VZV-associated acute retinal necrosis in a patient with MS treated with natalizumab

Natalizumab (NTZ) was the first approved humanized monoclonal antibody in highly active relapsing remitting MS (RRMS). Because of the mechanism of inhibiting the migration of immune cells through the blood-brain barrier into the CNS, NTZ is associated with an increased risk of progressive multifocal leukoencephalopathy (PML) by the John Cunningham virus (JCV). Infections with other neurotropic viruses are rarely reported. We present a case of rapid retinal necrosis induced by varicella zoster virus (VZV) in a patient with RRMS under long-term NTZ treatment

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies

Background The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of −53.0 μmol/L (P \u3c 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function

Rabl's model of the interphase chromosome arrangement tested in Chinise hamster cells by premature chromosome condensation and laser-UV-microbeam experiments

In 1885 Carl Rabl published his theory on the internal structure of the interphase nucleus. We have tested two predictions of this theory in fibroblasts grown in vitro from a female Chinese hamster, namely (1) the Rabl-orientation of interphase chromosomes and (2) the stability of the chromosome arrangement established in telophase throughout the subsequent interphase. Tests were carried out by premature chromosome condensation (PCC) and laser-UV-microirradiation of the interphase nucleus. Rabl-orientation of chromosomes was observed in G1 PCCs and G2 PCCs. The cell nucleus was microirradiated in G1 at one or two sites and pulse-labelled with 3H-thymidine for 2h. Cells were processed for autoradiography either immediately thereafter or after an additional growth period of 10 to 60h. Autoradiographs show unscheduled DNA synthesis (UDS) in the microirradiated nuclear part(s). The distribution of labelled chromatin was evaluated in autoradiographs from 1035 cells after microirradiation of a single nuclear site and from 253 cells after microirradiation of two sites. After 30 to 60h postincubation the labelled regions still appeared coherent although the average size of the labelled nuclear area fr increased from 14.2% (0h) to 26.5% (60h). The relative distance dr, i.e. the distance between two microirradiated sites divided by the diameter of the whole nucleus, showed a slight decrease with increasing incubation time. Nine metaphase figures were evaluated for UDS-label after microirradiation of the nuclear edge in G1. An average of 4.3 chromosomes per cell were labelled. Several chromosomes showed joint labelling of both distal chromosome arms including the telomeres, while the centromeric region was free from label. This label pattern is interpreted as the result of a V-shaped orientation of these particular chromosomes in the interphase nucleus with their telomeric regions close to each other at the nuclear edge. Our data support the tested predictions of the Rabl-model. Small time-dependent changes of the nuclear space occupied by single chromosomes and of their relative positions in the interphase nucleus seem possible, while the territorial organization of interphase chromosomes and their arrangement in general is maintained during interphase. The present limitations of the methods used for this study are discussed

Macrophage activation syndrome in autoimmune disease

Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of suspicion, as several characteristics of the disorder may be present in the underlying condition or infectious complications associated with the treatment thereof. Proposed treatment regimens include aggressive approaches that require validation in future controlled studies. This review discusses the major aspects of the pathophysiology, diagnosis, and management of MAS with a focus on the association with autoimmune disease

Inferring statistics of planet populations by means of automated microlensing searches

(abridged) The study of other worlds is key to understanding our own, and not only provides clues to the origin of our civilization, but also looks into its future. Rather than in identifying nearby systems and learning about their individual properties, the main value of the technique of gravitational microlensing is in obtaining the statistics of planetary populations within the Milky Way and beyond. Only the complementarity of different techniques currently employed promises to yield a complete picture of planet formation that has sufficient predictive power to let us understand how habitable worlds like ours evolve, and how abundant such systems are in the Universe. A cooperative three-step strategy of survey, follow-up, and anomaly monitoring of microlensing targets, realized by means of an automated expert system and a network of ground-based telescopes is ready right now to be used to obtain a first census of cool planets with masses reaching even below that of Earth orbiting K and M dwarfs in two distinct stellar populations, namely the Galactic bulge and disk. The hunt for extra-solar planets acts as a principal science driver for time-domain astronomy with robotic-telescope networks adopting fully-automated strategies. Several initiatives, both into facilities as well as into advanced software and strategies, are supposed to see the capabilities of gravitational microlensing programmes step-wise increasing over the next 10 years. New opportunities will show up with high-precision astrometry becoming available and studying the abundance of planets around stars in neighbouring galaxies becoming possible. Finally, we should not miss out on sharing the vision with the general public, and make its realization to profit not only the scientists but all the wider society.Comment: 10 pages in PDF format. White paper submitted to ESA's Exo-Planet Roadmap Advisory Team (EPR-AT); typos corrected. The embedded figures are available from the author on request. See also "Towards A Census of Earth-mass Exo-planets with Gravitational Microlensing" by J.P. Beaulieu, E. Kerins, S. Mao et al. (arXiv:0808.0005

I. Flux and color variations of the quadruply imaged quasar HE 0435-1223

aims: We present VRi photometric observations of the quadruply imaged quasar HE 0435-1223, carried out with the Danish 1.54m telescope at the La Silla Observatory. Our aim was to monitor and study the magnitudes and colors of each lensed component as a function of time. methods: We monitored the object during two seasons (2008 and 2009) in the VRi spectral bands, and reduced the data with two independent techniques: difference imaging and PSF (Point Spread Function) fitting.results: Between these two seasons, our results show an evident decrease in flux by ~0.2-0.4 magnitudes of the four lensed components in the three filters. We also found a significant increase (~0.05-0.015) in their V-R and R-i color indices. conclusions: These flux and color variations are very likely caused by intrinsic variations of the quasar between the observed epochs. Microlensing effects probably also affect the brightest "A" lensed component.Comment: 10 pages, 8 figure

A Unique Resource Mutualism between the Giant Bornean Pitcher Plant, Nepenthes rajah, and Members of a Small Mammal Community

The carnivorous pitcher plant genus Nepenthes grows in nutrient-deficient substrates and produce jug-shaped leaf organs (pitchers) that trap arthropods as a source of N and P. A number of Bornean Nepenthes demonstrate novel nutrient acquisition strategies. Notably, three giant montane species are engaged in a mutualistic association with the mountain treeshrew, Tupaia montana, in which the treeshrew defecates into the pitchers while visiting them to feed on nectar secretions on the pitchers' lids

Executive function and intelligence in the resolution of temporary syntactic ambiguity: An individual differences investigation

In the current study, we examined the role of intelligence and executive functions in the resolution of temporary syntactic ambiguity using an individual differences approach. Data were collected from 174 adolescents and adults who completed a battery of cognitive tests as well as a sentence comprehension task. The critical items for the comprehension task consisted of object/subject garden paths (e.g. While Anna dressed the baby that was small and cute played in the crib.), and participants answered a comprehension question (e.g. Did Anna dress the baby?) following each one. Previous studies have shown that garden-path misinterpretations tend to persist into final interpretations. Results showed that both intelligence and processing speed interacted with ambiguity. Individuals with higher intelligence and faster processing were more likely to answer the comprehension questions correctly, and specifically, following ambiguous as opposed to unambiguous sentences. Inhibition produced a marginal effect, but the variance in inhibition was largely shared with intelligence. Conclusions focus on the role of individual differences in cognitive ability and their impact on syntactic ambiguity resolution

Antibiotic resistance determinants in the interplay between food and gut microbiota

A complex and heterogeneous microflora performs sugar and lactic acid fermentations in food products. Depending on the fermentable food matrix (dairy, meat, vegetable etc.) as well as on the species composition of the microbiota, specific combinations of molecules are produced that confer unique flavor, texture, and taste to each product. Bacterial populations within such “fermented food microbiota” are often of environmental origin, they persist alive in foods ready for consumption, eventually reaching the gastro-intestinal tract where they can interact with the resident gut microbiota of the host. Although this interaction is mostly of transient nature, it can greatly contribute to human health, as several species within the food microbiota also display probiotic properties. Such an interplay between food and gut microbiota underlines the importance of the microbiological quality of fermented foods, as the crowded environment of the gut is also an ideal site for genetic exchanges among bacteria. Selection and spreading of antibiotic resistance genes in foodborne bacteria has gained increasing interest in the past decade, especially in light of the potential transferability of antibiotic resistance determinants to opportunistic pathogens, natural inhabitants of the human gut but capable of acquiring virulence in immunocompromised individuals. This review aims at describing major findings and future prospects in the field, especially after the use of antibiotics as growth promoters was totally banned in Europe, with special emphasis on the application of genomic technologies to improve quality and safety of fermented foods

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial

AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy)