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This paper tries to present morphological productivity of compound nouns in a corpus comprised of news, literary, academic and TV registers using an onomasiological approach, namely, the productivity at the level of word-formation rules. The productivity at the aforementioned level is the union of the productivity at the level of word-formation types and morphological types. By using manual, descriptive, analytic and statistical methods, we came to 571 examples of compound nouns that fell into 10 different conceptual categories (Agent, Action, Result, Object, Location, Instrument, Substance, Time, Quantity, State), i.e. clusters. Each cluster offered pieces of information on the interaction of different concepts within different word-formation types together with the morphological aspect through different morphological types, which was the aim of the paper. The results proved our initial hypothesis that the interaction of different elements is of the utmost significance for better understanding of compounding. The interaction of two concepts dominated all clusters while the combination of two stems, especially two nouns, dominated morphological types.

BackgroundTo address if the long-standing association between maternal infection, depression/anxiety in pregnancy and offspring neurodevelopmental disorder (NDD) is causal we conducted two negative-control studies.MethodsFour primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy and siblings) born between 1st January 1990 to 31st December 2017 were constructed.NDD included autism/autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, BMI (Body Mass Index), NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured.The NDD incidence rate among 1) children exposed during or outside of pregnancy and 2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders.ResultsThe analysis included 410,461 children of 297,426 mothers and 2,793,018 person-years of follow-up with 8900 NDD cases (incidence rate=3.2 per 1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy adjusted HR=1.58, 95%CI 1.46-1.72; 1-year adj.HR=1.49, 95%CI 1.39-1.60; 2-year adj.HR=1.62, 95%CI 1.50-1.74); and to a lesser extent, of infection (pregnancy adj. HR=1.16, 95%CI 1.10-1.22; 1-year adj.HR=1.20, 95%CI 1.14-1.27; 2-year adj.HR=1.19 95%CI 1.12-1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR=0.97, 95%CI 0.77-1.21 or infection HR=0.99, 95%CI 0.90-1.08.ConclusionsTriangulation of results from two negative control studies provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.

BackgroundImmune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19.MethodsStudy included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity.ResultsAntinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135).ConclusionIncreased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

Bakhtin’s views (1980:127-130) on the importance of studying speech representation and its interaction with authorial context incited prolific research in various disciplines. The research presented in this paper is based on Bakhtin’s crucial claims about speech representation, and on the theoretical framework of linguistic stylistics (Kovačević 2011, 2012, 2013, 2015; Katnić-Bakaršić 2001) and representology (Kovačević 2015:253-254). The aim of this paper is twofold—to identify the types of speech, thought and writing representation employed in the novel Sense and Sensibility and to describe their interaction with the authorial context. The method applied is‘word by word’ analysis, where in the first stage the modes of speech, thought and writing representation are identified; in the next stage their interaction with authorial context is described. The modes of speech are classified and differentiated by combining the classifications of representation modes in Serbian and English (Leech and Short 2007; Semino and Short 2004; Kovačević 2013). The results of the analysis prove that Jane Austen employs the following modes to repоrt speech, thought and writing: indirect speech/thought/writing, narrator’s report of speech act/ thought act/writing act, expressive indirect speech/thought, free indirect speech/thought, direct speech (monologue, dialogue, polylogue), free direct speech, line of dialogue, fragmental quote, hypothetical speech, direct thought, free direct thought, direct writing, embedded speech/thought. Predominantly, the line of interaction between authorial speech and direct speech involves the former being parenthetically embedded into foregrounded direct speech, amalgamating with the free indirect thought/speech or having as an attachment a ”package” of different embedded modes of speech/thought/writing representation. Primarily indirect thought, free indirect thought, direct thought, and free direct thought are the modes employed to characterise Elinor Dashwood, while on the other side the modes of direct speech, free direct speech, free indirect speech and direct writing combined with numerous mimetic markers prevail in depicting her sister Marianne. It is through the stylistically effective transitions between these modes and their interaction with the authorial context that the total antithetical effect regarding the sense and sensibility principles is obtained on the syntactic-stylistic level.

Although the use of high-frequency (higher than 20MHz) ultrasound dates back to the 1980s, its use has not yet become routine in everyday dermatological practice. High-frequency ultrasound is now used as an additional diagnostic method, primarily in the examination of cutaneous tumors. Only a few examinations dealt with the possibilities of high-frequency ultrasound in the examination of inflammatory skin changes We wanted to analyze the echographic manifestations of inflammation in different inflammatory dermatoses. The analyzed skin lesions were biopsied and the clinical diagnosis was confirmed pathohistologically, and the pathohistological characteristics were corelated with echographic manifestations. Regarding inflammation, cellularity of lesions (presence and amount of inflammatory infiltrate), oedema, dilated lumen of blood vessels was the most significant pathohistological changes that reflect on echosonografic manifestation of inflammatory skin lesions. In addition to collagen (its amount and distribution), the echogenicity of inflammatory skin changes is significantly affected by the cellularity of changes, and both hypercellularity (primarily inflammatory infiltrate) and hypocellularity (changes in the type of blisters). Monitoring of these data can potentially be used in monitoring the evolution of the disease, but also in monitoring the effectiveness of applied therapy in certain dermatoses.

Background: while reports indicate the association between obesity and back pain, its mechanism is still unclear. Thus, we aimed to investigate the effects of weight and its components on back pain in middle-aged women while considering direct mechanical and indirect effects via inflammatory and metabolic parameters.Methods: we used data from the Chingford 1000 Women Study, two follow-ups seven years apart. We assessed effects of weight, body mass index (BMI), total fat mass (TFM), total lean mass (TLM) and total bone mineral density (TBMD), measured by dual-energy X-ray absorptiometry, on back pain episode. We used inflammatory (C-reactive protein, interleukin-6, and tumour necrosis factor-alpha) and metabolic parameters (systolic and diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and fasting blood glucose) as mediators of indirect effects. We investigated associations of interest cross-sectionally and longitudinally using binary logistic regression and parallel mediation model.Results: we included 826 Chingford middle-aged women (mean age=60.7, SD=5.9) from the first used follow-up in cross-sectional and mediation analyses and 645 women that attended the follow-up seven years later, in longitudinal analyses. We found that increased weight was directly associated with increased odds of having back pain episode (OR=1.02; 95% CI 1.01-1.03), similarly as BMI (OR=1.05; 95% CI 1.02-1.08) and TFM (OR=1.03; 95% CI 1.01-1.04) consistently across the cross-sectional and longitudinal models, but not TLM or TBMD. However, we did not find consistent indirect effects of weight or its components through measured inflammatory or metabolic parameters on back pain.Conclusions: our results show that in middle-aged women, weight, BMI and TFM are directly related to back pain, indicating prominence of mechanical loading effect.

Objective We aimed to study 19-year body mass index (BMI) patterns and their (1) bidirectional relationship with musculoskeletal pain and (2) mortality risk. Study design and Setting We used data from the Chingford study and group-based trajectory modelling to define 19-year BMI patterns. We investigated whether baseline back, hand, hip, and knee pain (as single- and multi-site) predicted 19-year BMI trajectory, and whether 19-year BMI patterns predicted pain in year 20. We explored BMI trajectories and mortality risk over 25 years (life expectancy). Results We included 938 women (mean age: year-1=54, year-20=72) and found seven distinct 19-year BMI trajectories: two normal-weighted (reference), slightly overweight, lower and upper overweight-to-obese, lower and upper obese. BMI patterns capturing the increase overweight-to-obese (BMI 27-34 overtime) were bidirectionally related to knee and multi-site pain. The lower obese pattern (BMI 33-38) was unidirectionally associated with lower limb pain. Women with BMI above 40 had an increased all-cause and cardiovascular mortality risk. Conclusions For most postmenopausal women, the overweight WHO category was a transition. Two patterns capturing increase overweight-to-obese were mutually related to musculoskeletal pain, i.e., knee and multi-site pain contributed to becoming obese, and trajectories of becoming obese increased the odds of experiencing pain later.

Benzodiazepines and benzodiazepine-related medications (BBRMs) are anxiolytics and hypnotics acting on γ-amino butyric acid (GABA)A receptors. BBRMs are assumed to have a low potential for major congenital malformations, but research on more subtle and protracted developing symptoms of these medications is lacking. Therefore, we prospectively investigated the association between BBRM use in pregnancy and long-term effects on child behavior in a large population-based cohort study. The study population consisted of 104 children prenatally exposed to BBRM, 527 children exposed to maternal prenatal anxiety or phobic anxiety symptoms (without exposure to BBRM), and 5609 control children. At child age, 6 years, Oppositional Defiant Disorder (ODD), Aggressive Behavior and Anxiety Problems were assessed by the Child Behavior Checklist (CBCL) reported by the mother and the Teacher Report Form (TRF). Children prenatally exposed to BBRM had higher scores of ODD and aggressive behavior, but not of anxiety. However, these associations were explained by maternal anxiety symptoms during pregnancy. Moreover, prenatal exposure to anxiety (without exposure to BBRM) was associated with increased scores of child ODD, aggressive behavior, and anxiety. In conclusion, the current study demonstrates that prenatal BBRM exposure was not independently associated with ODD and aggressive behavior in childhood when prenatal anxiety symptoms were taken into account.

Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, plasma and synovial fluid IL-6 (p-IL-6, sf-IL-6) were measured in 104 end-stage knee OA patients. Contrast-enhanced magnetic resonance imaging (MRI) was used to semi-quantitatively assess an 11-point synovitis score; pain was assessed by the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and the Neuropathic Pain Questionnaire (NPQ). Linear regression was used to investigate associations between biomarkers and synovitis, and biomarkers and pain while controlling for age, sex and body mass index. We also tested whether associations between biomarkers and pain were confounded by synovitis. We found sf-IL-6 was associated with synovitis in the parapatellar subregion (B=0.006; 95% CI 0.003-0.010), and no association between p-IL-6 and synovitis. We also observed an association between C1M and synovitis in the peri-ligamentous subregion (B=0.013; 95% CI 0.003-0.023). Further, sf-IL-6, but not p-IL-6, was significantly associated with pain, WOMAC (B=0.022; 95% CI 0.004-0.040) and NPQ (B=0.043;95% CI 0.005-0.082). There was no association between C1M and WOMAC pain but we did find an association between C1M and NPQ (B=0.229; 95% CI 0.036-0.422). Lastly, synovitis explained both biomarker-NPQ associations, but not the biomarker-WOMAC association. These results suggest C1M and IL-6 are associated with synovitis and pain, and synovitis is an important confounding variable when studying biomarkers and neuropathic features in OA patients., 19 pages, 2 figures, 5 tables and 2 supplementary figures

Importance Previous studies, using mostly cross-sectional data, provide conflicting evidence of an association between lumbar spine radiographic changes and the severity of back pain–related disability. Such conflicting evidence may be associated with widely unnecessary diagnostic imaging of the lumbar spine. Objective To examine both cross-sectional and longitudinal associations between lumbar spine radiographic changes and the severity of back pain–related disability among middle-aged, community-dwelling women. Design, Setting, and Participants This population-based prospective cohort study used data from the Chingford 1000 Women Study. Analyses included data collected from year 6 (1994-1996; physical activity was measured), year 9 (1997-1999; treated as baseline), and year 15 (2003-2005), with a total length of follow-up for longitudinal analyses of 6 years. Data were analyzed from April 17 to November 3, 2020. Exposures Primary exposure was lumbar spine radiographic changes, defined using the Kellgren-Lawrence (K-L) grade. Secondary exposures were defined using presence of osteophytes and disc space narrowing. The composite score combined the number of lumbar spine segments with definite changes detected on radiographic images (ie, radiographic changes) (K-L grade ≥2, which means at least definite osteophyte and possible narrowing of disc space are present; osteophyte and disc space narrowing grade ≥1, which means at least mild or definite changes are present). Main Outcomes and Measures Self-reported back pain–related disability measured in years 9 and 15 assessed by the St Thomas disability questionnaire. Results Among 650 women (mean [SD] age, 61.3 [5.9] years) in cross-sectional analyses and 443 women (mean [SD] age, 60.6 [6.0] years) in longitudinal analyses, there was no evidence to support an association between higher number of lumbar segments with radiographic changes (K-L grade, osteophytes, and disc space narrowing) and more severe back pain–related disability (eg, cross-sectional analyses using the K-L grade; 1 segment vs 0 segment: adjusted odds ratio, 1.22 [95% CI, 0.76-1.96]). No interactions were found of an association between lumbar spine radiographic changes and the severity of back pain–specific disability with age, body mass index, or smoking status. Conclusions and Relevance In this cohort of middle-aged, community-dwelling women, there was no evidence to support an association between a higher number of lumbar segments with radiographic changes (K-L grade, osteophytes, and disc space narrowing) and more severe back pain–related disability cross-sectionally or over time. These findings provide further evidence against routinely using diagnostic imaging of the lumbar spine.

The paper aims to point out the necessity of creating a digital terminology database of the Serbian professional terminology which would provide systematically collecting, inventory making, precise identifying, defining, linguistic analyzing and interpreting terminologies of different professions for making a stable ground for the codification and standardization of professional terminology of the Serbian language. It also implicitly points to a need to organize terminology workshops through which the experts that “build” vocabularies of their profession would become familiar with the basic principles of creating or designing terminology expressed in the work with the database via the network interface and thus become more abler to work on different professional terminologies. In addition, the paper points out the most common mistakes in contemporary terminographic work as a result of lack of understanding of the meaning of inter- and multi-disciplinary approach to the study of terminology as a special branch of linguistic research. STATUS SRPSKE TERMINOLOŠKE LEKSIKOGRAFIJE U OKVIRIMA AKTUALNE JEZIČKE POLITIKE I JEZIČKOG PLANIRANJA U PERSPEKTIVI. PRIKAZ JEDNOG TERMONOLOŠKOG „ALGORITMA“ ‘Izgrađena’ na rezultatima savremenih naučnih studija na polju digitalnih pristupa lingvističkim istraživanjima i odatle na pojedinačnim postulatima moderne specijalizovane digitalne leksikografi je ova studija donosi predlog nacrta za elektronsko dizajniranje tzv. portreta odnosno svojevrsnih ‘biografi ja’ termina – ne samo onih koji pripadaju jezicima struka nego i onih iz okvira tzv. specijalističke narodne leksike – kroz novi terminološki algoritam, putem kojeg bi se u aplikacijama digitalnih nacionalnih terminoloških relacionih baza podataka u velikoj meri izbegle predvidive ali i one, u dosadašnjoj referentnoj literature, još uvek neprepoznate jezičke ‘zamke’, koje često stoje na putu savremenim terminolozima i terminografima, u procesu adaptacije nacionalnog sa internacionalnim digitalnim terminografskim opisom poštujući preporučeni ISO standard (/TK 37).

Tumor biomarker studies are integral to oncology clinical trials but may yield artifactual results owing to variation in sample procurement and processing. Ethanol, 70% vol/vol, was validated as a sample transport medium using markers of the PI3K/Akt/mTOR pathway. BT474 tumor xenografts were excised and slices were immediately placed into formaldehyde and fixed for 24 hours. Fixed tissue slices were immediately processed into paraffin or transferred to 70% vol/vol ethanol and stored at room temperature for 1, 2, and 4 weeks before further processing. Freshly cut tissue sections were evaluated for pAKTS473, HER2, pHER-2Y1248, pS6S235/236, and pS6S240/244, Ki-67, and HER2 by fluorescence in situ hybridization and stained with H&E and Masson trichrome. No significant changes were observed when comparing samples stored in 70% ethanol for up to 4 weeks with immediately processed tissue. Ethanol, 70% vol/vol, provides a safe storage medium for formaldehyde-fixed tumor tissue, facilitating sample transport during multicenter clinical trials.

Bone Marrow Lesions Are Associated With Pain, But Not With Inflammatory Biomarkers In End-Stage Knee Osteoarthritis Patients

Introduction Ultrasound guidance for central line placement in the subclavian vein (SCV) is more efficient and safer than landmark-based technique. The supraclavicular (SC) approach is an alternative to the infraclavicular (IC) approach, but the research is sparse. The objective was to determine which approach provides the best view. Methods This was a prospective anatomical survey of voluntary normovolemic patients. Four experienced emergency physicians and 1 resident scanned the right and left SCVs from SC and IC approaches. They assigned a score for the views obtained on a 5-point Likert scale. Results Ninety-eight patients were enrolled. Mean Likert scores for the 4 views were: right SC, 4.06 (95% confidence interval [CI], 0.22); right IC, 3.07 (95% CI, 0.25); left SC, 3.82 (95% CI, 0.23); left IC, 3.12 (95% CI, 0.25). When combining data from right and left, the mean score for the SC view was significantly higher than the mean score for the IC view: 3.94 (95% CI, 0.16) vs 3.10 (95% CI, 0.18). The following ratings were obtained: right SC view was good or excellent in 71.5%; left SC view was good or excellent in 66.3%; right IC view was good or excellent in 37.8%; and left IC view was good or excellent in 38.8%. Conclusion The SC approach allows for a better view of the SCV on ultrasound than the IC approach. Future research should determine if this translates to a greater success rate when placing central lines in the SCV.

Temporary henna tattooing has been very popular during recent years. Henna (Lawsonia inermis) is a plant from the Lythraceae family. For henna tattooing, henna dye is used. It is a dark green powder, made from the leaves of the plant, used for hair dyeing and body tattooing. Very often, para-phenylenediamine (PPD) is added to henna dye to make color blacker and to speed up dyeing. PPD may be a very potent contact sensitizer. We report a 9-year-old boy with allergic contact dermatitis due to temporary henna tattooing. Patch testing showed a positive reaction to PPD. After the treatment with topical corticosteroid and oral antihistamines, the lesion cleared with discrete residual hypopigmentation.

Protein binding can impair the potency of human immunodeficiency virus (HIV) protease inhibitors. Therefore, the activity of a novel compound, CGP 61755, was studied in the absence or presence of alpha1-acid glycoprotein (alpha1AGP). In MT-2 cells, the activity loss was 4-fold (EC90 without alpha1AGP, 29 nM vs. 122 nM with alpha1AGP). In primary lymphocytes, the loss was 8-fold (EC90, 45 nM vs. 364 nM). In identical experiments, the activity loss in MT-2 cells and lymphocytes was 2- and 3-fold, respectively, for indinavir, 11- and 10-fold for saquinavir, and 11- and 48-fold for ritonavir. For SC-52151, a 17-fold loss was seen in MT-2 cells, whereas no EC90 with alpha1AGP was reached in lymphocytes. This study demonstrates that the impact of alpha1AGP on in vitro activity varies greatly among different HIV protease inhibitors. The magnitude of such differences is greater in human lymphocytes than in a standard cell line.

Familija Gesneriaceae obuhvata biljne vrste pretežno rasprostranjene u tropskim u subtropskim oblastima Starog i Novog sveta. Samo mali broj vrsta naseljava umerene oblasti, a među njima je i jedinih 5 vrsta ove familije u Evropi: Ramonda myconi, endemit Pirinejskog poluostrva, kao i R. nathaliae, R. serbica, Haberlea rhodopensis i Jankaea heldreichii, četiri endemične vrste Balkanskog poluostrva. Svih pet vrsta su relikti Tercijera, vremena kada je klima u Evropi bila toplija i vlažnija. Za vreme Ledenog doba, one su našle skrovište u klisurama i kanjonima gde ih najčešće nalazimo i danas. Ovi „živi fosili“ danas nepovoljne uticaje spoljašnje sredine u velikoj meri preživljavaju zahvaljujući poikilohidričnosti, pa se još nazivaju i „biljke koje vaskrsavaju“. Danas se dve balkanske vrste roda Ramonda odlikuju disjunktnim arealima. Ramonda nathaliae zastupljena je u Makedoniji, S Grčkoj, na obroncima planine Šare na Kosovu i u JI Srbiji. Najveći deo areala vrste R. serbica nalazi se u Albaniji, a prisutna je i na SZ Grčke, u Z Makedoniji, JZ i SI Crnoj Gori, JZ, JI i SI Srbiji, kao i na SZ Bugarske. Jedina zona u kojoj se areali dve vrste susreću nalazi se u JI Srbiji, gde na dva lokaliteta, Oblik i Radovanski Kamen, obrazuju simpatrijske populacije. Obe vrste prevashodno naseljavaju krečnjačku podlogu, s tim što se R. nathaliae može naći i na serpentinitu, škriljcima i granitu. Ova vrsta, takođe, bolje podnosi otvorenija staništa, a njene populacije se mogu naći i na većem rasponu nadmorskih visina, zbog čega se smatra otpornijom i tolerantijom. Ciljevi ovog rada su višestruki: da se utvrde morfološke osobine polena i semena sve tri vrste roda Ramonda, jer detalji njihove građe do sada nisu istraživani; da se procene vijabilnost njihovog polena i klijavost semena; da se utvrdi broj hromozoma, kao i veličina genoma kod tri vrste; da se proveri da li postoje hibridne jedinke u simpatrijskim populacijama; da se pomoću molekularnih markera utvrdi stepen sličnosti i filogeografske veze između vrsta R. nathaliae i R. serbica. U tu svrhu, polen i seme analizirani su pomoću svetlosnog i scanning elektronskog mikroskopa, broj hromozoma određen je standardnim kariološkim tehnikama, veličina genoma procenjena je pomoću protočne citometrije, a genetički diverzitet primenom molekularne AFLP tehnike... Family Gesneriaceae comprises plant species mostly distributed in the tropics and subtropics of both the Old and New Worlds. Only a small number of species inhabits temperate regions. Among them, there are the only 5 species of this family in Europe: Ramonda myconi, endemic of the Iberian Peninusla, as well as R. nathaliae, R. serbica, Haberlea rhodopensis i Jankaea heldreichii, four endemic species of the Balkan Peninsula. All five species are Tertiary relicts, remnants from the times when the climate was much warmer and more humid. During the Ice Age, they have found shelter in canyons and gorges where can be often found today as well. These „living fossils“ are poikilohydric, „resurrection plants“ what helps them survive the inhospitable environmental conditions. Balkan species of the genus Ramonda are today characterized by disjunct distribution. Ramonda nathaliae is restricted to Macedonia, N Greece, slopes of Mt. Šara in Kosovo and few localities in SE Serbia. The largest part of the R. serbica range is situated in Albania, but is also present in NW Greece, W Macedonia, SW and NE Montenegro, SW, SE and NE Serbia and NE Bulgaria. The ranges of two species cooccur only in two localities in SE Serbia, Oblik and Radovanski Kamen, establishing sympatric populations. Both species prefer limestone rocks, but R. nathaliae can also be found on serpentine, schist and granite. This species is often found in more open habitats and in higher altitudes why it is considered as more resistant and tolerant than R. serbica. The aims of this study are: to investigate morphology of both pollen and seeds of three Ramonda species; to estimate pollen viability and germination capacity of their seeds; to determine chromosome numbers and genome size of three species; to explore if there are hybrids in sympatric populations; to look into genetic diversity and phylogeography of R. nathaliae and R. serbica. Pollen grains and seeds were examined by light and scanning electron microscopy, chromosome number by standard karyological techniques, genome size was estimated by flow cytometry and genetic diversity by molecular AFLP method...

Cephalosporins in aqueous solutions generate degradation products that inhibit in vitro HIV-1 replication in cell lines, as well as in primary cells (lymphocytes and macrophages). This effect is observed at concentrations that do not interfere with the normal functions of these cells. Upon chromatographic fractionation of an aqueous solution of hydrolysed ceftazidime, a high molecular weight fraction (MW 8000) with antiviral activity was isolated. The exact chemical nature of the active component responsible for the anti-HIV activity in vitro appears to be complex and is currently unknown. Inhibition of HIV-1 reverse transcriptase and RNase H activity was observed, however, higher concentrations than those needed to inhibit HIV replication were required. The inhibitory action of the hydrolysed ceftazidime was manifested during the early phase of the HIV-1 life-cycle. Despite a lack of a direct effect of the CD4/gp120 interaction, HIV-1 mediated cell fusion was inhibited by the hydrolysed ceftazidime, suggesting that the active principle acts in a very early stage of the viral life-cycle.

Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

In vitro exposure of human blood monocyte-derived macrophages to T-cell tropic human immunodeficiency virus (HIV) isolates fails to establish a productive viral infection. Several studies have shown that such preferential HIV-1 replication in T cells or in mononuclear phagocytes (HIV tropism) may be determined by distinct viral characteristics. In the present study it was demonstrated that transforming growth factor-beta (TGF-beta), a factor known to be produced by platelets, macrophages, and other cells present at a wound site, can act as a mediator in overcoming the lymphocytotropic restriction of several well-characterized viral isolates of HIV-1 (i.e., LAV, Z84, pLAI, NY5). Macrophages infected with these isolates show cytopathic changes comparable to those seen upon infection with the monocytotropic isolate ADA. To achieve this effect with TGF-beta, the factor must be present after the infection period. The emerging virus retains its original cellular tropism. Based on these observations the authors propose a role for TGF-beta in the establishment and progression of HIV infection and disease.

TGF-β at physiological concentrations, when added to monocyte-derived macrophages following HIV1 infection, has an enhancing effect upon the rate of virus production. This effect is observed with the monocytotropic isolate ADA, as well as with HIV1 IIIB, which poorly replicates in macrophages.

Cultured monocyte-derived macrophages were productively infected with human immunodeficiency virus in vitro. Treatment of these cells shortly after infection and several times thereafter with the free form of MTP-PE had an inhibitory effect on virus production. When the liposomal formulation of MTP-PE was used, higher levels of protection were achieved. The drug was not only effective when added to cells immediately after infection, but it also reduced virus production by cells with an established infection. When the liposomal formulation of MTP-PE was used only one treatment was required to achieve maximal effects. During these studies it was noted that the placebo liposomes had some effect in reducing the reverse transcriptase levels found in the supernatants of infected cells. This reduction could not be explained by direct cytotoxic effect. Both free and liposomal MTP-PE lipid significantly prevented formation of giant cells during the course of infection as well as reduced the cell associated viral antigen.