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Background: This study aims to investigate the integration of modern sources of patient information, such as videos, internet-based resources, and scientific abstracts, into the traditional patient informed consent process in outpatient elective surgeries. The goal is to optimize the informed consent experience, enhance patient satisfaction, and promote shared decision making (SDM) between patients and surgeons. By exploring different patient informed consent formats and their impact on patient satisfaction, this research seeks to improve healthcare practices and ultimately enhance patient outcomes. The findings of this study will contribute to the ongoing efforts to improve the informed consent process in public hospitals and advance patient-centred care. Methods: Data collection occurred at the day care clinic of a prominent German public hospital, forming an integral component of a prospective clinical investigation. The study exclusively focused on individuals who had undergone surgical intervention for skin cancer. For the purpose of meticulous data examination, the statistical software SPSS version 21 was harnessed. In the course of this study, a chi-square test was aptly employed. Its purpose was to scrutinize the nuances in patient experiences pertaining to informed consent across four distinct categories, viz., oral informed consent discussion (Oral ICD), written informed consent discussion (Written ICD), video-assisted informed consent discussion (video-assisted ICD), and digitally assisted informed consent discussion (digital-assisted ICD). The primary dataset of this inquiry was diligently gathered via a structured questionnaire administered to a targeted cohort of 160 patients. Within this sample, a balanced representation of genders was observed, encompassing 82 males and 78 females. Their collective age span ranged from 18 to 92 years, with an average age of 71 years. A randomized selection methodology was employed to include participants in this study during the period spanning from July 2017 to August 2018. Results: Significant differences were observed across the groups for all research questions, highlighting variations in patient responses. Video-assisted and digital-assisted IC were rated as superior in patient satisfaction with information compared to written and oral IC. Demographic profiles of the four study groups were found to be comparable. Conclusion: The findings of this study indicate that the incorporation of digital technologies in the informed consent process can enhance patient understanding during outpatient elective skin cancer surgeries. These results have important implications for increasing patient satisfaction and improving the SDM process within the hospital environment. [ABSTRACT FROM AUTHOR]

Background/aim: Mortality associated with hot tap water scalds remains significant, owing to a lack of up-to-date regulations on tap water temperature. We aimed to evaluate the effect of hot tap water scalds on patients admitted to our adult burn intensive care unit (BICU), and compare them to those with other scald types.Methods: We enrolled patients treated for scalds at the BICU of Cologne-Merheim Medical Center from 1989 to 2014, and retrospectively analyzed their age, sex-specific differences, characteristics, length of hospital stay, number of operations, and mortality. Patients were categorized into two groups: patients with hot tap water scalds and those with all other types of scalds.Results: A total of 333 patients were enrolled. In 23.4% (n=78) of the cases, the scalds were associated with hot tap water. Such injuries were more commonly observed in older men than women. Hot tap water scalds involved a significantly higher total burned surface area (TBSA) than other scalds, with TBSA values of 24.0% and 15.9% for men, and 21.8% and 10.9% for women, respectively. Hot tap water scald patients had a greater number of surgeries and longer BICU stays (27.8 days vs 9.1 days), and significantly higher mortality values (30.8% (n=24) vs 4.7% (n=12)) than those with the other scald types.Conclusions: Hot water scalds are associated with large TBSAs, long stays in the BICU, and worse outcomes compared to the other scald types. [ABSTRACT FROM AUTHOR]

Three studies tested scope and limits of children's implicit and explicit theory of mind. In Studies 1 and 2, three- to six-year-olds (N = 84) were presented with closely matched explicit false belief tasks that differed in whether or not they required an understanding of aspectuality. Results revealed that children performed equally well in the different tasks, and performance was strongly correlated. Study 3 tested two-year-olds (N = 81) in implicit interactive versions of these tasks and found evidence for dis-unity: children performed competently only in those tasks that did not require an understanding of aspectuality. Taken together, the present findings suggest that early implicit and later explicit theory of mind tasks may tap different forms of cognitive capacities. [ABSTRACT FROM AUTHOR]

Introduction: Facial burns occur frequently and depending on the injured skin layers often heal with scars which may cause permanent functional and cosmetic sequelae. Preservation of the sensitive facial skin layers, especially of the dermis is essential for scarless epithelialisation. Enzymatic debridement of deep thermal burns has already been shown to assist with preserving viable dermis. However, up to date, there are no published reports on wound healing and in the long term aesthetic outcome after enzymatic debridement of facial burns.Methods: Therefore we performed a-single centre clinical trial that included 26 subjects aged 18-78 years with facial burns clinically evaluated as deep dermal or deeper. Burns were treated either with enzymatic debridement or excisional surgical debridement. Then we compared both groups regarding debridement selectivity, wound closure and scar quality after more than 12 months.Results: Enzymatic debridement significantly reduced time to complete wound closure after admission (19.85 days versus 42.23 days, p=0.002), and after enzymatic eschar removal (18.92 days versus 35.62 days, p=0.042). The number of procedures to complete debridement were significantly lower in the enzymatic debridement group (1.00 versus 1.77, p=0.003). 77% of facial burns that had been debrided enzymatically were found to be more superficially burned than initially estimated. Wounds undergoing autografting of any size were significantly reduced by enzymatic debridement (15% versus 77%, p=0.002). Scar quality after enzymatic debridement was superior compared to surgical debridement after 12 months regarding pigmentation (p=0.016), thickness (p=0.16), relief (p=0.10), pliability (p=0.01), surface area (p=0.004), stiffness (p=0.023), thickness (0.011) and scar irregularity (p=0.011). Regarding erythema and melanin, viscoelasticity and pliability, trans-epidermal water loss or laser tissue oxygen saturation, haemoglobin level and microcirculation we found no significant differences for treated and untreated skin in the EDNX group.Conclusion: In our current study we found Bromelain based enzymatic debridement better in some aspects of tissue preservation in deep dermal facial burn. [ABSTRACT FROM AUTHOR]

Introduction: In a single-center, prospective, randomized clinical trial three different configured wound dressings Biobrane(®), Dressilk(®) and PolyMem(®) were compared with each other regarding objective and subjective healing parameters and cost efficiency.Methods: 28 burn patients received surgical treatment with split-thickness skin grafting, while utilizing Biobrane(®), Dressilk(®) and PolyMem(®) as a single bound donor site wound dressing in all patients. Following a standardized case report form, we monitored several parameters such as pain, transparency of the dressing, active bleeding, exudation and inflammation by using the Verbal Rating Scale 1-10 through out.Results: With regard to re-epithelialization, pain and acute bleeding all three dressings were equivalent. Dressilk(®) and Biobrane(®) presented clearly superior to PolyMem(®) in both wound assessment and in the reduction of mild inflammation and exudation. High subjective satisfaction rates were reported with Dressilk(®) and Biobrane(®) dressings in regard to comfort and mobility. During the continuous monitoring period Biobrane(®) outperformed Dressilk(®) by providing higher wound transparency rates and offering a better level of wound control during the entire study period. Regarding their cost efficiency, PolyMem(®) and Dressilk(®) are clearly superior to Biobrane(®).Conclusion: The "ideal" wound dressing maximizes patients' comfort while reducing pain and the risk of pulling off migrating epidermal cells from the wound surface. In addition reliable wound status evaluation (minimizing complications), an increase of treatment cost value efficacy, and reduced hospitalization rates should be provided. Dressilk(®) and Biobrane(®) were favored by patients and surgeons for providing an effective and safe healing environment, with overall low complication rates with respect to infection and exudation. Regarding cost-effectiveness PolyMem(®) and Dressilk(®) presented superior to Biobrane(®). [ABSTRACT FROM AUTHOR]

The production of therapeutic antibodies using mammalian cells remains a high-priority in the biopharmaceutical manufacturing industry. Bioengineers have targeted different cellular processes, including transcription, translation, secretion and post-translational modifications, to overcome the metabolic bottlenecks limiting production capacity and create high-producing mammalian cell lines. The polycomb group (PcG) proteins belong to a family of chromatin regulators with important roles in multicellular development. By overexpressing and screening genes from the PcG family, we have identified an epigenetic key player for biopharmaceutical manufacturing enhancement: the transcription factor Yin Yang 1 (YY1). The overexpression of YY1 led to an increase in the production of several product genes (SEAP, VEGF 165 , IgG including Rituximab), provided that human YY1 (hYY1) was expressed in human cells (HeLa, HT-1080, HEK-293T, FreeStyle™ 293-F) and Chinese hamster ovary cell-derived YY1 (cYY1) was expressed in CHO cells (CHO-K1, CHO-easyC, FreeStyle™ CHO-S, CHO-B13-24, CHO-IgG1). Ectopic expression of cYY1 in the stable CHO-derived IgG producer cell lines CHO-B13-24 and CHO-IgG1 increased the antibody titer up to 6-fold, suggesting that epigenetic engineering of mammalian production cell lines could become a new strategy to improve the manufacturing of complex protein pharmaceuticals. [ABSTRACT FROM AUTHOR]

Individuals avoid stimuli which are associated with aversive experience to preserve safety. However, behavioral avoidance also causes impairments and prevents the individual from attaining positive rewards. Little is known about the link between fear acquisition and the development of behavioral avoidance in the presence of potential rewards. Therefore, two experiments investigated the impact of fear conditioning on a subsequent gambling task. In an experimental group (« = 30) advantageous choices (higher reward probability) were linked to a fear-relevant stimulus that was associated with an aversive unconditioned stimulus (US) during fear conditioning (conditioned stimulus, CS-H). A disadvantageous choice (lower reward probability) was, however, linked to a safe stimulus that was never associated with the US (CS--). In a control group (n = 25), fear conditioning was followed by a similar gambling task with novel stimuli. A second experiment focused on individual predictors of avoidant decisions (« = 81). Compared with the control group, individuals in the experimental groups avoided the advantageous CS -I- choice despite fewer gains. The predictor analysis further clarified that avoidant decisions were pronounced in highly trait anxious participants who exhibited higher fear responses. On the other hand, findings also indicated a reduction in absolute avoidance across the task. Combined, these findings demonstrate that fear conditioning can lead to avoidant decision making, especially in vulnerable individuals. The resulting costs parallel impairments caused by behavioral avoidance. Such an emotional decision-making style may be a link between aversive experience and the development of habitual pathological avoidance. Introducing rewards for approach, however, may counteract avoidant decisions. [ABSTRACT FROM AUTHOR]

Since the discovery of Kepler-10, the system has received considerable interest because it contains a small, rocky planet which orbits the star in less than a day. The system's parameters, announced by the Kepler team and subsequently used in further research, were based on only five months of data. We have reanalyzed this system using the full span of 29 months of Kepler photometric data, and obtained improved information about its star and the planets. A detailed asteroseismic analysis of the extended time series provides a significant improvement on the stellar parameters: not only can we state that Kepler-10 is the oldest known rocky-planet-harboring system at 10.41 ± 1.36 Gyr, but these parameters combined with improved planetary parameters from new transit fits gives us the radius of Kepler-10b to within just 125 km. A new analysis of the full planetary phase curve leads to new estimates on the planetary temperature and albedo, which remain degenerate in the Kepler band. Our modeling suggests that the flux level during the occultation is slightly lower than at the transit wings, which would imply that the nightside of this planet has a non-negligible temperature. [ABSTRACT FROM AUTHOR]

Artificial carbon dioxide leakage into a shallow aquifer was monitored using stable carbon isotope measurements at a field site near the town of Wittstock, Brandenburg, Germany. Approximately 400?000 L of CO2 were injected into a shallow aquifer at 18 m depth over 10 days. The 13C/ 12C ratios of the CO2 were measured in both groundwater and soil gas samples to monitor the distribution of the injected CO2 plume and to evaluate the feasibility and reliability of this approach to detect potential CO2 leakage, for example from carbon capture and storage (CCS) sites. The isotopic composition of the injected CO2 (δ13C -30.5 ‰) was differentiable from the background CO2 (δ13C -21.9 ‰) and the artificial CO2 plume was monitored over a period spanning more than 204 days. The results demonstrate that this stable isotope monitoring approach can be used to identify CO2 sources and detect potential CO2 migration from CCS sites into overlying shallow aquifers or even into the upper subsurface. A significant difference between the isotope ratios of the natural background and the injected CO2 is required for this monitoring approach to be effective. [ABSTRACT FROM AUTHOR]

The neuropeptide corticotropin-releasing factor (CRF) plays a critical role in mediating anxiety-like responses to stressors, and dysfunction of the CRF system has been linked to the etiology of several psychiatric disorders. Extra-hypothalamic CRF can also modulate learning and memory formation, including amygdala-dependent learning. The basolateral nucleus of the amygdala (BLA) contains dense concentrations of CRF receptors, yet the distribution of these receptors on specific neuronal subtypes within the BLA has not been characterized. Here, we quantified the expression of CRF receptors on three nonoverlapping classes of GABAergic interneurons: those containing the calcium-binding protein parvalbumin (PV), and those expressing the neuropeptides somatostatin (SOM) or cholecystokinin (CCK). While the majority of PV+ neurons and roughly half of CCK+ neurons expressed CRF receptors, they were expressed to a much lesser extent on SOM+ interneurons. Knowledge of the distribution of CRF receptors within the BLA can provide insight into how manipulations of the CRF system modulate fear and anxiety-like behaviors. [ABSTRACT FROM AUTHOR]

Background: Most randomized controlled trials (RCTs) in the academic setting have limited resources for clinical trial management and monitoring. Inefficient conduct of trials was identified as an important source of waste even in well-designed studies. Thoroughly identifying trial-specific risks to enable focussing of monitoring and management efforts on these critical areas during trial conduct may allow for the timely initiation of corrective action and to improve the efficiency of trial conduct. We developed a risk-tailored approach with an initial risk assessment of an individual trial that informs the compilation of monitoring and management procedures in a trial dashboard. Methods: We performed a literature review to identify risk indicators and trial monitoring approaches followed by a contextual analysis involving local, national and international stakeholders. Based on this work we developed a risk-tailored management approach with integrated monitoring for RCTs and including a visualizing trial dashboard. We piloted the approach and refined it in an iterative process based on feedback from stakeholders and performed formal user testing with investigators and staff of two clinical trials. Results: The developed risk assessment comprises four domains (patient safety and rights, overall trial management, intervention management, trial data). An accompanying manual provides rationales and detailed instructions for the risk assessment. We programmed two trial dashboards tailored to one medical and one surgical RCT to manage identified trial risks based on daily exports of accumulating trial data. We made the code for a generic dashboard available on GitHub that can be adapted to individual trials. Conclusions: The presented trial management approach with integrated monitoring enables user-friendly, continuous checking of critical elements of trial conduct to support trial teams in the academic setting. Further work is needed in order to show effectiveness of the dashboard in terms of safe trial conduct and successful completion of clinical trials. [ABSTRACT FROM AUTHOR]

In our study, we aimed to explore the profile of the high-risk subgroup of suicide attempters that used a violent means compared to suicide attempters that chose a non-violent suicide means. Therefore, we recruited a sample of inpatients with recent suicide attempts in three psychiatric hospitals in Thuringia, Germany. We used a structured clinical interview to assess the psychiatric diagnoses, sociodemographic data, and characteristics of the suicide attempt. Furthermore, we used several validated clinical questionnaires to measure suicidal ideations, suicide intent, depression severity, hopelessness, impulsivity, aggression, anger expression, and childhood trauma. We compared 41 individuals using violent means to 59 using non-violent means with univariate and multivariate statistical analyses. We found significantly (corrected for multiple comparisons) higher levels of impulsivity-related sensation-seeking in violent suicide attempters in univariate and multivariate analyses, and additionally in anger expression directed inward at an uncorrected statistical threshold. Besides that, there were no significant differences between the two groups. We assume that underlying neurocognitive mechanisms, such as impaired decision-making processes and/or differences in risk/loss assessment, could explain the higher levels of questionnaire-based sensation-seeking in subjects who use violent suicide means. Further research is needed, including neuroimaging and biochemical techniques, to gain more insight into the mechanisms underlying the choice of a suicidal means. [ABSTRACT FROM AUTHOR]

Bruising, the result of capillary failure, is a common physical exam finding due to blunt trauma and, depending on location and severity, a potential indicator of abuse. Despite its clinical relevance, few studies have investigated the etiology of capillary failure. The goal of this study was to determine whether capillaries primarily fail under shear stress or hydraulic-induced tensile stress. An arteriole bifurcating into four capillaries was modeled using ANSYS 14.0 ®. The capillaries were embedded in muscle tissue and a pressure of 20.4 kPa was applied. Any tensile stress exceeding 8.4 × 104 Pa was considered failure. Results showed that failure occurred directly under the impact zone and where capillaries bifurcated, rather than along the line of greatest shear stress, indicating that internal tensile stress is likely the primary mode of capillary failure in bruising. These results are supported by the concept that bruising can occur via blunt trauma in which no shearing lacerations occur. [ABSTRACT FROM AUTHOR]

Background: Whether there is sufficient capacity and capability for the successful conduct and delivery of a clinical trial should be assessed by several stakeholders according to transparent and evidence-based criteria during trial planning. For this openly shared, user-tested, and validated tools are necessary. Therefore, we systematically examined the public availability and content of checklists which assess the study-level feasibility in the planning phase of clinical trials.Methods: In our scoping review we systematically searched Medline, EMBASE, and Google (last search, June 2021). We included all publicly available checklists or tools that assessed study level feasibility of clinical trials, examined their content, and checked whether they were user-tested or validated in any form. Data was analysed and synthesised using conventional content analysis.Results: A total of 10 publicly available checklists from five countries were identified. The checklists included 48 distinct items that were classified according to the following seven different domains of clinical trial feasibility: regulation, review and oversight; participant recruitment; space, material and equipment; financial resources; trial team resources; trial management; and pilot or feasibility studies. None of the available checklists appeared to be user-tested or validated.Conclusions: Although a number of publicly available checklists to assess the feasibility of clinical trials exist, their reliability and usefulness remain unclear. Openly shared, user-tested, and validated feasibility assessment tools for a better planning of clinical trials are lacking. [ABSTRACT FROM AUTHOR]

Background: Various synthetic and biological wound dressings are available for the treatment of superficial burns, and standard care differs among hospitals. Nevertheless, the search for an ideal wound dressing offering a safe healing environment as well as optimal scar quality while being economically attractive is a continuing process. In recent years, Dressilk®, which consists of pure silk, has become the standard of care for the treatment of superficial burns in our hospital. However, no long-term scar-evaluation studies have been performed to compare Dressilk® with the often-used and more expensive Suprathel® in the treatment of superficial burns. Methods: Subjective and objective scar evaluations were performed three, six, and twelve months after treatment in patients who received simultaneous treatment of 20 superficial burn wounds with both Suprathel® and Dressilk®. The evaluations were performed using the Vancouver Scar Scale, the Cutometer®, Mexameter®, Tewameter®, and the O2C®. Results: Both dressings showed mostly equivalent results in subjective scar evaluations. In the objective scar evaluations, the wounds treated with Dressilk® showed a faster return to the qualities of non-injured skin. Wound areas treated with the two dressings showed no significant differences in elasticity and transepidermal water loss after 12 months. Only oxygen saturation was significantly lower in wound areas treated with Suprathel® (p = 0.008). Subjectively, wound areas treated with Dressilk® showed significantly higher pigmentation after six months, which was not apparent after 12 months. Conclusion: Both wound dressings led to esthetically satisfying scar recovery without significant differences from normal uninjured skin after 12 months. Therefore, Dressilk® remains an economically and clinically interesting alternative to Suprathel® for the treatment of superficial burns. [ABSTRACT FROM AUTHOR]

Background: Optimal management of burns always starts with the first aid. Results of numerous studies carried out in different countries indicated in general a low awareness of first aid of burns irrespective of whether the income of the country was high, middle or low. The aim of the study was to investigate the knowledge in burn first aid in Germany and compare it to an Australian study from 2013.Methods: From January 2016 until August 2017 patients, visitors and medical personnel in the emergency room of two large hospitals in Southern and the Western part of Germany were asked to take part in a paper based multiple-choice survey.Results: Altogether 1229 people took part in the questionnaire, 588 from Bavaria and 641 from North Rhine-Westphalia; 45,2% males and 54.8% females. Their age ranged from 19 to 52 with a mean of 37.2 years. Hereby participants that had taken part in first aid training and people working in health care had significant more correct answers. Overall, only approximately a third of the given answers were correct.Conclusion: Our study suggests that there is room for improvement since only a minority of the German population is familiar with first aid principles dealing with burns. Although more than 40% had taken part in a first aid training, the questioned people gave less correct answers than the Australians in 2013. [ABSTRACT FROM AUTHOR]

Background: In the developed world, cardiovascular diseases still contribute to mortality and morbidity, leading to significantly increased deaths in recent years. Thus, it is necessary for a layperson to provide the best possible basic life support (BLS) until professional help is available. Since information on current BLS knowledge in Germany is not available, but necessary to be able to make targeted improvements in BLS education, we conducted this study. Methods: A cohort survey using convenience sampling (non-probability) method was conducted with questions found in emergency medicine education. People coming to the emergency room of two big university hospitals located in the South (Munich) and western part (Cologne) of Germany were asked to participate in the survey between 2016 and 2017. Primary outcome measures were the proportion of correct answers for each emergency scenario in relationship to age, region, profession and first-aid training. Results: Altogether 1003 people (504 from Cologne; 499 from Munich) took part in the questionnaire. 54.7% were female and 45.3% were male aging from 19 to 52 with a mean of 37.2 years. Although over 90% had taken part in first aid training, many people were lacking first aid knowledge, with less than 10% choosing the correct frequency for chest compression. Hereby demographic factors had a significant influence (p<0.05) in the given answers (Friedmann-and-Wilcoxon Test). Conclusion: Overall, results of our survey indicate a clear lack of BLS knowledge. With this information, targeted measures for improving BLS knowledge should be conducted. Additionally, further studies on the feasibility and efficiency of teaching methods are needed [ABSTRACT FROM AUTHOR]

Background: Grilling has become increasingly common in Germany. Although grilling is considered a non-negligible household burn hazard, few reports have assessed this type of injury. This study aimed to determine the patterns and characteristics of grill-related burn injuries and to compare these with other types of burn injuries.Methods: This retrospective observational study included all grill-related burn injuries admitted to Cologne Merheim Burn Center during 1989-2017. The collected data were analyzed descriptively and compared statistically with other fire injuries.Results: Of 1706 cases admitted with fire injuries during the study period, 160 (∼10%) involved grill-related injuries. Most cases (85%) involved men, with an average age of 34 years. Moreover, 48% and 38% of cases occurred in summer and spring, respectively. The most common mechanism of injury was ignition via fluid accelerant. The upper limb was the most commonly affected body part, followed by the head. Statistical analyses revealed that grill-related injuries were associated with a lower mean age and total body surface area, shorter in-hospital stay, and fewer complications than the other fire injury group.Conclusion: Grill-related injuries are a relatively common cause of admission to the Cologne Burn Center. Although grill-related injuries underwent a less aggressive approach than the other investigated fire injuries, the former represent a public health concern because they mainly affect the upper body, with both psychologic and aesthetic consequences. We recommend a German nationwide multi-centric study of the patterns and characteristics of burn injury. [ABSTRACT FROM AUTHOR]

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed. [ABSTRACT FROM AUTHOR]

PURPOSE: Conversion of tumor subtype frequently occurs in the course of metastatic breast cancer but is a poorly understood phenomenon. This study aims to compare molecular subtypes with subsequent lung or pleural metastasis. PATIENTS AND METHODS: In a cohort of 57 patients with breast cancer and lung or pleural metastasis (BCLPM), we investigated paired primary and metastatic tissues for differential gene expression of 269 breast cancer genes. The PAM50 classifier was applied to identify intrinsic subtypes, and differential gene expression and cluster analysis were used to further characterize subtypes and tumors with subtype conversion. RESULTS: In primary breast cancer, the most frequent molecular subtype was luminal A (lumA; 49.1%); it was luminal B (lumB) in BCLPM (38.6%). Subtype conversion occurred predominantly in lumA breast cancers compared with other molecular subtypes (57.1% v 27.6%). In lumA cancers, 62 genes were identified with differential expression in metastatic versus primary disease, compared with only 10 differentially expressed genes in lumB, human epidermal growth factor receptor 2 (HER2)–enriched, and basal subtypes combined. Gene expression changes in lumA cancers affected not only the repression of the estrogen receptor pathway and cell cycle–related genes but also the WNT pathway, proteinases (MME , MMP11), and motility-associated cytoskeletal proteins (CK5, CK14, CK17). Subtype-switched lumA cancers were further characterized by cell proliferation and cell cycle checkpoint gene upregulation and dysregulation of the p53 pathway. This involved 83 notable gene expression changes. CONCLUSION: Our results indicate that gene expression changes and subsequent subtype conversion occur on a large scale in metastatic luminal A–type breast cancer compared with other molecular subtypes. This underlines the significance of molecular changes in metastatic disease, especially in tumors of initially low aggressive potential. [ABSTRACT FROM AUTHOR]

Early separation of preterm infants from their mothers has adverse, long-term neurodevelopmental consequences. We investigated the effects of daily maternal separation (MS) of rat pups from postnatal days 2–10 (PND2–10) on neurobehavioural responses to brief isolation at PND12 compared with pups receiving controlled handling without MS. Ultrasonic vocalizations (USV) were measured at PND12 during two, 3-minute isolations occurring immediately before and after a 3-minute maternal reunion. There were no significant differences in acoustic characteristics between MS and control animals in the first isolation. However, in the second isolation, MS pups produced a greater proportion of high (~60 kHz) vs low (~40 kHz) frequency calls. During this isolation, control pups made longer and louder low frequency calls compared to the first isolation, whereas MS pups did the opposite. Maternal behaviour of control and MS mothers modulated pup acoustic characteristics in opposite directions; higher maternal care was associated with more low frequency calls in control pups but more high frequency calls in MS pups. We hypothesize that MS results in USV emission patterns reflective of a greater stress response to isolation. This translational model can be used to identify mechanisms and interventions that may be exploited to overcome the negative, long-term effects of MS. [ABSTRACT FROM AUTHOR]

Introduction: The aesthetic outcome after burn of exposed areas such as the hand and face is of high importance. A number of wound dressings used for the treatment of superficial and partial thickness burns promise rapid wound healing and reduced scarring. Previously, wound healing of hands and faces with superficial burns treated with Dressilk® compared to Biobrane® was evaluated intra-individually with similar results. Nevertheless, up to date objective information regarding the scarring after superficial burns treated with Dressilk® does not exist.Methods: Therefore, 30 patients with superficial burns of the hand and face that were treated with Dressilk® and Biobrane® simultaneously were included in the study. An objective scar evaluation was performed analyzing melanin and erythema levels, skin elasticity, trans-epidermal water loss and scar perfusion three and six and 12 months after injury. Furthermore, a subjective scar evaluation was performed with the patient and observer scar assessment scale (POSAS) and the Vancouver scar scale (VSS).Results: Dressilk® and Biobrane® both lead to an aesthetic pleasing outcome after superficial burns of the hands and faces. Regarding the objective scar evaluation only trans-epidermal water loss of burned hands after 6 months showed significant differences between the two dressings. However, these differences were not detected in the 12-month follow up examination. In the subjective scar evaluation no statistical differences could be found between the dressings. All patients stated high satisfaction of scar quality.Conclusion: Dressilk® is an interesting alternative to Biobrane® for the treatment of superficial burns of aesthetic and functional important areas. [ABSTRACT FROM AUTHOR]

Early debridement and/or eschar removal is regarded as a significant step in the treatment of deep partial and full thickness burns. It aims to control wound bioburden and allows early wound closure by conservative treatment or skin grafting. Preservation of viable dermis accompanied by early wound closure, is regarded as a necessary step to reduce scar related complication, e.g. functional limitations and/or unaesthetic scar formation. Aside from the classical techniques of surgical excision as tangential excision for eschar removal, hydro-surgery, maggot therapy, laser, enzymatic debridement have been described as additional techniques in the burn surgeon's armamentarium. It is widely accepted that early eschar removal within 72h improves the outcome of burn wound treatment by reducing bacterial wound colonization, infection and length of hospital stay. In contrast, the right technique for eschar removal is still a matter of debate. There is increasing evidence that enzymatic debridement is a powerful tool to remove eschar in burn wounds, reducing blood loss, the need for autologous skin grafting and the number of wounds requiring surgical excision. In order to assess the role and clinical advantages of enzymatic debridement by a mixture of proteolytic enzymes enriched in Bromelain (Nexobrid®) beyond the scope of the literature and in view of users' experience, a European Consensus Meeting was scheduled. The aim was to provide statements for application, based on the mutual experience of applying enzymatic debridement in more than 500 adult and pediatric patients by the consensus panelists. Issues to be addressed were: indications, pain management and anesthesia, timing of application, technique of application, after-intervention care, skin grafting after enzymatic debridement, blood loss, training strategies and learning curve and areas of future research needs. Sixty-eight (68) consensus statements were provided for the use of enzymatic debridement. The degree of consensus was remarkably high, with a unanimous consensus in 88.2% of statements, and lowest degree of consensus of 70% in only 3 statements. This consensus document may serve as preliminary guideline for the use of enzymatic debridement with user-oriented recommendations until further evidence and systematic guidelines are available. [ABSTRACT FROM AUTHOR]

Introduction: An ever-increasing number of commercially available dressings have been applied to treat superficial burns with the aim to reduce pain and inflammation and lead to a fast wound healing and scar reduction. Nevertheless the search for cheap and effective wound dressing proceeds. Dressilk® consisting of silkworm silk showed good results for wound healing in regards to scarring, biocompatibility and reduction of inflammation and pain. Therefore it seemed to be an interesting product for the treatment of superficial burns.Methods: In a prospective intra-individual study the healing of superficial burns was evaluated after the treatment with Dressilk® and Biobrane® in 30 patients with burns of the hand and face. During wound healing pain, active bleeding, exudation, dressing change and inflammation were evaluated using the Verbal Rating Scale 1-10. Three months later scar appearance was assessed by VSS (Vancouver Scar Scale) and POSAS (Patient and Observer Scar Scale).Results: With regard to re-epithelialization, pain, inflammation and acute bleeding both dressings were equivalent. High subjective satisfaction rates were reported for both Dressilk® and Biobrane® dressings in regard to comfort and mobility of the face. Biobrane®, applied as a glove was subjectively preferred for burns of the hand. Regarding their cost efficiency Dressilk® was clearly superior to Biobrane®. Long-term results were similar.Conclusion: The "ideal" wound dressing maximizes patients' comfort while reducing pain and promoting wound healing. Dressilk® and Biobrane® both provided an effective and safe healing environment, showing low overall complication rates with respect to infection and exudation on superficial burns of the hand and face. Therefore Dressilk®, being clearly superior to Biobrane® in cost efficiency is an interesting alternative especially for the treatment of superficial burns of faces. [ABSTRACT FROM AUTHOR]

Introduction: Burns often require special treatment in specialized burn centers. One of the specialized German burn centers is located in Cologne-Merheim. Only little is known about the etiology of burns in Germany, their monthly distribution and changes over the past 25 years.Methods: We therefore retrospectively analyzed the etiology for all patients treated at the burn intensive care unit (BICU) of Cologne in the last 25 years and categorized them into groups. Thereafter all groups were analyzed according to distribution of age, gender and occurrence.Results: In this way we were able to show that the number of severe burns did not decrease over the time under evaluation and that it did not show seasonal variation. Injured females were older than males but fewer in number. The highest numbers of burns were related to fire, followed by electricity, hot liquids, chemicals and heat contact. Work-related burns occurred mostly with males. However, most of the burns were not work-related for either gender.Conclusion: The number of burns in Germany and in the world is still high, and prevention strategies do not always have the desired effect. This study aims to fill the gap in published burn knowledge in Germany by way of describing the gender differences and etiology characteristics. It can therefore help to identify risks and expand effective burn prevention strategies. [ABSTRACT FROM AUTHOR]

In contrast to the developing testis, molecular pathways driving fetal ovarian development have been difficult to characterise. To date no single master regulator of ovarian development has been identified that would be considered the female equivalent of Sry. Using a genomic approach we identified a number of novel protein-coding as well as non-coding genes that were detectable at higher levels in the ovary compared to testis during early mouse gonad development. We were able to cluster these ovarian genes into different temporal expression categories. Of note, Lrrc34 and AK015184 were detected in XX but not XY germ cells before the onset of sex-specific germ cell differentiation marked by entry into meiosis in an ovary and mitotic arrest in a testis. We also defined distinct spatial expression domains of somatic cell genes in the developing ovary. Our data expands the set of markers of early mouse ovary differentiation and identifies a classification of early ovarian genes, thus providing additional avenues with which to dissect this process. [ABSTRACT FROM AUTHOR]

Given that aggressive DNA damaging chemotherapy shows suboptimal efficacy in chronic lymphocytic leukaemia (CLL), alternative therapeutic approaches are needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce tumour-specific apoptosis. However, apoptosis might be inhibited by elevated levels of X-linked inhibitor of apoptosis (XIAP). Use of XIAP-inhibiting compounds might sensitize primary CLL cells towards TRAIL-mediated apoptosis. A novel small molecule, compound A (CA), an inhibitor of XIAP, was used in combination with TRAIL to induce apoptosis in primary CLL cells ( n = 48). XIAP was significantly more highly expressed in primary CLL cells ( n = 28) compared to healthy B cells ( n = 16) ( P = 0·02). Our data obtained by specific knock-down of XIAP by siRNA identified XIAP as the key factor conferring resistance to TRAIL in CLL. Combined treatment with CA/TRAIL significantly increased apoptosis compared to untreated ( P = 8·5 × 10), solely CA ( P = 4·1 × 10) or TRAIL treated ( P = 4·8 × 10) CLL cells. CA rendered 40 of 48 (83·3%) primary CLL samples susceptible to TRAIL-mediated apoptosis. In particular, cells derived from patients with poor prognosis CLL (ZAP-70, IGHV unmutated, 17p-) were highly responsive to this drug combination. Our highly-effective XIAP inhibitor CA, in concert with TRAIL, shows potential for the treatment of CLL cases with poor prognosis and therefore warrants further clinical investigation. [ABSTRACT FROM AUTHOR]

Abstract: The alkylphosphocholine (APC) erufosine is a synthetic phospholipid analogue with antineoplastic activity. APC are known to interact with lipid metabolism and modulate cellular signaling pathways, particularly the phosphorylation of Akt. Here, in primary CLL cells induction of apoptosis was detected with an IC50 of 22μM whereas healthy donor PBMC were less sensitive towards erufosine. Treatment with erufosine caused dose-dependent cleavage of PARP, co-incubation with caspase inhibitor z-VAD almost completely abrogated the cytotoxic effect of erufosine indicating a caspase-dependent mechanism of erufosine. Erufosine was shown to induce apoptosis in primary CLL cells and merits further investigation regarding therapeutic options in CLL. [Copyright &y& Elsevier]