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Metabolic syndrome - a significant risk factor for cardiovascular morbidity and mortality - is twice as prevalent among psychiatric patients (21-63%) as general populations (20-24%). Although there is an inherent illness-associated metabolic risk, medications do contribute. Atypicals vary in metabolic risk from high (clozapine, olanzapine), moderate (risperidone, quetiapine) to low (aripiprazole, ziprasidone) (ADA, 2004). Few studies have comprehensively measured cardiovascular risk or directly compared antipsychotics. Limited controlled data show that antipsychotic-induced metabolic abnormalities may be reversible, rationalizing the switch to a lower-risk agent (DeNayer, 2004). Non-HDL-cholesterol encompasses all atherogenic cholesterols and provides a marker of CV risk: an increase of 29ng/dL in diabetics is associated with 50% increased risk (Jiang, 2004). Non-HDL-cholesterol is independently associated with increased risk of non-fatal myocardial infarction and angina.
Aim:
This study will provide cross-European data from 13 countries on MS rates in schizophrenia and will assess antipsychotic metabolic profiles and benefits of antipsychotic switching.
Methods:
In this ongoing, 16-week, open-label, European multicentre study, 258 schizophrenia patients treated for ≥3 months with olanzapine, risperidone or quetiapine and who have MS will be randomized to switch to aripiprazole (Week 1: 5mg/day; Week 2: 10mg/day; flexible 10-30mg/day after Week 2) or continue with previous antipsychotic. the primary objective is to demonstrate superiority of aripiprazole versus atypicals on mean percentage change of fasting non-HDL-cholesterol from baseline to Week 16.
Conclusion:
This study will provide the first direct and comprehensive comparison of metabolic risk with various atypicals in Europe and should impact the future management of schizophrenia.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
Cucumber powdery mildew is a destructive foliar disease caused by Podosphaera xanthii (formerly known as Sphaerotheca fuliginea) that substantially damages the yield and quality of crops. The control of this disease primarily involves the use of chemical pesticides that cause serious environmental problems. Currently, numerous studies have indicated that some plant extracts or products potentially have the ability to act as natural pesticides to control plant diseases. It has been reported that turmeric (Curcuma longa L.) and its extract can be used in agriculture due to their insecticidal and fungicidal properties. However, the most effective fungicidal component of this plant is still unknown. In the current study, the crude extract of C. longa L. was found to have a fungicidal effect against P. xanthii. Afterwards, eight fractions (Fr.1–Fr.8) were gradually separated from the crude extract by column chromatography. Fraction 1 had the highest fungicidal effect against this pathogen among the eight fractions. The active compound, (+)-(S)-ar-turmerone, was separated from Fr 1 by semi-preparative high-performance liquid chromatography and identified based on its 1H nuclear magnetic resonance (NMR) and 13C NMR spectrum data. The EC50 value of (+)-(S)-ar-turmerone was found to be 28.7 µg/ml. The compound also proved to have a curative effect. This is the first study to report that the compound (+)-(S)-ar-turmerone has an effect on controlling this disease. These results provide a basis for developing a new phytochemical fungicide from C. longa L. extract.
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.
Background: Ataluren is the first drug to treat the underlying cause of nmDMD. Methods: Phase 2 and 3 studies of ataluren in nmDMD were reviewed, with efficacy and safety/tolerability findings summarized. Results: Ataluren nmDMD trials include: a Phase 2a proof-of-concept study (N=38); a Phase 2b randomized controlled trial (RCT) (N=174); an ongoing US-based open-label safety extension study (N=108); an ongoing non-US-based open-label safety/efficacy extension study (N=94); and a Phase 3 RCT, ACT DMD (N=228), whose primary endpoint was change in six-minute walk distance (6MWD) over 48 weeks. The proof-of-concept study demonstrated increased dystrophin production in post-treatment muscle biopsies from ataluren-treated patients with nmDMD. The Phase 2b results demonstrated an ataluren treatment effect in 6MWD, timed function tests, and other measures of physical functioning, The Phase 3 ACT DMD results demonstrated an ataluren treatment effect in patients with nmDMD in both primary and secondary endpoints, particularly in those with a baseline 6MWD of 300-400m. Ataluren was consistently well-tolerated in all three trials, as well as in the ongoing extension studies. Trial findings will be presented in detail. Conclusions: The totality of the results demonstrates that ataluren enables nonsense mutation readthrough in the dystrophin mRNA, producing functional dystrophin and slowing disease progression.
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and
placental amino acid transporter gene expression have been associated with
development of the offspring in terms of body composition and bone structure.
Several amino acid transporter genes have vitamin D response elements in their
promoters suggesting the possible linkage of these two mechanisms. We aimed to
establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels
relate to expression of placental amino acid transporters. RNA was extracted
from 102 placental samples collected in the Southampton Women's Survey,
and gene expression was analysed using quantitative real-time PCR. Gene
expression data were normalised to the geometric mean of three housekeeping
genes, and related to maternal factors and childhood body composition. Maternal
serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal
25(OH)D and VDBP levels were positively associated with placental expression of
specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP
concentrations were correlated with the expression of specific placental amino
acid transporters, and thus may be involved in the regulation of amino acid
transfer to the fetus. The positive correlation of VDBP levels and placental
transporter expression suggests that delivery of vitamin D to the placenta may
be important. This exploratory study identifies placental amino acid
transporters which may be altered in response to modifiable maternal factors and
provides a basis for further studies.
When an environmental accident such as an oil spill occurs, several things happen. There can be immediate efforts to contain the damage to natural ecosystems or human structures or livelihoods. Steps can be taken to provide relief to the people or environments most immediately affected. If the accident is sufficiently large, media accounts can fuel responses by the broader public. For damages resulting from human-caused accidents, claims and counter-claims of the magnitude and extent of the accident and its consequences will be made and then amplified, often followed (in the United States, at least) by litigation. All of these consequences require knowledge of what really happened – where did the oil go, what natural resources or services were affected, and how persistent were these effects? As the chapters in this book amply demonstrate, the need for careful, rigorous, and objective science is paramount.
Just because there is a need for careful, rigorous, and objective science, however, does not mean that it is easily attainable. Because of demands for immediate action and the heightened emotions following an environmental accident, attempts to document the ecological effects and subsequent recovery run the risk of being hastily developed and inadequately designed. This can foster never-ending arguments about conclusions. Such accidents occur against a complex and dynamically varying environmental background, so they cannot be treated as traditional experiments to be analyzed with straightforward statistical procedures that are planned in advance. There is only a single replicate of the “treatment” (i.e., the accident), there are no pre-established controls, and a welter of other factors with varying degrees of intercorrelation confounds attempts to attribute observed changes to the environmental accident. After all, the real world is messy! Designing field studies and analyses that are quantitative, objective, and scientifically rigorous under such circumstances is difficult – yet it is essential.
To determine the association between contact precautions and depression or anxiety as well as feelings of anger, sadness, worry, happiness, or confusion.
Design.
Prospective frequency-matched cohort study.
Setting.
The University of Maryland Medical Center, a 662-bed tertiary care hospital in Baltimore, Maryland.
Participants.
A total of 1,876 medical and surgical patients over the age of 18 years were approached; 528 patients were enrolled from January through November 2010, and 296 patients, frequency matched by hospital unit, completed follow-up on hospital day 3.
Results.
The primary outcome was Hospital Anxiety and Depression Scale (HADS) scores on hospital day 3, controlling for baseline HADS scores. Secondary moods were measured with visual analog mood scale diaries. Patients under contact precautions had baseline symptoms of depression 1.3 points higher (P < .01) and anxiety 0.8 points higher (P = .08) at hospital admission using HADS. Exposure to contact precautions was not associated with increased depression (P = .42) or anxiety (P = .25) on hospital day 3. On hospital day 3, patients under contact precautions were no more likely than unexposed patients to be angry (20% vs 20%; P = .99), sad (33% vs 38%; P = .45), worried (51% vs 46%; P = .41), happy (58% vs 67%; P = .14), or confused (23% vs 24%; P = .95).
Conclusions.
Patients under contact precautions have more symptoms of depression and anxiety at hospital admission but do not appear to be more likely to develop depression, anxiety, or negative moods while under contact precautions. The use of contact precautions should not be restricted by the belief that contact precautions will produce more depression or anxiety.
To investigate the relationship between contact precautions and delirium among inpatients, adjusting for other factors.
Design.
Retrospective cohort study.
Setting.
A 662-bed tertiary care center.
Patients.
All nonpyschiatric adult patients admitted to a tertiary care center from 2007 through 2009.
Methods.
Generalized estimating equations were used to estimate the association between contact precautions and delirium in a retrospective cohort of 2 years of admissions to a tertiary care center.
Results.
During the 2-year period, 60,151 admissions occurred in 45,266 unique nonpsychiatric patients. After adjusting for comorbid conditions, age, sex, intensive care unit status, and length of hospitalization, contact precautions were significantly associated with delirium (as denned by International Classification of Diseases, Ninth Revision), medication, or restraint exposure (adjusted odds ratio [OR], 1.40 [95% confidence interval {CI}, 1.24–1.51]). The association between contact precautions and delirium was seen only in patients who were newly placed under contact precautions during the course of their stay (adjusted OR, 1.75 [95% CI, 1.60–1.92]; P< .01) and was not seen in patients who were already under contact precautions at admission (adjusted OR, 0.97 [95% CI, 0.86–1.09]; P = .60).
Conclusions.
Although delirium was more common in patients who were newly placed under contact precautions during the course of their hospital admission, delirium was not associated with contact precautions started at hospital admission. Patients newly placed under contact precautions after admission but during hospitalization appear to be at a higher risk and may benefit from proven delirium-prevention strategies.
Although deficient emotional self-regulation (DESR) is associated with attention deficit hyperactivity disorder (ADHD), little research investigates this association and little is known about its etiology. Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR in children.
Method
Subjects were 242 children with ADHD and 224 children without ADHD. DESR was operationalized using an aggregate score ⩾180 and <210 in the anxious/depressed, attention and aggression scales (AAA profile) of the Child Behavior Checklist (CBCL), termed the CBCL-DESR profile. The CBCL-bipolar (CBCL-BP) profile was defined as ⩾210 on the CBCL-AAA scale. We examined the familial transmission of ADHD and the CBCL-AAA scale in families selected through probands with and without these conditions.
Results
We found a linear increase in the prevalence of CBCL-DESR in siblings as indexed by the Control, ADHD, ADHD+CBCL-DESR and ADHD+CBCL-BP proband groups. While the ADHD siblings were at elevated risk for both the CBCL-DESR and CBCL-BP compared with non-ADHD siblings, a significantly higher rate of CBCL-BP in the siblings of ADHD+CBCL-BP probands was found compared with siblings of the Control probands.
Conclusions
ADHD shows the same degree of familial transmission in the presence or absence of DESR. CBCL-DESR and CBCL-BP are familial, but further work is needed to determine if these definitions are distinctly familial or represent a continuum of the same psychopathology.
We report an interesting property of carbon dots: they emit light under charge injection. We synthesized carbon dots in diameter about 20 nm using wet chemistry methods. The photoluminescence quantum efficiency of the carbon dots dissolved in water was about 11%. We observed strong electrogenerated chemiluminescence (ECL) from the sample. This observation of ECL from carbon dots indicates that they could be a good candidate material for carbon-based electroluminescent devices.
Influence of the linear energy-momentum relationship in graphene on conductance and magnetoresistance (MR) in ferromagnetic metal (FM)/graphene/FM lateral junctions is studied in a numerical simulation formulated using the Kubo formula and recursive Green’s function method in a tight-binding model. It is shown that the contribution of electron tunneling through graphene should be considered in the electronic transport in metal/graphene/metal junctions, and that the Dirac point (DP) is effectively shifted by the band mixing between graphene and metal electrodes. It is shown that MR appears due to spin-dependent shift of DP or spin-dependent change in the electronic states at DPs. It is shown that the MR ratio caused by the latter mechanism can be very high when certain transition metal alloys are used for electrodes. These results do not essentially depend on the shape of the junction structure. However, to obtain high MR ratios, the effects of roughness should be small.
Praziquantel (PZQ) is now widely used for the treatment of human schistosomiasis. However, in recent years, there has been a growing concern about the resistance of Schistosoma to PZQ. The mechanisms of PZQ action against Schistosoma and resistance of Schistosoma to PZQ are poorly understood. Here, we report differential susceptibilities to PZQ between male and female cercariae in the PZQ-susceptible and PZQ-resistant isolates of Schistosoma mansoni, using tail loss as a measurement of PZQ action. The miracidia were collected by hatching eggs collected from faeces of infected mice. Single-sex cercaria lines were made by infecting a single Biomphalaria glabrata snail with a single miracidium. The sex of each single-sex cercaria line was identified by a direct W1-specific polymerase chain reaction (PCR) technique. Single-sex cercariae of two isolates were exposed to four different concentrations of PZQ, respectively. The tail shedding of cercariae was observed under a dissecting microscope for five time points up to 100 min after adding PZQ. The results showed that male cercariae have higher tail-shedding rates than that of female cercariae when PZQ-susceptible isolates of S. mansoni are exposed to the same concentration of PZQ. But this phenomenon was not observed in the PZQ-resistant isolates. This sexual differential resistance phenomenon of S. mansoni suggests that resistance to PZQ is induced by decreasing the PZQ susceptibility of male worms. The experiment described here may also be useful for developing tests to detect PZQ resistance in the field.
1. Six cases of haemolytic disease in newborn foals apparently due to iso-immunization of pregnancy are described from their clinical, serological, haematological and pathological aspects. The findings agree closely with those seen in the same disease in newborn mules.
2. The disease may be diagnosed serologically by demonstrating the in vivo iso-sensitization of the foal's red cells by means of the direct antiglobulin-sensitization test. It is quite possible that after further investigation a modification of Diamond's albumin tube test may also be of value. Immune anti-red cell iso-antibodies of more than one specificity may be demonstrated in the dams' sera.
3. Despite the acute haemolytic process, very few reticulocytes and no erythroblasts are seen in the peripheral blood.
4. The morbid histology of the tissues of foals dying with the disease exhibits various points of interest which are discussed.
5. The clinical aspect is not described in this paper in any detail. However, a programme is suggested which would enable a successful exsanguino-transfusion of compatible blood to be carried out at very short notice. At present this seems to be the logical and most practical method of specific treatment.