Synthesis of Unsymmetrical Bis(imidoyl)dichlorides of Oxalic Acid

Unsymmetrical oxalic acid-bis(imidoyl)dichlorides were prepared from ethyl 2-chloro-2-oxoacetate in three steps

Veserecipiensek alkalmassága transzplantációra való behíváskor. A budapesti centrum tapasztalatai = Impact of the establishment of waiting list committee on recipient evaluation for kidney transplantation: experience of the Budapest Centre

2007. július 1-jén megalakult a vesetranszplantációs várólista-bizottság. A szerzők a várólista-bizottság működésének a transzplantáció előtti kivizsgálásra gyakorolt hatását kívánták felmérni. A szerzők ismeretei szerint a veseriadó során a szelekciós listán megjelenő betegek alkalmatlanságát elemző tanulmányt még nem közöltek. Módszerek: 2007. szeptember 1. és 2010. április 30. között elvégzett 354 veseátültetéshez 714 betegről kértünk telefoninformációt. Eredmények: Két 16 hónapos periódusban vizsgálva a veseriadókat, az elsőben 357 beteg közül 171 beteg (47,8%) nem volt alkalmas a vesetranszplantációra [telefoninformáció alapján 129 beteg (36,1%), behívás és klinikai vizsgálat alapján pedig 42 beteg (11,8%)]. A második időszakban 357 beteg közül 141 beteg (39,5%) volt alkalmatlan [80 beteg (22,4%) telefoninformáció és 61 beteg (17,1%)] a vizsgálatok alapján. A két vizsgálati időszakban a betegek 44%-a nem volt alkalmas a veseátültetésre; jelentős részük kardiológiai okok miatt volt alkalmatlan. A második periódusban több alkalmas beteg volt (60,5% vs. 52,1%) és kevesebb beteg volt telefoninformáció alapján alkalmatlan, mint az elsőben (22,4% vs. 36,1%). Az első időszakban a transzplantációra behívott, de alkalmatlannak bizonyult betegek száma 42 (11,7%), a másodikban pedig 61 (17,1%) volt. Következtetések: A szerzők a várólista-bizottságok munkáját hatékonynak ítélik. Orv. Hetil., 2011, 152, 190–195. | The aim of this study was to assess the impact of the establishment of waiting list committee on recipient evaluation for kidney transplantation. Studies on this issue have not been previously reported. Methods: Data of 714 patients were collected between September 1, 2007 and April 20, 2010. Of the 714 patients 354 were transplanted. Data from the first 16 months period were compared to those obtained during the second 16 months period. Results: During the first period 171 patients (47.9%) were unfit for transplantation [129 patients (36.1%) were refused after telephone information and 42 patients (11.8%) after clinical investigation]. During the second period 141 (39.5%) patients were found to be unsuitable [80 patients (22.4%) after telephone information and 61 patients (17.1)] after clinical examination. During the two periods of the study 44% of patients were unfit for transplantation. A considerable number of patients were refused because of cardiologic reasons. The percent of fit patients was 52.1% in the first period and 60.5% in the second period. In addition, the percent of unfit patients who were unsuitable for kidney transplantation after telephone information decreased from 36.1% to 22.4%, while the percent of unfit patients after clinical evaluation increased from 11.% to 17.1%. Conclusions: Authors conclude that waiting list committee made an effective work. Orv. Hetil., 2011, 152, 190–195

Adhesion, proliferation, and osteogenic differentiation of a mouse mesenchymal stem cell line (BMC9) seeded on novel melt-based chitosan/polyester 3D porous scaffolds

The aim of the present work was to study the biological behavior of a mouse mesenchymal stem cell line when seeded and cultured under osteogenic conditions onto novel processed melt-based chitosan scaffolds. Scaffolds were produced by compression molding, followed by salt leaching. Scanning electron microscopy (SEM) observations and lCT analysis showed the pore sizes ranging between 250 and 500 lm and the interconnectivity of the porous structure. The chitosan–poly(butylenes succinate) scaffolds presented high mechanical properties, similar to the ones of trabecular bone (E1%*75 MPa). Cytotoxicity assays were carried out using standard tests (accordingly to ISO/EN 10993 part 5 guidelines), namely, MTS test with a 24 h extraction period, revealing that L929 cells had similar metabolic activities to that obtained for the negative control. Cell culture studies were conducted using a mouse mesenchymal stem cell line (BMC9). Cells were seeded onto the scaffold and allowed to proliferate for 3 weeks under osteogenic conditions. SEM observations demonstrated that cells were able to proliferate and massively colonize the scaffolds structure. The cell viability assay MTS demonstrated that BMC9 cells were viable after 3 weeks of culture. The cells clearly evidenced a positive differentiation toward the osteogenic lineage, as confirmed by the high ALP activity levels. Moreover, energy dispersive spectroscopy (EDS) analysis revealed the presence of Ca and P in the elaborated extracellular matrix (ECM). These combined results indicate that the novel melt-based chitosan/polyester scaffolds support the adhesion, proliferation, and osteogenic differentiation of the mouse MSCs and shows adequate physicochemical and biological properties for being used as scaffolds in bone tissue engineering–related strategies

Mitochondrial dysfunction in liver failure requiring transplantation.

Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases

Evaluating case management for caregivers of children with spinal muscular atrophy type I and II—an exploratory, controlled, mixed-methods trial

IntroductionSpinal muscular atrophy (SMA) is a rare neuromuscular disease requiring various clinical specialists and therapists to provide care. Due to the disease's dynamic nature and the long distances between specialized centers and local providers, integrating care between disciplines can be challenging. Care that is inadequately integrated can compromise the quality of care and become a burden for patients and families. This trial aimed to improve the care of patients through a case management (CM) intervention.MethodsWe conducted an exploratory, controlled, two-arm trial with pre-, post-, and follow-up measures (process and outcome evaluation). Proof of efficacy based on statistical significance was not our primary study objective since we were investigating a rare disease. Primary outcomes were caregivers' HRQoL and caregiver-rated quality of care integration. Our secondary outcome was the children's HRQoL.ResultsQuestionnaires and semi-structured interviews yielded heterogeneous results depending on caregivers' level of experience and desire (or possibility) to delegate care tasks.DiscussionDespite differing perceptions, all participants supported the establishment of a care coordination model. We recommend CM immediately after diagnosis to provide the greatest benefit to families. We hope that our trial will support the further development of CM interventions that can be customized for specific diseases

A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions

Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains, including motricity, sleep, attention, emotion, learning and memory, and social and reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic DA levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine and amphetamines) were historically used to shape mood and cognition, but these substances typically lead to severe negative side effects (tolerance, abuse, addiction, and dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric and progressive brain disorders, including Parkinson's and Alzheimer diseases, drug addiction and dementia, resulting in devastating personal and familial concerns and high socioeconomic costs worldwide. The development of low-side-effect, new/selective medicaments with reduced abuse-liability and which ameliorate DA/DAT-related dysfunctions is therefore crucial in the fields of medicine and healthcare. Using the rat as experimental animal model, the present work describes the synthesis and pharmacological profile of (S)-MK-26, a new modafinil analogue with markedly improved potency and selectivity for DAT over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered (S)-MK-26 treatment, whereas in vivo experiments in the hole-board test showed only lesser effects on reference memory performance in aged rats. However, in effort-related FR5/chow and PROG/chow feeding choice experiments, (S)-MK-26 treatment reversed the depression-like behavior induced by the dopamine-depleting drug tetrabenazine (TBZ) and increased the selection of high-effort alternatives. Moreover, in in vivo microdialysis experiments, (S)-MK-26 significantly increased extracellular DA levels in the prefrontal cortex and in nucleus accumbens core and shell. These studies highlight (S)-MK-26 as a potent enhancer of transsynaptic DA and promoter of synaptic plasticity, with predominant beneficial effects on effort-related behaviors, thus proposing therapeutic potentials for (S)-MK-26 in the treatment of low-effort exertion and motivational dysfunctions characteristic of depression and aging-related disorders

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland