Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Caspofungin Disk Diffusion Breakpoints and Quality Control▿

Interpretive disk diffusion breakpoints for caspofungin are proposed by evaluating 762 isolates of Candida spp., representing 10 different species obtained as part of the caspofungin clinical trials. Standardized broth microdilution reference tests were compared to the zone diameters observed with 5-μg caspofungin disks produced by two different disk manufacturers. Disk diffusion breakpoints of ≥11 mm for susceptible are proposed. Compared to results from MIC testing, these zone diameters produced error rates that were ≤0.3% for all categories. In addition, an eight-laboratory disk diffusion quality control (QC) study was performed, and QC ranges are proposed for the four QC strains recommended by the CLSI

The Financial Assistance in LBO deals - Polish perspective

Wykup lewarowany (LBO) jest instytucją gospodarczo-prawną wciąż mało opisaną w polskiej literaturze biorąc pod uwagę jej rosnącą popularność w gospodarce. Wykup lewarowany to transakcja nabycia spółki finansowana długiem z wykorzystaniem aktywów posiadanych przez przejmowaną spółkę. Wykup menadżerski jest stosowany w krajach zachodnich od wielu lat, zwłaszcza w krajach anglosaskich. Jest to transakcja złożona i przez lata traktowana jako szkodliwa dla rynków głównie z powodu możliwości naruszania praw akcjonariuszy mniejszościowych oraz nieusprawiedliwionego narażania przejmowanej spółki na ryzyko niewypłacalności. W związku z tym w wielu reżimach prawnych powstały regulacje bądź zakazujące takich transakcji, bądź znacząco je ograniczające. Praktyka gospodarcza pokazała jednak, że powyższe regulacje nie były skuteczne, a ponadto zaczęto dostrzegać pozytywne aspekty wykupów lewarowanych. W związku z tym instytucja Financial Assistance kształtująca finansowanie nabywania akcji własnych spółki ewoluowała i doczekała się regulacji na poziomie prawa wspólnotowego. Niniejsza praca poświęcona jest analizie implementacji regulacji Financial Assistance do prawa polskiego. Poruszono zagadnienia związane z historią regulacji w prawie polskim, przesłankach stosowania, zakresie regulacji, skutkach naruszenia, a także podjęto próbę przeglądu interpretacji kluczowych pojęć regulacji instytucji Financial Assistance w polskiej doktrynie.W rozdziale pierwszym przedstawiono ogólną charakterystykę transakcji LBO, a więc rys historyczny, przebieg modelowej transakcji oraz zdefiniowaną specyfikę transakcji LBO w kontekście fuzji i przejęć (M&A). Rozdział drugi poświęcony jest powstaniu i ewolucji instytucji Financial Assistance w Europie, zarówno w prawie polskim jak i w prawie wspólnotowym oraz brytyjskim, gdzie regulacja Financial Assistance została wprowadzona najwcześniej. Rozdział trzeci określa przesłanki stosowania art 345 KSH będącego polską implementacją Financial Assistance. Rozdział czwarty poświęcony został określeniu zakresu regulacji, jej kluczowych definicji i rozbieżnościom ich rozumienia w doktrynie. Piąty rozdział przedstawia typowy dla transakcji części wykupów lewarowanych konflikt interesów pomiędzy zarządem, a akcjonariuszami wynikający z asymetrii informacji natomiast w rozdziale szóstym omówiono skutki naruszenia reżimu art 345 KSH oraz zakres odpowiedzialności członów poszczególnych organów spółki kapitałowej. Ponadto podsumowanie pracy zawiera uwagi de lege ferenda.Leveraged buyout (LBO) is an economic and legal institution that is still not enough described in Polish law literature. Leveraged buyout is a company debt purchase transaction financed with debt using the assets held by the acquired company. Management buy-outs have been used in Western countries for many years, especially in Anglo-Saxon countries. It is a complex transaction and for years treated as detrimental to markets mainly due to the possibility of infringing the rights of minority shareholders and unjustified exposure of the acquired company to the risk of insolvency. Therefore, in many legal regimes have been created various regulations that prohibit such transactions or significantly restrict them. Economic practice has shown, however, that the above regulations were not effective and the positive aspects of leveraged buyouts has began to be recognized.This paper is devoted to the analysis of the implementation of Financial Assistance regulations into Polish law. Issues related to the history of regulation in Polish law, conditions of application, scope of regulations, consequences of violation were discussed, and an attempt was made to review the interpretation of key concepts of Financial Assistance institutions in Polish doctrine. The first chapter presents the general characteristics of LBO transactions, ie the historical outline, the course of the model transaction and the defined specifics of LBO transactions in the context of mergers and acquisitions (M & A). The second chapter is devoted to the creation and evolution of Financial Assistance institutions in Europe, both in Polish and British law, where the Financial Assistance regulation was introduced at the earliest.The third chapter sets out the conditions for the application of Article 345 of the KSH (The Code of Commercial Companies), which is the Polish implementation of Financial Assistance.The fourth chapter is devoted to defining the scope of regulation, its key definitions and differences in their understanding in doctrine. The fifth chapter presents the typical for the transaction part of leveraged buyouts the conflict of interest between the management and shareholders resulting from the asymmetry of information, while the sixth chapter discusses the effects of violation of the Article 345 KSH regime and the scope of responsibiliy of the management and supervision boards in the company.The summary of the work includes de lege ferenda comments

In Vitro Antimicrobial Activity of a New Cephalosporin, Ceftaroline, and Determination of Quality Control Ranges for MIC Testing▿

The spectrum of activity of ceftaroline was evaluated against 1,247 bacterial isolates representing 44 different species or phenotypic groups. For the majority of species, the activity of ceftaroline was comparable or superior to that of ceftriaxone. MIC and/or disk diffusion quality control ranges of ceftaroline were determined for five standard ATCC reference strains

Broth Microdilution Susceptibility Testing of Brucella Species: Quality Control Limits for Ten Antimicrobial Agents against Three Standard Quality Control Strains

Brucella broth without supplementation is the recommended medium for broth microdilution susceptibility tests of Brucella abortus, B. melitensis, and B. suis. Based on an eight-laboratory collaborative study using a pH-adjusted modification of this medium, we propose MIC quality control ranges for three control strains against 10 antimicrobials that are potentially efficacious for treating infections caused by these agents of bioterrorism

In Vitro Activity of Doripenem against Pseudomonas aeruginosa and Burkholderia cepacia Isolates from both Cystic Fibrosis and Non-Cystic Fibrosis Patients

The in vitro activities of doripenem, imipenem, levofloxacin, piperacillin, ceftazidime, aztreonam, tobramycin, and cefepime were determined for 160 isolates of Pseudomonas aeruginosa (82 from cystic fibrosis [CF] patients) and 34 isolates of Burkholderia cepacia. Doripenem MIC(90)s were lower than those of all other comparative agents against all isolates combined and against all P. aeruginosa isolates. Doripenem was as active as levofloxacin and 2- to 32-fold more active than the other comparative agents against B. cepacia