Researchers at the German Center for Infection Research (DZIF) at Heidelberg University Hospital have decoded a previously unknown mechanism by which HIV-1 selects its integration targets in the human genome. A research team led by DZIF scientist Dr. Marina Lusic identified RNA:DNA hybrids (R-loops) as molecular signposts for the virus. These findings reveal a key vulnerability in the life cycle of HIV-1. The results, published in the renowned journal Nature Microbiology, provide new therapeutic approaches for specifically controlling HIV reservoirs in the body. This has been one of the biggest obstacles to long-term or curative HIV therapies.
Thanks to antiretroviral therapy, people living with HIV can lead almost normal lives. Antiretroviral drugs prevent the virus from multiplying, but must be taken daily for life. However, any interruption in treatment—due to limited access, supply disruptions, or adherence challenges—can result in rapid viral rebound and, more worryingly, the emergence of drug-resistant HIV variants.
The HIV virus primarily infects cells of the immune system, anchoring its genetic material in T cells in particular. Once integrated, these viral sequences create lifelong reservoir of infection. The HIV-1 integrase enzyme is responsible for inserting the virus into the host genome, forcing cells to produce new viruses and enabling the ongoing infection process. "Until now, it has been not entirely clear how HIV-1 integrase selects its integration targets in the genome. A deeper understanding of this process is crucial for developing new treatment strategies and tackling the persistent viral reservoirs that cannot be eliminated by existing therapies," says Dr. Marina Lusic, DZIF scientist at the Center for Integrative Infectious Disease Research (CIID) at Heidelberg University Hospital, who led the study.
The research team was able to prove that HIV-1 does not randomly invade the genome, but uses specific signposts: so-called RNA:DNA hybrids or “R-loops”, which mainly occur in non-coding regions of active genes. The researchers mapped these structures in human immune cells and demonstrated that the viral integrase docks precisely at these locations. “The virus follows these structures like signposts on a map and thus finds the appropriate integration sites,” explains Dr. Carlotta Penzo, senior postdoctoral researcher in Dr. Marina Lusic's team and first author of the study. “Another important result of our investigation is that a specific cellular partner, the enzyme Aquarius, helps the virus in R-loop recognition, enabling HIV-1 insertion into RNA:DNA hybrids.”
The splicing enzyme RNA helicase Aquarius (AQR) plays a key role in this process. It acts as a kind of door opener, binding to HIV-1 integrase and promoting integration by unwinding the R-loops. “Our results show that removing AQR significantly decreases the integration rate. The remaining integration events shift to R-loop-poor regions—clear evidence of the association between viral integration and AQR activity on R-loops,” says Penzo.
“This discovery opens a new avenue for HIV intervention. If we can disrupt the virus’s ability to use host RNA structures for integration, we may be able to limit or redirect where HIV hides and ultimately reduce or eliminate the need for lifelong therapy,” says Dr. Marina Lusic. “These findings are particularly significant in light of the increasing global instability in HIV care. In many regions, the continuous provision of antiretroviral therapies is not guaranteed—with the result that interruptions significantly increase the risk of treatment failure and the spread of resistant virus variants.”
The results reveal previously unknown targets for combating HIV. In the long term, the identified R-loop/Aquarius mechanism could help to specifically target HIV reservoirs in the body that existing therapies cannot eliminate—and thus point the way to new, effective, and potentially curative forms of treatment.
This study was supported by the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung, DZIF) and by the German Research Foundation (DFG) through the Special Collaborative Programme SFB 1129. It was conducted through a multidisciplinary collaboration led by the group of Dr. Marina Lusic, in partnership with colleagues from the Center for Integrative Infectious Disease Research (CIID) Heidelberg, including Prof. Oliver Fackler and Prof. Hans-Georg Kräusslich. Furthermore, the study was made possible by close pan-European collaboration, with contributions from bioinformatics, structural biology and retrovirology experts at research institutions in Zagreb, Padua, London and Bordeaux.
Source: DZIF
On 18 September, the five German Centers for Health Research (DZG) located in northern Germany met for the first DZG North Day to discuss existing collaborations and ways to strengthen their cooperation.
About 100 DZG researchers from Hamburg, Mecklenburg-Western Pomerania and Schleswig-Holstein gathered at the University Medical Center Hamburg-Eppendorf (UKE) for an intensive exchange.
The acting DZG spokesperson, Prof. Werner Seeger, welcomed the DZG scientists and provided an overview of the history, present and future of the DZGs. He stated that the vision should be: to avoid diseases completely. This would constitute true prevention and be one of the central themes of the DZGs. Seeger said that we work together to have a positive impact on the health of all people worldwide.
Board representatives from the northern DZG sites informed about structure and current research priorities of their centers. Individual research projects were then presented in two-minute speed talks on the topics infrastructure, translation, mechanisms, patients, prevention and diagnosis & therapy. These were then discussed in detail in the following poster session.
The afternoon began with welcome addresses by Maryam Blumenthal, Hamburg's Senator for Science, and Blanche Schwappach-Pignataro, UKE's Dean. Both emphasised the outstanding importance of the DZGs for health research in northern Germany. Senator Blumenthal expressed her continued support for the DZGs.
The afternoon focused on selected ongoing cooperation projects between the DZGs. These included machine learning approaches that can be applied to more than just cardiovascular diseases, and how to involve children and young people in research projects.
During the final session of DZG North Day, two patient representatives described their work on the patient advisory boards of their DZGs, explaining what motivates them: they are keen to contribute the perspectives of patients and their families and support initiatives that facilitate this, such as the DZGs.
In his closing remarks, Prof. Julian Schulze zur Wiesch, spokesperson for the DZIF site Hamburg/Lübeck/Borstel/Riems, emphasised the importance of the DZG North Day. Networking through personal contact is particularly possible at the local level. Follow-up events, this time in Schleswig-Holstein and Mecklenburg-Western Pomerania, are intended to further strengthen cooperation between the DZGs.
Type 1 diabetes develops when the immune system destroys the insulin-producing cells in the pancreas. While conventional therapies usually only take effect after the onset of the disease, a research team from Helmholtz Munich, the German Center for Diabetes Research (DZD) and Goethe University Frankfurt is investigating a novel drug that acts earlier. Vidofludimus calcium, which is already being tested for multiple sclerosis, could help to prevent type 1 diabetes by restoring balance to the immune system and stopping the misdirected immune response. The findings were published in 'Molecular Metabolism'.
Type 1 Diabetes (T1D) is a chronic autoimmune disease that destroys insulin-producing beta cells in the pancreas, resulting in lifelong insulin dependence and serious health complications. While early diagnosis can help manage the disease, researchers are urgently seeking treatments that can go beyond symptom management to slow or stop disease progression.
In a collaborative effort, researchers from the German Center for Diabetes (DZD) at the Research Unit Type 1 Diabetes Immunology (TDI) at Helmholtz Munich, together with scientists from the Goethe University Frankfurt, have identified a promising new therapeutic approach. Their study demonstrates the potential of vidofludimus calcium, a next-generation immunomodulatory drug, to alter the course of T1D by blocking a key metabolic pathway in immune cells.
Vidofludimus calcium, currently in phase 3 clinical trials for multiple sclerosis and developed by Immunic Therapeutics, selectively inhibits the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme plays a critical role in pyrimidine synthesis, which is essential for the proliferation of rapidly dividing immune cells involved in autoimmunity.
In two different pre-clinical mouse models of T1D, treatment with vidofludimus calcium significantly reduced disease incidence. On the cellular level, the drug both decreased the activation of pathogenic T cells and increased the frequency of protective regulatory T cells (Tregs) – a subtype of immune cells crucial for suppressing autoimmune responses.
“With this publication we discover for the first time that inhibiting the enzyme DHODH fosters immune-protective Tregs during islet autoimmunity and delays the progression to overt T1D in pre-clinical models,” says Prof. Carolin Daniel, the corresponding author of the study.
These findings represent a critical step toward immune-modulatory therapies for T1D that go beyond symptom management to directly influence the underlying autoimmune response. By restoring balance between harmful and protective immune cells, such approaches could offer a way to slow or prevent the progression of autoimmune diabetes in at-risk individuals.
Source: DZD
The OncoRay – National Center for Radiation Research in Oncology gets the world's first single-source photon-counting computer tomography (PCCT) system installed in a radiotherapy department. This system counts every single X-ray photon that passes through the patient, enabling the acquisition of more detailed images with more anatomical and functional information. The expected benefits of using PCCT technology in radiotherapy are now to be investigated and quantified in detail. This further highlights OncoRay's pioneering role in CT-based treatment planning for proton therapy.
Radiotherapy is one of the standard methods used to treat malignant tumors. The aim is to damage the tumor cells' DNA in order to ultimately destroy them. Proton radiotherapy is considered particularly gentle on patients.
OncoRay – supported by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR), the Medical Faculty of TU Dresden, and the Carl Gustav Carus University Hospital – is considered a pioneer in the development and clinical introduction of technological innovations in proton therapy. In 2019, OncoRay clinically implemented DirectSPR, the most accurate method to date for CT-based calculation of proton penetration depth in patients, into patient care. The problem is that due to uncertainty in the proton range, healthy tissue surrounding the tumor must also be irradiated to ensure complete tumor coverage. The DirectSPR method, which is based on dual-energy CT, has made it possible to reduce the required safety margins by around 35 percent. However, this procedure could only be used for immobile tumors, such as those in the head or pelvis.
This gap will now be closed with the new PCCT technology. Siemens Healthineers introduced this groundbreaking technology in 2021. Previously, it was used exclusively in radiology for diagnostic purposes. At the end of May of this year, Siemens Healthineers introduced the next generation of PCCT scanners, which are now approved for use in radiotherapy as well. The world's first installation of this new generation single-source, photon-counting CT scanner , the NAEOTOM Alpha.Prime, in a radiotherapy department has now been realized at OncoRay.
“Siemens Healthineers has been cooperating successfully with OncoRay for many years in the field of CT imaging for radiotherapy. We are proud to now provide our partner with photon-counting computed tomography for radiotherapy and proton therapy. With the introduction of the NAEOTOM Alpha class, we are delivering on our promise to make powerful photon-counting technology accessible to more physicians and patients," said Gabriel Haras, Head of Cancer Therapy Imaging at Siemens Healthineers.
For Prof. Christian Richter, Head of the Department of Medical Radiation Physics at OncoRay and Principal Investigator for CT imaging in radiotherapy at HZDR, photon-counting detectors are the future of CT technology. "PCCT technology combines several advantages for its application in radiotherapy. It provides better and more accurate CT datasets, allowing us to plan radiation treatments more precisely and with a reduced imaging dose. In ten years, I can't imagine anything other than all CTs used for quantitative imaging being based on this technology. As OncoRay prioritizes patient care and research equally, research and clinical treatments go hand in hand. This means that technological advantages are clinically implemented as quickly as possible, allowing patients to directly benefit from successful translational research.“
PCCT technology offers numerous advantages for radiotherapy that the researchers at OncoRay will now evaluate and quantify in detail. For example, it is possible to increase the spatial resolution of images compared to conventional CT technology, achieve the same image quality with a lower imaging dose, or possibly both simultaneously. The scientists also assume that proton therapy can be planned even more accurately. More precise quantitative information on tissue properties could lead to more accurate predictions of the proton range in patients, ultimately enabling a further reduction in the safety margin. Both, imaging and treatment, will therefore be gentler. Importantly, PCCT will also enable the use of the DirectSPR approach for moving targets, allowing more patients to benefit from highly precise proton therapy.
Prof. Mechthild Krause, Director of OncoRay and Spokesperson at the DKTK Partner site Dresden, emphasizes: “With the detailed evaluation of the new CT technology and its subsequent gradual introduction into clinical practice, we are further strengthening our position as a leading centre for translational research in radiation oncology.” Professor Esther Troost, Head of the HZDR Department of Image-Guided Radiooncology, Dean of the Faculty of Medicine and, alongside Professor Krause, Director of the Clinic and Polyclinic for Radiation Therapy and Radiooncology, expects that the new PCCT device will be introduced gradually into patient care following a testing period. “In addition to enabling radiotherapy with fewer side effects, the PCCT images may even allow us to predict how the tumor will respond to therapy. Then, we can adapt the radiation treatment accordingly.”
Around 2,500 tumor patients per year are irradiated at the Departement of Radiation Oncology.
The new PCCT device is expected to be ready for use by mid-July, after the systems installation and commissioning has been finalized. The Federal Ministry of Research, Technology and Space (BMFTR) is funding the purchase of the PCCT device at OncoRay with a total of two million euros.
Source: DKTK
Strengthening spin-offs of biomedical start-ups from academic institutions — the Forum Health Research has developed concrete recommendations for this purpose. The goal: to bring innovative biomedical products and technologies into practical and economic application as quickly as possible, thereby improving care for patients. To promote the transfer of research results through spin-offs, the Forum Health Research issues recommendations, among other things, to improve the framework conditions for spin-off processes as well as to strengthen the founding culture and education for entrepreneurship. The DZG are itself involved in the Forum Health Research and supports its recommendations.
Spin-offs of start-ups play an important role in transferring biomedical research results from academic institutions into economic application. Germany still has catching up to do in innovation transfer and spin-offs. To better utilize existing potentials and promote spin-offs in biomedical research, the Forum Health Research aims to contribute to improvement with its recommendation paper developed in exchange with numerous stakeholders. It is addressed to university and non-university research institutions and their researchers as well as to regulators, legislators, funding organizations, and investors.
Contributions from all involved actors are necessary to streamline the processes for spin-offs in biomedical research, create incentives, promote cultural change, and enable more flexibility. The recommendation paper shows numerous positive examples both in Germany and internationally and provides concrete recommendations on how these can be expanded, adapted, and further developed. The coalition agreement of the federal government also foresees measures to strengthen start-ups.
The 21 recommendations specifically and practically address the framework conditions for spin-off processes, the strengthening of founding culture and education for entrepreneurship, permeability between industry, start-ups, and academic institutions, capital acquisition, as well as the design of participation forms and licensing modalities.
Among other things, the Forum Health Research recommends:
The recommendations of the Forum Health Research are supplemented by a compilation of strategy papers, tools, and examples, as well as notes on current bureaucratic reduction processes and reimbursement pathways for innovations.
Download des Empfehlungspapiers (in German)
Source: DLR Projektträger
Obesity plays a crucial role in how severely blood vessels are damaged – and this depends on where excessive fat accumulates in the body. This is the finding of a research team from the German Centre for Cardiovascular Research (DZHK) and the University Medical Center Göttingen (UMG), working together with international collaborators.
Led by Prof. Andreas Fischer, director of the Department of Clinical Chemistry at the University Medical Center Göttingen, and Dr Sana Hasan, scientist at the same department, the researchers were able to show for the first time that so-called white adipose tissue in the abdomen and under the skin responds differently to overnutrition. This leads to varying degrees of damage to the blood vessels – a process that can cause inflammation, impaired blood flow, and ultimately cardiovascular disease.
The study adds an important piece to the puzzle of why abdominal fat is particularly harmful: in this visceral fat tissue, as it is known in medical terms, obesity triggers vascular remodeling that promotes inflammation and dysfunction. In contrast, the researchers found a special type of blood vessel cell in subcutaneous fat tissue – cells with tiny “windows” known as fenestrated endothelial cells. In a healthy state, these cells appear to support tissue function. However, in obesity, they become significantly reduced.
“Our findings show that vascular changes in obesity begin earlier than previously thought – and that they differ considerably depending on fat location,” explains Fischer. “This places the blood vessels themselves more at the center of research on obesity and metabolic diseases.”
The team also identified an important signaling molecule necessary for maintaining vascular structure in fat tissue – VEGFA. When VEGFA levels drop, for instance due to a long-term high-fat diet, the blood vessels begin to lose both structure and function. “This mechanism can be observed not only in mice but also in human fat tissue,” says Fischer. “It opens up new strategies for preserving or restoring vascular health in obesity.”
The published study combines cutting-edge single-cell analyses with imaging techniques and genetic experiments, offering an unprecedented level of detail. “These results provide a valuable foundation for future therapies – such as approaches to specifically improve blood vessel function in fat tissue and prevent secondary diseases like diabetes or heart attacks,” first author of the study Hasan concludes.
Source: DZHK
Researchers at the DZNE and the University Hospital Bonn are developing an AI-supported system to assist doctors in treating strokes. Using data from the 'German Stroke Registry' and additional brain images, they aim to improve predictions about health outcomes following thrombectomy, a minimally invasive treatment. This project is breaking new ground with 'Swarm Learning': sensitive patient data remains securely on site, while the algorithm travels digitally from clinic to clinic, learning locally and combining knowledge centrally. This creates a secure AI system. The ultimate goal is to establish a network of clinics that leverage AI to deliver faster and more effective stroke treatment.
A stroke is manifested by neurological symptoms, such as speech deficits or paralysis. The most common cause are blood clots: plugs in brain vessels that obstruct blood flow and thus oxygen supply. This situation is referred to as “ischemic” stroke. “In such an event millions of brain cells die every minute unless countermeasures are taken quickly. This is very time-critical. Time is brain, as they say,” explains Dr. Omid Shirvani, a physician and DZNE scientist.
Possible measures are for example medicinal dissolving of the blood clot or mechanical thrombectomy, a minimally invasive procedure that aims to remove vessel blockage by means of a special catheter. “The type of treatment is decided on a case-by-case basis, depending on factors such as for example the size of the occluded vessel. Based on all available information in an individual case, does thrombectomy have good prospects of success, or does it pose an excessive risk of complications? We aim to develop an AI-based decision-making tool to help with this assessment. It is intended to support doctors who need to act quickly in the event of a stroke. That is our long-term goal. Actual implementation will certainly take some time. But we want to lay the groundwork for this and prove in the current project that our approach does basically work,” says Shirvani.
He emphasizes: “We don’t want a black box, the predictions of our computer model should be comprehensible to doctors, so they can make an informed decision for the benefit of the individual patient. That is, our AI needs to have what is called “explainability” and show the features its assessment is based upon. In addition, clear criteria must be developed to ensure that the AI is applied only to patients whom it can assess with high reliability.”
AI relies on algorithms being trained on large amounts of data in order to recognize patterns. The larger the pool of training data, usually the better the AI will learn. The researchers therefore intend to combine data from the “German Stroke Registry” with additional brain images generated by magnetic resonance imaging (MRI) or computer tomography (CT). This central registry holds data on the treatment of ischemic strokes from over 20 hospitals across Germany. It contains thousands of cases.
“This information comes from the initial examination and follow-up care after a thrombectomy up to three months after intervention. These are primarily detailed entries from the medical records. Associated MRI or CT images of the brain are not included. However, in general, these are kept at the respective hospitals. And there are references in the registry so that images can be clearly assigned”, says Prof. Gabor Petzold, Director of the Department of Vascular Neurology at the UKB and Director of Clinical Research at DZNE. “These images contain information that cannot be fully documented in a medical report but which is very valuable for training our AI. That’s why we want to link this local data with the information from the central registry.”
This is where “Swarm Learning” comes into play. The innovative AI technology is the centerpiece of the current effort. “Traditionally, image data would be collected centrally. However, given the huge amounts of data involved, this is complex and difficult to scale if the network of partners is to grow. And since this is personal data, sharing it requires legal regulations that take a considerable amount of time to comply with. That’s why we’re taking a different approach. The image data available at the various sites remains local,” explains Dr. Anna Aschenbrenner, biomedical scientist at DZNE who is also playing a key role in the project.
“This allows us to easily comply with data protection regulations and means that we don’t have to move and duplicate large amounts of data. Instead, we send the algorithm to the data via the internet. We let the AI travel from place to place, so to speak, in order to learn. That is the core idea behind Swarm Learning.”
This approach was developed by DZNE in collaboration with IT company Hewlett Packard Enterprise and is currently being applied in various DZNE projects. The term “Swarm” refers to the partners interacting within the network. “With Swarm Learning, everyone involved benefits from the collective data pool without having to share their own data. This data remains on site and confidential in accordance with data protection regulations. This is because the algorithm only extracts parameters without any personal references,” explains Prof. Joachim Schultze, Director of Systems Medicine at DZNE, who is also a professor at the University of Bonn.
“The result is a trained AI that has learned at all network nodes. It has assimilated the collective knowledge and can even evolve as new data is introduced. In our specific case, we would then have an AI-based computer model that could support doctors in treating strokes. All network partners could use this tool. Regardless of whether they have large or small amounts of their own data, they would all benefit equally from participating in the swarm.”
Starting with three clinics, including the University Hospital Bonn, the researchers intend to gradually expand their approach to other members of the “German Stroke Registry”. For testing purposes, they will start with multicentric data from the “German Stroke Registry” available in Bonn and use it to simulate a swarm in DZNE’s computing center before transferring the system to geographically separate locations. “We want to lay the foundation for a nationwide network,” says Aschenbrenner. “Furthermore, we are already in talks with partners in the UK to continue our concept internationally. I think there is a lot of room for development.”
The project is being funded by the Helmholtz Association with 250,000 euros. The CISPA Helmholtz Center for Information Security is also involved.
Source: DZNE
According to a new representative study, almost 13 per cent of 18 to 59-year-olds in Germany have experienced sexualised violence at least once - an extrapolated figure of 5.7 million people. The study, initiated by the Central Institute of Mental Health, is the first to shed light not only on the frequency but also the contexts and consequences of such offences and also shows the growing importance of digital channels. Women are particularly affected, while the majority of perpetrators are men. Despite increased awareness of the problem, the number of unreported cases remains high.
Sexualised violence against children and adolescents is also a widespread phenomenon in Germany. Child protection and dealing with the consequences of early childhood abuse pose major challenges for medical care. For many years, there has been criticism that there is no scientifically reliable data on the extent of sexualised violence in Germany. In addition to the actual extent, too little is still known about the exact context of the offences to be able to take targeted and effective preventative measures.
In order to remedy this situation, the Central Institute of Mental Health (ZI), as part of the German Centre for Mental Health (DZPG), together with the University Clinic for Child and Adolescent Psychiatry in Ulm and the Institute of Criminology at Heidelberg University, has conducted the first Germany-wide, representative study that takes into account not only the extent but also the circumstances and consequences of the offences. According to the study, 12.7 per cent of respondents stated that they had experienced sexualised violence as a child or adolescent.
The study revealed that women are affected significantly more often than men: 20.6 percent of all women surveyed stated that they had experienced sexualised violence in childhood and adolescence (compared to 4.8 percent of men). In the younger age group of 18 to 29-year-olds, this proportion was even higher at 27.4 per cent.
‘The results indicate a considerable dark field that has not decreased compared to previous studies, although awareness of the problem has grown and prevention measures have been expanded in Germany,’ says Prof Dr Harald Dreßing, coordinator of the study and Head of Forensic Psychiatry at the ZI. When asked about the perpetrator, the majority of those affected stated that the perpetrator was male. Only 4.5 percent of those surveyed had experienced sexualised violence at the hands of a woman.
The context of the offences was also asked about in the study. According to the results, those affected most frequently reported having experienced sexualised violence within the family or through relatives. It was striking that men experienced sexualised violence significantly more often in sports and leisure facilities, in a church context and in the context of child, youth and family support. The research team makes it clear that these differences show the need to develop differentiated protection concepts for children and young people.
DZPG spokesperson Prof. Silvia Schneider says: ‘ Early childhood traumatisation, such as sexualised violence, significantly increases the risk of mental illness - from post-traumatic stress disorder and depression to anxiety and personality disorders. The current study shows: The mental health of those affected is significantly worse than that of people without such experiences of violence. In order to sustainably reduce the frequency of sexualised violence in Germany, we therefore urgently need to invest in evidence-based prevention measures to combat sexualised violence in families and institutions.’
Digital channels, such as social media, messenger services and chats, played an important role in almost a third of cases (31.7 per cent). These cases involved, among other things, the unwanted sending of pornographic material, requests for sexual acts or coercion and pressure to share sexual images and videos. 61.9 percent of those affected who have experienced sexualised violence in the real world have also experienced sexualised violence on social media.
Over a third (37.4 percent) of those affected had not previously spoken to other people about the sexualised violence they had experienced. Those affected often reported feelings of shame and the fear that they would not be believed as the reason for this. ‘This shows that there is still a considerable amount of darkness and that there is often a lack of protected spaces in which people can openly talk about what they have experienced without having to fear negative consequences,’ says Dreßing.
The study also clearly shows that the psychological well-being of those affected by sexualised violence is significantly worse than that of those not affected. ‘ It is important that we continue and advance research into the extent and contexts of sexualised violence. This is the only way we can really improve prevention concepts and targeted medical care for those affected,’ says Prof Dr Andreas Meyer-Lindenberg, Director of the ZI and spokesperson for the DZPG Mannheim-Heidelberg-Ulm site.
DZPG spokesperson Prof. Dr Peter Falkai also emphasises the importance of the research: ‘In collaboration with the Central Institute of Mental Health and other partners, the DZPG has carried out truly pioneering work with this study. For the first time, the actual extent of sexualised violence in childhood and adolescence in Germany is becoming visible on the basis of a representative sample. Despite increased social awareness, there is an urgent need for action in this area. Sexualised violence is the tip of the iceberg of traumatising experiences in childhood and adolescence, which include other forms of physical and verbal violence as well as neglect. The DZPG is intensively investigating the connection between these experiences and mental illness at the various levels of prevention, early intervention, specific treatment and improved care and is also addressing the political players in their responsibility.’
Together with the survey institute infratest dimap, 10,000 people aged between 18 and 59 were contacted in a written survey throughout Germany. Just over 3,000 people took part in the survey. This response rate is high and allows reliable statements to be made.
Source: DZPG (in German)
An increasing number of bacteria are becoming resistant to modern antibiotics, with potentially fatal consequences. This is particularly dangerous in the case of multi-resistant bacteria, which are no longer affected by several antibiotics. A Franco-German research team is aiming to change this. They plan to use novel natural substances that block the vital bacterial enzyme DNA gyrase in an entirely new way to combat even multi-resistant pathogens such as tuberculosis bacteria and gonococci.
Antibiotic resistance is one of the greatest challenges facing medicine today. Multi-resistant bacteria that cannot be controlled by modern antibiotics are making it increasingly difficult to treat patients with bacterial infections.
In collaboration with the renowned Institut Pasteur in Paris, researchers from Cologne and Saarbrücken are investigating how new natural substances can stop dangerous pathogens, such as tuberculosis bacteria and gonococci (the bacteria responsible for gonorrhoea), even when they are resistant to common drugs.
The German Research Foundation (DFG) and the French Agence National de la Recherche (ANR) are now funding the project "Characterization of novel natural product binding sites in the DNA gyrase of multidrug-resistant Mycobacterium tuberculosis and Neisseria gonorrhoeae (NaPGyr)", in which a new consortium is researching the development of antibiotics against multidrug-resistant bacteria. Professors Jan Rybniker and Rolf Müller, both from the German Center for Infection Research (DZIF), are part of the consortium.
The research focuses on DNA gyrase, an enzyme that is essential for bacteria. It plays a key role in replicating bacterial DNA. Without functioning gyrase, bacteria cannot multiply. Two natural substances, cystobactamides and corramycins, block DNA gyrase in a novel way. They are also effective against resistant bacteria because they utilise new binding sites on the enzyme that cannot be reached by other antibiotics. This means that there is no cross-resistance with known antibiotics. As part of the NaPGyr project, the Franco-German team is investigating these new binding sites in more detail.
"Gyrases as potential molecular targets have long been the subject of intense research, leading to the development of some initially effective antibiotics, so-called gyrase inhibitors. However, bacteria have already developed various mechanisms to protect themselves against the available agents and become resistant. Previous research has shown that two classes of natural products, cystobactamides and corramycins, are effective inhibitors of DNA synthesis, particularly in Neisseria gonorrhoeae and Mycobacterium tuberculosis, leading to rapid cell death of the bacteria," explains Prof. Rybniker.
The molecular targets of both classes are bacterial topoisomerases, including DNA gyrase. The NaPGyr project aims to structurally characterize the novel binding sites on DNA gyrase that are targeted by cystobactamides and corramycins. Although the substances are already highly active in the petri dish, they are now to be modified in such a way that they reach the infection sites in the body, e.g. the lungs, in sufficient quantities. Knowledge of the molecular interactions and the mechanism of action will enable the design and synthesis of further and improved derivatives, which can then potentially be used as antibiotics in the treatment of infectious diseases.
Source: DZIF
Using Impulse Oscillometry, early damage to the small airways can be detected—even before lung function shows a noticeable decline. This is the result of a study conducted by scientists from the German Center for Lung Research (DZL), designed as a companion study to the HANSE Study, which has now been published.
The HANSE Study* aimed to investigate the extent to which a population screening using low-dose CT could help detect lung cancer and reduce mortality from the disease. To this end, researchers at the DZL sites ARCN and BREATH examined 5,000 people at increased risk of lung cancer: current or former smokers between the ages of 55 and 79. Results are not yet available.
However, the results of a parallel companion study have now been published in the journal American Journal of Respiratory and Critical Care Medicine. The aim of this research was to determine the extent to which early damage to the small airways can be detected using so-called impulse oscillometry. For this method, participants only need to breathe into a device that measures the small airways using sound waves. The technique is increasingly being investigated in studies because—unlike conventional methods such as spirometry and body plethysmography—it does not require active cooperation from the participant. As a result, measurements are more reliable and less prone to error.
The study showed that damage to the small airways could be diagnosed in 39% of smokers using oscillometry. Among individuals whose impaired lung function was also detectable using spirometry, the proportion of those showing abnormalities in the small airways via oscillometry was 60%. Interestingly, even among 26% of those with initially normal lung function—as measured using spirometric pulmonary function testing—damage to the small airways was detectable using oscillometry. This corresponded to 16% of the entire study population. These individuals also had a higher risk of metabolic or cardiovascular diseases and reported a lower quality of life.
Dr. Mustafa Abdo from the Lung Clinic Grosshansdorf (DZL site ARCN) led this companion study. He is now working at the Thoraxklinik Heidelberg (DZL site TLRC). He is convinced that oscillometry is a suitable tool for the early diagnosis of damaged small airways: “This allows us to intervene preventively in a targeted way—before lung damage develops into classic COPD, with the risk of metabolic or cardiovascular comorbidities.”
In addition, the use of oscillometry in this study demonstrated that it can be applied easily and within a short time to a large number of participants: “This shows its potential for early detection as part of preventive health screenings,” said Abdo.
The HANSE Study is a collaborative project of the Lung Clinic Grosshansdorf, the University Hospital Schleswig-Holstein (Campus Lübeck), and Hannover Medical School at the DZL sites ARCN and BREATH. In addition, colleagues from the Thoraxklinik Heidelberg (DZL site TLRC) were involved in the analysis of the impulse oscillometry data. The study was funded by the DZL and AstraZeneca.
*HANSE: Holistic implementation study Assessing a Northern German interdisciplinary lung cancer Screening Effort
Source: DZL
Hodgkin's lymphoma is a form of lymph gland cancer. Children and young adults are particularly frequently affected. Researchers at the LMU Hospital in Munich have discovered a potential new weak point in Hodgkin's lymphoma: the CD86 molecule. With the help of AI, they have developed novel immunotherapies that could be more targeted and less aggressive than previous treatments - a glimmer of hope for young patients. The study was published in the scientific journal ‘Blood’.
Around one in seven children with a malignant tumour has Hodgkin's lymphoma. The disease also frequently occurs in young adults. It is one of the cancers with the highest cure rates, with over 90 per cent of those affected surviving in the long term following aggressive, high-dose chemotherapy.
However, many of the cured children and young adults have to contend with late effects in the course of their lives. These can be minor complications, such as hormonal imbalances or an increased susceptibility to infections. But they can also be serious illnesses, such as a recurrence of cancer or heart or lung failure.
‘The need for new, less aggressive therapies that act as specifically as possible on the cancer cells and the surrounding tumour environment is therefore very great,’ says Dr Adrian Gottschlich, first author of the study. Especially as Hodgkin's lymphomas build up an environment around the actual cancer cells that suppresses any activity of the immune system against the tumour particularly strongly and ‘reprograms’ immune cells for its growth.
Researchers at LMU Hospital led by Dr Adrian Gottschlich and Prof. Dr Sebastian Kobold, both scientists in the German Consortium for Translational Cancer Research (DKTK) at the partner site in Munich, have developed new immunotherapies for patients with Hodgkin's lymphoma in the laboratory. In other words, they could attack the tumour from different angles.
The team led by the Munich physicians has created the experimental prerequisites for new targeted therapies. The focus: a molecule called CD86. ‘With the help of artificial intelligence,’ explains Prof. Sebastian Kobold, ‘we were able to identify CD86 as a central control element in the tumour environment of Hodgkin's lymphomas, which protects the cancer cells from the immune system.’
The molecule is found both on the surface of the tumour cells themselves and on the surface of certain immune cells (phagocytes) that migrate into the cancer and support its growth instead of fighting it.
In order to prevent the fatal effect of CD86, the researchers blocked the molecule in a targeted manner and were thus able to abolish the dormant state of T cells, which emphasises the central importance of CD86 in the inhibition of these immune cells. In parallel, the team developed a CAR T cell therapy against CD86. ‘These anti-CD86 CAR T cells,’ reports Gottschlich, ‘showed outstanding efficacy in numerous disease models.’
The results make CD86 a promising target structure for new therapies against Hodgkin's lymphoma in humans. The Munich scientists are already working intensively on the production of anti-CD86 CAR T cells for use in a clinical trial.
This is no easy endeavour, as it requires various components and partners as well as the necessary funds. 'What's more,' says Kobold, "our research could introduce a new generation of immune checkpoint inhibitors. These drugs could then not only reactivate the immune system - as is currently the case - but also kill the cancer cells directly."
Source: DKTK (in German)
The German Centre for Cardiovascular Research (DZHK) is funding and coordinating the German arm of a global clinical study on coronary heart disease in women. The study is part of an internationally coordinated research initiative of the Global Cardiovascular Research Funders Forum (GCRFF), in which several countries undertake to support national study components in a coordinated manner.
In this way, the GCRFF enables multinational studies that can be analysed independently of industry with full or predominantly public funding - a model that strengthens scientific independence and international cooperation equally.
The scientific management of the German study arm lies with the DZHK site in Göttingen. Prof Dr Ingo Kutschka, Director of the Clinic for Cardiothoracic and Vascular Surgery at the University Medical Centre Göttingen (UMG), and Prof Dr Bernhard Danner, Senior Physician at the same clinic, are responsible. The aim is to clarify the question of which bypass technique provides the best long-term treatment results in women, a question that has not been sufficiently researched so far.
The study is investigating the use of multiple arterial bypasses compared to standard therapy with a single arterial bypass in women with coronary heart disease. The aim is to find out whether the choice of bypass technique provides better long-term results and can reduce the risk of serious cardiovascular events such as heart attacks, strokes or repeat operations. ‘Although bypass surgery is well established, there is still a lack of comprehensive knowledge about which method provides the best long-term results, especially for women,’ says Prof Dr Ingo Kutschka, co-study leader at the UMG.
According to current studies, women with CHD have a poorer prognosis after bypass operations than men - partly because their vessels are smaller and the symptoms are often less obvious. In addition, women have long been underrepresented in clinical studies or gender-related differences have not been analysed at all. The new study only includes female patients and thus addresses a long-standing research gap.
‘The study is an excellent example of how translational research directly reaches patients - and at the same time proof of the visibility and international connectivity of the DZHK,’ says the head office of the German Centre for Cardiovascular Research.
The randomised controlled study is being conducted in ten countries worldwide. With ROMA:Women, the DZHK is sending a strong signal in favour of gender-sensitive research in cardiac medicine. In future, the results will be used to develop new guidelines specifically for the treatment of women with coronary heart disease - a long overdue step towards more personalised and fairer medicine.
Source: DZHK
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