first-in-man study
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- MeSH
- ependym embryologie MeSH
- gestační stáří MeSH
- lidé MeSH
- mícha embryologie MeSH
- povrchové vlastnosti MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Refractory angina pectoris (AP) significantly impairs quality of life in patients with chronic coronary syndrome. Several minimally invasive methods (coronary sinus reducer, cell therapy, laser or shockwave revascularization, and spinal cord stimulation) or non-invasive methods (external counterpulzation) have been studied. However, their routine clinical use has not been widely implemented. Surgical or endoscopic sympathectomy is feasible for permanently relieving angina, but is often contraindicated due to the extent of complications associated with it. Neuromodulation by anaesthetic blockade of the left-sided stellate ganglion (SG) has been shown to relieve angina for days or weeks. To provide a long-term anti-anginal effect, novel pharmacological (phenol-based) or radiofrequency ablation techniques have been individually used to permanently destroy sympathetic pathways. CASE SUMMARY: We describe a first-in-man use of stereotactic radiosurgical SG ablation using a linear accelerator (CyberKnife) in a heart failure patient after myocardial infarction with chronic refractory AP. Repeated anaesthetic SG blockade in this patient resulted in a significant, but only short-term, clinical improvement. The left, and subsequently the right, SG was ablated by targeted irradiation. During the 1-year follow-up, the patient remained without angina. We did not observe any clinically relevant early or late complications. Atrial fibrillation that developed 2 months after the second procedure was deemed to be associated with a natural progression of co-existing heart failure. DISCUSSION: We conclude that stereotactic radiosurgical SG ablation has the potential to become a minimally invasive and low-risk procedure to treat refractory angina patients. However, this procedure needs to be evaluated in larger patient populations.
- Klíčová slova
- Case report, Refractory angina, Stellate ganglion blockade, Stereotactic radiosurgery, Upper thoracic sympathetic system,
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Alveolar Osteitis (AO) is a complication following the extraction of a tooth. AO manifests through localized pain in, and around, the extraction site, where the post-operative blood clot has been disintegrated. The aim of this single cohort study was to evaluate the outcome of a treatment of AO, using a pharmacological device composed of hyaluronic acid and octenidine dihydrochloride. The tested device is a sponge-like material, composed solely of a fully dissoluble medicaments (hyaluronic acid, calcium chloride, and octenidine dihydrochloride). It was designed to serve as a non-toxic, slow-dissolving antiseptic, that adheres to mucosa and obturates the wound. This study includes 58 subjects who were diagnosed with AO. The tested device was administered once daily until local pain subsided to < 20 mm of the Visual Analog Scale (VAS). The treatment was considered effective when the pain subsided to < 20 mm VAS in < 8 days of treatment; as per comparative studies. Our findings provide a statistically significant success rate of 96.0% (95.0% confidence interval of 75.75% to 97.8%) after pharmacological device administrations. No adverse medical effects were detected. Acquired data confirmed that lyophilized hyaluronic acid, combined with octenidine, is effective for the treatment of AO. The results are clinically important as AO is a common complication after third molar extractions.
- Klíčová slova
- alveolalgia, alveolar osteitis, alveolitis sicca dolorosa, clinical study, first-in-man study, octenidine dihydrochloride, sodium hyaluronate,
- MeSH
- antiinfekční látky lokální aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- extrakce zubů škodlivé účinky MeSH
- iminy MeSH
- kohortové studie MeSH
- kyselina hyaluronová aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- poextrakční zánět zubního lůžka farmakoterapie MeSH
- pyridiny aplikace a dávkování terapeutické užití MeSH
- vstřebatelné implantáty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiinfekční látky lokální MeSH
- iminy MeSH
- kyselina hyaluronová MeSH
- octenidine MeSH Prohlížeč
- pyridiny MeSH
The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.
- Klíčová slova
- 7α/β-hydroxy-androgens, DHEA, androstenediol, behavioral immune system, cortisol, disgust, estrogens, pregnancy, steroids, testosterone,
- MeSH
- dospělí MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladý dospělý MeSH
- odpor * MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- steroidy krev MeSH
- těhotenství MeSH
- třetí trimestr těhotenství krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- steroidy MeSH
18 chronic diseases were investigated in a population of 13,115 women living in six settings of West- (Avon UK, the Isle of Man), Central- (the Czech Republic and the Slovak Republic) and East-Europe (the Ukraine and Russia), that collaborate in the European Longitudinal Study of Pregnancy and Childhood (ELSPAC project). In prenatal questionnaires filled in after the first half of pregnancy, women reported 25,795 chronic diseases they ever suffered, out of them 11,188 having in present pregnancies. In the whole sample, lifelong prevalence was 11,2%, and prevalence in pregnancy 4,8% which means that 43,4% of all chronic diseases recurred in pregnancy. Up to mean age of 255 years in the whole sample, 39,6% women reported ever having indigestion, 29% back pains, 22,6% migraine, about 16% haemorrhoids, hay fever and eczema, about 10% varicose veins, anorexia nervosa, heavy depression and kidney diseases, over 5% rheumatism and 4% asthma. Less prevalent were infections of pelvic organs, febrile convulsions, joint inflammations, stomach ulcers, psoriasis and epilepsy. Lifetime prevalence of chronic diseases and their prevalence in pregnancy were the highest in the western zone and decreased eastwards, but recurrence grew in the opposite direction, being the highest in the eastern zone. The variation of each morbidity indicator is followed in all diseases between geographical zones as well as between individual study centres.
- MeSH
- chronická nemoc epidemiologie MeSH
- komplikace těhotenství epidemiologie MeSH
- lidé MeSH
- longitudinální studie MeSH
- morbidita trendy MeSH
- prevalence MeSH
- průzkumy a dotazníky MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
OBJECTIVE: Human resources are crucial for addiction treatment and prevention services, as well as for science and research. The aim of this historical case study is to explain and demonstrate the role of specialized university academic degree study programmes in addictions in the context of a national institutional infrastructure. This specific group of very highly specialized academic programmes represents the highest level of professional development and is producing a totally new generation of addiction specialists with a very distinctive professional identity. METHODS: The study protocol is based on a case study research design and the case is defined as the historical development of addiction specialized institutions closely related to self-help, prevention, and treatment activities on the historical territory of the Czech Republic. We identified relevant historical sources related to establishing and/or running activities or institutions according to the categories specified in our concept of the national institutional infrastructure. All the materials and sources that were collected were sorted according to a timeline and categories of institutions and we systematically determined the first recorded activity/institution in each particular category. For this simple sorting system we used open and selected coding according to Grounded Theory. RESULTS: The public health model developed by Thomas Babor recognizes six different structural mechanisms to support university-based programmes in addiction studies: specialized journals, research centres, professional societies, specialized libraries and documentation centres, training and education programmes and institutions, and funding agencies. We attempted to redefine the concept of addiction studies within the broader context of the addiction field and added three additional mechanisms of support: public interest groups, self-help groups, and service providers. Using a historical case study in the Czech Republic, we demonstrate the potential for a broader context and interaction between these support mechanisms and academic institutions hosting academic programmes in addiction studies. CONCLUSION: The process of establishing integrated addiction studies programmes at Charles University in the Czech Republic had its origins in, and support from, various national institutions and professional organizations. This allowed the university to develop academic programmes at the bachelor's, master's, and Ph.D. levels. The availability of career opportunities for advanced-level addiction professionals in the Czech Republic was also a critically important factor in developing sustainable academic programmes in addiction studies. Our experience is that the creation of successful and sustainable academic programmes for addiction professionals is difficult to achieve without broad infrastructure support, national advocacy efforts, and legislative change at the national level.
- Klíčová slova
- academic degree study programmes, implementation process, institutional infrastructure, public health, specialized addiction programmes,
- MeSH
- adiktologie výchova MeSH
- dějiny 21. století MeSH
- hodnocení programu MeSH
- lidé MeSH
- případové studie organizací MeSH
- studium lékařství dějiny organizace a řízení MeSH
- Check Tag
- dějiny 21. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- Geografické názvy
- Česká republika MeSH
AIMS: Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy. METHOD: We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group. RESULTS: The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70-4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre-gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18-2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on metformin with and without pre-gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference. CONCLUSION: Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.
- Klíčová slova
- diabetes, metformin, observational study, pregnancy, spontaneous abortion, teratogen,
- MeSH
- dospělí MeSH
- hypoglykemika aplikace a dávkování škodlivé účinky MeSH
- kohortové studie MeSH
- komplikace těhotenství farmakoterapie MeSH
- lidé MeSH
- metformin aplikace a dávkování škodlivé účinky MeSH
- narození mrtvého plodu epidemiologie MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- samovolný potrat epidemiologie MeSH
- těhotenství při diabetu farmakoterapie MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hypoglykemika MeSH
- metformin MeSH
Employing methods of cell biology and proteome analysis tools, we examined effects of an inhibitor of histone deacetylases, sodium butyrate (SB), on the proliferation/differentiation characteristics of chronic myelogenous leukemia (CML)-derived cells K562. SB suppressed proliferation of K562 cells by inducing cell cycle arrest in G1 phase, which was followed by their transition to G0 phase (decrease of Ki-67 antigen-positive cells) and erythroid differentiation (increased glycophorin A expression and synthesis of hemoglobins). Neither terminal apoptosis (low counts of TUNEL-positive cells) nor necrosis (moderate counts of propidium iodide-positive cells) occurred. Importantly, SB attenuated protein expression of CML-related chimeric kinase BCR-ABL that is responsible for the deregulated proliferation of CML cells. The proteomic analysis (2-D electrophoresis combined with MALDI-TOF mass spectrometry and/or Western blotting) revealed several proteins that were differentially expressed or their mobility was altered due to butyrate treatment, namely, HSP90, HSP70, p23, cyclophilin A (CYPA), prefoldin2 (PFD2) and alpha-, gamma-, epsilon-human globin chains. Perturbation of HSP90 multichaperone complex of which BCR-ABL is the client protein is presumably a cause of BCR-ABL suppression. Changes in other proteins with chaperonic functions, CYPA and PFD2, may reflect SB antiproliferative and cytodifferentiation effects.
- MeSH
- buněčná diferenciace účinky léků MeSH
- buňky K562 MeSH
- butyráty farmakologie MeSH
- G1 fáze účinky léků MeSH
- lidé MeSH
- proliferace buněk účinky léků MeSH
- proteom biosyntéza MeSH
- proteomika * MeSH
- regulace genové exprese u leukemie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- butyráty MeSH
- proteom MeSH
PROBLEM: Disgust contributes to anxiety-based psychopathology, and in turn, anxiety increases disgust proneness. BACKGROUND: Disgust and anxiety undergo significant changes in pregnancy, but no previous study has examined their longitudinal associations in this time period. AIM: This prospective longitudinal study aimed to identify longitudinal associations between disgust sensitivity and state anxiety across the three trimesters of pregnancy, while exploring the directionality of the effect between those two variables. METHODS: At each trimester of pregnancy, the pregnant women (n = 261) completed the Disgust Scale-Revised (DS-R), the Pathogen disgust domain of the Three Domains of Disgust Scale (TDDS), and the State-Trait Anxiety Inventory. A path analysis (structural equation model) was used to assess cross-lagged effects between disgust sensitivity and state anxiety across the three pregnancy trimesters. FINDINGS: We found significant cross-lagged associations between disgust and anxiety such that higher disgust (overall DS-R score, Core disgust subscale of DS-R and Pathogen disgust domain of TDDS) in the first trimester predicted greater anxiety in the third. No significant cross-lagged associations were found between Animal-reminder or Contamination disgust subscales of DS-R and state anxiety. State anxiety did not predict disgust sensitivity at any time point. DISCUSSION: Our results indicate a unidirectional association between disgust sensitivity and state anxiety in pregnant women such that disgust sensitivity in early pregnancy predicts state anxiety in late pregnancy, but anxiety does not predict disgust sensitivity at any time point. CONCLUSION: Assessing disgust in early pregnancy could help to identify women at risk of higher anxiety levels in advanced pregnancy.
- Klíčová slova
- COVID-19 pandemic, Cross-lagged path model, Disgust, Emotion, Longitudinal, Pregnancy, State anxiety,
- MeSH
- dospělí MeSH
- lidé MeSH
- longitudinální studie MeSH
- odpor * MeSH
- prospektivní studie MeSH
- průzkumy a dotazníky MeSH
- první trimestr těhotenství * psychologie MeSH
- psychometrie přístrojové vybavení metody MeSH
- těhotenství MeSH
- těhotné ženy * psychologie MeSH
- úzkost * psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Alcohol is a well-known, socially tolerated drug. Its harmfulness to human health, including its associated negative impact on the family of alcoholics, is well known. It is an interdisciplinary problem, whose solution requires financial contributions, society support, the involvement of a wider group of experts and finally also an active approach on young people and adults to this problem. The work is based on six lethal alcohol intoxication cases. The first case is devoted to a woman who dies in alcohol intoxication in the casino. The second case involves a man who died near the pond in alcohol intoxication. The third describes the course of the trip associated with drinking to the alcohol poisoning stage and the subsequent death of a man in a car. The fourth case is based on continual full-day drinking to the alcohol poisoning stage and subsequent death of a man. The fifth case describes the course of a riotous celebration, which ends with the death of an alcohol poisoned man. The last sixth case documents an alcohol poisoned man, which in combination with the ingestion of cannabinoids died on a bus station. The causes and reasons leading to such tragic events are discussed here. Attention is drawn to the dangers arising from the sudden drinking of occasional consumers and also to the dangers of the sudden drinking of persons who consume alcohol in excessive doses for a long time. Furthermore, the prevention of the use of alcoholic beverages by children and young people, including the prevention of alcoholism are discussed. Educational programs are proposed to create a remedial measure for de-tabooing this issue and format the attitudes of children, adolescents and adults to drinking alcohol, with the expectation of a reduction in deaths from alcohol intoxication in the future.
- Klíčová slova
- alcohol intoxication, alcoholism prevention, first health care help, sudden deaths, tragic deaths,
- MeSH
- alkoholismus * komplikace MeSH
- dítě MeSH
- dospělí MeSH
- ethanol MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladiství MeSH
- otrava alkoholem * komplikace prevence a kontrola MeSH
- pití alkoholu škodlivé účinky prevence a kontrola MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ethanol MeSH