ABSTRACT IN SLOVENE: Ceprav so v strokovni literaturi o nastanku Ljubljane navedena ze mnoga zgodovinsko dokazana dejstva, se vedno obstajajo stevilna pomembna vprasanja o prvotnem nastanku ...ljubljanske naselbine na sedanji lokacij, ki niso popolnoma raziskana. Med temi vprasanji so prav gotovo tudi vzroki, ki niso dovolj natancno obravnavani ne samo v zgodovinski, ampak tudi v obstojeci literaturi o urbanizmu in arhitekturi Ljubljane, predvsem o tem, kako so vojne in vojne dejavnosti vplivale na izbiro lokacije in razvoj tega mesta. Odgovore smo iskali s pomocjo poglobljene in sistematicne raziskave strateskih ali vojnih vplivov na obmocju Evrope, Sredozemlja in Bliznjega vzhoda. Razvoj Ljubljane smo podrobneje preucili v casovnem okviru od prazgodovine do trojnega naselbinskega jedra State Ljubljane (Stari trg, Novi trg in Mestni trg) v srednjem veku. Spoznanja, ki smo jih pridobili s to raziskavo, so nas priblizala odgovoru na zastavljeno vprasanje, ali je prvo naselbinsko jedro Ljubljane (Stari trg) nastalo le kot nakljucna naselbina ali pa je bila ta lokacija izbrana zaradi vpliva vojn na tem obmocju. // ABSTRACT IN ENGLISH: Even though there are many historically proven facts about the formation of Ljubljana in literature, a great number of important issues about the origin of the settlement at present-day Ljubljana still remain to be studied in detail. Among the issues that have not been covered in sufficient detail in historical literature as well as in the literature on the urban planning and architecture of Ljubljana are the influences of wars and warfare on location selection and the development of the city. To explore this topic, a thorough and systematic study of strategic and military influences in Europe, the Mediterranean and the Middle East has been carried out. The development of Ljubljana was carefully studied from prehistory to the Middle Ages, when Ljubljana had a triple settlement core: Old Square (Sln. Stari trg), New Square (Sln. Novi trg) and Town Square (Sln. Mestni trg). The findings help indicate whether Ljubljana's first settlement core (Old Square) was formed by chance or whether this location was selected due to the influence of wars in the area.
Čeprav so v strokovni literaturi o nastanku Ljubljane navedena že mnoga zgodovinsko dokazana dejstva, še vedno obstajajo številna pomembna vprašanja o prvotnem nastanku ljubljanske naselbine na ...sedanji lokacij, ki niso popolnoma raziskana. Med temi vprašanji so prav gotovo tudi vzroki, ki niso dovolj natančno obravnavani ne samo v zgodovinski, ampak tudi v obstoječi literaturi o urbanizmu in arhitekturi Ljubljane, predvsem o tem, kako so vojne in vojne dejavnosti vplivale na izbiro lokacije in razvoj tega mesta. Odgovore smo iskali s pomočjo poglobljene in sistematične raziskave strateških ali vojnih vplivov na območju Evrope, Sredozemlja in Bližnjega vzhoda. Razvoj Ljubljane smo podrobneje preučili v časovnem okviru od prazgodovine do trojnega naselbinskega jedra Stare Ljubljane (Stari trg, Novi trg in Mestni trg) v srednjem veku. Spoznanja, ki smo jih pridobili s to raziskavo, so nas približala odgovoru na zastavljeno vprašanje, ali je prvo naselbinsko jedro Ljubljane (Stari trg) nastalo le kot naključna naselbina ali pa je bila ta lokacija izbrana zaradi vpliva vojn na tem območju.
Even though there are many historically proven facts about the formation of Ljubljana in literature, a great number of important issues about the origin of the settlement at present-day Ljubljana ...still remain to be studied in detail. Among the issues that have not been covered in sufficient detail in historical literature as well as in the literature on the urban planning and architecture of Ljubljana are the influences of wars and warfare on location selection and the development of the city. To explore this topic, a thorough and systematic study of strategic and military influences in Europe, the Mediterranean and the Middle East has been carried out. The development of Ljubljana was carefully studied from prehistory to the Middle Ages, when Ljubljana had a triple settlement core: Old Square (Sln. Stari trg), New Square (Sln. Novi trg) and Town Square (Sln. Mestni trg). The findings help indicate whether Ljubljana’s first settlement core (Old Square) was formed by chance or whether this location was selected due to the influence of wars in the area.
Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly ...investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients' characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum β2-microglobulin, and
somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in
-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.
Introduction. Primary central nervous system lymphoma is a rare entity mostly
presenting with non-GCB diffuse large B-cell lymphoma, being confined to the
brain, spinal cord, meninges, and eyes. ...Diagnosis. The diagnosis is
frequently established by stereotactic or open the brain biopsy, but in some
cases with isolated leptomeningeal involvement, the only way is to identify
atypical/monoclonal lymphocytes in cerebrospinal fluid. By workup, we aim to
define the extent of disease in the central nervous system and to exclude
systemic involvement. Treatment. Treatment is tailored according to the
patient?s age, fitness, vital organ function, comorbidities, and available
therapy. The backbone of induction treatment is high-dose methotrexate,
usually within polychemotherapy. Consolidation phase is a matter of debate
between two approaches: 1. high dose chemotherapy with autologous stem cell
transplantation, which appears to be the preferable option for young fit
patients, and 2. whole brain radiotherapy, preserved for
transplant-ineligible ones. Whole brain radiotherapy has been raising
concerns because of frequent cognitive impairment, which has been
significantly diminished by reducing the irradiation dose. Despite a
comprehensive treatment approach, many patients relapse, and since the
prognosis of relapsed/refractory disease is devastating, there is a sense of
urgency for novel treatment strategies. Several targeted agents and
immunomodulatory drugs have been investigated in the settings of both
relapsed/refractory and initial therapy, but with limited success. Ibrutinib
monotherapy can induce durable remissions in the first line, but in
relapse/refractory settings, the results are controversial. Conclusion.
Adequate patient selection and new prospective trials should improve
survival and preserve the patient?s neurological status.
Diffuse large B-cell lymphoma, not otherwise specified, is the most common
type of non-Hodgkin lymphoma worldwide, accounting for 30-40% of all
lymphomas. It represents a collection of ...morphologically, genetically and
clinically different diseases. Therefore, it can be subdivided into
morphological variants, phenotypic subtypes, and molecular or genetic
categories. More recently, diffuse large B-cell lymphoma has witnessed
advances in molecular profiling and treatment of patients with refractory
and relapsed disease. The optimal management requires integrated
morphological and immunophenotypic analysis of cell and tissue, along with
chromosome and molecular analyses. Double-expressor lymphoma, defined as
overexpression of MYC and BCL2 proteins not related to underlying
chromosomal rearrangements, accounts for 20% to 30% of Diffuse large B-cell
lymphoma cases. In the latest, 5th edition of the World Health Organization
Classification of Hematolymphoid Tumors-lymphoid neoplasms, double-expressor
lymphoma is not defined as an independent entity, but it has been proven to
be a marker for poor outcome in diffuse large B-cell lymphoma. However, the
degree of adverse prognosis is lesser than in double-hit lymphomas. Although
double-expressor lymphoma feature is confirmed as adverse prognostic marker
for diffuse large B-cell lymphoma patients, currently no sufficient data is
available to support treatment intensification over standard rituximab,
cyclophosphamide, doxorubicin, vincristine and prednisone regimen.
Well-designed randomized clinical trials are mandatory in order to properly
respond to this substantial clinical dispute.
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