When is it safe to return to driving following first-ever seizure?

OBJECTIVES: The risk of recurrence following a first-ever seizure is 40-50%, warranting driving restriction during the early period of highest risk. This restriction must be balanced against the occupational, educational and social limitations that result from patients being ineligible to drive. The recommended duration of non-driving after a first seizure varies widely between jurisdictions, influenced by various factors including the community perception of an acceptable relative level of risk for an accident (the accident risk ratio; ARR). Driving restrictions may be based on individualised risk assessments or across-the-board guidelines, but these approaches both require accurate data on the risk of seizure recurrence. METHODS: 1386 patients with first-ever seizure were prospectively analysed. Seizure recurrence was evaluated using survival analysis. The duration of non-driving required for a range of risks of seizure recurrence and ARRs was calculated. Additionally, the actual occurrence of seizures while driving was prospectively determined during follow-up. RESULTS: For a risk of seizure recurrence to fall to 2.5% per month, corresponding to a monthly risk of a seizure while driving of 1.04 per thousand and an ARR of 2.6, non-driving periods of 8 months are required for unprovoked first-ever seizure, and 5 months for provoked first-ever seizure. Of patients with a seizure recurrence, 14 (2%) occurred while driving, with the monthly risk falling to less than 1/1000 after 6 months. CONCLUSIONS: Our data provide a quantitative approach to decisions regarding a return to driving in patients with first-ever provoked or unprovoked seizure.

First use of alemtuzumab in Balo's concentric sclerosis: a case report.

Balo's concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing-remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.

Two RNA-binding sites in plant fibrillarin provide interactions with various RNA substrates.

Fibrillarin, one of the major proteins of the nucleolus, plays several essential roles in ribosome biogenesis including pre-rRNA processing and 2'-O-ribose methylation of rRNA and snRNAs. Recently, it has been shown that fibrillarin plays a role in virus infections and is associated with viral RNPs. Here, we demonstrate the ability of recombinant fibrillarin 2 from Arabidopsis thaliana (AtFib2) to interact with RNAs of different lengths and types including rRNA, snoRNA, snRNA, siRNA and viral RNAs in vitro. Our data also indicate that AtFib2 possesses two RNA-binding sites in the central (138-179 amino acids) and C-terminal (225-281 amino acids) parts of the protein, respectively. The conserved GCVYAVEF octamer does not bind RNA directly as suggested earlier, but may assist with the proper folding of the central RNA-binding site.

Supporting the massive scale-up of antiretroviral therapy: the evolution of PEPFAR-supported treatment facilities in South Africa, 2005-2009.

BACKGROUND: South Africa has an estimated 1.5 million persons in need of antiretroviral therapy (ART). In 2004, the South African government began collaborating with the United States President's Emergency Plan for AIDS Relief (PEPFAR) to increase access to ART. We determined how PEPFAR treatment support changed from 2005-2009. METHODS: In order to describe the change in number and type of PEPFAR-supported ART facilities, we analyzed routinely collected program-monitoring data from 2005-2009. The collected data included the number, type and province of facilities as well as the number of patients receiving ART at each facility. RESULTS: The number of PEPFAR-supported facilities providing ART increased from 184 facilities in 2005 to 1,469 facilities in 2009. From 2005-2009 the number of PEPFAR-supported government facilities increased 10.1 fold from 54 to 546 while the number of PEPFAR-supported NGO facilities (including general practitioner and NGO facilities) increased 6.2 fold from 114 to 708. In 2009 the total number of persons treated at PEPFAR-supported NGO facilities was 43,577 versus 501,089 persons at PEPFAR-supported government facilities. Overall, the median number of patients receiving ART per site increased from 81 in 2005 to 136 in 2009. CONCLUSIONS: To mitigate the gap between those needing and those receiving ART, more facilities were supported. The proportion of government facilities supported and the median number of persons treated at these facilities increased. This shift could potentially be sustainable as government sites reach more individuals and receive government funding. These results demonstrate that PEPFAR was able to support a massive scale-up of ART services in a short period of time.

Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: antiproliferative effects of peptide analogues.

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone overproduction. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.

Effects of a mass media intervention on HIV-related stigma: 'Radio Diaries' program in Malawi.

HIV-related stigma has been recognized as a significant public health issue, yet gaps remain in development and evaluation of mass media interventions to reduce stigma. The Malawi 'Radio Diaries' (RD) program features people with HIV telling stories about their everyday lives. This study evaluates the program's effects on stigma and the additional effects of group discussion. Thirty villages with 10 participants each were randomized to listen to RD only, to the program followed by group discussion or to a control program. Post-intervention surveys assessed four stigma outcomes: fear of casual contact, shame, blame and judgment and willingness to disclose HIV status. Regression analyses indicated that fear of casual contact was reduced by the intervention. Shame was reduced by the radio program, but only for those reporting prior exposure to the radio program and for those who did not have a close friend or relative with HIV. Shame was not reduced when the radio program was followed by discussion. The intervention reduced blame for men and not women and for younger participants but not older participants. Including people with HIV/AIDS in mass media interventions has potential to reduce stigma.

U12-dependent intron splicing in plants.

U12-dependent (U12) introns have persisted in the genomes of plants since the ancestral divergence between plants and metazoans. These introns, which are rare, are found in a range of genes that include essential functions in DNA replication and RNA metabolism and are implicated in regulating the expression of their host genes. U12 introns are removed from pre-mRNAs by a U12 intron-specific spliceosome. Although this spliceosome shares many properties with the more abundant U2-dependent (U2) intron spliceosome, four of the five small nuclear RNAs (snRNAs) required for splicing are different and specific for the unique splicing of U12 introns. Evidence in plants so far indicates that splicing signals of plant U12 introns and their splicing machinery are similar to U12 intron splicing in other eukaryotes. In addition to the high conservation of splicing signals, plant U12 introns also retain unique characteristic features of plant U2 introns, such as UA-richness, which suggests a requirement for plant-specific components for both the U2 and U12 splicing reaction. This chapter compares U12 and U2 splicing and reviews what is known about plant U12 introns and their possible role in gene expression.

The role of the plant nucleolus in pre-mRNA processing.

The nucleolus is a multifunctional compartment of the eukaryotic nucleus. Besides its well-recognised role in transcription and processing of ribosomal RNA and the assembly of ribosomal subunits, the nucleolus has functions in the processing and assembly of a variety of RNPs and is involved in cell cycle control and senescence and as a sensor of stress. Historically, nucleoli have been tenuously linked to the biogenesis and, in particular, export of mRNAs in yeast and mammalian cells. Recently, data from plants have extended the functions in which the plant nucleolus is involved to include transcriptional gene silencing as well as mRNA surveillance and nonsense-mediated decay, and mRNA export. The nucleolus in plants may therefore have important roles in the biogenesis and quality control of mRNAs.

Long-range structure in ribonuclease P RNA.

Phylogenetic-comparative and mutational analyses were used to elucidate the structure of the catalytically active RNA component of eubacterial ribonuclease P (RNase P). In addition to the refinement and extension of known structural elements, the analyses revealed a long-range interaction that results in a second pseudoknot in the RNA. This feature strongly constrains the three-dimensional structure of RNase P RNA near the active site. Some RNase P RNAs lack this structure but contain a unique, possibly compensating, structural domain. This suggests that different RNA structures located at different positions in the sequence may have equivalent architectural functions in RNase P RNA.

Seasat low-rate data system.

The Seasat low-rate data system is a distributed, nonreal-time, magnetic-tape system for information processing. Its function is to apply the necessary calibrations, corrections, and conversions to yield geophysically meaningful products from raw spacecraft telemetry data. It also provides a remotely accessible catalog of satellite data.

Phytoplankton blooming off the u.s. East coast: a satellite description.

A "bloom" of near-surface phytoplankton occurs in the Atlantic Slope region of the western Atlantic Ocean off the U.S. East Coast in the spring. Satellite time series of sea-surface temperature and phytoplankton pigment concentration, derived from measurements of the National Oceanic and Atmospheric Administration NOAA-7 Advanced Very-High-Resolution Radiometer and the National Aeronautics and Space Administration Nimbus-7 Coastal Zone Color Scanner, respectively, give information on the spatial extent and temporal development of such a bloom for a 28-day period in April through May 1982. The phytoplankton concentration of the slope area is comparable to that of the Atlantic Shelf. Total primary productivity of the slope during this period is equivalent to that of the shelf. The primary productivity within a warm-core ring and in the Gulf Stream system is less by a factor of 2.

Role of the oestrogen receptors GPR30 and ERalpha in peripheral sensitization: relevance to trigeminal pain disorders in women.

Oestrogen increases facial allodynia through its actions on activation of the MAPK extracellular-signal regulated kinase (ERK) in trigeminal ganglion neurons. This goal of study was to determine which oestrogen receptor is required for behavioural sensitization. Immunohistochemical studies demonstrated the presence of oestrogen receptor alpha (ERalpha) in nuclei of larger neurons and cytoplasm of smaller neurons, and the novel oestrogen receptor G-protein coupled receptor 30 (GPR30) in small diameter neurons that also contained peripherin, a marker of unmyelinated C-fibres. Specific agonists for ERalpha (PPT) and GPR30 (G-1), but not ERbeta (DPN), activated ERK in trigeminal ganglion neurons in vitro. Both G-1 and PPT treatment increased allodynia after CFA injections into the masseter of ovariectomized Sprague-Dawley rats. Treatment with oestrogen increased expression of ERalpha but not GPR30, while masseter inflammation increased GRP30 but not ERalpha. Differential modulation of these ERK-coupled receptors by oestrogen and inflammation may play a role in painful episodes of temporomandibular disorder and migraine.

Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia.

The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), is activated in experimental models of chronic pain, and is also activated by oestrogen. We used an established model of inflammatory trigeminal pain, injection of Complete Freund's Adjuvant (CFA) into the masseter muscle, to determine whether ERK activation may play a role in hormone-related trigeminal pain disorders. We measured withdrawal responses to stimulation of the masseter (V3, primary allodynia) and whisker pad (V2, secondary allodynia) using graded monofilaments. Oestrogen treatment in the presence of inflammation increased withdrawal response to stimulation of both masseter and whisker pad compared with inflammation alone, indicating an additive effect of inflammation and oestrogen on both primary and secondary allodynia. We examined ERK activation in trigeminal ganglia from each treatment group using western blot and immunohistochemistry. Both masseter inflammation and oestrogen treatment increased ERK activation, and combined treatment had an additive effect. Both masseter inflammation and oestrogen increased the percentage of pERK immunoreactive neurons in divisions 1 and 2 (V1/2), and combined treatment increased pERK immunoreactivity in V1/2 compared with inflammation alone. We stereotactically administered ERK antagonist U0126, or inactive control U0124, to the trigeminal ganglion of CFA+E2-treated rats. U0126 decreased withdrawal responses to mechanical stimulation of the whisker pad compared with U0124-treated rats. Because the secondary allodynia in V2 after inflammation in V3 was reduced by antagonizing ERK activation in the periphery, these data suggest a peripheral component to secondary allodynia mediated through ERK activation.

The varieties of ribonuclease P.

Ribonuclease P is a ribozyme involved in tRNA processing that is present in all cells and organelles that synthesize tRNA. Most of our understanding of ribonuclease P derives from studies of the bacterial enzyme. This enzyme has been characterized biochemically and a secondary structure for the RNA subunit has been proposed. Isolation and characterization of ribonuclease P from diverse Archaea and Eukarya are now modifying and adding to our model of this unusual enzyme. The latter instances of RNase P differ from the bacterial version, but similarities are emerging.

Time-course and characterization of orolingual motor deficits in B6SJL-Tg(SOD1-G93A)1Gur/J mice.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease affecting upper and lower motor neurons. Symptom onset may occur in the muscles of the limbs (spinal onset) or those of the head and neck (bulbar onset). Bulbar involvement is particularly important in ALS as it is associated with increased morbidity and mortality. The purpose of this study was to characterize bulbar motor deficits in the B6SJL-Tg(SOD1-G93A)1Gur/J (SOD1-G93A) mouse model of familial ALS. We measured orolingual motor function by placing thirsty mice in a customized operant chamber that allows for measurement of tongue force and lick rhythm as animals lick water from an isometric disc. Testing spanned the pre-symptomatic, symptomatic, and end-stage segments of the disease. Rotarod performance, fore- and hindlimb grip strength, and locomotor activity were also monitored regularly during this period. We found that spinal involvement was apparent first, with both fore- and hindlimb grip strength being affected in SOD1-G93A mice from the onset of testing (64 days of age). Rotarod performance was affected by 71 days of age. Locomotor activity was not affected, even near end-stage. Bulbar involvement appeared much later, with tongue motility being affected by 100 days of age. Tongue force was affected by 115 days of age. To our knowledge, these findings are the first to describe the onset of bulbar versus spinal motor signs and characterize orolingual motor deficits in this preclinical model of ALS.

Impact and outcomes of an Iyengar yoga program in a cancer centre.

BACKGROUND: Individuals have increasingly sought complementary therapies to enhance health and well-being during cancer, although little evidence of their effect is available. OBJECTIVES: We investigated how an Iyengar yoga program affects the self-identified worst symptom in a group of participants. Whether quality of life, spiritual well-being, and mood disturbance change over the Iyengar yoga program and at 6 weeks after the program. How, from a participant's perspective, the Iyengar yoga program complements conventional cancer treatment. PATIENTS AND METHODS: This pre-post instrumental collective case study used a mixed methods design and was conducted at a private Iyengar yoga studio. The sample consisted of 24 volunteers (23 women, 1 man; 88% Caucasian; mean age: 49 years) who were currently on treatment or who had been treated for cancer within the previous 6 months, and who participated in ten 90-minute weekly Iyengar yoga classes. The main outcome measures were most-bothersome symptom (Measure Your Medical Outcome Profile 2 instrument), quality of life and spiritual well-being (Functional Assessment of Chronic Illness Therapy-General subscale and Spiritual subscale), and mood disturbance (Profile of Mood States-Short Form). Participant perspectives were obtained in qualitative interviews. RESULTS: Statistically significant improvements were reported in most-bothersome symptom (t((23)) = 5.242; p < 0.001), quality of life (F((2,46)) = 14.5; p < 0.001), spiritual well-being (F((2,46)) = 14.4; p < 0.001), and mood disturbance (F((2,46)) = 10.8; p < 0.001) during the program. At follow-up, quality of life (t((21)) = -3.7; p = 0.001) and mood disturbance (t((21)) = 2.4; p = 0.025) significantly improved over time. Categorical aggregation of the interview data showed that participants felt the program provided them with various benefits not included on the outcomes questionnaires. CONCLUSIONS: Over the course of the Iyengar Yoga for Cancer program, participants reported an improvement in overall well-being. The program was also found to present participants with a holistic approach to care and to provide tools to effectively manage the demands of living with cancer and its treatment.

Integrative practices of Canadian oncology health professionals.

OBJECTIVE: Cancer patients are increasingly known to use complementary medicine (CAM) during conventional treatment, but data are limited on how Canadian oncology health professionals attempt to assist patients with their use of cam in the context of conventional cancer care. As part of a larger qualitative study assessing the perceptions of Canadian oncology health professionals regarding integrated breast cancer care, we undertook an exploration of current integrative practices of oncology health professionals. DESIGN: Using an interpretive description research design and a purposive sampling, we conducted a series of in-depth qualitative interviews with various oncology health professionals recruited from provincial cancer agencies, hospitals, integrative clinics, and private practice settings in four Canadian cities: Vancouver, Winnipeg, Montreal, and Halifax. A total of 16 oncology health professionals participated, including medical and radiation oncologists, nurses, and pharmacists. RESULTS: Findings highlighted two main strategies used by oncology health professionals to create a more integrative approach for cancer patients: acting as an integrative care guide, and collaborating with other health professionals. CONCLUSIONS: Although few clear standards of practice or guidance material were in place within their organizational settings, health professionals discussed some integrative roles that they had adopted, depending on interest, knowledge, and skills, in supporting patients with cam decisions. Given that cancer patients report that they want to be able to confer with their conventional health professionals, particularly their oncologists, about their cam use, health professionals who elect to adopt integrative practices are likely offering patients much-welcomed support.

Small nuclear RNA genes transcribed by either RNA polymerase II or RNA polymerase III in monocot plants share three promoter elements and use a strategy to regulate gene expression different from that used by their dicot plant counterparts.

RNA polymerase (Pol) II- and RNA Pol III-transcribed small nuclear RNA (snRNA) genes of dicotyledonous plants contain two essential upstream promoter elements, the USE and TATA. The USE is a highly conserved plant snRNA gene-specific element, and its distance from the -30 TATA box, corresponding to approximately three and four helical DNA turns in Pol III and Pol II genes, respectively, is crucial for determining RNA Pol specificity of transcription. Sequences upstream of the USE play no role in snRNA gene transcription in dicot plants. Here we show that for expression of snRNA genes in maize, a monocotyledonous plant, the USE and TATA elements are essential, but not sufficient, for transcription. Efficient expression of both Pol II- and Pol III-specific snRNA genes in transfected maize protoplasts requires an additional element(s) positioned upstream of the USE. This element, named MSP (for monocot-specific promoter; consensus, RGCCCR), is present in one to three copies in monocot snRNA genes and is interchangeable between Pol II- and Pol III-specific genes. The efficiency of snRNA gene expression in maize protoplast is determined primarily by the strength of the MSP element(s); this contrasts with the situation in protoplasts of a dicot plant, Nicotiana plumbaginifolia, where promoter strength is a function of the quality of the USE element. Interestingly, the organization of monocot Pol III-specific snRNA gene promoters closely resembles those of equivalent vertebrate promoters. The data are discussed in the context of the coevolution of Pol II- and Pol III-specific snRNA gene promoters within many eukaryotic organisms.