Background: Inpatient as well as outpatient care does often not meet PD-patients' individual needs.
Introduction: Day-clinic concepts encompassing a multidisciplinary team as well as therapy adjustments accompanying everyday demands aim at filling this gap.
Methods: This is a retrospective study on short-term effects of a 3 week multidisciplinary rehabilitation program in patients with Parkinson's disease (PD) embedded in a specialized movement disorder day-clinic. We analyzed short-term outcome of motor and non-motor symptoms (NMS) in 143 PD-patients (mean age 65.3 +/- 11.9 years; Hoehn-and-Yahr-score 2.6 +/- 0.7) after 3 weeks with 7.4 +/- 1.8 active days of interdisciplinary day-care treatment. Participants attended the day-clinic in groups of five patients at a time. Improvements were evaluated by comparison of standardized physical therapy assessments, disease specific scores for motor symptoms (MDS-UPDRS III), mood (BDI), quality of life (PDQ39, SF36), sleep (PDSS, ESS), impulsiveness (QUIP), apathy (SAS), cognition (MMST), as well as change in medication before and directly after the intervention.
Results: MDS-UPDRS motor score improved significantly by 22.9 +/- 21.5% (p < 0.001) and was accompanied by a significant reduction of imbalance, immobility, and weakness ranging between 6% and 17% in standardized physical therapy tests. In addition, all disease-specific non-motor scales improved significantly.
Conclusions: A multidisciplinary day-clinic approach can support benefit on motor, non-motor symptoms and QoL in PD-patients. Given the increase in PD incidence and prevalence as well as the significant treatment effects shown here, more day-clinic treatment opportunities ought to be implemented to improve PD treatment adapted to everyday challenges while still reducing costs to the health care system.
View lessCalcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (I1)-1 beta, and I1-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies.
View lessPurpose: Artificial organs might serve as alternative solutions for whole organ transplantation. Decellularization of a liver provides a non-immunogenic matrix with the advantage of three afferent systems, the portal vein, the hepatic artery and the bile duct. This study aims to evaluate the recellularization of rat livers with islets of Langerhans via the bile duct and the portal vein for the comparison of different perfusion routes.
Methods: Rat livers were decellularized in a pressure-controlled perfusion manner and repopulated with intact isolated islets of Langerhans via either the portal vein or the bile duct.
Results: Repopulation via the portal vein showed islet clusters stuck within the vascular system demonstrated by ellipsoid borders of thick reticular tissue around the islet cluster in Azan staining. After recellularization via the bile duct, islets were distributed close to the vessels within the parenchymal space and without a surrounding reticular layer. Large clusters of islets had a diameter of up to 1000 mu m without clear shapes.
Conclusion: We demonstrated the bile duct to be superior to the portal vein for repopulation of a decellularized rat liver with islets of Langerhans. This technique may serve as a bioengineering platform to generate an implantable and functional endocrine neo-pancreas and provide scaffolds with the anatomic benefit of three afferent systems to facilitate co-population of cells.
View lessVarious studies have shown that immigrant women in comparison to non-immigrant women of the same parity have lower rates of epidural anesthesia (EDA). Data from two studies on immigrant obstetric care in Berlin, Germany were analyzed to answer the following question: What reasons do the medical staff see for the lower rate of EDA in immigrant women? Between May and August 2017, 34 interviews with obstetricians and midwives in four obstetric clinics in Berlin were conducted on the topic of obstetric care for immigrant women. After anonymizing the more than 20 h of interview material, transcripts were coded with MaxQDa and analyzed according to the qualitative content analysis.The quantitative data is from an online survey conducted between May and October 2017, in all but one obstetric clinic in Berlin with obstetricians and midwives. Regarding the research question, 121 questionnaires could be analyzed. In the online survey, (multiple answers were possible), the top reason for a lower rate of EDA given was mostly fear on the part of the immigrant women (64%). A language barrier, which results in logistic and time constrictions, is mentioned as the second most frequent reason (50%). The explorative analysis of the interviews shows that doctors and midwives regard cultural aspects such as different expectations on the birth experience as a reason for a lower EDA rate. Furthermore, within the medical staff the impression persists that in some cases the companion decides on the behalf of the patient about the application of an EDA, which from time to time is against the wish of the immigrant woman giving birth. In the view of the medical staff, the reasons for a lower rate of EDA during birth for immigrant women were varied. On one side, this is attributed to the wishes of the respective women ("demand") but on the other side this can be attributed to the health care system ("supply"). In the case of a language barrier, the "supply" and the access of EDA for immigrant women is limited and can be then shifted to the German-speaking companion to make a decision regarding EDA ("structural deprivation of self-determination").
View lessBilateral laryngeal abductor paralysis is a rare entity and the second most common cause of stridor in newborns. So far, no conclusive genetic or chromosomal aberration has been reported for X-linked isolated bilateral vocal cord paralysis, also referred to as Plott syndrome. Via whole genome sequencing (WGS), we identified a complex interchromosomal insertion in a large family with seven affected males. The 404 kb inserted fragment originates from chromosome 10q21.3, contains no genes and is inserted inversionally into the intergenic chromosomal region Xq27.1, 82 kb centromeric to the nearest gene SOX3. The patterns found at the breakpoint junctions resemble typical characteristics that arise in replication-based mechanisms with long-distance template switching. Non protein-coding insertions into the same genomic region have been described to result in different phenotypes, indicating that the phenotypic outcome likely depends on the introduction of regulatory elements. In conclusion, our data adds Plott syndrome as another entity, likely caused by the insertion of non-coding DNA into the intergenic chromosomal region Xq27.1. In this regard, we demonstrate the importance of WGS as a powerful diagnostic test in unsolved genetic diseases, as this genomic rearrangement has not been detected by current first-line diagnostic tests, i.e., exome sequencing and chromosomal microarray analysis.
View lessGambling problems are often associated with homelessness and linked to elevated psychiatric morbidity and homelessness chronicity. We performed a systematic review and meta-analysis on prevalence rates of problem gambling (PG) and gambling disorder (GD) in homeless people. Following PRISMA guidelines, we searched databases Medline, Embase and PsycINFO from inception of databases to 4th may 2021. We included studies reporting prevalence estimates on clinical gambling problems in representative samples of homeless people based on standardized diagnostics. Risk of bias was assessed. A random effects meta-analysis was performed, and subgroup analyses based on methodological characteristics of primary studies were conducted. We identified eight studies from five countries, reporting information on 1938 participants. Prevalence rates of clinically significant PG and GD ranged from 11.3 to 31.3%. There was evidence for substantial heterogeneity with I-2 = 86% (95% CI 63-97%). A subgroup of four low risk of bias studies displayed a significantly lower results ranging from 11.3 to 23.6%. Additionally, high rates of subclinical problem gambling were reported (11.6-56.4%). At least one in ten homeless persons experiences clinically significant PG or GD. Social support and health care services for the homeless should address this problem by implementing models for early detection and treatment.
View lessPurpose: Besides their developmental and neurological phenotype, most patients with MECP2/IRAK1 duplication syndrome present with recurrent and severe infections, accompanied by strong inflammation. Respiratory infections are the most common cause of death. Standardized pneumological diagnostics, targeted anti-infectious treatment, and knowledge of the underlying pathomechanism that triggers strong inflammation are unmet clinical needs. We investigated the influence of IRAK1 overexpression on the canonical NF-kappa B signaling as a possible cause for excessive inflammation in these patients.
Methods: NF-kappa B signaling was examined by measuring the production of proinflammatory cytokines and evaluating the IRAK1 phosphorylation and degradation as well as the I kappa B alpha degradation upon stimulation with IL-1 beta and TLR agonists in SV40-immortalized fibroblasts, PBMCs, and whole blood of 9 patients with MECP2/IRAK1 duplication syndrome, respectively.
Results: Both, MECP2/IRAK1-duplicated patients and healthy controls, showed similar production of IL-6 and IL-8 upon activation with IL-1 beta and TLR2/6 agonists in immortalized fibroblasts. In PBMCs and whole blood, both patients and controls had a similar response of cytokine production after stimulation with IL-1 beta and TLR4/2/6 agonists. Patients and controls had equivalent patterns of IRAK1 phosphorylation and degradation as well as I kappa B alpha degradation upon stimulation with IL-1 beta.
Conclusion: Patients with MECP2/IRAK1 duplication syndrome do not show increased canonical NF-kappa B signaling in immortalized fibroblasts, PBMCs, and whole blood. Therefore, we assume that these patients do not benefit from a therapeutic suppression of this pathway.
View lessIntroduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under double exposure with pollen ozone in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA(2)LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss (TEWL) as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function, increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE-duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms and are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose(time)-response relationship. The surface pH can be regarded as a possible modulatory mechanism.
View lessBackgroundSkin care is a basic, daily activity performed by formal and informal caregivers from birth until end of life. Skin care activities are influenced by different factors as e.g., culture, knowledge, industrial developments and marketing activities. Therefore, various preferences, traditions and behaviours exist worldwide including skin care of neonates and infants. Objective of this scoping review was to obtain an overview about the evidence of skin care activities in neonates and infants. Studies from 2010 were eligible if the population were (skin) healthy neonates and infants, if the concept were skin care interventions and if the context was at home, in a community setting, in a paediatric outpatient service or in a hospital. We searched for literature via OVID in Medline and Embase, in the Cochrane Library, in trial registries and for grey literature. SummaryWe identified 42 studies since 2010, which examined four main skin care interventions: bathing, wiping, washing, and topical application of leave-on products. Details of interventions were often not reported and if they were, they were not comparable. The four skin care interventions focused on 13 different care goals, mainly prevention of skin diseases, maintaining skin barrier function and improving (skin) health. We evaluated effects of skin care interventions using 57 different outcome domains; 39 of 57 were skin related and 18 were not. Mostly, laboratory or instrumental measurements were used. Key Messages Our scoping review identified four skin care interventions with a broad heterogeneity of product categories and application details. Studies in skin care interventions should include all relevant information about product category and application details to ensure comparability of study results. This would be helpful in developing recommendations for formal and informal caregivers. We identified 13 skin care goals. "Maintaining healthy skin/skin barrier function/skin barrier integrity", "prevention of atopic dermatitis", "cleansing" and "improving skin barrier function" were most often allocated to skin care interventions. There is substantial variability regarding outcome domains in skin care research. Our results support the need of developing core outcome sets in the field of skin care in healthy skin, especially in this age group of neonates and infants.
View lessEndoscopic lung volume reduction procedure with valves is a well-studied treatment option for advanced lung emphysema to target lung hyperinflation in carefully selected patients with COPD. Before valve implantation, collateral ventilation (CV) of the target lobe needs to be assessed to obtain an optimal treatment effect. The analysis of CV according to current standards occurs via an in vivo assessment with the Chartis (R) system (PulmonX Inc., Redwood City, CA, USA) and a computed tomography (CT) scan of the thorax with interlobar fissure analysis. The focus of this review is to provide detailed information about the Chartis (R) procedure and interpretation of Chartis (R) phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis (R) assessment should be performed by default to confirm interlobar fissure analysis in most emphysema patients. Based on the obtained results, lung volume reduction therapy options should be discussed in an interdisciplinary emphysema conference.
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Introduction: Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing. Effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Accordingly, a combination of these approaches should be particularly suited to investigate cognition-emotion interaction. Methods: Seventy five healthy subjects were investigated in a double-blind, placebo-controlled, randomized, single-dose, parallel-group study with three treatment conditions. All subjects underwent two scanning sessions (acute/post 24 h). Results: Compared to placebo, acute ketamine administration induced significant dissociative, psychotomimetic, and cognitive effects, as well as an increase in neural activity during WM for positive stimuli. Inhibition of glutamate release by pretreatment with lamotrigine did not influence ketamine's subjective effects, but significantly attenuated its impact on emotional WM and associated neural activity. There was no effect on these measures 24 h after ketamine administration. Conclusion: Our results demonstrate differential acute effects of modulated glutamate release and a swift restoration of disturbed neurobehavioral homeostasis in healthy subjects.
View lessTransition metal dichalcogenide heterostructures have garnered strong interest for their robust excitonic properties, mixed light–matter states such as exciton-polaritons, and tailored properties, vital for advanced device engineering. Two-dimensional heterostructures inherit their physics from monolayers with the addition of interlayer processes that have been particularly emphasized for their electronic and optical properties. Here, we demonstrate the interlayer coupling of the MoSe2 phonons to WSe2 excitons in a WSe2/MoSe2 heterostructure using resonant Raman scattering. The WSe2 monolayer induces an interlayer resonance in the Raman cross-section of the MoSe2 A1g phonons. Frozen-phonon calculations within density functional theory reveal a strong deformation-potential coupling between the A1g MoSe2 phonon and the electronic states of the close-by WSe2 layer approaching 20% of the intralayer coupling to the MoSe2 electrons. Understanding the vibrational properties of van der Waals heterostructures requires going beyond the sum of their constituents and considering cross-material coupling.
View lessIntroduction: Some cyanobacteria can use far-red light (FRL) to drive oxygenic photosynthesis, a phenomenon known as Far-Red Light Photoacclimation (FaRLiP). It can expand photosynthetically active radiation beyond the visible light (VL) range. Therefore, it holds promise for biotechnological applications and may prove useful for the future human exploration of outer space. Typically, FaRLiP relies on a cluster of ~20 genes, encoding paralogs of the standard photosynthetic machinery. One of them, a highly divergent D1 gene known as chlF (or psbA4), is the synthase responsible for the formation of the FRL-absorbing chlorophyll f (Chl f) that is essential for FaRLiP. The minimum gene set required for this phenotype is unclear. The desert cyanobacterium Chroococcidiopsis sp. CCMEE 010 is unusual in being capable of FaRLiP with a reduced gene cluster (15 genes), and it lacks most of the genes encoding FR-Photosystem I.
Methods: Here we investigated whether the reduced gene cluster of Chroococcidiopsis sp. CCMEE 010 is transcriptionally regulated by FRL and characterized the spectral changes that occur during the FaRLiP response of Chroococcidiopsis sp. CCMEE 010. In addition, the heterologous expression of the Chl f synthase from CCMEE 010 was attempted in three closely related desert strains of Chroococcidiopsis.
Results: All 15 genes of the FaRLiP cluster were preferentially expressed under FRL, accompanied by a progressive red-shift of the photosynthetic absorption spectrum. The Chl f synthase from CCMEE 010 was successfully expressed in two desert strains of Chroococcidiopsis and transformants could be selected in both VL and FRL.
Discussion: In Chroococcidiopsis sp. CCME 010, all the far-red genes of the unusually reduced FaRLiP cluster, are transcriptionally regulated by FRL and two closely related desert strains heterologously expressing the chlF010 gene could grow in FRL. Since the transformation hosts had been reported to survive outer space conditions, such an achievement lays the foundation toward novel cyanobacteria-based technologies to support human space exploration.
View lessA model for the motion of slender vortex filaments is extended to include the effect of gravity. The model, initially introduced by Callegari and Ting [“Motion of a curved vortex filament with decaying vortical core and axial velocity,” SIAM J. Appl. Math. 35, 148–175 (1978)], is based on a matched asymptotic expansion in which the outer solution, given by the Biot–Savart law, is matched with the inner solution derived from the Navier–Stokes equations. Building on recent work by Harikrishnan et al. [“On the motion of hairpin filaments in the atmospheric boundary layer,” Phys. Fluids 35, 076603 (2023)], the Boussinesq approximation is applied such that the density variations only enter in the gravity term. However, unlike Harikrishnan et al. [“On the motion of hairpin filaments in the atmospheric boundary layer,” Phys. Fluids 35, 076603 (2023)], the density variation enters at a lower order in the asymptotic expansion and, thus, has a more significant impact on the self-induced velocity of the vortex filament. In this regime, which corresponds to the regime studied by Chang and Smith [“The motion of a buoyant vortex filament,” J. Fluid Mech. 857, R1 (2018)], the effect of gravity is given by an alteration of the core constant, which couples the motion of the filament to the motion within the vortical core, in addition to a change in the compatibility conditions (evolution equations), which determine the leading order azimuthal and tangential velocity fields in the vortex core. The results are used to explain certain properties of buoyant vortex rings, as well as qualitatively explore the impact of gravity on tornado-type atmospheric vortices.
View lessPurpose: Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions.
Methods: We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome.
Results: The prevalence of neutralizing AABs to IFN-alpha and IFN-omega in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6-8), predominantly male (83%) patients (7.6%, 18/237 for IFN-alpha-AABs and 4.6%, 11/237 for IFN-omega-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE.
Conclusion: IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.
View lessPurpose: Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients.
Methods: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013-2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings.
Results: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii).
Conclusions: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed.
Implications for Cancer Survivors: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education.
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