ABSTRACT
OBJECTIVE: Although cognitive dysfunction persists through affective and euthymic states in bipolar disorder (BD), its neurobiological correlates remain undetermined. We explore whole-cortex intracortical myelin (ICM) and cognition in BD-I and controls. METHODS: T1 -weighted images (3T) optimized for ICM measurement were analyzed using a surface-based approach. MRI signal was sampled at cortical mid-depth. Cognitive performance was measured via standardized computerized battery and paper-and-pencil Trails B. RESULTS: ICM was associated with verbal memory (VM) in BD throughout a cortical network identified with pertinence to VM function, with strongest effects in left caudal middle temporal cortex and left dorsolateral prefrontal cortex (Pcorrected < 0.05). Subanalyses revealed specific association with correct word recognition, without delay. Processing speed, executive function, and reaction time were also predicted by ICM in BD, but not controls, although this did not survive Bonferroni correction. CONCLUSION: This is the first study to show VM association with ICM in BD. ICM has been implicated in the integrity of neural connections and neural synchrony. VM dysfunction is one of the most replicated cognitive abnormalities in BD. Therefore, these results provide a novel mechanism for understanding cognitive dysfunction in BD, which can aid in the development of targeted therapeutics to improve cognitive outcomes in BD.
Subject(s)
Bipolar Disorder/physiopathology , Cerebral Cortex/metabolism , Cognitive Dysfunction/physiopathology , Myelin Sheath/metabolism , Adolescent , Adult , Bipolar Disorder/complications , Cognitive Dysfunction/etiology , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
A model-based feedback system is presented enabling the simultaneous control of the stored energy through ßn and the toroidal rotation profile of the plasma in National Spherical Torus eXperiment Upgrade device. Actuation is obtained using the momentum from six injected neutral beams and the neoclassical toroidal viscosity generated by applying three-dimensional magnetic fields. Based on a model of the momentum diffusion and torque balance, a feedback controller is designed and tested in closed-loop simulations using TRANSP, a time dependent transport analysis code, in predictive mode. Promising results for the ongoing experimental implementation of controllers are obtained.
ABSTRACT
OBJECTIVES: The aim of the study was to evaluate for the presence of drug resistance to HIV medications in treatment-naive individuals in Botswana. METHODS: Two different populations were evaluated for evidence of HIV drug resistance at three different geographical locations in Botswana. In the first study population, consisting of pregnant females diagnosed with HIV during pregnancy, participants were enrolled at the time of their HIV diagnosis. The second population included pre-ART enrollees at Infectious Diseases Care Clinics (IDCCs) who had a CD4 T cell count >350 cells/µL. RESULTS: A total of 422 genotypes were determined: 234 for samples from antenatal clinic (ANC) participants and 188 for samples from IDCC participants. Between 2012 and 2014, 6 of 172 (3.5%) genotypes from ANC participants exhibited transmitted drug resistance (TDR), with 3 (1.7%) showing resistance to first-line ART. In a subset of samples from Gaborone, Botswana's capital and largest city, the TDR rate was 3 in 105 (2.9%), but only 1 in 105 (1.0%) showed first-line ART resistance. Between December 2014 and April 2015, the rate of resistance to any ART in Gaborone was 6 in 62 (9.7%), with 5 (8.1%) exhibiting first-line ART resistance. CONCLUSIONS: These data demonstrate that TDR rates for HIV differ geographically and temporally in Botswana, with significant increases in TDR observed at ANCs in Gaborone between 2012 and 2015. These findings stress the importance of continued testing for TDR, particularly as access to HIV treatment increases and guidelines recommend treatment at the time of HIV diagnosis.
Subject(s)
Drug Resistance, Viral , HIV Infections/transmission , HIV Infections/virology , HIV/drug effects , Adolescent , Adult , Aged , Botswana/epidemiology , Epidemiological Monitoring , Female , HIV/isolation & purification , HIV Infections/epidemiology , Humans , Male , Middle Aged , Pregnancy , Prevalence , Young AdultSubject(s)
Anesthesia, Epidural , Anesthesia, Obstetrical , Anesthetics, Local/adverse effects , Horner Syndrome/complications , Hypoglossal Nerve Diseases/complications , Trigeminal Nerve Diseases/complications , Adult , Anesthetics, Local/pharmacokinetics , Female , Horner Syndrome/therapy , Humans , Hypoglossal Nerve Diseases/therapy , Paralysis , Pregnancy , Trigeminal Nerve Diseases/therapySubject(s)
Posterior Leukoencephalopathy Syndrome/diagnosis , Puerperal Disorders/diagnosis , Adult , Anticonvulsants/therapeutic use , Cesarean Section , Female , Humans , Magnetic Resonance Imaging , Patient Readmission , Posterior Leukoencephalopathy Syndrome/drug therapy , Pregnancy , Puerperal Disorders/drug therapy , Treatment Outcome , Valproic Acid/therapeutic useABSTRACT
Cytochrome P450 102 (CYP102 or Cytochrome P450(BM)(-)(3)) is induced in Bacillus megaterium by barbiturates, perioxisome proliferators, estrogen, and nonsteroidal antiinflammatory drugs. We have previously demonstrated that a CYP102 construct (BMC 143) coupled with a luciferase reporter gene can be used to identify the inducers of CYP102. We now describe the effect of added phytochemicals on the induction of CYP102 by phenobarbital (PB) in B. megaterium. The isoflavones genistein, biochanin A, coumestrol, and equol, the green tea flavanoid epicatechin, and the fungal toxin zearalenone inhibit the induction of CYP102 by PB in a dose-dependent manner. However, the isoflavone daidzein, the phytoalexin glyceollin, and catechin, an epimer of epicatechin, failed to exhibit a similar inhibitory effect on PB-mediated CYP102 induction.
Subject(s)
Bacillus megaterium/enzymology , Bacterial Proteins , Cytochrome P-450 Enzyme System/biosynthesis , Glycine max/chemistry , Mixed Function Oxygenases/biosynthesis , Phenobarbital/pharmacology , Tea/chemistry , Catechin/pharmacology , Chromans/pharmacology , Coumestrol/pharmacology , Equol , Genistein/pharmacology , Isoflavones/pharmacology , NADPH-Ferrihemoprotein Reductase , Zearalenone/pharmacologyABSTRACT
CYP102 (Cytochrome P450BM-3) is induced in Bacillus megaterium by barbiturates, peroxisome proliferators, and nonsteroidal anti-inflammatory drugs. We now describe the induction of CYP102 in B. megaterium by 17 beta-estradiol and by 4-sec-butylphenol. These estrogens interact with the repressor protein Bm3R1, causing it to dissociate with the operator of the CYP102 gene and allowing transcription to occur. We have developed a stable transfection of a construct into B. megaterium of a truncated CYP102 gene coupled with the luciferase gene in a promoterless plasmid and have used this construct to test the induction of CYP102 by these estrogens. Estradiol demonstrated a dose-dependent induction of CYP102 which saturated at a 2-fold increase at 150 microM 4 hr post-addition. 4-sec-Butylphenol produced a dose-dependent and time-dependent induction up to 300 microM and 6 hr post-induction.
Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Estradiol/pharmacology , Estrogens/pharmacology , Mixed Function Oxygenases/biosynthesis , Phenols/pharmacology , Transcription Factors , Bacillus megaterium/drug effects , Bacterial Proteins/metabolism , Cytochrome P-450 Enzyme System/genetics , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Enzyme Induction , Genes, Reporter , Mixed Function Oxygenases/genetics , NADPH-Ferrihemoprotein Reductase , Protein Binding , Recombinant Proteins/biosynthesis , Repressor Proteins/metabolismABSTRACT
An evaluation was conducted of the approaches, costs, and quality-of-life outcomes associated with communication aid assessment programs for the speech-impaired provided by specialist Communication Aids Centres (CACs) in the United Kingdom. The average costs of CAC assessment programs was 410 pounds per client, which is not excessive. There was evidence of moderate quality-of-life benefits from clients' use of the recommended aids.
Subject(s)
Communication Aids for Disabled/economics , Quality of Life , Rehabilitation Centers/economics , Speech Disorders/rehabilitation , Adolescent , Adult , Child , Child, Preschool , Communication Aids for Disabled/statistics & numerical data , Costs and Cost Analysis , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Outcome and Process Assessment, Health Care/economics , Outcome and Process Assessment, Health Care/statistics & numerical data , Rehabilitation Centers/statistics & numerical data , Speech Disorders/economics , United KingdomABSTRACT
A survey of the functioning of the six communication aid centres (CACs) in England and Wales was undertaken. All CACs are specialist units drawing clients from a wide area of the country which means that referrals are more likely to come from outside, rather than from within the districts in which the CACs are located. All CACs have developed individual assessment procedures, with some CACs undertaking continuous assessment of clients, and others recommending an aid after a single session. Funding of aids was often a problem because CACs were only able to recommend aid provision and did not supply them; their stocks of aids were used in assessment sessions or for interim loan to clients until a definitive aid had been acquired. CAC staff engaged in a variety of other functions including the organisation of courses, acting as an advice and information service, and undertaking research.
Subject(s)
Communication Disorders/rehabilitation , Delivery of Health Care/standards , Rehabilitation Centers/organization & administration , Communication Aids for Disabled , England , Humans , WalesABSTRACT
This paper reports the findings of an evaluation (funded by the Department of Health) of six Communication Aid Centres established in 1983. The evaluation was undertaken to assess the effectiveness of these Centres in meeting their set objectives, and to examine service costs and client satisfaction. The findings show that the work of each Centre was effective in meeting its stated objectives, but that the work of individual Centres reflected its own specialised interests. Two problems with current funding arrangements were highlighted. First, the need to replace the original funding by locally based finance, and second, the funding of communication aids for clients. The findings also show that the specialist service provided by these Centres can be managed at costs per person assessed at, or below, non-specialist services in health districts. Client satisfaction with the services provided by the Centres was high.
Subject(s)
Communication Aids for Disabled/supply & distribution , Consumer Behavior/statistics & numerical data , Information Centers/standards , Costs and Cost Analysis , England , Financing, Government , Humans , Information Centers/organization & administration , Information Centers/statistics & numerical data , Personnel Staffing and Scheduling , WalesABSTRACT
The present study compares the effectiveness of 0.25% ropivacaine and 0.25% bupivacaine in 44 patients receiving a subclavian perivascular brachial plexus block for upper extremity surgery. The patients were assigned to two equal groups in this randomized, double-blind study; one group received ropivacaine 0.25% (112.5 mg) and the other, bupivacaine 0.25% (112.5 mg), both without epinephrine. Onset times for analgesia and anesthesia in each of the C-5 through T-1 brachial plexus dermatomes did not differ significantly between the two groups. The mean onset time for analgesia ranged from 11.2 to 20.2 min, and the mean onset time for anesthesia ranged from 23.3 to 48.2 min. The onset of motor block differed only with respect to paresis in the hand, with bupivacaine demonstrating a shorter onset time than ropivacaine. The duration of sensory and motor block also was not significantly different between the two groups. The mean duration of analgesia ranged from 9.2 to 13.0 h, and the mean duration of anesthesia ranged from 5.0 to 10.2 h. Both groups required supplementation with peripheral nerve blocks or general anesthesia in a large number of cases, with 9 of the 22 patients in the bupivacaine group and 8 of the 22 patients in the ropivacaine group requiring supplementation to allow surgery to begin. In view of the frequent need for supplementation noted with both 0.25% ropivacaine and 0.25% bupivacaine, we do not recommend using the 0.25% concentrations of these local anesthetics to provide brachial plexus block.
Subject(s)
Amides , Anesthetics, Local , Arm/surgery , Brachial Plexus , Bupivacaine , Nerve Block , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , RopivacaineABSTRACT
Little attention has been given to the preparation of the patient's family prior to surgery, even though nurses' clinical experience suggests that family members are often more anxious than the patient. This study explored the knowledge and anxiety of spouses and significant others of patients preparing for cardiac surgery. The subjects were selected by convenience from a preoperative class offered at the hospital where surgery was to occur. Before and after the class, the subjects completed a cardiac-surgery knowledge test and an anxiety test. The significant others were significantly more anxious than the patients prior to the class. The anxiety level of significant others was significantly reduced after the class. There were no statistically significant differences between patients and significant others on the cardiac-surgery knowledge test. These results suggest that significant others may benefit from preoperative instruction.
Subject(s)
Coronary Artery Bypass , Family/psychology , Health Education/standards , Preoperative Care , Stress, Psychological/nursing , Adaptation, Psychological , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Program Evaluation , Stress, Psychological/diagnosis , Stress, Psychological/psychology , Surveys and QuestionnairesABSTRACT
With the increasing cost of health care and the growing constraints made by third party payers, in-hospital time for preoperative teaching is quickly being reduced. Seventy-two patients attended preoperative instruction either as an inpatient the day before surgery or as an outpatient 4-8 days before surgery. Anxiety and knowledge levels were measured before and after class and the evening before surgery. No differences were found between the groups on a measure of anxiety levels. Both groups demonstrated a moderate anxiety level with no significant change over the testing period. Using the knowledge pretest as a covariate, repeated measures analysis of variance suggested the knowledge gained with the class was significantly greater for the outpatient group than the inpatient group (P = 0.018). There was also a significant positive relationship between the knowledge score and knowing someone who had cardiac surgery (t = 2.34, d.f. = 66, P = 0.022). The results suggest that it makes little difference whether patients receive information up to a week before surgery or just the day before; therefore, the more economical preadmission teaching may be the path of choice.