Background: Smartphone-based apps represent a major development in health care management. Specifically in headache care, the use of electronic headache diaries via apps has become increasingly popular. In contrast to the soaring volume of available data, scientific use of these data resources is sparse. Objective: In this analysis, we aimed to assess changes in headache and migraine frequency, headache and migraine intensity, and use of acute medication among people who showed daily use of the headache diary as implemented in the freely available basic version of the German commercial app, M-sense. Methods: The basic version of M-sense comprises an electronic headache diary, documentation of lifestyle factors with a possible impact on headaches, and evaluation of headache patterns. This analysis included all M-sense users who had entered data into the app on a daily basis for at least 7 months. Results: We analyzed data from 1545 users. Mean MHD decreased from 9.42 (SD 5.81) at baseline to 6.39 (SD 5.09) after 6 months (P<.001; 95% CI 2.80-3.25). MMD, AMD, and migraine intensity were also significantly reduced. Similar results were found in 985 users with episodic migraine and in 126 users with chronic migraine. Conclusions: Among regular users of an electronic headache diary, headache and migraine frequency, in addition to other headache characteristics, improved over time. The use of an electronic headache diary may support standard headache care.View less
Background: Lung cancer has been the focus of attention for many researchers in recent years due to its leading contribution to cancer-related death worldwide, with lung adenocarcinoma (LUAD) being the most common histological type. Ferroptosis, a novel iron-dependent form of regulated cell death, can be induced by sorafenib. Emerging evidence shows that triggering ferroptosis has potential as a cancer therapy. This work aimed to build a ferroptosis-related gene signature for predicting the outcome of LUAD. Methods: The TCGA-LUAD dataset was set as the training cohort, and the GSE72094 and GSE68465 datasets were set as the validation cohorts. Sixty-two ferroptosis-related genes were retrieved from the literature. A univariate Cox regression model was constructed for the training cohort to preliminarily screen for potential prognostic ferroptosis-related genes. A gene signature was generated from a LASSO Cox regression model and assessed with the training and validation cohorts through Kaplan-Meier, Cox, and ROC analyses. In addition, the correlation between the risk score and autophagy-related genes was determined by the Pearson test. Finally, GSEA and immune infiltrating analyses were performed to better study the functional annotation of the signature and the role of each kind of immune cell. Results: A ten-gene signature was constructed from the training cohort and validated in three cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognostic value in LUAD. Moreover, a ROC analysis conducted with all cohort data confirmed the predictive ability of the ten-gene signature for LUAD prognosis. A total of 62.85% (308/490) of autophagy-related genes were found to be significantly correlated with risk scores. GSEA detailed the exact pathways related to the gene signature, and immune-infiltrating analyses identified crucial roles for resting mast cells and resting dendritic cells in the prognosis of LUAD. Conclusions: We identified a novel ferroptosis-related ten-gene signature (PHKG2, PGD, PEBP1, NCOA4, GLS2, CISD1, ATP5G3, ALOX15, ALOX12B, and ACSL3) that can accurately predict LUAD prognosis and is closely linked to resting mast cells and resting dendritic cells.View less
Human faces can convey socially relevant information in various ways. Since the early detection of such information is crucial in social contexts, socially meaningful information might also have privileged access to awareness. This is indeed suggested by previous research using faces with emotional expressions. However, the social relevance of emotional faces is confounded with their physical stimulus characteristics. Here, we sought to overcome this problem by manipulating the relevance of face stimuli through classical conditioning: Participants had to learn the association between different face exemplars and high or low amounts of positive and negative monetary outcomes. Before and after the conditioning procedure, the time these faces needed to enter awareness was probed using continuous flash suppression, a variant of binocular rivalry. While participants successfully learned the association between the face stimuli and the respective monetary outcomes, faces with a high monetary value did not enter visual awareness faster than faces with a low monetary value after conditioning, neither for rewarding nor for aversive outcomes. Our results tentatively suggest that behaviorally relevant faces do not have privileged access to awareness when the assessment of the faces' relevance is dependent on the processing of face identity, as this requires complex stimulus processing that is likely limited at pre-conscious stages.View less
Background: Childhood trauma (CT) is associated with altered brain anatomy. These neuroanatomical changes might be more pronounced in individuals with a psychiatric disorder. Post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) are more prevalent in individuals with a history of CT.
Objective: In this study, we examined limbic and total brain volumes in healthy women with and without a history of CT and in females with PTSD or BPD and a history of CT to see whether neuroanatomical changes are a function of psychopathology or CT.
Method: In total, 128 women (N = 70 healthy controls without CT, N = 25 healthy controls with CT, N = 14 individuals with PTSD, and N = 19 individuals with BPD) were recruited. A T1- weighted anatomical MRI was acquired from all participants for Freesurfer-based assessment of total brain, hippocampus, and amygdala volumes. Severity of CT was assessed with a clinical interview and the Childhood Trauma Questionnaire. Group differences in hippocampal and amygdala volumes (adjusted for total brain volume) and total brain volume (adjusted for height) were characterized by analysis of covariance.
Results: Volume of the total brain, hippocampus, and amygdala did not differ between the four groups (p > .05). CT severity correlated negatively with total brain volume across groups (r = −0.20; p = .029).
Conclusions: CT was associated with reduced brain volume but PTSD or BPD was not. The association between CT and reduced brain volume as a global measure of brain integrity suggests a common origin for vulnerability to psychiatric disorders later in life.View less
The temperature-independent effects of electromagnetic fields (EMF) have been controversial for decades. Here, we critically analyze the available literature on non-thermal effects of radiofrequency (RF) and microwave EMF. We present a literature review of preclinical and clinical data on non-thermal antiproliferative effects of various EMF applications, including conventional RF hyperthermia (HT, cRF-HT). Further, we suggest and evaluate plausible biophysical and electrophysiological models to decipher non-thermal antiproliferative membrane effects. Available preclinical and clinical data provide sufficient evidence for the existence of non-thermal antiproliferative effects of exposure to cRF-HT, and in particular, amplitude modulated (AM)-RF-HT. In our model, transmembrane ion channels function like RF rectifiers and low-pass filters. cRF-HT induces ion fluxes and AM-RF-HT additionally promotes membrane vibrations at specific resonance frequencies, which explains the non-thermal antiproliferative membrane effects via ion disequilibrium (especially of Ca²+) and/or resonances causing membrane depolarization, the opening of certain (especially Ca²+) channels, or even hole formation. AM-RF-HT may be tumor-specific owing to cancer-specific ion channels and because, with increasing malignancy, membrane elasticity parameters may differ from that in normal tissues. Published literature suggests that non-thermal antiproliferative effects of cRF-HT are likely to exist and could present a high potential to improve future treatments in oncology.View less
Background: Clinical outcomes in neuromyelitis optica spectrum disorders (NMOSD) vary across different regions.
Objective: To describe clinical profiles in Japanese and German NMOSD patients.
Methods: Medical records of aquaporin-4-immunoglobulin G (AQP4-IgG) positive NMOSD patients from Japan (n = 54) and Germany (n = 38) were retrospectively analyzed.
Results: The disability status was similar between both cohorts, although Japanese patients had a longer disease duration (13.3 ± 11.1 vs. 8.1 ± 6.9 years, p = 0.018) but similar relapse rates. Optic neuritis and myelitis were the most frequent attacks in both cohorts. Brain attacks occurred more frequently in Japanese patients (40.7% vs. 15.8%, p = 0.020). The time from disease onset (median [interquartile range] 2.3 [0.3-10.1] vs. 0.6 [0.2-1.9] years, p = 0.009) and the number of attacks (2.5 [1-7] vs. 2 [1-3], p = 0.047) until start of the first immunotherapy were higher in the Japanese cohort. Rituximab was the most common drug in the German cohort (52.6%) and not given in the Japanese cohort (p < 0.001), where oral prednisolone was the most common drug (92.6% vs. 15.8%, p < 0.001). The frequency of autoimmune comorbidities was higher in the German cohort (39.5% vs. 18.5%, p = 0.047).
Conclusion: Compared with Japanese NMOSD patients, German patients presented with similar disability despite shorter disease duration and earlier and more frequent immunosuppressive therapy.View less
Background: Automated insulin delivery (AID) systems have been shown to be safe and effective in reducing hyperglycemia and hypoglycemia but are not universally available, accessible, or affordable. Therefore, user-driven open-source AID systems are becoming increasingly popular.
Objective: This study aims to investigate the motivations for which people with diabetes (types 1, 2, and other) or their caregivers decide to build and use a personalized open-source AID.
Methods: A cross-sectional web-based survey was conducted to assess personal motivations and associated self-reported clinical outcomes.
Results: Of 897 participants from 35 countries, 80.5% (722) were adults with diabetes and 19.5% (175) were caregivers of children with diabetes. Primary motivations to commence open-source AID included improving glycemic outcomes (476/509 adults, 93.5%, and 95/100 caregivers, 95%), reducing acute (443/508 adults, 87.2%, and 96/100 caregivers, 96%) and long-term (421/505 adults, 83.3%, and 91/100 caregivers, 91%) complication risk, interacting less frequently with diabetes technology (413/509 adults, 81.1%; 86/100 caregivers, 86%), improving their or child's sleep quality (364/508 adults, 71.6%, and 80/100 caregivers, 80%), increasing their or child's life expectancy (381/507 adults, 75.1%, and 84/100 caregivers, 84%), lack of commercially available AID systems (359/507 adults, 70.8%, and 79/99 caregivers, 80%), and unachieved therapy goals with available therapy options (348/509 adults, 68.4%, and 69/100 caregivers, 69%). Improving their own sleep quality was an almost universal motivator for caregivers (94/100, 94%). Significant improvements, independent of age and gender, were observed in self-reported glycated hemoglobin (HbA(1c)), 7.14% (SD 1.13%; 54.5 mmol/mol, SD 12.4) to 6.24% (SD 0.64%; 44.7 mmol/mol, SD 7.0; P<.001), and time in range (62.96%, SD 16.18%, to 80.34%, SD 9.41%; P<.001).
Conclusions: These results highlight the unmet needs of people with diabetes, provide new insights into the evolving phenomenon of open-source AID technology, and indicate improved clinical outcomes. This study may inform health care professionals and policy makers about the opportunities provided by open-source AID systems.View less
The Acute Respiratory Distress Syndrome (ARDS) is common in patients on the Intensive Care Unit and associated with significant mortality rates. In situations of severe respiratory insufficiency and failure of all possible conservative therapeutic approaches, veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a final option for temporary replacement of pulmonary function. ARDS as well as sepsis and VV ECMO treatment are all associated with intravascular hemolysis. The extent and relevance of intravascular hemolysis in the context of ARDS therapy is unclear. This systematic review aims to summarize the current evidence on the incidence and associated complications of intravascular hemolysis in adult patients with ARDS and treatment with VV ECMO. The databases MEDLINE, EMBASE and Web of Science were systematically searched and 19 publications fulfilled inclusion criteria. The incidence of hemolysis in patients with ARDS and treatment with VV ECMO ranged from 0 to 41% with survivors showing lower incidences and less severe hemolysis. A pump head thrombosis and high blood flows (>= 3 l/min) as well as use of dual-lumen cannulas but not different pump models were associated with increased hemolysis. In conclusion, intravascular hemolysis in patients with ARDS and treatment with VV ECMO is a common and relevant complication that appears associated with increased mortality. Apart from ECMO hardware-settings, no additional possible causes for increased red cell breakdown such as disease severity, duration of ECMO therapy, or number and quality of red blood cell transfusions were investigated. Further research is needed to determine the origin and relevance of intravascular hemolysis in patients with ARDS and treatment with VV ECMO.View less
Introduction: An advance directive (AD) is a written legal document in which a person can express wishes and preferences for medical treatment for the moment when that person is no longer able to make medical decisions because of a serious illness or injury. While ADs have emerged in public, it is unclear, how many adults in Germany have completed an AD, and frequencies differ among different patient cohorts and medical settings. The aim of this study was to evaluate how many patients visiting a trauma emergency room (ER) in an academic teaching hospital had completed an AD. Furthermore, patient characteristics were compared between patients who had completed an AD and those who had not completed an AD.
Methods: Patients with a traumatic injury or disease who attended the ER of an academic teaching hospital in the period from October 2015 to March 2016 (n = 499) were surveyed for completion rates of ADs.
Results: Prior to their visit to the ER, 12.8% of the included patients possessed a completed AD. Patients with a completed AD had a higher age (median age: 54 (IQR: 34-66) vs. 35 (IQR: 25-50) p<0.001) and were less often living in an urban residential location (UR) (UR: 23.5% vs. 39.4%, p=0.029). Groups did not differ between sex (p=0.115), frequencies of high school graduates (p=0.482), and possession of a private health insurance (p=0.072), disability insurance (p=0.291), or an accident insurance (p=0.790).
Conclusion: Completion rates of ADs remain low among patients visiting an ER of an academic teaching hospital in Germany. Increasing age but not factors such as sex, educational background, or insurance status were associated with a higher frequency of completed ADs.View less
Purpose: Nesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development.
Methods: In this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9 ± 3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3 ± 2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors.
Results: Sex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-γ, Interleukin-1β, IL-2, 4, 5, 6, 7, 10, 12 and TNF-α) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05).
Conclusion: As a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.View less
Purpose: Focal segmental glomerulosclerosis (FSGS) is a common cause for end-stage renal disease that can recur in the graft after kidney transplantation. The incidence of FSGS recurrence is reported in up to 47% of patients, predisposing those to possible poorer transplantation outcomes. Hence, we examined the incidence of FSGS recurrence and the effect on graft outcome in our patient cohort of living donor kidney transplantations (LDKT).
Patients and Methods: We analyzed 194 adult patients who received a LDKT between 2011 and 2017 of which 22 (11%) had FSGS as underlying disease. Demographic data and clinical outcomes, especially regarding recurrence of FSGS, were evaluated.
Results: FSGS recurrence was identified in three (14%) patients within three months after transplantation, of whom two patients (9%) lost their graft. There was no significant difference in graft survival comparing FSGS to other reasons for end-stage renal disease.
Conclusion: Incidence of FSGS recurrence in the present patient cohort was within the range reported in the literature and comparatively low. Our data support LDKT as a treatment option in patients with end-stage renal disease due to FSGS.View less
Background: Donor-specific antibodies (DSA) against donor human leukocyte antigen after liver transplantation, which are associated with histological changes, have been widely studied with respect to their sustained impact on transplant function. However, their long-term impact after liver transplantation remains unclear.
Methods: We performed a cross-sectional analysis from June 2016 to July 2017 that included all patients who presented themselves for scheduled follow-up after receiving a liver transplantation between September 1989 and December 2016. In addition to a liver protocol biopsy, patients were screened for human leukocyte antigen antibodies (HLAab) and donor-specific antibodies. Subsequently, the association between human leukocyte antigen antibodies, donor-specific antibodies, histologic and clinical features, and immunosuppression was analyzed.
Results: Analysis for human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was performed for 291 and 271 patients. A significant association between higher inflammation grades and the presence of human leukocyte antigen antibodies and donor-specific antibodies was detected, while fibrosis stages remained unaffected. These results were confirmed by multivariate logistic regression for inflammation showing a significant increase for presence of human leukocyte antigen antibodies and donor-specific antibodies (OR: 4.43; 95% CI: 1.67-12.6; p=0.0035). Furthermore, the use of everolimus in combination with tacrolimus was significantly associated with the status of negative human leukocyte antigen antibodies and donor-specific antibodies. Viral etiology for liver disease, hepatocellular carcinoma (HCC) and higher steatosis grades of the graft were significantly associated with a lower rate of human leukocyte antigen antibodies. The impact of human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was associated with higher levels of laboratory parameters, such as transaminases and bilirubin.
Conclusion: Donor-specific antibodies against donor human leukocyte antigen are associated with histological and biochemical graft inflammation after liver transplantation, while fibrosis seems to be unaffected. Future studies should validate these findings for longer observation periods and specific subgroups.View less
Background: Patients affected by chronic kidney disease are at a risk of cardiovascular morbidity and mortality. Body fluids unbalance is one of the main characteristics of this condition, as fluid overload is highly prevalent in patients affected by the cardiorenal syndrome. Summary: We describe the state of the art and new insights into body volume evaluation. The mechanisms behind fluid balance are often complex, mainly because of the interplay of multiple regulatory systems. Consequently, its management may be challenging in clinical practice and even more so out-of-hospital. Availability of novel technologies offer new opportunities to improve the quality of care and patients' outcome. Development and validation of new technologies could provide new tools to reduce costs for the healthcare system, promote personalized medicine, and boost home care. Due to the current COVID-19 pandemic, a proper monitoring of chronic patients suffering from fluid unbalances is extremely relevant. Key Message: We discuss the main mechanisms responsible for fluid overload in different clinical contexts, including hemodialysis, peritoneal dialysis, and heart failure, emphasizing the potential impact provided by the implementation of the new technologies.View less
In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, Black race, disagreement between creatinine- and cystatin C-based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.View less
Introduction: On the basis of the results of the IMBRAVE-150 trial, the combination of atezolizumab, a programmed cell death ligand 1 (PD-L1) antibody, as well as bevacizumab, a vascular endothelial growth factor (VEGF) antibody, represents a promising novel first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Despite favorable safety data, serious adverse events have been described. However, central nervous system complications such as encephalitis have rarely been reported. We present the case of a 70-year-old woman with hepatitis C virus (HCV)-related liver cirrhosis and advanced HCC who developed severe encephalitis after only one cycle of atezolizumab/bevacizumab.
Patient concerns: Ten days after administration, the patient presented with confusion, somnolence, and emesis. Within a few days, the patient's condition deteriorated, and mechanical ventilation became necessary.
Diagnosis: Cerebrospinal fluid (CSF) analysis showed increased cell count and elevated protein values. Further work-up revealed no signs of an infectious, paraneoplastic, or other autoimmune cause.
Intervention: Suspecting an atezolizumab/bevacizumab-related encephalitis, we initiated a high-dose steroid pulse therapy as well as repeated plasmapheresis, which resulted in clinical improvement and remission of CSF abnormalities.
Outcome: Despite successful weaning and transfer to a rehabilitation ward, the patient died of progressive liver cancer 76 days after initial treatment with atezolizumab/bevacizumab, showing no response.
Conclusion: This case illustrates that rapid immunosuppressive treatment with prednisolone can result in remission even of severe encephalitis. We discuss this case in the context of available literature and previously reported cases of atezolizumab-induced encephalitis in different tumor entities, highlighting the diagnostic challenges in oncologic patients treated with immune checkpoint-inhibitors.
Abbreviations: AE = adverse events, AFP = alfa-fetoprotein, BCLC = Barcelona Clinic of Liver Cancer, CK = creatine-kinase, CRP = C-reactive protein, CSF = cerebrospinal fluid, CT = computer tomography, CTCAE = Common Terminology Criteria for Adverse Events, CTLA-04 = cytotoxic T-lymphocyte-associated protein 4, EMG = electromyography, HCC = hepatocellular carcinoma, HCV = hepatitis C-virus, irAE = immune-related adverse events, MELD = Model of End-stage liver disease, MRI = magnetic resonance imaging, PDGFR = platelet-derived growth factor receptor, PD-L1 = programmed cell death ligand 1, TSH = thyroid-stimulating hormone, VEGF = vascular endothelial growth factor, VEGFR = vascular endothelial growth factor receptor.View less
The optimal fixation technique in periacetabular osteotomy (PAO) remains controversial. This study aims to assess the in vivo stability of fixation in PAO with and without the use of a transverse screw. We performed a retrospective study to analyse consecutive patients who underwent PAO between January 2015 and June 2017. Eighty four patients (93 hips) of which 79% were female were included. In 54 cases, no transverse screw was used (group 1) compared with 39 with transverse screw (group 2). Mean age was 26.5 (15–44) in group 1 and 28.4 (16–45) in group 2. Radiological parameters relevant for DDH including lateral center edge angle of Wiberg (LCEA), Tönnis angle (TA) and femoral head extrusion index (FHEI) were measured preoperatively, post-operatively and at 3-months follow-up. All patients were mobilized with the same mobilization regimen. Post-operative LCEA, TA and FHEI were improved significantly in both groups for all parameters (P ≤ 0.0001). Mean initial correction for LCEA (P = 0.753), TA (P = 0.083) and FHEI (P = 0.616) showed no significant difference between the groups. Final correction at follow-up of the respective parameters was also not significantly different between both groups for LCEA (P = 0.447), TA (P = 0.100) and FHEI (P = 0.270). There was no significant difference between initial and final correction for the respective parameters. Accordingly, only minimal loss of correction was measured, showing no difference between the two groups for LCEA (P = 0.227), TA (P = 0.153) and FHEI (P = 0.324). Transverse screw fixation is not associated with increased fragment stability in PAO. This can be taken into account by surgeons when deciding on the fixation technique of the acetabular fragment in PAO.View less
In the early medieval west, patronate, as adapted from Roman law, was a fundamental category in determining the legal status of freedmen. In many cases it entailed a basic set of obligations. In an increasing number of situations, however, the patron became an ecclesiastical institution, since slaves and freed persons were often given to churches and monasteries. As ecclesiastical institutions regarded their patronal rights over freed persons as part of inalienable church property, the patronal relationship became permanent and inheritable. In Eastern Francia (the Rhineland and beyond) this transformed ecclesiastical freedmen into religiously defined social groups with potentially distinct aims, religious tasks, and organizational structures, and a shared notion of freedom. From the Carolingian period onward, it even became attractive to enter voluntarily into this status. It is argued here that with its underlying network of socio-religious relations, patronate over ecclesiastical freedmen and censuales can be better understood when considered as an element of a ‘temple society’.View less
Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (p = 0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R-2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.View less
Background Fabry disease (FD) is a rare lysosomal storage disorder with multiorgan manifestation and associated with an increased morbidity and mortality. Fabry cardiomyopathy includes left ventricular `hypertrophy' (LVH), cardiac arrhythmias, and heart failure. We report a case of an untreated FD with characteristic findings in electrocardiogram (ECG) over a follow-up period of 10 years. Case summary A 53-year-old man with FD presented to our outpatient department. He suffered from symptomatic ventricular extrasystoles. Echocardiography detected LVH and reduced global longitudinal strain. Twelve years ago, first examination was conducted due to ventricular arrhythmias. Electrocardiogram showed a short PQ minus P-wave (PendQ) interval and negative T-waves. Over time, the number of leads with negative T-waves increased. Moreover, the echocardiography revealed a thickened left ventricular wall. Without any further examinations at that time, the patient was treated for arterial hypertension with proteinuria. Ten years after first symptoms appeared, FD was diagnosed utilizing cardiac magnetic resonance imaging and genetic tests. Hence, enzyme replacement therapy was initiated. Discussion The ECG is a fast diagnostic method and it may - even without additional organ manifestations - provide preliminary suspicion of FD. In particular, as shown in our case, a short PendQ and QT interval indicate FD. Over time, disease progression can be detected through ECG changes. T-waves correlate with an increasing LVH and a reduction in longitudinal function in echocardiographic examinations. Unexplained LVH must be followed by differential diagnosis. In case of confirmed FD, patients should be treated by multidisciplinary teams in experienced centres.View less
Objectives In this study, we investigated daily fluctuations in molecular (gene expression) and physiological (biomechanical muscle properties) features in human peripheral cells and their correlation with exercise performance. Methods 21 healthy participants (13 men and 8 women) took part in three test series: for the molecular analysis, 15 participants provided hair, blood or saliva time-course sampling for the rhythmicity analysis of core-clock gene expression via RT-PCR. For the exercise tests, 16 participants conducted strength and endurance exercises at different times of the day (9h, 12h, 15h and 18h). Myotonometry was carried out using a digital palpation device (MyotonPRO), five muscles were measured in 11 participants. A computational analysis was performed to relate core-clock gene expression, resting muscle tone and exercise performance. Results Core-clock genes show daily fluctuations in expression in all biological samples tested for all participants. Exercise performance peaks in the late afternoon (15-18 hours for both men and women) and shows variations in performance, depending on the type of exercise (eg, strength vs endurance). Muscle tone varies across the day and higher muscle tone correlates with better performance. Molecular daily profiles correlate with daily variation in exercise performance. Conclusion Training programmes can profit from these findings to increase efficiency and fine-tune timing of training sessions based on the individual molecular data. Our results can benefit both professional athletes, where a fraction of seconds may allow for a gold medal, and rehabilitation in clinical settings to increase therapy efficacy and reduce recovery times.View less