Immunosuppression seems to be the most important cause of BKPyV reactivation. Recently, a spectrum of diseases associated with BKPyV infection has been reported in HIV-infected patients. BKPyV ...isolates can be classified into four subtypes based on nucleotide polymorphisms within VP1 coding region. Mutations within the BC loop of the VP1 may be associated with an increase in the viral pathogenicity. The aims of this study were to determine prevalence and distribution of BKPyV subtypes, sequence variation and mutations within VP1 among HIV-infected patients and healthy donors. Urine samples from 114 HIV-infected patients and 120 healthy donors were collected. PCR followed by sequence analysis was carried out using primers specific for VP1 and NCRR of the virus genome. The predominant BKPyV subtype was I, followed by IV. In isolates from HIV-infected patients, the majority of non-synonymous alterations were located within the BC loop. BKV sequences from healthy donors showed non-synonymous alterations outside of the receptor loops in the β-sheets. The higher frequency of mutations in the BC loop of VP1 protein was detected among HIV-infected patients. The most frequent mutation was E82D. All HIV-infected patients who harbored mutations had CD4
+
cell counts less than 200 cell/mm
3
. It seems that immunosuppression is a very important factor for BKPyV reactivation that can increase viral replication rate and leads to higher frequency of mutations in the BC loop of the VP1. These mutations may change receptor specificity, and further studies are needed to determine the effect of these mutations on the biological properties of the BKPyV.
UVOD:Primarna Epstein-Barr virusna (EBV) infekcija može se manifestovati kao infektivna mononukloza (IM). Takođe, EBV infekcija može predstavljati važnu kariku u etiologiji velikog broja tumora, među ...kojima su najbrojniji limfomi, nazofaringealni (NFK) i gastrični karcinom, kao i limfoproloferativne bolesti kod imunosuprimiranih pacijenata. Brojna su istraživanja koja nagoveštavaju vezu između karakteristika pojedinih EBV genotipova i onkogenog potencijala. Pretpostavlja se i da postoji veza između geografske specifičnosti virusa sa potencijalno onkogenom strukturom njegovog genoma. CILJEVI:Ovim istraživanjem utvrđuje se dominacija EBV genotipa i određuju LMP-1 varijante i EBNA-1 subtipovi. Takođe, ciljevi se odnose i na identifikaciju novih i geografski specifičnih mutacija, kao i utvrđivanje moguće povezanosti polimorfizama različitih EBV gena, identifikovanih mutacija i prirode oboljenja. MATERIJAL I METODOLOGIJA:Studija je obuhvatila 360 pacijenata sa IM, transplantiranim organom (T) ili NFK tipa UCNT (engl. undifferentiated carcinoma of nasopharyngeal type). Korišćeni su uzorci krvi IM i T pacijenata, kao i parafinski kalupi tkiva UCNT pacijenata. Nested-PCR metod korišćen je za dokazivanje EBNA-2, LMP-1 i EBNA-1 gena, kao i za genotipizaciju EBNA-2 gena. Nakon DNK sekvenciranja specifičnih regiona LMP-1 i EBNA-1 gena, sledila je filogenetska analiza dobijenih sekvenci. Obrađene sekvence koristile su se za uzajamno poređenje varijabilnosti EBV gena, kao i za poređenje sa kliničkim parametrima pojedinačnih oboljenja. REZULTATI:Devedeset uzoraka (25%) bilo je pozitivno na prisustvo EBV DNK Dominantan genotip EBNA-2 izolata bio je genotip 1 (89,61%). Identifikovano je 4 od sedam poznatih LMP-1 varijanti: B95-8, Kina 1, SK (Severna Karolina) i Med (Mediteran) i 2, do sada nepoznate, varijante Srb 1 i Srb 2 (Srbija 1 i 2). Najučestalija bila je varijanta B95-8 (31%), a dokazana je i statistički značajna razlika u distribuciji varijanti među oboljenjima (p=0,039). LMP-1 delecije su otkrivene kod 39% izolata, i to: dve poznate delecije od 30-bp i 69-bp, i dve novoidentifikovane delecije od 27-bp i 147-bp. Prisustvo delecije nije bilo povezano sa određenim oboljenjem. Kod nekih LMP-1 varijanti pronađene su dodatne jedinstvene aminokiseline: kod B95-8 Ser na lokusu 309, kod Kine 1 Asn na lokusu 322, a kod SK Asn na lokusu 250. Takođe je pokazano da je kraća delecija povezana sa manjim brojem 33-bp ponovaka.Identifikovana su 4 EBNA-1 subtipa: P-thr, P-ala, V-val i V-ala. Distribucija subtipova nije se razlikovala među oboljenjima. Najčešći subtip P-thr, dalje je klasifikovan u 6 subvarijanti (sv-1 do sv-6) pri čemu su P-thr-sv-2, P-thr-sv-4, P-thr-sv-5 i P-thr-sv-6 novoidentifikovane subvarijante. P-thr-sv-5 dokazan je kao specifičan za UCNT izolate.Prisustvo EBV DNK koreliralo je sa težinom kliničke slike IM. Učestalost prisustva EBV DNK u UCNT biopsijama opadalo je sa rastom TNM gradusa. Najlošiji TNM gradus (N3) UCNT bioptata bio je povezan sa prisustvom LMP-1 delecije. Ispitivane su i kombinacije varijabilnosti između EBV gena, pa je identifikovano 10 različitih grupa polimorfizama. Dokazana je veza između genotip 1/Med/P-thr polimorfizma sa NFK, a genotip 1/Kina 1/P-thr sa IM. Pojedine LMP-1 varijante bile su povezane sa određenim EBNA-1 subtipom: Kina 1 sa P-thr, SK sa P-ala, dok je jedan Srb 1 izolat bio udružen sa Pthr. Takođe, izolati V-ala i P-ala subtipa uglavnom su bili udruženi sa LMP-1 bez delecije. Sa povišenim vrednostima AST kod IM izolata, bila su povezana 2 polimorfizma: “sa LMP1 del/P-thr” i “bez LMP-1 del/P-ala”. Kod povišenih vrednosti ALT, bio je prisutan samo polimorfizam “bez LMP-1 del/P-ala”. Kao mogući prediktori UCNT progresije, identifikovani su: genotip 1/≤4,5 33-bp pon/P-ala i genotip 1/>4,5 33-bp pon/P-thr.ZAKLJUČAK:Rezultati ove studije ukazuju na nova mesta za definisanje pojedinih kategorija varijabilnosti, opisuju novoidentifikovane mutacije, 2 nove LMP-1 delecije, LMP-1 varijante Srb1 i Srb2 i 5 EBNA-1 subvarijanti. Takođe, dokazane su posebne povezanosti između polimorfizama 2, odnosno 3 EBV gena. Identifikovane su i geografski specifične mutacije, ali i izmene genoma koje su u korelaciji sa kliničkim tokom oboljenja. Tako je utvrđena povezanost delecije u okviru LMP-1 gena sa najlošijim TNM gradusom (N3) UCNT izolata.
Surfactants, or surface-active substances (SAS), are amphipathic organic substances that adsorb on aquatic phase boundaries, including the air-sea interface that covers ~70% of Earth's surface. SAS ...thus mediate all mass transfer across the air-sea interface and are central to planetary scale biogeochemical processes. SAS are routinely quantified in seawater and freshwater in terms of total surfactant activity (SA), using alternating current (AC) out-of-phase voltammetry with a hanging mercury drop electrode (HMDE). Although this technique is well established, method modifications have been implemented and differing calibration procedures adopted in individual research laboratories. Increasing interest in the environmental roles of SAS prompts a timely inter-comparison of these varying analytical approaches. Using sea-surface microlayer (SML: uppermost 80 μm layer sampled) and sub-surface (SSW: 1 m depth sampled) seawater from Jade Bay (south-eastern North Sea), we carried out the first inter-laboratory comparison for SA, using methods and calibration protocols previously established in three participating laboratories. The internal calibration protocol follows direct calibrations of individual samples against the model surfactant Triton-X-100 during analysis, whereas external calibration produces independent Triton-X-100 calibration curves; both protocols express SAS concentrations in Triton-X-100 equivalents (T-X-100 eq.). There was no significant difference between SA derived via internal or external calibration protocols, or by using different analytical instruments (range in Kruskall-Wallis and Dunn-Bonferroni post-hoc test p-values: 0.062–1.000), except where freeze/thaw degradation was suspected to have occurred during transit (p < .001). We recommend using discrete calibration standards during external calibration. Irrespective of any differences in SA determined by the three laboratories, the SA enrichment factor (EF: =SASML/SASSW) was not affected for any sample; the root mean square error (±one standard deviation) between all laboratories was 0.156 ± 0. 226 (n = 45). We present and discuss recommendations for a standard analytical protocol to ensure the inter-laboratory compatibility of SAS measurements into the future.
•An inter-laboratory quantification of total surfactant activity (SA) in seawater•Different calibration protocols produced comparable SA measurements.•Discrete calibration standards must be used during external calibration method.•All tested procedures resulted in comparable SA enrichment factors.
Variants in the TTN gene have been associated with distal myopathies and other distinctive phenotypes involving skeletal and cardiac muscle. Through whole-exome sequencing we identified a novel ...stop-gain variant (c.107635C>T, p.(Gln35879Ter)) in the TTN gene, coding a part of the M-line of titin, in 14 patients with autosomal recessive distal myopathy and Serbian ancestry. All patients share a common 1 Mb core haplotype associated with c.107635C>T, suggesting a founder variant. In compound heterozygotes, nine other TTN variants were identified: four stop-gain, three frameshift, one missense and one splice donor variant. Patients homozygous for the common variant did not show significant clinical differences to the compound heterozygous patients. The clinical presentation of all patients was an adult onset distal myopathy with predominant lower limb involvement. In addition, most patients had normal to mildly elevated serum creatine kinase levels, myopathic electromyograms, normal cardiologic and respiratory tests and muscle pathology consistent with a dystrophic process. In this study, we describe a distinct phenotype for patients with distal myopathy associated with novel recessive TTN variants including a Serbian founder variant. Our results expand the phenotypic and genetic spectrum of titinopathies and will facilitate the diagnosis of this condition in patients of Serbian origin.
Background/Aim. Laryngeal carcinomas make 1%?3% of all head and neck malignancies.Treatment outcome and survival rates depend greatly on established stage of the disease. The purpose of this study ...was to examine the survival of the patients with advanced laryngeal carcinoma depending on gender, age, common risk factors (tobacco and alcohol use), primary tumor localization, histopathological tumor grade, clinical TNM (tumor, node and metastasis) stage and surgical treatment of the disease. Methods. Retrospective study included 252 patients treated surgically for advanced squamocellular carcinoma of the larynx in a threeyear period with five-year follow-up. Patients included in the study were treated primary with surgery, with postoperative radiotherapy and chemotherapy depending on the stage of the disease, intraoperative findings and tumor resection borders. Overall survival and disease-specific five-year survival of patients was calculated for demographical and clinical characteristics of the patients. Results. Overall 5-year survival of patients with operable advanced laryngeal cancer included in the study was 86.14% and disease-specific survival 86.51%. Lower overall and the disease-specific survival was associated with age, higher histological tumor grade and more extensive neck dissections. Conclusion. Primary total laryngectomy results in higher survival outcomes in cases of transglottic T3 and T4a laryngeal tumors. Patients should be informed of the likely increased mortality risks tied to the choice of surgical resection and treatment modality before their decision.
nema
Backround/Aim. Considering the distinct increase in the incidence of oropharyngeal cancer over oral cavity cancers and changing epidemiology with human papilloma virus (HPV) infection emerging as an ...important risk factor, there is a need to establish better treatment choices in specific groups of patients with oropharyngeal cancer. The aim of this study was to assess the quality of life (QOL) and functional performance and the impact of different demographical data, stage of disease, and treatment type on these parameters in patients with oropharyngeal cancer with successfully achieved locoregional control a year after the treatment. Methods. Study included 87 patients who underwent QOL and functional impairment assessment 12 to 14 months after finished oncological treatment with the following questionnaires: the European Organization for Research and Treatment of Cancer Quality-of Life-Questionnaire-C30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cancer Quality of- Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) and The Karnofsky Performance Scale (KPS). Results. Specific groups of patients had significantly different post-treatment QOL scores. The factors associated with the worse QOL scores were female gender, not being in a partnership, level of education and HPV status. Conclusion. Clinicians should consider socioeconomic factors and HPV status in planning the recovery after treatment of patients with oropharyngeal carcinoma. Gender, education level and employment are the variables that form a certain risk profiles associated with the lower QOL.
nema
Limb-girdle muscular dystrophy (LGMD) type 2A (calpainopathy) is an autosomal recessive disease caused by mutation in the
gene. The aim of this study was to examine genetic and phenotypic features of ...Serbian patients with calpainopathy. The study comprised 19 patients with genetically confirmed calpainopathy diagnosed at the Neurology Clinic, Clinical Center of Serbia and the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia during a ten-year period. Eighteen patients in this cohort had c.550delA mutation, with nine of them being homozygous. In majority of the patients, disease started in childhood or early adulthood. The disease affected shoulder girdle - upper arm and pelvic girdle - thigh muscles with similar frequency, with muscles of lower extremities being more severely impaired. Facial and bulbar muscles were spared. All patients in this cohort, except two, remained ambulant. None of the patients had cardiomyopathy, while 21% showed mild conduction defects. Respiratory function was mildly impaired in 21% of patients. Standard muscle histopathology showed myopathic and dystrophic pattern. In conclusion, the majority of Serbian LGMD2A patients have the same mutation and similar phenotype.
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