Targeting CD20 in multiple sclerosis — review of current treatment strategies

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that mostly manifests as irreversible disability. The aetiopathogenesis of MS is still unclear, although it was initially thought to be primarily mediated by T-cells. Research into the immune concepts of MS pathophysiology in recent years has led to a shift in the understanding of its origin i.e. from a T-cell-mediated to a B-cell-mediated molecular background. Thus, the use of B-cell-selective therapies, such as anti- -CD20 antibody therapy, as expanded therapeutic options for MS is now strongly supported. This review provides an up-to-date discussion on the use of anti-CD20 targeted therapy in MS treatment. We present a rationale for its use and summarise the results of the main clinical trials showing the efficacy and safety of rituximab, ocrelizumab, ofatumumab, and ublituximab. Future directions that show selectivity to a broader population of lymphocytes, such as the use of anti-CD19 targeted antibodies, as well as the concept of extended interval dosing (EID) of anti-CD20 drugs, are also discussed in this revie

Looking for novel, brain-derived, peripheral biomarkers of neurological disorders

The role of blood brain barrier (BBB) is to preserve a precisely regulated environment for proper neuronal signaling. In many of the central nervous system (CNS) pathologies, the function of BBB is altered. Thus, there is a necessity to evaluate a fast, noninvasive and reliable method for monitoring of BBB condition. It seems that revealing the peripheral diagnostic biomarker whose release pattern (concentration, dynamics) will be correlated with clinical symptoms of neurological disorders offers significant hope. It could help with faster diagnosis and efficient treatment monitoring. In this review we summarize the recent data concerning exploration of potential new serum biomarkers appearing in the peripheral circulation following BBB disintegration, with an emphasis on epilepsy, traumatic brain injury (TBI) and stroke. We consider the application of well-known proteins (S100β and GFAP) as serum indicators in the light of recently obtained results. Furthermore, the utility of molecules like MMP-9, UCHL-1, neurofilaments, BDNF, and miRNA, which are newly recognized as a potential serum biomarkers, will also be discussed

Efficacy of chemoimmunotherapy in a lung adenocarcinoma patient with mutations in the KRAS and STK11

Immunotherapy is a groundbreaking treatment method when it comes to cancer, and this includes non-small-cell lung cancer (NSCLC). In NSCLC patients, immunotherapy is used in a form of immune checkpoint inhibitors (ICIs), and depending on the proportion of tumor cells with programmed death ligand 1 (PD-L1) expression on them, it can be administered either in monotherapy (≥ 50%) or in combination with chemotherapy (< 50%). In this article, we would like to present a case of a female patient with Kirsten Rat Sarcoma Virus (KRAS)-mutated lung adenocarcinoma who was responding to chemoimmunotherapy for a long time despite the presence of co-mutation in the Serine/Threonine Kinase 11 (STK11) gene, known to worsen immunotherapy outcomes. In this patient, another mutation was found – in the nibrin (NBN) gene, which is of uncertain relevance, but it presumably could be connected to a better outcome as it encodes proteins involved in DNA repair. Deficiency in DNA repair may be marked by homologous recombination deficiency (HRD), and there already exists some evidence of better immunotherapy efficacy in patients with HRD. Considering the above, further investigation and thorough genetic diagnostics in NSCLC patients are required to fully understand the background of immunotherapy response

Tracing ephemeral human occupation through archaeological, palaeoenvironmental and molecular proxies at Łabajowa Cave

Confirming ephemeral human occupation is a crucial issue in cave archaeology. The project ‘Tracing human presence in caves of Polish Jura’ focuses on the application of molecular methods to decode the history of past human activities in cave sediments in the Kraków-Częstochowa Upland. The results will be compared with archaeological and palaeoecological proxies

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates

A one-pot lithiation–phosphonylation procedure was elaborated as a method to prepare heteroaromatic phosphonic acids. It relied on the direct lithiation of heteroaromatics followed by phosphonylation with diethyl chlorophosphite and then oxidation with hydrogen peroxide. This protocol provided the desired phosphonates with satisfactory yields. This procedure also had some limitations in its dependence on the accessibility and stability of the lithiated heterocyclic compounds. The same procedure could be applied to phosphonylation of aromatic compounds, which do not undergo direct lithiation and thus require the use of their bromides as substrates. The obtained compounds showed weak antiproliferative activity when tested on three cancer cell lines

Stroke masks – a case report

Introduction. Stroke is a common vascular disease encountered in the work of a practitioner. Despite this, his differentiation is difficult. This is due to a variety of diseases that can be a “mask” for stroke. These are neurological diseases other than vascular (brain tumors, epilepsy), head injuries and a number of metabolic disorders (fluctuations in glucose, electrolytes). Aim. This work aims to approximate the differentiation of this common disease entity. Case reports show both clinical view and diagnostic difficulties. Description of the cases. Case 1. The patient 59 years old treated for bipolar disorder, hypertension and alcohol abuse. Case 2. The patient 68 years old treated for type 2 diabetes, hypertension, ischemic heart disease, cholecystolithiasis – cholecystectomy. Conclusion. Stroke is a significant clinical and social problem both in Poland and in the world. Despite this, its diagnostics and especially differentiation is difficult. When analyzing the case of each patient with suspected sudden CNS vascular disease, all of them should be remembered. It should also be borne in mind that differential diagnosis cannot delay specific treatment for strok

Environmental and social effects of the change of heat sources on the example of a selected quarter of tenement houses in Wroclaw

The energy consumption for space heating and domestic hot water preparation are significant burdens of a polish household budget, especially in old tenement houses. Simultaneously, lowering the emission of pollutants is under the great importance and one of main goals to achieve in big cities. This policy results in the need of elimination of systems based on solid fuels. The article analyses the environmental and social consequences of the exchange of heat sources in such buildings in one of the quarters in Wroclaw. It presents how this change will affect the levels of low emission and costs of energy supply to tenement buildings

Login: biblioteka. Jak krok po kroku przygotowaliśmy i zrealizowaliśmy kurs e-learningowy dla bibliotekarzy

W latach 2010-2015, w ramach Programu Rozwoju Bibliotek, realizowaliśmy kurs e-learningowy dla bibliotekarzy pt. "Login: biblioteka". Prezentujemy podsumowanie projektu "Login: biblioteka" w postaci publikacji opisującej, krok po kroku, jak został przygotowany i przeprowadzony kurs. W publikacji można znaleźć wiele praktycznych wskazówek na temat tego, jak zrealizować szkolenie e-learningowe dla bibliotekarzy, z jakimi wyzwaniami wiąże się taki projekt i jak sobie z nimi radzić. Publikacja zawiera szczegółowy opis kursu, dane statystyczne, opinie uczestników oraz wnioski i refleksje realizatorów projektu "Login: biblioteka". Kurs "Login: biblioteka" zapewniał uczestnikom dostęp do różnorodnych materiałów edukacyjnych (m.in. prezentacji, ćwiczeń, quizów), wsparcie i konsultacje ze strony dyżurujących wirtualnie nauczycieli oraz możliwość wykonania zadań o charakterze praktycznych projektów, których cele i tematyka odpowiadały specyfice pracy bibliotekarza

The Involvement of RAGE and Its Ligands during Progression of ALS in SOD1 G93A Transgenic Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive degeneration of upper and lower motor neurons that causes paralysis and muscle atrophy. The pathogenesis of the disease is still not elucidated. Receptor for Advanced Glycation End Product (RAGE) is a major component of the innate immune system and has implications in ALS pathogenesis. Multiple studies suggest the role of RAGE and its ligands in ALS. RAGE and its ligands are overexpressed in human and murine ALS motor neurons, astrocytes, and microglia. Here, we demonstrated the expression of RAGE and its ligands during the progression of the disease in the transgenic SOD1 G93A mouse lumbar spinal cord. We observed the highest expression of HMGB1 and S100b proteins at ALS onset. Our results highlight the potential role of RAGE and its ligands in ALS pathogenesis and suggest that some of the RAGE ligands might be used as biomarkers in early ALS diagnosis and potentially be useful in targeted therapeutic interventions at the early stage of this devastating disease