examine the feasibility of the approach, the program's target group, if and why it is effective. In March 2022 an email was sent to all users who had completed the program. A link to a web-based survey regarding the target group's characteristics, its alcohol-use patterns, former attempts to change the problematic drinking behavior and experience with the program was introduced. The Alcohol Use Disorders Identification Test (AUDIT) was used prior and post intervention. A total of 718 participants completed the questionnaire. Of these, 99.2% suffered from AUD; 81.6% of participants were females, and about one third reported some form of psychiatric comorbidity; 46.6% did not use any additional help or assistance apart from the program; 78.3% reported to be abstinent after participation in the 30-day program, and the data show a significant AUDIT score reduction. Primary e-health interventions may contribute to the established addiction-help system. The intervention seems to reach predominantly highly educated and high-functioning females because of their characteristics.

Unemployment and Substance Use: An Updated Review of Studies from North America and Europe.

Since the industrial revolution, the relationship between unemployment and psychiatric disorders has been a subject of high interest. Currently, regarding the correlation between unemployment and substance-use disorders (SUDs), only older, often isolated and fragmented research results are available in the literature. This review was based on an extensive literature search of the European and North American literature in most relevant databases for "unemployment" and "substance use" related to "drugs", "alcohol", "nicotine", and "tobacco" between November 2022 and January 2023, according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) guidelines. A total of 59,117 papers were identified, of which only 33 articles were identified as relevant to the research objective. The literature showed significantly higher prevalence rates of SUDs involving divergent psychotropic substances among unemployed people. Unemployment was found to be a risk factor for SUD, and vice versa. However, the correlation between unemployment and relapses or smoking cessation was inconsistent. In addition, there appeared to be a mild effect of business cycles on SUD. The results showed significant multifaceted correlations between unemployment and SUD, indicating that prevention and early intervention are required to prevent harmful psychosocial consequences, such as social disintegration and severe psychiatric disorders.

Psychiatric Morbidity, Utilization and Quality of Mental Health Care in Long-Term Unemployed People.

Research has shown complex interactions between unemployment and mental health. However, the prevalence of specific mental disorders, utilization of mental health care services and influences on help-seeking behavior have been investigated surprisingly little in the past. In this study, we investigated a sample of long-term unemployed people in a cooperation program of the local unemployment agency and a psychiatric university hospital in a larger city in Germany. Mental disorders, treatment history, accordance of treatment to national treatment guidelines and factors influencing previous treatment were assessed. Participants (n = 879; male 56%, female 44%, mean age 43.9 years) showed a high psychiatric morbidity, mostly with diagnoses from the ICD-10 categories F1 (22%), F3 (61%) and F4 (68%). Currently, 18% were in psychiatric treatment, 6% were in psychotherapeutic treatment, and 28% received psychopharmacological treatment. Mostly young men underutilized the psychiatric-psychotherapeutic system, with middle-aged men and women being most frequently in psychopharmacological treatment. Of those treated, only about 10% of the subjects currently received a treatment according to national guidelines. The utilization of psychotherapeutic treatment was strikingly poor. This study identified high psychiatric morbidity and severe treatment gaps in unemployed people. These results can help to target subjects with specific needs for interventions and to modify counseling programs.

[Acceptance and use of web-based interventions for alcohol abstinence]. / Nutzung und Akzeptanz webbasierter Angebote zur Alkoholabstinenz.

INTRODUCTION: In Germany, the prevalence rates for alcohol use disorders amount to approx. 6%, while about 3% are diagnosed as being alcohol dependent. Only 10% of the patients are undergoing treatment. There are apparent deficits with respect to early interventions. The internet presence of "Ohne Alkohol mit Nathalie" (OAmN) (Abstinence with Nathalie) ameliorates options for early treatment interventions using a web-based design; however, this intervention has not been evaluated to date, especially with respect to previous treatments. METHODS: Over a 4-week period, 4 different channels of OAmN posted announcements for a survey participation introducing a link leading to a web-based survey questionnaire on the domain oamn.jetzt. The questionnaire offered open and closed as well as multiple choice questions regarding alcohol use patterns and attempts to change the problematic drinking behavior. RESULTS: Out of 2022 participants 84.3% (n = 1705) stated to have or have had a problem with alcohol use, 17.7% (n = 302) had a diagnosis of alcohol dependence by a physician or psychologist and only 21% (n = 529) had been in therapy before. The majority of responders (85.5%, n = 1457) had stopped alcohol use before participating in the survey. Most of them (48.5%, n = 705) were assisted by OAmN, 97.5% (n = 1662) had been employed while having the abovementioned problem use of alcohol, 34.3% (n = 570) rated their job performance as "very good" and 43.2% (n = 718) as "good". DISCUSSION: This pilot study revealed that OAmN can reach people affected by problematic drinking behavior who had not been in contact with the professional medical system for addiction treatment despite having a problematic alcohol use combined with the willingness to quit.

Stimulant abuse as a coping strategy-Forensic and criminal consequences of stimulant abuse for neuroenhancement.

Pharmacological neuroenhancement (PN) describes the use of divergent psychoactive substances to enhance mental performance (cognition) without medical need. This kind of substance abuse takes place predominantly in stressful situations. Users implicitly-or even explicitly-describe this kind of drug abuse to be a coping strategy. Regarding the decision making process whether to use PN drugs or not, users indicate that legal aspects to be decisive. However, the legal situation has been neglected so far. To elucidate the German legal situation, PN substances have to be divided into over-the-counter drugs, prescription drugs and illegal drugs. Amphetamines have the highest cognition-enhancing potential, followed by modafinil and caffeine-containing substances. It is pointed out that the use of both freely available and prescription PN substances and narcotics without medical indication have so far been largely exempt from punishment under German law. However, individuals (physicians, bus and truck drivers, etc.) taking PN substances may expose others at risk due to wrong decisions (driving or treatment), errors based on side effects of the used substances. Therefore, the protection of life and health of others could legitimize criminal regulation.

Treatment outcome, cognitive function, and psychopathology in methamphetamine users compared to other substance users.

BACKGROUND: The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group. Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited. Due to specific characteristics of methamphetamine users, the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well. We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances. AIM: To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes. METHODS: A total of 110 subjects were recruited for an observational, longitudinal study from a German inpatient addiction treatment center: 55 patients with methamphetamine dependence and 55 patients with dependence of other substances ("OS group"). Both groups were examined at beginning (baseline) and end of treatment (after 6 mo) with regard to treatment retention, craving, cognitive functioning, psychosocial resources, personality traits, depression, and other psychiatric symptoms. Instruments used were Raven's IQ test, Mannheimer craving scale, cognitrone cognitive test battery, NEO personality factors inventory, Hamilton depression scale, Becks depression inventory, and a symptom checklist. The statistical methods used were χ 2-test, t-test and multiple mixed ANOVAs. RESULTS: A total drop-out rate of 40% (methamphetamine-group: 36.4%; OS-group: 43.6%) was observed without significant differences between groups. At baseline, methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient, fewer years of education, slower working speed, and decreased working accuracy, as well as less cannabinoid and cocaine use. Methamphetamine-group subjects further showed a significantly lower score of conscientiousness, depressive, and psychiatric symptoms than subjects from the OS-group. In both groups, a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment. CONCLUSION: There are differences between methamphetamine users and users of other drugs, but not with regard to the effectiveness of treatment in this inpatient setting. There are differences in cognitive function and psychopathology between methamphetamine and other drugs users. The existing treatment options seem to be an effective approach in treating methamphetamine dependence.

Recent advances in the treatment of opioid use disorders-focus on long-acting buprenorphine formulations.

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders (OUDs). Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs: (1) CAM 2038 (Buvidal) for subcutaneous weekly and monthly application; (2) RBP-6000 (Sublocade™) as a monthly depot formulation; and (3) A six-month buprenorphine implant [Probuphine™]. The pharmacology, clinical efficacy and prospects of these medications are discussed.

Just "Like Coffee" or Neuroenhancement by Stimulants?

Introduction: Pharmacological neuroenhancement (PN) is a topic of increasing importance and prevalence among students. However, there is a lack of differentiating PN substances, according to their psychoactive effects. In particular, there is a lack of data about PN by caffeinated drinks, even if coffee is a common and broadly used Neuroenhancer because of its cognitively enhancing effects regarding wakefulness, alertness and concentration. Materials and Methods: A web-survey was developed for German students and alumni about the non-medical use of caffeine for PN contained questions about coffee, caffeinated drinks and energy drinks, caffeine pills and methylxanthine tea regarding frequency and further contextual factors. Results: Six hundred and eighty-three participants completed the survey. Nearly all participants knew about PN (97.7%). 88.1% admitted using some over-the-counter substances. For PN purposes, coffee was used by 72.9% followed by energy drinks (68.2%) and cola drinks (62.4%). Methylxanthine containing tea was used for PN purposes, too (black tea 52.3%, green tea 51.7%). 1.8% admitted using illegal substances or prescription drugs, too. Discussion: Using legal methylxanthine containing drinks for PN seems to be extremely common with coffee and energy drinks being the preferred substances, while illegal and prescription drugs are only minimally used. Further studies should investigate the awareness of methylxanthine containing drinks as well as its character to be a flavoring drink or a neuroenhancer.

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.

BACKGROUND: Recognition of viral nucleic acids is one of the primary triggers for a type I interferon-mediated antiviral immune response. Inborn errors of type I interferon immunity can be associated with increased inflammation and/or increased susceptibility to viral infections as a result of dysbalanced interferon production. NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. The role of ZNFX1 in the human immune response is not known. OBJECTIVE: We studied 15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic lymphohistiocytosis-like disease, early-onset seizures, and renal and lung disease. METHODS: Whole exome sequencing was performed on 13 patients from 8 families. We investigated the transcriptome, posttranscriptional regulation of interferon-stimulated genes (ISGs) and predisposition to viral infections in primary cells from patients and controls stimulated with synthetic double-stranded nucleic acids. RESULTS: Deleterious homozygous and compound heterozygous ZNFX1 variants were identified in all 13 patients. Stimulation of patient-derived primary cells with synthetic double-stranded nucleic acids was associated with a deregulated pattern of expression of ISGs and alterations in the half-life of the mRNA of ISGs and also associated with poorer clearance of viral infections by monocytes. CONCLUSION: ZNFX1 is an important regulator of the response to double-stranded nucleic acids stimuli following viral infections. ZNFX1 deficiency predisposes to severe viral infections and a multisystem inflammatory disease.

Psychiatric Comorbidity and Stress in Medical Students Using Neuroenhancers.

Background: Pharmacological neuroenhancement (PN) is a common healthcare problem at least among students. PN seems to be associated with stressful situations. There is a lack of data about personal characteristics, comorbidities, and coping strategies regarding stress and factors of resilience in students and medical staff. Methods: A web-based survey about the non-medical use of PN drugs with a focus on neuroenhancement was developed and distributed among medical students throughout Germany; the questionnaire was open in April and May of 2020. The survey contained questions about the use of well-known PN drugs, frequency, special purposes, reasons for the use, psychiatric disorders, use of psychotropic drugs apart from PN purposes, and factors of resilience using the brief resilience scale. Results: Data of 1,159 students of medicine were analyzed. The most frequently used substances for PN were coffee (78.8% lifetime prevalence rate), energy drinks (45.7%), caffeine tablets (24.3%), methylphenidate (5.2%), illicit amphetamines (2.0%), and cocaine (1.7%). 98.4% suspected that PN drug use could lead to addiction. PN drug use specifically for PN was significantly associated with the use of (a) any psychotropic drug (other than neuroenhancers), (b) any psychiatric disorder, and (c) higher values of feeling pressure to perform in professional/students' life and in private life as well as (d) the subjective feeling of pressure to perform to be burdening and (e) harmful to one's own health. PN drug use in general was significantly associated with being less resilient. The use of illicit PN drugs, over the counter drugs and prescription drugs was associated with being less resilient. Conclusion: This study indicates that PN with legal and illegal drugs is a widespread phenomenon among German medical students. Users seem to be more often burdened by psychiatric disorders, especially addictive disorders, the perception of stress, pressure to perform and low levels of resilience. These aspects should be considered in further investigation of PN drug use.

Facial Swelling in a Toddler Due to a Metastatic High-Risk Neuroblastoma.

Neuroblastoma is a malignant embryonal tumor derived from the neural crest cells of the sympathetic nervous system. Curative therapy is challenging, especially because early-stage diagnosis in toddlers is difficult. Successful treatment of high-risk neuroblastoma is only achieved in approximately half of the cases and requires an immediate interdisciplinary approach. We present a 34-month-old toddler with swelling of the left side of the face of three days duration and a mandibular mass of unknown duration, which was diagnosed as a metastasis of a neuroblastoma. He also had metastases in the kidney, long bones and skull. Despite the poor prognosis in cases of disseminated skeletal involvement and N-myc amplification, the young patient remained free of recurrence during a follow-up period of 36 months after multidisciplinary treatment. The purpose of this case report is to increase awareness of the clinical features of neuroblastoma among pediatric dentists to support early-stage diagnosis and highlight interdisciplinary management.

Melanotic neuroectodermal tumor of infancy to the skull: case-based review.

BACKGROUND: Melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor, which usually occurs in infants under the age of one. Early diagnosis and radical surgery seem to be critical for long-term cure. CASE PRESENTATION: We describe a case of a 4-month-old boy with a MNTI to the skull. The mass was first noticed at 4 month of age and grew very rapidly over a time of 2 weeks. Initially, a fine needle biopsy ruled out a sarcoma and led to the diagnosis. The tumor originated from the sphenoid wing and infiltrated the frontotemporal bone, the lateral wall of the right orbit, and the underlying dura mater. A total excision of the tumor, including the adjacent bone and dura, was achieved. Reconstruction of the bone was performed using absorbable plates and Tutobone. Histology confirmed the initial diagnosis, while molecular diagnosis showed high conformity of the MNTI with medulloblastoma group 3. The patient recovered well, while the reconstruction led to a good cosmetic result. A local recurrence occurred leading to a single-dose chemotherapy with Vincristine and a second surgery after 15 weeks. Thereafter, the patient developed recurrent large pseudomeningocele, which was treated by multiple shunt procedures and finally reconstruction of the bone using Palacos. Radiological follow-up 3 months after the second resection showed no tumor recurrence. CONCLUSION: Radical surgery for MNTI is to date the gold standard since it seems to minimize recurrence rates. Because of the rapid and destructive growth within the bone, reconstruction is necessary, which can be very challenging in infants.

Prognostic significance of emergency department bypass in stable and unstable patients with ST-segment elevation myocardial infarction.

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention, direct transport from the scene to the catheterisation laboratory bypassing the emergency department has been shown to shorten times to reperfusion. The aim of this study was to investigate the effects of emergency department bypass on mortality in both haemodynamically stable and unstable STEMI patients. METHODS: The analysis is based on a large cohort of STEMI patients prospectively included in the German multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial. RESULTS: Out of 13,219 STEMI patients who were brought directly from the scene by emergency medical service transportation and were treated with percutaneous coronary intervention, the majority were transported directly to the catheterisation laboratory bypassing the emergency department (n=6740, 51% with emergency department bypass). These patients had a significantly lower in-hospital mortality than their counterparts with no emergency department bypass (6.2% vs. 10.0%, P<0.0001). The reduced mortality related to emergency department bypass was observed in both stable (n=11,594, 2.8% vs. 3.8%, P=0.0024) and unstable patients presenting with cardiogenic shock (n=1625, 36.3% vs. 46.2%, P<0.0001). Regression models adjusted for the Thrombolysis In Myocardial Infarction (TIMI) risk score consistently confirmed a significant and independent predictive effect of emergency department bypass on survival in the total study population (odds ratio 0.64, 95% confidence interval 0.56-0.74, P<0.0001) and in the subgroup of shock patients (OR 0.69, 95% CI 0.54-0.88, P=0.0028). CONCLUSION: In STEMI patients, emergency department bypass is associated with a significant reduction in mortality, which is most pronounced in patients presenting with cardiogenic shock. Our data encourage treatment protocols for emergency department bypass to improve the survival of both haemodynamically stable patients and, in particular, unstable patients. Clinical Trial Registration: NCT00794001 ClinicalTrials.gov: NCT00794001.

Outcomes of cryoballoon or radiofrequency ablation in symptomatic paroxysmal or persistent atrial fibrillation.

AIMS: To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF). METHODS AND RESULTS: Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was 'atrial arrhythmia recurrence', secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm2 (RFA) (P < 0.001). Follow-up duration was 441 (CBA) and 511 days (RFA) (P < 0.0001). Primary endpoint occurred in 30.7% (CBA) and 39.4% patients (RFA) [adjusted hazard ratio (adjHR) 0.85, 95% confidence interval (CI) 0.70-1.04; P = 0.12). In paroxysmal AF, CBA resulted in a lower risk of recurrence (adjHR 0.80, 95% CI 0.64-0.99; P = 0.047). In persistent AF, the primary outcome was not different between groups. Major adverse cardiovascular and cerebrovascular event rates were 1.0% (CBA) and 2.8% (RFA) (adjHR 0.53, 95% CI 0.26-1.10; P = 0.088). Re-ablations (adjHR 0.46, 95% CI 0.34-0.61; P < 0.0001) and adverse events during follow-up (adjHR 0.64, 95% CI 0.48-0.88; P = 0.005) were less common after CBA. Higher rehospitalization rates with RFA were caused by re-ablations. CONCLUSIONS: The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.

Risk factors for contagious gastroenteritis in adult patients with diarrhoea in the emergency department - a prospective observational multicentre study.

BACKGROUND: Infectious gastroenteritis is common in the emergency department (ED). Patients infected with either Norovirus or toxigenic Clostridium difficile require special isolation procedures. The aims were to describe the aetiology of infectious gastroenteritis in the ED, evaluate whether current isolation procedures, based on clinical judgement are sufficient, and to identify information that might be used to identify patients requiring isolation. METHODS: Prospective, observational, multicentre study. We collected information on symptoms, vital signs, travel history, the recent use of antibiotics, and infectious contacts and tested faecal samples for Norovirus, C. difficile, and enteropathogenic bacteria. RESULTS: The study enrolled 227 patients, of whom 163 (71%) delivered a faecal sample for Norovirus analysis (13% positive), 171 (74%) for C. difficile (13% positive), and 173 (76%) for enteropathogenic bacteria (16% positive). In total 71% of the patients were isolated using strict precautions, 29% of the isolated patient and 14% of the patients who were not isolated had had a highly contagious GE. Risk factors for Norovirus included frequent vomiting (OR 5.5), recent admission of another patient with Norovirus (OR 2.6), and a short duration of diarrhoea. Risk factors for C. difficile infections included older age (OR 6.0), longer duration of diarrhoea (OR 5.2), mucus in stool (OR 3.5), and previous antibiotic use (OR 23.4). CONCLUSION: Highly contagious GE occurs in » of the GE patients in the EDs, isolation based on clinical judgement is not very efficient. Several risk factors can predict the presence of Norovirus or toxigenic Clostridium difficile. It is uncertain whether this knowledge can improve isolation practices in ED settings. TRIAL REGISTRATION: This study was retrospectively registered in the Clinical Trials Data Base ( NCT02685527 ) and prospectively approved by the Regional Committees on Health Research Ethics for Southern Denmark (project ID S20140200) and Ethics Committee at the Medical Association of Schleswig-Holstein ["Ethikkommission bei der Ärztekammer Schleswig-Holstein", project ID 120/15(I)] and registered with the Danish Data Protection Agency (project ID nr. 2008-58-0035/ 1608).

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project.

INTRODUCTION: We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting. METHODS: We collected CSF samples from 137 participants in eight local memory clinics. Amyloid ß(1-42) (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed. RESULTS: Biomarker results strongly correlated between assays with Spearman's ρ 0.94 for Aß42, 0.98 for t-tau, and 0.98 for p-tau. Using Gaussian mixture modeling, cohort-specific cut-points were estimated at 1092 pg/mL for Aß42, 235 pg/mL for t-tau, and 24 pg/mL for p-tau. We found an excellent concordance of biomarker abnormality between assays of 97% for Aß42 and 96% for both t-tau and p-tau. DISCUSSION: The high concordances between Elecsys and Innotest in this nonacademic, multicenter cohort support the use of Elecsys for CSF Alzheimer's disease diagnostics and allow conversion of results between methods.

Pharmacological neuroenhancement and the ability to recover from stress - a representative cross-sectional survey among the German population.

BACKGROUND: Pharmacological neuroenhancement (PNE) refers to the use of psychoactive substances without doctor's prescription to enhance cognitive performance or to improve mood. Although some studies have reported that drugs for PNE are also being used to cope with stressful life situations, nothing is known about the relationship of PNE and resilience, i.e. the ability to recover from stress. This study aimed at investigating the relationship of PNE and resilience in the first representative population sample. METHODS: A cross-sectional survey in a representative sample of 1128 adults (age ≥ 18 yrs.) living in Germany was conducted. The use of PNE and related attitudes, perceptions and behaviours were assessed by structured interviews and self-report questionnaires. Stepwise logistic regression with backward elimination was conducted to identify potential risk factors for PNE use. RESULTS: Lifetime prevalence for the use of stimulating prescription drugs without medical indication was 4.3%, 10.2% for stimulating illicit drugs, 20.3% for mood modulating prescription drugs, and 23.4% for cannabis. Coping with stressful situations was more frequently reported as underlying motive for using stimulant or mood modulating prescription drugs than stimulating illicit drugs or cannabis. The individual perceived stress increased the risk of using stimulating prescription drugs (OR: 2.86; 95% Cl: 1.49-5.46) and the individual ability to recover from stress decreased the risk of using any substance for PNE and especially mood modulating prescription drugs (OR: .62; 95% Cl: .47-.81). CONCLUSIONS: The non-medical use of prescription drugs for PNE appears to be more prevalent in subjects who are less resilient to stress. Tailored resilience interventions that improve the ability to adapt to and recover from stressors may prevent the use of prescription medication for PNE. Further research should disentangle the association between psychological resilience and PNE as well as examine the efficacy of resilience interventions in the prevention of PNE.

Coadsorbate-Induced Reversal of Solid-Liquid Interface Dynamics.

Coadsorbed anions are well-known to influence surface reactivity and dynamics at solid-liquid interfaces. Here we demonstrate that the chemical nature of these spectator species can entirely determine the microscopic dynamic behavior. Quantitative in situ video-STM data on the surface diffusion of adsorbed sulfur atoms on Cu(100) electrodes in aqueous solution covered by bromide and chloride spectators, respectively, reveal in both cases a strong exponential potential dependence, but with opposite sign. This reversal is highly surprising in view of the isostructural adsorbate arrangement in the two systems. Detailed DFT studies suggest an anion-induced difference in the sulfur diffusion mechanism, specifically an exchange diffusion on the Br-covered surface. Experimental evidence for the latter is provided by the observation of Cu vacancy formation in the Br system, which can be rationalized by a side reaction of the sulfur exchange diffusion.

Effects of IL-10 and Th 2 cytokines on human Mφ phenotype and response to CSF1R inhibitor.

Tumor-associated Mφs display a plastic phenotype that is regulated by the local tumor milieu. Gene expression analysis and functional characterization of Mφs exposed in vitro to individual cytokines aids to delineate the cross-talk between defined cytokines shaping the complex Mφ phenotype. Human monocyte-derived Mφs can be differentiated in vitro with the T helper cell type 2 response cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking antibody emactuzumab. However, under physiologic conditions, the Mφ phenotype is regulated by cytokine combination. Hence, in this study, we characterized the plasticity of IL-4 or IL-13-differentiated Mφs upon exposure to the immunosuppressive IL-10. Although IL-4-differentiated Mφs sustained their molecular phenotype in the presence of IL-10, IL-13-differentiated Mφs were skewed towards the IL-10 phenotype. Gene expression profiling revealed unique IL-4+IL-10 and IL-13+IL-10 Mφ signatures associated with up-regulation of canonical NF-κB or Wnt/ß-catenin signaling pathways, respectively. Although IL-10 was able to alter the surface marker and gene expression profile of IL-13-differentiated Mφs, addition of IL-10 did not restore emactuzumab susceptibility. Combining NF-κB and Wnt/ß-catenin signaling inhibitors with emactuzumab had no effect on viability. On average 3-5% of cancer patients overexpressed IL-4, IL-13, or IL-10 mRNA in silico. Although a small patient subset overexpressed IL-10+IL-13, IL-4+IL-10 lacked co-expression. In vitro characterization of CSF1R inhibitor-refractory Mφ phenotypes can support novel pharmacological approaches to specifically target these cells.