Drinking spout orifice size affects licking behavior in inbred mice

Using a lickometer, we assessed the effect of drinking spout orifice size on the licking behavior of inbred mice [C57BL/6J, SWR/J, 129P3/J and DBA/2J]. Animals licked from drinking spout sipper tubes that had what were defined as either a large (2.7 mm) or a small (1.5 mm) orifice. Mice took approximately twice as many licks from a stationary single small orifice drinking spout than when licking from a spout with a large orifice during separate 30-min sessions. However, their total intake volume was approximately the same. We calculated that mice received a mean of 0.55 muL per lick from the drinking tubes with a small orifice and a mean of 1.15 muL per lick from the drinking tubes with a large orifice. Thus, the animals appear to have regulated their fluid intake by proportionally adjusting their licking as a function of the lick volume. On average, this regulation occurred through modulation of the size of licking bursts and not their frequency. However, strain differences in compensation strategy were observed. When licking was restricted to a series of 5-s trials in a 30-min brief access test session, the smaller orifice size increased the range of responsiveness that was expressed. Mice increased their average licks per trial by 20% and took 60% more trials when licking from a spout with a small orifice. Interestingly, when the orifice size was quasi-randomly varied within a brief access session, licking was greater from large orifice drinking spouts, suggesting that water delivered from the two orifice sizes differs in its reinforcement efficacy. These findings demonstrate that drinking spout orifice size can significantly influence experimental outcomes in licking tests involving mice and care should be taken in controlling this variable in testing the effects of taste or other factors on ingestive behavior.     

Influence of Mansonella perstans microfilaraemia on total IgE levels in Gabonese patients co-infected with Loa loa

Mansonella (M.) perstans filariasis is widely found in Africa, including Gabon where Loa loa is also endemic. This study reports the total IgE titres according to different bioclinical forms of single or co-infection with L. loa and M. perstans in 138 patients and 20 healthy controls. The median parasite density was significantly higher in cases of loiasis. IgE titres were higher in patients with microscopic dual-infection and in the group of patients with occult loiasis plus M. perstans microfilaraemia (8425 [5292–20,679] KUI/L and 6304 [1045–10,326] KUI/L, respectively), compared to individuals with either microfilaraemic Loa loa (3368 [1414–7074] KUI/L) or Mansonella (4370 [1478–7334] KUI/L) single infections (p < 0.01). IgE levels were positively correlated with M. perstans microfilaraemia (rho = 0.27; p < 0.01). Compared to single infections, dual M. perstans–L. loa infection induces very high total IgE titres. Studies correlating IgE titres and clinical symptoms are needed to confirm the involvement of this immunoglobulin in the pathological processes during filariasis.     

A randomized controlled trial demonstrates that a novel closed-loop propofol system performs better hypnosis control than manual administration

Purpose

The purpose of this randomized control trial was to determine the performance of a novel rule-based adaptive closed-loop system for propofol administration using the bispectral index (BIS®) and to compare the system’s performance with manual administration. The effectiveness of the closed-loop system to maintain BIS close to a target of 45 was determined and compared with manual administration.

Methods

After Institutional Review Board approval and written consent, 40 patients undergoing major surgery in a tertiary university hospital were allocated to two groups using computer-generated block randomization. In the Closed-loop group (n = 20), closed-loop control was used to maintain anesthesia at a target BIS of 45, and in the Control group (n = 20), propofol was administered manually to maintain the same BIS target. To evaluate each technique’s performance in maintaining a steady level of hypnosis, the BIS values obtained during the surgical procedure were stratified into four clinical performance categories relative to the target BIS: ≤ 10%, 11-20%, 21-30%, or > 30% defined as excellent, good, poor, or inadequate control of hypnosis, respectively. The controller performance was compared using Varvel’s controller performance indices. Data were compared using Fisher’s exact test and the Mann-Whitney U test, P < 0.05 showing statistical significance.

Results

In the Closed-loop group, four females and 16 males (aged 54 ± 20 yr; weight 79 ± 7 kg) underwent anesthesia lasting 143 ± 57 min. During 55%, 29%, 9%, and 7% of the total anesthesia time, the system showed excellent, good, poor, and inadequate control, respectively. In the Control group, five females and 15 males (aged 59 ± 16 yr; weight 75 ± 13 kg) underwent anesthesia lasting 157 ± 81 min. Excellent, good, poor, and inadequate control were noted during 33%, 33%, 15%, and 19% of the total anesthesia time, respectively. In the Closed-loop group, excellent control of anesthesia occurred significantly more often (P < 0.0001), and poor and inadequate control occurred less often than in the Control group (P < 0.01). The median performance error and the median absolute performance error were significantly lower in the Closed-loop group compared with the Control group (-1.1 ± 5.3% vs -10.7 ± 13.1%; P = 0.004 and 9.1 ± 1.9% vs 15.7 ± 7.4%; P < 0.0001, respectively).

Conclusion

The closed-loop system for propofol administration showed better clinical and control system performance than manual administration of propofol. (Clinical Trials gov. NCT 01019746).     

A diagnostic genetic test for the physical mapping of germline rearrangements in the susceptibility breast cancer genes BRCA1 and BRCA2

The BRCA1 and BRCA2 genes are involved in breast and ovarian cancer susceptibility. About 2 to 4% of breast cancer patients with positive family history, negative for point mutations, can be expected to carry large rearrangements in one of these two genes. We developed a novel diagnostic genetic test for the physical mapping of large rearrangements, based on molecular combing (MC), a FISH-based technique for direct visualization of single DNA molecules at high resolution. We designed specific Genomic Morse Codes (GMCs), covering the exons, the noncoding regions, and large genomic portions flanking both genes. We validated our approach by testing 10 index cases with positive family history of breast cancer and 50 negative controls. Large rearrangements, corresponding to deletions and duplications with sizes ranging from 3 to 40 kb, were detected and characterized on both genes, including four novel mutations. The nature of all the identified mutations was confirmed by high-resolution array comparative genomic hybridization (aCGH) and breakpoints characterized by sequencing. The developed GMCs allowed to localize several tandem repeat duplications on both genes. We propose the developed genetic test as a valuable tool to screen large rearrangements in BRCA1 and BRCA2 to be combined in clinical settings with an assay capable of detecting small mutations.