Reaction-Induced Phase Separation of PPG/PEO/HDI based bi-Soft Segment Polyurethanes

The presented thesis explores the physicochemical background of reaction-induced phase separation (RIPS) in bi-soft segment isocyanate-terminated polyurethanes (ITPUs). ITPUs are a preliminary product in the synthesis of various PU products like foams, dispersions or elastomers. Typically, only one soft segment is used but it was shown in the literature that the application of two different soft segments can lead to an improvement of morphological properties. In this work, it is hypothesized that the combination of two soft segments can lead to RIPS during the ITPU formation process. It is suggested that the occurrence and the extent of phase separation is closely related to the initial phase diagram of the reactants. In order to study the proposed relationship, the initial ternary phase diagram of the reaction mixture, consisting of poly (ethylene oxide) (PEO), poly (propylene oxide) (PPG) and 1,6-hexamethylene diisocyanate (HDI) is determined at first. Secondly, detailed experimental observation of the RIPS is conducted to identify critical parameters. Furthermore, the composition and morphology of the phase separated products are studied briefly. The ternary phase diagram is determined by theoretical and experimental methods. Flory-Huggins theory and solubility parameters are applied in order to calculate equilibrium compositions of demixed phases in the binary (PEO/PPG) and ternary (PEO/PPG/HDI) mixtures. The obtained data is in qualitative agreement with experimental cloud points and equilibrium compositions. The results demonstrate that HDI acts as a solvent for PEO and PPG. Reaction monitoring by NCO%-content titration, FTIR- and UV-Vis spectroscopy revealed a dependency between the onset of phase separation and the reaction conversion. It is found that an increase of the initial HDI content leads to a delayed onset of phase separation. The competing second order kinetic of the reaction is studied by 1H-NMR analysis. DSC analysis reveals that the phase separation is a consequence of the incompatibility of the soft segment structures. The composition and molar weight distribution found in isolated phases of the ITPUs indicate that the phase separation is controlled thermodynamically. Overall, the findings support the hypothesis that mechanism and extent of the phase separation are closely related to the ternary phase diagram of the reactants. This work comprises a comprehensive description of the phase behaviour during the reaction towards bi-soft segment ITPUs and provides a basis for future studies on this topic

Betwixt and between student and professional identities: UK medical students during COVID times

The COVID-19 pandemic lockdown in Spring 2020 brought about unprecedented disruption to medical education in the United Kingdom (UK). Medical students were encouraged to take up paid roles in the National Health Service to help with workforce shortages. This article explores medical students’ views and experiences of the COVID-19 pandemic vis-à-vis their professional identity formation. Semi-structured interviews were conducted with 22 medical students from all five undergraduate years in one UK medical school, between April and June 2020. Three themes were generated: (1) disruption to medical education involving suspension of clinical placements, cancellation of assessments and ceremonial markers; (2) decision-making around joining the clinical workforce, decisions which were influenced by students’ sense of professional obligation, perceived personal gains, and health and safety considerations; (3) experiences of working in clinical settings during the pandemic, including reflections about managing risks and challenges, learning on the job and becoming a better doctor. The findings provide evidence that the UK’s first lockdown destabilised many medical students’ expectations tied to their educational and career trajectory, requiring them to improvise to address gaps in learning and professional development. Taking on a paid healthcare role catapulted them into a liminal period, working in a space ‘betwixt and between’ a medical student and healthcare professional. This swift readjustment of roles and responsibilities accelerated their identity formation as ‘future doctors’. Support for medical students around negotiating such dual role is important in present and future public health crises

Betwixt and between student and professional identities : UK medical students during COVID times

The COVID-19 pandemic lockdown in Spring 2020 brought about unprecedented disruption to medical education in the United Kingdom (UK). Medical students were encouraged to take up paid roles in the National Health Service to help with workforce shortages. This article explores medical students’ views and experiences of the COVID-19 pandemic vis-à-vis their professional identity formation. Semi-structured interviews were conducted with 22 medical students from all five undergraduate years in one UK medical school, between April and June 2020. Three themes were generated: (1) disruption to medical education involving suspension of clinical placements, cancellation of assessments and ceremonial markers; (2) decision-making around joining the clinical workforce, decisions which were influenced by students’ sense of professional obligation, perceived personal gains, and health and safety considerations; (3) experiences of working in clinical settings during the pandemic, including reflections about managing risks and challenges, learning on the job and becoming a better doctor. The findings provide evidence that the UK’s first lockdown destabilised many medical students’ expectations tied to their educational and career trajectory, requiring them to improvise to address gaps in learning and professional development. Taking on a paid healthcare role catapulted them into a liminal period, working in a space ‘betwixt and between’ a medical student and healthcare professional. This swift readjustment of roles and responsibilities accelerated their identity formation as ‘future doctors’. Support for medical students around negotiating such dual role is important in present and future public health crises.peer-reviewe

Intraoperative 3-D mapping of parathyroid adenoma using freehand SPECT

Background: Freehand single photon emission computed tomography (fSPECT) is a three-dimensional (3-D) tomographic imaging modality based on data acquisition with a handheld detector that is moved freely, in contrast to conventional, gantry-mounted gamma camera systems. In this pilot study, we evaluated the feasibility of fSPECT for intraoperative 3-D mapping in patients with parathyroid adenomas. Methods: Three patients (range 30 to 45 years) diagnosed with hyperparathyroidism (one primary and two tertiary) underwent parathyroid scintigraphy with technetium-99m sestamibi (99mTc-MIBI) to localize parathyroid adenomas. Two patients were referred with persistent hyperparathyroidism after conventional parathyroidectomy. In all three patients, a planar scintigraphy of the neck was performed 10 min after injection (p.i.) followed by SPECT/CT (Symbia T2, Siemens Healthcare) and a correlative ultrasound 2 h p.i. 99mTc-MIBI scan was performed the day before surgery in two patients and at the same day in one patient. fSPECT images were acquired intraoperatively using declipse SPECT (SurgicEyeTM). Results: A total of five parathyroid adenomas were successfully located with SPECT/CT. fSPECT allowed intraoperative detection of all adenomas, and successful parathyroidectomy was accomplished. Parathyroid hormone level decreased intraoperatively in all three patients, on average, by 79% (range 72% to 91%). Conclusion: In this preliminary study, we could demonstrate that intraoperative localization of parathyroid adenomas is feasible using the freehand SPECT technology, thus allowing an image-guided parathyroidectomy

Experimental Porcine Toxoplasma gondii

Porcine infections are currently not the state-of-the-art model to study human diseases. Nevertheless, the course of human and porcine toxoplasmosis is much more comparable than that of human and murine toxoplasmosis. For example, severity of infection, transplacental transmission, and interferon-gamma-induced antiparasitic effector mechanisms are similar in pigs and humans. In addition, the severe immunosuppression during acute infection described in mice does not occur in the experimentally infected ones. Thus, we hypothesise that porcine Toxoplasma gondii infection data are more representative for human toxoplasmosis. We therefore suggest that the animal model chosen must be critically evaluated for its assignability to human diseases

Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy

Multiple system atrophy (MSA) is a progressive late onset neurodegenerative α-synucleinopathy with unclear pathogenesis. Recent genetic and pathological studies support a central role of α-synuclein (αSYN) in MSA pathogenesis. Oligodendroglial cytoplasmic inclusions of fibrillar αSYN and dysfunction of the ubiquitin–proteasome system are suggestive of proteolytic stress in this disorder. To address the possible pathogenic role of oligodendroglial αSYN accumulation and proteolytic failure in MSA we applied systemic proteasome inhibition (PSI) in transgenic mice with oligodendroglial human αSYN expression and determined the presence of MSA-like neurodegeneration in this model as compared to wild-type mice. PSI induced open field motor disability in transgenic αSYN mice but not in wild-type mice. The motor phenotype corresponded to progressive and selective neuronal loss in the striatonigral and olivopontocerebellar systems of PSI-treated transgenic αSYN mice. In contrast no neurodegeneration was detected in PSI-treated wild-type controls. PSI treatment of transgenic αSYN mice was associated with significant ultrastructural alterations including accumulation of fibrillar human αSYN in the cytoplasm of oligodendroglia, which resulted in myelin disruption and demyelination characterized by increased g-ratio. The oligodendroglial and myelin pathology was accompanied by axonal degeneration evidenced by signs of mitochondrial stress and dysfunctional axonal transport in the affected neurites. In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA

Drug-Induced Parkinsonism

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead