Helix 8 in chemotactic receptors of the complement system.

Host response to infection involves the activation of the complement system leading to the production of anaphylatoxins C3a and C5a. Complement factor C5a exerts its effect through the activation of C5aR1, chemotactic receptor 1, and triggers the G protein-coupled signaling cascade. Orthosteric and allosteric antagonists of C5aR1 are a novel strategy for anti-inflammatory therapies. Here, we discuss recent crystal structures of inactive C5aR1 in terms of an inverted orientation of helix H8, unobserved in other GPCR structures. An analysis of mutual interactions of subunits in the C5aR1-G protein complex has provided new insights into the activation mechanism of this distinct receptor. By comparing two C5aR receptors C5aR1 and C5aR2 we explained differences between their signaling pathways on the molecular level. By means of molecular dynamics we explained why C5aR2 cannot transduce signal through the G protein pathway but instead recruits beta-arrestin. A comparison of microsecond MD trajectories started from active and inactive C5aR1 receptor conformations has provided insights into details of local and global changes in the transmembrane domain induced by interactions with the Gα subunit and explained the impact of inverted H8 on the C5aR1 activation.

Chemokine Receptors-Structure-Based Virtual Screening Assisted by Machine Learning.

Chemokines modulate the immune response by regulating the migration of immune cells. They are also known to participate in such processes as cell-cell adhesion, allograft rejection, and angiogenesis. Chemokines interact with two different subfamilies of G protein-coupled receptors: conventional chemokine receptors and atypical chemokine receptors. Here, we focused on the former one which has been linked to many inflammatory diseases, including: multiple sclerosis, asthma, nephritis, and rheumatoid arthritis. Available crystal and cryo-EM structures and homology models of six chemokine receptors (CCR1 to CCR6) were described and tested in terms of their usefulness in structure-based drug design. As a result of structure-based virtual screening for CCR2 and CCR3, several new active compounds were proposed. Known inhibitors of CCR1 to CCR6, acquired from ChEMBL, were used as training sets for two machine learning algorithms in ligand-based drug design. Performance of LightGBM was compared with a sequential Keras/TensorFlow model of neural network for these diverse datasets. A combination of structure-based virtual screening with machine learning allowed to propose several active ligands for CCR2 and CCR3 with two distinct compounds predicted as CCR3 actives by all three tested methods: Glide, Keras/TensorFlow NN, and LightGBM. In addition, the performance of these three methods in the prediction of the CCR2/CCR3 receptor subtype selectivity was assessed.

Impact of COVID-19 Pandemic on Daily Mobility of the Elderly Living in Small Cities in Lodz Province.

The article presents a study into the impact that the COVID-19 pandemic had on the daily mobility of those over 60 residing in small towns in the Lodz Province. The study determines the impact on the trip destination, trip frequency, preferred means of transport, distance and duration of trips, and length of the target activity. To achieve these objectives, a survey was conducted using the CATI technique (Computer Assisted Telephone Interviewing), which comprised 500 residents of small towns in the Lodz Province aged 60+, who were divided into three classes of small towns (by population size). In order to determine the impact of the COVID-19 pandemic on the daily mobility of those over 60, the tools the authors decided to use descriptive statistics and hypothesis testing. Overall, the pandemic was found to have had only a minor impact on the changes in transport behavior of those over 60 in small towns. Only 9% of respondents declared any effect on their daily mobility. The impact mainly involved a reduction in travel time and frequency, primarily among the oldest residents. Since a low level of daily mobility leads to low social activity, especially for the elderly-with a consequent sense of loneliness or even depression-towns should take measures to improve the already poor situation, one that has been further exacerbated by the pandemic.

Elevating Healthcare: Rapid Literature Review on Drone Applications for Streamlining Disaster Management and Prehospital Care in Saudi Arabia.

Saudi Arabia's health sector faces pressing challenges in disaster and prehospital care delivery, such as prolonged response times, limited access to remote areas, and strained medical resources. Integrating drone technology has emerged as an innovative approach to address these challenges and revolutionize healthcare delivery. Drones can significantly enhance response times, increase access to underserved areas, and reduce the burden on existing medical infrastructure. A detailed analysis of global case studies demonstrates the successful use of drones in healthcare delivery, emphasizing the importance of regulatory frameworks and public-private partnerships. These examples provide valuable insights into Saudi Arabia's health sector transformation. The potential benefits of integrating drone technology include improved patient outcomes, increased efficiency, and cost savings. To ensure the successful implementation of this transformative approach, it is crucial to establish clear regulatory guidelines, invest in research and development, and foster collaboration between the government, private sector, and healthcare stakeholders. The aim of this study is to explore the potential of drone technology in transforming healthcare delivery in Saudi Arabia, particularly within disaster response and prehospital care services.

The Moral, Ethical, Personal, and Professional Challenges Faced by Physicians during the COVID-19 Pandemic.

The COVID-19 pandemic, apart from the main problems concerning the health and life of patients, sparked a discussion about physicians' moral and social professional attitudes. During a pandemic, physicians have the same ethical, moral, and medical responsibilities, however, the situation is different since they are self-exposed to a danger, which may influence their willingness to work. The problem of the professional moral attitudes of health care workers, recurring in ethical discussions, prompts us to define the limits of the duties of physicians in the event of a pandemic, hence this research aimed to assess these duties from an ethical perspective and to define their boundaries and scope. The study was conducted in May and June 2020 in the city of Lublin, covering all medical centers, and the questionnaire was completed by 549 physicians. The research was conducted in four areas: emergency standby in the event of a disaster, even if it is not requested; willingness to work overtime in the event of a disaster, even without payment; willingness to take health risks by caring for people who are infectious or exposed to hazardous substances; readiness to be transferred to other departments in the event of a disaster. Although most of the respondents declared to be agreed on personal sacrifices in the performance of professional duties, they were not prepared for a high level of personal risk when working in a pandemic. Excessive workload, its overwhelming nature, and personal risk are not conducive to readiness to work overtime, especially without pay. Research shows how important it is to respect the rights and interests of all parties involved in a pandemic. Physicians' duty to care for a patient is also conditioned by the duty to protect themselves and should not be a tool for intimidating and depersonalizing their social and professional lives.