Association of variants in AGTR1, ACE, MTHFR genes with microalbuminuria and risk factors for the onset of diabetic nephropathy in adolescents with type 1 diabetes in the population of Serbia.

INTRODUCTION: Genetic studies may provide valuable information about patients who are at high risk of developing diabetes nephropathy. Before the appearance of albuminuria, there are genetic mutations that can predispose the development of kidney disease. MATERIAL AND METHODS: The study included 130 adolescents with type 1 diabetes. Patients were divided into two groups according to the presence of microalbuminuria. This study was performed to examine clinical and laboratory differences between adolescents with type 1 diabetes with and without microalbuminuria and the distribution of the ACE, AGTR1, and MTHFR gene polymorphisms. RESULTS: The mean microalbuminuria in the first group 6.41±7.35 significantly differs from the second group 0.82±0.48 (p<0.001). HbA1c, 24-hour proteinuria, and day-time systolic blood pressure were significantly higher in the MA group (p<0.05). Smaller systolic blood pressure percentage nocturnal decline was observed in the microalbuminuric group (p 0.030). The frequencies of the ACE DD, ID, and II genotypes were 12.5%, 50.0%, and 37.5%, respectively, among T1D patients with MA, and 19.3%, 56.1%, 24.6%, in the control group without MA (P = .510). The frequencies of the AGTR1 AA, AC, and CC genotypes were 62.5%, 25.0%, and 12.5% among TID patients with MA, and 49.1%, 43.9%, 8.0%, in the group without MA (p 0.326). The frequencies of the MTHFR CC, CT and TT genotypes were 37.5%, 50.0%, 12.5% among TID patients with MA, and 37.7%, 45.6%, 16.7% in the group without MA (p 0.901). CONCLUSION: Our data suggest that common variants in the AGTR1, ACE, and MTHFR genes are not strongly associated with diabetic nephropathy in our patients with type 1 diabetes.

Systemic sclerosis and environment: an intriguing and still debated association.

Systemic sclerosis (SSc) is characterised by a heterogeneous clinical expression probably reflecting the different genetic background of each patient. Progress has been made in the definition of the principal pathogenetic events of the disease that can be summarised in endothelial damage and dysfunction, inflammation with activation of immune system and fibrosis. The aetiology of the disease still remains to be clarified and probably the first events are attributable to the repeated action of environmental stimuli in genetically predisposed subjects.The aim of the present manuscript is to review the most recent and relevant data regarding the association of SSc with environmental factors.

Can Combination Therapy with Endothelin Receptor Antagonist and PDE5 Inhibitors Prevent Echocardiographic Findings Suspicious for Pulmonary Arterial Hypertension? Description of a Real-Life Case Series.

OBJECTIVE: To retrospectively evaluate the incidence rate (IR) of elevated echocardiographic estimated systolic pulmonary artery pressure (sPAP), suspected for pulmonary hypertension (PH), in systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. METHODS: Patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old with a history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months, were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic, and instrumental data (pulmonary function tests, echocardiographic estimation of sPAP, and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected of pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years. RESULTS: Thirty-five patients were enrolled; the mean disease duration was 12.82 years (SD 5.92). The mean duration of the combination treatment was 81.03 (SD 43.1.3) months, and the total at-risk time was 2674 months. Two patients (5.7%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 9/1000 patients-years (95% CI 7.95-10.12). In one of the two patients, right heart catheterism (RHC) excluded PAH, while the other patient refused to undergo RHC, and PAH could not be confirmed/excluded. The stability of PFTs and echocardiographic sPAP was observed during the observation time. CONCLUSIONS: The results of this retrospective study suggest that combination therapy with endothelin receptor antagonists and phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on a larger population are needed to improve knowledge in this field.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.

What is a B chromosome? Early definitions revisited.

Since the discovery of B chromosomes, multiple different definitions of these selfish genetic elements have been put forth. We reconsidered early definitions in light of recently published studies. While there are many characteristics that vary among different B chromosomes, such as their evolutionary origins, size, segregation behaviors, gene content, and function, there is one defining trait of all B chromosomes: they are nonessential for the organism. The points raised here may be useful for framing future B chromosome studies and help guide the categorization of new chromosomal elements that are uncovered in genomic studies.

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

Cryptic species Hydatigera kamiyai and other taeniid metacestodes in the populations of small mammals in Serbia.

BACKGROUND: Hydatigera (Cestoda: Taeniidae) is a recently resurrected genus with the description of a new species, Hydatigera kamiyai, a cryptic entity within the Hydatigera taeniaeformis species complex. Rodents are intermediate hosts and correct taxonomic identification of H. taeniaeformis sensu lato (s.l.) species is difficult without the use of molecular methods. The aim of this study was to identify and explore the genetic diversity of Hydatigera and other taeniid species. METHODS: Ten different small mammals species (856 individuals) (Rattus rattus, three Apodemus, three Arvicolinae and three Soricidae species) were examined from 2013 to 2023. Captured animals were visually examined for cysts and visible lesions. Two markers were used for amplification and sequencing: cox1 and 12S rDNA. RESULTS: Molecular analysis of cysts and visible lesions revealed four taeniid species: Hydatigera kamiyai, H. taeniaeformis sensu stricto (s.s.), Taenia martis and T. crassiceps. Hydatigera kamiyai was found in Apodemus flavicollis, A. agrarius, Microtus arvalis and Crocidrua leucodon, while H. taeniaeformis s.s. is registered in R. rattus. Hydatigera kamiyai cox1 sequences clustered with European populations and showed at least 25 nucleotid differences compared to Asian, African, Australian and one of our isolates of H. taeniaeformis s.s acquired from a rat, followed by large sequence distances (9.4% to 12.9%), indicating clear molecular distinction of two species. CONCLUSIONS: This is one of the few mitochondrial gene-based studies performed after the description of cryptic entities within the Hydatigera taeniaeformis s.l. complex and represents a valuable contribution to understanding of genetic diversity, host suitability and geographic distribution of these tapeworm species. Also, our study provides an important basis of molecular data from this part of Europe for further studies. We emphasize the importance of additional studies of intermediate hosts, especially rats from Europe and Apodemus spp. and voles from Asia and Africa.

Non-invasive investigation of Polychromophilus parasite infections in bat populations in Serbia using bat flies.

BACKGROUND: Haemosporidian parasites of the genus Polychromophilus infect bats worldwide. They are vectored by obligate ectoparasitic bat flies of the family Nycteribiidae. Despite their global distribution, only five Polychromophilus morphospecies have been described to date. The two predominant species, Polychromophilus melanipherus and Polychromophilus murinus, are broadly distributed and mainly infect miniopterid and vespertilionid bats, respectively. In areas where species from different bat families aggregate together, the infection dynamics and ability of either Polychromophilus species to infect other host families is poorly characterized. METHODS: We collected 215 bat flies from two bat species, Miniopterus schreibersii and Rhinolophus ferrumequinum, which sometimes form mixed clusters in Serbia. Miniopterus schreibersii is known to be frequently infected with P. melanipherus, whereas R. ferrumequinum has been observed to be incidentally infected with both Polychromophilus species. All flies were screened for Polychromophilus infections using a PCR targeting the haemosporidian cytb gene. Positive samples were subsequently sequenced for 579 bp of cytochrome b (cytb) and 945 bp of cytochrome oxidase subunit 1 (cox1). RESULTS: Polychromophilus melanipherus DNA was detected at six out of nine sampling locations and in all three examined bat fly species collected from M. schreibersii (Nycteribia schmidlii, n = 21; Penicillidia conspicua, n = 8; Penicillidia dufourii, n = 3). Four and five haplotypes were found for cytb and cox1, respectively. Evidence for multiple Polychromophilus haplotypes was found in 15 individual flies. These results point to a high diversity of P. melanipherus parasites in Miniopterus hosts and efficient transmission throughout the study area. A single Phthiridium biarticulatum bat fly collected from R. ferrumequinum screened positive for P. melanipherus, but only yielded a partial cox1 sequence fragment. Nevertheless, this result suggests that secondary hosts (both bat and fly species) are regularly confronted with this parasite. CONCLUSIONS: The results of this study provide new insights into the prevalence and distribution of Polychromophilus parasites in European bats and their nycteribiid vectors. The use of bat flies for the non-invasive investigation of Polychromophilus infections in bat populations has proven to be efficient and thus represents an alternative for large-scale studies of infections in bat populations without the need to invasively collect blood from bats.

Sharing roosts but not ectoparasites: high host-specificity in bat flies and wing mites of Miniopterus schreibersii and Rhinolophus ferrumequinum (Mammalia: Chiroptera).

Schreiber's bent-winged bat Miniopterus schreibersii and the greater horseshoe bat Rhinolophus ferrumequinum are widespread and common cavernicolous species across southern Europe that host numerous specialized ectoparasite species. The objective of this study was to characterize the species assemblage, genetic diversity, and host specificity of bat flies (Nycteribiidae, Diptera) and wing mites (Spinturnicidae, Acari) found on these bat hosts in Serbia and Bosnia and Herzegovina. Notably, while bat flies lay puparia on the cave walls and can thus be transmitted indirectly, wing mites require direct body contact for transmission. Morphological identification and sequencing of a 710-bp fragment of cytochrome oxidase I gene of 207 bat flies yielded 4 species, 3 on M. schreibersii and 1 on R. ferrumequinum. Sequencing of a 460-bp small subunit ribosomal RNA fragment, in all 190 collected wing mites revealed 2 species, 1 per host. In no case was a parasite associated with 1 host found on the other host. Species and genetic diversity of flies were higher in M. schreibersii, likely reflecting their host's larger colony sizes and migratory potential. Mite species of both hosts showed similarly low diversity, likely due to their faster life history and lower winter survival. Our findings highlight a remarkably high host-specificity and segregation of ectoparasite species despite direct contact among their hosts in the roost, suggesting a defined host preference in the investigated ectoparasite species. Furthermore, the differences in ectoparasite genetic diversity exemplify the interplay between host and parasite life histories in shaping parasite population genetic structure.

Host-Parasite Relationship-Nematode Communities in Populations of Small Mammals.

Nematode burdens and variation in morphological characteristics were assessed in eighty-eight animals from three host species (Apodemus sylvaticus, Apodemus flavicollis, and Myodes glareolus) from eight localities in Serbia. In total, 15 species of nematodes were identified, and the overall mean parasite species richness (IndPSR) was 1.61 per animal (1.98 in A. flavicollis, 1.43 in M. glareolus, and 0.83 in A. sylvaticus). Furthermore, the studied host species significantly differed in individual parasite load (IndPL) and in the following morphological characters: spleen mass, body condition index (BCI), and body mass. We aimed to analyze the relationship between the burden of intestinal nematodes, on one hand, and the body conditions of the host and its capability to develop immune defends on the other. Spleen mass was considered as a measure of immune response. In all host species, larger animals with a better condition (higher BCI) were infected with more parasites species (IndPSR), while parasite load was not related to BCI. Only in A. flavicollis were males significantly larger, but females of the same sizes were infected with more parasite species. This female-biased parasitism is contrary to the theoretical expectation that males should be more parasitized, being larger, more active, with a wider home range. Although the spleen size was significantly correlated with body condition and body mass, IndPSR was not related to spleen mass in any studied species, but in M. galareolus, we found that a smaller spleen was related to higher infection intensity (IndPL).

The new highest number of B chromosomes (Bs) in Leisler's bat Nyctalusleisleri (Kuhl, 1817).

B chromosomes (Bs) are supernumerary to the standard chromosome set, from which they prevalently derive. Variation in numbers both among individuals or populations and among cells within individuals is their constant feature. Leisler's bat Nyctalusleisleri (Kuhl, 1817) is one of only four species of Chiroptera with detected Bs. Four males of N.leisleri were collected from two localities on the territory of Serbia and cytogenetically analysed. All animals had Bs with interindividual variability ranging from two to five heterochromatic micro Bs. The highest number of Bs was detected in this species. Among mammals, Rodentia and Chiroptera are orders with the largest number of species, but Bs frequently appear in rodents and rarely in chiropterans. Possible explanations for this difference are offered.

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19.

OBJECTIVE: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.

The positive side of the coin: Sars-Cov-2 pandemic has taught us how much Telemedicine is useful as standard of care procedure in real life.

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.

Canalization and developmental stability of the yellow-necked mouse (Apodemus flavicollis) mandible and cranium related to age and nematode parasitism.

BACKGROUND: Mammalian mandible and cranium are well-established model systems for studying canalization and developmental stability (DS) as two elements of developmental homeostasis. Nematode infections are usually acquired in early life and increase in intensity with age, while canalization and DS of rodent skulls could vary through late postnatal ontogeny. We aimed to estimate magnitudes and describe patterns of mandibular and cranial canalization and DS related to age and parasite intensity (diversity) in adult yellow-necked mice (Apodemus flavicollis). RESULTS: We found the absence of age-related changes in the levels of canalization for mandibular and cranial size and DS for mandibular size. However, individual measures of mandibular and cranial shape variance increased, while individual measures of mandibular shape fluctuating asymmetry (FA) decreased with age. We detected mandibular and cranial shape changes during postnatal ontogeny, but revealed no age-related dynamics of their covariance structure among and within individuals. Categories regarding parasitism differed in the level of canalization for cranial size and the level of DS for cranial shape. We observed differences in age-related dynamics of the level of canalization between non-parasitized and parasitized animals, as well as between yellow-necked mice parasitized by different number of nematode species. Likewise, individual measures of mandibular and cranial shape FA decreased with age for the mandible in the less parasitized category and increased for the cranium in the most parasitized category. CONCLUSIONS: Our age-related results partly agree with previous findings. However, no rodent study so far has explored age-related changes in the magnitude of FA for mandibular size or mandibular and cranial FA covariance structure. This is the first study dealing with the nematode parasitism-related canalization and DS in rodents. We showed that nematode parasitism does not affect mandibular and cranial shape variation and covariance structure among and within individuals. However, parasite intensity (diversity) is related to ontogenetic dynamics of the levels of canalization and DS. Overall, additional studies on animals from natural populations are required before drawing some general conclusions.

Intestinal helminth infections in the golden jackal (Canis aureus L.) from Vojvodina: Hotspot area of multilocular echinococcosis in Serbia.

In the present study, 64 golden jackals were examined for intestinal helminths in three regions of Vojvodina, Serbia. Among the examined jackals 57.8% were infected with at least one parasite species. Using the intestinal scraping technique (SCT), eight species of intestinal helminths were found: Alaria alata (7.8%), Toxascaris leonina (9.4%), Toxocara canis (4.7%), Uncinaria stenocephala (20.3%), Echinococcus multilocularis (14.1%), Mesocestoides sp. (42.2%), Taenia pisiformis, and Taenia hydatigena (the overall prevalence of Taenia infection was 6.3%). To the best of our knowledge, this is the first report of T. leonina in jackals from Serbia. In comparison with the SCT results, coprological tests were less sensitive and specific for parasite identification, as only two nematode species (T. leonina and T. canis) as well as ancylostomatid and taeniid eggs were identified. The total prevalence of intestinal helminths was higher in males (71.9% males, 45% females), but the difference was not statistically significant (χ 2 = 3.76; P = 0.052). Co-infection with two species of intestinal helminths was found in 35% of the examined golden jackal individuals, three-species co-infection was demonstrated in 21.6%, whereas four-species co-infection was detected in 2.7% of the golden jackals examined. Echinococcus multilocularis has previously been recorded in jackals and foxes in Serbia, but only in Vojvodina. Our results corroborate the findings of previous studies, and indicate that the Vojvodina Province, more specifically the Srem region, is probably a high-risk area for E. multilocularis transmission to humans.

New Data on Organization and Spatial Localization of B-Chromosomes in Cell Nuclei of the Yellow-Necked Mouse Apodemus flavicollis.

The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are not randomly localized in a nucleus. The purpose of this work was to study the organization and three-dimensional spatial arrangement of Bs in the interphase nucleus. Using microdissection of Bs and autosome centromeric heterochromatic regions of the yellow-necked mouse (Apodemus flavicollis) we obtained DNA probes for further two-dimensional (2D)- and three-dimensional (3D)- fluorescence in situ hybridization (FISH) studies. Simultaneous in situ hybridization of obtained here B-specific DNA probes and autosomal C-positive pericentromeric region-specific probes further corroborated the previously stated hypothesis about the pseudoautosomal origin of the additional chromosomes of this species. Analysis of the spatial organization of the Bs demonstrated the peripheral location of B-specific chromatin within the interphase nucleus and feasible contact with the nuclear envelope (similarly to pericentromeric regions of autosomes and sex chromosomes). It is assumed that such interaction is essential for the regulation of nuclear architecture. It also points out that Bs may follow the same mechanism as sex chromosomes to avoid a meiotic checkpoint.

B Chromosomes' Sequences in Yellow-Necked Mice Apodemus flavicollis-Exploring the Transcription.

B chromosomes (Bs) are highly polymorphic additional chromosomes in the genomes of many species. Due to the dispensability of Bs and the lack of noticeable phenotypic effects in their carriers, they were considered genetically inert for a long time. Recent studies on Bs in Apodemus flavicollis revealed their genetic composition, potential origin, and spatial organization in the interphase nucleus. Surprisingly, the genetic content of Bs in this species is preserved in all studied samples, even in geographically distinct populations, indicating its biological importance. Using RT-PCR we studied the transcription activity of three genes (Rraga, Haus6, and Cenpe) previously identified on Bs in A. flavicollis. We analysed mRNA isolated from spleen tissues of 34 animals harboring different numbers of Bs (0-3).The products of transcriptional activity of the analysed sequences differ in individuals with and without Bs. We recorded B-genes and/or genes from the standard genome in the presence of Bs, showing sex-dependent higher levels of transcriptional activity. Furthermore, the transcriptional activity of Cenpe varied with the age of the animals differently in the group with and without Bs. With aging, the amount of product was only found to significantly decrease in B carriers. The potential biological significance of all these differences is discussed in the paper.

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real-life DeSScipher study.

INTRODUCTION: DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1. METHOD: Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed. RESULTS: The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p < 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p < 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone. CONCLUSIONS: Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention. Key Points • The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors. • More than half of the patients with recurrent DU received bosentan and/or sildenafil. • However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.

Pregnancy in Systemic Sclerosis: Results of a Systematic Review and Metaanalysis.

OBJECTIVE: Through a systematic literature search (SLR) and metaanalysis, to determine maternal and fetal outcomes in pregnancies involving systemic sclerosis (SSc), to analyze the effect of pregnancy on disease activity, and to examine predictors of fetal and maternal outcomes. METHODS: An SLR was performed for articles on SSc and pregnancy published between 1950 and February 1, 2018. Reviewers double-extracted articles to obtain agreement on > 95% of predefined critical outcomes. RESULTS: Out of 461 publications identified, 16 were included in the metaanalysis. The metaanalysis showed that pregnancies involving SSc were at higher risk of miscarriage (OR 1.6, 95% CI 1.22-2.22), fetuses with intrauterine growth retardation (IUGR; OR 3.2, 95% CI 2.21-4.53), preterm births (OR 2.4, 95% CI 1.14-4.86), and newborns with low birth weight (OR 3.8, 95% CI 2.16-6.56). Patients with SSc had a 2.8 times higher chance of developing gestational hypertension (HTN; OR 2.8, 95% CI 2.28-3.39) and a 2.3 times higher chance of cesarean delivery compared to controls (OR 2.3, 95% CI 1.37-3.8). The definitions of disease worsening/new visceral organ involvement were too inexact to have any confidence in the results, although worsening or new disease manifestations during pregnancy in 44/307 cases (14.3%) and 6 months postpartum in 32/306 cases (10.5%) were reported. The data did not permit definition of predictors of disease progression and of maternal and fetal outcomes. CONCLUSION: Pregnancies involving SSc have increased frequency of miscarriages, IUGR, preterm deliveries, and newborns with low birth weight compared to healthy controls. Women with SSc were more prone to develop gestational HTN and to undergo cesarean delivery. Disease manifestations seem to remain stable or improve in most patients.