Diagnostic accuracy of MRI in differentiating hepatocellular adenoma from focal nodular hyperplasia: prospective study of the additional value of gadoxetate disodium.
The purpose of this article is to prospectively determine the sensitivity of hepatobiliary phase gadoxetate disodium-enhanced MRI combined with standard MRI in differentiating focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). Patients suspected of having FNH or HCA larger than 2 cm underwent gadoxetate disodium-enhanced MRI. Standard MRI was evaluated separately from the additional hepatobiliary phase by two blinded radiologists. For the largest lesion in each patient, findings were compared with histologic diagnosis. Sensitivity, positive predictive value (PPV), and distinctive features were analyzed using McNemar and analysis of variance tests. Fifty-two patients completed the study. Histologic diagnosis revealed 24 HCAs and 28 FNHs. Characterization on standard MRI was inconclusive in 40% (21/52) and conclusive in 60% (31/52) of lesions. The sensitivity of standard MRI for HCA was 50% (12/24) with a PPV of 100% (12/12). The sensitivity for FNH was 68% (19/28) with a PPV of 95% (18/19). After review of hepatobiliary phase, the sensitivity for HCA improved to 96% (23/24) with a PPV of 96% (23/24). The sensitivity for FNH improved to 96% (27/28) with a PPV of 96% (27/28). Features with significant predictive value for diagnosis in HCA included bleeding (p < 0.001), fat (p = 0.010), and glycogen (p = 0.024). The presence of a central scar was predictive for FNH (p < 0.001). This study shows high sensitivity of gadoxetate disodium-enhanced MRI when standard series are combined with the hepatobiliary phase for differentiation of FNH and HCA in lesions larger than 2 cm.


Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells.
Oxidative modification of lipoproteins is believed to be important in the genesis of atherosclerosis. We established cultures of smooth muscle cells (SMC) and exposed them to native LDL or oxidized LDL. Oxidized LDL, but not native LDL, was mitogenic as measured by incorporation of [3H]-thymidine into DNA. This effect was concentration dependent, averaged 288% of control, and was blocked by a platelet-activating factor (PAF) receptor antagonist. We hypothesized that phospholipids with PAF-like activity were generated during the oxidation of LDL. To test this hypothesis we extracted phospholipids from copper-oxidized LDL and assayed for PAF-like activity. Phospholipids extracted from oxidized LDL and purified by HPLC induced neutrophil adhesion equivalent to PAF (10 nM) and were mitogenic for smooth muscle cells. These effects were not seen with phospholipids extracted from native LDL and were blocked by two structurally different, competitive antagonists of the PAF receptor. The effects of these lipids were also abolished by pretreating them with PAF acetylhydrolase. Finally, we used Chinese hamster ovary cells that had seen stably transfected with a cDNA for the PAF receptor to confirm that phospholipids from oxidized LDL act via this receptor. We found that PAF (control) and the oxidized phospholipids each induced release of arachidonic acid from the transfected cells, but had no effect on wildtype Chinese hamster ovary cells, which lack the PAF receptor. This effect was also blocked by a PAF receptor antagonist. Thus, phospholipids generated during oxidative modification of LDL may participate in atherosclerosis by stimulating SMC proliferation and leukocyte activation.


Reconstruction From Multiple Particles for 3D Isotropic Resolution in Fluorescence Microscopy.
The imaging of proteins within macromolecular complexes has been limited by the low axial resolution of optical microscopes. To overcome this problem, we propose a novel computational reconstruction method that yields isotropic resolution in fluorescence imaging. The guiding principle is to reconstruct a single volume from the observations of multiple rotated particles. Our new operational framework detects particles, estimates their orientation, and reconstructs the final volume. The main challenge comes from the absence of initial template and a priori knowledge about the orientations. We formulate the estimation as a blind inverse problem, and propose a block-coordinate stochastic approach to solve the associated non-convex optimization problem. The reconstruction is performed jointly in multiple channels. We demonstrate that our method is able to reconstruct volumes with 3D isotropic resolution on simulated data. We also perform isotropic reconstructions from real experimental data of doubly labeled purified human centrioles. Our approach revealed the precise localization of the centriolar protein Cep63 around the centriole microtubule barrel. Overall, our method offers new perspectives for applications in biology that require the isotropic mapping of proteins within macromolecular assemblies.


Genome-wide analysis of cytogenetic aberrations in ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia.
The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1-positive childhood ALL patients by single nucleotide polymorphism array to explore acquired copy number alterations (CNAs) at diagnosis. The mean number of CNAs was 2·82 (range 0-14). Concordance with available G-band karyotyping and comparative genomic hybridization was 93%. Based on three major protein-protein complexes disrupted by these CNAs, patients could be categorized into four distinct subgroups, defined by different underlying biological mechanisms relevant to the aetiology of childhood ALL. When recurrent CNAs were evaluated by an oncogenetic tree analysis classifying their sequential order, the most common genetic aberrations (deletions of 6q, 9p, 13q and X, and gains of 10 and 21) seemed independent of each other. Finally, we identified the most common regions with recurrent gains and losses, which comprise microRNA clusters with known oncogenic or tumour-suppressive roles. The present study sheds further light on the genetic diversity of ETV6/RUNX1-positive childhood ALL, which may be important for understanding poor responses among this otherwise highly curable subset of ALL and lead to novel targeted treatment strategies.


Noise propagation in resolution modeled PET imaging and its impact on detectability.
Positron emission tomography imaging is affected by a number of resolution degrading phenomena, including positron range, photon non-collinearity and inter-crystal blurring. An approach to this issue is to model some or all of these effects within the image reconstruction task, referred to as resolution modeling (RM). This approach is commonly observed to yield images of higher resolution and subsequently contrast, and can be thought of as improving the modulation transfer function. Nonetheless, RM can substantially alter the noise distribution. In this work, we utilize noise propagation models in order to accurately characterize the noise texture of reconstructed images in the presence of RM. Furthermore we consider the task of lesion or defect detection, which is highly determined by the noise distribution as quantified using the noise power spectrum. Ultimately, we use this framework to demonstrate why conventional trade-off analyses (e.g. contrast versus noise, using simplistic noise metrics) do not provide a complete picture of the impact of RM and that improved performance of RM according to such analyses does not necessarily translate to the superiority of RM in detection task performance.


Field assessment of dried Plasmodium falciparum samples for malaria rapid diagnostic test quality control and proficiency testing in Ethiopia.
Rapid diagnostic tests (RDTs) are now widely used for laboratory confirmation of suspected malaria cases to comply with the World Health Organization recommendation for universal testing before treatment. However, many malaria programmes lack quality control (QC) processes to assess RDT use under field conditions. Prior research showed the feasibility of using the dried tube specimen (DTS) method for preserving Plasmodium falciparum parasites for use as QC samples for RDTs. This study focused on the use of DTS for RDT QC and proficiency testing under field conditions. DTS were prepared using cultured P. falciparum at densities of 500 and 1,000 parasites/μL; 50 μL aliquots of these along with parasite negative human blood controls (0 parasites/μL) were air-dried in specimen tubes and reactivity verified after rehydration. The DTS were used in a field study in the Oromia Region of Ethiopia. Replicate DTS samples containing 0, 500 and 1,000 parasites/μL were stored at 4°C at a reference laboratory and at ambient temperatures at two nearby health facilities. At weeks 0, 4, 8, 12, 16, 20, and 24, the DTS were rehydrated and tested on RDTs stored under manufacturer-recommended temperatures at the RL and on RDTs stored under site-specific conditions at the two health facilities. Reactivity of DTS stored at 4°C at the reference laboratory on RDTs stored at the reference laboratory was considered the gold standard for assessing DTS stability. A proficiency-testing panel consisting of one negative and three positive samples, monitored with a checklist was administered at weeks 12 and 24. At all the seven time points, DTS stored at both the reference laboratory and health facility were reactive on RDTs stored under the recommended temperature and under field conditions, and the DTS without malaria parasites were negative. At the reference laboratory and one health facility, a 500 parasites/μL DTS from the proficiency panel was falsely reported as negative at week 24 due to errors in interpreting faint test lines. The DTS method can be used under field conditions to supplement other RDT QC methods and health worker proficiency in Ethiopia and possibly other malaria-endemic countries.


Hepatitis C virus non-structural 3/4A protein interferes with intrahepatic interferon-γ production.
The non-structural (NS) 3/4A protease/helicase of the hepatitis C virus is known to modulate signalling pathways in the infected hepatocyte by cleaving CARD adaptor inducing IFNβ (Cardif), T-cell protein tyrosine phosphatase (TC-PTP) and TIR domain-containing adaptor inducing IFNβ (TRIF), but the effects of NS3/4A in vivo still remain unclear. To investigate the influence of NS3/4A on intracellular and intercellular signalling in vivo by analysing the intrahepatic inflammatory response of naïve, lipopolysaccharide (LPS)/D-galactosamine (D-galN) or tumour necrosis factor-α (TNFα)/D-galN-treated NS3/4A-transgenic (Tg) mice. The intrahepatic immunity of naïve and LPS/D-galN- or TNFα/D-galN-treated NS3/4A-Tg mice was determined using western blot, ELISA, real-time PCR, flow cytometry and survival monitoring. The injection of cytokines or antibodies against signalling components was performed to analyse the relevance of the respective pathways for the investigated issues. A Tg mouse lineage expressing an inactivated NS3/4A protease (NS3/4A(Ile1073Ala)-Tgs) was generated to examine if protective effects were NS3/4A protease dependent. The activation of hepatic signal transducer and activator of transcription 1 and 2 was impaired in NS3/4A-Tg mice after treatment with LPS/D-galN or TNFα/D-galN. This was paralleled by a reduction in hepatic interferon-γ (IFNγ). Reconstitution of IFNγ reverted the resistance to LPS/TNFα in NS3/4A-Tg mice. Subsequently, blocking IFNγ in vivo rendered wild-type mice resistant against treatment with LPS/TNFα. A new Tg mouse expressing an inactivated NS3/4A protease had the same phenotype as wild-type mice with respect to hepatic IFNγ levels and sensitivity to LPS/d-galN. Finally, the chemokine profile was altered in the NS3/4A-Tg mice towards an anti-inflammatory state, which helps to explain the altered immune cell subsets and reduction in hepatic IFNγ production. Our data demonstrate that the NS3/4A protease reduces the intrahepatic production of IFNγ and alters TNFα-mediated effects, thereby impairing the hepatic inflammatory response. This may contribute to viral persistence.


Weakly Anisotropic Dielectric Properties of Water Droplets at the Nanoscale.
The slab-confined water at the nanoscale exhibits anomalous dielectric properties compared to bulk water, for example, significantly low dielectric constant. In this work, we study the dielectric properties of nanoscale water droplets at room temperature using molecular dynamics simulations. We find that the nanoscale water droplets feature weakly anisotropic dielectric constant: the radial component of dielectric constants is distinctly smaller than the tangential component although they both decrease with reducing droplet size in a similar way. Such dielectric behavior is closely related to the orientational preference of water molecules near the convex surface. The molecular dipole prefers to slightly orientate toward the interior of droplets in contrast to the out-of-plane preference for free-standing water films and slab-confined water, which suppresses the fluctuation of dipole moments in the radial direction. Meanwhile, it facilitates the formation of the open hydrogen-bond network in the surface layer and ultimately leads to the relatively weak suppression of tangential fluctuations. The differential suppression is responsible for the anisotropic dielectric constant of water droplets. This anisotropic characteristic is also found in dielectric relaxation: both the radial and the tangential relaxation are consistently slowed down upon approaching surface but the latter is universally slower.


Fibrolamellar hepatocellular carcinoma.
Fibrolamellar hepatocellular carcinoma is a primary malignant tumor of the liver that usually affects adolescents and young adults. If detected early, this cancer is frequently resectable, with a much longer survival time than in classic hepatocellular carcinoma. Fibrolamellar hepatocellular carcinoma has distinct radiographic and pathologic features. Serum unsaturated vitamin B12 binding capacity and plasma neurotensin may be used as tumor markers.


Growth Effects on Velopharyngeal Anatomy From Childhood to Adulthood.
Purpose The observed sexual dimorphism of velopharyngeal structures among adult populations has not been observed in the young child (4- to 9-year-old) population. The purpose of this study was to examine the age at which sexual dimorphism of velopharyngeal structures become apparent and to examine how growth trends vary between boys and girls. Method Static 3-dimensional magnetic resonance imaging velopharyngeal data were collected among 202 participants ranging from 4 to 21 years of age. Participants were divided into 3 groups based on age, including Group 1: 4-10 years of age, Group 2: 11-17 years of age, and Group 3: 18-21 years of age. Nine velopharyngeal measures were obtained and compared between groups. Results Significant sex effects were evident for levator length ( p = .011), origin to origin ( p = .018), and velopharyngeal ratio ( p = .036) for those in Group 2 (11-17 years of age). Sex effects became increasingly apparent with age, with 7 of 9 variables becoming significantly different between male and female participants in Group 3. Boys, in general, displayed a delayed growth peak in velopharyngeal growth compared to girls. Conclusion Results from this study demonstrate the growth of velopharyngeal anatomy with sexual dimorphism becoming apparent predominantly after 18 years of age. However, velopharyngeal variables displayed variable growth trends with some variables presenting sexual dimorphism at an earlier age compared to other velopharyngeal variables.


Environmental enrichment holds promise as a novel treatment for anesthesia-induced neurocognitive disorders.
In recent years, since the need for anesthetic interventions in pregnant women, newborns, and older patients has been increasing, the anesthesia-induced cognitive impairment has received widespread attention and highlighted the urgent requirement for preventive and therapeutic measures with low risk of side effects. Environmental enrichment (EE), a novel and easy-to-implement rehabilitation treatment strategy, exerts its protective potential on the cognitive abilities of developing and aging brains after anesthetic exposure. This review summarizes the improvement of cognition by EE described in recent studies and explores the molecular mechanisms by which EE exerts neuroprotective effects. The literature indicates that the intervention mode, timing, and duration of EE are vital to its effect.


[Optimization of obtaining magnetic resonance images in relation to ultra-low fields].
The authors discuss possible approaches to optimization of magnetic resonance images in connection with ultralow fields with consideration for external and internal factors modifying the contrast. Of the internal factors the crucial role is played by protonic density and relaxation time of different tissues; the internal factors significant are magnetic induction, characteristics of the device and programs, radiofrequency sequence and its parameters, as well as use of special contrast agents. Practical measures whose use helps optimize a magnetic resonance image, that is, the choice of an adequate pulse sequence, a greater number of repetitions, a larger imaging field, a thicker section and its better orientation, are described. Standard schemes for obtaining MR images of various organs with due account of the before factors with an ultralow field tomographer have been developed.


Identifying treatment effects of an informal caregiver education intervention to increase days in the community and decrease caregiver distress: a machine-learning secondary analysis of subgroup effects in the HI-FIVES randomized clinical trial.
Informal caregivers report substantial burden and depressive symptoms which predict higher rates of patient institutionalization. While caregiver education interventions may reduce caregiver distress and decrease the use of long-term institutional care, evidence is mixed. Inconsistent findings across studies may be the result of reporting average treatment effects which do not account for how effects differ by participant characteristics. We apply a machine-learning approach to randomized clinical trial (RCT) data of the Helping Invested Family Members Improve Veteran's Experiences Study (HI-FIVES) intervention to explore how intervention effects vary by caregiver and patient characteristics. We used model-based recursive partitioning models. Caregivers of community-residing older adult US veterans with functional or cognitive impairment at a single VA Medical Center site were randomized to receive HI-FIVES (n = 118) vs. usual care (n = 123). The outcomes included cumulative days not in the community and caregiver depressive symptoms assessed at 12 months post intervention. Potential moderating characteristics were: veteran age, caregiver age, caregiver ethnicity and race, relationship satisfaction, caregiver burden, perceived financial strain, caregiver depressive symptoms, and patient risk score. The effect of HI-FIVES on days not at home was moderated by caregiver burden (p < 0.001); treatment effects were higher for caregivers with a Zarit Burden Scale score ≤ 28. Caregivers with lower baseline Center for Epidemiologic Studies Depression Scale (CESD-10) scores (≤ 8) had slightly lower CESD-10 scores at follow-up (p < 0.001). Family caregiver education interventions may be less beneficial for highly burdened and distressed caregivers; these caregivers may require a more tailored approach that involves assessing caregiver needs and developing personalized approaches. ClinicalTrials.gov, ID:NCT01777490. Registered on 28 January 2013.


Interventions for HIV clients with co-occurring substance use and personality disorders.
Many HIV/AIDS clients who currently need some form of psychosocial intervention are individuals diagnosed with substance use, a mental health problem, or both. In any setting a proportion of these clients, because of their behaviors, present myriad challenges to individual providers in terms of engagement in medical care, medication adherence, and difficulty with interpersonal skills. These clients struggle with how to appropriately express their needs. Providers struggle to understand and respond to clients' escalating and disruptive behaviors in a therapeutic, concerned, and consistent manner. This case-based article, which highlights strategies, interventions, and client vignettes, will focus on these issues.


[Particulate matter in indoor environments--exposure situation in residences, schools, pubs, and related recreational spaces].
Numerous epidemiological studies have been carried out during the last decades which have demonstrated an association between the pollution of outside air with toxic substances and the occurrence of health-related effects. Against the background of these findings, particularly in recent years, the focus of research has clearly shifted towards particulate matter (PM), notable fine and ultrafine particles. While diverse measurements of PM in the outside air have been conducted, only few data on indoor air pollution are available. The concentration of PM in the indoor environment is highly variable in time and space due to various influencing factors like type of the source, building and room characteristics, the activities of users and the airing behaviour. In this article we aim to summarise and discuss the exposure situation regarding PM in indoor environments. In residences, European studies have found mean PM (2.5) values between 10 and 87 microg/m (3). Especially in smokers' homes, a high background level was observed, reaching very high concentrations of some hundred microg/m (3) when active smoking took place. There are some studies on air quality in schools and similar public places which show that exposure to particulate matter in these environments is high. The main causes of this situation appear to be an insufficient ventilation routine as well as the low frequency and quality of cleaning. In combination with the high number of pupils in relation to room area and volume and their sometimes high physical activity, this leads to a continued resuspension of particles from the room's surfaces. A very high concentration of PM can be observed in those recreational places where smoking is not prohibited, such as discotheques, pubs and restaurants. Here, the mean PM values can reach some hundred microg/m (3). Specific strategies are necessary to especially protect the health of non-smokers in such places. Further investigations are needed to characterise the composition of indoor particles and their toxicological properties compared to particles from outdoor origin.


Bronchial epithelial cell-cytokine interactions in airway inflammation.
A variety of cytokine bronchial cell interactions may play an important role in normal host defense as well as in the pathogenesis of inflammatory airway disorders such as asthma, cystic fibrosis, acute and chronic bronchitis, and bronchiectasis. First, airway epithelial cells may participate in local cytokine networks by synthesizing interleukins, chemokines, colony stimulating factors and growth factors in response to inflammatory mediators. Bronchial epithelial cell derived cytokines may thereby amplify ongoing inflammatory processes via the recruitment and activation of specific subsets of inflammatory cells, as well as by prolonging their survival in the airway microenvironment. Second, airway epithelial cells can initiate inflammatory cascades by generating cytokines in direct response to viral and bacterial products, noxious gases, and sensitizing chemicals. Third, airway epithelial cells represent targets for paracrine acting cytokines, which may then modulate bronchial epithelial cell functions. Finally, airway epithelial cells may modulate ongoing inflammatory events in the airway microenvironment via the shedding of soluble TNF receptors. Cytokine-bronchial epithelial cell interactions represent an important mechanism by which inflammatory events in the airway microenvironment can be regulated and represent potential targets for novel anti-inflammatory therapies in airway disorders.


Genetic Manipulation of Human Embryonic Stem Cells.
One of the great advantages of embryonic stem (ES) cells over other cell types is their accessibility to genetic manipulation. They can easily undergo genetic modifications while remaining pluripotent, and can be selectively propagated, allowing the clonal expansion of genetically altered cells in culture. Since the first isolation of ES cells in mice, many effective techniques have been developed for gene delivery and manipulation of ES cells. These include transfection, electroporation, and infection protocols, as well as different approaches for inserting, deleting, or changing the expression of genes. These methods proved to be extremely useful in mouse ES cells, for monitoring and directing differentiation, discovering unknown genes, and studying their function, and are now being extensively implemented in human ES cells (HESCs). This chapter describes the different approaches and methodologies that have been applied for the genetic manipulation of HESCs and their applications. Detailed protocols for generating clones of genetically modified HESCs by transfection, electroporation, and infection will be described, with special emphasis on the important technical details that are required for this purpose. All protocols are equally effective in human-induced pluripotent stem (iPS) cells.


Community education for cardiovascular disease prevention. Morbidity and mortality results from the Minnesota Heart Health Program.
The Minnesota Heart Health Program was a community trial of cardiovascular disease prevention methods that was conducted from 1980 to 1990 in three Upper Midwestern communities with three matched comparison communities. A 5- to 6-year intervention program used community-wide and individual health education in an attempt to decrease population risk. A major hypothesis was that the incidence of validated fatal and nonfatal coronary heart disease and stroke in 30- to 74-year-old men and women would decline differentially in the education communities after the health promotion program was introduced. This hypothesis was investigated using mixed-model regression. The intervention effect was modeled as a series of annual departures from a linear secular trend after a 2-year lag from the start of the intervention program. In the education communities, 2,394 cases of coronary heart disease and 818 cases of stroke occurred, with 2,526 and 739 cases, respectively, being seen in the comparison communities. The overall decline in coronary heart disease incidence was 1.8 percent per year in men (p = 0.03) and 3.6 percent per year in women (p = 0.007). For stroke, there were no significant secular trends. The authors recently published findings showing minimal effects of sustained intervention on risk factor levels. In the current report, there was no evidence of a significant intervention effect on morbidity or mortality, either for coronary heart disease or for stroke.


Effect of a broad-specificity chemokine-binding protein on brain leukocyte infiltration and infarct development.
Expression of numerous chemokine-related genes is increased in the brain after ischemic stroke. Here, we tested whether post-stroke administration of a chemokine-binding protein (CBP), derived from the parapoxvirus bovine papular stomatitis virus, might reduce infiltration of leukocytes into the brain and consequently limit infarct development. The binding spectrum of the CBP was evaluated in chemokine ELISAs, and binding affinity was determined using surface plasmon resonance. Focal stroke was induced in C57Bl/6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion for 23 or 47 hours. Mice were treated intravenously with either bovine serum albumin (10 μg) or CBP (10 μg) at the commencement of reperfusion. At 24 or 48 hours, we assessed plasma levels of the chemokines CCL2/MCP-1 and CXCL2/MIP-2, as well as neurological deficit, brain leukocyte infiltration, and infarct volume. The CBP interacted with a broad spectrum of CC, CXC, and XC chemokines and bound CCL2/MCP-1 and CXCL2/MIP-2 with high affinity (pM range). Stroke markedly increased plasma levels of CCL2/MCP-1 and CXCL2/MIP-2, as well as numbers of microglia and infiltrating leukocytes in the brain. Increases in plasma chemokines were blocked in mice treated with CBP, in which there was reduced neurological deficit, fewer brain-infiltrating leukocytes, and ≈50% smaller infarcts at 24 hours compared with bovine serum albumin-treated mice. However, CBP treatment was no longer protective at 48 hours. Post-stroke administration of CBP can reduce plasma chemokine levels in association with temporary atten uation of brain inflammation and infarct volume development.


Activation of Group II Metabotropic Glutamate Receptors Promotes LTP Induction at Schaffer Collateral-CA1 Pyramidal Cell Synapses by Priming NMDA Receptors.
It is well established that selective activation of group I metabotropic glutamate (mGlu) receptors induces LTD of synaptic transmission at Schaffer collateral-CA1 synapses. In contrast, application of 1S,3R-ACPD, a mixed agonist at group I and group II mGlu receptors, induces LTP. Using whole-cell recordings from CA1 pyramidal cells and field recordings in the hippocampal CA1 region, we investigated the specific contribution of group II mGlu receptors to synaptic plasticity at Schaffer collateral-CA1 synapses in acute slices of adult mice. Pharmacological activation of group II mGlu receptors (mGlu2 and mGlu3 receptors) with the specific agonist LY354740 in conjunction with electrical stimulation induced postsynaptic LTP. This form of plasticity requires coactivation of NMDA receptors (NMDARs). Group II mGlu receptor activation led to PKC-dependent phosphorylation of the GluN1 subunit. We found that both synaptic and extrasynaptic NMDARs, which are differentially modulated by mGlu2 and mGlu3 receptors, contribute to LTP induction. Furthermore, LTP initiated by activation of group II mGlu receptors was not occluded by LTP induced with high-frequency trains of stimuli. However, the phosphorylation of NMDARs mediated by group II mGlu receptor activation led to a priming effect that enhanced subsequent high-frequency stimulation-induced LTP. These findings reveal a novel metaplastic mechanism through which group II mGlu receptors modulate synaptic function at the Schaffer collateral input to CA1 pyramidal cells, thereby lowering the threshold to induce plasticity. The group II metabotropic glutamate (mGlu II) receptors exert a well characterized action on presynaptic neuron terminals to modulate neurotransmitter release. Here, we show that these receptors also have postsynaptic effects in promoting the induction of synaptic plasticity. Using an electrophysiological approach including field and whole-cell patch recording in hippocampi from wild-type and transgenic mice, we show that activation of group II mGlu receptors enhances NMDA receptor (NMDAR)-mediated currents through PKC-dependent phosphorylation. This priming of NMDARs lowers the threshold for the induction of LTP of synaptic transmission. These findings may also provide new insights into the mechanisms through which drugs targeting mGlu II receptors alleviate hypoglutamatergic conditions such as those occurring in certain brain disorders such as schizophrenia.


[Inversion recovery RARE: clinical use of a T2-weighted CSF-suppressed rapid sequence].
Inversion-Recovery RARE is a strongly T2-weighted fast sequence in which the CSF appears dark. This sequence was used in more than 100 patients. Retrospective analysis of 80 patients with cerebrovascular and inflammatory disease was carried out. The IR-RARE sequence proved to be particularly suitable for identifying small lesions in the neighbourhood of the subarachnoid space. We illustrate the typical contrast provided by this sequence, and describe its characteristics, exemplifying the advantages it offers for the diagnosis of multiple sclerosis, cerebral microangiopathy and brain infarction.


Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes.
Hyponatremia is the most common electrolyte abnormality in clinical practice, yet little is known about its frequency in patients with cancer or its impact on their clinical outcomes. Retrospective analysis of prospectively collected data. Patients with cancer admitted to the University of Texas M.D. Anderson Cancer Center in 2006 for 3 months. Serum sodium levels categorized as eunatremia (serum sodium, 135-147 mEq/L) and mild (134-130 mEq/L), moderate (129-120 mEq/L), and severe (<120 mEq/L) hyponatremia. (1) Length of hospital stay and (2) 90-day mortality. In 4,702 admissions in 3,357 patients with cancer, hyponatremia (serum sodium <135 mEq/L) was noted in 47% of admissions. It was mild in 36%, moderate in 10%, and severe in 1%. Hyponatremia was acquired during the hospital stay in 24%. Using the first admission data, mean length of stay was 5.6 ± 5.0 days for patients with eunatremia and 9.9 ± 9.2, 13.0 ± 14.1, and 11.5 ± 12.6 days for those with mild, moderate, and severe hyponatremia, respectively. The respective HRs in the multivariate Cox model for longer hospital stay, using patients with eunatremia as reference, were 1.92 (95% CI, 1.75-2.13; P < 0.01), 2.94 (95% CI, 2.56-3.45; P < 0.01), and 2.32 (95% CI, 1.32-4.00; P = 0.01). 283 (8.4%) deaths occurred during 90 days, and in the multivariate model, the respective HRs for 90-day mortality for mild, moderate, and severe hyponatremia were 2.04 (95% CI, 1.42-2.91; P < 0.01); 4.74 (95% CI, 3.21-7.01; P < 0.01), and 3.46 (95% CI, 1.05-11.44; P = 0.04). These findings were consistent when analyses were repeated with sodium levels in tertiles. Observational study, retrospective, inability to adjust for all comorbid conditions. Hyponatremia in patients with cancer is associated with longer hospital stay and higher mortality. Whether long-term correction of hyponatremia would improve these outcomes remains to be determined.


Adaptogenic herb ginseng (Panax) as medical food: Status quo and future prospects.
Ginseng, an herbaceous plant, belonging to the family Araliaceae is a traditional medicinal herb. Also, it is emerging as a functional food and potent adjunct medicine. Saponin ginsenosides (protopanaxadiol and protopanaxatriol) are the signature phytochemicals of this plant. With the surfacing of scientific validations, ginseng is gaining unprecedented attention from consumers as well as researchers. As a number of drug-herb interaction-caused health issues have emerged, the medicinal relevance of this plant has been critically assessed here. In this regard, the recent publications on health benefits of ginseng have been extracted from NCBI and ScienceDirect database. The claimed antioxidant, anti-inflammation, anti-fatigue, antidiabetic, antitumor, immunomodulation, anti-obesity, cardioprotective, antimicrobial, neuroprotective and aphrodisiac properties have been analyzed. This review presents a fair assessment and insights on complementary and alternative medicine (CAM) potential of this herb.


Oxidized lipid accumulates in the presence of alpha-tocopherol in atherosclerosis.
Oxidative modification of low-density lipoproteins in the arterial wall is a key feature of atherogenesis and widely believed to cause and/or accelerate lesion development. Linked to this is the expectation that vascular antioxidants are depleted during oxidation in vivo. However, whether alpha-tocopherol (vitamin E), an important lipid-soluble antioxidant, is depleted early in atherogenesis and can prevent lipid peroxidation in vivo is unresolved. To address this we examined the content of specific configurational isomers (cis/trans) of lipid hydro(pero)xides in lesions, which represent the major non-enzymic oxidation products, as formation and accumulation of cis/trans isomers is influenced by alpha-tocopherol in studies in vitro. Concordant with our previous findings that large amounts of oxidized lipid co-exist with relatively normal alpha-tocopherol levels in human lesions, we now show that cis/trans isomers predominate over other products in human carotid and aortic lesions and in lesion lipoproteins. Further, dietary vitamin E supplementation of rabbits after arterial injury significantly increases both the aortic levels of alpha-tocopherol and the overall content of cis/trans isomers. These data are fully consistent with alpha-tocopherol acting as a hydrogen donor during lipid oxidation in vivo and suggest that alpha-tocopherol does not prevent lipoprotein lipid oxidation in the diseased vessel wall.


Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study.
Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. Gastric bypass surgery. Incidence of new DR and other diabetic ocular complications. The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6% (1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5% (1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P < .001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment.


Effect of salivary stimulation on erosion of human and bovine enamel subjected or not to subsequent abrasion: an in situ/ex vivo study.
This in situ/ex vivo study evaluated whether saliva stimulated by chewing gum could prevent or reduce the wear and the percent change in microhardness (%SMH) of bovine and human enamel submitted to erosion followed by brushing abrasion immediately or after 1 h. During 2 experimental 7-day crossover phases, 9 previously selected volunteers wore intraoral palatal devices, with 12 enamel specimens (6 human and 6 bovine). In the first phase, the volunteers immersed the device for 5 min in 150 ml of cola drink, 4 times per day (at 8, 12, 16 and 20 h). Immediately after the immersions, no treatment was performed in 4 specimens, 4 other specimens were immediately brushed (0 min) using a fluoride dentifrice, and the device was replaced into the mouth. After 60 min, the remaining 4 specimens were brushed. In the second phase, the procedures were repeated, but after the immersions, the volunteers stimulated the salivary flow rate by chewing a sugar-free gum for 30 min. Changes in wear and %SMH were measured. ANOVA and Tukey's test showed statistical differences (p<0.05) for the following comparisons. The chewing gum promoted less wear and %SMH. A decreasing %SMH and an increasing enamel wear were observed in the following conditions: erosion only, 60 min and 0 min. The human enamel presented greater %SMH and less wear compared to bovine enamel. The data suggest that the salivary stimulation after an erosive or erosive/abrasive attack can reduce the dental wear and the %SMH.


Fission yeast Rad26 is a regulatory subunit of the Rad3 checkpoint kinase.
Fission yeast Rad3 is a member of a family of phosphoinositide 3-kinase -related kinases required for the maintenance of genomic stability in all eukaryotic cells. In fission yeast, Rad3 regulates the cell cycle arrest and recovery activities associated with the G2/M checkpoint. We have developed an assay that directly measures Rad3 kinase activity in cells expressing physiological levels of the protein. Using the assay, we demonstrate directly that Rad3 kinase activity is stimulated by checkpoint signals. Of the five other G2/M checkpoint proteins (Hus1, Rad1, Rad9, Rad17, and Rad26), only Rad26 was required for Rad3 kinase activity. Because Rad26 has previously been shown to interact constitutively with Rad3, our results demonstrate that Rad26 is a regulatory subunit, and Rad3 is the catalytic subunit, of the Rad3/Rad26 kinase complex. Analysis of Rad26/Rad3 kinase activation in rad26.T12, a mutant that is proficient for cell cycle arrest, but defective in recovery, suggests that these two responses to checkpoint signals require quantitatively different levels of kinase activity from the Rad3/Rad26 complex.


Development and validation of spectrophotometric methods for determination of ceftazidime in pharmaceutical dosage forms.
Two spectrophotometric methods for the determination of ceftazidime (CFZM) in either pure form or in its pharmaceutical formulations are described. The first method is based on the reaction of 3-methylbenzothiazolin-2-one hydrazone (MBTH) with ceftazidime in the presence of ferric chloride in acidic medium. The resulting blue complex absorbs at lambdamax 628 nm. The second method describes the reaction between the diazotized drug and N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA) to yield a purple colored product with lambdamax at 567 nm. The reaction conditions were optimized to obtain maximum color intensity. The absorbance was found to increase linearly with increasing the concentration of CFZM; the systems obeyed the Beer's law in the range 2-10 and 10-50 microg mL-1 for MBTH and NEDA methods, resp. LOD, LOQ and correlation coefficient values were 0.15, 0.79 and 0.50, 2.61. No interference was observed from common excipients present in pharmaceutical formulations. The proposed methods are simple, sensitive, accurate and suitable for quality control applications.


Sex Differences in Ablation Strategy, Lesion Sets, and Complications of Catheter Ablation for Atrial Fibrillation: An Analysis From the GWTG-AFIB Registry.
When presenting for atrial fibrillation (AF) ablation, women, compared with men, tend to have more nonpulmonary vein triggers and advanced atrial disease. Whether this informs differences in AF ablation strategy is not well described. We aimed to characterize ablation strategy and complications by sex, using the Get With The Guidelines-AF registry. From the Get With The Guidelines-AF registry ablation feature, we included patients who underwent initial AF ablation procedure between January 7, 2016, and December 27, 2019. Patients were stratified based on AF type (paroxysmal versus nonparoxysmal) and sex. We compared patient demographics, ablation strategy, and complications by sex. Among 5356 patients from 31 sites who underwent AF ablation, 1969 were women (36.8%). Women, compared with men, were older (66.8±9.6 versus 63.4±10.6, P<0.0001) and were more likely to have paroxysmal AF (59.4% versus 49.5%, P<0.0001). In women with nonparoxysmal AF, left atrial linear ablation was more frequent (roof line: 53.9% versus 45.3%, P=0.0002; inferior mitral isthmus line: 10.2% versus 7.0%, P=0.01; floor line: 46.1% versus 40.6%, P=0.02) than in men. In multivariable analysis, the association between patient sex and complications from ablation was not statistically significant. In this US wide AF ablation quality improvement registry, women with nonparoxysmal AF were more likely to receive adjunctive lesion sets compared with men. These findings suggest that patient sex may inform ablation strategy in ways that may not be strongly supported by evidence and emphasize the need to clarify optimal ablation strategies by sex.


Optimization and validation of a bioanalytical HPLC-UV technique for simultaneous determination of underivatized phenylalanine and tyrosine in the blood for phenylketonuria diagnosis and monitoring.
This study aimed to develop a fast, accurate, and precise high-performance liquid chromatography with UV detection method for simultaneous analysis of underivatized phenylalanine (Phe) and tyrosine (Tyr) in biological samples. Separation of the analytes was accomplished using a Discovery HS F5-3 column, which offered better retention and peak symmetry for the tested analytes. Chromatographic conditions were optimized using central composite experimental design, and three factors were investigated: the concentration of ammonium acetate (A), the acetonitrile proportion in the mobile phase (B) and the column oven temperature (C). The approach was verified using β-expectation tolerance intervals for total error measurement that did not exceed 15%. Optimal settings were A = 50 mm, B = 24% and C = 28°C. The method applicability was determined using human plasma from 75 volunteers. The limits of detection and quantification of the technique were satisfactory at 9 and 29 μm for Phe and 4 and 13 μm for Tyr. The mean analytical bias in spiking levels was acceptable, ranging from -1.649 to +1.659% for both substances, with RSD <5% in all instances. The suggested approach was successfully used to analyze Phe and Tyr in human blood samples and calculate the Phe/Tyr ratio.


Pancreatic cancer: utility of dynamic contrast-enhanced MR imaging in assessment of antiangiogenic therapy.
To prospectively evaluate the utility of dynamic contrast material-enhanced magnetic resonance (MR) imaging in predicting the response of locally advanced pancreatic cancer to combined chemotherapy and antiangiogenic therapy. This prospective, institutional review board-approved, HIPAA-compliant study with informed consent assessed dynamic contrast-enhanced MR imaging in 11 patients (mean age, 54.3 years; six men and five women) with locally invasive pancreatic cancer before and 28 days after combined chemotherapy and antiangiogenic therapy. Axial perfusion images were obtained after injection of 0.1 mmol gadopentetate dimeglumine per kilogram of body weight. Sagittal images of the upper abdominal aorta were obtained for arterial input function calculation. A two-compartment kinetic model was used to calculate the perfusion parameters K(trans) (the rate constant that represents transfer of contrast agent from the arterial blood into the extravascular extracellular space), K(ep) (the rate constant that represents transfer of contrast agent from the extravascular extracellular space to the blood plasma), and volume of distribution (v(e)). Semiquantitative measurements, peak tissue gadolinium concentration (C(peak)), maximum slope of gadolinium increase (slope), and area under the gadolinium curve at 60 seconds (AUC(60)) were also calculated. Perfusion parameters and tumor size changes were correlated with carbohydrate antigen 19-9 levels. Comparisons between pre- and posttreatment studies were performed by using the Wilcoxon signed rank test, and comparisons between responders and nonresponders were performed by using the Mann-Whitney test. After therapy, K(trans), v(e), C(peak), slope, and AUC(60) decreased significantly (P = .02, .001, .002, .007, and .01, respectively). Tumor size and K(ep) were not significantly changed. Pretreatment K(trans) and K(ep) were significantly higher (P = .02 and .006, respectively) in tumors that showed marker response than in those that did not. A pretreatment K(trans) value (milliliters of blood per milliliter of tissue times minutes) of more than 0.78 mL/mL . min was 100% sensitive and 71% specific for subsequent tumor response. Semiquantative parameters and tumor size were not different between the groups. Pretreatment K(trans) measurement in pancreatic tumors can predict response to antiangiogenic therapy. All perfusion parameters showed substantial reduction after 28 days of combined chemotherapy and antiangiogenic therapy.


Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial.
The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.


AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech.
Recent studies demonstrated that allograft inflammatory factor-1 (AIF-1) and RNASET2 act as chemoattractants for macrophages and modulate the inflammatory processes in both vertebrates and invertebrates. The expression of these proteins significantly increases after bacterial infection; however, the mechanisms by which they regulate the innate immune response are still poorly defined. Here, we evaluate the effect of bacterial lipopolysaccharide injection on the expression pattern of these genes and the interrelation between them during innate immune response in the medicinal leech, an invertebrate model with a simple anatomy and a marked similarity with vertebrates in inflammatory processes. Collectively, prokaryotic-eukaryotic co-cultures and in vivo infection assays suggest that RNASET2 and AIF-1 play a crucial role in orchestrating a functional cross-talk between granulocytes and macrophages in leeches, resulting in the activation of an effective response against pathogen infection. RNASET2, firstly released by granulocytes, likely plays an early antibacterial role. Subsequently, AIF-1+ RNASET2-recruited macrophages further recruit other macrophages to potentiate the antibacterial inflammatory response. These experimental data are in keeping with the notion of RNA-SET2 acting as an alarmin-like molecule whose role is to locally transmit a "danger" signal (such as a bacterial infection) to the innate immune system in order to trigger an appropriate host response.


Major infectious diseases causing excess morbidity in the Hispanic population.
Current data indicate that there are a number of infectious diseases, ie, acquired immunodeficiency syndrome/human immunodeficiency virus infections, cysticercosis, hepatitis A, syphilis, tuberculosis, and typhoid fever, among others that cause disproportionately increased morbidity in Hispanics. The greater rate of poverty with its associated socioenvironmental problems, increased barriers to health care, and importation of infectious diseases endemic in the mother country are some of the major reasons that probably account for this disparity in disease burden in Hispanics. This formidable health problem can be addressed by targeting efforts at improving health education of family units and communities, environmental improvements, elimination or reduction of barriers to health care management and disease prevention, and appropriate screening programs. A comprehensive and uniform assessment of the impact of infectious diseases on Hispanics (and other minorities) in this country remains elusive, but is of paramount importance in establishing priorities and effective/efficient strategies to address this issue.


Colitis and colon cancer in cotton-top tamarins (Saguinus oedipus oedipus) living wild in their natural habitat.
The cotton-top tamarin is a nonhuman primate noted for susceptibility to juvenile onset colitis and subsequent colon cancer. About 80% develop colitis in captive environments outside the tropics. The aim was to determine the prevalence of colitis and colorectal cancer in tamarins living wild in their tropical habitat. Endoscopic biopsy was used to compare severity of colitis, inflammatory/immune cell densities, mucosal dysplasia, and occurrence of cancer in wild tamarins in a tropical habitat with tamarins living captive in a temperate climate. Six colon biopsies from each of 69 captives showed severe colitis in 64.5% of biopsies and moderate colitis in 19.5%. Severe colitis was not found in 88 wild tamarins; 13% had moderate colitis. Densities of polymorphonuclear leukocytes, plasma cells, and mononuclear cells in the lamina propria were related directly to the severity of four grades of colitis (normal, mild, moderate, and severe). Histologic or gross signs of carcinoma were detected in 12 captives and low- or high-grade dysplasia in 15. Neither cancer nor dysplasia was found in any of the wild tamarins. The observations suggest that colitis and cancer in the tamarin model are linked to environmental factors.


Is there a Neurobiological Rationale for the Utility of the Iowa Gambling Task in Parkinson's Disease?
Up to 23% of newly diagnosed, non-demented, Parkinson's disease (PD) patients experience deficits in executive functioning (EF). In fact, EF deficits may occur up to 39-months prior to the onset of motor decline. Optimal EF requires working memory, attention, cognitive flexibility, and response inhibition underlying appropriate decision-making. The capacity for making strategic decisions requires inhibiting imprudent decisions and are associated with noradrenergic and dopaminergic signaling in prefrontal and orbitofrontal cortex. Catecholaminergic dysfunction and the loss of noradrenergic and dopaminergic cell bodies early in PD progression in the aforementioned cortical areas likely contribute to EF deficits resulting in non-strategic decision-making. Thus, detecting these deficits early in the disease process could help identify a significant portion of individuals with PD pathology (14-60%) before frank motor impairment. A task to evaluate EF in the domain of non-strategic decision-making might be useful to indicate the moderate loss of catecholamines that occurs early in PD pathology prior to motor decline and cognitive impairment. In this review, we focus on the potential utility of the Iowa Gambling Task (IGT) for this purpose, given significant overlap between in loss of dopaminergic and noradrenergic cells bodies in early PD and the deficits in catecholamine function associated with decreased EF. As such, given the loss of catecholamines already well-underway after PD diagnosis, we evaluate the potential utility of the IGT to identify the risk of therapeutic non-compliance and a potential companion approach to detect PD in premotor stages.


Beyond diagnostic accuracy: the clinical utility of diagnostic tests.
Like any other medical technology or intervention, diagnostic tests should be thoroughly evaluated before their introduction into daily practice. Increasingly, decision makers, physicians, and other users of diagnostic tests request more than simple measures of a test's analytical or technical performance and diagnostic accuracy; they would also like to see testing lead to health benefits. In this last article of our series, we introduce the notion of clinical utility, which expresses--preferably in a quantitative form--to what extent diagnostic testing improves health outcomes relative to the current best alternative, which could be some other form of testing or no testing at all. In most cases, diagnostic tests improve patient outcomes by providing information that can be used to identify patients who will benefit from helpful downstream management actions, such as effective treatment in individuals with positive test results and no treatment for those with negative results. We describe how comparative randomized clinical trials can be used to estimate clinical utility. We contrast the definition of clinical utility with that of the personal utility of tests and markers. We show how diagnostic accuracy can be linked to clinical utility through an appropriate definition of the target condition in diagnostic-accuracy studies.


Translation and cultural adaptation of the fundamentals of care framework: Are we there yet?
This paper aims to explore and describe the translation and cultural adaptation of the Fundamentals of Care framework to a Swedish context, and highlight the need for a translated version. An exploratory, descriptive approach was adopted. A structured forward-backward translation process and cultural adaptation were used, considering situation and recipient as recommended for such process. Data such as literature and documents were collected during 2019-2021. The authors took systematic steps in collaboration with a strategic sample of experts: professional language service providers, clinicians, educators and a linguist. The framework was mainly translated verbatim. A few fundamental care elements were adjusted to the Swedish language, context and clinical practice. Also, this work clarified the relational elements to be coherently seen as nursing actions. Addressing the need for a translated version was illustrated in activities in research, education and clinical practice. This paper highlights the importance of translating the Fundamentals of Care framework into a country's native language to gain acceptance and application there. Sharing the framework's translated version impacts nursing science, generating a consistent language in the development and conducting of research for the comparison and transferability or generalizability of findings. Together with a cultural adaptation, the translated framework can support and guide researchers, educators and nursing leaders in articulating fundamental nursing care for enacting change. By disseminating the first Swedish version of the framework we encourage a global discussion and sharing of examples of translation and cultural adaptation by others. The framework's English version has limitations in various context. This paper shows a systematic translation and cultural adaptation process of the framework. We proclaim that this is necessary for nursing leaders and nurses to be able to apply it in guiding nursing practice and leading change.


Helping mothers to get the message about influenza: are texts the future for increased immunization?
Pregnant women and children are at increased risk of severe influenza infections. Despite existing recommendations, uptake of influenza vaccine in these vulnerable groups remains low. Text message reminder-recalls are a feasible and scalable method for promoting influenza vaccination. In randomized controlled trials, text message interventions have demonstrated small but significant increases in influenza vaccine coverage. They should be considered one of many tools available for increasing vaccination and thus improving maternal and child health.


Characteristics of computed tomography in hemodynamically unstable blunt trauma patients: Experience at a tertiary care center.
Emergent exploratory laparotomy is recommended for hemodynamically unstable blunt trauma patients suspected of having hemoperitoneum. However, given the unreliability of ultrasonography and rapid scan speed of computed tomography (CT), CT might help clinicians provide accurate information even in hemodynamically unstable trauma patients. This observational study aimed to describe the bleeding site and hospital course of severe blunt trauma patients with hemoperitoneum diagnosed by CT scan.We enrolled all consecutive adult blunt trauma patients (≥18 years old) who underwent whole-body CT before operation between February 2012 and October 2016. Patients with hemoperitoneum on CT images were included and categorized into hemodynamically stable and unstable (persistent hypotension despite fluid resuscitation) groups.Among 1723 severe blunt trauma patients, 136 patients with hemoperitoneum were included. Of these, 98 (72.1%) patients had documented intraperitoneal injury, and the liver (60.2%) was most frequently damaged site, followed by spleen (23.5%) and mesentery (23.5%). The rate of intraperitoneal organ injury did not differ between hemodynamically stable (n = 107) and unstable (n = 29) groups (69.2% vs 82.8%, P = .15), while the documented active internal bleeding was high in the unstable group (29.9% vs 69.0%, P < .001). In the unstable group, 14 (48.3%) patients underwent emergent operation, while 3 patients underwent embolization, and the others were treated in a conservative manner.Even in hemodynamically unstable hemoperitoneum patients, 17.2% had no documented intraperitoneal injury and over half of the patients were treated without emergent operation.


Phosphatidylinositol 3-kinase and the actin network are not required for the stimulation of glucose transport caused by mitochondrial uncoupling: comparison with insulin action.
In L6 myotubes insulin stimulates glucose transport through the translocation of glucose transporters GLUT1, GLUT3 and GLUT4 from intracellular stores to the plasma membrane. An intact actin network and phosphatidylinositol 3-kinase activity are required for this process. Glucose transport is also stimulated by the mitochondrial ATP-production uncoupler dinitrophenol. We show here that, in serum-depleted myotubes, dinitrophenol induced translocation of GLUT1 and GLUT4, but not GLUT3. This response was not affected by inhibiting phosphatidylinositol 3-kinase or disassembling the actin network. Insulin, but not dinitrophenol, caused tyrosine phosphorylation of several polypeptides, including the insulin-receptor substrate-1 and mitogen-activated protein kinase. Similarly, insulin, but not dinitrophenol, caused actin reorganization, which was inhibited by wortmannin. We conclude that insulin and dinitrophenol stimulate glucose transport by different mechanisms.


Alternative Payment Models and Associations With Stroke Outcomes, Spending, and Service Utilization: A Systematic Review.
Stroke contributes an estimated $28 billion to US health care costs annually, and alternative payment models aim to improve outcomes and lower spending over fee-for-service by aligning economic incentives with high value care. This systematic review evaluates historical and current evidence regarding the impacts of alternative payment models on stroke outcomes, spending, and utilization. Included studies evaluated alternative payment models in 4 categories: pay-for-performance (n=3), prospective payments (n=14), shared savings (n=5), and capitated payments (n=14). Pay-for-performance models were not consistently associated with improvements in clinical quality indicators of stroke prevention. Studies of prospective payments suggested that poststroke spending was shifted between care settings without consistent reductions in total spending. Shared savings programs, such as US Medicare accountable care organizations and bundled payments, were generally associated with null or decreased spending and service utilization and with no differences in clinical outcomes following stroke hospitalizations. Capitated payment models were associated with inconsistent effects on poststroke spending and utilization and some worsened clinical outcomes. Shared savings models that incentivize coordination of care across care settings show potential for lowering spending with no evidence for worsened clinical outcomes; however, few studies evaluated clinical or patient-reported outcomes, and the evidence, largely US-based, may not generalize to other settings.


Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease.
The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease (AD), perhaps through effects on amyloid-beta (Abeta) metabolism. Detailed analyses of various Abeta parameters in aging APP(V717F+/-) transgenic mice expressing mouse apoE, no apoE, or human apoE2, apoE3, or apoE4 demonstrate that apoE facilitates, but is not required for, Abeta fibril formation in vivo. Human apoE isoforms markedly delayed Abeta deposition relative to mouse apoE, with apoE2 (and apoE3 to a lesser extent) having a prolonged ability to prevent Abeta from converting into fibrillar forms. Isoform-specific effects of human apoE on Abeta levels and neuritic plaque formation mimicked that observed in AD (E4 > E3 > E2). Importantly, observation of an apoE-dependent decrease in percent soluble Abeta and enrichment of Abeta in membrane microdomains prior to Abeta deposition indicates that apoE influences Abeta metabolism early in the amyloidogenic process and provides a possible novel mechanism by which apoE affects AD pathogenesis.


Idiopathic subglottic stenosis.
To review our patients with subglottic stenosis and describe a rare subclass of patients in whom the cause of subglottic scarring and narrowing remains unknown. A retrospective chart review and clinical update were performed on all patients seen with the diagnosis of subglottic stenosis. The patient pool represents a collection of primary care patients within a suburb of Boston, Mass, and tertiary referrals from community and out-of-state otolaryngologists. The charts of 80 patients were reviewed, and 10 of the 80 patients fulfilled the criteria for idiopathic subglottic stenosis. Diagnostic and therapeutic intervention ranged from laboratory tests, topography, flexible bronchoscopy, rigid endoscopy and biopsy, laser-assisted dilation, and resection and repair of the lesion. Attention was directed toward the character of the lesion, treatment modality, and clinical outcome. From 1985 to 1992, 10 patients with idiopathic subglottic stenosis were treated at the Lahey Clinic, Burlington, Mass. Eight patients required therapy for exertional dyspnea. Endoscopic laser incision and dilation were performed in all eight patients, with good initial results. Four patients were treated successfully with endoscopy alone: three required only one dilation, and the fourth required a second dilation. The remaining four patients, who had longer and more complex stenoses, have had repeated restenosis at intervals ranging from 1.5 to 12 months. Two of these patients have undergone laryngotracheal resection and reconstruction and were without evidence of restenosis 10 and 20 months after surgery. There exists a subclass of patients with subglottic stenosis of unknown cause. Symptomatic idiopathic subglottic stenosis may be treated successfully with laser incision and dilation if the stenosis is simple and short. More complex, longer stenoses are prone to recurrence and are more definitively managed by resection and reconstruction of the narrowed area.


Lymph node ratio predicts disease-specific survival in melanoma patients.
The objectives of this analysis were to compare various measures associated with lymph node (LN) dissection and to identify threshold values associated with disease-specific survival (DSS) outcomes in patients with melanoma. Patients with lymph node-positive melanoma who underwent therapeutic LN dissection of the neck, axilla, and inguinal region were identified from the SEER database (1988-2005). We performed Cox multivariate analyses to determine the impact of the total number of LNs removed, number of negative LNs removed, and LN ratio on DSS. Multivariate cut-point analyses were conducted for each anatomic region to identify the threshold values associated with the largest improvement in DSS. The LN ratio was significantly associated with DSS for all LN regions. The LN ratio thresholds resulting in the greatest difference in 5-year DSS were .07, .13, and .18 for neck, axillary, and inguinal regions, respectively, corresponding to 15, 8, and 6 LNs removed per positive lymph node. After adjustment for other clinicopathologic factors, the hazard ratios (HRs) were .53 (95% confidence interval [CI], .40 to .71) in the neck, .52 (95% CI, .42 to .65) in the axillary, and .47 (95% CI, .36 to .61) in the inguinal regions for patients who met the LN ratio threshold. Among the prognostic factors examined, LN ratio was the best indicator of the extent of LN dissection, regardless of anatomic nodal region. These data provide evidence-based guidelines for defining adequate LN dissections in melanoma patients.


[Differences in the photodestruction parameters of flavin fluorescence in normal and tumor cells at a decreased pH of the incubation medium].
Further investigation of the peculiarities of flavin fluorescence photodestruction in malignant cells was made. In normal cells incubated in low pH (3.0-3.2) physiological solutions, the decrease in the oxidized flavoprotein fluorescence intensity under irradiation is the same as in normal pH condition, whereas in tumor cell in low pH solutions a significant increase in the photodestruction level was noticed. The cells isolated from foci of transformation, following treatment of 3T3 NIH fibroblasts with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, displayed the photodestruction parameters similar to those in tumor cells. A two-step analysis of cells is proposed for distinguishing between the normal and malignant cells.


Duration of action of intravitreal ranibizumab and bevacizumab in exudative AMD eyes based on macular volume measurements.
Sequential macular volume and central foveal point thickness (CFPT) measurements on optical coherence tomography (OCT) were used to determine the efficacy and duration of action of ranibizumab versus bevacizumab in wet age-related macular degeneration (AMD). Retrospective chart review of patients who received their first treatment of intravitreal ranibizumab or bevacizumab for exudative AMD. 316 patients (202 ranibizumab;114 bevacizumab) who received 823 injections (313 ranibizumab;510 bevacizumab) were identified. 74 patients had pre- and post-treatment OCTs performed to determine CFPT and macular volume changes. Ranibizumab caused a significant reduction in CFPT (278 (SD 84) before treatment vs 227 (80) microm after treatment; p = 0.001) and macular volume (7.22 (0.96) vs 6.69 (0.74) mm(3); p = 0.002). Intravitreal bevacizumab caused a similar reduction in CFPT (288 (94) vs 220 (55) microm; p = 0.008) and macular volume (7.36 (1.08) vs 6.50 (0.42) mm(3); p<0.001). The mean duration of action was 74.0 (19.1) days for ranibizumab compared with 101.8 (16.6) days for bevacizumab (p = 0.036; t test). The ratio of the relative duration of action of bevacizumab versus ranibizumab was 1.40 (0.19). Both drugs are equally effective at reducing CFPT or macular volume. Bevacizumab appears to take longer to achieve the minimum macular volume, and its effects take longer to wear off, suggesting it can be given less often.


The epidemiology and disease outcomes of human T-lymphotropic virus type II.
Human T-lymphotropic virus type II (HTLV-II) is a human retrovirus which is endemic in Amerindian and pygmy tribes. Molecular subtypes show geographic segregation consistent with an ancient origin of this virus within humans in Africa or South America. More recently, injection drug users in the United States and Europe have become infected with HTLV-II, and secondary sexual transmission has introduced the virus at low levels into the general population and blood donors. HTLV-II has been linked with a spastic paraparesis called HTLV-associated myelopathy / tropical spastic paraparesis (HAM/TSP), and perhaps with other neurological syndromes. It is also associated with an increased incidence of pneumonia and bronchitis, inflammatory conditions such as arthritis, and perhaps with increased mortality. Except for a few cases of cutaneous lymphoma in patients coinfected with HIV, there is no evidence that HTLV-II causes lymphoproliferative disease. HTLV-II and HIV coinfection has not been proven to alter the course of HIV disease, but such patients may have altered levels of CD4+ and CD8+ lymphocytes, and antiretroviral therapy may paradoxically increase HTLV-II proviral load.


Validity of rheumatoid arthritis diagnoses listed in the Saskatchewan Hospital Separations Database.
A Saskatchewan hospital separations database was compared to abstracted hospital records to determine the reliability of the database (i.e. accuracy with which the computer data reflect the charts from which they were coded) and the validity of classifying rheumatoid arthritis status with the database (i.e. the extent to which rheumatoid arthritis mentioned in the database reflected the condition of the patient). A sample of hospitalized subjects fell into three categories: 144 who never had a database diagnosis of any arthritis, 146 who had a database diagnosis of osteoarthritis, and 142 who had a database diagnosis of rheumatoid arthritis. These 432 people experienced 1717 hospitalizations eligible to match a hospital database listing by date, and 1618 matched. Of the remaining 99, 35 were relatively recent and probably had not yet been entered into the database, 39 were possibly entered incorrectly, and 25 could not be matched in any way. Of 150 hospitalizations with a database diagnosis of rheumatoid arthritis, this diagnosis was in the hospital record for 125. Chart documentation of rheumatoid arthritis status was greatest for subjects who, according to the database, were hospitalized by a rheumatologist: of 73 subjects in this category, abstractions showed 69.9% met > or = 5 American Rheumatism Association criteria, 15.1% met < 5 criteria but had a rheumatologist's diagnosis of rheumatoid arthritis, 1.3% met < 5 criteria and had a rheumatoid arthritis diagnosis by a non-rheumatologist, and 13.7% had no mention of rheumatoid arthritis or its symptoms in any medical record abstracted. In summary, reliability of the database was excellent, but validity depended on the source of diagnosis.


Reversible and irreversible hemichrome generation by the oxygenation of nitrosylmyoglobin.
The repeated oxygenation/reduction/nitrosylation of nitrosylmyoglobin produces low-spin ferric heme hemichromes which have been characterized by electron spin resonance spectroscopy. The predominant myoglobin hemichrome is a chemically reversible dihistidyl complex identified by the g values 1.53, 2.21, and 2.97. Also present is a low-spin ferric hydroxide derivative which is represented by the g values 1.83, 2.18, and 2.59. The formation of these species goes undetected by UV-vis spectroscopy, but the oxygenation of myoglobin to metmyoglobin is correlated with complete conversion of nitric oxide to nitrate which is released following a clear induction period. These results are interpreted in terms of the intermediates generated during the MbNO oxygenation reaction.


Occurrence of glycosphingolipids in chicken egg yolk.
Chicken egg yolk was found to contain a unique glycosphingolipid pattern not seen in other types of tissue or cell. These glycosphingolipids were isolated in pure form and their structures established by sequential enzymic hydrolysis and permethylation analysis. The major gangliosides in chicken egg yolk are N-acetylneuraminosylgalactosylceramide, N-acetylneuraminosyl-lactosylceramide and di-N-acetylneuraminosyl-lactosylceramide. The only neutral glycosphingolipid found in chicken egg yolk is galactosylceramide.


ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies.
The International Conference on Harmonization (ICH) guidance ICH E14 provides recommendations, focusing on a clinical 'thorough QT/QTc (TQT) study', to evaluate the QT liability of a drug during its development. An Implementation Working Group (IWG) was also established to assist the sponsors with any uncertainties and clarify any ambiguities. In April 2012, the IWG updated its June 2008 version of the Questions and Answers document to address additional issues. These include the gender of the study population, a reasonable approach to evaluating QTc changes in late stage clinical development and the recommended approach to correcting the measured QT interval. This commentary provides our observations and, when appropriate, recommendations, on these issues. We review briefly evidence that suggests that (i) the greater QT effect observed in females is not entirely related to differences in drug exposure and (ii) the Fridericia correction of measured QT interval is adequate for a majority of TQT studies. Until further evidence suggests otherwise, we recommend balanced gender representation in TQT studies, unless warranted otherwise, and for positive studies, subgroup analysis of key data by common demographic variables including the gender and ethnicity. We provide a general scheme for ECG monitoring in late phase clinical trials and consider that while intensive monitoring and centralized reading of ECGs in late phase clinical trials is the norm when a TQT study is positive, there are other circumstances that also call for high quality ECG reading. Therefore, locally read ECGs should only be acceptable as long as accurate high quality ECG data can be guaranteed.


Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China.
The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China. From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis. Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001). The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.


CD98 at the crossroads of adaptive immunity and cancer.
Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer.


Rat infarct model of myocardial infarction and heart failure.
This review outlines the development and current use of the rat coronary artery ligation model of heart failure. The techniques to ligate the left coronary artery and to obtain morphologic/hemodynamic measurements are described. The authors show how the pathology seen in this model relates to clinical ischemic heart disease. An effort is made throughout the review to relate the changes that occur in this model to clinically relevant observations. For example, the progression to heart failure in these rats is similar to what happens when a patient sustains a large myocardial infarction, survives, but goes on to develop heart failure without another ischemic insult. In both rats and people with large infarctions, the noninfarcted myocardium, even though not damaged at the time of the infarct, cannot compensate sufficiently to prevent the eventual development of heart failure. In addition to being a good approximation of human disease, the responses to pharmacologic interventions, like angiotensin converting enzyme inhibitors, in rats has proved useful in predicting what will happen in humans given the same treatment. More recent data on the molecular control of ventricular remodeling emphasizes how this model will provide important information in the study of integrated physiology by examining biochemical, pharmacologic, and physiologic changes in the same tissue.


The effect of brefeldin A on terbutaline-induced sodium absorption in fetal rat distal lung epithelium.
We studied the effect of brefeldin A, which inhibits the intracellular trafficking of membrane proteins from the cytosolic pool to the cell surface, on terbutaline (a beta2-specific adrenergic agonist)-induced alterations in ion transport by primary monolayer cultures of fetal rat distal lung epithelium. The amiloride-sensitive short circuit current (Isc) increased 2.5-fold 50 min after application of terbutaline (10 microM) from basolateral side; this response was abolished by pretreatment with brefeldin A (1 microg/ml). Brefeldin A did not suppress the Na+/K+ pump capacity. Single channel patch clamp experiments demonstrated that terbutaline increased the density of amiloride-sensitive Na+-permeable nonselective cation channels on the apical cell membrane and this action was blocked by brefeldin A. These observations suggest that beta2-specific adrenergic agonists promote the trafficking of amiloride sensitive Na+-permeable nonselective cation channels to the apical cell surface.


Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort.
Recent studies have suggested the involvement of loci on the Y chromosome in prostate cancer. We studied the relative risk (RR) of prostate cancer in relation to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed from the birth of their offspring (in 1964 through 1976) until 2005. Cox models were used to adjust for changes in incidence over time, age, the man's year of birth, and social and ethnic variables. A total of 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to 2.43), respectively. Men with no daughters showed no statistically significantly altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the number of sons increased (P(trend)<.0001) but did not change with the number of daughters. These findings suggest that a Y chromosome locus may be involved in prostate cancer risk in this population.


Effects of temperature on the bactericidal activities of ciprofloxacin and levofloxacin against Staphylococcus aureus and Staphylococcus epidermidis.
The bactericidal activities of the 4-quinolones ciprofloxacin and levofloxacin against Staphylococcus aureus and Staphylococcus epidermidis in nutrient broth were dramatically reduced when the temperature of incubation was decreased from 37 to 20 degrees C. For S. aureus the relative reduction in the activities was 86- and 46-fold with ciprofloxacin or levofloxacin, respectively. For S. epidermidis the corresponding reduction in activities was 82- and 19-fold, respectively. At infectious sites which are at lower-than-body temperature the reduced activity of 4-quinolones may contribute to clinical failure and/or the development of resistance. Levofloxacin was more bactericidal than ciprofloxacin against either of the staphylococci at every temperature tested. These results tend to suggest that levofloxacin may be preferable to ciprofloxacin for staphylococcal infections especially at skin and soft-tissue sites.


High prevalence of Echinococcus multilocularis in urban red foxes (Vulpes vulpes) and voles (Arvicola terrestris) in the city of Zürich, Switzerland.
Over a period of 26 months from January 1996 to February 1998, 388 foxes from the city of Zürich, Switzerland, were examined for intestinal infections with Echinococcus multilocularis and other helminths. The prevalence of E. multilocularis in foxes sampled during winter increased significantly from 47% in the urban to 67% in the adjacent recreational area, whereas prevalence rates of other helminths were similar in both areas. Seasonal differences in the prevalence of E. multilocularis were only found in urban subadult male foxes which were significantly less frequently infected in summer than in winter. The distribution of the Echinococcus biomass, as expressed by worm numbers per fox was overdispersed in 133 infected foxes randomly sampled in winter. Ten of these foxes (8%) were infected with more than 10,000 specimens and carried 72% of the total biomass of E. multilocularis (398,653 worms). Prevalences did not differ significantly in these foxes in regard to age and sex but worm burdens were significantly higher in subadult foxes as compared with adult foxes. In voles (Arvicola terrestris) trapped in a city park of Zürich, E. multilocularis metacestodes were identified by morphological examination and by PCR. The prevalence was 20% among 60 rodents in 1997 and 9% among 75 rodents in 1998. Protoscoleces occurred in 2 of the cases from 1997. The possible risk for human infection is discussed with respect to the established urban E. multilocularis cycle.


Safety and effectiveness of strategies to reduce radiation exposure to proceduralists performing cardiac catheterization procedures: a systematic review.
The objective of this systematic review was to synthesize the best available evidence on the effect of various radiation protection strategies on radiation dose received by proceduralists performing cardiac catheterization procedures involving fluoroscopy. Cardiac catheterization procedures under fluoroscopy are the gold standard diagnostic and treatment method for patients with coronary artery disease. The growing demand of procedures means that proceduralists are being exposed to increasing amounts of radiation, resulting in an increased risk of deterministic and stochastic effects. Standard protective strategies and equipment such as lead garments reduce radiation exposure; however, the evidence surrounding additional equipment is contradictory. Randomized controlled trials that compared the use of an additional radiation protection strategy with conventional radiation protection methods were considered for inclusion. The primary outcome of interest was the radiation dose received by the proceduralist during cardiac catheterization procedures. A three-step search was conducted in MEDLINE, CINAHL, Embase, and the Cochrane Library (CENTRAL). Trials published in the English language with adult participants were included. Trials published from database inception until July 2019 were eligible for inclusion. The methodological quality of the included studies was assessed using the JBI critical appraisal checklist for randomized controlled trials. Quantitative data were extracted from the included papers using the JBI data extraction tool. Results that could not be pooled in meta-analysis were reported in a narrative form. Fifteen randomized controlled trials were included in the review. Six radiation protection strategies were assessed: leaded and unleaded pelvic or arm drapes, transradial protection board, remotely controlled mechanical contrast injector, extension tubing for contrast injection, real-time radiation monitor, and a reduction in frame rate to 7.5 frames per second. Pooled data from two trials demonstrated a statistically significant decrease in the mean radiation dose (P < 0.00001) received by proceduralists performing transfemoral cardiac catheterization on patients who received a leaded pelvic drape compared to standard protection. One trial that compared the use of unleaded pelvic drapes placed on patients compared to standard protection reported a statistically significant decrease (P = 0.004) in the mean radiation dose received by proceduralists.Compared to standard protection, two trials that used unleaded arm drapes for patients, one trial that used a remotely controlled mechanical contrast injector, and one trial that used a transradial protection board demonstrated a statistically significant reduction in the radiation dose received by proceduralists.Similarly, using a frame rate of 7.5 versus 15 frames per second and monitoring radiation dose in real-time radiation significantly lowered the radiation dose received by the proceduralist. One trial demonstrated no statistically significant difference in proceduralist radiation dose among those who used the extension tubing compared to standard protection (P = 1). This review provides evidence to support the use of leaded pelvic drapes for patients as an additional radiation protection strategy for proceduralists performing transradial or transfemoral cardiac catheterization. Further studies on the effectiveness of using a lower fluoroscopy frame rate, real-time radiation monitor, and transradial protection board are needed.


Incidence of lower respiratory tract infections caused by Mycoplasma, Chlamydia and Legionella: an Italian Multicenter Survey.
A collaborative retrospective study based on serologic diagnosis was conducted to assess the etiological role sustained by privileged pathogens in Italy. The results obtained indicate the Mycoplasma, Chlamydia and Legionella are important etiologic agents of lower respiratory tract infections in Italy since they account for about 31% of the cases taken into consideration in this survey. We found a high incidence of M. pneumoniae (12.3%), C. pneumoniae (10.5%) and L. pneumophila (8.3%). These results are in line with similar figures reported in the recent literature. While the data gathered in our survey do not allow us to clarify the nature of the agents involved in the etiology of the majority (70%) of the respiratory infections occurring in Italy, it seems safe to assume that after Streptococcus pneumoniae and Haemophilus influenzae, the privileged pathogens represent the most common cause of lower respiratory tract infections.


Quantification of Cable Bacteria in Marine Sediments via qPCR.
Cable bacteria (Deltaproteobacteria, Desulfobulbaceae) are long filamentous sulfur-oxidizing bacteria that generate long-distance electric currents running through the bacterial filaments. This way, they couple the oxidation of sulfide in deeper sediment layers to the reduction of oxygen or nitrate near the sediment-water interface. Cable bacteria are found in a wide range of aquatic sediments, but an accurate procedure to assess their abundance is lacking. We developed a qPCR approach that quantifies cable bacteria in relation to other bacteria within the family Desulfobulbaceae. Primer sets targeting cable bacteria, Desulfobulbaceae and the total bacterial community were applied in qPCR with DNA extracted from marine sediment incubations. Amplicon sequencing of the 16S rRNA gene V4 region confirmed that cable bacteria were accurately enumerated by qPCR, and suggested novel diversity of cable bacteria. The conjoint quantification of current densities and cell densities revealed that individual filaments carry a mean current of ∼110 pA and have a cell specific oxygen consumption rate of 69 fmol O2 cell-1 day-1. Overall, the qPCR method enables a better quantitative assessment of cable bacteria abundance, providing new metabolic insights at filament and cell level, and improving our understanding of the microbial ecology of electrogenic sediments.


A multisite physician's office laboratory evaluation of an immunological method for the measurement of HbA1c.
To evaluate the clinical performance of a new immunological HbA1c method in physicians' office laboratories. Three physicians' offices participated in the evaluations. The clinicians routinely use HbA1c test results to monitor their patients' long-term blood glucose control. Precision and interlaboratory variability were assessed using three levels of lyophilized controls. Correlation of the method's results to currently available laboratory methods was made. Comparison of finger-stick (capillary) results to venous EDTA whole blood results was made on 134 patients. Physician and laboratory personnel input was evaluated with regard to the clinical utility of the system. The CVW and CVB were a maximum of 4.5 and 4.4% for the immunoassay system on three levels of control materials at the three sites. Interlaboratory variability among the control means was found to be 4.9-5.4, 8.0-8.3, and 11.7-12.0% HbA1c. Correlation coefficients (r) ranged from 0.95 to 0.99. There was a positive bias by the DCA 2000 compared with the in-house method at site 1. Minimal negative biases were seen by the DCA 2000 with comparative methods used at sites 2 and 3. Median percentage differences with the comparative methods were 12, -1.4, and -5.6%. Comparison of capillary to venous sample results, from the DCA 2000, showed no clinically significant differences. Operator and physician feedback were positive with respect to technical ease in performance of the test and accuracy of results. Precision was acceptable and interlaboratory variability was low. The immunological method correlated well with manual ion-exchange and automated HPLC methods. The small sample size and good comparison between capillary and venous sample results make fingerstick sampling acceptable. The method provided immediate test results (within 9 min) to the clinicians.