Effects of psychological and pharmacological interventions on anxiety symptoms in patients with bipolar disorder in full or partial remission: A systematic review.

BACKGROUND: Anxiety symptoms are prevalent in bipolar disorder (BD) even during periods of remission and impede treatment efficacy, prognosis and functional capacity. This highlights a pressing clinical need to identify novel effective anxiety treatments. This systematic review aimed to evaluate the evidence within the field. METHODS: Following PRISMA guidelines, we conducted a systematic search on PubMed, PsycInfo, EMBASE and Cochrane Library for randomised controlled trials (RCTs) targeting anxiety in remitted BD patients. RESULTS: We identified 10 RCTs investigating the effects of psychological or pharmacological treatments on anxiety in remitted BD patients. Two studies of transdiagnostic personalised cognitive behavioural therapy (CBT) found a treatment-related reduction in anxiety. This evidence was preliminary given small sample size and use of self-report measures in a single-blind trial design, respectively. The remaining six psychological intervention trials provided more preliminary evidence due to several methodological challenges. The two pharmacological studies found anxiolytic effects of add-on olanzapine or methylene blue to lithium treatment, respectively. Nevertheless, this evidence should be interpreted with caution given high drop-out rates and substantial side-effects that may have impeded blinding. LIMITATIONS: We did not conduct a quantitative meta-analysis. CONCLUSIONS: There is preliminary evidence for beneficial effects of modified CBT and add-on pharmacotherapy on residual anxiety in BD. Future trials should pre-screen participants for anxiety, define one clinician-rated anxiety measurement as a primary outcome, and employ intention-to-treat analysis to assess treatment effect. This will advance treatment development and enable personalised approaches to address residual anxiety in BD, which has great clinical relevance.

Contaminating viral sequences in high-throughput sequencing viromics: a linkage study of 700 sequencing libraries.

OBJECTIVES: Sample preparation for high-throughput sequencing (HTS) includes treatment with various laboratory components, potentially carrying viral nucleic acids, the extent of which has not been thoroughly investigated. Our aim was to systematically examine a diverse repertoire of laboratory components used to prepare samples for HTS in order to identify contaminating viral sequences. METHODS: A total of 322 samples of mainly human origin were analysed using eight protocols, applying a wide variety of laboratory components. Several samples (60% of human specimens) were processed using different protocols. In total, 712 sequencing libraries were investigated for viral sequence contamination. RESULTS: Among sequences showing similarity to viruses, 493 were significantly associated with the use of laboratory components. Each of these viral sequences had sporadic appearance, only being identified in a subset of the samples treated with the linked laboratory component, and some were not identified in the non-template control samples. Remarkably, more than 65% of all viral sequences identified were within viral clusters linked to the use of laboratory components. CONCLUSIONS: We show that high prevalence of contaminating viral sequences can be expected in HTS-based virome data and provide an extensive list of novel contaminating viral sequences that can be used for evaluation of viral findings in future virome and metagenome studies. Moreover, we show that detection can be problematic due to stochastic appearance and limited non-template controls. Although the exact origin of these viral sequences requires further research, our results support laboratory-component-linked viral sequence contamination of both biological and synthetic origin.

Disease pattern in Danish patients with Peutz-Jeghers syndrome.

PURPOSE: In this paper, we aimed to collect genetic and medical information on all Danish patients with Peutz-Jeghers syndrome (PJS), in order to contribute to the knowledge of phenotype and genotype. Peutz-Jeghers syndrome is a hereditary syndrome characterized by multiple hamartomatous polyps in the GI tract, mucocutaneous pigmentations, and an increased risk of cancer in the GI tract and at extraintestinal sites. Over 90 % of patients harbour a pathogenic mutation in STK11. METHODS: Based on the Danish Pathology Data Bank, the Danish National Patient Register, as well as information from relevant departments at Danish hospitals, we identified patients and collected clinical and genetic information. RESULTS: We identified 43 patients of which 14 were deceased. The prevalence was estimated to be ∼1 in 195,000 individuals. The median age at first symptom was 27.5 with invagination of the small bowel as the most frequent presenting symptom. We noted 18 occurrences of cancer at various anatomical sites, including a case of thyroid cancer and penile cancer. Eight of the deceased patients had died of cancer. Eighteen different mutations in STK11 had been detected in 28 patients. CONCLUSION: This is the first comprehensive study of patients with Peutz-Jeghers syndrome in the Danish population identified from nationwide registers and databases. We have demonstrated that the expressivity of Peutz-Jeghers syndrome varies greatly among the patients, even within the same families, underlining the great phenotypic spectrum. Patients with PJS should be offered surveillance from childhood in order to prevent morbidity and reduce mortality.

Impacts of Combustion Conditions and Photochemical Processing on the Light Absorption of Biomass Combustion Aerosol.

The aim was to identify relationships between combustion conditions, particle characteristics, and optical properties of fresh and photochemically processed emissions from biomass combustion. The combustion conditions included nominal and high burn rate operation and individual combustion phases from a conventional wood stove. Low temperature pyrolysis upon fuel addition resulted in "tar-ball" type particles dominated by organic aerosol with an absorption Ångström exponent (AAE) of 2.5-2.7 and estimated Brown Carbon contributions of 50-70% to absorption at the climate relevant aethalometer-wavelength (520 nm). High temperature combustion during the intermediate (flaming) phase was dominated by soot agglomerates with AAE 1.0-1.2 and 85-100% of absorption at 520 nm attributed to Black Carbon. Intense photochemical processing of high burn rate flaming combustion emissions in an oxidation flow reactor led to strong formation of Secondary Organic Aerosol, with no or weak absorption. PM1 mass emission factors (mg/kg) of fresh emissions were about an order of magnitude higher for low temperature pyrolysis compared to high temperature combustion. However, emission factors describing the absorption cross section emitted per kg of fuel consumed (m(2)/kg) were of similar magnitude at 520 nm for the diverse combustion conditions investigated in this study. These results provide a link between biomass combustion conditions, emitted particle types, and their optical properties in fresh and processed plumes which can be of value for source apportionment and balanced mitigation of biomass combustion emissions from a climate and health perspective.

Novel mutation in ATP13A2 widens the spectrum of Kufor-Rakeb syndrome (PARK9).

Kufor-Rakeb syndrome (KRS) is a rare autosomal recessive inherited juvenile parkinsonian syndrome caused by mutations in ATP13A2. We describe six patients from a consanguineous Greenlandic Inuit family, homozygous for a novel frame-shift mutation in exon 22 of ATP13A2 (c.2473C>AA, p.Leu825AsnfsX32). Disease onset varied from 10 to 29 years of age, the latest reported, and the clinical features were highly variable within a wide spectrum of an extrapyramidal-pyramidal syndrome with cognitive/psychiatric features. Ataxia was seen in two patients and axonal neuropathy in one, features not previously related to KRS. Dopamine transporter scans showed symmetrical, severely reduced uptake in striatum in two patients. Magnetic resonance imaging was without atrophy in one patient despite disease duration of 17 years, and cerebral and cerebellar atrophy was seen in another patient after 4 years of disease duration. The molecular pathogenic mechanisms of ATP13A2 mutations are discussed. The observation that the mutant transcript is not degraded by nonsense-mediated RNA decay and the fact that none of the eight heterozygous carriers from the family have KRS symptoms suggest that the mutant protein does not interfere and destroy the function of the wild-type ATP13A2 protein.

Transcatheter aortic valve replacement in high risk patients with different anaesthetic techniques.

INTRODUCTION: Percutaneous retrograde transfemoral or transsubclavian aortic valve replacement is a minimally invasive method of aortic valve replacement in elderly and high-risk patients with symptomatic aortic stenosis considered too fragile to go through conventional heart surgery. The purpose of this study was to compare two different anaesthetic techniques for percutaneous retrograde transfemoral or transsubclavian aortic valve replacement in terms of anaesthetic depth, hemodynamic stability and need for vasoactive drugs. METHODS: Forty-eight elderly or high risk patients, two third of them in their eighties, were scheduled for percutaneous retrograde transfemoral or transsubclavian aortic valve replacement. Anaesthetic induction was standardized, but anaesthesia was afterwards maintained alternately with either propofol infusion or sevoflurane. Need for vasoactive drugs was recorded and anaesthetic depth was estimated from acoustic evoked potential measuring and clinical observation. RESULTS: Twenty-eight percent of the patients in the sevoflurane group and 30% of the patients in the propofol group required vasoactive therapy (P=0.84). Forty-four percent of the patients in the sevoflurane group and 57% of the patients in the propofol group had episodes of superficial anaesthesia recorded(P=0.38). CONCLUSIONS: We found no significant difference in the use of vasoactive drugs or in anaesthetic depth between propofol and sevoflurane anaesthesia. Both can be recommended for percutaneous aortic valve replacement.

Transthoracic ultrasonography-guided core needle biopsy of pleural-based lung lesions: prospective randomized comparison between a Tru-cut-type needle and a modified Menghini-type needle.

PURPOSE: The diagnostic yield of the different types of cutting needles used to perform transthoracic biopsy is scarcely investigated. Aim of the study was to compare a Tru-cut-type (TCT) needle and a modified Menghini-type needle (MMT) in ultrasonography (US)-guided biopsy of pulmonary lesions. MATERIALS AND METHODS: 307 subjects (191 males and 116 females, mean age 58 years) with peripheral lung lesions selected to undergo US-guided biopsy were randomized to undergo biopsy by using an 18-gauge TCT or MMT needle. The specimens were imprinted on two to three slides for cytology and then put into a formalin solution for histology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Fisher's exact test was used to compare histology recovery rate (HRR), diagnostic accuracy, and diagnostic yield of the combination of cytology and histology in comparison with cytology alone and histology alone. RESULTS: 155 biopsies were performed using the MMT needle, 152 using the TCT needle. HRR was 112 / 155 (72.3 %) and 144 / 152 (94.7 %), respectively (p < 0.0001). Sensitivity, specificity, PPV, and NPV were 81.6 %, 100 %, 100 %, and 62 % for the former, respectively, and 93.6 %, 100 %, 100 %, and 86 % for the latter. A correct diagnosis was achieved in 133 / 155 biopsies (85.8 %) performed with the MMT needle, and in 145 / 152 biopsies (95.4 %) performed with the TCT needle (p = 0.0041). The combination of cytology and histology had a higher diagnostic yield than cytology alone (p < 0.001) and histology alone (p < 0.001). CONCLUSION: The TCT needle performs better than the MMT needle, and improves the diagnostic accuracy of US-guided transthoracic biopsy of superficial lung lesions.

Biradicalic excited states of zwitterionic phenol-ammonia clusters.

Phenol-ammonia clusters with more than five ammonia molecules are proton transferred species in the ground state. In the present work, the excited states of these zwitterionic clusters have been studied experimentally with two-color pump probe methods on the nanosecond time scale and by ab initio electronic-structure calculations. The experiments reveal the existence of a long-lived excited electronic state with a lifetime in the 50-100 ns range, much longer than the excited state lifetime of bare phenol and small clusters of phenol with ammonia. The ab initio calculations indicate that this long-lived excited state corresponds to a biradicalic system, consisting of a phenoxy radical that is hydrogen bonded to a hydrogenated ammonia cluster. The biradical is formed from the locally excited state of the phenolate anion via an electron transfer process, which neutralizes the charge separation of the ground state zwitterion.

Characterization of neutral fragments issued from the photodissociation of protonated tryptophane.

New information on the photo-fragmentation of biomolecules is obtained from the detection of neutral and ionic fragments using a time and position resolved coincidence technique that reveals whether an ionic photofragment is associated with one or more neutral fragments. In the case of a sequential dissociation, both fragmentation channels are identified as well as their time ordering.

Comprehensive characterization of the photodissociation pathways of protonated tryptophan.

The photofragmentation of protonated tryptophan has been investigated in a unique experimental setup, in which ion and neutral issued from the photofragmentation are detected in coincidence, in time and in position. From these data are extracted the kinetic energy, the number of neutral fragments associated with an ion, their masses, and the order of the fragmentation steps. Moreover, the fragmentation time scale ranging from tens of nanoseconds to milliseconds is obtained. From all these data, a comprehensive fragmentation mechanism is proposed.

S1 and S2 excited States of gas-phase Schiff-base retinal chromophores.

Photoabsorption studies of 11-cis and all-trans Schiff-base retinal chromophore cations in the gas phase have been performed at the electrostatic ion storage ring in Aarhus. A broad absorption band due to the optically allowed excitation to the first electronically excited singlet state (S1) is observed at around 600 nm. A second "dark" excited state (S2) just below 400 nm is reported for the first time. It is located approximately 1.2 eV above S1 for both chromophores. The S2 state was not visible in a solution measurement where only one highly blueshifted absorption band corresponding to the first excited state was visible. Knowledge of the position of the excited states in retinal is essential for the understanding of the fast photoisomerization in, for example, visual pigments.

How similar are commonly combined criteria for EDSS progression in multiple sclerosis?

INTRODUCTION: Measuring disease progression is an important aspect of multiple sclerosis (MS) clinical trials. Commonly applied disability endpoints include time to clinically meaningful Expanded Disability Status Scale (EDSS) change, or the number of patients in whom such a change has occurred. Typically, clinically meaningful EDSS change has been defined as a change of 1.0 point on Kurtzke's EDSS in patients with an entry EDSS score of 5.5 or lower, or 0.5 point in patients with a higher EDSS score. Our goal was to evaluate whether these changes can be considered as similar. Therefore, we compared EDSS changes to corresponding changes in the Guy's Neurological Disability Scale (GNDS), which is a measure of patient perceived disability, and the Multiple Sclerosis Functional Composite (MSFC), which is an examination-based quantitative scoring of neurological impairment. METHODS: From a large longitudinal database, we selected two groups of patients with a clinically meaningful change in EDSS score according to the usual criteria: patients with EDSS change > or = 1.0 for baseline EDSS < or = 5.5 and patients with EDSS change > or = 0.5 for baseline EDSS > or = 6.0. We compared changes in GNDS sum score and in MSFC score between both groups. RESULTS: In the group with baseline EDSS > or = 6.0, GNDS and MSFC changes were higher than in patients with baseline EDSS < or = 5.5. The difference in change was 1.00 (95% confidence interval (CI): -0.35 to 2.36) for the GNDS and 0.412 (95% CI: 0.300-0.525) for the MSFC. CONCLUSION: Our results indicate that a 0.5 point EDSS change in patients with baseline EDSS > or = 6.0 cannot be considered equal to a 1.0 point change in patients with baseline EDSS < or = 5.5.

Absorption spectra of photoactive yellow protein chromophores in vacuum.

The absorption spectra of two photoactive yellow protein model chromophores have been measured in vacuum using an electrostatic ion storage ring. The absorption spectrum of the isolated chromophore is an important reference for deducing the influence of the protein environment on the electronic energy levels of the chromophore and separating the intrinsic properties of the chromophore from properties induced by the protein environment. In vacuum the deprotonated trans-thiophenyl-p-coumarate model chromophore has an absorption maximum at 460 nm, whereas the photoactive yellow protein absorbs maximally at 446 nm. The protein environment thus only slightly blue-shifts the absorption. In contrast, the absorption of the model chromophore in aqueous solution is significantly blue-shifted (lambda(max) = 395 nm). A deprotonated trans-p-coumaric acid has also been studied to elucidate the effect of thioester formation and phenol deprotonation. The sum of these two changes on the chromophore induces a red shift both in vacuum and in aqueous solution.

Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease.

OBJECTIVE: Some epidemiological studies found a lower risk of cardiovascular disease among wine drinkers than among drinkers of other types of ethanol. This difference might be due to an effect of nonalcohol compounds in wine on important cardiovascular risk factors. The objective of this study was to compare the effect of red wine, nonalcohol compounds of red wine and placebo on established cardiovascular risk factors. DESIGN: A parallel, four-armed intervention study. SUBJECTS: A total of 69 healthy 38-74-y-old men and women. INTERVENTIONS: Subjects were randomised to either 1: red wine (males: 300 ml/day, 38.3 g alcohol/day, female subjects: 200 ml/day, 25.5 g alcohol/day), 2: water + red grape extract tablets (wine-equivalent dose), 3: water + red grape extract tablets (half dose), or 4: water + placebo tablets for a period of 4 weeks. No other sources of alcohol or anthocyanin were allowed. Plasma high-density lipoprotein (HDL)-cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C), HDL-C/LDL-C-ratio, very-low-density lipoprotein (VLDL)-triacylglycerol, total cholesterol, fibrinogen, factor VII coagulant activity (FVIIc), blood pressure, and body weight were determined before and after intervention. RESULTS: Wine consumption was associated with a significant 11-16% increase in fasting HDL-C and 8-15% decrease in fasting fibrinogen relative to not drinking wine. There were no significant treatment effects on fasting LDL-C, HDL-C/LDL-C-ratio, VLDL-triacylglycerol, total cholesterol, FVIIc, or blood pressure. Drinking wine was associated with relative body weight increments closely corresponding to the energy contributed by the alcohol component. CONCLUSION: Moderate red wine consumption for 4 weeks is associated with desirable changes in HDL-C and fibrinogen compared with drinking water with or without red grape extract. The impact of wine on the measured cardiovascular risk factors thus seems primarily explained by an alcohol effect. Our finding suggests that the putative difference in cardiac risk associated with wine vs other alcoholic beverages might be rather explained by other life-style confounders than by red wine contents of nonalcohol components.

Measurements of scattered light on a microchip flow cytometer with integrated polymer based optical elements.

Flow cytometry is widely used for analyzing microparticles, such as cells and bacteria. In this paper, we report an innovative microsystem, in which several different optical elements (waveguides, lens and fiber-to-waveguide couplers) are integrated with microfluidic channels to form a complete microchip flow cytometer. All the optical elements, the microfluidic system, and the fiber-to-waveguide couplers were defined in one layer of polymer (SU-8, negative photoresist) by standard photolithography. With only a single mask procedure required, all the fabrication and packaging processes can be finished in one day. Polystyrene beads were measured in the microchip flow cytometer, and three signals (forward scattering, large angle scattering and extinction) were measured simultaneously for each bead. To our knowledge this is the first time forward scattered light and incident light extinction were measured in a microsystem using integrated optics. The microsystem can be applied for analyzing different kinds of particles and cells, and can easily be integrated with other microfluidic components.

Cholestasis Familiaris Groenlandica/Byler-like disease in Greenland--a population study.

OBJECTIVES: Cholestasis Familiaris Groenlandica (CFG, or progressive familiar intrahepatic cholestasis type 1 (PFIC1)) is a very common lethal recessive inherited disease in Greenland. A missense mutation, 1660G>A (asp554asn) in the gene ATP8B1 causes the disease (Klomp et al. 2000). STUDY DESIGN: A family study examining medical files from the period 1951-2003 from East Greenland resulted in 46 cases of PFIC1 and more than 220 relatives showing carrier status. Further, random blood sample testing 953 anonymous persons from 11 major cities or districts all over Greenland have been analysed for carrier status of the mutation. METHODS: A sensitive PCR method is developed to distinguish between normal and mutant alleles for ATP8B1 in the Greenland population. RESULTS: The mutation 1660G>A is found in all areas of Greenland, and the frequency of the mutant allele vary all over the country. A shockingly high frequency for the mutant allele is found in East Greenland in Ittoqqortoormiit (0.16) and in Tasiilaq (0.077), whereas in Northwest Greenland lower frequencies are found in Uummannaq and Ilulissat (0.032), and Maniitsoq (0.005). CONCLUSIONS: The high frequency of the mutation in East and Northwest Greenland strongly indicates that routine screening of the population for carrier status should be done.

Cholestasis Familiaris Groenlandica: an epidemiological, clinical and genetic study.

OBJECTIVES: Accumulation of Cholestasis Familiaris Groenlandica (CFG) or progressive familial intrahepatic cholestasis type 1 (PFIC1) occurs in indigenous Inuit families in Greenland. It is an autosomal recessive inherited liver disease. From early childhood the children suffer from failure to thrive, jaundice, pruritus and enlarged liver. Affected persons generally die very young. STUDY DESIGN: Patients' information has been collected from the Greenlandic death register and hospital records. METHODS: Detailed genealogy including clinical description and examination if possible. Interviews of parents and relatives, linkage and DNA analysis of the probands and the closest relatives have been studied. RESULTS: 46 affected cases from a highly inbred population have been diagnosed since 1943. The disease is caused by a missense mutation in the FIC1 gene ATP8B1, chromosome 18q21. Six affected children are alive aged 1-21 years. Among the tested relatives 220 are heterozygote. One prenatal diagnosis has been performed. CONCLUSION: The mutation causing Cholestasis Familiaris Groenlandica is widespread in Greenland, but accumulation is seen in certain areas. The disease is burdensome for the child, the parents and the Greenlandic society. Genetic counselling and carrier screening are strongly recommended.

Epilepsy among children in Greenland.

INTRODUCTION: Epilepsy has been considered to be more frequent in Greenland than in Denmark, where the prevalence among children is 0.40%. STUDY DESIGN: Evaluation of the prevalence, diagnosis and treatment of epilepsy among children in Greenland aged 0-15 years. METHODS: During autumn 2000, 13 out of 18 hospitals in Greenland were visited. The population of children in the areas visited was 11,965 of a total of 15,226 in Greenland. All children with the diagnosis of epilepsy were referred for evaluation and the diagnosis was confirmed. When possible, informed consent was obtained to collect data from medical records. RESULTS: 43 children (18 boys) had the diagnosis of epilepsy. For 38 (15 boys) further data were obtained. Mean age was 8.5 years (3-14) for boys and 7.9 years (2-14) for girls. The age at diagnosis was 4.9 years (1-11) for boys and 4.2 years (0-10) for girls. The prevalence of epilepsy was 0.34%. In 31 cases an electroencephalograph (EEG) recording was done, comprising sleep recordings in 26 cases. Medication was according to recommendations in Denmark. CONCLUSION: The prevalence of epilepsy in children and the medical treatment of epilepsy among children in Greenland is the same as in Denmark.

Cognitive dysfunction after minor surgery in the elderly.

BACKGROUND: Major surgery is frequently associated with postoperative cognitive dysfunction (POCD) in elderly patients. Type of surgery and hospitalization may be important prognostic factors. The aims of the study were to find the incidence and risk factors for POCD in elderly patients undergoing minor surgery. METHODS: We enrolled 372 patients aged greater than 60 years scheduled for minor surgery under general anesthesia. According to local practice, patients were allocated to either in- (199) or out-patient (173) care. Cognitive function was assessed using neuropsychological testing preoperatively and 7 days and 3 months postoperatively. Postoperative cognitive dysfunction was defined using Z-score analysis. RESULTS: At 7 days, the incidence (confidence interval) of POCD in patients undergoing minor surgery was 6.8% (4.3-10.1). At 3 months the incidence of POCD was 6.6% (4.1-10.0). Logistic regression analysis identified the following significant risk factors: age greater than 70 years (odds ratio [OR]: 3.8 [1.7-8.7], P = 0.01) and in- vs. out-patient surgery (OR: 2.8 [1.2-6.3], P = 0.04). CONCLUSIONS: Our finding of less cognitive dysfunction in the first postoperative week in elderly patients undergoing minor surgery on an out-patient basis supports a strategy of avoiding hospitalization of older patients when possible.

A three-dimensional evaluation of the upper airway in adolescents.

The link between the facial growth and airway function has been a subject of controversy in orthodontics for many years. This study investigates how well lateral cephalometric headfilms depict three-dimensional upper airway structures. Subjects are 11 normal adolescent children, ages 7-16 years old. Airway information over the same anatomic area in the nasopharynx is compared between lateral cephalometric headfilms and three-dimensional cone beam computed tomography (CT) scans. Intra-subject proportion of airway volume to area shows moderate variability. CT airway volume shows more variability than corresponding headfilm airway area.