Neurological examination course in an interactive webinar as a solution during a pandemic. An overview of the implementation, optimization as well as critical considerations.

Situation: The COVID-19 pandemic made the traditional bedside teaching inaccessible for medical students. Problem: Within a short period of time, established bedside teaching concepts had to be converted into online formats to meet the requirements of the health authorities. Approach: The Department of Neurology at the University Hospital Essen transformed the examination course in the 5th clinical semester into a live stream, taking into account data protection guidelines. This enabled students to participate from a distance, allowing them to take the medical history from a patient and to interact with the medical examiners. Thus, this concept goes beyond the video-based formats of the examination course. Optimization: During the course, we performed online evaluations to ensure an immediate feedback from the students. This enabled us to implement ongoing changes that had a positive impact on the course format, for example using better equipment to ensure a better video and audio quality. In the future, we hope to create a clinic's own online channel to further increase data security.

Combined radiotherapy and concurrent tumor treating fields (TTFields) for glioblastoma: Dosimetric consequences on non-coplanar IMRT as initial results from a phase I trial.

BACKGROUND: Glioblastoma is a rapidly proliferating tumor. Patients bear an inferior prognosis with a median survival time of 14-16 months. Proliferation and repopulation are a major resistance promoting factor for conventionally fractionated radiotherapy. Tumor-Treating-Fields (TTFields) are an antimitotic modality applying low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz) alternating electric-fields. More recently interference of TTFields with DNA-damage-repair and synergistic effects with radiotherapy were reported in the preclinical setting. This study aims at examining the dosimetric consequences of TTFields applied during the course of radiochemotherapy. METHODS: Cone-beam-computed-tomography (CBCT)-data from the first seven patients of the PriCoTTF-phase-I-trial were used in a predefined way for dosimetric verification and dose-accumulation of the non-coplanar-intensity-modulated-radiotherapy (IMRT)-treatment-plans as well as geometric analysis of the transducer-arrays by which TTFields are applied throughout the course of treatment. Transducer-array-position and contours were obtained from the low-dose CBCT's routinely made for image-guidance. Material-composition of the electrodes was determined and a respective Hounsfield-unit was assigned to the electrodes. After 6D-fusion with the planning-CT, the dose-distribution was recalculated using a Boltzmann-equation-solver (Acuros XB) and a Monte-Carlo-dose-calculation-engine. RESULTS: Overdosage in the scalp in comparison to the treatment plan without electrodes stayed below 8.5% of the prescribed dose in the first 2 mm below and also in deeper layers outside 1cm2 at highest dose as obtained from dose-volume-histogram comparisons. In the clinical target volume (CTV), underdosage was limited to 2.0% due to dose attenuation by the electrodes in terms of D95 and the effective-uniform-dose. Principal-component-analysis (PCA) showed that the first principal-position-component of the variation of repeated array-placement in the direction of the largest variations and the perpendicular second-component spanning a tangential plane on the skull had a standard deviation of 1.06 cm, 1.23 cm, 0.96 cm, and 1.11 cm for the frontal, occipital, left and right arrays for the first and 0.70 cm, 0.71 cm, 0.79 cm, and 0.68 cm, respectively for the second-principal-component. The variations did not differ from patient-to-patient (p > 0.8, Kruskal-Wallis-tests). This motion led to a diminution of the dosimetric effects of the electrodes. CONCLUSION: From a dosimetric point of view, dose deviations in the CTV due to transducer-arrays were not clinically significant in the first 7 patients and confirmed feasibility of combined adjuvant radiochemotherapy and concurrent TTFields. PriCoTTF Trial: A phase I/II trial of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma. DRKS-ID: DRKS00016667. Date of Registration in DRKS: 2019/02/26. Investigator Sponsored/Initiated Trial (IST/IIT): yes. Ethics Approval/Approval of the Ethics Committee: Approved. (leading) Ethics Committee Nr.: 18-8316-MF, Ethik-Kommission der Medizinischen. Fakultät der Universität Duisburg-Essen. EUDAMED-No. (for studies acc. to Medical Devices act): CIV-18-08-025247.

Is sexuality a problem? A follow-up of patients with severe burns 6 months to 7 years after injury.

PURPOSE AND AIMS: This is the first study investigating sexuality from 6 months up to 7 years after burn. The aim was to examine sexuality in females and males by using the BSHS-B sexuality subscale and to examine possible contributing factors with regard to sociodemographics, burn characteristics, personality traits, and previous psychiatric disorders. METHODS: A cohort of 107 patients consecutively admitted to a Swedish national burn center was followed up at 6, 12, and 24 months after burn, and 67 individuals were followed up at 2-7 years after burn. The present study utilized the BSHS-B sexuality subscale, and multiple regression analyses were used to examine possible contributing factors. RESULTS: Women were less satisfied than men, and sexuality mean scores improved over time, even up to 7 years after-burn, in both men and women. The strongest contributing factors for worse outcome regarding sexuality were a history of psychiatric morbidity, neuroticism and burn severity. CONCLUSIONS: As some patients experience sexual problems after burns, even many years later, it is important to identify these individuals. The BSHS-B sexuality subscale may be used as a screening tool, but more in-depth assessment might be needed to address all aspects of sexuality.

Health-related quality of life in Swedish pediatric burn patients and associations with burn and family characteristics.

Although many children with burns recover well and have a satisfying quality of life after the burn, some children do not adjust as well. Health-related quality of life (HRQoL) focuses on the impact health status has on quality of life. The aim of this study was to assess HRQoL with the American Burn Association/Shriners Hospitals for Children Burn Outcomes Questionnaire (BOQ) in a nationwide Swedish sample of children with burns 0.3-9.0 years after injury. Participants were parents (n=109) of children aged up to 18 years at the time of investigation who were treated at the Linköping or Uppsala Burn Center between 2000 and 2008. The majority of children did not have limitations in physical function and they did not seem to experience much pain. However, there were indications of psychosocial problems. Parents of preschool children reported most problems with the children's behavior and family disruption, whereas parents of children aged 5-18 years reported most problems with appearance and emotional health. There were mainly burn-related variables associated with suboptimal HRQoL in children aged 5-18 years, while family-related variables did not contribute as much.

Resentment, hate, and hope in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease. Despite much research having been conducted about psychological issues involved in living with ALS, anger, and resentment have yet to be investigated. Moreover, the construct of "hope" has received little attention, so far. An online survey was created to investigate hate, resentment, and hope issues in people with ALS, in relation to the willingness to adopt a strict nutrient-dense diet if it were shown to increase longevity. Results indicate that there is a high level of hope in the sample. People who have lived with ALS for more time expressed a higher level of hope to live 10 years or more. Those who are married were more likely to have hope of living 10 years or longer and more likely to have lower levels of hate against ALS. Dietary self-care choices appear to be related to hope issues. Resentment and hate tended to be higher in people who have had ALS for less time, and in women. Despite some methodological limitations, the results suggest that hope, hate, and resentment could be important issues to explore in future studies.

Comparative study of DNA encapsulation into PLGA microparticles using modified double emulsion methods and spray drying techniques.

Recently, several research groups have shown the potential of microencapsulated DNA as adjuvant for DNA immunization and in tissue engineering approaches. Among techniques generally used for microencapsulation of hydrophilic drug substances into hydrophobic polymers, modified WOW double emulsion method and spray drying of water-in-oil dispersions take a prominent position. The key parameters for optimized microspheres are particle size, encapsulation efficiency, continuous DNA release and stabilization of DNA against enzymatic and mechanical degradation. This study investigates the possibility to encapsulate DNA avoiding shear forces which readily degrade DNA during this microencapsulation. DNA microparticles were prepared with polyethylenimine (PEI) as a complexation agent for DNA. Polycations are capable of stabilizing DNA against enzymatic, as well as mechanical degradation. Further, complexation was hypothesized to facilitate the encapsulation by reducing the size of the macromolecule. This study additionally evaluated the possibility of encapsulating lyophilized DNA and lyophilized DNA/PEI complexes. For this purpose, the spray drying and double emulsion techniques were compared. The size of the microparticles was characterized by laser diffractometry and the particles were visualized by scanning electron microscopy (SEM). DNA encapsulation efficiencies were investigated photometrically after complete hydrolysis of the particles. Finally, the DNA release characteristics from the particles were studied. Particles with a size of <10 microm which represent the threshold for phagocytic uptake could be prepared with these techniques. The encapsulation efficiency ranged from 100-35% for low theoretical DNA loadings. DNA complexation with PEI 25?kDa prior to the encapsulation process reduced the initial burst release of DNA for all techniques used. Spray-dried particles without PEI exhibited high burst releases, whereas double emulsion techniques showed continuous release rates.

Cationic microparticles consisting of poly(lactide-co-glycolide) and polyethylenimine as carriers systems for parental DNA vaccination.

Cationic microparticles for DNA adsorption were formulated by blending poly(lactide-co-glycolide) (PLGA) (50:50), with different cationic agents, either PEI 25 kDa (polyethylenimine) or CTAB (cetyl-trimethyl-ammonium-bromide). The aim was to create adjuvant delivery systems increasing the efficiency of DNA vaccines. Microparticles formulated with 10% PEI exhibited a highly positive zeta-potential, small particle sizes, in contrast to particles prepared with CTAB, which revealed highly aggregated structures in scanning electron micrographs. PEI 10% microparticles efficiently adsorbed DNA and protected DNA from enzymatic degradation. Microparticles with up to 10% PEI did not affect membrane integrity whereas CTAB particles showed higher LDH release. Transfection efficiencies were assessed using a luciferase reporter gene assay compared to naked DNA and PEI/DNA polyplexes. DNA adsorbed onto microspheres with 10% or 50% PEI generally had higher transfection efficiencies than CTAB but reached lower expression levels than PEI/DNA polyplexes alone. This documented the intact release of DNA. The mechanism of gene delivery to non-phagocytic cells was studied via covalent fluorescence labeling of both the DNA and PEI by confocal microscopy and suggested uptake of DNA. Immunization of mice was performed using plasmids encoding immunodominant antigens of Listeria monocytogenes adsorbed onto RG 502 H+PEI 10% microparticles. The efficiency was tested by intravenous challenge with an otherwise lethal dose of L. monocytogenes. PLGA+PEI microspheres can be used as adjuvant delivery systems for DNA but further optimization is necessary to exploit their full potential.

In situ forming parenteral drug delivery systems: an overview.

Biodegradable injectable in situ forming drug delivery systems represent an attractive alternative to microspheres and implants as parenteral depot systems. Their importance will grow as numerous proteins will lose their patent protection in the near future. These devices may offer attractive opportunities for protein delivery and could possibly extend the patent life of protein drugs. The controlled release of bioactive macromolecules via (semi-) solid in situ forming systems has a number of advantages, such as ease of administration, less complicated fabrication, and less stressful manufacturing conditions for sensitive drug molecules. For these reasons, a number of polymeric drug delivery systems with the ability to form a drug reservoir at the injection site are under investigation. Here, we review various strategies used for the preparation of in situ forming parenteral drug depots and their potential benefits/draw-backs, especially with regard to the delivery of protein drug candidates.

Human medulloblastomas lack point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene.

Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of the cerebellum occurring predominantly in childhood. The association of monosomy of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours (AT/RTs) of the brain share clinical and histological features with MBs and supratentorial PNETs (sPNETs). In particular, AT/RTs can be misdiagnosed as MBs and sPNETs because AT/RTs frequently contain areas of primitive neuroepithelial cells similar to PNETs. Recently, mutations of the tumour suppressor gene hSNF5/INI1, located on 22q11.23, have been described in AT/RTs, MBs and sPNETs, with conflicting data on the prevalence of hSNF5/INI1 mutations in the latter entities. Therefore, we screened MBs for point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene. In 90 MBs, no mutations of the hSNF5/INI1 gene were identified. Thus, our study virtually rules out hSNF5/INI1 as a tumour suppressor gene involved in the pathogenesis of medulloblastoma.

The experience of pervasive loss: children and young people living in a family where parental gambling is a problem.

Gambling research has contributed much to our understanding of the effects of gambling on families, yet we have only the most cursory understanding of the child's perspective on what it is like to grow up in such a family. The aim of this qualitative study was to gain a deeper understanding of the experiences of Australian children who live in families where a parent or caregiver has a serious gambling problem by exploring the perspectives and understandings of the children and young people themselves. This paper reports a central finding, the experience of 'Pervasive Loss,' from our interviews with 15 young people, 11 males and 4 females, aged between 7 and 18 years. Their sense of loss encompassed both physical and existential aspects of the child's life, including their parent(s), relationships, trust, security, sense of home, and material goods. The dimensions of this experience of pervasive loss are explored from the child's perspective. Children living in families where gambling is a problem experience threats to their overall well-being to the extent that parental problem gambling must now considered to be a significant child health as well as social problem.

Children of parent(s) who have a gambling problem: a review of the literature and commentary on research approaches.

Problem gambling is becoming an increasingly widespread and damaging social and health problem. As opportunities for gambling become more accessible, especially through lotteries and electronic gaming machines, it is likely that more people will develop serious gambling problems. Given the worldwide increasing spending on gambling activities and the increasing number of problem gamblers, it is unfortunate but likely that the children who grow up in problem gambling families will become an important area of concern for child health and social workers. Considerable research has been undertaken into problem gambling and the adult problem gambler, but within the gambling and child health literature there is almost no recognition of the experiences of children who live in problem-gambling families. Drawing on the findings of the landmark Productivity Commission Report, this review explores the marked increase in gambling and its social effects, especially from the Australian perspective. The damaging social effects of problem gambling on families and children are reviewed and the comparative invisibility of children and young people in such research is discussed. The pervasive influence of developmentalism is critiqued and highlighted in relation to the exclusion of children's perspectives from our research understandings. The review concludes by proposing that adoption of some of the emerging 'new paradigm' approaches to childhood and children's experiences could markedly enhance our understandings of the lives and experiences of this significant group of children and young people.

Diagnostic and therapeutic dilemmas of a large scrotal lesion in an AIDS patient.

In the setting of HIV infection, chronic genital ulcerations may be challenging both diagnostically and therapeutically. The differential diagnosis of these lesions is very broad, and the causes can be multifactorial. We present a case of a chronic, extensive, ulcerating scrotal mass and review the salient clinical, diagnostic, and therapeutic considerations.

Cutaneous leishmaniasis following local trauma: a clinical pearl.

Cutaneous leishmaniasis is acquired from the bite of an infected sand fly and can result in chronic skin lesions that develop within weeks to months after a bite. Local trauma has been implicated as a precipitating event in the development of skin lesions in patients who have been infected with Leishmania species. Here we report a case series and review the literature on patients who developed cutaneous leishmaniasis after local trauma, which may familiarize clinicians with this presentation.

Safety and efficacy of intravenous sodium stibogluconate in the treatment of leishmaniasis: recent U.S. military experience.

The efficacy and toxicity of sodium stibogluconate (SSG) at a dosage of 20 mg/(kg.d) for either 20 days (for cutaneous disease) or 28 days (for visceral, mucosal, or viscerotropic disease) in the treatment of leishmaniasis is reported. Ninety-six U.S. Department of Defense health care beneficiaries with parasitologically confirmed leishmaniasis were prospectively followed for 1 year. One patient was infected with human immunodeficiency virus; otherwise, comorbidity was absent. Clinical cure occurred in 91% of 83 cases of cutaneous disease and 93% of 13 cases of visceral/viscerotropic disease. Adverse effects were common and necessitated interruption of treatment in 28% of cases, but they were generally reversible. These included arthralgias and myalgias (58%), pancreatitis (97%), transaminitis (67%), headache (22%), hematologic suppression (44%), and rash (9%). No subsequent mucosal leishmaniasis was identified, and there were no deaths attributable to SSG or leishmaniasis.

Herpes zoster and lymphopenia associated with sodium stibogluconate therapy for cutaneous leishmaniasis.

A review of 84 patients with cutaneous leishmaniasis treated with sodium stibogluconate (Pentostam) at our institution revealed that three had developed herpes zoster during or shortly after receiving therapy. Because zoster has been associated with depressed cellular immunity, we prospectively followed serial lymphocyte subpopulations in eight patients with cutaneous leishmaniasis who received Pentostam. By day 7 of therapy, the white blood cell count had fallen by a median of 1.15/mm3, the total lymphocyte count by a median of 804/mm3, and the CD4+ lymphocyte count by a median of 306/mm3 (67% of baseline; confidence interval, 52%-78%). An in vitro cell-viability assay demonstrated that Pentostam is not toxic to human mononuclear cells. The administration of Pentostam for the treatment of cutaneous leishmaniasis results in lymphopenia that may be related to the subsequent occurrence of herpes zoster.

Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism.

Multiple cell types contribute to the pulmonary barrier including Type I and Type II alveolar epithelium. The objective of this research was to establish and characterize an in vitro model of Type II alveolar epithelium using the A549 human lung adenocarcinoma cell line. A549 cells form confluent monolayers with Type II characteristic morphology and tannic acid staining for typical lamellar bodies. A549 cells possess P450 IA1 and P450 IIB6 as determined by Western blots. Both CYPIA1 and CYPIIB6 P450 isozymes were determined to be functional with the fluorescent resorufin assay. Only the IA1 isozyme was observed to be inducible with selected polycyclic hydrocarbons. Uptake and transport experiments were carried out in cluster plates and in Snapwells. Cationized ferritin, a nonspecific absorbtive marker, was found to be taken up by the cells in a concentration-, time-, and temperature-dependent fashion. Lucifer yellow, a fluid-phase marker, was not internalized by the A549 cells. Transferrin, a representative receptor-mediated endocytic marker, was found to be taken up by the cells in a concentration-dependent and competitive fashion. Transport experiments involving fluorescein-transferrin also showed that A549 monolayers were polarized, with a greater amount of intracellular transferrin being transported out of the basolateral side of the cells. The experimental data agree favorably with literature for primary cultures of Type II pulmonary epithelial cells. These results indicated that the A549 cell line may be useful for the studying the metabolic and macromolecule processing contributions of alveolar Type II cells to mechanisms of drug delivery at the pulmonary epithelium.