Role of DDR2 in synovial cell invasion: implications for rheumatoid arthritis

A hallmark of rheumatoid arthritis (RA) is cartilage erosion by pannus — an inflamed, hyperplastic and highly invasive synovial tissue. Cartilage degradation is primarily mediated by invading synovial fibroblasts. At the cartilage invasion front of the pannus, these cells destroy the tissue, leading to the permanent loss of joint structure and function. It has been shown that membrane type 1 metalloproteinase (MT1-MMP) plays a key role in promoting RA synovial fibroblast invasion into the cartilage. However little is known about regulatory mechanisms of MT1-MMP in RA synovial fibroblasts. MT1-MMP is highly upregulated in RA synovium, but mechanisms regulating its expression are not well understood. Interestingly, several reports show high MT1-MMP levels in fibroblasts at the pannus-cartilage junction. In addition, MT1- MMP expression and activity in cultured cells can be induced by collagen. We hypothesised that cartilage, more specifically cartilage collagen, induces MT1-MMP activity in the pannus. In this study, I have confirmed that both collagen and cartilage induce MT1-MMP activity and expression in RA synovial fibroblasts. To understand mechanisms of collagen signalling I have also investigated the role of collagen receptors, namely integrins and discoidin domain receptor 2 (DDR2), in MT1-MMP activation. Knockdown of DDR2, but not collagen-binding integrins, resulted in decreased MT1-MMP activity and expression upon collagen stimulation. DDR2 knockdown also inhibited MT1-MMP-dependent collagen degradation and invasion by RA synovial fibroblasts. Analysis of DDR2 binding to intact or telopeptide-devoid collagens indicates that collagen structure might influence cell signalling. Furthermore, activation of MT1-MMP by cartilage, which is also mediated by DDR2, is enhanced by removal of proteoglycans. In summary, I have demonstrated that cartilage signalling through collagen receptor DDR2 induces MT1-MMP activity in RA synovial fibroblasts.Open Acces

OBIEKTY BIUROWE W STRUKTURZE MIASTA – PRZYKŁAD WROCŁAWIA

The aim of the study was to identify the characteristic features of office properties in the city space: in particular, the relationship between the total rentable area and the area of a typical floor of office buildings and the time of their construction and distance from the center was taken into account. The work covers only objects with a uniform ownership structure and the area of which is entirely intended for rent. The study took into account all such buildings that obtained an occupancy permit or were subject to comprehensive modernization in the period from the fourth quarter of 1999 to the fourth quarter of 2019. As the case study was chosen Wrocław – the third regional market in terms of the volume of office space supply in Poland.Celem pracy była identyfikacja charakterystycznych cech nieruchomości biurowych w przestrzeni miasta: w szczególności uwzględniono zależności między całkowitą powierzchnią do wynajęcia oraz powierzchnią typowego piętra obiektów biurowych a czasem ich powstania oraz odległością od centrum. W pracy uwzględniono jedynie obiekty, które posiadają jednolitą strukturę właścicielską oraz których powierzchnia w całości przeznaczona jest na wynajem. W badaniu wzięto pod uwagę wszystkie takie budynki, które uzyskały pozwolenie na użytkowanie bądź podlegały kompleksowej modernizacji w okresie od IV kwartału 1999 do IV kwartału 2019 roku. Jako studium przypadku wybrano Wrocław – trzeci rynek regionalny pod względem wielkości podaży powierzchni biurowej w Polsce

Economic and social cost of epilepsy in Poland : 5-year analysis

Introduction: Epilepsy affects nearly 50 million people around the world. As a common and chronic disease generates a high cost burden for healthcare system and patients. Aim: We aimed to determine the most current direct and indirect costs of epilepsy in Poland from the social perspective for the years 2014–2018, to analyze the changes of expenditures over time, indicate trends and to determine key cost-drivers. Material and Methods: Direct and indirect costs using a top-down approach were estimated based on the public institutions' data for the ICD-10 codes G40 and G41. Direct costs included pharmacotherapy, hospitalizations, outpatient specialist care and rehabilitation. A human capital approach was used to estimate loss of productivity due to sick leaves and long-term inability to work. Results: Annual total direct and indirect costs related to epilepsy accounted for EUR 410 million in 2014 and decreased in subsequent years to EUR 361 million in 2018. The indirect costs were dominant (76–83% of total costs) and in the majority related to the long-term absenteeism (87–92% of total indirect costs). In 2014–2018, patients with epilepsy generated EUR 341 million to EUR 282 million of indirect costs. Annual direct costs for patients with epilepsy were EUR 69 million in 2014 and increased to EUR 80 million in 2018. The biggest expenses were the costs of drugs (> 50%) and hospitalizations (~ 40%). Conclusions: Epilepsy is an expensive disorder in terms of consumption of resources and social costs. Decision-makers should take it under special consideration

An Empirical Study of Affective and Cognitive Functions in Compulsive Sexual Behavior Disorder

BACKGROUND AND AIMS: Despite the inclusion of the Compulsive Sexual Behavior Disorder (CSBD) in the International Classification of Diseases, very little is known about the underlying affective and cognitive processes. To fill this gap, we compared CSBD subjects and Healthy-Controls (HC) across negative/positive valence, cognitive and sensorimotor systems, as proposed by the Research Domain Criteria framework. METHODS: 74 heterosexual CSBD and 66 matched HC males were studied with 10 questionnaires and 8 behavioral tasks. Analyses were conducted with frequent and Bayesian statistics. RESULTS: CSBD individuals showed significantly higher (than HC) punishment sensitivity, anxiety, depression, compulsivity, and impulsivity symptoms. Frequentist statistical analysis revealed significant interaction between subject group and condition in Incentive Delay Task, concerning the strength of motivation and hedonic value of erotic rewards. Bayesian analysis produced evidence for the absence of group differences in Facial Discrimination Task, Risk-Ambiguity Task, and Learning Task. Also, Bayesian methods provided evidence for group differences in the Emotional Stroop Task and the Incentive Delay Task. Sexual Discounting Task, Attentional Network Task, and Stop Signal Task produced mixed results. CONCLUSIONS: Higher punishment sensitivity and impulsivity among CSBD subjects, along with significant interaction between these groups and erotic vs. non-erotic reward processing is in line with previous findings on negative/positive valence alterations in CSBD patients. This result shows that there are similarities to substance and behavioral addictions. The absence of group differences and mixed results related to cognitive and sensorimotor systems raise concerns to what extent CSBD resembles a wide spectrum of impairments observed in disorders, and demand further research

OBIEKTY BIUROWE W STRUKTURZE MIASTA – PRZYKŁAD WROCŁAWIA

The aim of the study was to identify the characteristic features of office properties in the city space: in particular, the relationship between the total rentable area and the area of a typical floor of office buildings and the time of their construction and distance from the center was taken into account. The work covers only objects with a uniform ownership structure and the area of which is entirely intended for rent. The study took into account all such buildings that obtained an occupancy permit or were subject to comprehensive modernization in the period from the fourth quarter of 1999 to the fourth quarter of 2019. As the case study was chosen Wrocław – the third regional market in terms of the volume of office space supply in Poland.Celem pracy była identyfikacja charakterystycznych cech nieruchomości biurowych w przestrzeni miasta: w szczególności uwzględniono zależności między całkowitą powierzchnią do wynajęcia oraz powierzchnią typowego piętra obiektów biurowych a czasem ich powstania oraz odległością od centrum. W pracy uwzględniono jedynie obiekty, które posiadają jednolitą strukturę właścicielską oraz których powierzchnia w całości przeznaczona jest na wynajem. W badaniu wzięto pod uwagę wszystkie takie budynki, które uzyskały pozwolenie na użytkowanie bądź podlegały kompleksowej modernizacji w okresie od IV kwartału 1999 do IV kwartału 2019 roku. Jako studium przypadku wybrano Wrocław – trzeci rynek regionalny pod względem wielkości podaży powierzchni biurowej w Polsce

Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound MMP that is highly expressed in cells with invading capacity, including fibroblasts and invasive cancer cells. However, pathways of MT1-MMP up-regulation are not clearly understood. A potential physiological stimulus for MT1-MMP expression is fibrillar collagen, and it has been shown that it up-regulates both MT1-MMP gene and functions in various cell types. However, the mechanisms of collagen-mediated MT1-MMP activation and its physiological relevance are not known. In this study, we identified discoidin domain receptor 2 (DDR2) as a crucial receptor that mediates this process in human fibroblasts. Knocking down DDR2, but not the β1 integrin subunit, a common subunit for all collagen-binding integrins, inhibited the collagen-induced MT1-MMP-dependent activation of pro-MMP-2 and up-regulation of MT1-MMP at the gene and protein levels. Interestingly, DDR2 knockdown or pharmacological inhibition of DDR2 also inhibited the MT1-MMP-dependent cellular degradation of collagen film, suggesting that cell-surface collagen degradation by MT1-MMP involves DDR2-mediated collagen signaling. This DDR2-mediated mechanism is only present in non-transformed mesenchymal cells as collagen-induced MT1-MMP activation in HT1080 fibrosarcoma cells and MT1-MMP function in MDA-MB231 breast cancer cells were not affected by DDR kinase inhibition. DDR2 activation was found to be noticeably more effective when cells were stimulated by collagen without the non-helical telopeptide region compared with intact collagen fibrils. Furthermore, DDR2-dependent MT1-MMP activation by cartilage was found to be more efficient when the tissue was partially damaged. These data suggest that DDR2 is a microenvironment sensor that regulates fibroblast migration in a collagen-rich environment

Original articleInsertion/deletion polymorphism of angiotensin I converting enzyme gene and left ventricular hypertrophy in patients with type 2 diabetes mellitus

Introduction: Left ventricular hypertrophy (LVH) is a well known risk factor of death from cardiovascular causes. Patients with type 2 diabetes mellitus are at particularly high risk of developing cardiovascular disease, which accounts for 80% of deaths in this group. Type 2 diabetes mellitus is probably related to increased left ventricular mass (LVM). Existing data show that the renin-angiotensin-aldosterone (RAA) system may play a role in the development of LVH. Since the I/D polymorphism of angiotensin-converting enzyme (ACE) gene influences the activity of RAA, it is likely that it could also have an impact on LVH. Aim: To assess the relationship between I/D polymorphism of the ACE gene and the severity of LVH assessed by echocardiography (Echo) in patients with type 2 diabetes mellitus. Methods: The study group consisted of 103 patients (37 women and 66 men; mean age 60.1±9.1 years) suffering from type 2 diabetes mellitus with a mean duration of 9.0±6.5 years. BMI, waist-to-hip ratio (WHR), arterial blood pressure, LVM and LVM index (LVM indexed for body surface area [g/m2] or height raised to the power 2.7 [g/m2.7]) were evaluated. I/D polymorphism of the ACE gene was determined using polymerase chain reaction (PCR). Results: Distribution of I/D polymorphism of the ACE gene in the study group was as follows: genotype II – 32.0%, ID – 42.7%, DD – 25.2% of patients. LVH was diagnosed in 43-71% of patients (depending on criteria used). Distribution of individual genotypes was similar in patients with and without LVH. Genotypes II, ID and DD were observed in 37.3%, 31.4% and 31.4% of patients without LVH (according to the Levy criteria) and in 26.9%, 53.9%, 19.2% in the LVH group, respectively. In persons with DD genotype, when compared to group II, significantly higher values of systolic and diastolic blood pressure were noted (147.7±20.2 vs 138.2±16.7 mmHg, p=0.03 and 89.4±9.7 vs 81.9±8.7 mmHg, p=0.004, respectively). Conclusions: In patients with type 2 diabetes mellitus there is no relationship between I/D polymorphism of the ACE gene and LVHWstęp: Przerost lewej komory serca (LVH) jest uznanym czynnikiem ryzyka zgonu z przyczyn sercowo-naczyniowych. Grupę szczególnego ryzyka schorzeń układu krążenia stanowią chorzy z cukrzycą typu 2, u których 80% zgonów spowodowane jest chorobami tego układu. Wydaje się, że cukrzyca typu 2 wiąże się ze zwiększoną masą lewej komory (LVM). Istnieją dowody, iż układ renina-angiotensyna-aldosteron (RAA) może odgrywać rolę w rozwoju LVH. Ponieważ polimorfizm I/D genu konwertazy angiotensyny I (ACE) wpływa na aktywność układu RAA, prawdopodobny wydaje się także jego wpływ na LVH. Cel: Ocena zależności między obecnością polimorfizmu I/D genu ACE a stopniem przerostu lewej komory mięśnia sercowego, ocenianego za pomocą ultrasonografii (UKG) u osób z cukrzycą typu 2. Metodyka: Grupa badana: 103 osoby (37 kobiet i 66 mężczyzn) chore na cukrzycę typu 2, trwającą średnio 9,0±6,5 lat, w wieku średnio 60,1±9,1 lat. Oceniane parametry: BMI, wskaźnik talia/biodra (WHR), ciśnienie tętnicze, LVM oraz wskaźnik LVM [LVM odniesiona do powierzchni ciała (g/m2) lub wzrostu podniesionego do potęgi 2,7 (g/m2,7)]. Polimorfizm I/D genu ACE oznaczano metodą łańcuchowej reakcji polimerazy (PCR). Wyniki: W badanej grupie rozkład polimorfizmu I/D genu ACE przedstawiał się następująco: genotyp II – 32,0%, ID – 42,7%, DD – 25,2% chorych. LVH rozpoznano u 43–71% chorych (w zależności od przyjętych kryteriów). Rozkład poszczególnych genotypów był podobny w grupie osób z LVH i bez LVH. W grupie z LVH (wg kryteriów Levy) genotypu II, ID oraz DD występowały odpowiednio u 37,3%, 31,4% i 31,4% badanych, a w grupie bez LVH odpowiednio u 26,9%, 53,9% i 19,2%. U osób z genotypem DD obserwowano istotnie większe, w porównaniu z grupą II, wartości ciśnienia tętniczego skurczowego (147,7±20,2 vs 138,2±16,7 mmHg, p=0,03) i rozkurczowego (89,4±9,7 vs 81,9±8,7 mmHg, p=0,004). Wnioski: Polimorfizm I/D genu ACE u chorych z cukrzycą typu 2 nie wykazuje związku z LVH

Assessment of house-dust mite allergen-blocking effectiveness of newly developed barrier fabrics „ARGO plus” for antiallergic covers

Wprowadzenie: Alergeny roztoczy mogą łatwo gromadzić się w materacach i na powierzchniach tekstylnych, głównie na pościeli. Zatwierdzone strategie ograniczania narażenia na alergeny roztoczy obejmują stosowanie pokrowców z certyfikowanej tkaniny barierowej. Pokrowce mogą znacząco zwiększyć komfort i bezpieczeństwo nocnego snu oraz zapobiegać występowaniu zaostrzeń alergii atopowych i astmy. Celem pracy była ocena skuteczności blokowania alergenów przez nowo opracowane tkaniny barierowe przeznaczone na pokrowce antyalergiczne. Metody: Tkaniny barierowe z włókien poliestrowo-bawełnianych z jednostronną powłoką polimerową zostały opracowane i wytworzone przez Łukasiewicz-Instytut Włókiennictwa. Skuteczność barierową opracowanych tkanin i kontrolnej tkaniny bawełnianej, przed alergenem kurzu i roztoczy kurzu domowego Der p 1, badano zgodnie z wcześniej opisaną i opatentowaną metodą.[1,2]. W skrócie: próbki kurzu domowego odsysano odkurzaczem przez badane tkaniny, a kurz i alergeny zbierano na filtrach. Po ekstrakcji filtrów oznaczono stężenia alergenu roztoczy Der p 1 komercyjną metodą ELISA. Skuteczność barierową określono jako % przepuszczalności tkanin powlekanych w stosunku do kontrolnej tkaniny bawełnianej. Wyniki: Zbadano łącznie sześć rodzajów tkanin powlekanych i wybrano jedną o najlepszych właściwościach, zapobiegających przenikaniu kurzu i Der p 1. Ten opracowany materiał (nazwany Argo Plus) charakteryzował się wysoką skutecznością barierową wobec alergenu Der p 1 (0,15 % przepuszczalności ) oraz przepuszczalnością pary wodnej i powietrza. Po 20 cyklach prania tkanina Argo Plus zachowała swoją funkcję barierową. Wniosek: Stosując naszą oryginalną metodę badania tkanin barierowych, mogliśmy wybrać materiał włókienniczy o optymalnych właściwościach barierowych, który można wykorzystać do produkcji pokrowców na pościel i materace - barierowych wobec alergernów roztoczy kurzu domowego.Background: Mite allergens can easily accumulate in mattresses and on textile surfaces, mainly on linen. Approved strategies for reducing exposure to dust mite allergens include the use of covers from certified barrier fabric. Covers may significantly increase the comfort and safety of nighttime sleep and prevent the occurrence of exacerbations of atopic allergies and asthma. The aim of this study was to evaluate the allergen-blocking effectiveness of newly developed barrier fabrics designed for antiallergic covers. Methods: The barrier fabrics made of polyester/cotton woven structure with one-sided polymer coating were developed and manufactured by the Łukasiewicz-Textile Research Institute. Barrier effectiveness of designed fabrics and control cotton woven fabric against dust and house dust mite allergen Der p 1 was tested according to the previously described and patent method.[1,2]. In brief, house dust samples were sucked onto the tested textile material with a vacuum cleaner and the allergen was collected on filters. Following a filter extraction, the mite allergen Der p 1 concentration was determined with commercial ELISA method. Barrier effectiveness was defined as the % of permeability of tested fabrics in relation to control cotton fabric. Results: A total of six fabrics types were tested and the one with the best performance in preventing dust and Der p 1 penetration was chosen. This developed textile material (named Argo Plus) was characterized by a high barrier effectiveness against Der p 1 allergen (0,15 % permeability), but at the same time had sufficient permeability to the air and water vapor. When subjected to 20 washing cycles the Argo Plus fabric retained its barrier function. Conclusion: Using our original method for barrier fabrics testing, we were able to select a textile material with optimal barrier characteristics, which may be used to manufacture mattress covers

Home Environment in Early-Life and Lifestyle Factors Associated with Asthma and Allergic Diseases among Inner-City Children from the REPRO_PL Birth Cohort

Objective. We hypothesized that, in our REPRO_PL cohort, exposure to indoor allergens and lifestyle factors in early life are associated with risk of asthma, atopic dermatitis, and allergic rhinitis at ten years of age. Methods. We only examined children who had lived in the same house from birth. Children’s exposure to tobacco smoke was assessed based on cotinine levels in urine. House dust samples were collected. Results. Higher Fel d1 concentration in house dust was associated with significantly higher risk of developing asthma at age 10 years (95% CI,10.87 to 20.93; p < 0.001). Frequent house cleaning was associated with development of atopic dermatitis (odds ratio 0.61; 95% CI 0.37 to 0.99; p = 0.045). Clustering of exposure to HDM revealed two types of environment. Cluster 1, defined as lower HDM (dust), in contrast to Cluster 2, defined as higher HDM, was characterized by old-type windows, lower fungus and dampness levels, as well as more frequent house cleaning. Conclusion. Exposure to cat allergens and new-type buildings that limit air flow while increasing the condensation of steam on the windows and thereby stimulating the growth of fungi are risk factors for the development of asthma