The sodium-dependent di- and tricarboxylate transporter, NaCT, is not responsible for the uptake of D-, L-2-hydroxyglutarate and 3-hydroxyglutarate into neurons

Multi-objective evolutionary algorithms (MOEAs) have become increasingly popular as multi-objective problem solving techniques. Most studies of MOEAs are empirical. Only recently, a few theoretical results have appeared. It is acknowledged that more theoretical research is needed. An important open problem is to understand the role of populations in MOEAs. We present a simple bi-objective problem which emphasizes when populations are needed. Rigorous runtime analysis point out an exponential runtime gap between a population-based algorithm (SEMO) and several single individual-based algorithms on this problem. This means that among the algorithms considered, only the populationbased MOEA is successful and all other algorithms fail

Mechanical concept of the neurosurgical robot ‘Minerva'

We describe a robot capable of performing all procedures necessary to carry out a complete stereotactic neurosurgical operation under the control and supervision of a surgeon. The operation consists of the introduction of a small probe with diameter 2-3 mm through a hole without trepanation. The robot has been built and is now being tested and evaluated. The accompanying control software as well as various medical probes are either in development or partially tested. The installation will be able to carry out a complete intervention under the surveillance of a computed tomography scanner. In this article we emphasize the design choices required to eliminate gearing backlash in a crucial degree of freedo

An annotated checklist of the jumping plant-lice (Insecta: Hemiptera: Psylloidea) from the Mercantour National Park, with seven new records for France and one new synonymy

A total of 68 psyllid species are listed from the Mercantour National Park in Southeast France, where a targeted collecting campaign was conducted between 2009 and 2012, as part of the project "ATBI+M" Mercantour. The insects were collected using Malaise traps, flight intercept traps and sweep nets to sample in the vegetation. Additional information on distribution, biology and host-plants is provided for each species. Seven species are recorded for the first time from France: Craspedolepta artemisiae (Foerster, 1848), Craspedolepta nebulosa (Zetterstedt, 1828), Cacopsylla propinqua (Schaefer, 1949), Cyamophila prohaskai (Priesner, 1927), Eryngiofaga cf. refuga (Loginova, 1966), Bactericera parastriola Conci, Ossiannilsson & Tamanini, 1988 and Trioza flixiana Burckhardt & Lauterer, 2002. Trioza (Trioza) rapisardai Conci & Tamanini, 1984 is a new subjective synonym of Trioza brachyceraea Hodkinson & White, 1979, which was previously known only from the male holotype. The abundance, distribution and introduction status of some species are discussed

Estudos de prospecção e biodiversidade de Psylloidea: Hemiptera.

Resumo

New AMP-forming acid:CoA ligases from Streptomyces lividans, some of which are posttranslationally regulated by reversible lysine acetylation

In nature, organic acids are a commonly used source of carbon and energy. Many bacteria use AMP‐forming acid:CoA ligases to convert organic acids into their corresponding acyl‐CoA derivatives, which can then enter metabolism. The soil environment contains a broad diversity of organic acids, so it is not surprising that bacteria such as Streptomyces lividans can activate many of the available organic acids. Our group has shown that the activity of many acid:CoA ligases is posttranslationally controlled by acylation of an active‐site lysine. In some cases, the modification is reversed by deacylases of different types. We identified eight new acid:CoA ligases in S. lividans TK24. Here, we report the range of organic acids that each of these enzymes can activate, and determined that two of the newly identified CoA ligases were under NAD⁺‐dependent sirtuin deacylase reversible lysine (de)acetylation control, four were not acetylated by two acetyltransferases used in this work, and two were acetylated but not deacetylated by sirtuin. This work provides insights into the broad organic‐acid metabolic capabilities of S. lividans, and sheds light into the control of the activities of CoA ligases involved in the activation of organic acids in this bacterium

Characteristics associated with inappropriate hospital use in elderly patients admitted to a general internal medicine service

Our objective was to identify patient characteristics associated with inappropriate hospital days in a cohort of elderly medical inpatients. This prospective cohort study included a total of 196 patients aged 75 years and older, who were consecutively admitted over eight months to the internal medicine service of a regional, non-academic public hospital located in a rural area of Western Switzerland. Patients with severe cognitive impairment, terminal disease, or previously living in a nursing home were excluded. Data on demographics, medical, physical, social and mental status were collected at admission. A blinded hospitalization review was performed concurrently using a modified version of the Appropriateness Evaluation Protocol (AEP). Subjects' mean age was 82.4 years; 63.3% were women. Median length of stay was 8 days. Overall, 68 patients (34.7%) had at least one inappropriate day during their stay, including 18 patients (9.2%) whose hospital admission and entire stay were considered inappropriate. Most inappropriate days were due to discharge delays (87.1%), primarily to nursing homes (59.3%). Univariate analysis showed that subjects with inappropriate days were more likely to be living alone (69.1 vs 48.4%, p=0.006), and receiving formal in-home help (48.5 vs 32.8%, p=0.031). In addition, they were more impaired in basic and instrumental activities of daily living BADLs, and IADLs, p<0.001 and p=0.015, respectively), and more frequently had a depressed mood [29.4 vs 10.9%, p=0.001 with a score ≥ 6 at the Geriatric Depression Scale (GDS), short form]. Using multivariate analysis, independent associations remained for patients living alone (OR 2.6, 95%CI 1.2-5.8, p=0.016), those with a depressed mood (OR 2.8, 95%CI 1.1-7.3, p=0.032), with BADL dependencies (OR 1.5, 95%CI 1.2-1.8, p=0.001), and IADL dependencies (OR 1.3, 95%CI 1.0-1.6, p=0.032). Cardiovascular (OR 0.2, 95%CI 0.1-0.7, p=0.008) and pulmonary admission diagnoses (OR 0.1, 95%CI 0.0-0.7, p=0.022) were inversely associated with inappropriate hospital days. In conclusion, patients living alone, functionally impaired and showing depressive symptoms were at increased risk for inappropriate hospital days. These characteristics might permit better targeting for early discharge planning in these at-risk subjects, and contribute to avoiding premature discharge of other vulnerable elderly patients. Whether these interventions for at-risk patients will also result in prevention of hospitalization hazards, such as deconditioning and related functional decline, will require further stud

Oksalat – od okoliša do bubrežnih kamenaca

Oxalate urolithiasis (nephrolithiasis) is the most frequent type of kidney stone disease. Epidemiological research has shown that urolithiasis is approximately twice as common in men as in women, but the underlying mechanism of this sex-related prevalence is unclear. Oxalate in the organism partially originate from food (exogenous oxalate) and largely as a metabolic end-product from numerous precursors generated mainly in the liver (endogenous oxalate). Oxalate concentrations in plasma and urine can be modified by various foodstuffs, which can interact in positively or negatively by affecting oxalate absorption, excretion, and/or its metabolic pathways. Oxalate is mostly removed from blood by kidneys and partially via bile and intestinal excretion. In the kidneys, after reaching certain conditions, such as high tubular concentration and damaged integrity of the tubule epithelium, oxalate can precipitate and initiate the formation of stones. Recent studies have indicated the importance of the SoLute Carrier 26 (SLC26) family of membrane transporters for handling oxalate. Two members of this family [Sulfate Anion Transporter 1 (SAT-1; SLC26A1) and Chloride/Formate EXchanger (CFEX; SLC26A6)] may contribute to oxalate transport in the intestine, liver, and kidneys. Malfunction or absence of SAT-1 or CFEX has been associated with hyperoxaluria and urolithiasis. However, numerous questions regarding their roles in oxalate transport in the respective organs and male-prevalent urolithiasis, as well as the role of sex hormones in the expression of these transporters at the level of mRNA and protein, still remain to be answered.Oksalatna urolitijaza (nefrolitijaza) najučestaliji je tip bolesti bubrežnih kamenaca. Rezultati epidemioloških istraživanja pokazali su da je urolitijaza približno dvostruko učestalija u muškaraca nego u žena, ali osnovni mehanizam nastanka ove spolno-ovisne prevalencije nije razjašnjen. Oksalat u organizmu dijelom potječe iz hrane (egzogeni oksalat), a glavninom nastaje kao konačni produkt metabolizma raznih preteča u jetrima (endogeni oksalat). Na koncentraciju oksalata u plazmi i urinu utječu razne tvari iz hrane, koje mogu pozitivno ili negativno djelovati na apsorpciju, metaboličke puteve i/ili izlučivanje oksalata. Oksalat se iz organizma izlučuje u manjem obimu putem žuči u crijevo, a glavninom bubrezima. U bubrezima, pri odgovarajućim uvjetima kao što su visoka koncentracija oksalata i oštećenje epitela bubrežnih kanalića, oksalat može precipitirati i time potaknuti stvaranje kamenaca. Rezultati novih istraživanja upućuju na važnost membranskih prijenosnika otopljenih tvari (SoLute Carriers) iz obitelji 26 (SLC26) za prijenos oksalata u specifičnim organima. Smatra se da dva člana ove obitelji: prijenosnik sulfatnog aniona (Sulfate Anion Transporter 1; SAT-1; SLC26A1) i izmjenjivač klora i mravlje kiseline (Chloride/Formate EXchanger; CFEX; SLC26A6), imaju značajnu ulogu u prijenosu oksalata u crijevima, jetrima i bubrezima; hiperoksalurija i nefrolitijaza utvrđeni su pri slaboj aktivnosti ili nedostatku SAT-1 i CFEX proteina. Međutim, još uvijek postoje brojne nejasnoće glede prijenosa oksalata u navedenim organima, mehanizma nastanka spolnih razlika u nefrolitijazi i utjecaja spolnih hormona na ekspresiju proteina i mRNA za navedene prijenosnike

Intravenous iron preparations transiently generate non-transferrin-bound iron from two proposed pathways

Intravenous iron-carbohydrate complex preparations (IVIPs) are non-interchangeable pro-drugs: their pharmacokinetics (PK) varies determined by semi-crystalline iron core and carbohydrate shell structures, influences pharmacodynamics (PD) and thus efficacy and safety. Examining PK/PD relationships of 3 IVIPs we identify a two-pathway model of transient NTBI generation following single dose administration. 28 hypoferremic non-anemic patients randomized to 200mg iron as ferric carboxymaltose (Fe-carboxymaltose), iron sucrose (Fe-sucrose), iron isomaltoside 1000 (Fe-isomaltoside-1000), n=8/arm, or placebo, n=4, on a 2-week PK/PD study, had samples analysed for total serum iron, IVIP-iron, transferrin-bound iron (TBI) by HPLC-ICP-MS, transferrin saturation (TSAT), serum ferritin (s-Ferritin) by standard methods, non-TBI (NTBI) and hepcidin as published before. IVIP-dependent increases in these parameters returned to baseline in 48-150h, except for s-Ferritin and TSAT. NTBI was low with Fe-isomaltoside-1000 (0.13µM at 8h), rapidly increased with Fe-sucrose (0.8µM at 2h, 1.25µM at 4h), and delayed for Fe-carboxymaltose (0.57µM at 24h). NTBI AUCs were 7-fold greater for Fe-carboxymaltose and Fe-sucrose than for Fe-isomaltoside-1000. Hepcidin peak time varied, but not AUC or mean levels. s-Ferritin levels and AUC were highest for Fe-carboxymaltose and greater than placebo for all IVIPs. We propose 2 mechanisms for the observed NTBI kinetics: rapid and delayed NTBI appearance consistent with direct (circulating IVIP-to-plasma) and indirect (IVIP-to-macrophage-to-plasma) iron release based on IVIP plasma half-life and s-Ferritin dynamics. IVIPs generate different, broadly stability- and PK-dependent, NTBI and s-Ferritin signatures, which may influence iron bioavailability, efficacy and safety. Longer-term studies should link NTBI exposure to subsequent safety and efficacy parameters and potential clinical consequences

Verifying linearizability on TSO architectures

Linearizability is the standard correctness criterion for fine-grained, non-atomic concurrent algorithms, and a variety of methods for verifying linearizability have been developed. However, most approaches assume a sequentially consistent memory model, which is not always realised in practice. In this paper we define linearizability on a weak memory model: the TSO (Total Store Order) memory model, which is implemented in the x86 multicore architecture. We also show how a simulation-based proof method can be adapted to verify linearizability for algorithms running on TSO architectures. We demonstrate our approach on a typical concurrent algorithm, spinlock, and prove it linearizable using our simulation-based approach. Previous approaches to proving linearizabilty on TSO architectures have required a modification to the algorithm's natural abstract specification. Our proof method is the first, to our knowledge, for proving correctness without the need for such modification