Female sex and burden of depressive symptoms predict insufficient response to telemedical treatment in adult attention-deficit/hyperactivity disorder: results from a naturalistic patient cohort during the COVID-19 pandemic.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence. However, data on telemedical treatment outcomes in adult patients with ADHD is scarce. Methods: We report here the sub-cohort analysis of a naturalistic cohort of adult patients (N = 254) recruited between April 2020-April 2021, comparing the effects of telemedical treatment on participants either clinically diagnosed with depression (N = 54) or ADHD (N = 67). Participants were asked to fill out the WHO-5 repetitively during >12 weeks of telemedical treatment. Furthermore scores of WHO-5, SCL-90R and BDI-II, psychopathology, psychosocial functioning, sociodemographic data, medical records and a feedback survey were analyzed for both groups and compared. Participants with ADHD were further stratified according to the development of well-being during the study period in order to identify factors associated with a satisfactory treatment outcome. Results: Participants with depression reported a significant improvement of well-being during the course of the study, while no such effect could be seen in participants with ADHD on a group level. Despite the good outcome, participants with depression were more severely affected at baseline, with significantly worse psychopathology and a more precarious labor and financial situation. A detailed analysis of ADHD participants without clinical improvement revealed significantly higher BDI-II scores than for ADHD participants with a satisfactory outcome (p = 0.03, Mann-Whitney-U-Test), suggesting successful treatment was hampered by the combination of ADHD and depressive symptoms. Furthermore, female sex among ADHD patients was correlated with an unfavorable treatment outcome during the course of the study (p = 0.001, Spearman correlation) as well as living with children (p = 0.02, Spearman correlation). Conclusion: Besides screening for depressive symptoms before telemedical treatment, future research should address the specific needs of female ADHD patients as these patients may be at a particularly high risk of being overburdened with family work.

EXPLORE: a novel deep learning-based analysis method for exploration behaviour in object recognition tests.

Object recognition tests are widely used in neuroscience to assess memory function in rodents. Despite the experimental simplicity of the task, the interpretation of behavioural features that are counted as object exploration can be complicated. Thus, object exploration is often analysed by manual scoring, which is time-consuming and variable across researchers. Current software using tracking points often lacks precision in capturing complex ethological behaviour. Switching or losing tracking points can bias outcome measures. To overcome these limitations we developed "EXPLORE", a simple, ready-to use and open source pipeline. EXPLORE consists of a convolutional neural network trained in a supervised manner, that extracts features from images and classifies behaviour of rodents near a presented object. EXPLORE achieves human-level accuracy in identifying and scoring exploration behaviour and outperforms commercial software with higher precision, higher versatility and lower time investment, in particular in complex situations. By labeling the respective training data set, users decide by themselves, which types of animal interactions on objects are in- or excluded, ensuring a precise analysis of exploration behaviour. A set of graphical user interfaces (GUIs) provides a beginning-to-end analysis of object recognition tests, accelerating a fast and reproducible data analysis without the need of expertise in programming or deep learning.

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications. Though global CNS delivery of antibodies can be achieved by intrathecal application, these procedures are invasive. A non-invasive method to bring antibodies into the CNS reliably and reproducibly remains an important unmet need in neurology. In the present study, we show that intranasal application of a mouse monoclonal antibody against the neurite growth-inhibiting and plasticity-restricting membrane protein Nogo-A leads to a rapid transfer of significant amounts of antibody to the brain and spinal cord in intact adult rats. Daily intranasal application for 2 wk of anti-Nogo-A antibody enhanced growth and compensatory sprouting of corticofugal projections and functional recovery in rats after large unilateral cortical strokes. These findings are a starting point for clinical translation for a less invasive route of application of therapeutic antibodies to CNS targets for many neurological indications.

[Public Health and Participation of Experts from Experience in Austria: a First Exploratory Survey]. / Public Health und Partizipation von Expertinnen und Experten aus Erfahrung in Österreich: erste explorative Erhebung.

Participation is a basic principle of health promotion and public health. Citizen and patient participation in health care is considered to be poor in Austria and the existing practice is not very visible. An explorative online survey was conducted among members of the Austrian Public Health Association. The aim was to identify the current state of participation of experts from experience ("affected persons") in research, strategy development and practice. 29 organisations working on participation were identified. The survey revealed participation practice was methodologically diverse. Orientation towards participatory models, as the lowest common denominator, can provide a basis for further exchange and shared learning of participation.

Patients with affective disorders profit most from telemedical treatment: Evidence from a naturalistic patient cohort during the COVID-19 pandemic.

Background: During the COVID-19 pandemic telemedicine became essential in maintaining diagnostic procedures and treatment in psychiatry. However, it is still an open question if telemedicine is a feasible treatment option for all groups of psychiatric patients alike. This prospective monocentric observational trial was conducted to assess the general applicability of telemedical treatment in a naturalistic psychiatric outpatient cohort and to identify groups of disorders and clusters of psychopathology that respond particularly well to telemedical treatment considering sociodemographic characteristics and patients' perspectives. Methods: Patients were recruited April 2020-April 2021 and asked to fill out the WHO-5 and the SCL-90R at baseline, after 4-6 and 8-12 weeks and a feedback-survey. Additionally, medical records, psychopathology, psychosocial functioning, and socio-demographic data were analyzed. Primary outcomes were well-being, psychopathology and functioning during treatment. Secondly, diagnostic groups and psychopathology linked to a superior treatment-response were determined with respect to patients' subjective experiences. Results: Out of 1.385 patients, 254-mostly with hyperkinetic (35.3%) and depressive disorders (24.6%)-took part. Well-being and SCL-90R total scores improved substantially (both p < 0.001). CGI and GAF scores were worse in depressed subjects (both p < 0.05). Improvement was mainly seen in depressed patients; chronic disorders experienced a decline in well-being. Sociodemographic characteristics could not explain this difference. Particularly female (r = 0.413) patients found telepsychiatry equivalent to conventional treatment. The more virtual sessions participants attended the more likely they were to find telepsychiatry equal to conventional treatment (r = 0.231). Conclusion: Telemedicine is an effective treatment for patients with depression under naturalistic conditions. Telemedical consultations are a simple and reliable way of monitoring symptom severity and directing treatment choices during the treatment of depressive disorders. Patients with depression benefited more from telemedical treatment compared to participants with chronic non-episodic psychiatric disorders. Future research needs to concentrate on improving telemedical treatment options suited for the latter conditions. Psychiatric telemedicine yielded overall high degrees of satisfaction among users.

Biomonitoring of arsenic, cadmium and lead in two artisanal and small-scale gold mining areas in Zimbabwe.

People living and working in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to elemental mercury (Hg), which is used for gold extraction. However, additional exposure to other toxic metals such as arsenic (As), cadmium (Cd) and lead (Pb) may result from mining-related activities and could be ingested via dust, water or food. In these areas, only limited biomonitoring data is available for toxic metals other than Hg. In particular, data about the exposure to As, Cd and Pb is unavailable for the Zimbabwean population. Therefore, we conducted a cross-sectional study in two ASGM areas in Zimbabwe to evaluate the internal exposure to these metals. In total, urine and blood samples from 207 people that identified themselves as miners were collected and analysed for As and Cd in urine as well as Pb in blood by GF-AAS. Median levels (interquartile ranges in µg/l) of As and Pb were 9.7 µg/l (4.0, 18.5) and 19.7 µg/l (12.5, 34.5), respectively. The 25th percentile and the median for Cd were below the limit of detection (0.5 µg/l); the 75th percentile was at 0.9 µg/l. The results were compared to reference values found for the general population in the USA and Germany, and a significant number of participants exceeded these values (As, 33 %; Cd, 27 %; Pb, 32 %), indicating a relevant exposure to toxic metals. Although not representative for the Zimbabwean population, our results demonstrate that the exposure to toxic metals is relevant for the public health in Zimbabwe and requires further investigation.

Analysis of the Mercury Distribution in Blood as a Potential Tool for Exposure Assessment - Results from Two Artisanal and Small-Scale Gold Mining Areas in Zimbabwe.

People in artisanal and small-scale gold mining (ASGM) areas are frequently exposed to high levels of mercury (Hg). Hg analyses in urine and whole blood are the gold standard of biomonitoring, although this may not provide sufficient information about the source of exposure, e.g., due to the use of Hg for gold extraction or due to nutrition. To evaluate, whether the pharmacokinetic properties of individual Hg species may be useful for exposure assessment, we determined the Hg levels in different blood components from 199 participants. Therefore, whole blood was centrifuged on-site to yield erythrocytes and plasma. Globin was isolated from the erythrocytes by precipitation with ethyl acetate. Albumin was isolated from plasma by gradual precipitation with saturated ammonium sulfate solution. Hg levels in all samples were determined by using a direct Hg analyzer. Median Hg levels for whole blood, erythrocytes, and plasma were 2.7, 3.7, and 1.3 µg/l, respectively. In globin and albumin, median Hg levels were 10.3 and 7.9 µg/kg, respectively. The distribution of Hg was strongly correlated with whole blood Hg levels (p < 0.01) and the time between the last use of Hg and the date of the participation (p < 0.01). The results suggest that the distribution of Hg in blood is substantially affected by the extent and the frequency of the exposure to elemental Hg. Therefore, the analysis of Hg in erythrocytes and plasma may be a valuable tool for Hg exposure assessment in ASGM areas.

Inflammation Mediated Epileptogenesis as Possible Mechanism Underlying Ischemic Post-stroke Epilepsy.

Post-stroke Epilepsy (PSE) is one of the most common forms of acquired epilepsy, especially in the elderly population. As people get increasingly older, the number of stroke patients is expected to rise and concomitantly the number of people with PSE. Although many patients are affected by post-ischemic epileptogenesis, not much is known about the underlying pathomechanisms resulting in the development of chronic seizures. A common hypothesis is that persistent neuroinflammation and glial scar formation cause aberrant neuronal firing. Here, we summarize the clinical features of PSE and describe in detail the inflammatory changes after an ischemic stroke as well as the chronic changes reported in epilepsy. Moreover, we discuss alterations and disturbances in blood-brain-barrier leakage, astrogliosis, and extracellular matrix changes in both, stroke and epilepsy. In the end, we provide an overview of commonalities of inflammatory reactions and cellular processes in the post-ischemic environment and epileptic brain and discuss how these research questions should be addressed in the future.

Prevention of middle ear barotrauma with oxymetazoline/fluticasone treatment.

Middle ear barotrauma (MEB) is a common complication of hyperbaric oxygen (HBO2) therapy. It has been reported in more than 40% of HBO2 treatments and can interrupt the sequence of HBO2. MEB may lead to pain, tympanic membrane rupture, and even hearing loss. The aim of this study was to determine if pretreatment with intranasal fluticasone and oxymetazoline affected the incidence of MEB. We conducted a retrospective chart review of subjects undergoing HBO2 at our institution between February 1, 2014, and May 31, 2019. Subjects in the fluticasone/oxymetazoline (FOT) treatment group used intranasal fluticasone 50 mcg two times per day and oxymetazoline 0.05% one spray two times per day beginning 48 hours prior to initial HBO2. Oxymetazoline was discontinued after four days. Fluticasone was continued for the duration of HBO2 therapy. A total of 154 unique subjects underwent 5,683 HBO2 treatments: 39 unique subjects in the FOT group underwent 1,501 HBO2; 115 unique subjects in the nFOT (no oxymetazoline or fluticasone treatment) group underwent 4,182 HBO2 treatments. The incidence of MEB was 15.4% in the FOT group and 16.2% in the nFOT group. This was not a statistically significant difference (OR = 0.77; p = 0.636). Treatment pressure, age over 65 years, male sex, and BMI were not associated with a difference in MEB incidence. In summary, pretreatment with intranasal oxymetazoline and fluticasone in patients undergoing HBO2 did not significantly reduce MEB. More investigation with larger numbers of participants and prospective studies could further clarify this issue.

Rapid Support for Older Adults during the Initial Stages of the COVID-19 Pandemic: Results from a Geriatric Psychiatry Helpline.

BACKGROUND: The COVID-19 pandemic and governmental lockdown measures disproportionally impact older adults. This study presents the results from a psychiatric helpline for older adults in Mannheim, Germany, during the lockdown, set up to provide information and psychosocial support. We aim to elucidate the needs of older adults, their reported changes, and the psychological impact during the initial stages of the health crisis. METHODS: A total of 55 older adults called the psychiatric helpline between April and June 2020. Information on demographics, medical and psychiatric history. as well as changes in daily life due to the pandemic was collected anonymously. Mental health status was assessed using the 7-Item Hamilton Depression Rating Scale (HAMD-7) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Most callers were women, older adults (M = 74.69 years), single, and retired. In total, 69% of callers reported new or an increase in psychiatric symptoms, with anxiety and depressive symptoms being the most common ones. Age was significantly negatively correlated to higher levels of anxiety and depression symptoms. Individuals with a previous diagnosis of a psychiatric disease reported significantly higher levels of depressive and anxiety symptoms than those without a diagnosis. CONCLUSION: In older adults, the perceived psychological impact of the COVID-19 crisis appears to ameliorate with age. Individuals with a history of psychiatric disease are most vulnerable to negative mental health outcomes. Rapid response in the form of a geriatric helpline is a useful initiative to support the psychosocial needs of older adults during a health crisis.

Non-invasive monitoring of carboxyhemoglobin during hyperbaric oxygen therapy.

Introduction: This study aimed to assess the capability of a pulse CO-oximeter to continuously monitor carboxyhemoglobin (COHb) during hyperbaric oxygen (HBO2) therapy. We estimated limits of agreement (LOA) between blood gas analysis and pulse CO-oximeter for COHb during HBO2 therapy in patients suffering from acute CO poisoning. Furthermore, we did a medicotechnical evaluation of the pulse CO-oximeter in hyperbaric conditions. Methods: We conducted a prospective, non-clinical, observational study in which we included n=10 patients with acute CO poisoning referred for HBO2 therapy. We did five repeated measurements of COHb for each patient during the HBO2 therapy. Bland-Altman analysis for multiple observations per individual was used to assess the agreement. The a priori LOA was ±6% for COHb. For the medicotechnical evaluation continuous measurements were obtained throughout each complete HBO2 therapy. The measurements were visually inspected and evaluated. Results: The Bland-Altman analysis showed that the pulse CO-oximeter overestimated COHb by 2.9 % [±1.0%] and the LOA was ±7.3% [±1.8%]. The continuous measurements by pulse CO-oximetry showed fluctuating levels of COHb and summarized saturations reached levels above 100%. Measurements were not affected by changes in pressure. Conclusion: To our knowledge, this study is the first to assess LOA and demonstrate use of a non-invasive method to measure COHb during HBO2 therapy. The pulse CO-oximeter performed within the manufactures reported LOA (±6%) despite hyperbaric conditions and was unaffected by changes in pressure. However, summarized saturations reached levels above 100%.

Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats.

Antibody-based therapeutics targeting CNS antigens emerge as promising treatments in neurology. However, access to the CNS is limited by the blood-brain barrier. We examined the effects of a neurite growth-enhancing anti-Nogo A antibody therapy following 3 routes of administration-intrathecal (i.t.), intravenous (i.v.), and subcutaneous (s.c.)-after large photothrombotic strokes in adult rats. Intrathecal treatment of full-length IgG anti-Nogo A antibodies enhanced recovery of the grasping function, but intravenous or subcutaneous administration had no detectable effect in spite of large amounts of antibodies in the peripheral circulation. Thus, in contrast to intravenous and subcutaneous delivery, intrathecal administration is an effective and reliable way to target CNS antigens. Our data reveal that antibody delivery to the CNS is far from trivial. While intrathecal application is feasible and guarantees defined antibody doses in the effective range for a biological function, the identification and establishment of easier routes of administration remains an important task to facilitate antibody-based future therapies of CNS disorders.

Measurement of peripheral arterial tonometry in patients with diabetic foot ulcers during courses of hyperbaric oxygen treatment.

INTRODUCTION: Treatment of diabetic foot ulcers is complex and often protracted. Hyperbaric oxygen treatment (HBOT) improves wound healing in diabetic ulcers and serves as an important adjunct to regular diabetic wound care. Endothelial dysfunction plays a central role in diabetes-related vascular complications and may be evaluated by a non-invasive technique called peripheral arterial tonometry which measures a reactive hyperaemia index (RHI). We hypothesized that endothelial function measured by peripheral arterial tonometry is impaired in diabetic foot ulcer patients and that HBOT might improve endothelial function. METHODS: Endothelial function was prospectively assessed by peripheral arterial tonometry in 22 subjects with diabetic foot ulcers and 17 subjects without diabetes during courses of HBOT. Endothelial function was evaluated before first (baseline) and 30th treatments, and at 90-day follow-up. Serum insulin growth factor-I (IGF-I) concentrations were determined by immunoassay. Results were compared to 23 healthy subjects. RESULTS: No baseline differences were found in endothelial function between subjects with diabetes, HBOT patients without-diabetes and healthy control subjects (RHI; 1.26, 1.61 and 1.81, respectively). No significant changes in RHI were found in patients with (P = 0.17) or without (P = 0.30) diabetes during courses of HBOT. At 90-day follow-up IGF-I was significantly reduced in the subjects with diabetes (P = 0.001) and unchanged in the group without diabetes (P = 0.99). CONCLUSIONS: We found no significant differences in RHI between subjects with diabetic foot ulcers and patients without diabetes, nor improvement in endothelial function assessed by peripheral arterial tonometry during courses of HBOT.

Context-dependent limb movement encoding in neuronal populations of motor cortex.

Neuronal networks of the mammalian motor cortex (M1) are important for dexterous control of limb joints. Yet it remains unclear how encoding of joint movement in M1 depends on varying environmental contexts. Using calcium imaging we measured neuronal activity in layer 2/3 of the M1 forelimb region while mice grasped regularly or irregularly spaced ladder rungs during locomotion. We found that population coding of forelimb joint movements is sparse and varies according to the flexibility demanded from individual joints in the regular and irregular context, even for equivalent grasping actions across conditions. This context-dependence of M1 encoding emerged during task learning, fostering higher precision of grasping actions, but broke apart upon silencing of projections from secondary motor cortex (M2). These findings suggest that M1 exploits information from M2 to adapt encoding of joint movements to the flexibility demands of distinct familiar contexts, thereby increasing the accuracy of motor output.

A single session of hyperbaric oxygen therapy demonstrates acute and long-lasting neuroplasticity effects in humans: a replicated, randomized controlled clinical trial.

PURPOSE: Animal studies have demonstrated anti-inflammatory, and anti-nociceptive properties of hyperbaric oxygen therapy (HBOT). However, physiological data are scarce in humans. In a recent experimental study, the authors used the burn injury (BI) model observing a decrease in secondary hyperalgesia areas (SHA) in the HBOT-group compared to a control-group. Surprisingly, a long-lasting neuroplasticity effect mitigating the BI-induced SHA-response was seen in the HBOT-preconditioned group. The objective of the present study, therefore, was to confirm our previous findings using an examiner-blinded, block-randomized, controlled, crossover study design. PATIENTS AND METHODS: Nineteen healthy subjects attended two BI-sessions with an inter-session interval of ≥28 days. The BIs were induced on the lower legs by a contact thermode (12.5 cm2, 47C°, 420 s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O2, 90 min) or ambient conditions ([AC]; 1 ATA, 21% O2), dividing cohorts equally into two sequence allocations: HBOT-AC or AC-HBOT. All sensory assessments performed during baseline, BI, and post-intervention phases were at homologous time points irrespective of sequence allocation. The primary outcome was SHA, comparing interventions and sequence allocations. RESULTS: Data are mean (95% CI). During HBOT-sessions a mitigating effect on SHA was demonstrated compared to AC-sessions, ie, 18.8 (10.5-27.0) cm2 vs 32.0 (20.1-43.9) cm2 (P=0.021), respectively. In subjects allocated to the sequence AC-HBOT a significantly larger mean difference in SHA in the AC-session vs the HBOT-session was seen 25.0 (5.4-44.7) cm2 (P=0.019). In subjects allocated to the reverse sequence, HBOT-AC, no difference in SHA between sessions was observed (P=0.55), confirming a preconditioning, long-lasting (≥28 days) effect of HBOT. CONCLUSION: Our data demonstrate that a single HBOT-session compared to control is associated with both acute and long-lasting mitigating effects on BI-induced SHA, confirming central anti-inflammatory, neuroplasticity effects of hyperbaric oxygen therapy.

Case report: a giant arachnoid cyst masking Alzheimer's disease.

BACKGROUND: Intracranial arachnoid cysts are usually benign congenital findings of neuroimaging modalities, sometimes however, leading to focal neurological and psychiatric comorbidities. Whether primarily clinically silent cysts may become causally involved in cognitive decline in old age is neither well examined nor understood. CASE PRESENTATION: A 66-year old caucasian man presenting with a giant left-hemispheric frontotemporal cyst without progression of size, presented with slowly progressive cognitive decline. Neuropsychological assessment revealed an amnestic mild cognitive impairment (MCI) without further neurological or psychiatric symptoms. The patient showed mild medio-temporal lobe atrophy on structural MRI. Diffusion tensor and functional magnetic resonance imaging depicted a rather sustained function of the strongly suppressed left hemisphere. Amyloid-PET imaging was positive for increased amyloid burden and he was homozygous for the APOEε3-gene. A diagnosis of MCI due to Alzheimer's disease was given and a co-morbidity with a silent arachnoid cyst was assumed. To investigate, if a potentially reduced CSF flow due to the giant arachnoid cyst contributed to the early manifestation of AD, we reviewed 15 case series of subjects with frontotemporal arachnoid cysts and cognitive decline. However, no increased manifestation of neurodegenerative disorders was reported. CONCLUSIONS: With this case report, we illustrate the necessity of a systematic work-up for neurodegenerative disorders in patients with arachnoid cysts and emerging cognitive decline. We finally propose a modus operandi for the stratification and management of patients with arachnoid cysts potentially susceptive for cognitive dysfunction.

Early reduced behavioral activity induced by large strokes affects the efficiency of enriched environment in rats.

The majority of stroke patients develop post-stroke fatigue, a symptom which impairs motivation and diminishes the success of rehabilitative interventions. We show that large cortical strokes acutely reduce activity levels in rats for 1-2 weeks as a physiological response paralleled by signs of systemic inflammation. Rats were exposed early (1-2 weeks) or late (3-4 weeks after stroke) to an individually monitored enriched environment to stimulate self-controlled high-intensity sensorimotor training. A group of animals received Anti-Nogo antibodies for the first two weeks after stroke, a neuronal growth promoting immunotherapy already in clinical trials. Early exposure to the enriched environment resulted in poor outcome: Training intensity was correlated to enhanced systemic inflammation and functional impairment. In contrast, animals starting intense sensorimotor training two weeks after stroke preceded by the immunotherapy revealed better recovery with functional outcome positively correlated to the training intensity and the extent of re-innervation of the stroke denervated cervical hemi-cord. Our results suggest stroke-induced fatigue as a biological purposeful reaction of the organism during neuronal remodeling, enabling new circuit formation which will then be stabilized or pruned in the subsequent rehabilitative training phase. However, intense training too early may lead to wrong connections and is thus less effective.