Clinical aspects of cardiac pacing for bradyarrhythmias

Since 1977, technological advances have made it possible, to incorporate a microprocessor in an implantable pacemaker. In 1980, the first devices with a microprocessor became available for patient use. At present, a single chip measuring a few square millimeters, contains more than a million active elements. The development of these micro-circuits is very expensive and therefore economically risky for small and medium sized pacemaker companies. Large investments in funds, design and evaluation time forced the pacemaker industry to employ multi-purpose micro-circuits. Microtechnology renders the feasibility to produce almost fully programmable pacemakers and provide the physician with the ability to adapt the device to specific patients needs. Telemetry functions are bidirectional, from programmer to pacemaker and visa versa. Real time intracardiac electrograms can be analyzed and malfunctions of battery or lead performance can be detected. Telemetry and programming functions have significantly decreased the need for surgical reinterventions. Clearly, microtechnology has created the progression from single-chamber fixed rate stimulation to dual-sensor rate- mediated dual-chamber pacing. Optimal cardiac pacing is critically dependent on the pacing mode, the underlying conduction disturbance and the myocardial function. Predictors of patient survival, hemodynamic and electrophysiological factors and the possibility of an adequate follow-up are factors to be considered for selection of the optimal pacing modality

A new strain of Shewanella putrefaciens isolated from the dead sea of Jordan

Halophilic bacteria flourish in environments with high salinities such as the Dead Sea of Jordan. In this current study, a new strain, assigned as DS4, was isolated from the Dead Sea of Jordan. The strain was identified based on biochemical and physiological characteristics, and it was further identified by 16S rDNA sequence analysis. DS4 was shown to be Gramnegative,oxidase-positive, non-lactose fermenting, and sulfide-producing on TSI medium. The strain was found to lack the following exoenzymes: amylase, gelatinase, and protease. Strain DS4 was able to grow at high salinity range of 3.4–4.5% NaCl and optimally at 4% NaCl. Furthermore, the 16S rRNA gene analysis revealed that the gene was 99% identical with the genes of several strains of Shewanella putrefaciens deposited in the public nucleotide database. Moreover, the antibiogram of this new strain was determined by well diffusion method. The strain was found to be sensitive to various antibiotics (at concentration of 10 mg ml-1) including cloxacillin, chloramphenicol, tetracycline, penicillin, and cyclohexamide. In view of all the above characteristics of strain DS4, it can be concluded that this isolate represents a new mild halophilic strain of Shewanella putrefaciens from the Dead Sea of Jordan

Inhibition of MT1-MMP proteolytic function and ERK1/2 signalling influences cell migration and invasion through changes in MMP-2 and MMP-9 levels

Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14) is a unique protease that cleaves extracellular proteins, activates proMMPs, and initiates intracellular signalling. MCF-7 cells are non-invasive and deficient in MT1-MMP, MMP-2, and MMP-9 expression. We created an MCF-7 cell line (C2) that stably produces active MT1-MMP and demonstrated increased ERK1/2 phosphorylation. MAPK inhibition in this cell line showed an inverse relationship in MMP-2 and MMP-9 transcripts where levels of these genes increased and decreased, respectively. Using invasive MDA-MB 231 cells that endogenously produce MT1-MMP and have naturally high pERK levels, we demonstrated the identical inverse relationship between MMP-2 and -9 transcript and protein levels, suggesting that this novel relationship is conserved amongst MT1-MMP positive breast cancer cells. To further analyze the relationship between MMP-2 and -9 levels, we chemically inhibited activation and catalytic activity of MT1-MMP using a furin and MMP inhibitor, respectively, to show that interference with the functions of MT1-MMP induced changes in MMP-2 and 9 transcript levels that were always inverse of each other, and likely mediated by differential transcriptional activity of the NF-κB transcription factor. Furthermore, we analyzed the functional consequences of these expression changes to show MMP, and in particular ERK, inhibition decreased migration and invasion using 2D culture, and inhibits the formation of an invasive phenotype in Matrigel 3D culture. This study demonstrated a novel inverse transcriptional relationship between MMP-2 and -9 levels and MT1-MMP activity that have functional consequences, and also showed that increases in the levels of MMPs does not necessarily correlate with an invasive phenotype

Studies on Parafilaria bovicola Tubangui, 1934 : 2. Chemotherapy and pathology

The filaricidal effects of trichlorphon, arsenic trioxide, sodium antimony biscathecol disulphonate and nitroxynil against Parafilaria bovicola were the subject of this investigation . Levamisole hydrochloride was retested in a separate trial to assess the time required for healing after successful treatment. A comparison of carcass lesions and the percentage of lesion area in untreated controls with those in treated animals reconfirmed the efficacy of levamisole hydrochloride, while nitroxynil gave more promising results. Both lesions and lesion area were reduced by 76% by the former and by 93% by the latter compound. The other drugs only slightly suppressed P. bovicola activity. After treatment with levamisole hydrochloride, active lesions were still present for 1-4 weeks and visible lesions on slaughter for 8 weeks. Since the visible lesions during the 8 weeks varied from acute to chronic and as they disappeared 9 weeks post treatment, it is suggested that provision should be made for a healing period of at least 9 weeks.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Effect of Changes in Climate and Emissions on Future Sulfate-Nitrate-Ammonium Aerosol Levels in the United States

Global simulations of sulfate, nitrate, and ammonium aerosols are performed for the present day and 2050 using the chemical transport model GEOS-Chem. Changes in climate and emissions projected by the IPCC A1B scenario are imposed separately and together, with the primary focus of the work on future inorganic aerosol levels over the United States. Climate change alone is predicted to lead to decreases in levels of sulfate and ammonium in the southeast U.S. but increases in the Midwest and northeast U.S. Nitrate concentrations are projected to decrease across the U.S. as a result of climate change alone. In the U.S., climate change alone can cause changes in annually averaged sulfate-nitrate-ammonium of up to 0.61 μg/m3, with seasonal changes often being much larger in magnitude. When changes in anthropogenic emissions are considered (with or without changes in climate), domestic sulfate concentrations are projected to decrease because of sulfur dioxide emission reductions, and nitrate concentrations are predicted to generally increase because of higher ammonia emissions combined with decreases in sulfate despite reductions in emissions of nitrogen oxides. The ammonium burden is projected to increase from 0.24 to 0.36 Tg, and the sulfate burden to increase from 0.28 to 0.40 Tg S as a result of globally higher ammonia and sulfate emissions in the future. The global nitrate burden is predicted to remain essentially constant at 0.35 Tg, with changes in both emissions and climate as a result of the competing effects of higher precursor emissions and increased temperature.Engineering and Applied Science

Social behavior assessment in cognitively impaired older adults using a passive and remote smartphone application

BACKGROUND: In Alzheimer's Disease (AD), loss of social interactions has a major impact on well-being. Therefore, AD patients would benefit from early detection of symptoms of social withdrawal. Current measurement techniques such as questionnaires are subjective and rely on recall, in contradiction to smartphone applications, which measure social behavior passively and objectively. Here, we examine social interactions through passive remote monitoring with the smartphone application BEHAPP in cognitively impaired participants. This study aims to investigate (1) the association between demographic characteristics and BEHAPP outcome variables in cognitively normal (CN) older adults, (2) if social behavior as measured using the passive smartphone app BEHAPP is impaired in cognitively impaired (CI) participants compared to subjects with subjective cognitive decline (SCD), and CN older adults. In addition, we explored in a subset of individuals the association between BEHAPP outcomes and neuropsychiatric symptoms. METHOD: CN (n=209), SCD (n=55) and CI (n=22) participants, older than 45 years, installed the BEHAPP app on their own Android smartphone for 7-42 days. CI participants had a clinical diagnosis of mild cognitive impairment or AD-type dementia. The app continuously measured communication events, application usage and location. Neuropsychiatric Inventory (NPI) total scores were available from 20 SCD and 22 CI participants. RESULT: We found that older cognitively healthy participants called less frequently and made less use of apps. No sex effects were found. Linear models corrected for age, sex and education showed that compared to the CN and SCD groups, CI participants called less unique contacts and contacted the same contacts relatively more often (Figure 1). They also made less use of apps, visited less unique places and traveled less far from home. Higher total NPI scores were associated with more unique stay points and further travelling. Similar behavior patterns were found when correcting for multiple comparisons. CONCLUSION: Cognitively impaired individuals show reduced social activity, as measured by the smartphone application BEHAPP. Neuropsychiatric symptoms seemed only marginally associated with social behavior as measured with BEHAPP. This research shows that a passive and remote smartphone application is able to objectively and passively measure altered social behavior in a cognitively impaired population

Variable expression of subclinical phenotypes instead of reduced penetrance in families with mild triphalangeal thumb phenotypes

Backgroun: The of zone of polarizing activity regulatory sequence (ZRS) is a regulatory element residing in intron 5 of LMBR1 and regulates Sonic Hedgehog expression in the limb bud. Variants in the ZRS are generally fully penetrant and can cause triphalangeal thumb (TPT) and polydactyly in affected families. Objective: In thisreport, we describe two families with mild phenotypical presentation Methods: Weperformed a field study for clinical evaluation and sequenced the ZRS for variantsusing Sanger sequencing. Results: In familyI, a novel 165A>G variant in the ZRS(g.156584405A>G, GRCh37/Hg19) was found. Infamily II, we identified a 295T>C variant inthe ZRS (g.156584535T>C, GRCh37/Hg19). Family members of both families who werepresumed to be unaffected shared the variant in the ZRS with affected familymembers, suggesting reduced penetrance of the genotype. However, clinicalexamination of these unaffected family members revealed minor anomalies likebroad thumbs and lack of thumb opposition. As the phenotype in affected patients is remarkably mild, we suggest that theseZRS variants are minimally disruptive for Sonic Hedgehog expression andtherefore can result in subclinical phenotypes. Conclusion: Our study underlines the importance of accurate clinical examination and appropriate genetic counselling in families with mild cases of TPT

3-D Shape Estimation of DNA Molecules from Stereo Cryo-Electron Micro-Graphs Using a Projection-Steerable Snake

We introduce a three-dimensional (3-D) parametric active contour algorithm for the shape estimation of DNA molecules from stereo cryo-electron micrographs. We estimate the shape by matching the projections of a 3-D global shape model with the micrographs; we choose the global model as a 3-D filament with a B-spline skeleton and a specified radial profile. The active contour algorithm iteratively updates the B-spline coefficients, which requires us to evaluate the projections and match them with the micrographs at every iteration. Since the evaluation of the projections of the global model is computationally expensive, we propose a fast algorithm based on locally approximating it by elongated blob-like templates. We introduce the concept of projection-steerability and derive a projection-steerable elongated template. Since the two-dimensional projections of such a blob at any 3-D orientation can be expressed as a linear combination of a few basis functions, matching the projections of such a 3-D template involves evaluating a weighted sum of inner products between the basis functions and the micrographs. The weights are simple functions of the 3-D orientation and the inner-products are evaluated efficiently by separable filtering. We choose an internal energy term that penalizes the average curvature magnitude. Since the exact length of the DNA molecule is known a priori, we introduce a constraint energy term that forces the curve to have this specified length. The sum of these energies along with the image energy derived from the matching process is minimized using the conjugate gradients algorithm. We validate the algorithm using real, as well as simulated, data and show that it performs well

Personal preferences for treatment and care during and after a First Episode Psychosis:A qualitative study

Aim: A first episode of psychosis (FEP) is a stressful, often life-changing experience. Scarce information is available about personal preferences regarding their care needs during and after a FEP. Whereas a more thorough understanding of these preferences is essential to aid shared decision-making during treatment and improve treatment satisfaction.Methods: Face-to-face interviews with participants in remission of a FEP were set up, addressing personal preferences and needs for care during and after a FEP. The interviews were conducted by a female and a male researcher, the latter being an expert with lived experience.Results: Twenty individuals in remission of a FEP were interviewed, of which 16 had been hospitalized. The distinguished themes based on personal preferences were tranquillity, peace and quietness, information, being understood, support from significant others, and practical guidance in rebuilding one's life. Our findings revealed that the need for information and the need to be heard were often not sufficiently met. For 16/20 participants, the tranquillity of inpatient treatment of the FEP was predominantly perceived as a welcome safe haven. The presence and support of family and close friends were mentioned as an important factor in the process of achieving remission.Conclusions: The current exploratory study showed that patients were able to indicate their personal needs. Important findings are the need for information and the need to be heard. Interestingly, hospitalization was mostly seen as an opportunity to achieve tranquillity. More lived experience expertise is needed to elucidate the needs of individuals in the early phase of a FEP to aid people who are recovering from their first psychosis in rebuilding their lives again.</p

High energy behaviour of gamma gamma to f f(bar) processes in SM and MSSM

We compute the leading logarithms electroweak contributions to gamma gamma to f f(bar) processes in SM and MSSM. Several interesting properties are pointed out, such as the importance of the angular dependent terms, of the Yukawa terms, and especially of the $\tan^2\beta$ dependence in the SUSY contributions. These properties are complementary to those found in e+e- to f f(bar). These radiative correction effects should be largely observable at future high energy gamma gamma colliders. Polarized beams would bring interesting checks of the structure of the one loop corrections. We finally discuss the need for two-loop calculations and resummation.Comment: 22 pages and 12 figures. e-mail: [email protected]