Diversity, variability, and suboesophageal connectivity of antennal lobe neurons in D. melanogaster larvae

Whereas the "vertical" elements of the insect olfactory pathway, the olfactory receptor neurons and the projection neurons, have been studied in great detail, local interneurons providing "horizontal" connections in the antennal lobe were ignored for a long time. Recent studies in adult Drosophila demonstrate diverse roles for these neurons in the integration of odor information, consistent with the identification of a large variety of anatomical and neurochemical subtypes. Here we focus on the larval olfactory circuit of Drosophila, which is much reduced in terms of cell numbers. We show that the horizontal connectivity in the larval antennal lobe differs largely from its adult counterpart. Only one of the five anatomical types of neurons we describe is restricted to the antennal lobe and therefore fits the definition of a local interneuron. Interestingly, the four remaining subtypes innervate both the antennal lobe and the suboesophageal ganglion. In the latter, they may overlap with primary gustatory terminals and with arborizations of hugin cells, which are involved in feeding control. This circuitry suggests special links between smell and taste, which may reflect the chemosensory constraints of a crawling and burrowing lifestyle. We also demonstrate that many of the neurons we describe exhibit highly variable trajectories and arborizations, especially in the suboesophageal ganglion. Together with reports from adult Drosophila, these data suggest that wiring variability may be another principle of insect brain organization, in parallel with stereotypy.     

Analysis of the outcome of intracytoplasmic sperm injection using fresh or frozen sperm

Study Type – Diagnostic (retrospective cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? The results of ICSI using fresh or frozen sperm on the site of sperm retrieval remains controversial with respect to outcome. The results of this study showed no difference in outcome using ICSI either with respect to the site of retrieval or whether the sperm used was fresh or frozen. It also showed that the outcome of ICSI is not related to the underlying cause of the azoospermia.

OBJECTIVES

? To compare the outcome of first‐attempt intracytoplasmic sperm injection (ICSI) ICSI–embryo transfer (ET) cycles using frozen‐thawed testicular sperm (FTTS), fresh testicular sperm (FTS), frozen‐thawed epididymal sperm (FTES) and fresh epididymal sperm (FES) so as to determine which of these has the most successful ICSI outcome with respect to fertilization rate (FR), pregnancy rate (PR) and birth rate. ? To assess the outcomes according to the underlying aetiology of azoospermia.

PATIENTS AND METHODS

? The records of 493 patients undergoing first‐attempt ICSI between 1993 and 2008 were reviewed retrospectively. FTS was used in 112 cycles, FTTS in 43 cycles, FES in 279 cycles, and FTES in 59 cycles. ? Within each group, the aetiology of the azoospermia was recorded according to history, clinical examination and histological analysis (n= 316). ? The FR, clinical PR and delivery rate were calculated for each group with respect to the type of sperm retrieval used.

RESULTS

? Analysis of the data showed no significant differences between any of the four groups in the FR, PR or delivery rate (P > 0.05). ? There were no significant differences seen between fresh sperm (FTS and FES) and frozen sperm (FTTS and FTES) or between epididymal sperm (FES and FTES) and testicular sperm (FTS and FTTS) in any of the outcomes measured (P > 0.05). However, sub‐set analysis showed a statistically higher FR and PR for FTTS over fresh sperm. ? When comparing aetiologies, there was no significant difference in the FR, clinical PR and delivery rate between obstructive azoospermia (OA) and non‐obstructive azoospermia (NOA) groups. However, sub‐set analysis showed a higher PR and birth rate for FTTS over fresh sperm in both OA and NOA groups.

CONCLUSIONS

? The results of the present study suggest that using frozen sperm in ICSI cycles is a reliable and favourable method with the same outcome as fresh sperm. ? Testicular and epididymal sperm have similar ICSI outcomes for both fresh and frozen samples. However, results suggest a tendency for higher PRs and birth rates for frozen than for fresh testicular sperm in both OA and NOA aetiologies. ? The aetiology of azoospermia does not significantly affect the outcome of first‐attempt ICSI. The higher rates in the frozen groups suggest that these patients have had better quality semen when they were initially harvested and frozen.     

The effect of serum concentration of leukaemia inhibitory factor on in vitro fertilization treatment outcome

PROBLEM: To evaluate the association of peripheral leukaemia inhibitory factor (LIF) levels on implantation and miscarriage rates after in vitro fertilization (IVF) treatment. METHODS: Prospective observational study of 120 randomly selected women who underwent IVF treatment. The concentration of LIF in serum was determined by enzyme-linked immunosorbent assay. RESULTS: There was no significant differences with regard to the systemic mean LIF concentration between the pregnant (42 patients, LIF: 11.55 pg/mL +/- 5.3 S.D.) and non-pregnant (66 patients, LIF: 13.47 pg/mL +/- 5.1 S.D.) women after IVF treatment. Likewise, for those women who have positive pregnancy after IVF treatment, the systemic mean LIF levels were not significantly different between women who have an ongoing pregnancy (34 ongoing pregnancy, LIF: 11.26 pg/mL +/- 5.2 S.D.) and those who had miscarriage (eight miscarriage, LIF: 12.78 pg/mL +/- 5.6 S.D.). CONCLUSION: The systemic levels of LIF concentration have no association with implantation rate or miscarriage rate in women undergoing IVF treatment. Measuring serum LIF concentration prior to embryo transfer in IVF treatment has no predictive value of implantation rate or miscarriage rate.     

Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction

Background

Recent studies have suggested that the microRNAs miR-133a and miR-423-5p may serve as useful biomarkers in patients with left ventricular (LV) heart failure or with LV remodeling after myocardial infarction (MI). These results were however obtained in small series of patients and control subjects were used as reference groups. Whether these microRNAs may be indicators of the degree of LV remodeling after MI is unknown.

Methods

246 patients with a first anterior Q-wave MI were included. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI and analyzed at a core laboratory. We investigated the temporal profile (baseline, 1, 3 and 12 months) of circulating miR-133a and miR-423-5p and their relations with cardiac biomarkers (B-type natriuretic peptide, C-reactive protein, and cardiac troponin I) and LV remodeling during the 1 year follow-up.

Results

There were time-dependent changes in the levels of circulating miR-133a and miR-423-5p with significant increase of miR-133a at 12 months compared to 3 months and significant increase of miR-423-5p at 1, 3, and 12 months compared to baseline. However, miR-133a and miR-423-5p were not associated with indices of LV function and LV remodeling serially assessed during a 1 year period after an acute anterior MI, nor with B-type natriuretic peptide.

Conclusions

Circulating levels of miR-133a and miR-423-5p are not useful biomarkers of LV remodeling after MI.     

Serial estimation of Th1:th2 cytokines profile in women undergoing in-vitro fertilization-embryo transfer

PROBLEM: To investigate changes in the ratio of T-cell subpopulations expressing intracellular T helper1 (Th1) and T helper 2 (Th2) cytokines in women with a history of recurrent failed implantation under going in-vitro fertilization (IVF)-embryo transfer. METHOD OF STUDY: Twenty-eight peripheral blood samples were obtained at two time points, from 14 women undergoing IVF treatment; eight women with a history of recurrent failed implantation, who did not get pregnant in the index IVF cycle and six who had one or more previous successful IVF pregnancy and who became pregnant in the index IVF cycle. The proportion of lymphocytes expressing interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 4 (IL-4) and the Th1:Th2 ratios of IFN-gamma:IL-4, and TNF-alpha:IL-4 in T helper cells was measured by flow cytometry, in samples obtained before commencing IVF treatment and in samples obtained after ovarian stimulation (on the day of oocyte retrieval). RESULTS: In samples collected during oocyte retrieval, women with a history of recurrent failed implantation had a higher IFN-gamma:IL-4 and TNF-alpha:IL-4 ratio than the control group, (18.6+/-9.3 versus 6.47+/-1.68, P=0.009) and (39.1+/-15.7 versus 11.53+/-3.76, P=0.001) respectively. In women with a history of recurrent failed implantation the ratio of IFN-gamma:IL-4 and TNF-alpha:IL-4 at oocyte retrieval was higher than pre-treatment ratios (18.6+/-9.3 versus 12.01+/-9.8, P=0.018) and 39.10+/-15.7 versus 18.66+/-11.42, P=0.010) respectively, showing a Th1 bias. In women with a successful IVF the converse was true; the ratio at oocyte retrieval was significantly lower than pre-treatment ratios (6.47+/-1.68 versus 9.37+/-6.8, P=0.035) and 11.53+/-3.76 versus 18.60+/-12.9, P=0.027) respectively, representing a Th2 bias. CONCLUSION: Women with a history of unexplained recurrent failed IVF treatment have a Th1 bias and this polarization is more enhanced following hormonal manipulations during IVF treatment. Comparing pre-treatment ratios of IFN-gamma:IL-4 and TNF-alpha:IL-4 to ratios obtained at oocyte retrieval may be clinically useful. Women with recurrent failed IVF have increasing ratios.     

SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation

Asthma is a chronic condition with unknown pathogenesis, and recent evidence suggests that enhanced airway epithelial chloride (Cl^–) secretion plays a role in the disease. However, the molecular mechanism underlying Cl^– secretion and its relevance in asthma pathophysiology remain unknown. To determine the role of the solute carrier family 26, member 9 (SLC26A9) Cl^– channel in asthma, we induced Th2-mediated inflammation via IL-13 treatment in wild-type and Slc26a9-deficient mice and compared the effects on airway ion transport, morphology, and mucus content. We found that IL-13 treatment increased Cl^– secretion in the airways of wild-type but not Slc26a9-deficient mice. While IL-13–induced mucus overproduction was similar in both strains, treated Slc26a9-deficient mice exhibited airway mucus obstruction, which did not occur in wild-type controls. In a study involving healthy children and asthmatics, a polymorphism in the 3′ UTR of SLC26A9 that reduced protein expression in vitro was associated with asthma. Our data demonstrate that the SLC26A9 Cl^– channel is activated in airway inflammation and suggest that SLC26A9-mediated Cl^– secretion is essential for preventing airway obstruction in allergic airway disease. These results indicate that SLC26A9 may serve as a therapeutic target for airway diseases associated with mucus plugging.