Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic ...form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease.
Aspergillosis encompasses a wide range of clinical conditions based on the interaction between
Aspergillu
s and the host. It ranges from colonization to invasive aspergillosis. The human lung ...provides an entry door for
Aspergillus
.
Aspergillus
has virulence characteristics such as conidia, rapid growth at body temperature, and the production of specific proteins, carbohydrates, and secondary metabolites that allow
A. fumigatus
to infiltrate the lung’s alveoli and cause invasive aspergillosis. Alveolar epithelial cells play an important role in both fungus clearance and immune cell recruitment via cytokine release. Although the innate immune system quickly clears conidia in immunocompetent hosts,
A. fumigatus
has evolved multiple virulence factors in order to escape immune response such as ROS detoxifying enzymes, the rodlet layer, DHN-melanin and toxins. Bacterial co-infections or interactions can alter the immune response, impact
Aspergillus
growth and virulence, enhance biofilm formation, confound diagnosis, and reduce treatment efficacy. The gut microbiome’s makeup influences pulmonary immune responses generated by
A. fumigatus
infection and vice versa. The real-time PCR for
Aspergillus
DNA detection might be a particularly useful tool to diagnose pulmonary aspergillosis. Metagenomics analyses allow quick and easy detection and identification of a great variety of fungi in different clinical samples, although optimization is still required particularly for the use of NGS techniques. This review will analyze the current state of aspergillosis in light of recent discoveries in the microbiota and mycobiota.
Myotonic dystrophy type 1 (DM1) is one of the most variable monogenic diseases at phenotypic, genetic, and epigenetic level. The disease is multi-systemic with the age at onset ranging from birth to ...late age. The underlying mutation is an unstable expansion of CTG repeats in the
gene, varying in size from 50 to >1000 repeats. Generally, large expansions are associated with an earlier age at onset. Additionally, the most severe, congenital DM1 form is typically associated with local DNA methylation. Genetic variability of DM1 mutation is further increased by its structural variations due to presence of other repeats (e.g., CCG, CTC, CAG). These variant repeats or repeat interruptions seem to confer an additional level of epigenetic variability since local DNA methylation is frequently associated with variant CCG repeats independently of the expansion size. The effect of repeat interruptions on DM1 molecular pathogenesis is not investigated enough. Studies on patients indicate their stabilizing effect on
expansions because no congenital cases were described in patients with repeat interruptions, and the age at onset is frequently later than expected. Here, we review the clinical relevance of repeat interruptions in DM1 and genetic and epigenetic characteristics of interrupted
expansions based on patient studies.
A method for optimal planning of radial distribution networks is presented in detail based upon a combination of the steepest descent and the simulated annealing approaches. The object of ...investigation is the complete network of available routes and the optimization goal is to find the routes that provide the minimal total annual cost. The minimum capital cost oriented solution created by applying the steepest descent approach is used as the initial solution for the optimization procedure that is further improved by simulated annealing to obtain the minimum total cost solution. The method takes into account the capital recovery, energy loss and undelivered energy costs.
•Congenital myotonic dystrophy type 1 (CMD1) is a rare neuromuscular disease.•CDM1 is characterized by neonatal hypotonia, weakness, feeding and respiratory difficulties.•Many CMD1 patients suffer ...from hypoxic ischemic encephalopathy (HIE).•HIE, preterm delivery, resuscitation and hypothermia treatment are poor prognostic factors for survival.•Respiratory insufficiency is the main life-threatening factor in CDM1.
Congenital myotonic dystrophy type 1 (CDM1) is a rare neuromuscular disease. The aim of our study was to evaluate clinical variability of CDM1 and factors that may influence survival in CDM1. Research included 24 pediatric patients with CDM1. Most of our patients had some form of hypoxic ischemic encephalopathy (HIE) (74 %), from mild to severe. Prolonged and complicated deliveries (75 %), high percentage of children resuscitated at birth (57 %) and respiratory insufficiency (46 %) with consequent hypoxia were the main reasons that could explain high percentage of HIE. Therapeutic hypothermia was applied in three children with poor outcome. Median survival of all CDM1 was 14.2 ± 1.5 years. Six patients had a fatal outcome (25 %). Their mean age of death was 3.0 ± 2.8 years. Poor prognostic factors for the survival of our CDM1 patients were: preterm delivery, resuscitation at birth, severe HIE, hypothermia treatment and permanent mechanical ventilation. Respiratory insufficiency was the main life-threatening factor. Our data clearly indicates the need to develop natural history studies in CDM1 in order to enhance the standards of care and to develop clinical trials investigating causative therapies in pediatric patients with CDM1.
The aim of the paper is to present the oral health profile of 12- and 15-year-old schoolchildren in Serbia. Basic Methods for Oral Health Surveys of the WHO were implemented to record: Decayed, ...Missing, and Filled Teeth/Surfaces Index (DMFT/DMFS), gingival bleeding, enamel fluorosis and other structural anomalies, dental erosion, dental trauma, and oral mucosal lesions. In addition, Silness and Löe plaque index and orthodontic status were assessed. A total of 36% of 12-year-olds and 22% of 15-year-olds in Serbia were caries-free. The mean DMFT was 2.32 ± 2.69 for 12-year-olds and 4.09 ± 3.81 for 15-year-olds. DMFT was made up largely by the decayed component. Gingival bleeding was present in 26% of examined 12-year-old and 18% of 15-year-old children. Dental plaque was observed in 63% of both 12- and 15-year-olds. Fluorosis, structural anomalies, dental erosion, dental trauma, and oral mucosal lesion were rarely detected. Low prevalence of malocclusions was found. Oral disease is still a common public health problem among schoolchildren in Serbia. A significant increase in the prevalence of caries disease between 12- and 15-year-old groups implies that preventive care for adolescents requires special attention. Corrective actions and reforms to the current school-based oral health prevention program are needed to further improve oral health in Serbian children.
Genome-wide association studies (GWAS) have provided strong evidence that early- and late-onset MG have different genetic backgrounds. Recent in silico analysis based on GWAS results revealed ...rs231735 and rs231770 variants within CTLA-4 locus as possible MG causative genetic factors. We aimed to explore the association of rs231735 and rs231770 with MG in a representative cohort of Serbian patients. We conducted an age-, sex-, and ethnicity-matched case-control study. Using TaqMan allele discrimination assays, the frequency of rs231735 and rs231770 genetic variants was examined in 447 AChR-MG patients and 447 matched controls. There was no significant association of rs231735 and rs231770 with the entire MG cohort (P > 0.05). Nevertheless, when stratifying patients into early-onset (n = 183) and late-onset MG (n = 264), we found early-onset patients had a significantly lower frequency of the rs231735 allele T compared to controls (OR = 0.734, 95% CI = 0.575-0.938, p10e6 permutation < 0.05), and rs231735 genotype TT and rs231770 genotype TT had a protective effect on early-onset MG (OR = 0.548, 95% CI = 0.339-0.888, and OR = 0.563, 95% CI = 0.314-1.011, p10e6 permutation < 0.05). Consequently, we found that individuals with the rs231735-rs231770 haplotype GC had a higher risk for developing early-onset MG (OR = 1.360, P = 0.027, p10e6 permutation < 0.05). Our results suggest that CTLA-4 rs231735 and rs231770 may be risk factors only for patients with early-onset MG in Serbian population.
Abstract Aim To analyze quality of life (QoL) in a large cohort of myotonic dystrophy type 2 (DM2) patients in comparison to DM1 control group using both generic and disease specific questionnaires. ...In addition, we intended to identify different factors that might affect QoL of DM2 subjects. Patients and Method 49 DM2 patients were compared with 42 adult-onset DM1 patients. Patients completed SF-36 questionnaire and individualized neuromuscular quality of life questionnaire (INQoL). Following measures were also included: Medical Research Council 0–5 point scale for muscle strength, Addenbrooke's cognitive examination revised for cognitive status, Hamilton rating scale for depression, Krupp's fatigue severity scale and daytime sleepiness scale (DSS) Results SF-36 total score and physical composite score did not differ between DM1 and DM2 patients ( p > 0.05). However, role emotional and mental composite score were better in DM2 ( p < 0.05). INQoL total score was similar in both groups ( p > 0.05), although DM2 patients showed less impairment in independence ( p < 0.05) and body image domains ( p < 0.01). Regarding symptoms assessed by INQoL, DM2 patients showed less severe complaint of myotonia ( p < 0.01). Multiple linear regression analysis showed that significant predictors of worse QoL in DM2 patients were older age, worse muscle strength and higher level of fatigue. Conclusion QoL reports of DM2 patients with the most severe form of the disease are comparable to those of DM1 patients. Special attention of clinicians should be paid to DM2 patients with older age, more severe muscle weakness and higher level of fatigue since they may be at higher risk to have worse QoL.
Neuropsychological examinations in myotonic dystrophy (DM) patients show a great variability of results from a condition of intellectual disability to the subtle cognitive impairments. It is unclear ...if different clusters of neuropsychological deficits appear in different phenotypes of DM, or if there are patients with no cognitive deficit at all. The aim of this study is to assess cognitive impairments among patients with different phenotypes of DM type 1 (DM1) and type 2 (DM2), and to potentially define cognitive clusters in these disorders. Study comprised 101 DM1 and 46 DM2 adult patients who were genetically confirmed. Patients underwent analysis of five cognitive domains (visuospatial, executive, attention, memory and language). Virtually all DM1 patients had cognitive defect with approximately 2–3 cognitive domains affected. On the other hand, one-third of DM2 patients had completely normal neuropsychological findings, and in other two-thirds approximately 1–2 domains were affected. Cluster analysis showed that in both diseases visuospatial and executive dysfunctions seemed to be the main cognitive defects, while memory and language impairments appeared in more severe phenotypes. Our results showed that a single form of DM1 or DM2 may consist of several cognitive clusters. Understanding of cognitive impairments in DM is very important to follow positive and side effects in ongoing and future clinical trials.
Introduction
Myotonic dystrophy type 2 (DM2) is a rare autosomal dominant multisystemic disease with highly variable clinical presentation. Several case reports and one cohort study suggested a ...significant association between DM2 and autoimmune diseases (AIDs).
Aim
The aim of this study is to analyze the frequency and type of AIDs in patients with DM2 from the Serbian DM registry.
Patients and Methods
A total of 131 patients with DM2 from 108 families were included, 62.6% women, mean age at DM2 onset 40.4 (with standard deviation 13) years, age at entering the registry 52 (12.8) years, and age at analysis 58.4 (12.8) years. Data were obtained from Akhenaten, the Serbian registry for DM, and through the hospital electronic data system.
Results
Upon entering the registry, 35 (26.7%) of the 131 patients with DM2 had AIDs including Hashimoto thyroiditis (18.1%), rheumatoid arthritis, diabetes mellitus type 1, systemic lupus, Sjogren's disease, localized scleroderma, psoriasis, celiac disease, Graves's disease, neuromyelitis optica, myasthenia gravis, and Guillain-Barre syndrome. At the time of data analysis, one additional patient developed new AIDs, so eventually, 36 (28.8%) of 125 DM2 survivors had AIDs. Antinuclear antibodies (ANAs) were found in 14 (10.7%) of 63 tested patients, including 12 without defined corresponding AID (all in low titers, 1:40 to 1:160). Antineutrophil cytoplasmic antibodies (ANCAs) were negative in all 50 tested cases. The percentage of women was significantly higher among patients with AIDs (82.9% vs. 55.2%,
p
<0.01).
Conclusion
AIDs were present in as high as 30% of the patients with DM2. Thus, screening for AIDs in DM2 seems reasonable. Presence of AIDs and/or ANAs may lead to under-diagnosis of DM2.
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