KCNQ/M currents in sensory neurons: Significance for pain therapy

Neuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents [I-K(M)] play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 subunits, the molecular correlates of I-K(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. I-K(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 muM) and XE991 (IC50, 0.26 muM) and enhanced by retigabine (10 muM). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that I-K(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target

An Examination of Statistical Disclosure Issues Related to Publication of Aggregate Statistics in the Presence of a Known Subset of the Dataset Using Baseball Hall of Fame Ballots

Each year the members of the Baseball Writers Association of America (BBWAA) vote for eligible former players to be inducted into the Baseball Hall of Fame. The BBWAA tabulates and releases vote totals, but individual ballots remain private. However, many voters forgo their ballot privacy to publish their ballots through various media channels. These publicly available ballots can be aggregated to create a subset of the true ballots. Using these released ballots and the totals released by the BBWAA, this research assesses what can be learned about the group of voters who chose to not disclose their ballot. Attributes of the known and unknown ballot groups are studied by looking at differences in voting preference for individual players as well as voting differences between classes of voters that are defined using latent class analysis (LCA)

Label-free photoacoustic microscopy of peripheral nerves

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies

Population dynamics, delta vulnerability and environmental change: comparison of the Mekong, Ganges–Brahmaputra and Amazon delta regions

Tropical delta regions are at risk of multiple threats including relative sea level rise and human alterations, making them more and more vulnerable to extreme floods, storms, surges, salinity intrusion, and other hazards which could also increase in magnitude and frequency with a changing climate. Given the environmental vulnerability of tropical deltas, understanding the interlinkages between population dynamics and environmental change in these regions is crucial for ensuring efficient policy planning and progress toward social and ecological sustainability. Here, we provide an overview of population trends and dynamics in the Ganges–Brahmaputra, Mekong and Amazon deltas. Using multiple data sources, including census data and Demographic and Health Surveys, a discussion regarding the components of population change is undertaken in the context of environmental factors affecting the demographic landscape of the three delta regions. We find that the demographic trends in all cases are broadly reflective of national trends, although important differences exist within and across the study areas. Moreover, all three delta regions have been experiencing shifts in population structures resulting in aging populations, the latter being most rapid in the Mekong delta. The environmental impacts on the different components of population change are important, and more extensive research is required to effectively quantify the underlying relationships. The paper concludes by discussing selected policy implications in the context of sustainable development of delta regions and beyond

An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease

Background: Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable sideeffects. Identifying patient responsiveness early could guide therapy. Methods: Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry. Results: At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a signifccant decrease in GAG at week 2 (P < 0 05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0 05) and a continued reduction in perfusion (P < 0 001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein. Conclusions: This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response

Equilibrium and stability properties of a coupled two-component Bose-Einstein condensate

The equilibrium and stability properties of a coupled two-component BEC is studied using a variational method and the one-dimensional model of Williams and collaborators. The variational parameters are the population fraction, translation and scaling transformation of the condensate densities, assumed to have a Gaussian shape. We study the equilibrium and stability properties as a function of the strength of the laser field and the traps displacement. We find many branches of equilibrium configurations, with a host of critical points. In all cases, the signature of the onset of criticality is the collapse of a normal mode which is a linear combination of the out of phase translation and an in phase breathing oscillation of the condensate densities. Our calculations also indicate that we have symmetry breaking effects when the traps are not displacedComment: 13 pages,3 figure

Modulation of urban atmospheric electric field measurements with the wind direction in Lisbon (Portugal)

Atmospheric electric field measurements (potential gradient, PG) were retrieved in the urban environment of the city of Lisbon (Portugal). The measurements were performed with a Benndorf electrograph at the Portela Meteorological station in the suburbs of the city (NE from the centre). The period of 1980 to 1990 is considered here. According to wind direction, different content and types of ions and aerosols arrive at the measurement site causing significant variations to the PG. To the south there are significant pollution sources while to the north such sources are scarcer . The Iberian Peninsula is found east of the station and the Atlantic Ocean covers the western sector, Wind directions are divided in four sectors: i) NW: 270º ≤ θ ≤ 360º; ii) NE: 0 ≤ θ ≤ 90º; iii) SE: 90 ≤ θ ≤ 180º; iv) SW: 180º ≤ θ ≤ 270º. Analysis of weekly cycle, caused by anthropogenic pollution related with urban activity, was undertaken for each wind sector. NW sector has been shown to be less affected by this cycle, which is attributed to the effect of marine air. The daily variation of NE sector for weekends reveals a similar behaviour to the Carnegie curve, which corresponds to a clean air daily variation of PG, following universal time, independent of measurement site

Impact of the Madden-Julian oscillation on extreme precipitation over the western Maritime Continent and Southeast Asia

The western Maritime Continent (MC) and Southeast Asia lie at the heart of the largest area of high precipitation on Earth. Extreme precipitation is one of the major high-impact weather events to affect the population of over 500 million in this region. The deep convection associated with this extreme precipitation is difficult to forecast, even with modern high-resolution numerical weather prediction with explicit convection. However, larger-scale organised convective systems, such as the Madden–Julian Oscillation (MJO), can be skilfully predicted to 3–5 weeks lead time. The MJO has a well-known precipitation signal, and it is likely that it also modulates extreme precipitation. Here, the extreme precipitation signal of the MJO is analysed in detail for the western MC and Southeast Asia using 19 years of high-resolution Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM IMERG) data. The probability of experiencing extreme precipitation increases robustly by a factor of two, and decreases by a factor of half, dependent on location and the phase of the MJO. The spatial pattern of these changes in extreme precipitation does not describe a smooth eastward propagation, but shows rapid variation over short distances, tied to the complex distribution of land and sea within the archipelago. There is also a seasonal dependence of this MJO modulation in some locations. A more detailed analysis of the effect of the MJO on extreme precipitation is presented for the major cities in the region. Extreme precipitation days over the MC are generally linked with an amplification of the diurnal cycle. However, although an active MJO increases the frequency of extreme precipitation days and therefore an amplified diurnal cycle, there was no further amplification of the diurnal cycle in the active MJO, compared with extreme precipitation days during non-active MJO periods