Materialno-prawne i procesowe aspekty umorzenia utraconego weksla

The legal course of litigation presented in this article constitutes an exception from the strict rule, due to which the vindication of bill of exchange (promissory note) rights is immanently connected to the possession of the document. In principle, the vindication of a claim expressed in a bill of exchange, demands return of the document to the debtor. Consequently, the loss or the destruction of this specifi c security should render vindication impossible, and in result, lead to extinction of rights. This, in turn, could act to creditor’s detriment. It is, however, possible to avoid this legal consequence. The civil code, as well as the law on bills of exchange and promissory notes, provides the possibility of the amortization of a bill of exchange (promissory note). The judgment in this matter deprives the bill of exchange of validity on one side, and constitutes its surrogate on the other, which enables the vindication of rights originally embodied by the bill. Ratio legis of the above-mentioned exception is to prevent unjustifi ed enrichment of the debtor at the creditor’s expense

Acute periodontal lesions

This is a review and update on acute conditions affecting the gingival tissues, including abscesses in the periodontium, necrotizing periodontal diseases, and other acute conditions that cause gingival lesions with acute presentation, such as infectious process not associated with oral bacterial biofilms, muco-cutanenous disorders, and traumatic and allergic lesions. A periodontal abscess is clinically important since it is a relatively frequent dental emergency, it can compromise the periodontal prognosis of the affected tooth, and because bacteria within the abscess have been identified, mainly by the type of etiology, and there are clear diffrences between those affecting a previously existing periodontal pocket ahd those affecting healthy sites. Therapy for this acute condition consists of drainage and tissue debridement, with individual evaluation of the need for systemic antimicrobial therapy. the definitive treatment of the pre-existing condition should be accomplished after the acute phase is controlled. Necrotizing periodontal disease (NPD) present three typical clinical features : papilla necrosis, gingival bleeding, and pain. Although the prevalence of these diseases is not high, their importance is clear, since they represent the most severe conditions associated with dental biofilm, with very rapid tissue destruction. In adittion to bacteria, the etiology of NPD includes numerous factors that alter the host response and predispose to these diseases, including HIV infection, malnutrition, stress, and tobacco smoking. The treatment consists of superficial debridement, careful mechanical oral hygiene, rinsing with chlorhexidine, and daily re-evaluation. Systemic antimicrobials may be used adjunctively in severe cases or in non-responding conditions and the best option is metronidazole.Once the acute disease is under control, definitive treatment should be provided, including the adequate therapy for the pre-existing gingivitis or periodontitis. Among other acute conditions affecting the periodontal tissues, but not caused by the microorganisms present in oral biofilms , are infectious diseases, muco-cutaneous diseases and traumatic or allergic lesions. In most cases, the gingival envolvement is not severe, though they are common and may prompt a dental emergency visit. These conditions may the direct result of a trauma or the consequence of the breaking of vesicles and bullae. A proper differential diagnosis is important for an adequate management of the case

Wismodegib w leczeniu zaawansowanego raka podstawnokomórkowego skóry — polskie doświadczenia kliniczne w ramach programu lekowego

Wstęp. Wismodegib to małocząsteczkowy inhibitor szlaku sygnałowego Hedgehog zarejestrowany do leczenia pacjentów, u których stwierdzono raka podstawnokomórkowego w fazie choroby przerzutowej lub miejscowo zaawansowanego raka podstawnokomórkowego niespełniającego kryteriów leczenia chirurgicznego lub radiote- rapeutycznego. Od 1 stycznia 2017 roku dostępne jest na terenie Polski leczenie w ramach programu lekowego refundowanego przez NFZ.  Celem pracy była analiza grupy chorych zakwalifikowanych do terapii wismodegibem, uwzględniająca ocenę częstości występowania działań niepożądanych wraz z określeniem ich stopnia nasilenia według CTCAE oraz wyniki leczenia po 6 i 12 miesiącach zgodnie z kryteriami RECIST 1.1. Materiał i metody. Dane dotyczące chorych pochodziły z trzech ośrodków, które w sumie prowadziły 42/78 (53,8%) pacjentów leczonych w Polsce od początku trwania programu lekowego. Czas leczenia chorych był bardzo zróżnicowany i zawierał się pomiędzy 3 tygodniami a 68 miesiącami. Mediana czasu leczenia wyniosła 8,25 miesiąca (0,75–68), mediana czasu obserwacji pacjentów leczonych krócej lub dłużej niż 12 miesięcy — wyniosła odpowiednio 8 miesięcy (6–11) i 14 miesięcy (12–68).  Wyniki. Podsumowanie danych po 6 i 12 miesiącach leczenia było możliwe odpowiednio u 29/42 i 17/42 chorych. Całkowitą odpowiedź uzyskano u 3/29 (10,3%) oraz u 3/16 (17,6%) pacjentów po odpowiednio 6 i 12 miesiącach leczenia, częściową odpowiedź odnotowano odpowiednio u 13/29 (44,8%) i 5/16 (29,4%) pacjentów, stabilizację choroby uzyskano odpowiednio u 13/29 (44,8%) i 8/16 (50,0%). Progresję choroby stwierdzono u 7 z 42 chorych (16,6%) w okresie 3–28 miesięcy od rozpoczęcia leczenia. Odnotowano 1 przypadek zgonu z powodu progresji choroby u pacjenta z obecnymi przerzutami do mózgu w momencie kwalifikacji do udziału w programie. Działania niepożądane wystąpiły u 31/42 (73,8%), a liczne działania niepożądane u tego samego pacjenta wystąpiły u 22/42 (52,3%) chorych. Nie odnotowano żadnego przypadku poważnych działań niepożądanych

Vismodegib in the treatment of basal cell carcinoma — Polish clinical experience in the frame of therapeutic program

Introduction. Vismodegib is a small-molecule inhibitor of the sonic hedgehog pathway, registered for the treat- ment of patients with metastatic or locally advanced basal cell carcinoma, who were disqualified from surgical excision or radiotherapy. The full treatment refund from the National Health Fund has been available in Poland since 1st January 2018. The aim of the study was to analyse the frequency of occurrence of adverse events based on CTCAE and the treatment results based on the RECIST 1.1 criteria, in a group of patients treated for six or 12 months with vismodegib.  Material and methods. The patient database was gathered from three sites and consisted of 42 patients, who represented 53.8% of the patients treated with vismodegib in Poland. The duration of the treatment ranged between three weeks and 68 months. The median of the treatment period was 8.25 months (0.75–68); the median of the observation of patients treated for less than 12 months was eight months (6–11), and for those treated for more than 12 months it was 14 months (12–68).  Results. The summary of the treatment results after six and 12 months was performed on 29/42 and 17/42 patients accordingly. Complete response was achieved in 3/29 (10.3%) and 3/16 (17.6%) patients after six and 12 months of treatment, respectively, partial response in 13/29 (44.8%) and 5/16 (29.4%) patients, respectively, and stable disease in 13/29 (44.8%) and 8/16 (50.0%) patients, respectively. Progression of the disease was experienced by 7/42 (16.6%) patients within the period of 3–28 months of treatment. One patient with brain metastases died due to the progression of the disease. Adverse events were reported in 31/42 (73.8%) patients, more than one adverse event in a single patient was reported in 22/42 (52.3%) patients. No serious adverse events were observed.

Charged and Hydrophobic Surfaces on the A Chain of Shiga-Like Toxin 1 Recognize the C-Terminal Domain of Ribosomal Stalk Proteins

Shiga-like toxins are ribosome-inactivating proteins (RIP) produced by pathogenic E. coli strains that are responsible for hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A1 chain of Shiga-like toxin 1 (SLT-1), a representative RIP, first docks onto a conserved peptide SD[D/E]DMGFGLFD located at the C-terminus of all three eukaryotic ribosomal stalk proteins and halts protein synthesis through the depurination of an adenine base in the sarcin-ricin loop of 28S rRNA. Here, we report that the A1 chain of SLT-1 rapidly binds to and dissociates from the C-terminal peptide with a monomeric dissociation constant of 13 µM. An alanine scan performed on the conserved peptide revealed that the SLT-1 A1 chain interacts with the anionic tripeptide DDD and the hydrophobic tetrapeptide motif FGLF within its sequence. Based on these 2 peptide motifs, SLT-1 A1 variants were generated that displayed decreased affinities for the stalk protein C-terminus and also correlated with reduced ribosome-inactivating activities in relation to the wild-type A1 chain. The toxin-peptide interaction and subsequent toxicity were shown to be mediated by cationic and hydrophobic docking surfaces on the SLT-1 catalytic domain. These docking surfaces are located on the opposite face of the catalytic cleft and suggest that the docking of the A1 chain to SDDDMGFGLFD may reorient its catalytic domain to face its RNA substrate. More importantly, both the delineated A1 chain ribosomal docking surfaces and the ribosomal peptide itself represent a target and a scaffold, respectively, for the design of generic inhibitors to block the action of RIPs

RNAstructure: software for RNA secondary structure prediction and analysis

<p>Abstract</p> <p>Background</p> <p>To understand an RNA sequence's mechanism of action, the structure must be known. Furthermore, target RNA structure is an important consideration in the design of small interfering RNAs and antisense DNA oligonucleotides. RNA secondary structure prediction, using thermodynamics, can be used to develop hypotheses about the structure of an RNA sequence.</p> <p>Results</p> <p>RNAstructure is a software package for RNA secondary structure prediction and analysis. It uses thermodynamics and utilizes the most recent set of nearest neighbor parameters from the Turner group. It includes methods for secondary structure prediction (using several algorithms), prediction of base pair probabilities, bimolecular structure prediction, and prediction of a structure common to two sequences. This contribution describes new extensions to the package, including a library of C++ classes for incorporation into other programs, a user-friendly graphical user interface written in JAVA, and new Unix-style text interfaces. The original graphical user interface for Microsoft Windows is still maintained.</p> <p>Conclusion</p> <p>The extensions to RNAstructure serve to make RNA secondary structure prediction user-friendly. The package is available for download from the Mathews lab homepage at <url>http://rna.urmc.rochester.edu/RNAstructure.html</url>.</p

The TFE-induced transient native-like structure of the intrinsically disordered [Formula: see text] domain of Escherichia coli RNA polymerase.

The transient folding of domain 4 of an E. coli RNA polymerase [Formula: see text] subunit ([Formula: see text]) induced by an increasing concentration of 2,2,2-trifluoroethanol (TFE) in an aqueous solution was monitored by means of CD and heteronuclear NMR spectroscopy. NMR data, collected at a 30 % TFE, allowed the estimation of the population of a locally folded [Formula: see text] structure (CSI descriptors) and of local backbone dynamics ((15)N relaxation). The spontaneous organization of the helical regions of the initially unfolded protein into a TFE-induced 3D structure was revealed from structural constraints deduced from (15)N- to (13)C-edited NOESY spectra. In accordance with all the applied criteria, three highly populated α-helical regions, separated by much more flexible fragments, form a transient HLHTH motif resembling those found in PDB structures resolved for homologous proteins. All the data taken together demonstrate that TFE induces a transient native-like structure in the intrinsically disordered protein