HIV-related neuropathy: current perspectives

Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP) related to human immunodeficiency virus (HIV) is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pai

Distance-generalized Core Decomposition

The $k$-core of a graph is defined as the maximal subgraph in which every vertex is connected to at least $k$ other vertices within that subgraph. In this work we introduce a distance-based generalization of the notion of $k$-core, which we refer to as the $(k,h)$-core, i.e., the maximal subgraph in which every vertex has at least $k$ other vertices at distance $\leq h$ within that subgraph. We study the properties of the $(k,h)$-core showing that it preserves many of the nice features of the classic core decomposition (e.g., its connection with the notion of distance-generalized chromatic number) and it preserves its usefulness to speed-up or approximate distance-generalized notions of dense structures, such as $h$-club. Computing the distance-generalized core decomposition over large networks is intrinsically complex. However, by exploiting clever upper and lower bounds we can partition the computation in a set of totally independent subcomputations, opening the door to top-down exploration and to multithreading, and thus achieving an efficient algorithm

Diffractive Meson Production and the Quark-Pomeron Coupling

Diffractive meson production at HERA offers interesting possibilities to investigate diffractive processes and thus to learn something about the properties of the pomeron. The most succesful phenomenological description of the pomeron so far assumes it to couple like a $C = +1$ isoscalar photon to single quarks. This coupling leads, however, to problems for exclusive diffractive reactions. We propose a new phenomenological pomeron vertex, which leads to very good fits to the known data, but avoids the problems of the old vertex.Comment: 20 pages, latex with uuencoded postscript, revised versio

A family of thermostable fungal cellulases created by structure-guided recombination

SCHEMA structure-guided recombination of 3 fungal class II cellobiohydrolases (CBH II cellulases) has yielded a collection of highly thermostable CBH II chimeras. Twenty-three of 48 genes sampled from the 6,561 possible chimeric sequences were secreted by the Saccharomyces cerevisiae heterologous host in catalytically active form. Five of these chimeras have half-lives of thermal inactivation at 63°C that are greater than the most stable parent, CBH II enzyme from the thermophilic fungus Humicola insolens, which suggests that this chimera collection contains hundreds of highly stable cellulases. Twenty-five new sequences were designed based on mathematical modeling of the thermostabilities for the first set of chimeras. Ten of these sequences were expressed in active form; all 10 retained more activity than H. insolens CBH II after incubation at 63°C. The total of 15 validated thermostable CBH II enzymes have high sequence diversity, differing from their closest natural homologs at up to 63 amino acid positions. Selected purified thermostable chimeras hydrolyzed phosphoric acid swollen cellulose at temperatures 7 to 15°C higher than the parent enzymes. These chimeras also hydrolyzed as much or more cellulose than the parent CBH II enzymes in long-time cellulose hydrolysis assays and had pH/activity profiles as broad, or broader than, the parent enzymes. Generating this group of diverse, thermostable fungal CBH II chimeras is the first step in building an inventory of stable cellulases from which optimized enzyme mixtures for biomass conversion can be formulated

Sociolinguistic functions of politeness in school debate: A road to peace education

Abstract: Schools and even difficult terrains can be used for structured argumentation for children of different socioethnic backgrounds. Debate educated the children about values of tolerance in a more practical way by organizing a competition outside classroom. Similarly, the debate taught the participants different pedagogies to promote cultural tolerance among children which include, human rights, encouragement of the participants to express their views and feelings regarding all issues without feeling restricted. Similarly, the debate exposed the children to discussing issues with their fellow age mates unrestrictedly in an open environment which is less boredom compared to classroom. Regardless of medium of deliverance, peace education as the kind in this paper provided the learner with much skills of understanding how other people think, behave and respond to situations even if they are unfavorable. Similarly, the type exercise provided in this paper offered unique opportunities for both participants and non participants alike to live in harmony with people unconditionally

Seasonal and interannual variability of cladoceran communities in two peri-alpine lakes: uncoupled response to the 2003 heat wave

Seasonal and interannual dynamics of cladoceran species were analyzed during the period 1995–2003 in two deep peri-alpine lakes morphologically different but subjected to similar regional climatic forcing. The seasonal succession of cladoceran species was characterized and the impact of extreme climatic events on the annual pattern of species succession was assessed. Using a multivariate method, we show that the cladoceran species display marked seasonality patterns that differed in the two lakes. The differences observed between the lakes were driven by their trophic state, the plankton species composition and the abundance of predators. We show that the sensitivity of the annual pattern of species succession to extreme weather changes, illustrated by the 2003 heat wave, differs markedly in these two lakes. In Lake Annecy, the annual pattern of cladoceran succession observed in 2003 is not different from the one usually observed. In contrast, in Lake Geneva, the annual pattern recorded in 2003 is unusual and characterized by the maintenance of herbivorous cladocera during summer. These findings underline the need to consider the morphology of lakes and trophic state in the assessment of ecological responses to global warming. Our results contribute to the debate about the predictability of the impacts of climate change on aquatic ecosystems, and their extrapolation from one site to another