Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram.

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

Test-retest repeatability of the pupil light response to blue and red light stimuli in normal human eyes using a novel pupillometer.

In this study, we evaluated the repeatability of pupil responses to colored light stimuli in healthy subjects using a prototype chromatic pupillometer. One eye of 10 healthy subjects was tested twice in the same day using monochromatic light exposure at two selected wavelengths (660 and 470 nm, intensity 300 cd/m(2)) presented continuously for 20 s. Pupil responses were recorded in real-time before, during, and after light exposure. Maximal contraction amplitude and sustained contraction amplitude were calculated. In addition, we quantified the summed pupil response during continuous light stimulation as the total area between a reference line representing baseline pupil size and the line representing actual pupil size over 20 s (area under the curve). There was no significant difference in the repeated measure compared to the first test for any of the pupil response parameters. In conclusion, we have developed a novel prototype of color pupillometer which demonstrates good repeatability in evoking and recording the pupillary response to a bright blue and red light stimulus.

Dysmegakaryopoiesis predicting response to therapy in acute myeloid leukaemia. A histologic and clinical study

With standard induction therapy between 50 to 85% of patients with Acute Myeloid Leukaemia (AML) achieve Complete Remission (CR). We investigated whether any morphological feature of bone marrow (BM) plastic embedded biopsies could predict failure of therapy. We reviewed BM plastic embedded biopsies from 54 adult patients presenting with untreated AML. The main histologic parameters analysed were cellularity, dysmegakaryopoiesis (DysM), percentage of marrow blasts and fibrosis. CR was obtained in 34 of 49 treated patients (69%). The rate of CR was significantly lower in the group of patients presenting with DysM: CR was achieved in 54% of the 28 treated patients with DysM and in 90% of the 21 treated patients without DysM (p less than 0.02). Patients with DysM had a significantly lower blood count and bone marrow blasts at presentation. Median age was not significantly different in the 2 groups. Cellularity and fibrosis were not predictive. DysM may be the hallmark of an AML subgroup with distinct clinical behaviour and lower rate of CR with conventional therapy. DysM should be carefully looked for on BM marrow biopsies and aspirate from AML patients at diagnosis.

Response to topical clonazepam in patients with burning mouth syndrome: a clinical study

Burning Mouth Syndrome (BMS) is a difficult disease for patients and clinicians. Moreover, there is not a general consensus on how to treat the disease. The main objective of this paper is to evaluate BMS patients' response to topical clonazepam treatment. A double blind study was performed. Among a total of 66 patients, 33 were treated with tablets of clonazepam and another 33 were treated with a placebo. Symptoms were evaluated after 1 month and 6 months of treatment and scored on an analogical scale from 0 to 10. Among the 33 patients treated with clonazepam, 23 showed at least a 50% reduction in symptoms after 1 month of treatment. On the contrary, only 4 in the placebo group exhibited significant improvement. After 6 months, significant differences were observed again, as 23 of the 33 patients treated with the drug reported at least a 50% reduction in symptoms, whereas only 2 among those treated with the placebo significantly improved. However, when measured in terms of a complete cure (lack of symptoms), the differences were not significant: 5 drug-treated patients and one belonging to the placebo group were asymptomatic after one month of treatment. In summary, it seems that clonazepam applied topically was effective in treating BMS in a large proportion of patients

Quantitative developmental response to the length of exposure to long photoperiod in wheat and barley

The present study was designed to analyse the effect of the length of exposure to a long photoperiod imposed c. 3 weeks after sowing in spring wheat (cv. UQ189) and barley (cv. Arapiles) to (i) establish whether the response to the number of cycles of exposure is quantitative or qualitative, (ii) determine the existence of a commitment to particular stages well before the stage has been observable, and (iii) study the interrelationships between the effects on final leaf number and phyllochron when the stimulus is provided several days after seedling emergence. Both wheat and barley seemed to respond quantitatively to the number of long-day cycles they were exposed to. However, wheat showed a requirement of approximately 4 long-day cycles to be able to produce a significant response in time to heading. The barley cultivar used in the study was responsive to the minimum length of exposure. The response to extended photoperiod cycles during the stem elongation phase was due to the ‘ memory’ photoperiod effects being related, in the case of wheat, to the fact that the pre-terminal spikelet appearance phase saturated its photoperiod response well before that stage was reached. Therefore, the commitment to the terminal spikelet appearance in wheat may be reached well before this stage could be recognized. As the response in duration to heading exceeded that of the final leaf number, and the stem elongation phase responded to memory effects of photoperiod, the phyllochron of both cereals was responsive to the treatments accelerating the average phyllochron when exposed to longer periods of long days. The response in average phyllochron was due to a switch from bi-linear to linear models of leaf number v. time when the conditions were increasingly inductive, with the phyllochron of the initial (6–8) leaves being similar for all treatments (within each species), and from then on increased.

Atypical coordination of cortical oscillations in response to speech in autism.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.

Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study.

OBJECTIVES: Gender-specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal access to cART over a 14-year period. METHODS: Analyses included treatment-naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men. RESULTS: A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV-1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV-related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression. CONCLUSIONS: Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.

Idiosyncratic evolution of maternal effects in response to juvenile malnutrition in Drosophila.

Maternal effects often affect fitness traits, but there is little experimental evidence pertaining to their contribution to response to selection imposed by novel environments. We studied the evolution of maternal effects in Drosophila populations selected for tolerance to chronic larval malnutrition. To this end, we performed pairwise reciprocal F1 crosses between six selected (malnutrition tolerant) populations and six unselected control populations and assessed the effect of cross direction on larval growth and developmental rate, adult weight and egg-to-adult viability expressed under the malnutrition regime. Each pair of reciprocal crosses revealed large maternal effects (possibly including cytoplasmic genetic effects) on at least one trait, but the magnitude, sign and which traits were affected varied among populations. Thus, maternal effects contributed significantly to the response to selection imposed by the malnutrition regime, but these changes were idiosyncratic, suggesting a rugged adaptive landscape. Furthermore, although the selected populations evolved both faster growth and higher viability, the maternal effects on growth rate and viability were negatively correlated across populations. Thus, genes mediating maternal effects can evolve to partially counteract the response to selection mediated by the effects of alleles on their own carriers' phenotype, and maternal effects may contribute to evolutionary trade-offs between components of offspring fitness.

Do we need to revise the tripartite subdivision hypothesis of the human subthalamic nucleus (STN)? Response to Alkemade and Forstmann.

Recently in this journal, Alkemade and Forstmann again challenged the evidence for a tripartite organisation to the subthalamic nucleus (STN) (Alkemade & Forstmann 2014). Additionally, they raised specific issues with the earlier published results using 3T MRI to perform in vivo diffusion weighted imaging (DWI) based segmentation of the STN (Lambert et al. 2012). Their comments reveal a common misconception related to the underlying methodologies used, which we clarify in this reply, in addition to highlighting how their current conclusions are synonymous with our original paper. The ongoing debate, instigated by the controversies surrounding STN parcellation, raises important implications for the assumptions and methodologies employed in mapping functional brain anatomy, both in vivo and ex vivo, and reveals a fundamental emergent problem with the current techniques. These issues are reviewed, and potential strategies that could be developed to manage them in the future are discussed further.