From dichotic listening to the irrelevant sound effect: a behavioural and neuroimaging analysis of the processing of unattended speech

The assumption that ignoring irrelevant sound in a serial recall situation is identical to ignoring a non-target channel in dichotic listening is challenged. Dichotic listening is open to moderating effects of working memory capacity (Conway et al., 2001) whereas irrelevant sound effects (ISE) are not (Beaman, 2004). A right ear processing bias is apparent in dichotic listening, whereas the bias is to the left ear in the ISE (Hadlington et al., 2004). Positron emission tomography (PET) imaging data (Scott et al., 2004, submitted) show bilateral activation of the superior temporal gyrus (STG) in the presence of intelligible, but ignored, background speech and right hemisphere activation of the STG in the presence of unintelligible background speech. It is suggested that the right STG may be involved in the ISE and a particularly strong left ear effect might occur because of the contralateral connections in audition. It is further suggested that left STG activity is associated with dichotic listening effects and may be influenced by working memory span capacity. The relationship of this functional and neuroanatomical model to known neural correlates of working memory is considered.     

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

Invasive mucormycosis of the maxillary sinus: extensive destruction with an indolent presentation

BACKGROUND: Mucormycosis (zygomycosis) is a rare, aggressive, invasive fungal infection that usually afflicts immunosuppressed patients. Indolent presentations are rare, especially in the setting of immune suppression. METHODS: Case report and review of the pertinent English-language literature. CASE REPORT: A 64-year-old male patient with diabetes mellitus and rheumatoid arthritis, treated chronically with infliximab, presented with toothache, headache, and right facial numbness. Therapy with intravenous glucocorticoids and antibiotics resulted in transitory improvement before his referral to a tertiary-care center, where imaging studies and biopsy revealed rhinocerebral mucormycosis. Four weeks after initial presentation, a radical right maxillectomy, followed by long-term therapy with amphotericin B lipid complex, resulted in clinical improvement. Five reconstructive procedures were required to obliterate the facial defect and restore contour. Although biopsies during the reconstructive procedures revealed persistent fungal colonization, there was no clinical recurrence during nearly five years of followup. CONCLUSIONS: Indolent rhinocerebral mucormycosis is rare and is seldom survived by immunosuppressed patients. Multimodal therapy with surgical debridement and antifungal chemotherapy is required for an optimal outcome. Discontinuance of immunosuppressive therapy, if possible, is a cornerstone of management.     

Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations

For 29 days, rats were given a daily opportunity to take a sweetened ethanol solution (ES) or water when deprived of water. Under this regimen, and throughout all procedures, rats gained weight normally. They eventually took considerable amounts of ethanol (E). Across the next days of the regimen, one group was given an injection of morphine (MOR), 2.5 mg/kg, 30 min before each of 6 consecutive daily opportunities to drink. MOR enhanced intake of ES on every day of injections. Naloxone (NX) (2.5 mg/kg, 10 min before opportunity to drink) was given to rats having had many daily opportunities to take ES. NX reduced intakes day after day. Rats given NX from the first opportunity to take ES did not develop an avidity for ES as other rats given placebo-injections. MOR increased intakes among rats not deprived of water, among rats housed in groups as well as individually, among rats taking unsweetened ES, and among rats presented with various flavors of ES as the only solution during an hour-long session. The data confirm and extend the conclusion that small doses of MOR enhance E-intake, indicate that the effects of opioids on E-intake do not tolerate with repeated administrations, and generally support the idea that an endogenous opioid system is involved in the reinforcement derived from E.     

Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness

Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G>C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G>C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild‐type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol‐specific phospholipase C‐induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI‐anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI‐anchorage.     

The Application of Science- and Risk-Based Concepts to Drug Substance Stability Strategies

The International Conference on Harmonization (ICH) has provided practical guidance on the amount and type of drug substance stability data needed to support marketing applications (International Conference on Harmonization 2001, 2002, 2003a, b). Additional guidance has been issued by the World Health Organization (WHO 2009). Recent scientific advances and practices have resulted in improved scientific understanding of the chemical and physical attributes that contribute directly or indirectly to drug substance stability. Combining this improved understanding with the science- and risk-based approaches detailed in ICH Q8, Q9, and Q10 allows for alternative and more scientifically driven approaches to meet the scientific and regulatory objectives for drug substance stability (International Conference on Harmonization 2005, 2008, 2009). In this paper, proposals are presented to more fully leverage enhanced product knowledge to design improved stability strategies. The chemical and physical attributes that potentially impact drug substance stability are discussed, and strategies that leverage accelerated stability studies are presented.     

Predictors of successful labor induction with oral or vaginal misoprostol

Objective: To identify independent predictors of successful labor induction with oral or vaginal misoprostol.

Methods: Women enrolled in four previous randomized trials involving oral or vaginal misoprostol for cervical ripening and labor induction were included in the present cohort study, with dosing of 25–50?μg every 4 to 6?h vaginally (n?=?574) or 50?μg every 4?h orally (n?=?207). Multiple logistic regression was performed to identify factors independently associated with successful labor induction – defined as vaginal delivery within 12?h, vaginal delivery within 24?h and spontaneous vaginal delivery. Predictors of Cesarean birth and the need for only one dose of misoprostol were also identified. Variables included in the models were maternal age, weight, height, parity, gravidity, membrane status, route of misoprostol, gestational age, birth weight, and Bishop score and its individual components.

Results: Maternal age, height, weight, parity, birth weight, dilatation, effacement and cervical station were associated with vaginal delivery within 24?h of induction. Maternal age, height, weight, nulliparity, birth weight and route of misoprostol were associated with Cesarean birth, with oral misoprostol being associated with a lower rate of Cesarean birth. The need for only one dose of misoprostol was predicted by maternal height, weight, parity, gestational age, Bishop score and route of misoprostol.

Conclusion: Characteristics of the woman (height, weight, parity), the fetus (birth weight) and some of the individual components of the Bishop score, were associated with successful labor induction, with oral misoprostol being associated with a lower rate of Cesarean birth.     

ROLE OF EPIDURAL MEDICATION IN LUMBOSCIATIC SYNDROME

Role of epidural medication through caudal route was studied in 109 patients having lumbago with or without sciatica to highlight the value of this mode of treatment which relieved symptoms in more than 70% of cases without hospitalisation and without being off work for long periods as in usual methods of conservative treatment.KEY WORDS: Epidural medication, Backache, Lumbago, Sciatica