A ubiquitous property of bacteria is their ability to move toward more suitable environments, which can also facilitate host-associated activities like colonization and offer the cell several benefits such as bacteria moving towards a favorable gradient or away from a harmful gradient is known as chemotaxis. Bacteria achieve this by rotating flagella in clockwise and anticlockwise directions resulting in "run" and "tumble." This ability of bacteria to sense and respond to any type of change in the environmental factors like pH, osmolarity, redox potential, and temperature is a standard signal transduction system that depends on coupling proteins, which is the bacterial chemotaxis system. There are two architectures for the coupling proteins in the chemotaxis system: CheW and CheV. Typically, a signal transduction system for chemotaxis to form a core signaling complex couples CheA activity to chemoreceptor control: two CheW coupling protein molecules span a histidine kinase CheA dimer and two chemoreceptors (also known as methyl-accepting chemotaxis protein, MCP) trimers of dimers which further transfer the signal to the flagellar motor through CheY. The current review summarizes and highlights the molecular mechanism involved in bacterial chemotaxis, its physiological benefits such as locating suitable nutrients and niches for bacterial growth, and various assay techniques used for the detection of chemotactic motility.

• MeSH
• Bacteria * metabolism   genetics   MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Chemotaxis * physiology   MeSH
• Flagella physiology   MeSH
• Bacterial Physiological Phenomena * MeSH
• Methyl-Accepting Chemotaxis Proteins metabolism   MeSH
• Signal Transduction MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: In patients resuscitated after cardiac arrest, a higher mean arterial pressure (MAP) may increase cerebral perfusion and attenuate hypoxic brain injury. Here we present the protocol of the mean arterial pressure after cardiac arrest and resuscitation (MAP-CARE) trial aiming to investigate the influence of MAP targets on patient outcomes. METHODS: MAP-CARE is one component of the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) 2 x 2 x 2 factorial randomized trial. The MAP-CARE trial is an international, multicenter, parallel-group, investigator-initiated, superiority trial designed to test the hypothesis that targeting a higher (>85 mmHg) (intervention) versus a lower (>65 mmHg) (comparator) MAP after resuscitation from cardiac arrest reduces 6-month mortality (primary outcome). Trial participants are adults with sustained return of spontaneous circulation who are comatose following resuscitation from out-of-hospital cardiac arrest. The two other components of the STEPCARE trial evaluate sedation and temperature control strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. Neurological prognostication will be performed according to European Resuscitation Council and European Society of Intensive Care Medicine guidelines by a physician blinded to allocation group. The sample size of 3500 participants provides 90% power with an alpha of 0.05 to detect a 5.6 absolute risk reduction in 6-month mortality, assuming a mortality of 60% in the control group. Secondary outcomes will be poor functional outcome 6 months after randomization, patient-reported overall health 6 months after randomization, and the proportion of participants with predefined severe adverse events. CONCLUSION: The MAP-CARE trial will investigate if targeting a higher MAP compared to a lower MAP during intensive care of adults who are comatose following resuscitation from out-of-hospital cardiac arrest reduces 6-month mortality.

• MeSH
• Arterial Pressure * physiology   MeSH
• Adult MeSH
• Equivalence Trials as Topic MeSH
• Cardiopulmonary Resuscitation * methods   MeSH
• Coma etiology   MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Randomized Controlled Trials as Topic MeSH
• Resuscitation * MeSH
• Heart Arrest * therapy   physiopathology   mortality   MeSH
• Treatment Outcome MeSH
• Out-of-Hospital Cardiac Arrest * therapy   physiopathology   mortality   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH

BACKGROUND: Fever is associated with brain injury after cardiac arrest. It is unknown whether fever management with a feedback-controlled device impacts patient-centered outcomes in cardiac arrest patients. This trial aims to investigate fever management with or without a temperature control device after out-of-hospital cardiac arrest. METHODS: The TEMP-CARE trial is part of the 2 × 2 × 2 factorial Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial, a randomized, international, multicenter, parallel-group, investigator-initiated, superiority trial that will evaluate sedation strategies, temperature management, and blood pressure targets simultaneously in nontraumatic/nonhemorrhagic out-of-hospital cardiac arrest patients following hospital admission. For the temperature management component of the trial described in this protocol, patients will be randomly allocated to fever management with or without a feedback-controlled temperature control device. For those managed with a device, if temperature ≥37.8°C occurs within 72 h post-randomization the device will be started targeting a temperature of ≤37.5°C. Standard fever treatment, as recommended by local guidelines, including pharmacological agents, will be provided to participants in both groups. The two other components of the STEPCARE trial evaluate sedation and blood pressure strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. A physician blinded to the intervention will determine the neurological prognosis following European Resuscitation Council and European Society of Intensive Care Medicine guidelines. The primary outcome is all-cause mortality at six months post-randomization. To detect a 5.6% absolute risk reduction (90% power, alpha .05), 3500 participants will be enrolled. Secondary outcomes include poor functional outcome at six months, intensive care-related serious adverse events, and overall health status at six months. CONCLUSION: The TEMP-CARE trial will investigate if post-cardiac arrest management of fever with or without a temperature control device affects patient-important outcomes after cardiac arrest.

• MeSH
• Fever * therapy   MeSH
• Cardiopulmonary Resuscitation * MeSH
• Humans MeSH
• Multicenter Studies as Topic MeSH
• Randomized Controlled Trials as Topic MeSH
• Body Temperature MeSH
• Hypothermia, Induced * instrumentation   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH

BACKGROUND: Basic management for patients who have suffered a cardiac arrest and are admitted to an intensive care unit (ICU) after resuscitation includes setting targets for blood pressure and managing sedation and temperature. However, optimal targets and management are unknown. METHODS: The STEPCARE (Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation) trial is a multicenter, parallel-group, randomized, factorial, superiority trial in which sedation, temperature, and blood pressure strategies will be studied in three separate comparisons (SED-CARE, TEMP-CARE, and MAP-CARE). The trial population will be adults admitted to intensive care who are comatose after resuscitation from out-of-hospital cardiac arrest. The primary outcome will be all-cause mortality, and the secondary outcomes will be poor functional outcome (modified Rankin Scale 4-6), Health-Related Quality of Life using EQ-VAS, and specific serious adverse events in the intensive care unit predefined for each trial. All outcomes will be assessed at 6 months after randomization. The prognosticators, outcome assessors, statisticians, data managers, steering group, and manuscript writers will be blinded to treatment allocation. This statistical analysis plan includes a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Analyses will be conducted according to the intention-to-treat principle, that is, all randomized participants with available data will be included. The analyses will be performed independently by two statisticians following the present plan. CONCLUSION: This statistical analysis plan describes the statistical analyses for the STEPCARE trial in detail. The aim of this predefined statistical analysis plan is to minimize the risk of analysis bias.

• MeSH
• Cardiopulmonary Resuscitation * methods   MeSH
• Blood Pressure * MeSH
• Quality of Life MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Body Temperature MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Clinical Trial Protocol MeSH

BACKGROUND: Sedation is often provided to resuscitated out-of-hospital cardiac arrest (OHCA) patients to tolerate post-cardiac arrest care, including temperature management. However, the evidence of benefit or harm from routinely administered deep sedation after cardiac arrest is limited. The aim of this trial is to investigate the effects of continuous deep sedation compared to minimal sedation on patient-important outcomes in resuscitated OHCA patients in a large clinical trial. METHODS: The SED-CARE trial is part of the 2 × 2 × 2 factorial Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, a randomized international, multicentre, parallel-group, investigator-initiated, superiority trial with three simultaneous intervention arms. In the SED-CARE trial, adults with sustained return of spontaneous circulation (ROSC) who are comatose following resuscitation from OHCA will be randomized within 4 hours to continuous deep sedation (Richmond agitation and sedation scale (RASS) -4/-5) (intervention) or minimal sedation (RASS 0 to -2) (comparator), for 36 h after ROSC. The primary outcome will be all-cause mortality at 6 months after randomization. The two other components of the STEPCARE trial evaluate sedation and temperature control strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. Neurological prognostication will be performed according to European Resuscitation Council and European Society of Intensive Care Medicine guidelines by a physician blinded to the allocation group. To detect an absolute risk reduction of 5.6% with an alpha of 0.05, 90% power, 3500 participants will be enrolled. The secondary outcomes will be the proportion of participants with poor functional outcomes 6 months after randomization, serious adverse events in the intensive care unit, and patient-reported overall health status 6 months after randomization. CONCLUSION: The SED-CARE trial will investigate if continuous deep sedation (RASS -4/-5) for 36 h confers a mortality benefit compared to minimal sedation (RASS 0 to -2) after cardiac arrest.

• MeSH
• Conscious Sedation * methods   MeSH
• Adult MeSH
• Deep Sedation * methods   MeSH
• Cardiopulmonary Resuscitation * methods   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Comparative Study MeSH

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

• MeSH
• Tissue Donors statistics & numerical data   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Perfusion * methods   instrumentation   MeSH
• Graft Survival * MeSH
• Aged MeSH
• Hypothermia, Induced methods   MeSH
• Liver Transplantation * methods   adverse effects   MeSH
• Organ Preservation * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

The circadian clock in choroid plexus (ChP) controls processes involved in its physiological functions, but the signals that synchronize the clock have been sparsely studied. We found that the ChP clock in the fourthventricle (4V) is more robust than that in the lateral ventricle (LV) and investigated whether both clocks use information about mealtime as a signal to synchronize with the current activity state. Exposure of mPer2Luc mice to a 10-day reverse restricted feeding (rRF) protocol, in which food was provided for 6 h during daytime, advanced the phase of the ChP clock in 4V and LV, as evidenced by shifted (1) PER2-driven bioluminescence rhythms of ChP explants ex vivo and (2) daily profiles in clock gene expression in both ChP tissues in vivo. In contrast, clocks in other brain regions (DMH, ARC, LHb) of the same mice did not shift. The 4V ChP responded more strongly than the LV ChP to rRF by modulating the expression of genes to ensure a decrease in resistance to cerebrospinal fluid drainage and increase the secretory capacity of ChP cells. Mechanistically, rRF affects the ChP clock through food-induced increases in insulin, glucose and temperature levels, as in vitro all three signals significantly shifted the clocks in both ChP tissues, similar to rRF. The effect of glucose was partially blocked by OSMI-1, suggesting involvement of O-linked N-acetylglucosamine posttranslational modification. We identified mechanisms that can signal to the brain the time of feeding and the associated activity state via resetting of the ChP clock.

• MeSH
• Circadian Clocks * physiology   genetics   MeSH
• Period Circadian Proteins metabolism   genetics   MeSH
• Circadian Rhythm physiology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Choroid Plexus * metabolism   physiology   MeSH
• Gene Expression Regulation MeSH
• Feeding Behavior * physiology   MeSH
• Lateral Ventricles metabolism   physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Směrnice, které se zaměřují na proces sterilizace zdravotnických prostředků pomocí páry a tepla. Určeno odborné veřejnosti.

• MeSH
• Steam MeSH
• Reproducibility of Results MeSH
• Quality Control MeSH
• Health Care Sector MeSH
• Sterilization MeSH
• Hot Temperature MeSH
• Equipment and Supplies MeSH
• Publication type
• Guideline MeSH
• Geographicals
• Czech Republic MeSH
• Europe MeSH

• Conspectus
• Metrologie. Standardizace
• NML Fields
• technika lékařská, zdravotnický materiál a protetika

Zoonózy se každoročně v České republice významně podílejí na počtu hlášených infekčních onemocnění. Stoupající tendence výskytu zoonotických virů, jako je virus zika virus, virus horečky dengue, virus chikungunyi a virus západonilské horečky, přenášených invazivními tropickými druhy komárů, je v první řadě důsledkem dlouhodobého, postupného a prakticky nezastavitelného šíření tohoto hmyzu po evropském kontinentu, včetně severských států. Evropa nyní již pravidelně zažívá opakované každoroční vlny veder, stejně jako časté záplavy. Navyšuje se nejen počet letních dnů s tropickými teplotami, ale období léta jako takového se významně prodlužuje. Stírají se jarní a podzimní období, rychlost nástupu letních teplot po období zim je často až drastická. Tento proces navozuje příznivé životní podmínky pro etablování tropických druhů komárů na našem území. Například ještě v roce 2013 se invazivní druh komára Aedes albopictus, původem z Asie, vyskytoval „pouze" v osmi evropských zemích a zasaženo bylo 114 regionů. O pouhých deset let později byl jeho výskyt potvrzen již ve třinácti zemích a 337 oblastech, včetně České republiky. Tento trend bude pokračovat, je proto nutné očekávat nárůsty autochtonních infekcí, včetně komplikovaných průběhů infekcí a úmrtí, obzvláště v rizikových skupinách rychle stárnoucí evropské populace. Kromě nutnosti hledat nové způsoby kontroly populací komárů, vývoje nových desinsekčních a larvicidních chemikálií je třeba zásadně posilovat programy surveillance napříč spolupracující Evropou, prosazovat používání osobních ochranných pomůcek a jednoznačně posílit výzkum a vývoj specifických antivirotik a nových očkovacích látek.

Zoonoses contribute significantly to the number of reported infectious diseases in the Czech Republic each year. The rising trend in zoonotic viruses such as Zika virus, dengue virus, Chikungunya virus, West Nile virus, transmitted by invasive tropical mosquito species, is primarily due to the long-term, gradual and virtually unstoppable spread of these insects across the European continent, including the Nordic countries. Europe now regularly experiences recurrent annual heat waves as well as frequent flooding. Not only are the number of summer days with tropical temperatures increasing, but the summer period itself is being significantly extended. The spring and autumn seasons are becoming shorter, and the speed of the onset of summer temperatures after winter is often drastic. This process creates favorable living conditions for the establishment of tropical mosquito species in our territory. For example, as recently as 2013, the invasive mosquito species Aedes albopictus, native to Asia, was present in "only" eight European countries and 114 regions were affected. In 2023, its presence has already been confirmed in thirteen countries and 337 regions, including the Czech Republic. This trend is set to continue, so increases in autochthonous infections, including complicated infection patterns and deaths, are to be expected, especially in at-risk groups of the rapidly ageing European population. In addition to the need to find new ways of controlling mosquito populations, the development of new disinsecticidal and larvicidal chemicals, surveillance programs across a cooperating Europe need to be substantially strengthened, the use of personal protective equipment needs to be promoted, and research and development of specific antivirals and new vaccines needs to be clearly stepped up.

• Keywords
• tropičtí komáři,
• MeSH
• Culicidae MeSH
• Zika Virus Infection epidemiology   transmission   therapy   MeSH
• Mosquito Vectors * MeSH
• Humans MeSH
• Zika Virus * isolation & purification   drug effects   MeSH
• Zoonoses * epidemiology   transmission   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

Fibroblast growth factors (FGFs) control organ morphogenesis during development as well as tissue homeostasis and repair in the adult organism. Despite their importance, many mechanisms that regulate FGF function are still poorly understood. Interestingly, the thermodynamic stability of 22 mammalian FGFs varies widely, with some FGFs remaining stable at body temperature for more than 24 h, while others lose their activity within minutes. How thermodynamic stability contributes to the function of FGFs during development remains unknown. Here we show that FGF10, an important limb and lung morphogen, exists as an intrinsically unstable protein that is prone to unfolding and is rapidly inactivated at 37 °C. Using rationally driven directed mutagenesis, we have developed several highly stable (STAB) FGF10 variants with a melting temperature of over 19 °C more than that of wildtype FGF10. In cellular assays in vitro, the FGF10-STABs did not differ from wildtype FGF10 in terms of binding to FGF receptors, activation of downstream FGF receptor signaling in cells, and induction of gene expression. In mouse embryonal lung explants, FGF10-STABs, but not wildtype FGF10, suppressed branching, resulting in increased alveolarization and expansion of epithelial tissue. Similarly, FGF10-STAB1, but not FGF10 wildtype, inhibited the growth of mouse embryonic tibias and markedly altered limb morphogenesis when implanted into chicken limb buds, collectively demonstrating that thermal instability should be considered an important regulator of FGF function that prevents ectopic signaling. Furthermore, we show enhanced differentiation of human iPSC-derived lung organoids and improved regeneration in ex vivo lung injury models mediated by FGF10-STABs, suggesting an application in cell therapy.

• MeSH
• Fibroblast Growth Factor 10 * metabolism   genetics   chemistry   MeSH
• Humans MeSH
• Mice MeSH
• Lung metabolism   embryology   MeSH
• Receptors, Fibroblast Growth Factor metabolism   MeSH
• Signal Transduction * MeSH
• Protein Stability MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH