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P. Grubor, Traumatološka klinika Umc Banja Luka, M. Grubor, M. Biscevic, Rade Tanjga, Ul.Mladena Stojanovića Banja Luka Zu Dr Grubor, U. S. B. I. H. Klinika za ortopediju i traumatologiju

J. Bojanić, Herzegovina

APSTRAKT Vaccines have made a major contribution to global public health, including the eradication of one deadly disease, small pox, and the near eradication of another, poliomyelitis. In the future, vaccination will be expected to eliminate the remaining childhood infectious diseases. Development of new, safe and effective adjuvants is also an important part of vaccine research. The new technologies minimize the risks associated with the new generation of vaccines. Research is also taking place into ways of making vaccines more thermostable, reducing the need for a cold chain for their storage and delivery. There are already needleand pain-free vaccines that can be given as a nasal spray or taken orally, but researchers are coming close to releasing a new form of vaccine delivery called vaccine patches. Vaccines can be used as a prevention of the development of a cancer or control of a cancer, but also to help to control chronic non-infectious diseases in adults. A large number of very important vaccines such as vaccines against human papilloma virus, enterovirus 71, malaria, herpes zoster, meningococcal type B, as well as the first nasal vaccine and the first quadrivalent influenza vaccine etc. have been approved since 2000, and a great number of vaccines are currently under investigation.

Introduction: Progressive pseudorheumatoid dysplasia (PPD) is an autosomal recessive genetic disorder reported to be caused by gene alterations of the Wnt1-inducible signaling pathway protein 3 corresponding gene (WISP3) located on chromosome position 6q22.  Up to date, there is only a handful of WISP3 mutations identified in Europe, whereas most mutations are identified in Asia and Middle East.  According to our knowledge, this is the first report of genetic dissection of WISP3 associated with spondyloepiphyseal dysplasia tarda from Bosnia and Herzegovina. Based on clinical examination findings (general manifestations, physical examination, characteristics of their bones on X-ray and laboratory results), an index patient was directed to WISP3 genotyping for confirmation of suspected diagnosis of PPD.Methods: DNA was extracted from peripheral blood leukocytes. All 5 exons and their exon-intron boundaries of the WISP3 gene were amplified by polymerase chain reaction (PCR) and sequenced by Sanger method. Segregation analysis was done to confirm the familial carrier status.Results: A missense mutation (C223G) - homozygous T to G transition at c.667 in exon 4 was identified in index patient. This mutation changed codon CAG to TAG and resulted in a subsequent change of the cysteine to glycine codon. Same mutation was observed in both parents in heterozygous form confirming the familial segregation.Conclusion: Due to its nature, the identified mutation C223G in exon 4 in WISP3 gene is the most probably causative for PPD in described patient. Here we describe the PCR based method for genotyping of specific mutation in WISP3 gene. The identification of this mutation might be a valuable addition to a regional databases on rare genetic variant although a functional analysis should be performed to explain its pathological effect.

N. Toplak, M. Debeljak, T. Avčin

Familial Mediterranean fever (FMF) is a rare disease in Central and Eastern European countries and phenotype -genotype correlation in this population is not well established.

Background PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum and acne) is a rare autosomal-dominant autoinflammatory disease caused by mutations in PSTPIP1gene. Typically presents with recurrent sterile, erosive arthritis in childhood, occurring spontaneously or after minor trauma, occasionally resulting in significant joint destruction. By puberty, joint symptoms tend to subside and cutaneous symptoms increase. Cutaneous manifestations include pathergy, frequently with abscesses at the sites of injections, severe cystic acne, and recurrent nonhealing sterile ulcers, often diagnosed as PG.

Slobodan Simovic, V. Laković, Nadežda Gudelj

Covecanstvo je vekovima funkcionisalo na principu tržista ponude, a u poslednjih pedeset godina to je zamenjeno tržistem potražnje. Danas svet ulazi u tržiste znanja, koje implicira da se poseduje znanje, tj; informacija. Države se sada bore za primat u strukturi znanja. Tako da moc odlazi iz ruku kapitalno bogatih u ruke intelektualno bogatih. Danas, u 57 zemalja sveta postoje državne institucije koje se bave prikupljanjem tajnih informacija ove vrste, a vlade jos barem 100 zemalja trose deo nacionalnog dohotka na pokrivanje troskova industrijske spijunaže. U tome se posebno isticu Nemacka, Japan i Francuska, a za petama su im Rusija, Kina i Južna Koreja. Savremeno ustrojstvo sveta, karakterisu i savremeni međunarodni odnosi, a ove odnose karakterise globalizacija. Posebno mesto i ulogu u tome imaju transnacionalne kompanije (TNK), kojima je osnovni cilj dominacija i kontrola tržista, a to iziskuje izuzetnu potrebu ovladavanja znanjima u svim njegovim vidovima. U borbi za tržista, znanje je najmocnije oružje, a do "ubojitog oružja" se uvek dolazilo na sve moguce nacine, a sada se, kao sredstvo najcesce koristi industrijska spijunaža. ---------------------- New structure of the world is increasingly imposing economic game instead of military conflict. This game, unfortunately, is not characterized by fair play.There is no war on international scale, but for many years lasts, "first world economic war." Economic competition has become planetary. Every nation wants to export more, all over the world. Every serious nation wants to win this new kind of war in which the victims are companies,states, but above all,individuals. Once again comes another era of domination of industrial espionage in the world,espionage , which follows the man's activity from the oldest historical periods. Industrial espionage now becomes main job of the traditional spies.State institutions and industrial companies now employ spies to steal information. In many cases these are former military and civilian spies, but there are also native spies who switched to the broking of industrial information. The modern structure of the world is also characterized by contemporary international relations, and these relations are characterized by globalization. The special place has TNK whose main goal is the domination and control of the market, and it requires an exceptional need for mastery of knowledge in all its aspects. In the battle for market knowledge is the most powerful weapon, and a "lethal weapon" has ever been reached in every possible way, and now, as a mean that is commonly used is industrial espionage.

Arthur Gatouillat, Héloïse Bleton, J. VanSwearingen, S. Perera, Scott Thompson, Traci Smith, E. Sejdić

Gait is a complex process involving both cognitive and sensory ability and is strongly impacted by the environment. In this paper, we propose to study of the impact of a cognitive task during gait on the cerebral blood flow velocity, the blood flow signal features and the correlation of gait and blood flow features through a dual task methodology. Both cerebral blood flow velocity and gait characteristics of eleven participants with no history of brain or gait conditions were recorded using transcranial Doppler on mid-cerebral artery while on a treadmill. The cognitive task was induced by a backward counting starting from 10,000 with decrement of 7. Central blood flow velocity raw and envelope features were extracted in both time, frequency and time-scale domain; information-theoretic metrics were also extracted and statistical significances were inspected. A similar feature extraction was performed on the stride interval signal. Statistical differences between the cognitive and baseline trials, between the left and right mid-cerebral arteries signals and the impact of the antropometric variables where studied using linear mixed models. No statistical differences were found between the left and right mid-cerebral arteries flows or the baseline and cognitive state gait features, while statistical differences for specific features were measured between cognitive and baseline states. These statistical differences found between the baseline and cognitive states show that cognitive process has an impact on the cerebral activity during walking. The state was found to have an impact on the correlation between the gait and blood flow features.

Arthur Gatouillat, Héloïse Bleton, J. VanSwearingen, S. Perera, Scott Thompson, Traci Smith, E. Sejdić

Gait is a complex process involving both cognitive and sensory ability and is strongly impacted by the environment. In this paper, we propose to study of the impact of a cognitive task during gait on the cerebral blood flow velocity, the blood flow signal features and the correlation of gait and blood flow features through a dual task methodology. Both cerebral blood flow velocity and gait characteristics of eleven participants with no history of brain or gait conditions were recorded using transcranial Doppler on mid-cerebral artery while on a treadmill. The cognitive task was induced by a backward counting starting from 10,000 with decrement of 7. Central blood flow velocity raw and envelope features were extracted in both time, frequency and time-scale domain; information-theoretic metrics were also extracted and statistical significances were inspected. A similar feature extraction was performed on the stride interval signal. Statistical differences between the cognitive and baseline trials, between the left and right mid-cerebral arteries signals and the impact of the antropometric variables where studied using linear mixed models. No statistical differences were found between the left and right mid-cerebral arteries flows or the baseline and cognitive state gait features, while statistical differences for specific features were measured between cognitive and baseline states. These statistical differences found between the baseline and cognitive states show that cognitive process has an impact on the cerebral activity during walking. The state was found to have an impact on the correlation between the gait and blood flow features.

E. Sejdić, Alexandre Millecamps, J. Teoli, M. Rothfuss, Nicholas G. Franconi, S. Perera, A. Jones, J. Brach et al.

Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults.

M. Aleckovic-Halilovic, D. Nel, A. Woywodt

Two articles in this issue deal with granulomatous acute interstitial nephritis (GIN), a rare disorder seen in 0.5–0.9% of native and 0.6% of transplant renal biopsies [1]. In the first article, Agrawal and co-workers report 10 years of experience with GIN in a tertiary centre in India [2]. In contrast to the experience from Western countries, tuberculosis accounted for more than half of cases. The authors emphasize the challenge of making the diagnosis and recommend a high degree of suspicion [2]. In a second article, Shah and colleagues from the USA [3] review GIN and also highlight current challenges in describing the interesting case of a 69-year-old man with GIN ascribed to doxycycline in whom a positive quantiferon test was received and who eventually died from multi-organ failure. Without autopsy we will never know whether he actually had tuberculosis but their case also reminds us that even with sophisticated testing the cause of GIN remains unclear in a proportion of patients. In this comment, we reflect on both articles and provide some context with an emphasis on pathology and disease patterns worldwide, pitfalls and the diagnostic approach in clinic.

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