The Impact of Cognitive Impairment in Adults with Multiple Sclerosis and Their Family Caregivers

Background: Cognitive impairment is a prominent feature of multiple sclerosis. However, the impact that cognitive symptoms have on daily life, and the effect this has on persons with multiple sclerosis and their relationship with spouses/partners, remains unclear. This qualitative study sought information on the nature of cognitive impairments experienced, and the impact of cognitive impairments on the daily lives of both adults with multiple sclerosis and their partners, to gain further insights into how healthcare professionals can best support families. / Methods: Fifteen persons with multiple sclerosis and their spouses/partners participated in separate telephone semi-structured interviews. / Results: Six themes were identified from the data, along with several subthemes. These were: the social impact of cognitive impairments in MS, changes to daily living, relationship quality, communication, ways of coping with MS, and the desire for help in managing MS. / Conclusions: Our results identified types of support that couples needed and wanted; ways that multiple sclerosis affects couples' social lives; that there are difficulties negotiating changes in roles due to cognitive challenges; that there are difficulties coping with the impact of cognitive challenges on daily living; that couples often have difficulty communicating about the impact of cognitive changes on daily living and related issues, which also contributes to relationship strain; and finally, that most participants felt that they did not understand enough about the cognitive symptoms of multiple sclerosis. We outline key areas to address these needs identified

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

A Population-Based Cohort Study Examining the Incidence and Impact of Psychotic Experiences From Childhood to Adulthood, and Prediction of Psychotic Disorder.

OBJECTIVE: The authors investigated the incidence, course, and outcome of psychotic experiences from childhood through early adulthood in the general population and examined prediction of psychotic disorder. METHODS: This was a population-based cohort study using the semistructured Psychosis-Like Symptoms Interview at ages 12, 18, and 24 (N=7,900 with any data). Incidence rates were estimated using flexible parametric modeling, and positive predictive values (PPVs), sensitivity, specificity, and area under the curve were estimated for prediction. RESULTS: The incidence rate of psychotic experiences increased between ages 13 and 24, peaking during late adolescence. Of 3,866 participants interviewed at age 24, 313 (8.1%, 95% CI=7.2, 9.0) had a definite psychotic experience since age 12. A total of 109 individuals (2.8%) met criteria for a psychotic disorder up to age 24, of whom 70% had sought professional help. Prediction of current psychotic disorder at age 24 (N=47, 1.2%), by both self-report and interviewer-rated measures of psychotic experiences at age 18 (PPVs, 2.9% and 10.0%, respectively), was improved by incorporating information on frequency and distress (PPVs, 13.3% and 20.0%, respectively), although sensitivities were low. The PPV of an at-risk mental state at age 18 predicting incident disorder at ages 18-24 was 21.1% (95% CI=6.1, 45.6) (sensitivity, 14.3%, 95% CI=4.0, 32.7). CONCLUSIONS: The study results show a peak in incidence of psychotic experiences during late adolescence as well as an unmet need for care in young people with psychotic disorders. Because of the low sensitivity, targeting individuals in non-help-seeking samples based only on more severe symptom cutoff thresholds will likely have little impact on population levels of first-episode psychosis.The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This study was funded by the Medical Research Council (MRC) Grant MR/M006727/1. The following authors acknowledge support: S.Z by the NIHR Biomedical Research Centre (BRC) at University Hospitals Bristol NHS Foundation Trust and the University of Bristol; A.S.D and G.H by the NIHR BRC at University College London Hospital; P.B.J. by the NIHR CLAHRC East of England, NIHR PGfAR RP-PG-0616-20003 (TYPPEX) and the Wellcome Trust Neuroscience in Psychiatry Network (095844/Z/11/Z); PCF by the Wellcome Trust (206368/Z/17/Z) and the Bernard Wolfe health Neuroscience Fund; M.C. by a European Research Council Consolidator Award (iHEAR 724809). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Car

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

Chemistry courses as the turning point for premedical students

Previous research has documented that negative experiences in chemistry courses are a major factor that discourages many students from continuing in premedical studies. This adverse impact affects women and students from under-represented minority (URM) groups disproportionately. To determine if chemistry courses have a similar effect at a large public university, we surveyed 1,036 students from three entering cohorts at the University of California, Berkeley. We surveyed students at the beginning of their first year at the university and again at the end of their second year. All subjects had indicated an interest in premedical studies at the time they entered the university. We conducted follow-up interviews with a stratified sub-set of 63 survey respondents to explore the factors that affected their level of interest in premedical studies. Using a 10-point scale, we found that the strength of interest in premedical studies declined for all racial/ethnic groups. In the follow-up interviews, students identified chemistry courses as the principal factor contributing to their reported loss of interest. URM students especially often stated that chemistry courses caused them to abandon their hopes of becoming a physician. Consistent with reports over more than 50 years, it appears that undergraduate courses in chemistry have the effect of discouraging otherwise qualified students, as reflected in their admission to one of the most highly selective public universities in the US, from continuing in premedical studies, especially in the case of URM students. Reassessment of this role for chemistry courses may be overdue

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders