Pharmacokinetics and Bioequivalence of Isavuconazole Administered as Isavuconazonium Sulfate Intravenous Solution via Nasogastric Tube or Orally in Healthy Subjects.

For critically ill patients with invasive fungal infections, a nasogastric (NG) tube can be an alternative route for administration of isavuconazonium sulfate (ISAVUSULF). This was a randomized, open-label, 2-period, 2-sequence single-dose crossover study comparing single doses of 372 mg ISAVUSULF intravenous (i.v.) solution via NG tube (test formulation) to 372-mg ISAVUSULF capsules for oral administration (reference formulation) in healthy male and female subjects. A single dose of ISAVUSULF was administered under fasting conditions on day 1 of each period, with a washout of 30 days between periods. Pharmacokinetic (PK) samples were collected predose through day 21. Standard safety and tolerability assessments were conducted in each period. The analysis of variance estimate of the study population demonstrates that the isavuconazole i.v. NG tube administration geometric least-squares (LS) mean values of the observed maximum concentration (Cmax), area under the plasma concentration-time curve (AUC) to the last measurable concentration (AUClast), AUC to time infinity (AUCinf), and AUC from start of dosing to 72 h (AUC72) were 105.3%, 97.6%, 99.3%, and 97.8%, respectively, of the corresponding oral-administration values. The geometric LS mean ratio and 90% confidence intervals for the PK parameters were completely contained within the prespecified limits of 80% to 125%. There were no deaths or serious adverse events that led to the withdrawal of treatment during the study. The study met its primary endpoint of bioequivalence between the two routes of administration. Both routes of administration were well tolerated.

Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study.

AIMS: To evaluate the efficacy and safety of mirabegron in children and adolescents (aged 3 to <18 years) with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization. METHODS: In this open-label, multicenter, baseline-controlled, Phase III study (NCT02751931), participants received once-daily mirabegron at an adult dose equivalent of 25 mg. Dose was increased to 50 mg equivalent unless there were safety/tolerability concerns. The primary efficacy endpoint was change from baseline to Week 24 in maximum cystometric capacity (MCC). Secondary urodynamic assessments, Pediatric Incontinence Questionnaire (PIN-Q), Patient Global Impression of Severity (PGI-S), Clinician Global Impression of Change (CGI-C), and Acceptability questionnaires were included. RESULTS: Overall, 86 participants (55 aged 3 to <12 years, 31 aged 12 to <18 years) received treatment; 68 were included in efficacy assessments. A statistically significant increase in MCC from baseline to Week 24 was observed (87.20 ml, 95% confidence interval: 66.07, 108.33; p < .001); this increase was apparent from Week 4. Significant increases in bladder compliance, bladder volume until first detrusor contraction, average volume per catheterization, maximum daytime catheterized volume and number of dry days per week. Significant decreases in detrusor pressure and number of leakage episodes per day were also observed. Significant improvement in PGI-S but not PIN-Q was observed. Most participants reported their condition had either much or very much improved using the CGI-C. Mirabegron was well tolerated in this population with a profile aligned with that in adults. CONCLUSIONS: Mirabegron was effective and well-tolerated in the treatment of pediatric patients with NDO.

An enzyme immunoassay for determining albumin in human urine samples using an ultra-microanalytical system.

Microalbuminuria is a term to describe a moderate increase in the level of albumin in urine. It is an important prognostic marker for kidney damage in diseases such as diabetes mellitus and hypertension. A simple sandwich-type ultramicroELISA assay (UMELISA) has been developed for the measurement of albumin in human urine samples. Strips coated with a high affinity monoclonal antibody directed against albumin are used as solid phase, to ensure the specificity of the assay. The albumin assay was completed in 1 hr and 30 min, with a measuring range of 1.44-200 ng/mL. The intra- and inter-assay coefficients of variation were 3.98-4.35% and 7.59-8.92%, respectively, depending on the albumin concentrations evaluated. Percentage recovery ranged from 94.26 to 98.50%. Regression analysis showed a good correlation with the commercial quantitative turbidimetric test Microalbumin-turbilatex (n = 240, r = 0.994, p < .01). The analytical performance characteristics of our UMELISA MICROALBUMINA endorse its use for the quantification of albumin in human urine samples. This test will make a cost-effective diagnostic kit accessible to low-income countries such as Latin American countries and is now available in the Cuban Public Health System.

What's Religion Got to Do with It? Exploring College Students' Sexual and Reproductive Health Knowledge and Awareness of Sexual and Reproductive Health Services in Relation to Their Gender and Religiosity.

The purpose of this study was to examine the relationship between religiosity and sexual and reproductive health (SRH) knowledge and awareness of campus SRH services among college students on a racially and ethnically diverse college campus. The sample included 996 undergraduate students at a large public university in California. For women, there was a consistent pattern across religious affiliations of more frequent attenders reporting lower SRH knowledge than less frequent attenders. These findings suggest that higher rates of religious attendance among Catholic, Protestant, and Evangelical women pose a risk for lower SRH knowledge. The results suggest the need for SRH outreach and educational materials targeting men in general, who had lower levels of SRH knowledge and awareness of SRH services overall, and taking religiosity into account, particularly with regard to women.

Imaging Intra-abdominal Burkitt's Lymphoma: From Discrete Bowel Wall Thickening to Diffuse Soft Tissue Infiltration.

Burkitt's lymphoma is a highly aggressive non-Hodgkin's B-cell lymphoma, which often presents with intra-abdominal involvement. The purpose of this pictorial review is to illustrate the various intra-abdominal imaging findings of Burkitt's lymphoma. Extranodal disease at presentation is common, including involvement of the bowel, stomach, pancreas, spleen, and mesentery.

Prevalence of Extracranial Venous Narrowing on Magnetic Resonance Venography Is Similar in People With Multiple Sclerosis, Their Siblings, and Unrelated Healthy Controls: A Blinded, Case-Control Study.

PURPOSE: The study sought to assess and compare the prevalence of narrowing of the major extracranial veins in subjects with multiple sclerosis and controls, and to assess the sensitivity and specificity of magnetic resonance venography (MRV) for describing extracranial venous narrowing as it applies to the chronic cerebrospinal venous insufficiency theory, using catheter venography (CV) as the gold standard. METHODS: The jugular and azygos veins were assessed with time-of-flight MRV in this assessor-blinded, case-control study of subjects with multiple sclerosis, their unaffected siblings, and unrelated controls. The veins were evaluated by diameter and area, and compared with CV. Collateral vessels were also analyzed for maximal diameter, as a potential indicator of compensatory flow. RESULTS: A high prevalence of extracranial venous narrowing was demonstrated in all study groups, collectively up to 84% by diameter criteria and 90% by area, with no significant difference between the groups when assessed independently (P = .34 and .63, respectively). There was high interobserver variability in the reporting of vessel narrowing (kappa = 0.32), and poor vessel per vessel correlation between narrowing on MRV and CV (kappa = 0.064). Collateral neck veins demonstrated no convincing difference in maximum size or correlation with jugular narrowing. CONCLUSION: There is a high prevalence of narrowing of the major extracranial veins on MRV in all 3 study groups, with no significant difference between them. These findings do not support the chronic cerebrospinal venous insufficiency theory. Although MRV has shown a high sensitivity for identifying venous narrowing, time-of-flight imaging demonstrates poor interobserver agreement and poor specificity when compared with the gold standard CV.

Comparing Two Review Processes for Determination of Preventability of Maternal Mortality in Illinois.

OBJECTIVES: To compare the results of two maternal death review processes conducted from 2002 to 2012 by Illinois regionalized perinatal centers with those conducted by the Illinois Department of Public Health's (IDPH's) statewide multidisciplinary external Maternal Mortality Review Committee (MMRC). METHODS: This is a retrospective record review linking MMRC case assessment forms to the IDPH's Maternal Mortality Review Form database to compare causes of death and potential preventability as determined by both review processes. RESULTS: MMRC records for 76 maternal death reviews were linked to the IDPH maternal mortality review form database. Most deaths reviewed by the statewide MMRC were due to pregnancy-related causes. The statewide MMRC differed from the regional perinatal centers on cause of death in 55.3% (n = 42) of cases and on the disposition of potential preventability in 48.7% (n = 37) of cases. The statewide MMRC judged 69.7% (n = 53) of cases potentially preventable, compared with 40.8% (n = 31) for the regional perinatal centers. The MMRC identified more preventable provider and systems factors for potentially preventable deaths compared with regional perinatal centers which identified more preventable patient factors. CONCLUSIONS FOR PRACTICE: The statewide MMRC found more potential preventability and determined that preventability was associated with provider and systems factors, not patient factors. Observed discrepancies between regional perinatal center and statewide MMRC reviews were likely due to the complexity of cases selected for review, the multidisciplinary external composition of the review team, and the de-identification of cases. Multidisciplinary statewide expert panels should be implemented in addition to local and regionalized reviews.

Assessing preventability of maternal mortality in Illinois: 2002-2012.

OBJECTIVE: We sought to describe the potential preventability of pregnancy-related deaths in Illinois from 2002 through 2012 as determined by perinatal centers following the Illinois maternal death review process. STUDY DESIGN: We conducted a retrospective review of all known maternal deaths in the state from 2002 through 2012 with complete records in the Illinois Department of Public Health's Maternal Mortality Review Form database. The association between causes of death and potential preventability was analyzed for pregnancy-related deaths. RESULTS: There were 610 maternal deaths in Illinois during the study period (31.8 per 100,000 live births). One-third of maternal deaths (n = 210) were directly or indirectly related to pregnancy, 7.0% (n = 43) were possibly related, and 52.6% (n = 321) were unrelated. Vascular causes were the most common cause of pregnancy-related death, followed by cardiac causes and hemorrhage. One-third of deaths directly or indirectly related to pregnancy were deemed potentially preventable. Hemorrhage and deaths due to psychiatric causes were most likely to be considered avoidable, while cancer and vascular-related deaths were generally not considered preventable. CONCLUSION: This analysis of pregnancy-related deaths in Illinois, the first in >60 years, found similar causes of death and potential preventability as pregnancy-related death reviews in other states. Analyzing the causes of pregnancy-related death is a critical and necessary step in improving maternal health outcomes, particularly in decreasing potentially preventable pregnancy-related deaths. Greater attention should be directed toward intervening on the provider, systems, and patient factors contributing to preventable deaths.

Cocaine-induced psychotic disorders: presentation, mechanism, and management.

Cocaine, the third mostly commonly used illicit drug in the United States, has a wide range of neuropsychiatric effects, including transient psychotic symptoms. When psychotic symptoms occur within a month of cocaine intoxication or withdrawal, the diagnosis is cocaine-induced psychotic disorder (CIPD). Current evidence suggests those with CIPD are likely to be male, have longer severity and duration of cocaine use, use intravenous cocaine, and have a lower body mass index. Differentiating CIPD from a primary psychotic disorder requires a detailed history of psychotic symptoms in relation to substance use and often a longitudinal assessment. Treatment includes providing a safe environment, managing agitation and psychosis, and addressing the underlying substance use disorder. This review begins with a clinical case and summarizes the literature on CIPD, including clinical presentation, differential diagnosis, mechanism and predictors of illness, and treatment.

Naphthenic acids quantification in organic solvents using fluorescence spectroscopy.

Quantification of naphthenic acids in water has been traditionally performed after extraction with organic solvents followed by analytic methods that are complex and costly for preliminary research or for continuous monitoring purposes. This study examines the application of fluorescence in organic solvents as an effective alternative, and the role of organic solvents on quantification results. Nine organic solvents were used: three polar protic alcohols (methanol, ethanol, and propanol), three polar aprotic (dichloromethane, acetone, and acetonitrile) and three non-polar (hexane, toluene, and diethyl ether). The calibration curves of the polar protic solvents performed the best; they had lower light scattering and higher method sensitivity than polar aprotic and non-polar. Methanol was selected for further experiments having a strong linearity for concentrations lower than 250 mg/L (R(2) > 0.99), and a low relative standard deviation (< 10%). The method sensitivity was improved by 70% using a methanol-deionized water mixture (50:50) as a solvent. The synchronous fluorescence mode with a reduced offset value of Δλ = 10 nm demonstrated potential for fingerprinting. The fluorescence technique for quantifying total naphthenic acids directly in organic solvents is a cost-effective analytical method compatible with the solid phase extraction of the sample.

Intravenous Cetirizine Premedication to Mitigate Infusion-Related Reactions.

Infusion-related reactions (IRRs) are a recognized concern for chemotherapy, biologic agents, and newer immunotherapies. Antihistamines are frequently recommended to prevent or manage these reactions. For over 60 years, diphenhydramine has been the only H1 antihistamine for intravenous (IV) administration. It has been considered the standard of care as part of premedication regimens to prevent IRRs associated with these therapies despite the lack of a US Food and Drug Administration (FDA)-approved indication and no evidence of efficacy data. Intravenous cetirizine was approved in 2019 for acute urticaria treatment, making it the only second-generation H1 antihistamine that can be administered intravenously. Compared with diphenhydramine, cetirizine has an improved safety profile with less sedation, fewer contraindications, lower incidence of anticholinergic side effects, and minimal risk of adverse events in elderly patients. A head-to-head study demonstrated that IV cetirizine is as effective as IV diphenhydramine in reducing IRRs and may decrease chair time, treatment center visits, and the need for rescue medication. Over the past 3 decades, the FDA has addressed the issue of IRRs by mandating language regarding the requirement or recommendation for premedication in the label of over 50 FDA-approved infusion products. As more therapeutics have premedication required or recommended, IV cetirizine should be considered an antihistamine for preventing and treating IRRs. In this article, we describe a patient whose IRR was successfully managed with IV cetirizine and discuss first- vs. second-generation H1 antihistamines and their use in treating and preventing IRRs.

Selective ß3-adrenoceptor agonists for the treatment of overactive bladder.

PURPOSE: The bladder effects of isoprenaline, and selective ß1 and ß2-adrenoceptor agonists reported in early studies suggest that bladder ß-adrenoceptors are atypical. Since there is a lack of alternatives to antimuscarinics in the treatment of overactive bladder symptoms, there has been an intensive search for new drug targets. Discovery of the ß3-adrenoceptor with high expression in the bladder suggested that this receptor, which mediates detrusor relaxation, could be a target for overactive bladder symptoms. MATERIALS AND METHODS: An overview of the published literature on ß-adrenoceptor and the bladder was performed using MEDLINE. The United States Food and Drug Administration website, clinicaltrials.gov and controlled-trials.com online trial registries were searched for English language articles containing the terms ß3-adrenoceptors and ß3-adrenoceptor agonists. In addition, abstracts from recent international scientific meetings were searched for randomized, controlled trials of ß3-adrenoceptor agonists. RESULTS: Stimulation of ß3-adrenoceptors relaxes detrusor smooth muscle, decreases afferent signaling from the bladder, improves bladder compliance upon filling and increases bladder capacity. Randomized, controlled trials show that the selective ß3-adrenoceptor agonist mirabegron, for which most information is available and which is approved in Japan, the United States and Europe, decreases the number of micturitions and incontinence episodes in a 24-hour period compared with placebo. The most common adverse effects recorded are dry mouth (placebo level) and gastrointestinal disturbances, rated as mild to moderate. Small increases in mean heart rate (1 beat per minute) and blood pressure (1 mm Hg) were noted in patients with overactive bladder. CONCLUSIONS: Available information suggests that ß3-adrenoceptor agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder. However, further clinical experience outside clinical trials and information on long-term use in terms of efficacy, safety and tolerability are warranted to optimally characterize the position of ß3-adrenoceptor agonists in the treatment algorithm for overactive bladder.

Urodynamics and safety of the ß3-adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction often presents as storage and voiding symptoms. We investigated urodynamic parameters in men with lower urinary tract symptoms and bladder outlet obstruction treated with the ß3 agonist mirabegron, a new therapy for overactive bladder symptoms. MATERIALS AND METHODS: A total of 200 men 45 years old or older with lower urinary tract symptoms and bladder outlet obstruction were randomized to receive once daily mirabegron 50 mg (70) or 100 mg (65), or placebo (65) for 12 weeks. The primary urodynamic parameters assessed were change from baseline to end of treatment in maximum urinary flow and detrusor pressure at maximum urinary flow (noninferiority margins -3 ml per second and 15 cm H2O, respectively). We evaluated adverse events and vital signs. RESULTS: Treatment with mirabegron 50 and 100 mg was noninferior to placebo based on the lower and upper limits of the 95% CI, respectively, for maximum urinary flow and detrusor pressure at maximum urinary flow. The adjusted mean difference vs placebo was 0.40 (95% CI -0.63, 1.42) and 0.62 ml per second (95% CI -0.43, 1.68) for maximum urinary flow, and -5.94 (95% CI -13.98, 2.09) and -1.39 cm H2O (95% CI -9.73, 6.96), respectively, for detrusor pressure at maximum urinary flow. The incidence of adverse events was similar for mirabegron and placebo. CONCLUSIONS: Mirabegron did not adversely affect voiding urodynamics (maximum urinary flow and detrusor pressure at maximum urinary flow) compared with placebo after 12 weeks of treatment.

Results of a randomized phase III trial of mirabegron in patients with overactive bladder.

PURPOSE: Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a ß3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder. MATERIALS AND METHODS: A randomized, double-blind, placebo controlled trial was conducted in the United States and Canada. After a 2-week placebo run-in period, adults with overactive bladder symptoms for 3 or more months were randomized 1:1:1 to receive placebo, 50 or 100 mg mirabegron once daily for 12 weeks. Efficacy data were collected via patient completed diaries and quality of life assessments. Co-primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours. Key secondary micturition and incontinence end points were also evaluated. Safety assessments included treatment emergent adverse events, laboratory assessments, vital signs, electrocardiograms and post-void residual volume. RESULTS: Compared to placebo, 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases (95% CI) from baseline for incontinence episodes (-1.13 [-1.35, -0.91], -1.47 [-1.69, -1.25] and -1.63 [-1.86, -1.40]) and micturitions (-1.05 [-1.31, -0.79], -1.66 [-1.92, -1.40] and -1.75 [-2.01, -1.48]) per 24 hours (p <0.05). Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo. The incidence of frequently reported treatment emergent adverse events (hypertension, urinary tract infection, headache, nasopharyngitis) was similar in the mirabegron and placebo groups. Dry mouth was reported for 1.5%, 0.5% and 2.1% of patients in the placebo, 50 and 100 mg mirabegron groups, respectively. CONCLUSIONS: Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial.

BACKGROUND: Antimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a ß3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points - mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability. METHODS: Patients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate. RESULTS: Mirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo. CONCLUSION: In this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.

Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.

CONTEXT: Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. OBJECTIVE: We aimed to assess efficacy/safety of fezolinetant for treatment of moderate to severe VMS associated with menopause. METHODS: In this double-blind, placebo-controlled, 12-week phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to week 4 (W4) and W12 in VMS frequency and severity. Safety was also assessed. RESULTS: Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P < .05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P < .05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. CONCLUSION: Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause.

Comparison of MERGE and axial T2-weighted fast spin-echo sequences for detection of multiple sclerosis lesions in the cervical spinal cord.

OBJECTIVE: The purpose of our study was to compare axial multiple-echo recombined gradient echo (MERGE) with axial T2-weighted fast spin-echo (FSE) imaging for the detection of multiple sclerosis (MS) lesions in the cervical spinal cord on MRI. MATERIALS AND METHODS: Twenty-nine cervical spine MRI studies of patients with MS lesions and 29 control cases were reviewed retrospectively. Two blinded neuroradiologists independently assessed randomized axial MERGE and axial T2-weighted FSE sequences from each study, documenting the location and number of cord lesions, the degree of confidence in calling each lesion, and the presence of artifacts. The reference standard was determined by an unblinded consensus review of all sequences performed for each case, with lesions considered present if detected on two or more sequences. Lesion detection rates and conspicuity, false-positive findings, and reader confidence and artifact scores were compared for the sequences, and interreader agreement was assessed. RESULTS: Eighty-three lesions were assessed. The mean true-positive lesion detection rate was 87% (95% CI, 79-93%) with MERGE and 67% (60-75%) with T2-weighted FSE, with interreader positive agreement scores of 74% and 75%, respectively. A greater number of false-positive findings were seen with MERGE for both the MS and control cases. Average confidence and artifact scores were similar for both sequences. Subjectively, lesions were more conspicuous in 21 cases with MERGE and four cases with T2-weighted FSE and were equally conspicuous in four cases. CONCLUSION: MERGE and T2-weighted FSE sequences are complementary. MERGE provided greater sensitivity for cord lesions whereas axial T2-weighted FSE provided improved lesion specificity. Further investigation is required to assess the clinical impact of MERGE in the diagnosis and management of MS.

The importance of substate surveillance in detection of geographic oral health inequalities in a small state.

CONTEXT: Considering that 42% of children and adolescents and 91% of dentate adults experience dental caries, oral disease is a public health problem. Although the population's oral health is improving, certain subgroups remain at increased risk for dental disease. OBJECTIVE: To assess the oral health status at the substate level and explore the possibility of geographic oral health inequalities in New Hampshire while building upon existing surveillance data sets. DESIGN: We used the Third Grade Oral Health and NH Behavioral Risk Factor Surveillance System surveys. We ensured the availability of substate level data and compared county/region specific estimates. SETTING: New Hampshire. PARTICIPANT: Adults and third-grade students in public schools. MAIN OUTCOME MEASURES: The prevalence of dental caries, untreated caries, and dental sealants among children; and the insurance status, utilization of dental services, and edentulism among adults. RESULTS: Of the 10 counties, the northernmost Coos County had consistently worse outcomes when compared with other counties. Only 64% of adult Coos County residents reported a dental visit in the past year; of these, 66% reported dental cleaning. Among adults 65 years and older, 29% were edentulous. In comparison with the state overall, these estimates were 76%, 77%, and 19%, respectively. Coos County third-grade students had the highest prevalence of dental caries experience (64% compared with 44% in New Hampshire) and untreated caries (31% compared with 12%), and only 24% had dental sealants (state prevalence is 60%). CONCLUSIONS: Overall oral health status in our state is favorable and comparable with the nation, yet significant geographic inequalities exist among children and adults. The oral health status of disparate groups can be improved using tailored interventions such as community water fluoridation or expansion of school-based dental sealant programs. Surveillance at the substate level is an essential part of the planning, targeting, and progress monitoring.

Jordan-3: measuring visual reversals in children as symptoms of learning disability and attention-deficit/hyperactivity disorder.

The purpose of this research was to establish new norms for the Jordan-3 for children ages 5 to 18 years. The research also investigated the frequency of visual reversals in children previously identified as having reading disability, attention-deficit/hyperactivity disorder, and broader learning disabilities. Participants were regular education students, ages 5 through 18 years, and special education students previously diagnosed with attention-deficit/hyperactivity disorder, reading disability, or broader learning disability. Jordan-3 Accuracy and Error raw scores were compared to assess if there was a significant difference between the two groups. Mean Accuracy and Error scores were compared for males and females. Children with learning disability and attention-deficit/hyperactivity disorder had higher reversals when compared to regular education children, which lends continued support to the Jordan-3 as a valid and reliable measure of visual reversals in children and adolescents. This study illustrates the utility of the Jordan-3 when assessing children who may require remediation to reach their academic potential.

Mechanism and a peptide motif for targeting peripheral proteins to the yeast inner nuclear membrane.

Trm1 is a tRNA specific m(2)(2)G methyltransferase shared by nuclei and mitochondria in Saccharomyces cerevisiae. In nuclei, Trm1 is peripherally associated with the inner nuclear membrane (INM). We investigated the mechanism delivering/tethering Trm1 to the INM. Analyses of mutations of the Ran pathway and nuclear pore components showed that Trm1 accesses the nucleoplasm via the classical nuclear import pathway. We identified a Trm1 cis-acting sequence sufficient to target passenger proteins to the INM. Detailed mutagenesis of this region uncovered specific amino acids necessary for authentic Trm1 to locate at the INM. The INM information is contained within a sequence of less than 20 amino acids, defining the first motif for addressing a peripheral protein to this important subnuclear location. The combined studies provide a multi-step process to direct Trm1 to the INM: (i) translation in the cytoplasm; (ii) Ran-dependent import into the nucleoplasm; and (iii) redistribution from the nucleoplasm to the INM via the INM motif. Furthermore, we demonstrate that the Trm1 mitochondrial targeting and nuclear localization signals are in competition with each other, as Trm1 becomes mitochondrial if prevented from entering the nucleus.