Effects of deep brain stimulation on cognitive functioning in treatment-resistant depression: a systematic review and meta-analysis.

Deep brain stimulation (DBS) is a promising intervention for treatment-resistant depression (TRD). Effects on cognitive functioning are unclear since they have been studied in small samples. We aim to estimate the impact of DBS on cognitive functioning in TRD with a systematic review and meta-analyses. After systematically searching PubMed we included 10 studies which compared standardized neuropsychological tests before and after DBS or between active and sham DBS in TRD. Different random-effects meta-analyses were done for different cognitive (sub-)domains and for different follow-up time windows (<6 months, 6-18 months, and >18 months). We found no significant differences in cognitive functioning up to 6 months of DBS. After 6-18 months of DBS small to moderate improvements were found in verbal memory (Hedge's g = 0.22, 95% CI = [0.01-0.43], p = 0.04), visual memory (Hedge's g = 0.37, 95% CI = [0.03-0.71], p = 0.04), attention/psychomotor speed (Hedge's g = 0.26, 95% CI = [0.02-0.50], p = 0.04) and executive functioning (Hedge's g = 0.37, 95% CI = [0.15-0.59], p = 0.001). Not enough studies could be retrieved for a meta-analysis of effects after >18 months of DBS or for the comparison of active and sham DBS. Qualitatively, generally no differences in cognitive functioning between active and sham DBS were found. No cognitive decline was found in this meta-analysis up to 18 months of DBS in patients with TRD. Results even suggest small positive effects of DBS on cognitive functioning in TRD, although this should be interpreted with caution due to lack of controlled data.

Product ion isotopologue pattern: A tool to improve the reliability of elemental composition elucidations of unknown compounds in complex matrices.

RATIONALE: Elucidation of the elemental compositions of unknown compounds (e.g., in metabolomics) generally relies on the availability of accurate masses and isotopic ratios. This study focuses on the information provided by the abundance ratio within a product ion pair (monoisotopic versus the first isotopic peak) when isolating and fragmenting the first isotopic ion (first isotopic mass spectrum) of the precursor. METHODS: This process relies on the capability of the quadrupole within the Q Orbitrap instrument to isolate a very narrow mass window. Selecting only the first isotopic peak (first isotopic mass spectrum) leads to the observation of a unique product ion pair. The lighter ion within such an isotopologue pair is monoisotopic, while the heavier ion contains a single carbon isotope. The observed abundance ratio is governed by the percentage of carbon atoms lost during the fragmentation and can be described by a hypergeometric distribution. RESULTS: The observed carbon isotopologue abundance ratio (product ion isotopologue pattern) gives reliable information regarding the percentage of carbon atoms lost in the fragmentation process. It therefore facilitates the elucidation of the involved precursor and product ions. Unlike conventional isotopic abundances, the product ion isotopologue pattern is hardly affected by isobaric interferences. Furthermore, the appearance of these pairs greatly aids in cleaning up a 'matrix-contaminated' product ion spectrum. CONCLUSIONS: The product ion isotopologue pattern is a valuable tool for structural elucidation. It increases confidence in results and permits structural elucidations for heavier ions. This tool is also very useful in elucidating the elemental composition of product ions. Such information is highly valued in the field of multi-residue analysis, where the accurate mass of product ions is required for the confirmation process. Copyright © 2016 John Wiley & Sons, Ltd.

Spectroscopic, Biological, and Topological Insights on Lemonol as a Potential Anticancer Agent.

A monoterpene alcohol known as lemonol was investigated experimentally as well as theoretically in order to gain insights into its geometrical structure, vibrational frequencies, solvent effects on electronic properties, molecular electrostatic potential, Mulliken atomic charge distribution, natural bond orbital, and Nonlinear Optical properties. The frontier molecular orbital energy gap values of 5.9084 eV (gas), 5.9261 eV (ethanol), 5.9185 eV (chloroform), 5.9253 eV (acetone), and 5.9176 eV (diethyl ether) were predicted, and it shows the kinetic stability and chemical reactivity of lemonol. Topological studies were conducted using Multiwfn software to understand the binding sites and weak interactions in lemonol. The antiproliferative effect of lemonol against the breast cancer cell line Michigan Cancer Foundation (MCF-7) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while nuclear damage, condensation, and reactive oxygen species generation were identified using acridine orange/ethidium bromide, propidium iodide, and dichlorodihydrofluorescein diacetate staining. The theoretical and experimental findings are highly correlated, confirming the structure, and the results of in vitro studies suggest that lemonol acts as a potent inhibitor against the human breast cancer cell line MCF-7, highlighting its strong antiproliferative activity.

Chemical reactivity, molecular electrostatic potential and in-silico analysis on benzimidazole fungicide benomyl.

We are reporting theoretical concepts and biological activity of benomyl using different techniques. The molecular orbital contributions are studied by using Total Density of States (TDOS) analysis. The chemical reactivity of the molecule have been determined with the help of global reactivity descriptors. Molecular electrostatic potential is calculated by the density functional method and predicts the most reactive part in the molecule. In-silico molecular analysis is conducted for Benomyl compound.

Regional ecotoxicological hazards associated with anthropogenic enrichment of heavy metals.

Regional geochemical data of heavy metals are commonly used for environmental risk assessment and management. Often these data are based on so-called total concentrations, whereas the exposure to the mobile or reactive fraction of these elements finally determines whether the exposed ecosystem is at risk and to which extent. The objective of our research was to develop a wider applicable method for quantitative hazard assessment of soil metal contamination attributable to the activity of man, based on and illustrated with data from the Netherlands. Since chemical availability (0.43 M HNO3 extractable concentrations) of Cd, Cu, Pb and Zn appeared strongly related to the estimated anthropogenic enrichment, we used these concentrations to assess the hazard of human-induced enrichment of these metals. We expressed the enrichment hazard using the toxic pressure concept, which estimates the fraction of biological species (varying between 0 and 1) potentially affected due to the level of exposure to single metals or their local mixtures. This is done using logistic (enrichment) concentration/response models parameterized with ecotoxicological effect data from toxicity tests and mixture models. Hazards varied from very low toxic pressures (lower than 0.01) to (most often) toxic pressure less than 0.05, whereby the latter relates to the so-called 95%-protection criterion used in some soil protection legislations. In rare cases, the toxic pressure exceeded the value of 0.05, to an upper limit of 0.054 for Cd. The rank order of metal enrichment hazards suggests that Cd enrichment induces the largest hazard increase. There are limited (rank order) differences in enrichment hazards between soil types. Comparing the judgement of soils based on soil screening levels and based on toxic pressure of anthropogenic Cd, Cu, Pb and Zn enrichments, the soil screening values appear to more conservative. This exemplifies the use of soil screening values as a method to note regulatory concern, but not always indicating an actual hazard or risk. When screening values are exceeded, refined hazard insights can be obtained, as illustrated in this paper. This provides a more refined insight in the ecotoxic implications of human-induced metal enrichments in soils, as refined basis for risk management decisions.

Perioperative bridging of anticoagulation: towards a more reserved approach.

BACKGROUND: Most invasive procedures require the interruption of oral anticoagulation. In 2015, an international randomised trial demonstrated that perioperative bridging caused more harm than benefit in most anticoagulated patients with atrial fibrillation, leading to a more restrictive Dutch national guideline in April 2016. The objective of the present study was to analyse the integration of the 2016 Dutch guideline for perioperative antithrombotic management from after publication until update of hospital protocols. METHODS: This is a retrospective cohort study of patients on vitamin K antagonists undergoing a surgical procedure between April 2016 and June 2017. RESULTS: The proportion of high-risk patients with venous thromboembolism or atrial fibrillation receiving bridging therapy decreased from 91% and 77%, respectively at the start of the study to 33% in both groups in the last months. In high-risk patients with a mechanical heart valve, the bridging rate remained stable at 70-80% for 12 months and increased to 100% in the last 3 months. Protocol adherence for high-risk patients decreased from 80% to below 43%. The 30-day incidence of major bleeding was 4.1% (15.2% in bridged patients and 0.7% in non-bridged patients) and 10.3% for clinically relevant non-major bleeding (23.9% in bridged patients and 6.0% in non-bridged patients). The incidence of thrombo-embolism was 0.5%. CONCLUSION: New evidence from the Dutch national guideline on perioperative bridging was adopted by physicians before the local hospital protocol was updated. Low incidence of thromboembolism in non-bridged patients and high incidence of bleeding in bridged patients support a more restrictive bridging policy.

Structural activity, fungicidal activity and molecular dynamics simulation of certain triphenyl methyl imidazole derivatives by experimental and computational spectroscopic techniques.

The main objective of the study is to analyze the structural behaviour and fungicidal activity of clotrimazole by experimental and theoretical spectroscopic techniques. Its computational results are correlated with three triphenyl imidazole derivative compounds. The clotrimazole-water complexes formed by hydrogen bonding interactions are investigated at the B3LYP/6-311G(d,p) level. The distributions of the vibrational bands are carried out with the help of normal coordinate analysis (NCA). Hirshfeld surface analysis of clotrimazole is done and the obtained finger print plots reveal the interactions within the compound. The stability of the compounds in water has been investigated by using molecular dynamics simulation (MDS). Molecular docking is done on the compounds in comparison with the native ligand (Lanosterol 14α-demethylase) and standard drug (fluconazole) to study the hydrogen bond energy interaction. The antifungal activity of clotrimazole is analyzed by using two fungal pathogens.

Elastic compression stockings one year after DVT diagnosis: Who might discontinue?

BACKGROUND: Elastic compression stockings (ECS) are uncomfortable to wear but may prevent post-thrombotic syndrome (PTS). The ability to predict PTS may help clinical decision making regarding the optimal duration of ECS after deep vein thrombosis (DVT). AIMS: Predefined endpoint analysis of the Octavia study that randomized patients who compliantly used ECS up to one year after DVT to continue or discontinue ECS treatment. Primary aim was to identify predictors of PTS. METHODS: Patient characteristics were collected and ultrasonography was performed to assess reflux, residual thrombosis and persistent thrombus load 12 months after DVT. Multivariable analyses were performed to identify factors related to PTS. RESULTS: Thrombus score ≥ 3, BMI ≥ 26, duration of symptoms before DVT diagnosis ≥ 8 days and a Villalta score of 2-4 points were statistically significant predictors of PTS. The predictive value for PTS for the assessed variables was not different between the 2 treatment groups. In the stop ECS group, 3.2% (95%CI 0.08-18) of patients without any predictors for PTS were diagnosed with mild PTS during follow-up, and none with severe PTS, for a sensitivity of 98% (95% CI 89-100), a specificity of 14% (95% CI 10-20), a positive predictive value of 20% (95% CI 19-22), and a negative predictive value of 97% (95% CI 81-100). CONCLUSION: We identified 4 predictors of PTS occurring in the 2nd year after DVT. Our findings may be used to decide on whether to continue ECS treatment for an additional year, after one year of compliant ECS use, keeping in mind that patients with none of the predictors will have the lowest PTS incidence.

Predicting Post-Thrombotic Syndrome with Ultrasonographic Follow-Up after Deep Vein Thrombosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Post-thrombotic syndrome (PTS) is a common and potential severe complication of deep venous thrombosis (DVT). Elastic compression stocking therapy may prevent PTS if worn on a daily basis, but stockings are cumbersome to apply and uncomfortable to wear. Hence, identification of predictors of PTS may help physicians to select patients at high risk of PTS. AIMS: This article identifies ultrasonography (US) parameters assessed during or after treatment of DVT of the leg, that predict PTS. METHODS: This is a systematic review and meta-analysis study. Databases were searched for prospective studies including consecutive patients with DVT who received standardized treatment, had an US during follow-up assessing findings consistent with vascular damage after DVT and had a follow-up period of at least 6 months for the occurrence of PTS assessed by a standardized protocol. RESULTS: The literature search revealed 1,156 studies of which 1,068 were irrelevant after title and abstract screening by three independent reviewers. After full-text screening, 12 relevant studies were included, with a total of 2,684 analysed patients. Two US parameters proved to be predictive of PTS: residual vein thrombosis, for a pooled odds ratio (OR) of 2.17 (95% confidence interval [CI], 1.79-2.63) and venous reflux at the popliteal level, for a pooled OR of 1.34 (95% CI, 1.03-1.75). CONCLUSION: The US features reflux and residual thrombosis measured at least 6 weeks after DVT predict PTS. Whether these features may be used to identify patients who may benefit from compression therapy remains to be assessed in further studies.

Radiography of the distal extremity of the manus in the donkey foal: Normal images and quantitative characterization from birth to 2 years of age: A pilot study.

This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero-medial radiographs with and without barium marker at the coronary band and dorso-palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20-21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.

One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial.

OBJECTIVE:  To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. DESIGN:  Multicentre single blind non-inferiority randomised controlled trial. SETTING:  Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. PARTICIPANTS:  Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. INTERVENTIONS:  Continuation or cessation of ECS 12 months after deep venous thrombosis. MAIN OUTCOME MEASURES:  The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). RESULTS:  518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. CONCLUSION:  Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial. TRIAL REGISTRATION:  Netherlands Trial Register NTR1442.

Plasma lysozyme levels and decay of neutrophilic granulocytes in patients with Crohn's disease.

In patients with Crohn's disease, the lysozyme concentration in plasma was compared with the Crohn's disease activity index, the granulocyte lysozyme content, the number of circulating neutrophilic granulocytes in peripheral blood and the unsaturated vitamin B12-binding capacity of the plasma cobalophilins as an index for the granulocyte decay. There was no difference in the lysozyme content of granulocytes from patients and controls. Patients with increased plasma lysozyme levels suffered from a more active disease and had larger numbers of circulating granulocytes in their blood than those with normal plasma lysozyme levels. The plasma lysozyme levels correlated well with the cobalophilin levels, in patients with increased levels even more markedly than in those with normal levels. The results suggest that in patients with Crohn's disease increased plasma lysozyme levels are due to an increase in granulocyte decay.

[Implantation of stents in Blalock-Taussig shunt in an adult patient with pulmonary atresia and interventricular septal defect]. / Implantación de stents en la fístula de Blalock-Taussig en un adulto con atresia pulmonar y comunicación interventricular.

We present the case of a 26 years-old woman with pulmonary atresia and interventricular septal defect. Classical Blalock-Taussig and Waterston-Cooley shunts were performed in infancy. When she was 14 years old related progressive cyanosis and dyspnea and angiography showed severe stenosis of the Blalock-Taussig. Cardiac catheterization performed 12 years later demonstrated complete obstruction of the shunt. A new surgical palliation was precluded by hemorrhagic complications. Two self-expandable stents were successfully deployed in Blalock-Taussig anastomosis: previously, a balloon-expandable stent was implanted in right pulmonary artery. Oxygen saturation increased from 68% to 89% after stents implantation. Twelve months later clinical and laboratory tests are still improved, and Doppler confirmed patency of the shunt.

Odour and ammonia removal from pig house exhaust air using a biotrickling filter.

Odour from agricultural activities, such as the spreading of manure and the housing of animals, is increasingly being considered a nuisance in densely populated countries like the Netherlands. The objective of this research was to study the odour removal from pig house exhaust air by a biotrickling filter that had been implemented for ammonia abatement. At a regular pig production farm, the performance of a running full-scale biotrickling filter was studied for 72 days. Ammonia and odour removal efficiency were on average 79% and 49% respectively. Ammonia removal appeared to be based on an unintended accumulation of ammonium and nitrite in the system, instead of on production and discharge of nitrate. The odour removal efficiency showed a large variation that, for a major part, about 80%, could be attributed to actual changes in the performance of the biotrickling filter. These changes were probably caused by variations in the composition of the air that were not completely reflected by the olfactometrically measured odour concentration, as the many different components that make up the odour each have different removal characteristics. It seemed that the biotrickling filter was operated below its maximum absolute odour removal capacity [OUE/(m3 filter)/s], which means that the absolute odour removal will probably rise at increasing load. It was, however, not possible to distinguish between the influence of either the odour load or the odour concentration on the odour removal, because of a positive correlation between the odour concentration and the air flow. To increase the odour removal efficiency (%), the design of the filter probably needs to be optimised for both well and poorly water-soluble odour components.

The effect of two ammonia-emission-reducing pig housing systems on odour emission.

Odour nuisance from agricultural activities is increasing in densely populated countries like the Netherlands. To develop adequate regulations, a large-scale, government-financed monitoring programme was started in the mid-1990s to establish odour emission levels for both conventional and low ammonia emission housing systems for cattle, pigs and poultry. The results indicate that high- and low-odour emission housing are difficult to distinguish because of the large variation within housing systems. Measurements on different farm locations within the same housing system show both a large variation between locations and within one location (in time). The latter, however, is significantly smaller, which suggests that farm management is an important determinant in odour emission that interferes with the effects of housing systems. The current research was aimed at determining the effect of two common ammonia-reducing pig-housing systems on odour emissions compared to conventional housing systems under similar management conditions. The respective reduction principles of these systems are reducing the emitting surface of the manure pit and cooling of manure in the manure pit (both pits beneath slatted floor). Five farms that combined conventional housing with one low-ammonia system (three reduced emitting surface and two manure cooling) were selected for a direct, pair-wise comparison of (olfactometric) odour emission measurements. The results show a highly significant effect (p < 0.01) for two of the three reduced emitting surface systems and for one of the two manure cooling system. The average odour reduction percentages of these systems are 35% (from 24.9 to 16.0 OUE/s per animal) and 23% (from 30.1 to 24.0 OUE/s per animal) respectively. Although odour emission reduction through the type of housing system is possible, management factors interact with the system and thereby determine whether the system reduces odour emission or not.

A widening health gap in general practice? Socio-economic differences in morbidity between 1975 and 2000 in The Netherlands.

BACKGROUND: During the past two decades, socio-economic inequalities in health have been a major research theme in Western Europe. Research has shown that there are persistent differences in health between people with a high socio-economic status (SES) compared with people with a low SES. There are also indications for a widening health gap. The present paper aimed to find out whether this widening health gap exists in The Netherlands using morbidity data from a general practice (GP) registry. METHODS: Incidence data from a GP registry were used, involving over 12,000 patients. Morbidity data from 1975 to 2000 were grouped into 25 disease categories. SES was based on household occupational status. Poisson regression was used to determine the relationship between morbidity and SES and its changes over time. Separate analyses were performed for men and women. RESULTS: In most disease categories, a clear SES gradient disadvantageous to the lowest-SES group was identified: 17 out of 22 morbidity categories for men and 17 out of 24 for women. For seven (men) and eight (women) morbidity categories out of 17, the SES gradient increased between 1975 and 2000. CONCLUSIONS: This study provides new evidence for a widening gap in health between higher and lower SES in The Netherlands, using GP-defined disease data and a wide range of morbidity categories.

A possible role of Eubacterium and Peptostreptococcus species in the aetiology of Crohn's disease.

The faecal flora of patients with Crohn's disease has been found to contain higher numbers of anaerobic gram-negative rods and gram-positive coccoid rods than the flora of healthy subjects. In a considerable percentage of sera from patients with Crohn's disease, agglutinating antibodies were found against four strains of the coccoid rods, in contrast to sera from patients with ulcerative colitis, other diseases and healthy subjects. In the present study, coccoid strains C18, Me46 and Me47 were found to activate complement by the alternative pathway. IgG antibodies to strains Me44, C18 and Me47 had opsonic properties but those to strain Me46 failed to induce phagocytosis. The data suggest an inadequate immune defence against strain Me46 in patients with Crohn's disease. The possible role of strain Me46 in the pathogenesis of Crohn's disease is discussed.