Epidemiology of alopecia areata and population-wide comorbidities in Germany: analysis of longitudinal claims data.

BACKGROUND: Alopecia areata (AA) is a chronic, immune-mediated disease characterized by acute-onset hair loss. The hair loss can range from small, circumscribed hairless areas on the scalp to complete loss of hair on the head and body hair. However, data on the epidemiology of AA are limited. Current evaluations are lacking in Germany. The aim of this study was to evaluate the epidemiology and comorbidity of AA in Germany based on claims data. METHODS: A representative 40% sample of all adults who were insured with a German statutory health insurance company (DAK-Gesundheit) between 2016 and 2020 was evaluated (n = 2.88 million). Based on at least one relevant outpatient or inpatient diagnosis of International Classification of Diseases (ICD)-10 L63, the annual AA prevalence and incidence (ICD-10 L63) were calculated for 2016 to 2020. Different case definitions were used for diagnosis validation. In addition, the occurrence of comorbidities in patients with AA was investigated. RESULTS: In 2020, AA prevalence was 210 cases per 100 000 and incidence 72 cases per 100 000. Compared with persons without AA, those with AA significantly more often had atopic dermatitis [rate ratio (RR) 2.9], pruritus (RR 2.7), lupus erythematosus (RR 2.4), urticaria (RR 2.3) and psoriasis (RR 2.2). Women were affected slightly more often than men (0.2% vs. 0.1%). On a regional level, higher prevalence and incidence rates were found in Brandenburg (prevalence 332 cases per 100 000; incidence 116 cases per 100 000), Hesse (prevalence 344 cases per 100 000; incidence 124 cases per 100 000) and Mecklenburg-Western Pomerania (prevalence 303 cases per 100 000; incidence 111 per 100 000). CONCLUSIONS: AA is a common immune-mediated skin condition with marked regional variations in Germany. For a complete understanding of epidemiology, complementary population-based studies including clinical characteristics of AA are useful.

Utilization and related harms of systemic glucocorticosteroids for atopic dermatitis: claims data analysis.

BACKGROUND AND OBJECTIVES: Systemic glucocorticosteroids (SGCs) are used in the short-term treatment of atopic dermatitis (AD), but are not recommended for long-term use since associated with severe side effects. This study aimed to characterize the utilization and potentially negative effects of SGC use for AD in German statutory health insurance (SHI) claims data. PATIENTS AND METHODS: Cross-sectional and longitudinal analysis of a large nationwide SHI dataset. SGC drug prescriptions and incidences of predefined comorbidities after drug initiation known as potentially harmful side effects were analysed. The SGC use was quantified by 1) the number of quarters with at least one SGC prescription and 2) the defined daily doses (DDD). Adjustments in comparisons were made for age, gender and morbidity. RESULTS: The AD prevalence was 4.07% in 2020 (4.12% women, 3.71% men). During this period 9.91% of persons with AD were prescribed SGCs compared with 5.54% in persons without AD (p < 0.01). Prescribing of SGCs was significantly higher in women (10.20% vs.9.42% in men, p=<0.01) and the elderly. AD and sGC prevalence varied regionally. In a three-year follow-up period, 51% of persons with AD receiving a SGC were prescribed SGCs in > 1 quarter and 15% in > 6 quarters. The odds of developing osteoporosis (odds ratio 3.95 [approach 1] and 1.80 [approach 2]) and diabetes (odds ratio 1.90 [approach 1] and 1.38 [approach 2]) were significantly higher in people with AD on sGCS, especially in the frequently prescribed group compared with the rarely prescribed group, regardless of quantified use. CONCLUSION: A considerable number of persons with AD in Germany are prescribed longterm SGCs. The onset of medical conditions known to be harmful effects from steroids was significantly more frequent in SGC "frequently prescribers", indicating the need for optimized health care.

Ticks and tick-borne diseases from Mallorca Island, Spain.

Ixodid ticks are obligate blood-feeding arthropods and important vectors of pathogens. In Mallorca, almost no data on the tick fauna are available. Herein, we investigated ticks and tick-borne pathogens in ticks collected from dogs, a cat and humans in Mallorca as result of a citizen science project. A total of 91 ticks were received from German tourists and residents in Mallorca. Ticks were collected from March to October 2023 from dogs, cat and humans, morphologically and genetically identified and tested for pathogens by PCRs. Six tick species could be identified: Ixodes ricinus (n = 2), Ixodes ventalloi (n = 1), Hyalomma lusitanicum (n = 7), Hyalomma marginatum (n = 1), Rhipicephalus sanguineus s.l. (n = 71) and Rhipicephalus pusillus (n = 9). Rhipicephalus sanguineus s.l. adults were collected from dogs and four females from a cat and the 16S rDNA sequences identified it as Rh. sanguineus s.s. Hyalomma lusitanicum was collected from 1 human, 1 dog and 5 specimens were collected from the ground in the community of Santanyi, together with one H. marginatum male. This is the first report of Hyalomma marginatum in Mallorca. Both I. ricinus were collected from humans and I. ventalloi female was collected from a dog. All ticks tested negative for Anaplasma phagocytophilum, Coxiella spp., Francisella spp., and piroplasms. In 32/71 (45%) specimens of Rh. sanguineus s.s., Rickettsia spp. could be detected and in 18/32 (56.2%) sequenced tick DNAs R. massiliae was identified. Ixodes ventalloi female and both I. ricinus tested positive in the screening PCR, but the sequencing for the identification of the Rickettsia sp. failed.

Prevalence of psoriasis and psoriatic arthritis in Germany - analysis of claims data.

BACKGROUND AND OBJECTIVES: Few studies are available on the epidemiology of psoriasis and psoriatic arthritis in Germany. The aim of this study was to estimate this prevalence based on different case definitions. METHODS: Statutory health insurance (SHI) data were examined (2017 to 2019). Prevalence was analyzed and validated using three different case definitions: (1) At least one inpatient or outpatient diagnosis within one year, (2) additionally at least two outpatient diagnoses within one year, (3) additionally within three years. RESULTS: The administrative prevalence of psoriasis including psoriatic arthritis ranged from 1.90% to 2.51%. For all case definitions, the prevalence increased with age, decreasing from the age of 70 with psoriasis and from the age of 65 with psoriatic arthritis. Males were more likely to be affected at an older age (p <0.0001), while in the under-20 age group, more girls were affected (p  =  0.04). CONCLUSIONS: Psoriasis is a common skin disease in Germany. The internal diagnoses validation showed that in future studies with claims data, the narrow and broad criteria should be used to identify patients with psoriasis, depending on the research question.

Cognitive functioning in postural orthostatic tachycardia syndrome among different body positions: a prospective pilot study (POTSKog study).

PURPOSE: Approximately 96% of patients with postural orthostatic tachycardia syndrome (PoTS) report cognitive complaints. We investigated whether cognitive function is impaired during sitting and active standing in 30 patients with PoTS compared with 30 healthy controls (HCs) and whether it will improve with the counter manoeuvre of leg crossing. METHODS: In this prospective pilot study, patients with PoTS were compared to HCs matched for age, sex, and educational level. Baseline data included norepinephrine plasma levels, autonomic testing and baseline cognitive function in a seated position [the Montreal Cognitive Assessment, the Leistungsprüfsystem (LPS) subtests 1 and 2, and the Test of Attentional Performance (TAP)]. Cognitive functioning was examined in a randomized order in supine, upright and upright legs crossed position. The primary outcomes were the cognitive test scores between HCs and patients with PoTS at baseline testing, and among the different body positions. RESULTS: Patients with PoTS had impaired attention (TAP median reaction time) in the seated position and impaired executive functioning (Stroop) while standing compared with HC. Stroop was influenced by position (supine versus upright versus upright legs crossed) only in the PoTS group. Leg crossing did not result in an improvement in executive function. In patients with PoTS, there was a negative correlation of Stroop with norepinephrine plasma levels while standing. CONCLUSION: Compared with HCs, PoTS participants showed impaired cognitive attention and executive function in the upright position that did not improve in the legs crossed position. Data provide further evidence for orthostatic cognitive deterioration in patients with PoTS. TRIAL REGISTRATION INFORMATION: The study was registered at ClinicalTrials.gov (NCT03681080).

Informing the development of a decision aid: Expectations and wishes from service users and psychiatrists towards a decision aid for antipsychotics in the inpatient setting.

OBJECTIVES: Decision aids (DAs) are promising tools to foster evidence-based shared decision-making between practitioners and service users. Nevertheless, it is still obscure how an evidence-based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we conducted focus groups with psychiatrists and service users to collect and assess their expectations and wishes regarding an evidence-based DA. From these findings, we derived immediate recommendations for the future development of DAs. METHODS: We held two group interviews with service users (n = 8) and three group interviews with psychiatrists (n = 10). We used an open, large-scale topic guide. First, we presented data from a current meta-analysis on antipsychotics to the interviewees and, in a second step, asked for their expectations and wishes towards a DA that integrates these data. RESULTS: Our thematic analysis revealed six key themes addressed by the respondents: (1) general considerations on the importance and usefulness of such a DA, (2) critical comments on psychiatry and psychopharmacotherapy, (3) communicative prerequisites for the use of a DA, (4) form and content of the DA, (5) data input, data processing and output as well as (6) application of the DA and possible obstacles. CONCLUSIONS: Participants identified several important features for the development of DAs for selecting antipsychotics in inpatient psychiatric treatment. The digital format was met with the greatest approval. Especially the adaptability to different needs, users and psychopathologies and the possibility to outsource information dissemination via app seemed to be a decisive convincing argument. Further research is required to test specific features of DAs to be developed in clinical settings.

Influence of antiresorptive/antiangiogenic therapy on the extension of experimentally induced peri-implantitis lesions.

OBJECTIVES: To investigate the extension of experimentally induced peri-implantitis lesions under various antiresorptive and antiangiogenic medications. MATERIAL AND METHODS: Fourty-eight albino rats had randomly received the following medications (dual application, n = 8 each): (1) amino-bisphosphonate (zoledronate) (Zo), (2) RANKL inhibitor (denosumab) (De), (3) antiangiogenic (bevacizumab) (Be), (4) Zo+Be, (5) De+Be, or (6) no medication (Co). Ligature- and lipopolysaccharide-induced peri-implantitis lesions were established at 2 maxillary implants over a period of 16 weeks. Histological (e.g., apical extension and surface area of the inflammatory cell infiltrate-aICT, ICT; defect length; defect width; CD68 positive cells) and bone micromorphometric (µCT) outcomes were assessed. The animal was defined as a statistical unit. RESULTS: A total of n = 38 animals (Zo = 6, De = 6, Be = 8, Zo + Be = 6, De + Be = 5, Co = 7) were analyzed. ICT's were commonly marked by a positive CD68 antigen reactivity. Comparable median aICT (lowest-Zo: 0.53 mm; highest-Be: 1.22 mm), ICT (lowest-De + Be: 0.00 mm2; highest-Co: 0.49 mm2), defect length (lowest-Zo: 0.90 mm; highest-Co: 1.93 mm) and defect width (lowest-De+Be: 1.27 mm; highest-Be: 1.80 mm) values were noted in all test and control groups. Within an inner (diameter: 0.8 mm) cylindric volume of interest, the bone microstructure did not significantly differ between groups. CONCLUSIONS: The present analysis did not reveal any marked effects of various antiresorptive/ antiangiogenic medications on the extension of experimentally induced peri-implantitis lesions. CLINICAL RELEVANCE: The extension of peri-implantitis lesions may not be facilitated by the antiresorptive and antiangiogenic medications investigated.

Do we still need to screen our patients?-Orthopaedic scoring based on motion tracking.

PURPOSE: Orthopaedic scores are essential for the clinical assessment of movement disorders but require an experienced clinician for the manual scoring. Wearable systems are taking root in the medical field and offer a possibility for the convenient collection of motion tracking data. The purpose of this work is to demonstrate the feasibility of automated orthopaedic scorings based on motion tracking data using the Harris Hip Score and the Knee Society Score as examples. METHODS: Seventy-eight patients received a clinical examination and an instrumental gait analysis after hip or knee arthroplasty. Seven hundred forty-four gait features were extracted from each patient's representative gait cycle. For each score, a hierarchical multiple regression analysis was conducted with a subsequent tenfold cross-validation. A data split of 70%/30% was applied for training/testing. RESULTS: Both scores can be reproduced with excellent coefficients of determination R2 for training, testing and cross-validation by applying regression models based on four to six features from instrumental gait analysis as well as the patient-reported parameter 'pain' as an offset factor. CONCLUSION: Computing established orthopaedic scores based on motion tracking data yields an automated evaluation of a joint function at the hip and knee which is suitable for direct clinical interpretation. In combination with novel technologies for wearable data collection, these computations can support healthcare staff with objective and telemedical applicable scorings for a large number of patients without the need for trained clinicians.

Chronic vestibular syndromes in the elderly: Presbyvestibulopathy-an isolated clinical entity?

BACKGROUND AND PURPOSE: Recently, the Classification Committee of the Bárány Society defined the new syndrome of "presbyvestibulopathy" for elderly patients with chronic vestibular symptoms due to a mild bilateral peripheral vestibular hypofunction. However, control of stance and gait requires multiple functioning systems, for example, the somatosensory, visual, auditory, musculoskeletal, and cardio- and cerebrovascular systems. The aim of this cross-sectional database-driven study was to evaluate the frequency and characteristics of presbyvestibulopathy and additional gait-relevant comorbidities. METHODS: In total, 707 patients aged ≥60 years with chronic vertigo/dizziness were admitted to our tertiary hospital and received detailed neurological, neuro-orthoptic, and laboratory audiovestibular examination. Medical history, comorbidities, functional impairment, and quality of life (Dizziness Handicap Inventory [DHI], European Quality of Life Scale, Vestibular Activities and Participation) were compared between presbyvestibulopathy and bilateral vestibulopathy in a matched-paired study. RESULTS: In 95.5% of patients, complaints were better accounted for by another vestibular, neurological, cardiac, or psychiatric disease, and 32 patients (4.5%) met the diagnostic criteria for presbyvestibulopathy. Of these 32 patients, the majority showed further relevant comorbidities in other sensorimotor systems. Only one patient of 707 had "isolated" presbyvestibulopathy (0.14%). The mean total DHI scores indicated lower moderate impairment in presbyvestibulopathy than in bilateral vestibulopathy (40.6 vs. 49.0), which was confirmed by significant differences in the matched-paired analysis (p < 0.001). CONCLUSIONS: Isolated presbyvestibulopathy is a very rare entity. It is regularly accompanied by other multisensory dysfunctions. These results indicate a potential role of mild vestibular hypofunction as a cofactor in multifactorial impairment. Thus, patients should be treated in an interdisciplinary setting with an awareness of diverse comorbidities.

Exploring the Reduction Mechanism of 99Tc(VII) in NaClO4: A Spectro-Electrochemical Approach.

Technetium (Tc) is an environmentally relevant radioactive contaminant whose migration is limited when Tc(VII) is reduced to Tc(IV). However, its reaction mechanisms are not well understood yet. We have combined electrochemistry, spectroscopy, and microscopy (cyclic voltammetry, rotating disk electrode, X-ray photoelectron spectroscopy, and Raman and scanning electron microscopy) to study Tc(VII) reduction in non-complexing media: 0.5 mM KTcO4 in 2 M NaClO4 in the pH from 2.0 to 10.0. At pH 2.0, Tc(VII) first gains 2.3 ± 0.3 electrons, following Tc(V) rapidly receives 1.3 ± 0.3 electrons yielding Tc(IV). At pH 4.0-10.0, Tc(IV) is directly obtained by transfer of 3.2 ± 0.3 electrons. The reduction of Tc(VII) produced always a black solid identified as Tc(IV) by Raman and XPS. Our results narrow a significant gap in the fundamental knowledge of Tc aqueous chemistry and are important to understand Tc speciation. They provide basic steps on the way from non-complexing to complex media.

Primary emotions as predictors for fear of COVID-19 in former inpatients with Major Depressive Disorder and healthy control participants.

INTRODUCTION: There are reports of an increase in depressive symptoms and fear during the COVID-19 pandemic, in particular in patients with depression. This study investigates factors related to fear of COVID-19 in former inpatients suffering from depression and healthy controls by assessing variables typically associated with depression and anxiety disorders, i.e. stressful life events (SLEs), the primary emotions SADNESS, PLAY and SEEKING as well as dysfunctional emotion regulation strategies with respect to suppression and reappraisal. METHODS: Data of n = 44 former inpatients suffering from depression and n = 49 healthy controls were collected. The study had a longitudinal design with two measurement points. Before the pandemic, SLEs, primary emotions, emotion regulation and depression severity were assessed. During the pandemic, COVID-19 associated stressors and life events, emotion regulation, depression severity and fear of COVID-19 were assessed. RESULTS: Fear of COVID-19 and depression severity during the pandemic were significantly higher in former inpatients than in healthy controls. Depression diagnosis, SLEs and depression severity before the pandemic were significant positive predictors of fear of COVID-19. The primary emotion PLAY was a significant negative predictor of fear of COVID-19. Depression severity did not change significantly in healthy controls. CONCLUSION: The results show that risk factors for depression might be risk factors for high fear of COVID-19. In addition, a playful personality could help preventing mental stress in pandemic situations. Thus, positivity based interventions could counteract elevated fear scores during a pandemic.

Evidence-based Shared-Decision-Making Assistant (SDM-assistant) for choosing antipsychotics: protocol of a cluster-randomized trial in hospitalized patients with schizophrenia.

BACKGROUND: Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-established, there is no clear framework for the communication of the evidence between physicians and patients. For this reason, we developed an evidence-based shared-decision making assistant (SDM-assistant) that presents high-quality evidence from network meta-analysis on the efficacy and side-effect profile of antipsychotics and can be used as a basis for shared-decision making between physicians and patients when selecting antipsychotic medications. METHODS: The planned matched-pair cluster-randomised trial will be conducted in acute psychiatric wards (n = 14 wards planned) and will include adult inpatients with schizophrenia or schizophrenia-like disorders (N = 252 participants planned). On the intervention wards, patients and their treating physicians will use the SDM-assistant, whenever a decision on choosing an antipsychotic is warranted. On the control wards, antipsychotics will be chosen according to treatment-as-usual. The primary outcome will be patients' perceived involvement in the decision-making during the inpatient stay as measured with the SDM-Q-9. We will also assess therapeutic alliance, symptom severity, side-effects, treatment satisfaction, adherence, quality of life, functioning and rehospitalizations as secondary outcomes. Outcomes could be analysed at discharge and at follow-up after three months from discharge. The analysis will be conducted per-protocol using mixed-effects linear regression models for continuous outcomes and logistic regression models using generalised estimating equations for dichotomous outcomes. Barriers and facilitators in the implementation of the intervention will also be examined using a qualitative content analysis. DISCUSSION: This is the first trial to examine a decision assistant specifically designed to facilitate shared-decision making for choosing antipsychotic medications, i.e., SDM-assistant, in acutely ill inpatients with schizophrenia. If the intervention can be successfully implemented, SDM-assistant could advance evidence-based medicine in schizophrenia by putting medical evidence on antipsychotics into the context of patient preferences and values. This could subsequently lead to a higher involvement of the patients in decision-making and better therapy decisions. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00027316 , registration date 26.01.2022).

Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2.

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

Dimeric and Trimeric Uranyl(VI)-Citrate Complexes in Aqueous Solution.

This research addresses a subject discussed controversially for almost 70 years. The interactions between the uranyl(VI) ion, U(VI), and citric acid, H3Cit, were examined using a multi-method approach comprising nuclear magnetic resonance (NMR), ultraviolet-visible (UV-vis), attenuated total reflectance Fourier-transform infrared (ATR FT-IR), and extended X-ray absorption fine-structure (EXAFS) spectroscopies as well as density functional theory (DFT) calculations. Combining 17O NMR spectroscopy and DFT calculation provided an unambiguous decision on complex configurations, evidencing for the first time that the dimeric complex, (UO2)2(HCit-H)22-, exists as two diastereomers with the syn-isomer in aqueous solution strongly favored over the anti-isomer. Both isomers interconvert mutually with exchange rates of ∼30 s-1 at -6 °C and ∼249 s-1 at 60 °C in acidic solution corresponding to an activation barrier of about 24 kJ mol-1. Upon increasing the pH value, ternary dimeric mono- and bis-hydroxo as well as trimeric complexes form, that is, (UO2)2(HCit-H)2(OH)3-, (UO2)2(HCit-H)2(OH)24-, (UO2)3(O)(Cit-H)38-, and (UO2)3(O)(OH)(Cit-H)25-, respectively. Stability constants were determined for all dimeric and trimeric species, with log ß° = -(8.6 ± 0.2) for the 3:3 species being unprecedented. Additionally, in the 6:6 sandwich complex, formed from two units of 3:3 species, the 17O NMR resonance of the trinuclear uranyl(VI) core bridging µ3-O is shown for the first time. Species distribution calculations suggest that the characterized polynuclear U(VI)-citrate species do not significantly increase uranium(VI) mobility in the environment. Furthermore, we revise the misconceptions in the aqueous U(VI)-citric acid solution chemistry, that is, structures proposed and repeatedly taken up, and outline generalized isostructural considerations to provide a basis for future U(VI) complexation studies.

Complexation of Np(V) with the Dicarboxylates, Malonate, and Succinate: Complex Stoichiometry, Thermodynamic Data, and Structural Information.

The complexation of Np(V) with malonate and succinate is studied by different spectroscopic techniques, namely, attenuated total reflection Fourier transform infrared (ATR FT-IR) and extended X-ray absorption fine-structure (EXAFS) spectroscopy, as well as by quantum chemistry to determine the speciation, thermodynamic data, and structural information of the formed complexes. For complex stoichiometries and the thermodynamic functions (log ßn°(Θ), ΔrHn°, ΔrSn°), near infrared absorption spectroscopy (vis/NIR) is applied. The complexation reactions are investigated as a function of the total concentration of malonate ([Mal2-]total) and succinate ([Succ2-]total), ionic strength [Im = 0.5-4.0 mol kg-1 Na+(Cl-/ClO4-)], and temperature (Θ = 20-85 °C). Besides the solvated NpO2+ ion, the formation of two Np(V) species with the stoichiometry NpO2(L)n1-2n (n = 1, 2, L = Mal2-, Succ2-) is observed. With increasing temperature, the molar fractions of both complex species increase and the temperature-dependent conditional stability constants log ßn'(Θ) at given ionic strengths are determined by the law of mass action. The log ßn'(Θ) are extrapolated to IUPAC reference-state conditions (Im = 0) according to the specific ion interaction theory (SIT), revealing thermodynamic log ßn°(Θ) values. For all formed complexes, [NpO2(Mal)-: log ß1°(25 °C) = 3.36 ± 0.11, NpO2(Mal)23-: log ß2°(25 °C) = 3.95 ± 0.19, NpO2(Succ)-: log ß1°(25 °C) = 2.05 ± 0.45, NpO2(Succ)23-: log ß2°(25 °C) = 0.75 ± 1.22], an increase of the stability constants with increasing temperature was observed. This confirmed an endothermic complexation reaction. The temperature dependence of the log ßn°(T) values is described by the integrated Van't Hoff equation, and the standard reaction enthalpies and entropies for the complexation reactions are determined. Furthermore, the sum of the specific binary ion-ion interaction coefficients Δεn°(Θ) for the complexation reactions are obtained as a function of the t from the respective SIT modeling as a function of the temperature. In addition to the thermodynamic data, the structures of the complexes and the coordination modes of malonate and succinate are investigated using EXAFS spectroscopy, ATR-FT-IR spectroscopy, and quantum chemical calculations. The results show that in the case of malonate, six-membered chelate complexes are formed, whereas for succinate, seven-membered rings form. The latter ones are energetically unfavorable due to the limited space in the equatorial plane of the Np(V) ion (as NpO2+ cation).

Sensitivity of two SARS-CoV-2 variants with spike protein mutations to neutralising antibodies.

SARS-CoV-2 infections elicit a humoral immune response capable of neutralising the virus. However, multiple variants have emerged with mutations in the spike protein amongst others, the key target of neutralising antibodies. We evaluated the neutralising efficacy of 89 serum samples from patients, infected with SARS-CoV-2 in the beginning of 2020, against two virus variants isolated from acutely infected patients and harbouring spike protein mutations. One isolate was assigned to lineage B.1.351 (MUC-IMB-B.1.351) whilst the other (MUC-484) was isolated from an immunocompromised patient, sharing some but not all mutations with B.1.351 and representing a transitional variant. Both variants showed a significant reduction in neutralisation sensitivity compared to wild-type SARS-CoV-2 with MUC-IMB-B.1.351 being almost completely resistant to neutralisation. The observed reduction in neutralising activity of wild-type-specific antibodies against both variants suggests that individual mutations in the spike protein are sufficient to confer a potent escape from the humoral immune response. In addition, the effect of escape mutations seems to accumulate, so that more heavily mutated variants show a greater loss of sensitivity to neutralisation up to complete insensitivity as observed for MUC-IMB-B.1.351. From a clinical point of view, this might affect the efficacy of (monoclonal) antibody treatment of patients with prolonged infections as well as patients infected with variants other than the donor. At the same, this could also negatively influence the efficacy of current vaccines (as they are based on wild-type spike protein) emphasising the need to thoroughly surveil the emergence and distribution of variants and adapt vaccines and therapeutics accordingly.

Factors related to age at depression onset: the role of SLC6A4 methylation, sex, exposure to stressful life events and personality in a sample of inpatients suffering from major depression.

BACKGROUND: An early onset of depression is associated with higher chronicity and disability, more stressful life events (SLEs), higher negative emotionality as described by the primary emotion SADNESS and more severe depressive symptomatology compared to depression onset later in life. Additionally, methylation of the serotonin transporter gene (SLC6A4) is associated with SLEs and depressive symptoms. METHODS: We investigated the relation of SLEs, SLC6A4 methylation in peripheral blood, the primary emotions SADNESS and SEEKING (measured by the Affective Neuroscience Personality Scales) as well as depressive symptom severity to age at depression onset in a sample of N = 146 inpatients suffering from major depression. RESULTS: Depressed women showed higher SADNESS (t (91.05) = - 3.17, p = 0.028, d = - 0.57) and higher SLC6A4 methylation (t (88.79) = - 2.95, p = 0.02, d = - 0.55) compared to men. There were associations between SLEs, primary emotions and depression severity, which partly differed between women and men. The Akaike information criterion (AIC) indicated the selection of a model including sex, SLEs, SEEKING and SADNESS for the prediction of age at depression onset. SLC6A4 methylation was not related to depression severity, age at depression onset or SLEs in the entire group, but positively related to depression severity in women. CONCLUSIONS: Taken together, we provide further evidence that age at depression onset is associated with SLEs, personality and depression severity. However, we found no associations between age at onset and SLC6A4 methylation. The joint investigation of variables originating in biology, psychology and psychiatry could make an important contribution to understanding the development of depressive disorders by elucidating potential subtypes of depression.

Vaccine breakthrough infection and onward transmission of SARS-CoV-2 Beta (B.1.351) variant, Bavaria, Germany, February to March 2021.

A breakthrough infection occurred in a fully Comirnaty (BNT162b2) vaccinated healthcare worker with high levels of neutralising antibodies with the SARS-CoV-2 B.1.351 (Beta) variant in February 2021. The infection was subsequently transmitted to their unvaccinated spouse. Sequencing revealed an identical virus in both spouses, with a match of all nine single nucleotide polymorphisms typical for B.1.351. To the best of our knowledge, no transmission of any variant of SARS-CoV-2 from a fully vaccinated person has been described before.

New Insights into 99Tc(VII) Removal by Pyrite: A Spectroscopic Approach.

99Tc(VII) uptake by synthetic pure pyrite at 21 °C was studied in a wide pH range from 3.50 to 10.50 using batch experiments combined with scanning electron microscopy, X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS), and Raman microscopy. We found that pyrite removes Tc quantitatively from solution (log Kd = 5.0 ± 0.1) within 1 day at pH ≥ 5.50 ± 0.08. At pH < 5.50 ± 0.08, the uptake process is slower, leading to 98% Tc removal (log Kd = 4.5 ± 0.1) after 35 days. The slower Tc uptake was explained by higher pyrite solubility under acidic conditions. After 2 months in contact with oxygen at pH 6.00 ± 0.07 and 10.00 ± 0.04, Tc was neither reoxidized nor redissolved. XAS showed that the uptake mechanism involves the reduction from Tc(VII) to Tc(IV) and subsequent inner-sphere complexation of Tc(IV)-Tc(IV) dimers onto a Fe oxide like hematite at pH 6.00 ± 0.07, and Tc(IV) incorporation into magnetite via Fe(III) substitution at pH 10.00 ± 0.04. Calculations of Fe speciation under the experimental conditions predict the formation of hematite at pH < 7.50 and magnetite at pH > 7.50, explaining the formation of the two different Tc species depending on the pH. XPS spectra showed the formation of TcSx at pH 10.00 ± 0.04, being a small fraction of a surface complex, potentially a transient phase in the total redox process.

Nutritional status and quality of nutrition in chronic wound patients.

Malnutrition is a negative confounding factor influencing wound healing. The prevalence of malnutrition increases with age, as do chronic wounds. The aim of this prospective study was to analyse the nutritional status of patients with chronic wounds. Data collection of sociodemographic and nutritional parameters was based on an inter-professionally developed questionnaire as well as the Mini Nutritional Assessment (MNA). A total of 90 patients with chronic wounds of different aetiologies were included. Pain and dental health were found to be significant factors: Patients with malnutrition or the risk of malnutrition had significantly lower tooth and oral health scores (rs = -0.218, P = .039), and higher pain levels at rest (rs = 0.339, P < .001), while dressing (rs = 0.268, P = .014), and upon exercising (rs = 0.303, P = .005). Our data address the impact of nutrition on chronic wounds and confirm the relationship between pain, dental health, and nutritional status. Clinicians should be aware of adequate pain management and dental health care in chronic wound patients. Further studies, particularly on characterisation of preventive and therapeutic measures in the nutrition of chronic wound patients, are of great importance.