Two autosomal recessive neuromuscular disorders - FRDA and LGMD2A, in a single Bulgarian pedigree

Here we report a single pedigree affected by two different recessive neuromuscular disorders, namely Friedreich ataxia (FRDA) and Limb-Girdle Muscular Dystrophy Type 2A. The molecular genetic testing showed that in this family FRDA is caused by an expanded GAA repeat in compound heterozygous state with a novel point mutation c.442C>T, p.Gln148* on the second allele of the FXN gene. This case of two siblings (male and female) is the first report of Bulgarian FRDA case carrying a point mutation in the FXN gene. The LGMD2A affected individual was found to be compound heterozygous for the two most common CAPN3 mutations for the Bulgarian population (c.550delA, p.Thr184Argfs; c.967G>T, p.Glu323*). To the best of our knowledge we are reporting the first Bulgarian family with two neurological disorders caused by mutations in genes on different chromosomes and segregating independently in the family. This single pedigree with four different mutations is an example for the high genetic heterogeneity of the Bulgarian population

Molecular-genetic diagnosis of a Bulgarian family with multiple endocrine neoplasia, type IIA

INTRODUCTION: Multiple Endocrine Neoplasia (MEN) is a rare autosomal dominant disease with frequency 1:30 000 and it is classified in 3 subtypes: MEN 2A (Sipple syndrome), familial medullary thyroid carcinoma (FMTC), MEN 2B. The MEN 2A subtype constitutes approximately 70%-80% of cases of MEN 2. The onset age of the MEN 2A is prior to age 35 years. MEN 2A has an increased risk for parathyroid hyperplasia or adenoma. The clinical diagnosis is suspected when at least 2 specific endocrine tumors are detected in one patient or close relatives (MTC, pheochromocytoma, parathyroid adenomas). MTC is suspected in case of increased serum levels of calcitonin. The biochemical phenotype of MTC is revealed between age 5 and 25 (mean age 15 years). The tumor formation in the neck area is between age of 15 and 20 (2). Although there is controversy surrounding the definition of CCH, its utility to identify or confirm MEN 2 has been essentially replaced by RET (REarranged during Transfection) protooncogene testing. This allows the early surgery interventions, proper genetic counseling and prenatal diagnostics.MATERIAL AND METHODS: We report on a Caucasian male with complains of general weakness and weight loss (10 kg for 2 month). The patient`s mother has been diagnosed at 47 as bilateral pheochromocytomas and struma nodosa and died at age of 51. In the index patient abdominal ultrasound examination with biopsy of adrenal glands and histological analysis revealed pheochromocytoma on the right side; elevated plasma calcitonin concentration and US scan with biopsy of thyroid tissue detected medular thyroid cancer. The index patient has two elder brothers - it turned out that one of them had been surgically treated for medular thyroid cancer in the past; bilateral pheocromocytomas were detected in the family screening process.RESULTS AND CONCLUSION: MEN 2A diagnosis was suspected and we performed sequencing of RET protooncogene. The genetic analysis of the family affected members revealed c.1902C>G, p.Cys634Trp heterozygous mutation. Unfortunately, two kids in the families of 2 of the brothers have also inherited the mutation. All adult family members were offered genetic counseling. The standard therapy and the prophylactic thyroidectomy include the surgical removal of the thyroid gland, followed by parathyroid gland autotransplantation. In case codon 634 mutation the surgery is recommended before age of 5 years. All affected relatives are going through monitoring for residual disease. The screening protocol includes plasma levels of calcitonin. The stimulation tests are more sensitive than calcitonin measurements alone so they are recommended

Principle of work in the process of digitization and reconstruction of model of belt buckle by photogrammetry and 3D computer design

Българската женска народна носия е богата на множество символи, елементи и детайли. Един от най-характерните са пафтите – елемент от колана. Освен като символика със специално преднаначение, пафтите със своята уникална идентичност принадлежат към национално – историческото наследство на България. В настоящото изследване е дигитализиран и реконструиран модел на пафта, притежаващ изящество и красота. Реализацията на завършения тримерен компютърен модел преминава през етапи на фотограметрия и компютърен дизайн със специални скулптуриращи инструменти.Bulgarian female folk costume is rich in multiple characters, elements and details. One of the most characteristic is the belt buckles. As well as specially designed symbolism, the belt buckle - with their unique identity belong to the national - historical heritage of Bulgaria. In the present study a model of a belt buckle is digitized and reconstructed, and possessing grace and beauty. The realization of the completed three-dimensional computer model goes through stages of photogrammetry and computer design with special sculpting tools

Application of modern technological means in the process of digitization of models of national and historical value

България е известна с богатата си история още от древни времена. В рамките на сегашната си територия, страната обхваща най-различни култури, които носят своята характерна специфика и идентичност. Настоящото изследване  цели дигитализацията на модели с национална и историческа стойност, като се прилагат съвременни технологични средства. За осъществяване на целта се използва методичен процес, оптимизиращ взаимодействието на различните работни етапи.Bulgaria has been known for its rich history since ancient times. Within its current territory, the country encompasses a variety of cultures that bear their specific specificity and identity. The present study aims at the digitization of models of national and historical value, applying modern technological means. To achieve the goal, a methodical process is used to optimize the interaction of the different working steps

The role of the newborn screening programme (NSP) for the diagnosis of a 17-year-old boy with congenital Adrenal Hyperplasia (cah) due to 21 OH deficiency

A newborn boy was diagnosed with CAH via the 2010 implemented NSP in Bulgaria. The 17-OH-progesterone (17-OHP) from the 1st filter paper card (FPC) was 44.6 nmol/l, from the 2nd FPC 80 nmol/l. The examination on day 15th revealed as `only` sign slight hyperpigmentation of the scrotum. The screening suspicion `classical CAH` was confirmed by the increased serum levels of 17-OHP (normal electrolytes) and treatment with hydrocortisone was started. The MLPA analysis revealed a hemizygous del3-4, c.622T>A; p.I173N. Family history: 2nd son of relatively short parents - mother`s height - 152 cm (SDSh = -2.12), father`s height - 164 cm (SDSh= -1.96), MPH- 158 cm, SDS MPH= -2.54. The height of his older brother is 157 cm (SDSh= -3.01), while his target height of 164.5 cm (SDSh= -1.88) was markedly above the actual height. At 7 years he had initial pubarche and was the tallest boy in his class. He was taller than the average for his age until 12 years then he stopped growing. The older boy was also brought to a pediatric endocrinologist at 17 years of age. Elevated levels of 17-OHP in the serum >60 nmol/l (157.4) and on FPC:>285 nmol/l (537), together with the genetically verified CAH in the younger brother lead to the diagnosis `simple virilizing 21 OHD`, so treatment with hydrocortisone was started.Conclusion: Some of the simple virilizing forms of CAH may remain unrecognized, esp. in `index-families`. The newly implemented CAH NSP represents a useful diagnostic tool also in such cases. Ultrasound of the adrenals and testes for testicular rest tumors is important initially and during follow up

Case Report: Transthyretin Glu54Leu—a rare mutation with predominant cardiac phenotype

We report two unrelated Bulgarian families with hereditary transthyretin (ATTR) amyloidosis due to a rare p.Glu74Leu (Glu54Leu) pathogenic variant found in seven individuals—three of them symptomatic. Only one family with the same variant and with a Swedish origin has been clinically described so far. Our patients are characterized by predominant cardiac involvement, very much similar to the Swedish patients. Although the initial complaint was bilateral carpal tunnel syndrome, advanced amyloid cardiomyopathy was found in two symptomatic carriers at diagnosis with heart failure manifestations. The neurological involvement was considered as mild, with mainly sensory signs and symptoms being present. We followed a non-biopsy algorithm to confirm the diagnosis. Tafamidis 61 mg has been initiated as the only approved disease modifying treatment for ATTR cardiomyopathy. Clinical stability in the absence of adverse events has been observed at follow up

Holistic ecological design: Sustainable building practices striving to promote positive engagement with the environment

RESEARCH QUESTION How can urban housing development employ holistic ecological design techniques to positively engage with the environment and enhance sustainable building practices? ABSTRACT Humans cannot live without impacting the environment, but this should not stop designers from creating sustainable buildings. Urban developments are moving further away from nature, with little to no integration with the biosphere, separating humans from the living world day by day. Cities are never-ending destructive developments that are constantly changing and growing. These built environments treat the planet as a pit of endless resources by unsustainably consuming natural and non-renewable resources and then simply throwing them away. The research aims to produce a design with minimal environmental impact and thoughtful integration into the biosphere through a holistic ecological design. Literature, precedents, site and life-cycle reviews will be used to inform the design decisions throughout the project, with embodied carbon energy research backing up the concepts and design decisions applied within the project. The scope of the project is focused on the construction methods of buildings. There are many elements to sustainability, with ecological design being one of the many theories used to achieve it. Designing passive and self-sufficient homes are common within the current solutions to creating sustainable buildings with the structural system commonly overlooked within sustainable design. Linear economy buildings cannot continue to be designed and developed as they produce large amounts of waste and negatively impact the environment through a lack of life-cycle considerations, producing large amounts of waste and raw materials that end up in landfills to be lost forever. The project has focused on challenging ways in which Architecture can promote sustainable building practices, showcasing a modular and adaptable building that allows for disassembly and reuse of the materials used to construct it. However, sustainable design cannot be broken into singular elements; in order to achieve a fully sustainable design, it needs to consider every element as a whole. The whole infrastructure of the building, its life-cycle and how people occupy it all play large roles in the impacts a building have on the environment. The structure of a building is simply one piece of the puzzle

Chemical speciation in mining affected waters: the case study of Asarel-Medet mine

The inorganic chemical species in Maresh and Luda Yana rivers affected by the Cu-Mo Asarel-Medet mine, Bulgaria were determined during a low-flow and a high-flow period. The mining activities, the weathering and the oxidation processes strongly influenced the physicochemical processes in the whole water system. The main pollution source was a small lake receiving the acid effluents of the mining activities. High levels of SO42-, Cu, Mg, Al, Mn and Fe were determined at the mining polluted and affected stations. Cu2+ and CuCO30 species (1: 1) were present in the reference waters and Cu2+ and CuSO40 species (1: 1) in the polluted and affected waters; Cu2+ species was dominating downstream. Me2+ followed by MeSO40 (Me = Mn, Zn, Cd and Pb), PbCO30 and PbHCO3+ species as well as Fe(OH)(2)(+), Al(OH)(4)(-), Al(OH)(2)(+), Al(OH)(3)(0) were prevailing in the system. MeSO4+ ans Me(SO4)(2)(-) (Me = Fe, Al), Me(SO4)(2)(2-) (Me = Zn, Cd and Pb), Me(SO4)(3)(4-) (Me = Zn, Cd) and Cd(SO4)(4)(6-) species appeared in polluted and affected waters.The trace element concentrations decreased downstream due to dilution, sorption processes and precipitation, but the percentage of free metal species, which are more toxic, increased. An exception was iron and aluminum of which the dominant hydroxy colloidal and sulphate species were easily incorporated into the suspended phase

Invasive Alien Species of Benthic Macroinvertebrates and Fish in the Bulgarian Sector of the Danube River—Results of the Joint Danube Survey 4 (JDS4)

The aim of this study was to assess the status of aquatic invasive alien species (IAS) in the shoreline zone of the Bulgarian sector of the Danube River, Danube tributaries, and adjacent standing water bodies in the frame of the Joint Danube Survey 4 (JDS4). Seven benthic macroinvertebrates and seven fish IAS were identified. The crayfish Faxonius limosus was frequently found and abundant in the tributaries. The mussels Corbicula fluminea, Dreissena rostriformis bugensis, and Sinanodonta woodiana dominated in the Danube River and the middle and lower reaches of the tributaries, while the fish Carassius gibelio, Perccottus glenii, and Lepomis gibbosus were most abundant in the standing water bodies. The integrated biocontamination estimated by taxonomic groups (crayfish, molluscs, and fish), sampling methods, and type of water bodies ranged from moderate in the shoreline zone of the Danube River, through moderate to high in the canals and lakes, to severe in the Danube tributaries and the reservoirs. The results demonstrate the importance of IAS in the assessment of the ecological status/potential of the water bodies in the DRB. The comprehensive evaluation of the aquatic IAS pressure will provide valuable information and support for the implementation of the national and EU IAS and water policies in the DRB