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Introduction: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking.
Methods: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]).
Results: Compared to HCBN, patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency.
Discussion: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.
Encouraging clinical results were reported on a novel cone-in-cone coupling for the fixation of dental implant-supported crowns (Acuris, Dentsply Sirona Implants, Mölndal, Sweden). However, the presence or absence of a microgap and a potential bacterial leakage at the conometric joint has not yet been investigated. A misfit and a resulting gap between the conometric components could potentially serve as a bacterial reservoir that promotes plaque formation, which in turn may lead to inflammation of the peri-implant tissues. Thus, a two-fold study set-up was designed in order to evaluate the bidirectional translocation of bacteria along conometrically seated single crowns. On conometric abutments filled with a culture suspension of anaerobic bacteria, the corresponding titanium nitride-coated (TiN) caps were fixed by friction. Each system was sterilized and immersed in culture medium to provide an optimal environment for microbial growth. Positive and negative controls were prepared. Specimens were stored in an anaerobic workstation, and total and viable bacterial counts were determined. Every 48 h, samples were taken from the reaction tubes to inoculate blood agar plates and to isolate bacterial DNA for quantification using qrt-PCR. In addition, one Acuris test system was subjected to scanning electron microscopy (SEM) to evaluate the precision of fit of the conometric coupling and marginal crown opening. Throughout the observational period of one week, blood agar plates of the specimens showed no viable bacterial growth. qrt-PCR, likewise, yielded a result approaching zero with an amount of about 0.53 × 10−4 µg/mL DNA. While the luting gap/marginal opening between the TiN-cap and the ceramic crown was within the clinically acceptable range, the SEM analysis failed to identify a measurable microgap at the cone-in-cone junction. Within the limits of the in-vitro study it can be concluded that the Acuris conometric interface does not allow for bacterial translocation under non-dynamic loading conditions.
Background: Glucose metabolism in the tumor-microenvironment is a fundamental hallmark for tumor growth and intervention therein remains an attractive option for anti-tumor therapy. Whether tumor-derived factors such as microRNAs (miRs) regulate glucose metabolism in stromal cells, especially in tumor-associated macrophages (TAMs), to hijack them for trophic support, remains elusive.
Methods: Ago-RIP-Seq identified macrophage lactate dehydrogenase B (LDHB) as a target of tumor-derived miR-375 in both 2D/3D cocultures and in murine TAMs from a xenograft mouse model. The prognostic value was analyzed by ISH and multiplex IHC of breast cancer patient tissues. Functional consequences of the miR-375-LDHB axis in TAMs were investigated upon mimic/antagomir treatment by live metabolic flux assays, GC/MS, qPCR, Western blot, lentiviral knockdown and FACS. The therapeutic potential of a combinatorial miR-375-decoy/simvastatin treatment was validated by live cell imaging.
Results: Macrophage LDHB decreased in murine and human breast carcinoma. LDHB downregulation increase aerobic glycolysis and lactagenesis in TAMs in response to tumor-derived miR-375. Lactagenesis reduced fatty acid synthesis but activated SREBP2, which enhanced cholesterol biosynthesis in macrophages. LDHB downregulation skewed TAMs to function as a lactate and sterol/oxysterol source for the proliferation of tumor cells. Restoring of LDHB expression potentiated inhibitory effects of simvastatin on tumor cell proliferation.
Conclusion: Our findings identified a crucial role of LDHB in macrophages and established tumor-derived miR-375 as a novel regulator of macrophage metabolism in breast cancer, which might pave the way for strategies of combinatorial cancer cell/stroma cell interventions.
In combination with radiotherapy, immunotherapy is becoming an increasingly used strategy in treating advanced, recurrent, or metastatic cancer. The evident impact of radiotherapy on local and systemic immune response is an indication of the synergistic effect of these two modalities. There is a strong rationale to combine radiotherapy and immunotherapy to enhance response rates and overcome resistances. Therefore, the combination of radio- and immunotherapy holds a variety of opportunities as well as challenges in treating primary cancer and is progressively tested in curative settings. Brachytherapy is also known as internal radiation therapy and only offers a local therapy option at first glance: due to tumor-specific antigens, released by a high local radiation dose, a systemic immune response could be plausible and eminent. Accordingly, brachytherapy could be an underestimated partner with immuno-therapeutic approaches in both curative and palliative settings, to generate local and systemic response. In this review, we summarized the potential benefit of a potential combination of brachytherapy and immuno-therapeutic approaches vs. the background of limited data.
Background: In developed countries worldwide, the number of older patients is increasing. Pulmonary complications are common in multiple injured patients with chest injuries. We assessed whether geriatric patients develop lung failure following multiple trauma with concomitant thoracic trauma more often than younger patients.
Methods: A retrospective analysis of severely injured patients with concomitant blunt thoracic trauma registered in the TraumaRegister DGU® (TR-DGU) between 2009 and 2018 was performed. Patients were categorized into four age groups: 55–64 y, 65–74 y, 75–84 y, and ≥ 85 y. Adult patients aged 18–54 years served as a reference group. Lung failure was defined as PaO2/FIO2 ≤ 200 mm Hg, if mechanical ventilation was performed.
Results: A total of 43,289 patients were included, of whom 9238 (21.3%) developed lung failure during their clinical stay. The rate of posttraumatic lung failure was seen to increase with age. While lung failure markedly increased the length of hospital stay, duration of mechanical ventilation, and length of ICU stay independent of the patient’s age, differences between younger and older patients with lung failure in regard to these parameters were clinically comparable. In addition, the development of respiratory failure showed a distinct increase in mortality with higher age, from 16.9% (18–54 y) to 67.2% (≥ 85 y).
Conclusion: Development of lung failure in severely injured patients with thoracic trauma markedly increases hospital length of stay, length of ICU stay, and duration of mechanical ventilation in patients, regardless of age. The development of respiratory failure appears to be related to the severity of the chest trauma rather than to increasing patient age. However, the greatest effects of lung failure, particularly in terms of mortality, were observed in the oldest patients.
Background: In order to classify and analyze the parameters of upper body posture, a baseline in the form of standard values is demanded. To this date, standard values have only been published for healthy men aged 18–35 and 41–50 years. Data for male adults aged between 31 and 40 years are lacking.
Methods: The postural parameters of 101 symptom-free male volunteers aged 31–40 (35.58 ± 2.88) years were studied. The mean height of the men was 179.89 ± 7.38 cm, with a mean body weight of 86.36 ± 11.58 kg and an average BMI of 26.70 ± 3.35 kg/m2. By means of video rasterstereography, a 3-dimensional scan of the upper back surface was measured in a habitual standing position. The means or medians, confidence interval, tolerance range, and group comparisons and correlations of BMI and physical activity were calculated for all parameters.
Results: The habitual standing position was found to be almost symmetrical and the axis aligned in the spine, pelvis, and shoulder region, while the spine position was marginally inclined ventrally. The kyphosis angle of the thoracic spine was greater than the lordosis angle of the lumbar spine. All deviations fell under the measurement error margin of 1 mm/1°. The greater the BMI, the greater was the pelvic and scapular distance. The lower the BMI, the further caudally positioned was the right shoulder. The pelvic and scapular distances were also lower with the increasing athleticism of the participants.
Conclusion: The upper body posture of men between the ages of 31 and 40 years was found to be almost symmetrical and axis-conforming, with the kyphosis angle, pelvic distance, and shoulder distance enlarging with increasing BMI. Consequently, postural parameters presented in this survey allow for comparisons with other studies, as well as the evaluation of clinical diagnostics and applications.
Hintergrund und Ziel: Lebenslimitierend erkrankte Kinder und Jugendliche mit komplexem Symptomgeschehen haben Anspruch auf eine spezialisierte ambulante Palliativversorgung (SAPV). In der Richtlinie zur SAPV heißt es lediglich: „Den besonderen Belangen von Kindern und Jugendlichen ist Rechnung zu tragen.“ Das Ziel der Studie ist es deshalb, diese besonderen Belange zu identifizieren und Empfehlungen zur Überarbeitung der SAPV-Richtlinie zu formulieren.
Methoden: Sequenzielles Mixed-Methods-Design mit Fragebogenerhebungen, qualitativen Interviews, teilnehmenden Beobachtungen und Fokusgruppendiskussionen mit Angehörigen, Patient*innen und Leistungserbringer*innen der SAPV in Hessen sowie der Auswertung von Dokumentationsdaten der hessischen SAPV-Teams.
Ergebnisse: Kinder und Jugendliche in der SAPV leiden an komplexen, oftmals seltenen Erkrankungen und bedürfen einer besonders aufwendigen Palliativversorgung durch ein Team mit pädiatrischer Expertise. Die SAPV muss die gesamte Familie einbeziehen und oftmals überregional verteilte Versorger*innen koordinieren. Zudem ist eine besonders aufwendige psychosoziale Versorgung von Patient*innen und Angehörigen notwendig. Die SAPV für Kinder und Jugendliche ist weniger bekannt als die SAPV für Erwachsene und der Zugang für die Familien deshalb oft schwierig. Für lebenslimitierend erkrankte Kinder und Jugendliche, die zwar einer aufsuchenden Palliativversorgung bedürfen, jedoch keinen Bedarf an einer so intensiven Betreuung wie in der SAPV haben, besteht eine Versorgungslücke.
Fazit: Die SAPV von Kindern und Jugendlichen sowie von volljährigen Patient*innen, die seit dem Kindes- und Jugendalter erkrankt sind, bedarf einer eigenständigen Versorgungsform mit Vergütungsmodalitäten, die den besonderen Versorgungsbedarf und -aufwand abbilden.
Background: Routine human papillomavirus (HPV) testing is performed in cervival cancer and is required for classification of some head and neck cancers. In penile cancer a statement on HPV association of the carcinoma is required. In most cases p16 immunohistochemistry as a surrogate marker is applied in this setting. Since differing clinical outcomes for HPV positive and HPV negative tumors are described we await HPV testing to be requested more frequently by clinicians, also in the context of HPV vaccination, where other HPV subtypes are expected to emerge.
Method: Therefore, a cohort of archived, formalin-fixed paraffin embedded (FFPE) penile neoplasias was stained for p16 and thereafter tested for HPV infection status via PCR based methods. Additionally to Sanger sequencing, we chose LCD-Array technique (HPV 3.5 LCD-Array Kit, Chipron; LCD-Array) for the detection of HPV in our probes expecting a less time consuming and sensitive HPV test for our probes.
Results: We found that LCD-Array is a sensitive and feasible method for HPV testing in routine diagnostics applicable to FFPE material in our cohort. Our cohort of penile carcinomas and carcinomas in situ was associated with HPV infection in 61% of cases. We detected no significant association between HPV infection status and histomorphological tumor characteristics as well as overall survival.
Conclusions: We showed usability of molecular HPV testing on a cohort of archived penile carcinomas. To the best of our knowledge, this is the first study investigating LCD-Array technique on a cohort of penile neoplasias.
The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface.
Driven by globalization, urbanization and climate change, the distribution range of invasive vector species has expanded to previously colder ecoregions. To reduce health-threatening impacts on humans, insect vectors are extensively studied. Population genomics can reveal the genomic basis of adaptation and help to identify emerging trends of vector expansion. By applying whole genome analyses and genotype-environment associations to populations of the main dengue vector Aedes aegypti, sampled along an altitudinal gradient in Nepal (200–1300 m), we identify putatively adaptive traits and describe the species' genomic footprint of climate adaptation to colder ecoregions. We found two differentiated clusters with significantly different allele frequencies in genes associated to climate adaptation between the highland population (1300 m) and all other lowland populations (≤800 m). We revealed nonsynonymous mutations in 13 of the candidate genes associated to either altitude, precipitation or cold tolerance and identified an isolation-by-environment differentiation pattern. Other than the expected gradual differentiation along the altitudinal gradient, our results reveal a distinct genomic differentiation of the highland population. Local high-altitude adaptation could be one explanation of the population's phenotypic cold tolerance. Carrying alleles relevant for survival under colder climate increases the likelihood of this highland population to a worldwide expansion into other colder ecoregions.
There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus (“hit and run” theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL.
Observed weather and projected climate change suggest an increase in the transmission of vector-borne diseases (VBDs) in the Hindu Kush Himalayan (HKH) region. In this study, we systematically explore the literature for empiric associations between the climate variables and specific VBDs and their vectors in the HKH region. We conducted a systematic synthesis of the published literature on climate variables, VBDs and vectors in the HKH region until the 8th of December 2020. The majority of studies show significant positive associations of VBDs with climatic factors, such as temperature, precipitation, relative humidity, etc. This systematic review allowed us to identify the most significant variables to be considered for evidence-based trend estimates of the effects of climate change on VBDs and their vectors in the HKH region. This evidence-based trend was set into the context of climate change as well as the observed expansion of VBDs and disease vectors in the HKH region. The geographic range of VBDs expanded into previously considered non-endemic areas of highlands (mountains) in the HKH region. Based on scarce, but clear evidence of a positive relationship of most climate variables and VBDs and the observed climatic changes, we strongly recommend an expansion of vector control and surveillance programmes in areas of the HKH region that were previously considered to be non-endemic.
Background: The number of operations by the German emergency medical service almost doubled between 1994 and 2016. The associated expenses increased by 380% in a similar period. Operations with treatment on-site, which retrospectively proved to be misallocated (OFF-Missions), have a substantial proportion of the assignment of the emergency medical service (EMS). Besides OFF-Missions, operations with patient transport play a dominant role (named as ON-Missions). The aim of this study is to work out the medical and economic relevance of both operation types.
Methods: This analysis examined N = 819,780 missions of the EMS and patient transport service (PTS) in the catchment area of the emergency medical dispatch centre (EMDC) Bad Kreuznach over the period from 01/01/2007 to 12/31/2016 in terms of triage and disposition, urban-rural distribution, duration of operations and economic relevance (p < .01).
Results: 53.4% of ON-Missions are triaged with the indication non-life-threatening patient transport; however, 63.7% are processed by the devices of the EMS. Within the OFF-Mission cohort, 78.2 and 85.8% are triaged or dispatched for the EMS. 74% of all ON-Missions are located in urban areas, 26% in rural areas; 81.3% of rural operations are performed by the EMS. 66% of OFF-Missions are in cities. 93.2% of the remaining 34% of operations in rural locations are also performed by the EMS. The odds for both ON- and OFF-Missions in rural areas are significantly higher than for PTS (ORON 3.6, 95% CI 3.21–3.30; OROFF 3.18, 95% CI 3.04–3.32). OFF-Missions last 47.2 min (SD 42.3; CI 46.9–47.4), while ON-Missions are processed after 79.7 min on average (SD 47.6; CI 79.6–79.9). ON-Missions generated a turnover of more than € 114 million, while OFF-Missions made a loss of almost € 13 million.
Conclusions: This study particularly highlights the increasing utilization of emergency devices; especially in OFF-Missions, the resources of the EMS have a higher number of operations than PTS. OFF-Missions cause immensely high costs due to misallocations from an economic point of view. Appropriate patient management appears necessary from both medical and economic perspective, which requires multiple solution approaches.
Background: The adequate allocation of inpatient care resources requires assumptions about the need for health care and how this need will be met. However, in current practice, these assumptions are often based on outdated methods (e.g. Hill-Burton Formula). This study evaluated floating catchment area (FCA) methods, which have been applied as measures of spatial accessibility, focusing on their ability to predict the need for health care in the inpatient sector in Germany.
Methods: We tested three FCA methods (enhanced (E2SFCA), modified (M2SFCA) and integrated (iFCA)) for their accuracy in predicting hospital visits regarding six medical diagnoses (atrial flutter/fibrillation, heart failure, femoral fracture, gonarthrosis, stroke, and epilepsy) on national level in Germany. We further used the closest provider approach for benchmark purposes. The predicted visits were compared with the actual visits for all six diagnoses using a correlation analysis and a maximum error from the actual visits of ± 5%, ± 10% and ± 15%.
Results: The analysis of 229 million distances between hospitals and population locations revealed a high and significant correlation of predicted with actual visits for all three FCA methods across all six diagnoses up to ρ = 0.79 (p < 0.001). Overall, all FCA methods showed a substantially higher correlation with actual hospital visits compared to the closest provider approach (up to ρ = 0.51; p < 0.001). Allowing a 5% error of the absolute values, the analysis revealed up to 13.4% correctly predicted hospital visits using the FCA methods (15% error: up to 32.5% correctly predicted hospital). Finally, the potential of the FCA methods could be revealed by using the actual hospital visits as the measure of hospital attractiveness, which returned very strong correlations with the actual hospital visits up to ρ = 0.99 (p < 0.001).
Conclusion: We were able to demonstrate the impact of FCA measures regarding the prediction of hospital visits in non-emergency settings, and their superiority over commonly used methods (i.e. closest provider). However, hospital beds were inadequate as the measure of hospital attractiveness resulting in low accuracy of predicted hospital visits. More reliable measures must be integrated within the proposed methods. Still, this study strengthens the possibilities of FCA methods in health care planning beyond their original application in measuring spatial accessibility.
The aim of this study was to investigate gender-specific influences of different symmetric and asymmetric occlusion conditions on postural control during standing and walking. The study involved 59 healthy adult volunteers (41 f/19 m) aged between 22 and 53 years (30.2 ± 6.3 years). Postural control measurements were carried out using a pressure plate by measuring plantar pressure distribution during standing and walking test conditions. Seven different occlusion conditions were tested. Prior to a MANOVA model analysis, the relationship between the two test conditions were checked using a factor analysis with a varying number of factors (between 2 and 10). The plantar pressure distributions during walking and standing are independent test conditions. The coefficient of variance across all variables between the conditions and genders was not significant: t(46) = 1.51 (p = 0.13). No statement can be made whether, or not, the influence of gender is greater than the influence of the conditions. Healthy male and female test subjects did not show any difference between seven occlusion conditions on the plantar pressure distribution while standing or walking. No differences between the genders were found for any of the investigated variables. In contrast to custom-made occlusion splints, simple cotton rolls appear not to influence the neuromuscular system in a systematic manner.