IL-17 mediates immune protection from fungi and bacteria, as well as it promotes autoimmune pathologies. However, the regulation of the signal transduction from the IL-17 receptor (IL-17R) remained elusive. We developed a novel mass spectrometry-based approach to identify components of the IL-17R complex followed by analysis of their roles using reverse genetics. Besides the identification of linear ubiquitin chain assembly complex (LUBAC) as an important signal transducing component of IL-17R, we established that IL-17 signaling is regulated by a robust negative feedback loop mediated by TBK1 and IKKε. These kinases terminate IL-17 signaling by phosphorylating the adaptor ACT1 leading to the release of the essential ubiquitin ligase TRAF6 from the complex. NEMO recruits both kinases to the IL-17R complex, documenting that NEMO has an unprecedented negative function in IL-17 signaling, distinct from its role in NF-κB activation. Our study provides a comprehensive view of the molecular events of the IL-17 signal transduction and its regulation.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• kinasa I-kappa B genetika   metabolismus   MeSH
• lidé MeSH
• protein-serin-threoninkinasy genetika   metabolismus   MeSH
• receptory interleukinu-17 genetika   metabolismus   MeSH
• signální transdukce * MeSH
• zpětná vazba fyziologická * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.

• MeSH
• encefalomyelitida autoimunitní experimentální * genetika   MeSH
• interleukin-17 metabolismus   MeSH
• lidé MeSH
• myši MeSH
• proteiny obsahující MARVEL doménu genetika   MeSH
• psoriatická artritida * MeSH
• psoriáza * MeSH
• receptory interleukinu-17 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE OF THE STUDY The pilot study deals with the current situation in proximal femoral fractures in culturally diverse regions, namely in Afghanistan (AFG) and in the Czech Republic (CZ). The study aimed to find out whether there are any differences in proximal femoral fractures in dependence on the selected criteria between the two culturally diverse areas. The study used the data of patients who underwent surgery for proximal femoral fracture at the Department of Orthopaedics of the 1 s t Medical Faculty of the Charles University and the Military University Hospital and at the Military Base Hospital Kabul. MATERIAL AND METHODS The study included patients aged 21 years or older who sustained a proximal femoral fracture in the period from October 2013 to February 2014. For the period concerned, the evaluation comprised 44 patients with a proximal femoral fracture from the Military Base Hospital Kabul, of whom 25 women and 19 men, and a total of 71 patients with a proximal femoral fracture from the Department of Orthopaedics of the 1st Medical Faculty of the Charles University and the Military University Hospital, of whom 43 women and 28 men. Based on the medical documentation, the following evaluation parameters were selected: age, sex, type of fracture. The data was processed using descriptive statistics, one-way and multifactorial analysis (ANOVA) and the POST-HOC test (Fisher LSD test, confidence interval = 95%) RESULTS The mean age of all the patients who suffered a fracture of proximal femur in AFG (58 years) was considerably lower (p < 0.001) than in patients in CZ (81 years). Similarly, a significant difference (p <0.001) was identified in the age of men and women treated for a proximal femoral fracture in both the countries. In AFG there was a statistically significant difference (p = 0.002) between the age of men and women, where women sustaining fractures were younger (54 years) compared to men (63 years). In CZ no significant age difference was reported (83 years vs 78 years). In AFG, the observed fractures occurred generally in their 6th and 7th decade, whereas in CZ only in their 9th decade. The incidence of proximal femoral fractures in Afghan women is the highest in their 5th and 6th decade. Pertrochanteric fractures and intracapsular fractures prevailed in both countries. The lowest age in both types of the fracture was reported in Afghan women (52 years in femoral neck fracture, p <0.001, 54 years in trochanteric fracture, p = 0.039). DISCUSSION Significant differences between the patients in AFG and CZ concern several factors. Afghanistan is a country with the lowest average life expectancy. In the Afghan population a major Vitamin D deficiency was confirmed. This is related to the conservative dress code, especially in women, when the Vitamin D synthesis is suppressed. That can cause the occurrence of osteoporosis in women at a considerably younger age than in the population in the Czech Republic, which is subsequently accompanied by an increased incidence of proximal femoral fractures. Similar results, however, were also obtained in men. One of the risk factors of osteoporosis development is also low physical activity throughout the lifetime. This risk factor is significant primarily in female population in the Muslim world. Afghanistan also faces serious malnutrition. All of that is reflected in low life expectancy in the given country, incidence of osteoporosis and injuries in this region. There is reasonable evidence that the mortality in a causal relationship with proximal femoral fracture is substantially higher in this region than in Western Europe. CONCLUSIONS The results of the pilot study showed that there are significant differences in age and frequency of fractures in dependence on sex and country. The obtained results can be considered valuable since there are virtually no scientific or professional studies on osteoporosis and fractures in the given area that would help physicians get ready for significant differences. These results may become a source of valuable information not only for medical practitioners coming to Afghanistan to help as volunteers in the framework of developmental assistance from all over the world, but also for physicians from Europe, with respect to the wave of migrants coming from this area. Key words: proximal femur, fracture, gender, age, Afghanistan, Czech Republic.

• MeSH
• fraktury femuru epidemiologie   etiologie   MeSH
• fraktury krčku femuru epidemiologie   etiologie   MeSH
• fraktury kyčle epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoporotické fraktury epidemiologie   etiologie   MeSH
• pilotní projekty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Afghánistán MeSH
• Česká republika MeSH

PURPOSE OF STUDY Based on the selected criteria the study presents the evaluation of data of patients who underwent a surgery for proximal femoral fracture at the Department of Orthopaedic Trauma of the 1 st Faculty of Medicine and Military University Hospital Prague in the period 2013-2016. The paper aimed to determine whether there are any differences in proximal femoral fractures depending on the selected criteria. MATERIAL AND METHODS The study comprised 805 patients (562 women and 243 men) older than 21 years with proximal femoral fractures who were treated between January 1, 2013 and December 31, 2016. In the study, the patient s data on gender, age, a type of fracture (according to the AO classification), a level of mobility, time of injury and month of injury were analysed. The data was evaluated using the methods of descriptive statistics, one-way analysis of variance, two-way analysis by ANOVA and by following select POST-HOC test (Fisher LSD test) were utilized, 95% confidence interval was selected . RESULTS In the group of treated patients, the men were outnumbered by women (70% vs. 30%). In women the fractures occurred at a significantly (p < 0.001) older age (82 years) compared to men (77 years). Until the 8 th decade the fractures in men dominated, while from the 9th decade the fractures were more frequent in women. A sharp increase in the number of fractures in women was reported exactly in the 9th decade (56% of the total number of fractures in women). The group of women showed a significant difference (p = 0.027) between the age of femoral neck fractures and the age of trochanteric femoral fractures (80 years vs. 84 years). In both genders intracapsular and pertrochanteric fractures prevailed. In women and men with a limited mobility, fractures were sustained at the highest mean age (85 years in women, 84 years in men) compared to the other levels of mobility. In mobile patients, a significant difference (p < 0.001) was found between the age of women and men at which the fracture was sustained (79 years vs. 71 years). The largest significant difference (p < 0.001) in the age of fracture is seen in night time (84 years in women, 71 years in men). The highest number of injuries was suffered in the months of October to January, whereas the lowest number was reported in the period from June to July. DISCUSSION The epidemiological studies underline a notably higher incidence of proximal femoral fractures in women than in men, which was also confirmed by our study. The mean age of women with proximal femoral fracture was significantly higher compared to men. Similar conclusions have been drawn also by other studies. The incidence of fractures in dependence on the age group was the highest in women and men in their 9th decade, which compared to the previous studies was at a later age. This finding can be justified by aging of the Czech population, with the growing number of persons in the 9 th decade age group between 2012 and 2017 by 40,000. Nonetheless, men prevailed in fractures until the 9 th decade, while from the 9 th decade there is a marked growth in the number of these fractures sustained by women. This corresponds with the findings of other authors. As to the individual types of fractures (neck, trochanteric fracture) no difference was revealed in the percentage of women and men. In both genders intracapsular and petrochanteric fractures prevailed. Neither the level of pre-fracture mobility, nor the time of injury have been sufficiently monitored and evaluated with regard to the age of patients, therefore there is no adequate data to compare our results with. The lowest mean age at the time of injury was achieved by fully mobile men (71 years), which can be attributable to their sports and social activities performed at this age. The highest number of proximal femoral fractures was reported in the period from October to January, whereas their lowest number was reported in the period from June to July, which corresponds with the majority of other conducted studies in this area of research. CONCLUSIONS A considerably higher incidence of proximal femoral fractures in women was confirmed. The mean age of women with proximal femoral fracture was significantly higher than in men (82 vs. 77 years). Men prevailed in the number of fractures up to the 9 th decade, whereas from the 9 th decade the number of proximal femoral fractures in women significantly grew. In individual types of fractures (neck, trochanteric fractures), no difference in percentage of women and men was found. In both the genders intracapsular and pertrochanteric fractures significantly prevailed. The lowest mean age (71 years) at the time of injury was achieved by fully mobile men. The same age was identified in men also with respect to injuries sustained at night. The highest number of proximal femoral fractures was reported in the period from October to January, the lowest in the period from June to July. The knowledge of these seasonal variations can help plan the health care in the medical facility concerned. Key words: proximal femur, fracture, gender, mobility, day-time, seasonality.

• MeSH
• dospělí MeSH
• fraktury femuru * epidemiologie   chirurgie   MeSH
• fraktury krčku femuru * epidemiologie   chirurgie   MeSH
• fraktury kyčle * epidemiologie   chirurgie   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• omezení pohyblivosti MeSH
• rizikové faktory MeSH
• roční období MeSH
• senioři MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• vnitřní fixace fraktury * metody   statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Cílem práce bylo zhodnotit současnou situaci v oblasti hodnot body mass indexu (BMI) v celosvětové populaci z hlediska geografického původu a kulturních a ekonomických odlišností. Byla testována hypotéza existence rozdílů v hodnotách BMI v závislosti na geografickém původu, kulturních a ekonomických odlišnostech. Na základě statistického zhodnocení dat z let 2010 a 2014, poskytnutých Světovou zdravotnickou organizací, bylo zjištěno, že došlo ke statisticky nevýznamnému nárůstu BMI v jednotlivých oblastech světa. První místo zaujala za obě sledovaná období v dosažené hodnotě BMI Severní Amerika, naopak nízké hodnoty BMI vykázaly státy Subsaharské Afriky. Mezi většinou hodnocených oblastí existovaly signifikantní rozdíly (p < 0,05) v hodnotách BMI, obdobně byl signifikantní rozdíl (p < 0,05) mezi ekonomicky vyspělými a ekonomicky méně vyspělými státy. Vzrůst hodnot BMI mezi lety 2010 a 2014 byl však u obou ekonomik statisticky neprůkazný. Nejvyšší BMI vykazovaly za sledované roky státy s křesťanskou kulturou, poté státy s islámskou kulturou a nakonec státy s buddhizmem a hinduizmem. V této souvislosti je třeba konstatovat, že u ekonomicky méně vyspělých států bylo dosaženo nejvyšších hodnot BMI u křesťanských států, naopak z ekonomicky vyspělých států měly nejvyšší hodnotu BMI státy islámské. Mezi ekonomicky méně vyspělými státy a ekonomicky vyspělými státy s buddhizmem a hinduizmem neexistoval signifikantní rozdíl v hodnotách BMI. Testovaná hypotéza byla potvrzena.

The aim of this work was to evaluate the current situation of body mass index (BMI) values within the global population in terms of geographical region, cultural and economic differences. It was used to test the hypothesis that BMI values differ according to geographical region, culture, and economic performance. Based on statistical evaluation of data from 2010 and 2014 provided by the World Health Organisation (WHO), there has been a statistically insignificant increase in BMI in specific areas of the world. In both periods in question, North America led with the highest BMI values, whereas countries in the sub-Saharan Africa had the lowest BMI values. There were significant differences (p < 0.05) in the values of BMI between most evaluated areas. Similarly, there was a significant difference (p < 0.05) between economically developed and economically less developed countries. However, the increase in BMI values between 2010 and 2014 was statistically inconclusive in both economies. The highest BMI in the monitored period was detected in Christian countries, followed by Islamic countries, and finally in countries where Buddhism and Hinduism are the dominant religions. In this context, among economically less-developed countries, Christian countries had the highest BMI values, whereas among economically developed countries Islamic countries had the highest BMI values. There was no significant difference in BMI values between economically developed and economically less-developed Buddhist and Hinduism countries. Thus, the hypothesis was judged correct.

• MeSH
• epidemiologické studie MeSH
• etnicita MeSH
• index tělesné hmotnosti MeSH
• kultura MeSH
• lidé MeSH
• obezita * epidemiologie   MeSH
• rozvojové země MeSH
• vyspělé země MeSH
• Check Tag
• lidé MeSH

• MeSH
• aerosoly MeSH
• dárci krve MeSH
• kovy MeSH
• spektrofotometrie atomová MeSH
• vlasy, chlupy MeSH
• Geografické názvy
• Slovenská republika MeSH

• MeSH
• biochemická analýza krve MeSH
• dárci krve MeSH
• lidé MeSH
• moč chemie   MeSH
• odběr biologického vzorku MeSH
• stopové prvky krev   moč   MeSH
• vlasy, chlupy MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• lidé MeSH

• MeSH
• cytogenetika MeSH
• dospělí MeSH
• fagocytóza MeSH
• hutnictví MeSH
• imunita MeSH
• kovy analýza   MeSH
• lidé MeSH
• neutrofily MeSH
• pracovní expozice MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

• MeSH
• chrom analýza   imunologie   škodlivé účinky   MeSH
• chromozomální aberace MeSH
• dospělí MeSH
• eozinofilie MeSH
• hutnictví MeSH
• kouření MeSH
• lidé MeSH
• pracovní expozice MeSH
• vlasy, chlupy analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

BACKGROUND: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. METHODS: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. FINDINGS: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). INTERPRETATION: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. FUNDING: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

• Publikační typ
• časopisecké články MeSH