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Chronic bronchitis is increasingly reported as a healthcare challenge in clinical settings partially due to the disease's bad prognosis and unresponsiveness to therapy, including the ineffectiveness of glucocorticoids. The ineffectiveness could have a link with genetic polymorphism of receptor genes resulting in inappropriate glucocorticoid pharmacodynamics. We sought to identify the role of gene polymorphism in the response of patients with chronic bronchitis to prednisolone therapy. To do so, a total of 60 newly diagnosed chronic bronchitis patients enrolled in the present study. Prednisolone at a dose of 30mg/day for two weeks was given and respiratory parameters [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC were measured before and after therapy. Blood samples were withdrawn for genetic profiling of genes involved in glucocorticoids pharmacodynamics, including BCII (rs41423247), N363S (rs56149945), and ER22/23EK (rs6189/rs6190) measured for their homozygous versus heterozygous gene splice variants.Results: Gene splice variants for BCII (rs41423247), N363S (rs56149945), and ER22/23EK (rs6189/rs6190) homozygous (73.3%, 98.7%, and 95%) represented a higher percentage than heterozygous (26.7%, 1.7%, and 5%). The respiratory parameters FEV1, FVC, and FEV1/FVC have shown significantly (p<0.05) better values at baseline in homozygous versus heterozygous, correspondingly, the responsiveness to therapy has shown significantly (p<0.05) better values in homozygous versus heterozygous.Conclusion: The study has provided a good template for genetic behaviour toward individualised medicine in our locality providing that these genes could be a cornerstone for discovering issues related to the pharmacodynamics profiling of drugs in clinical settings.
- MeSH
- chronická bronchitida * diagnóza genetika MeSH
- glukokortikoidy farmakologie MeSH
- lidé MeSH
- polymerázová řetězová reakce metody MeSH
- polymorfismus genetický genetika MeSH
- prednisolon farmakologie terapeutické užití MeSH
- protein - isoformy genetika MeSH
- receptory glukokortikoidů * genetika účinky léků MeSH
- respirační funkční testy metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
In 1715, two Slovenian physicians, Johann Baptist Werloschnig de Perenberg and Antonius Loigk, published an extensive volume on the last plague epidemic in Central Europe. Hidden within its pages is a description of smallpox inoculation, which predates any record of this procedure in Europe by several years. The procedure was personally witnessed by Loigk in Vienna in or before 1714. Very little is currently known about the context of this event. We do not know how many inoculators there were, how many patients were treated and, crucially, how the procedure was received by the medical establishment in Austria. All these pieces of information would be necessary to understand the impact of this discovery on early 18th-century Austrian (and, by extension, Eastern European) society. In order to sketch out the possible connections, we will focus on a reconstruction of the intellectual network of both Slovenians as it appears in the academic literature of the time. We hope that these links may reveal something about a group of physicians who may have had early knowledge about this important anti-epidemic measure.
- MeSH
- dějiny 18. století MeSH
- lékaři * dějiny MeSH
- lidé MeSH
- pravé neštovice * dějiny prevence a kontrola MeSH
- vakcinace * dějiny MeSH
- Check Tag
- dějiny 18. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Rakousko MeSH
- Slovinsko MeSH
INTRODUCTION: Threats to our survival are often posed by the environment in which humans have evolved or live today. Animal and human ancestors developed complex physiological and behavioral response systems to cope with two types of threats: immediate physical harm from predators or conspecifics, triggering fear, and the risk of infections from parasites and pathogens leading to the evolution of the behavioral immune system (BIS) with disgust as the key emotion. Here we ask whether the BIS has adapted to protect us from pandemic risks or poisoning by modern toxic substances. METHODS: We have developed a survey comprised of 60 vignettes describing threats evoking fear and disgust belonging to one of the three main categories of threats: (1) ancestral, (2) modern, and (3) pandemic of airborne disease. Each vignette was evaluated on a 7-point Likert scale based on fear, disgust, and anger. Respondents also completed an assessment battery. RESULTS: The results show that the strongest fear is triggered by modern threats (electricity, car accidents), while the highest disgust is evoked by ancient threats (body waste products, worms). Disgust does not respond to modern threat stimuli such as toxic substances or radioactivity as these evoke mainly fear and anger. A discriminant factor analysis classified nine out of 10 pandemic disgust vignettes into the ancestral disgust category, convincingly assigning the pandemic disgust threats to the ancestral type. Gender, age, and type of education were significant moderators of emotional responses across all threat categories. DISCUSSION: Our study reveals that while fear is more context-dependent, particularly triggered by modern threats, disgust operates on an evolutionarily hardwired basis, making it less effective against contemporary risks. Furthermore, disgust experienced during a pandemic outbreak is more closely aligned with ancestral disgust-related threats tapping into evolutionary ancient survival circuits of the BIS. However, as disgust declines with age, the brain must adaptatively shift the emotional processing from disgust to fear to protect older adults from contamination risks. Finally, our study reveals that pandemic fear is better predicted by specific behaviors rather than general anxiety, suggesting a need for new assessments.
- Publikační typ
- časopisecké články MeSH
- MeSH
- benigní pemfigoid sliznice * diagnostické zobrazování farmakoterapie patologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- hyperemie farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- kyselina mykofenolová aplikace a dávkování MeSH
- lidé MeSH
- nemoci spojivky * diagnostické zobrazování farmakoterapie patologie MeSH
- prednisolon aplikace a dávkování MeSH
- rituximab aplikace a dávkování MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
We report avian cervical vertebrae from the Quercy fissure fillings in France, which are densely covered with villi-like tubercles. Two of these vertebrae stem from a late Eocene site, another lacks exact stratigraphic data. Similar cervical vertebrae occur in avian species from Eocene fossils sites in Germany and the United Kingdom, but the new fossils are the only three-dimensionally preserved vertebrae with pronounced surface sculpturing. So far, the evolutionary significance of this highly bizarre morphology, which is unknown from extant birds, remained elusive, and even a pathological origin was considered. We note the occurrence of similar structures on the skull of the extant African rodent Lophiomys and detail that the tubercles represent true osteological features and characterize a distinctive clade of Eocene birds (Perplexicervicidae). Micro-computed tomography (μCT) shows the tubercles to be associated with osteosclerosis of the cervical vertebrae, which have a very thick cortex and much fewer trabecles and pneumatic spaces than the cervicals of most extant birds aside from some specialized divers. This unusual morphology is likely to have served for strengthening the vertebral spine in the neck region, and we hypothesize that it represents an anti-predator adaptation against the craniocervical killing bite ("neck bite") that evolved in some groups of mammalian predators. Tuberculate vertebrae are only known from the Eocene of Central Europe, which featured a low predation pressure on birds during that geological epoch, as is evidenced by high numbers of flightless avian species. Strengthening of the cranialmost neck vertebrae would have mitigated attacks by smaller predators with weak bite forces, and we interpret these vertebral specializations as the first evidence of "internal bony armor" in birds.
- Klíčová slova
- apremilast,
- MeSH
- antiflogistika nesteroidní aplikace a dávkování MeSH
- dolní končetina patologie MeSH
- inhibitory fosfodiesterasy 4 * aplikace a dávkování MeSH
- kombinovaná farmakoterapie metody MeSH
- lidé MeSH
- prednisolon aplikace a dávkování škodlivé účinky MeSH
- pyoderma gangrenosum * farmakoterapie komplikace patologie MeSH
- senioři MeSH
- syndromy imunologické nedostatečnosti farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The major organelles of the endomembrane system were in place by the time of the last eukaryotic common ancestor (LECA) (~1.5 billion years ago). Their acquisitions were defining milestones during eukaryogenesis. Comparative cell biology and evolutionary analyses show multiple instances of homology in the protein machinery controlling distinct interorganelle trafficking routes. Resolving these homologous relationships allows us to explore processes underlying the emergence of additional, distinct cellular compartments, infer ancestral states predating LECA, and explore the process of eukaryogenesis itself. Here, we undertake a molecular evolutionary analysis (including providing a transcriptome of the jakobid flagellate Reclinomonas americana), exploring the origins of the machinery responsible for the biogenesis of lysosome-related organelles (LROs), the Biogenesis of LRO Complexes (BLOCs 1,2, and 3). This pathway has been studied only in animals and is not considered a feature of the basic eukaryotic cell plan. We show that this machinery is present across the eukaryotic tree of life and was likely in place prior to LECA, making it an underappreciated facet of eukaryotic cellular organisation. Moreover, we resolve multiple points of ancient homology between all three BLOCs and other post-endosomal retrograde trafficking machinery (BORC, CCZ1 and MON1 proteins, and an unexpected relationship with the "homotypic fusion and vacuole protein sorting" (HOPS) and "Class C core vacuole/endosomal tethering" (CORVET) complexes), offering a mechanistic and evolutionary unification of these trafficking pathways. Overall, this study provides a comprehensive account of the rise of the LROs biogenesis machinery from before the LECA to current eukaryotic diversity, integrating it into the larger mechanistic framework describing endomembrane evolution.
BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.
- MeSH
- chronická zánětlivá demyelinizační polyneuropatie * diagnóza terapie farmakoterapie MeSH
- dospělí MeSH
- intravenózní imunoglobuliny terapeutické užití aplikace a dávkování MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prednisolon terapeutické užití aplikace a dávkování MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
The nearest-neighbour distance is an important property of a group, as individuals can obtain environmental information more quickly and easily from nearby individuals. We examined whether distance to the nearest neighbour affected two components of escape behaviour - alert distance (AD) and flight initiation distance (FID) - in an urban population of hooded crows Corvus cornix, while controlling for confounding variables. We did not find evidence that AD and FID were influenced by the nearest neighbour distance. However, both AD and FID were negatively affected by feeding activity of individuals - focal crows alerted later and escaped at shorter distance if they were feeding during our approach. In addition, AD and FID were positively related to starting distance and grass coverage. The lack of evidence for the nearest neighbour effect on escape behaviour of crows may be due to: (1) disturbance by close neighbours that may impede antipredator behaviour of focal birds, (2) variable distribution of familiar, dominant or experienced individuals within a flock, and (3) dynamic change in position of the nearest neighbour during the potential predator approach.
- MeSH
- chování zvířat fyziologie MeSH
- stravovací zvyklosti fyziologie MeSH
- úniková reakce * fyziologie MeSH
- vrány * fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
