Blended care in the treatment of subthreshold symptoms of depression and psychosis in emerging adults: A randomised controlled trial of Acceptance and Commitment Therapy in Daily-Life (ACT-DL).
In this study, the feasibility and efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), ACT augmented with a daily life application, was investigated in 55 emerging adults (age 16 to 25) with subthreshold depressive and/or psychotic complaints. Participants were randomized to ACT-DL (n = 27) or to active control (n = 28), with assessments completed at pre- and post-measurement and 6- and 12-months follow-up. It took up to five (ACT-DL) and 11 (control) months to start group-based interventions. Participants attended on average 4.32 out of 5 ACT-DL sessions. On the app, they filled in on average 69 (48%) of signal-contingent beep-questionnaires, agreed to 15 (41%) of offered beep-exercises, initiated 19 on-demand exercises, and rated ACT-DL metaphors moderately useful. Relative to active control, interviewer-rated depression scores decreased significantly in ACT-DL participants (p = .027). Decreases in self-reported depression, psychotic-related distress, anxiety, and general psychopathology did not differ between conditions. ACT-DL participants reported increased mean NA (p = .011), relative to active controls. Mean PA did not change in either group, nor did psychological flexibility. ACT-DL is a feasible intervention, although adaptations in future research may improve delivery of and compliance with the intervention. There were mixed findings for its efficacy in reducing subthreshold psychopathology in emerging adults. Dutch Trial Register no.: NTR3808.


Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.
Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca2+ cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.


The Effect of Denture Cleansing Solutions on the Retention of Precision Attachments: An In Vitro Study.
This study aimed to investigate the effect of different cleansing solutions on the retention of precision attachments. A precision attachment patrix was embedded into acrylic resin and the matrix was placed onto the patrix. The red (high retention, 8 N), yellow (regular retention, 6 N), and green (reduced retention, 4 N) plastic matrixes of the attachments (n = 32) were soaked in three different denture cleansing solutions (sodium laureth sulfate, sodium bicarbonate-sodium perborate, sodium bicarbonate) for a duration simulating 6 months of clinical use. The control group was soaked in tap water. A universal testing machine was used to measure the retention values of attachments after they were soaked in denture cleansers. The retention values were compared among the groups with repeated-measures analysis of variance followed by the Tukey HSD test (p = 0.05). Yellow attachments were affected by sodium laureth sulfate, sodium bicarbonate-sodium perborate, and water (p = 0.012). Green attachments' retention increased after immersion in sodium laureth sulfate (p = 0.04) and water (p = 0.02). Red attachments' retention increased after immersion in sodium laureth sulfate or sodium bicarbonate-sodium perborate (p = 0.045). Water did not affect the retention of red attachments. Because sodium bicarbonate tablets did not affect the retention of attachments, clinicians may recommend their use as a cleanser. Clinicians also may inform patients using fixed and removable partial prostheses with precision attachments of a possible increase in retention after the use of sodium laureth sulfate or when using sodium bicarbonate-sodium perborate with yellow and red attachments.


Selenium absorption and retention from a selenite- or selenate-fortified milk-based formula in men measured by a stable-isotope technique.
The present study was designed to determine the apparent absorption and retention of the inorganic Se compounds SeO3(2-) and SeO4(2-), which are commonly used for Se fortification of clinical nutrition products and infant formulas. Ten healthy men were fed a milk-based formula labelled with 40 microg Se as 74SeO3(2-) or 76SeO4(2-) on two consecutive days using a randomised crossover design. Se stable-isotope analysis of 9 d complete collections of urine and faeces was used to calculate apparent Se absorption and retention. Se retention from 74SeO3(2-) (41.0 (SD 8.4) %) and from 76SeO4(2-) (46.0 (SD 7.9) %) was not significantly different (P > 0.05). However, Se absorption was significantly higher from SeO4(2-) than from SeO3(2-) (91.3 (SD 1.4) % v. 50.2 (SD 7.8) %, P < 0.05). Urinary excretion of the administered dose was 9.2 (SD 1.8) % for 74SeO3(2-) and 45.3 (SD 8.2) % for 76SeO4(2-) (P < 0.05). Urinary Se excretion kinetics differed significantly for the two Se compounds; 90 % of the total urinary Se was excreted after 121 h for 74SeO32- and after 40 h for 76SeO42- These results suggest that although Se absorption and urinary excretion differ for SeO3(2-) and SeO4(2-), both Se compounds are equally well retained when administered at a relatively low dose (40 microg Se). The nutritional impact of Se fortification of foods would thus be expected to be similar when SeO4(2-) or SeO3(2-) are used.


Estimation of stage duration distributions and mortality under repeated cohort censuses.
Many processes in nature can be viewed as arising from subjects progressing through sequential stages and may be described by multistage models. Examples include disease development and the physiological development of plants and animals. We develop a multistage model for sampling designs where a small set of subjects is followed and the number of subjects in each stage is assessed repeatedly for a sequence of time points, but for which the subjects cannot be identified. The motivating problem is the laboratory study of developing arthropods through stage frequency data. Our model assumes that the same individuals are censused at each time, introducing among sample dependencies. This type of data often occur in laboratory studies of small arthropods but their detailed analysis has received little attention. The likelihood of the model is derived from a stochastic model of the development and mortality of the individuals in the cohort. We present an MCMC scheme targeting the posterior distribution of the times of development and times of death of individuals. This is a novel type of MCMC that uses customized proposals to explore a posterior with disconnected support arising from the fact that individual identities are unknown. The MCMC algorithm may be used for inference about parameters governing stage duration distributions and mortality rates. The method is demonstrated by fitting the development model to stage frequency data of a mealybug cohort placed on a grape vine.


Anatomic applications of xenon-enhanced CT scanning: visual image analysis and brain-blood partition coefficient studies in man.
The inhalation of nonradioactive xenon, an inert gas that diffuses freely across the blood-brain barrier, resulted in brain enhancement which was quantitated and visualized by computed tomography (CT). Serial CT scans obtained during the buildup and equilibrium phase of xenon inhalation were used in a numerical and visual analysis of xenon accumulation in multiple selected gray- and white-matter regions in 12 patients. The calculated brain-blood partition coefficient (lambda) in normal gray matter was 0.92 +/- 0.11 and in normal white matter, 1.38 +/- 0.14. Asymmetries and delays in xenon enhancement were often visually apparent. The estimated partition coefficient was diminished more with cerebral infarction, intracerebral hematoma, and vasogenic edema than with hypoxic encephalopathy or glioblastoma multiforme. An increase in the rate of xenon accumulation was apparent by visual inspection of the motor cortex contralateral to complex hand movements. Technical factors and potential difficulties in conducting xenon-enhanced CT studies are discussed.


Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease.
Leukocyte adhesion molecules are important in cell-cell interactions of the immune system. Lymphocyte function-associated antigen 1 (cluster designation 11a) mediates interactions between T cells and mononuclear phagocytes through its ligand, the intercellular adhesion molecule 1 (CD54), whereas complement receptors 3 (CD 11b) and 4 (CD11c) are involved in complement-mediated phagocytosis. Expression of CD11 molecules and intercellular adhesion molecule 1 was studied in colonic biopsy specimens from 20 patients with inflammatory bowel disease and 10 normal controls. In normal colon, few mononuclear phagocytes expressed lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1 at high densities. The major adhesion molecule was CD11c. Thus, the largest population of normal colonic mononuclear phagocytes was represented by quiescent, resident macrophages with likely phagocytic function. In inflammatory bowel disease, mononuclear phagocytes showed only a slight increase in CD11a expression and no significant change in expression of CD11b and CD11c. By contrast, the percentage of mononuclear phagocytes expressing intercellular adhesion molecule 1 was increased from 6.9% +/- 3.9% in controls to 69.2% +/- 12.8% in ulcerative colitis (P less than 0.001) and to 45.7% +/- 22.8% in Crohn's disease (P less than 0.01), showing a close relationship with histological activity. The increased expression of intercellular adhesion molecule 1 in inflammatory bowel disease indicates a state of immunological activation induced by local release of inflammatory cytokines. Such induction of intercellular adhesion molecule 1 on mononuclear phagocytes may be important in the maintenance of chronic inflammation by facilitating interactions with T cells and T-cell antigen recognition.


[Diagnosis of muscle hematomas and pseudotumors in hemophilia].
Two hundred and twenty-six patients with haemophilia A and B were examined by CT. In 135 cases, some form of bleeding was demonstrated. CT permits exact anatomical localisation of the haematoma and its delineation from neighbouring structures. Measurements of the densities of the haematomas make it possible to determine their age from the change in absorption values. Computed tomography makes it easier for the clinician to choose between conservative or surgical treatment and to determine the duration of treatment during the regression of the haematoma.


The importance of incorporating age and sex when backcalculating length in bullhead Cottus gobio.
The present study backcalculated body length for a data set of a bullhead Cottus gobio population located at different sampling sites in a river network. Model comparison between various growth models, which included successively new parameters, showed the effect and importance of taking sex, age and the location in the river network into account. The data sets obtained by backcalculation were fitted by the von Bertalanffy growth function, which revealed the effect of the backcalculation formula on the estimation of the von Bertalanffy growth parameters. Fitting results and parameter estimates showed again the importance of incorporating age and sex when backcalculating body length in the C. gobio population studied.


The importance of low visfatin values in osteoid osteoma patient: a prospective study.
Visfatin is currently a cytokine that is extensively researched in the field of bone diseases. In this prospective study, we aimed to investigate the potential of serum visfatin levels as a biomarker for the diagnosis of osteoid osteoma. This study included a cohort of 20 patients diagnosed with osteoid osteoma (Group 1) and 30 healthy individuals (Group 2). The age, gender, cyst sizes, and visfatin values of all participants were documented and analyzed. There was a significant difference in visfatin levels between the two groups. The median visfatin level in Group 1 was 6.13 ng/ml (IQR: 4.21-8.08), while in Group 2, it was 15.83 ng/ml (IQR: 11.11-20.6). The difference was statistically significant (p<0.000). The optimal cut-off value for visfatin was found to be 7.74 ng/ml, which had a 93% sensitivity and 78% specificity. An area under the curve of receiver operating characteristic (ROC) analysis of 0.85 indicates good diagnostic performance. Our study revealed a significant decrease in visfatin levels among patients diagnosed with osteoid osteomas in comparison to the healthy control group. The ROC analysis revealed that visfatin exhibited a commendable diagnostic capacity, indicating its potential utility as a biomarker for osteoid osteoma.


Impact of intrauterine fetal resuscitation with oxygen on oxidative stress in the developing rat brain.
Use of maternal oxygen for intrauterine resuscitation is contentious because of the lack of evidence for its efficacy and the possibility of fetal harm through oxidative stress. Because the developing brain is rich in lipids and low in antioxidants, it remains vulnerable to oxidative stress. Here, we tested this hypothesis in a term pregnant rat model with oxytocin-induced fetal distress followed by treatment with either room air or 100% oxygen for 6 h. Fetal brains from both sexes were subjected to assays for biomarkers of oxidative stress (4-hydroxynonenal, protein carbonyl, or 8-hydroxy-2'-deoxyguanosine), expression of genes mediating oxidative stress, and mitochondrial oxidative phosphorylation. Contrary to our hypothesis, maternal hyperoxia was not associated with increased biomarkers of oxidative stress in the fetal brain. However, there was significant upregulation of the expression of select genes mediating oxidative stress, of which some were male-specific. These observations, however, were not accompanied by changes in the expression of proteins from the mitochondrial electron transport chain. In summary, maternal hyperoxia in the setting of acute uteroplacental ischemia-hypoxia does not appear to cause oxidative damage to the developing brain.


Optical tweezers for trapping in a microfluidic environment.
Optical tweezers use the force from a light beam to implement a precise gripping tool. Based purely on an optical principle, it works without any bodily contact with the object. In this paper we describe an optical tweezers that targets an application within the framework of nuclear magnetic resonance (NMR) spectroscopy of small objects, which are embedded inside a microfluidic channel that will be integrated in a micro-NMR detector. In the project's final stages, the whole system will be installed within the wide bore of a superconducting magnet. The aim is to precisely maintain the position of the object to be measured, without the use of susceptibility disturbing materials or geometries. In this contribution we focus on the design and construction of the tweezers. For the optical force simulation of the system we used a geometrical optics approach, which we combined with a ray fan description of the output beam of an optical system. By embedding both techniques within an iterative design process, we were able to design efficient optical tweezers that met the numerous constraints. Based on details of the constraints and requirements given by the application, different system concepts were derived and studied. Next, a highly adapted and efficient optical trapping system was designed and manufactured. After the components were characterized using vertical scanning interferometry, the system was assembled to achieve a monolithic optical component. The proper function of the optical tweezers was successfully tested by optical trapping of fused silica particles.


Combination chemotherapy with Zyflamend reduced the acquired resistance of bladder cancer cells to cisplatin through inhibiting NFκB signaling pathway.
Cisplatin-based chemotherapy is mainstay treatment in urinary bladder cancer (UBC). However, tumor recurrence frequently occurs with the acquisition of cisplatin resistance. We explored the potential effect of a polyherbal preparation, Zyflamend, on UBC cells resistant to cisplatin treatment. To establish a cisplatin-resistant human bladder cancer cell line, T24 cells were cultured in increasing concentrations of cisplatin for more than 10 months. These cells (T24R) were then treated with different concentrations of Zyflamend, and both proliferation and activity of nuclear factor kappaB (NFκB) signaling pathway were examined. To test the synergistic effect between Zyflamend and cisplatin, we treated T24R cells either with Zyflamend or cisplatin alone, or in combination. Apoptotic effect was evaluated by Annexin V/propidium iodide double staining, and the levels of the proteins involved in cell cycle and anti-apoptosis were examined by Western blotting. Finally, mice with palpable xenograft were treated either with cisplatin and Zyflamend alone or in combination for 28 days before they were sacrificed for measuring the sizes and weights of the tumor tissues. In addition, proliferation and apoptosis markers were examined by immunohistochemistry. Comparing to that in the parental T24 cells, NFκB is constitutively active in cisplatin-resistant T24R cells. Zyflamend is capable of inhibiting the growth of T24, T24R, as well as another UBC cell line J82 in a concentration-dependent manner. Mechanistically, Zyflamend suppresses NFκB-mediated cell proliferation, survival, and invasion/angiogenesis and induces apoptosis. In addition, Zyflamend significantly increased the sensitivity of T24R and J82 cells to cisplatin treatment and these findings were confirmed in T24R xenograft model with reduced proliferation index and decreased expression of RelA and its downstream target MMP9. Zyflamend is capable of counteracting bladder cancer resistance to cisplatin by repressing proliferation and inducing apoptosis through targeting NFκB signaling pathway.


Risk Factors and Prevalence of Occupational Musculoskeletal Pain among Endodontists in the United States.
A musculoskeletal disorder (MSD) of pain, weakness, numbness, or paresthesia is a common issue for dental health care providers. The aims of this study were to (1) identify the prevalence of MSDs among endodontists in the United States, (2) to identify risk factors of MSDs among United States endodontists, and (3) to compare these findings with other published findings for dental providers. A 24-question survey regarding the demographics, potential risk factors, and prevalence of MSDs was formulated and distributed to 5394 members of the American Association of Endodontists. Data were then analyzed using descriptive statistics and chi-square analysis to find significance at α = 0.05. Six hundred twenty participants responded to the survey for an overall response rate of 12%. Of the submitted surveys, 527 of them confirmed to be endodontists practicing in the United States, and all results were derived from those 527 surveys. Seventy-four percent of respondents reported having experienced MSDs in the last 12 months, and 88% reported having experienced at least 1 MSD thus far during their career. Eighty-five percent of female participants reported an MSD within the past 12 months compared with 70% of males. MSDs have a high prevalence among endodontists in the United States. The neck and lower back were the areas of highest MSD prevalence. Female sex and the frequent adoption of awkward postures were factors associated with significantly higher rates of reported MSDs in the last 12 months.


Molecular simulation of liquid crystals: progress towards a better understanding of bulk structure and the prediction of material properties.
This tutorial review covers recent progress in the field of computer simulation of liquid crystals. The development of the main "molecular-based" models for liquid crystals is described. These include lattice models, coarse-grained single site models based on hard and soft interaction potentials, atomistic models and multi-site coarse-grained models. A brief historical review is followed by an assessment of some of the new areas in this field, with an emphasis on understanding of molecular structure in liquid crystal phases and the prediction of bulk material properties. The article also looks to link the field of liquid crystal simulation with important developments in areas such as polymer simulation, lyotropic liquid crystals and model membranes.


Platelet-derived growth factor up-regulates the expression of transcription factors NF-E2, GATA-1 and c-Fos in megakaryocytic cell lines.
Platelet-derived growth factor (PDGF) is a platelet alpha-granule protein. In previous reports, we demonstrated the expression of PDGF receptors on platelets and megakaryocytic cells and that PDGF enhanced the proliferation of megakaryocytic progenitor cells. In this study, we investigated the effects of PDGF on mRNA and protein expressions of megakaryocyte-associated transcription factors, c-Fos, GATA-1, NF-E2 and PU.1, in two human megakaryocytic cell lines CHRF-288-11 and DAMI. RT-PCR/Southern blot analysis and Real-time PCR demonstrated that PDGF increased the mRNA expression of c-Fos, GATA-1 and NF-E2, but not PU.1 in a dose- and time-dependent manner. The activation was confirmed at the protein level by Western blot analysis of both total cell and nuclear lysates. The addition of increasing concentrations of Tyrphostin AG1295, an inhibitor of PDGF receptor kinase, blocked the stimulatory effect of PDGF on the mRNA and protein expressions of these transcription factors. The up-regulation of c-Fos, GATA-1 and NF-E2 protein by PDGF was inhibited by actinomycin D and cycloheximide, suggesting that mRNA and protein synthesis might be involved in the mechanism. Our data suggest a direct stimulatory effect of PDGF on c-Fos, GATA-1 and NF-E2 expressions and we speculate that these transcription factors might be involved in the signal transduction of PDGF on the regulation of megakaryocytopoiesis.


Reduced levels of membrane-bound alkaline phosphatase are common to lepidopteran strains resistant to Cry toxins from Bacillus thuringiensis.
Development of insect resistance is one of the main concerns with the use of transgenic crops expressing Cry toxins from the bacterium Bacillus thuringiensis. Identification of biomarkers would assist in the development of sensitive DNA-based methods to monitor evolution of resistance to Bt toxins in natural populations. We report on the proteomic and genomic detection of reduced levels of midgut membrane-bound alkaline phosphatase (mALP) as a common feature in strains of Cry-resistant Heliothis virescens, Helicoverpa armigera and Spodoptera frugiperda when compared to susceptible larvae. Reduced levels of H. virescens mALP protein (HvmALP) were detected by two dimensional differential in-gel electrophoresis (2D-DIGE) analysis in Cry-resistant compared to susceptible larvae, further supported by alkaline phosphatase activity assays and Western blotting. Through quantitative real-time polymerase chain reaction (qRT-PCR) we demonstrate that the reduction in HvmALP protein levels in resistant larvae are the result of reduced transcript amounts. Similar reductions in ALP activity and mALP transcript levels were also detected for a Cry1Ac-resistant strain of H. armigera and field-derived strains of S. frugiperda resistant to Cry1Fa. Considering the unique resistance and cross-resistance phenotypes of the insect strains used in this work, our data suggest that reduced mALP expression should be targeted for development of effective biomarkers for resistance to Cry toxins in lepidopteran pests.


Disabilities and the level of affected activities of daily living.
Definition and magnitude of the disability problem and the level of affected activities in daily living (ADL) are discussed on the basis of findings from several epidemiological studies. Prevalence of various disabilities for ADL and functional ability level by age and sex in the light of various aspects of health and satisfaction with life are summarised. Such disabilities have an important effect on consequences in daily living and might or might not be associated with loss of autonomy and with further development of dependency in the process of ageing. Inter-relation of various conditions of health and activities of daily living in the light of several coping abilities which compensate various disabilities on the individual level, are underlined.


[Effects mangrove conversion to pasture on density and shell size of two gastropods in the Turbo River Delta (Urabá Gulf, Caribbean coast of Colombia)].
Mangrove deforestation is widespread in the Greater Caribbean but its impact on macrobenthos has not been evaluated to date. In order to assess the impact of mangrove conversion to pasture, densities and shell sizes of two dominant gastropods (Neritina virginea and Melampus coffeus) were compared among four mangrove types: 1) Rhizophora mangle-dominated fringing mangroves, 2) Avicennia germinans-dominated basin mangroves, 3) Mixed-species basin mangroves, and 4) A. germinans- basin mangroves converted to pastures, in the Turbo River Delta (Urabá Gulf, Colombia). Mangrove types were polygon-delimited with satellite images and color aerial photographs were taken in 2009. Various (n<5) polygons per mangrove type were sampled in January, July and December 2009, and a total (n<20) 0.025m2-quadrats were randomly placed along each polygon. Forest structure variables, pore-water physicochemical variables and sediment-grain metrics were measured in the four mangrove types. Mean density and size of both gastropod species were measured. The results showed that the mean density and size of both species were significantly greater in R. mangle-fringing mangroves. N. virginea density decreased gradually towards the A. germinans-basin mangroves seemly related to the diadromous life-history. This species nearly disappeared in the neighboring pastures because individuals were constrained to a few remaining flooded areas. In the pastures, M. coffeus individuals were clumped in the remaining A. germinans trees due to its climbing behavior as a pulmonate. We hypothesize that the decline of these two gastropods was related to physical microhabitat (e.g. trees, prop roots, and seedlings) degradation, and alteration of soil properties (e.g. temperature, pH, organic matter content). Finally, we also hypothesize that the local extinction of N. virginea due to clear-cutting may exert strong negative effects on the ecosystem function because it is a dominant omnivore.


Neonatal T cells in an adult lung environment are competent to resolve Pneumocystis carinii pneumonia.
Initiation of the pulmonary inflammatory response to Pneumocystis carinii is delayed by 3 wk in mice infected as neonates compared with adults. There was no difference in the proliferative response of draining lymph node T cells from mice infected as neonates compared with adults when stimulated in vitro with either Con A or anti-CD3 mAB: However, TNF-alpha and IFN-gamma mRNA expression in the lungs of P. carinii-infected neonates was significantly lower than in adults indicating a lack of appropriate activation signaling in the local environment. This may have been due to active suppression because TGF-beta mRNA expression was significantly elevated in neonatal lungs compared with adults. To determine whether T cells from 10-day-old mice would effect resolution of P. carinii if harbored in an adult lung environment, cells were adoptively transferred to SCID mice with established P. carinii infections. There was no difference in the kinetics of T cell migration into the lungs or of clearance of P. carinii organisms when SCID mice were reconstituted with splenocytes from young mice as compared with adult mice. Furthermore, splenocytes from young mice stimulated both TNF-alpha and IFN-gamma mRNA expression to levels that were similar to that in the lungs of SCID mice reconstituted with adult cells. These data indicate that neonatal lymphocytes are competent to resolve P. carinii infection when harbored in an adult lung environment, suggesting that the neonatal lung environment, and not the T cells, is ineffective at responding to P. carinii infection.


Reorganization and in vivo dynamics of microtubules during Arabidopsis root hair development.
Root hairs emerge from epidermal root cells (trichoblasts) and differentiate by highly localized tip growth. Microtubules (MTs) are essential for establishing and maintaining the growth polarity of root hairs. The current knowledge about the configuration of the MT cytoskeleton during root hair development is largely based on experiments on fixed material, and reorganization and in vivo dynamics of MTs during root hair development is at present unclear. This in vivo study provides new insights into the mechanisms of MT (re)organization during root hair development in Arabidopsis (Arabidopsis thaliana). Expression of a binding site of the MT-associated protein-4 tagged with green fluorescent protein enabled imaging of MT nucleation, growth, and shortening and revealed distinct MT configurations. Depending on the dynamics of the different MT populations during root hair development, either repeated two-dimensional (x, y, t) or repeated three-dimensional (x, y, z, t) scanning was performed. Furthermore, a new image evaluation tool was developed to reveal important data on MT instability. The data show how MTs reorient after apparent contact with other MTs and support a model for MT alignment based on repeated reorientation of dynamic MT growth.


From molecular structure to Alzheimer therapy.
Clinical trials in the USA, Japan and Europe have confirmed the hypothesis that a steady state increase of acetylcholine resulting from cholinesterase inhibition in the brain results in an improvement of cognitive function in mild to moderate Alzheimer disease (AD) patients. During the last decade, a systematic effort to develop a pharmacological treatment for AD has resulted in two drugs being registered for the first time in the USA and Europe for this specific indication. Both are cholinesterase inhibitors (ChEI). Based on these first positive results, several second generation ChEI are being developed. An additional effect of certain ChEI is to maintain cognitive function at a constant level during a 6 months to one year period of treatment as compared to placebo. It is possible that the drug effect is one of slowing down cognitive deterioration. Comparison of clinical effects of 5 ChEI demonstrates a rather similar magnitude of improvement. For some drugs, this may represent a limit, while for others it may be possible to increase the benefit further. To maximize and prolong positive drug effects, it is important to start early and adjust the dosage during the treatment. Other strategies may involve combinations with other cholinergic drugs such as muscarinic or nicotinic agonists. A second important class of drugs which is being developed is that of muscarinic m1 agonists. However, their clinical use is still limited by side effects. The increased knowledge and recognition of the beta-amyloid molecule as a central focus of AD pathology has strongly stimulated research with the hope of finding ways of influencing its processing and deposition. At this point, no product in this line of development has reached clinical trial level. Other pharmacological approaches are related to preventive and neuroprotective interventions (estrogens, anti-oxidants and anti-inflammatories). In conclusion, given the relatively short time of research in this field, results are encouraging.


Histologic evaluation of platinum coil embolization in an aneurysm model in rabbits.
To characterize the histologic response to platinum coil embolization by using a rabbit aneurysm model. Saccular aneurysms were created in New Zealand White rabbits by using vessel ligation with intraluminal elastase incubation. Aneurysms were subsequently embolized by using platinum coils. Subjects were sacrificed at various intervals up to 12 weeks following coil embolization. The aneurysm cavities and adjacent vessels were embedded in methylmethacrylate, were sectioned, and were stained for histologic examination. Two weeks following coil implantation, aneurysms were filled predominantly with unorganized thrombus. Six weeks following coil implantation, histologic features included complete filling of the aneurysm lumen with either prominent laminated but unorganized thrombus or areas of unorganized thrombus interspersed among areas of cellular infiltration. At 12 weeks following coil implantation, aneurysms were filled with the loosely packed, disordered cells contained within the extracellular matrix. Fibrosis or smooth muscle cell infiltration was not present in any of the 6- or 12-week samples. Platinum coils placed into experimental saccular aneurysms in New Zealand White rabbits failed to elicit a fibrotic response. This model can be used for the testing of biologic modifications of platinum coils aimed at increasing intra-aneurysmal fibrosis.


The cerebellum participates in mental activity: tomographic measurements of regional cerebral blood flow.
Measurements in man of regional cerebral blood flow (rCBF) have demonstrated a number of cortical and subcortical events coupled to sensory stimulation or motor performance. It has also been shown that local activity changes take place in the cortex during 'pure' mental activity such as motor imagery (unaccompanied by sensory input or motor output). Thus, our group has previously shown that imagination of hand movements gives predominantly a frontal cortical rCBF activation while the corresponding hand movement activates the rolandic hand area mainly. In this paper we report tomographic rCBF measurements with a 133-Xenon SPECT technique during imagined tennis movements and silent counting. Both procedures gave rise to a significant cerebellar activation in addition to cortical rCBF changes. Apparently, the cerebellum may participate in pure mental activity. It possibly plays a role for the temporal organization of neuronal events related to cognition.


Imaging single cells in a beam of live cyanobacteria with an X-ray laser.
There exists a conspicuous gap of knowledge about the organization of life at mesoscopic levels. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers can probe structures at the relevant length scales and may reach sub-nanometer resolution on micron-sized living cells. Here we show that we can introduce a beam of aerosolised cyanobacteria into the focus of the Linac Coherent Light Source and record diffraction patterns from individual living cells at very low noise levels and at high hit ratios. We obtain two-dimensional projection images directly from the diffraction patterns, and present the results as synthetic X-ray Nomarski images calculated from the complex-valued reconstructions. We further demonstrate that it is possible to record diffraction data to nanometer resolution on live cells with X-ray lasers. Extension to sub-nanometer resolution is within reach, although improvements in pulse parameters and X-ray area detectors will be necessary to unlock this potential.


Fluid flow structures gut microbiota biofilm communities by distributing public goods.
Bacterial gut commensals experience a biologically and physically complex mucosal environment. While many chemical factors mediate the composition and structure of these microbial communities, less is known about the role of mechanics. Here, we demonstrate that fluid flow impacts the spatial organization and composition of gut biofilm communities by shaping how different species interact metabolically. We first demonstrate that a model community composed of Bacteroides thetaiotaomicron (Bt) and Bacteroides fragilis (Bf), two representative human commensals, can form robust biofilms in flow. We identified dextran as a polysaccharide readily metabolized by Bt but not Bf, but whose fermentation generates a public good enabling Bf growth. By combining simulations with experiments, we demonstrate that in flow, Bt biofilms share dextran metabolic by-products, promoting Bf biofilm formation. By transporting this public good, flow structures the spatial organization of the community, positioning the Bf population downstream from Bt. We show that sufficiently strong flows abolish Bf biofilm formation by limiting the effective public good concentration at the surface. Physical factors such as flow may therefore contribute to the composition of intestinal microbial communities, potentially impacting host health.


The ligand-binding domain of CD22 is needed for inhibition of the B cell receptor signal, as demonstrated by a novel human CD22-specific inhibitor compound.
CD22 is a B cell-specific transmembrane protein of the Siglec family. It binds specifically to alpha2,6-linked sialic acid (Sia) residues, which are also present on glycoproteins on the B cell surface. CD22 acts as a negative regulator in B cell receptor-mediated signaling by recruitment of Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 to its intracellular tail. To analyze how ligand-binding of CD22 influences its intracellular signaling domain, we designed synthetic sialosides as inhibitors for the lectin domain of CD22. One of these compounds inhibited binding of human CD22-Fc to target cells over 200-fold better than Sia and was highly selective for human CD22. When Daudi cells or primary B cells were stimulated with anti-immunoglobulin (Ig)M in presence of this sialoside inhibitor, a higher Ca(2+) response was observed, similar to CD22-deficient B cells. Accordingly, a lower tyrosine-phosphorylation of CD22 and SHP-1 recruitment was demonstrated in presence of the sialoside. Thus, by interfering with ligand binding of CD22 on the B cell surface, we have shown for the first time that the lectin domain of CD22 has a direct, positive influence on its intracellular inhibitory domain. Also, we have developed a novel low molecular weight compound which can enhance the response of human B cells.


Aberrant MicroRNA Expression in Patients With Endometrial Cancer.
Current evidence suggests that no single serum biomarker displays satisfactory diagnostic performance in patients with endometrial carcinoma (EC), the most frequent gynecological cancer in developed countries. However, aberrant tissue microRNA (miRNA) expression has been recently described in EC. Therefore, this study aimed to investigate the differential expression of 4 serum miRNAs and their association with CA125 (cancer antigen 125) and HE4 (human epididymis protein 4) in EC patients and in a control population. Forty-six consecutive women with EC and 28 matched control subjects without a history of cancer or other diseases were enrolled. Total serum RNA was extracted using mirVana PARIS Kit. TaqMan MicroRNA Assay was used for quantitative real-time reverse transcriptase-polymerase chain reaction on ABI 7500 Sequence Detection System to assess differential miRNAs expression. The relative expression levels of 4 miRNAs (miR-222, miR-223, miR-186, and miR-204) were normalized to miR-16 and calculated using the 2-△Ct approach. Serum levels of miR-186, miR-222, and miR-223 appeared to be significantly higher in patients compared with control subjects (P = 0.004, P = 0.002, and P < 0.0001). Contrarily, serum miR-204 was found to be significantly lower in EC patients (P < 0.0001). The diagnostic performance of miRNAs was found to be significantly better than that of CA125. Among the various biomarker tested, serum miR-204 and HE4 exhibited the best diagnostic performance for discriminating EC patients from control subjects. These results underpin that the 4 miRNAs that we have investigated are implicated in development and progression of EC, thus opening new avenues in EC diagnostics.


Being there: the effect of the user's presence on MEDLINE search results.
An evaluation was conducted at the University of Iowa Health Sciences Library to determine what effect the user's presence had on MEDLINE search results. One hundred users participated over a four-month period. Three main criteria were used: search precision, search recall, and user satisfaction. Each MEDLINE search was processed twice, once prior to the user's arrival and a second time during the scheduled appointment with the user. The two searches for each user were processed by different searchers, and four searchers alternated processing the user-absent or the user-present search. Users were asked to compare the citations on the two searchers by checking each printout for relevant citations. A short questionnaire was administered to determine general information about users and satisfaction measures for each search. The extensiveness of the interview for the user-absent search was varied in order to determine if the depth of the initial interview would affect the search results. Evaluation of the findings indicated an increase in precision, recall, and user satisfaction for the user-present search. Some difficulties in designing the experiment are discussed and implications of the evaluation results are considered.


Acoustic Description of the Soundscape of a Real-Life Intensive Farm and Its Impact on Animal Welfare: A Preliminary Analysis of Farm Sounds and Bird Vocalisations.
Poultry meat is the world's primary source of animal protein due to low cost and is widely eaten at a global level. However, intensive production is required to supply the demand although it generates stress to animals and welfare problems, which have to be reduced or eradicated for the better health of birds. In this study, bird welfare is measured by certain indicators: CO2, temperature, humidity, weight, deaths, food, and water intake. Additionally, we approach an acoustic analysis of bird vocalisations as a possible metric to add to the aforementioned parameters. For this purpose, an acoustic recording and analysis of an entire production cycle of an intensive broiler Ross 308 poultry farm in the Mediterranean area was performed. The acoustic dataset generated was processed to obtain the Equivalent Level (Leq), the mean Peak Frequency (PF), and the PF variation, every 30 min. This acoustical analysis aims to evaluate the relation between traditional indicators (death, weight, and CO2) as well as acoustical metrics (equivalent level impact (Leq) and Peak Frequency) of a complete intensive production cycle. As a result, relation between CO2 and humidity versus Leq was found, as well as decreases in vocalisation when the intake of food and water was large.


Increased body mass index and bronchial impairment in allergic rhinitis.
Several studies have outlined a possible relationship between an increased body mass index (BMI) and respiratory allergic diseases, such as asthma and allergic rhinitis (AR). The aim of this study was to analyze the relationship among BMI, spirometry, bronchial hyperreactivity (BHR), and fractional concentration of exhaled nitric oxide (FeNO) in a cohort of AR patients. The study included 155 patients with persistent AR alone and 155 healthy controls. All subjects were evaluated performing skin-prick test, spirometry, bronchoprovocation test with methacholine, and FeNO measurement. BMI values were significantly higher in AR patients than in control subjects (p = 0.038). Overweight/obese AR patients had more altered functional and inflammatory parameters than normal weight patients. BMI > 25 is a risk factor for (i) early bronchial airflow limitation (odds ratio [OR], 3.81), (ii) high FeNO values (OR, 1.96), and BHR (OR, 3.29). The present study may suggest that BMI assessment should be routinely considered in AR patients for assessing risk for early bronchial impairment, such as suggesting possible evolution to asthma.


MALT lymphoma associated genetic aberrations occur at different frequencies in primary and secondary intestinal MALT lymphomas.
Limited data are available on intestinal MALT lymphoma owing to its relatively rare occurrence. The frequency of associated genetic changes was therefore analysed in intestinal MALT lymphoma to determine whether primary and secondary examples may be distinguished by their genetic profile. Patients diagnosed with MALT lymphoma involving the intestine were evaluated and compared with 71 cases with localised gastric MALT lymphoma. Paraffin embedded samples were evaluated for t(11;18)(q21;q21) by reverse transcription polymerase chain reaction, and by fluorescence in situ hybridisation for t(14;18)(q32;q21), t(1;14)(p22;q32), and trisomies 3 and 18. 30 consecutive patients with MALT lymphoma involving the intestine were identified: 16 had primary intestinal lymphoma and 14 had secondary MALT lymphoma. t(11;18)(q21;q21) was found in one third of the patients, but there was a significant difference between the secondary MALT lymphomas and the primary intestinal and gastric MALT lymphoma groups (57% v 12.5%, p = 0.019, and 57% v 24%, p = 0.022). Two patients with primary intestinal MALT lymphomas were positive for t(1;14)(p22;q32) and none was positive for t(14;18)(q32;q21). Primary intestinal MALT lymphoma had a significantly higher frequency of trisomies 3 or 18 (81% v 36%, p = 0.024; 81% v 14%, p<0.001), in contrast to secondary intestinal MALT lymphomas and localised gastric MALT lymphomas. The genetic profile of primary intestinal MALT lymphomas appears to be different from that of secondary intestinal or local gastric MALT lymphomas. Because of the high prevalence of trisomy 3 or 18, or both, in primary intestinal lymphoma, these numerical aberrations might be regarded as a genetic hallmark of the disease.


Differential expression of carcinoembryonic antigen in early gastric adenocarcinomas versus benign gastric lesions defined by monoclonal antibodies reactive with restricted antigen epitopes.
Murine monoclonal antibodies (MAbs) reactive with distinct epitopes on carcinoembryonic antigen (CEA) have been analyzed systematically by radioimmunoassays, Western blotting, and immunohistochemical assays to define CEA expression in adenocarcinomas, benign lesions, and normal tissues of the stomach. Each of four COL-MAbs (COL-1, COL-4, COL-6, and COL-12) reacted preferentially with cell extracts of adenocarcinomas versus those of normal mucosae in solid-phase radioimmunoassays. Using Western blotting analyses MAbs COL-1, COL-4, COL-6, and COL-12 detected only the Mr 180,000 molecule characteristic of CEA in adenocarcinoma of the stomach; no reactivity was observed in an extract of normal gastric mucosa. Antibody competition radioimmunoassays were then carried out to define relations among COL-MAbs using 125I-radiolabeled MAbs, and nonradiolabeled MAbs as competitors. A spectrum of formalin-fixed, paraffin-embedded normal, benign, and malignant tissue sections of the stomach were examined for immunoreactivities with COL-MAbs using immunohistochemical assays to define whether the COL-MAbs were able to detect CEA expression in early foci of gastric carcinomas. All of the COL-MAbs generally demonstrated selective reactivities to adenocarcinomas (n = 40) versus benign lesions (n = 15) and normal mucosae (n = 6) of the stomach. From 72 to 100% of adenocarcinomas at early stage (n = 18) were reactive with the COL-MAbs, suggesting that these MAbs might serve as immunohistochemical diagnostic tools to detect early foci of gastric carcinoma. The data reported here indicate that the COL-MAbs can potentially be utilized as radioimmunological and immunohistochemical adjuncts to differentiate early adenocarcinomas from normal mucosae or benign lesions of the stomach on the basis of differential CEA expression.


New Perspectives on the Adverse Effects of NSAIDs in Cancer Pain: An Italian Delphi Study from the Rational Use of Analgesics (RUA) Group.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs for cancer pain. We used the Delphi methodology to evaluate the opinions of clinicians on NSAIDs and paracetamol, with a specific focus on their safety profile. Consensus was reached on seven statements. A high level of consensus was reached regarding the use of NSAIDs and gastrointestinal, cardiovascular, and renal risk in patients taking low-dose aspirin and assessment of liver function during long-term treatment with paracetamol. Consensus was also reached that assessment and monitoring of eGFR are important in the elderly being administered NSAIDs. It was further agreed that NSAIDs can often play a key role in association with opioids in the treatment of cancer pain and that paracetamol is the analgesic of first choice for patients with mild chronic pain. When NSAIDs are administered in combination with steroids, it was agreed that the risk of gastrointestinal damage is increased since steroids delay the healing of ulcers and that paracetamol can be used during pregnancy and does not affect the health of the fetus. This Delphi study highlights that there is poor agreement on how these drugs are routinely prescribed. However, a consensus was reached for seven key statements and may represent a valid contribution to daily practice.


A Brief Mindfulness Intervention for Parents and Children before Pediatric Venipuncture: A Randomized Controlled Trial.
Routine needle procedures can be distressing for parents and children. Mindfulness interventions may be helpful for parents and children but have not been examined for pediatric needle procedures despite showing benefits in the context of pediatric chronic pain and in lab-based pain tasks. This preregistered (NCT03941717) two-arm, parallel-group randomized controlled trial examined the effects of a 5 min mindfulness intervention before pediatric venipuncture for parents and children (aged 7-12) compared to a control group on primary outcomes of child pain and fear, secondary outcomes of parent distress, and tertiary outcomes of parent ratings of child pain and fear. Moderators of parent and children's responses to the intervention were examined: state catastrophizing, trait mindfulness, and experiential avoidance. Sixty-one parent-child dyads were randomized (31 mindfulness; 30 control). Parents and children completed measures, listened to a 5 min audio recording (mindfulness or control), and parents accompanied their child during routine venipuncture. The mindfulness intervention involved breathing and encouraging nonjudgmental attention to one's experiences, while the control condition involved an unfocused attention task. Three between-subject MANCOVAs assessed for group differences. Child pain and fear rated by children and their parents did not differ between groups. Parents in the mindfulness group were less distressed during the venipuncture than the controls. Parent state catastrophizing may have moderated the intervention effects, such that parents with moderate and high catastrophizing levels had lower distress following the mindfulness intervention versus control. The intervention did not reduce child pain or fear but reduced parent distress. It appeared most helpful for parents catastrophizing about their child's pain, which is noteworthy as these children are prone to worse outcomes.


Tillage shapes the soil and rhizosphere microbiome of barley-but not its susceptibility towards Blumeria graminis f. sp. hordei.
Long-term agricultural practices are assumed to shape the rhizosphere microbiome of crops with implications for plant health. In a long-term field experiment, we investigated the effect of different tillage and fertilization practices on soil and barley rhizosphere microbial communities by means of amplicon sequencing of 16S rRNA gene fragments from total community DNA. Differences in the microbial community composition depending on the tillage practice, but not the fertilization intensity were revealed. To examine whether these soil and rhizosphere microbiome differences influence the plant defense response, barley (cultivar Golden Promise) was grown in field or standard potting soil under greenhouse conditions and challenged with Blumeria graminis f. sp. hordei (Bgh). Amplicon sequence analysis showed that preceding tillage practice, but also aboveground Bgh challenge significantly influenced the microbial community composition. Expression of plant defense-related genes PR1b and PR17b was higher in challenged compared to unchallenged plants. The Bgh infection rates were strikingly lower for barley grown in field soil compared to potting soil. Although previous agricultural management shaped the rhizosphere microbiome, no differences in plant health were observed. We propose therefore that the management-independent higher microbial diversity of field soils compared to potting soils contributed to the low infection rates of barley.


A linear diffusion model for ion current across blocking grain boundaries in oxygen-ion and proton conductors.
We demonstrate the applicability of the linear diffusion model recently proposed for the current-voltage, Igb-Ugb, characteristics of blocking grain boundaries in solid electrolytes to various oxygen-ion and proton conductors: the model precisely reproduces the Igb-Ugb characteristics of La-, Sm-, Gd-, and Y-doped ceria as well as Y-doped barium zirconate to provide accurate explanations to the "power law" behavior of the Igb-Ugb relationship, i.e. Igb ∝ Ugb(n), experimentally observed. The model also predicts that the grain-boundary potential, Ψgb, in doped ceria weakly depends on temperature, if the trapped charge remains constant, and that the value of Ψgb can be determined from the value of the power n. Furthermore, the model provides a plausible explanation for the increase in the Ψgb with temperature observed for the proton conductor in which the concentration of the charge carrier decreases with temperature. Hence, it is evident that the linear diffusion model is robust and applicable to grain boundaries in a large variety of practically important solid electrolytes.


Exenatide upregulates gene expression of glucagon-like peptide-1 receptor and nerve growth factor in streptozotocin/nicotinamide-induced diabetic mice.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including the brain. The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex, and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer's disease to diabetic neuropathies. Exenatide, a potent and selective agonist for the GLP-1 receptor, is currently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to assess the effect of chronic exenatide treatment on the hippocampal gene expression levels of GLP-1 receptor and NGF in diabetic mice. The effects of chronic exenatide treatment (0.1 μg/kg, s.c., twice daily for 2 weeks) on GLP-1 receptor and NGF gene expression levels in the hippocampus of streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice were assessed by quantitative real-time polymerase chain reaction (RT-PCR). The results of this study revealed that hippocampal gene expression of GLP-1 receptor and NGF were downregulated in diabetic mice. Importantly, a significant increase in the gene expression level of GLP-1 receptor and NGF was determined after 2 weeks of exenatide administration. Increased gene expression level of GLP-1 receptor and NGF may underlie the beneficial action of exenatide in STZ/NA-induced diabetes.


Serological differentiation of acute and chronic schistosomiasis using Schistosoma mansoni recombinant protein RP26.
We obtained a recombinant protein encoded by Schistosoma mansoni gene which was able to differentiate acute from chronic schistosomiasis when applied as antigen in enzyme-linked immunosorbent assay (ELISA). A cDNA clone encoding a 26 kDa recombinant protein (RP26) was selected by screening of an adult worm S. mansoni lambdaZAP expression library with rabbit sera produced against PIII, an adult worm protein fraction already known to possess protective and immunomodulating effects. The clone cDNA presented 99% identity with S. mansoni Sm22.3 gene. We assayed IgG reactivity of sera from 18 patients with acute, 25 patients with chronic S. mansoni infection and 20 uninfected donors with RP26 in ELISA. Our results showed that 89% of sera were positive in acute schistosomiasis group, and only 26% in chronic group, without false-positive reactions in uninfected group. In mice the immune response to RP26 increased up to week 9 after infection and then diminished. We proposed that production of antibodies binding to RP26 stopped at the chronic stage of disease. The testing of sera from eight other parasitic infections with RP26 revealed no positive reactions in majority of sera. However, we observed low positive reaction in sera from 20% of leishmaniasis patients. Our results indicate that a recombinant protein RP26 can be used as immunodiagnostic reagent for detection of acute phase of schistosomiasis mansoni.


In situ high temperature powder x-ray diffraction technique using a sapphire single-crystal flat cell.
Understanding the behaviors of materials in their operating and manufacturing environments is essential not only in the scientific field, but also in the context of designing industrial materials for target applications. In this study, we developed a high-temperature x-ray diffraction (XRD) system, using a small microscope heating stage at the BL02B2 beamline in SPring-8. Newly designed sample cells composed of sapphire single crystals were employed to perform XRD experiments using powdered samples at high temperatures and under oxidization/reduction gas atmospheres, with a short sample exchange time. More specifically, XRD experiments were conducted under vacuum, air, inert gas (maximum temperature: ∼1400 °C), and reduction gas flow conditions (maximum temperature: ∼900 °C). In addition, to monitor the changes in the exhausted gas composition during the chemical reactions, the developed heating system was combined with in situ gas-analysis tools (a remote gas-pressure control system, gas chromatograph, and mass spectrometer), which allowed analysis of the gas-adsorption/desorption and solid-gas reaction processes. Several heating experiments, such as the observation of the reduction of Fe oxides, phase transitions of ZrO2 and BaCO3, and synthesis of BaZrO3, demonstrated the validity and usefulness of this system.


[Clinical and pathogenetic aspects of the chronic occupational intoxication with fluorine compounds in modern reality].
Multi-year follow-up of 358 workers of aluminum pot rooms, including 165 individuals suffering from fluorosis, has shown significant changes in the clinical picture of the chronic occupational fluorine intoxication, developed under modern conditions of production, at lower concentrations of fluorine compounds in the air of working area. In this connection, the pathology of the musculoskeletal system plays the dominating role in this clinical picture and has the large variability of combinations of the individual sections destructions of the bone tissue. The main criterion to establish the phase of the disease is still the number and severity of the signs of this destruction. The visceral pathology in contemporary production circumstances is registered with less frequency and loses a number of the previously described clinical manifestations, however, is still of some importance to identify the early signs of the disease and to prevent the dental fluorosis on time.


Feeling more together: group attention intensifies emotion.
The idea that group contexts can intensify emotions is centuries old. Yet, evidence that speaks to how, or if, emotions become more intense in groups remains elusive. Here we examine the novel possibility that group attention--the experience of simultaneous coattention with one's group members--increases emotional intensity relative to attending alone, coattending with strangers, or attending nonsimultaneously with one's group members. In Study 1, scary advertisements felt scarier under group attention. In Study 2, group attention intensified feelings of sadness to negative images, and feelings of happiness to positive images. In Study 3, group attention during a video depicting homelessness led to greater sadness that prompted larger donations to charities benefiting the homeless. In Studies 4 and 5, group attention increased the amount of cognitive resources allocated toward sad and amusing videos (as indexed by the percentage of thoughts referencing video content), leading to more sadness and happiness, respectively. In all, these effects could not be explained by differences in physiological arousal, emotional contagion, or vicarious emotional experience. Greater fear, gloom, and glee can thus result from group attention to scary, sad, and happy events, respectively.


Results of surgical treatment of muscular torticollis for patients greater than 6 years of age.
From 1983-1989, 37 patients with muscular torticollis were treated surgically by partial resection of the distal portion of the sternocleidomastoid muscle. Of these, 19 patients who at surgery were greater than 6 years of age (average 11 years 2 months) were followed for greater than 1 year (average 2 years 2 months). Although both function and cosmesis were improved in all cases, scoliosis was a residual deformity in some cases, especially in girls.


The interplay of cell-cell and cell-matrix interactions in the invasive properties of brain tumors.
Impairment of tissue cohesion and the reorganization of the extracellular matrix are crucial events during the progression toward invasive cell phenotype. We studied the in vitro invasion patterns of nine brain tumor cell lines in three-dimensional collagen gels. Cell-cell and cell-matrix interactions were quantified and correlated with the expression level of specific molecules: N-cadherin, matrix metalloproteinases, and their inhibitor. Pattern evolution was studied as a function of time and collagen concentration. Cells with low metalloproteinase expression or high tissue cohesion showed limited invasive potential. Higher metalloproteinase expression and intermediate tissue cohesion resulted in configurations with hypercellular zones surrounding regions mostly devoid of cells and with digested collagen, akin to pseudopalisades in surgically removed malignant astrocytoma specimens. In physical terms, these configurations arise as the result of competition between cell-cell and cell-matrix interactions. Our findings suggest specific ways to characterize, control, or engineer cell migratory patterns and hint at the importance of the interplay between biophysical and biomolecular factors in the characterization of invasive cell behavior and, more generally, in epithelial-mesenchymal transitions.


Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey.
Asthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. This Swedish cohort (age 17-76 years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network (GA(2) LEN) survey. The Mini Asthma Quality of Life Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and peak nasal inspiratory flow were used. Subjects having both asthma and CRS have lower mAQLQ scores in all domains (P < 0.001) and a lower EQ-5D index value and EQ-5D VAS value (P < 0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P < 0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS (P < 0.0001), lower lung function (P = 0.008), current smoking (P = 0.01), BMI > 30 kg/m2 (P = 0.04), high age (P = 0.03), and a negative SPT (P = 0.04). Comorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma.


Rational design of organic asymmetric donors D1-A-D2 possessing broad absorption regions and suitable frontier molecular orbitals to match typical acceptors toward solar cells.
A series of donors have been designed based on three building blocks, i.e., triphenylamine (TPA), 4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole (DBT), and oligothiophenes (5Th), to investigate suitable molecules toward solar cell materials. The donors are built by two donor fragments (TPA as D1 and 5Th as D2) and one acceptor fragment (DBT as A) in three topologies with or without linkages and electron-withdrawing groups. Their electronic and optical properties have been characterized by the PBE0/6-31G(d,p) and the TD-PBE0/6-31+G(d,p) approaches. The calculated results reveal that the asymmetric donor in the topology of D1-A-D2 with vinyl linkage and -NO(2) groups is a rational strategy to design novel material possessing a small HOMO-LUMO gap, broad and intense absorption spectra, and higher charge transfer ability. The promising donors for [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM), bisPCBM, and PC70BM as acceptors are recommended theoretically for the first time for solar cells based on the proper match for frontier molecular orbitals between donors and acceptors.


Flare during tapering of biological DMARDs in patients with rheumatoid arthritis in routine care: characteristics and predictors.
To identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs). Sustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses. Of 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007). The majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.


Dark states and delocalization: Competing effects of quantum coherence on the efficiency of light harvesting systems.
Natural light harvesting systems exploit electronic coupling of identical chromophores to generate efficient and robust excitation transfer and conversion. Dark states created by strong coupling between chromophores in the antenna structure can significantly reduce radiative recombination and enhance energy conversion efficiency. Increasing the number of the chromophores increases the number of dark states and the associated enhanced energy conversion efficiency yet also delocalizes excitations away from the trapping center and reduces the energy conversion rate. Therefore, a competition between dark state protection and delocalization must be considered when designing the optimal size of a light harvesting system. In this study, we explore the two competing mechanisms in a chain-structured antenna and show that dark state protection is the dominant mechanism, with an intriguing dependence on the parity of the number of chromophores. This dependence is linked to the exciton distribution among eigenstates, which is strongly affected by the coupling strength between chromophores and the temperature. Combining these findings, we propose that increasing the coupling strength between the chromophores can significantly increase the power output of the light harvesting system.


Structural analysis of Arabidopsis thaliana chromosome 5. IX. Sequence features of the regions of 1,011,550 bp covered by seventeen P1 and TAC clones.
In this series of projects sequencing the entire genome of Arabidopsis thaliana chromosome 5, non-redundant P1 and TAC clones have been sequenced according to the fine physical map, and as of May 7, 1999, the sequences of 16.2 Mb representing approximately 60% of chromosome 5 have been accumulated and released at our web site. In parallel, structural features of the sequenced regions have been analyzed by applying a variety of computer programs, and to date we have predicted a total of 2380 potential protein-coding genes in the 10,154,580 bp regions, which are covered by 142 P1 and TAC clones. In this paper, we newly analyzed the structural features of the 1,011,550 bp regions covered by additional 17 P1 and TAC clones, and predicted 298 protein-coding genes. The average density of the genes identified was 1 gene per 3394 bp. Introns were observed in 67% of the genes, and the average number per gene and the average length of the introns were 3.2 and 159 bp, respectively. The gene density became higher than the value estimated in the previously analyzed regions (1 gene per 4,267 bp), as the data in this paper were compiled based on a new standard of gene assignment including the computer-predicted hypothetical genes. The regions also contained 8 tRNA genes when searched by similarity to reported tRNA genes and the tRNA scan-SE program. The sequence data and information on the potential genes are available on the database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.


Diffuse panbronchiolitis with multiple tumorlets. A quantitative study of the Kultschitzky cells and the clusters.
An autopsy case of diffuse panbronchiolitis with incidentally observed multiple tumorlets was reported. Quantitative study revealed the distribution and number of single Kultschitzky cell and its cluster. These cells were more frequently observed in the present case than in 20 control cases, and moreover, they tended to occur more frequently in the pulmonary segment in which tumorlets were found and there was an apparent transition of them into tumorlets. Immunohistochemically, gastrin-releasing peptide, calcitonin, and serotonin were demonstrable in the cells which consisted of both tumorlets and Kultschitzky cell clusters. It is suggested that the Kultschitzky cell is a precursor cell of the tumorlet and that tumorlet is benign, being hyperplastic in nature.


In vitro porcine blastocyst development in three-dimensional alginate hydrogels.
Appropriate embryonic and fetal development significantly impact pregnancy success and, therefore, the efficiency of swine production. The pre-implantation period of porcine pregnancy is characterized by several developmental hallmarks, which are initiated by the dramatic morphological change that occurs as pig blastocysts elongate from spherical to filamentous blastocysts. Deficiencies in blastocyst elongation contribute to approximately 20% of embryonic loss, and have a direct influence on within-litter birth weight variation. Although factors identified within the uterine environment may play a role in blastocyst elongation, little is known about the exact mechanisms by which porcine (or other species') blastocysts initiate and progress through the elongation process. This is partly due to the difficulty of replicating elongation in vitro, which would allow for its study in a controlled environment and in real-time. We developed a three dimensional (3-D) culture system using alginate hydrogel matrices that can encapsulate pig blastocysts, maintain viability and blastocyst architecture, and facilitate reproducible morphological changes with corresponding expression of steroidogenic enzyme transcripts and estrogen production, consistent with the initiation of elongation in vivo. This review highlights key aspects of the pre-implantation period of porcine pregnancy and the difficulty of studying blastocyst elongation in vivo or by using in vitro systems. This review also provides insights on the utility of 3-D hydrogels to study blastocyst elongation continuously and in real-time as a complementary and confirmatory approach to in vivo analysis.


Novel combination therapy for melanoma induces apoptosis via a gap junction positive feedback mechanism.
Metastatic melanoma cells overexpressing gap junctions were assayed for their ability to propagate cell death by a novel combination therapy that generates reactive oxygen species (ROS) by both 1) non-thermal plasma (NTP) and 2) tirapazamine (TPZ) under hypoxic conditions. Results demonstrate additive-to-synergistic effects of combination therapy compared to each agent individually. NTP induces highly localized cell death in target areas whereas TPZ partially reduces viability over the total surface area. However, when high gap junction expression was induced in melanoma cells, effects of combination NTP+TPZ therapy was augmented, spreading cell death across the entire plate. Similarly, in vivo studies of human metastatic melanoma in a mouse tumor model demonstrate that the combined effect of NTP+TPZ causes a 90% reduction in tumor volume, specifically in the model expressing gap junctions. Treatment with NTP+TPZ increases gene expression in the apoptotic pathway and oxidative stress while decreasing genes related to cell migration. Immune response was also elicited through differential regulation of cytokines and chemokines, suggesting potential for this therapy to induce a cytotoxic immune response with fewer side effects than current therapies. Interestingly, the gap junction protein, Cx26 was upregulated following treatment with NTP+TPZ and these gap junctions were shown to maintain functionality during the onset of treatment. Therefore, we propose that gap junctions both increase the efficacy of NTP+TPZ and perpetuate a positive feedback mechanism of gap junction expression and tumoricidal activity. Our unique approach to ROS induction in tumor cells with NTP+TPZ shows potential as a novel cancer treatment.


Study On Synthesis and Biological Activity of Some Pyridopyridazine Derivatives.
In this study, new pyrido[3,4-d]pyridazine derivatives were synthesized and evaluated for their in vitro antibacterial, antifungal and antimycobacterial activities. Among the synthesized compounds, compound 10 (1-(4-benzylpiperazin-1-yl)pyrido[3,4-d]pyridazin-4(3H)-one) and compound 12 (1-(4-benzylpiperidin-1-yl)pyrido[3,4-d]pyridazin-4(3H)-one) were found to have the highest antimycobacterial activity. However, all compounds were found ineffective against tested Gram-positive, Gram-negative bacteria and fungus.


Speech-Driven Facial Animations Improve Speech-in-Noise Comprehension of Humans.
Understanding speech becomes a demanding task when the environment is noisy. Comprehension of speech in noise can be substantially improved by looking at the speaker's face, and this audiovisual benefit is even more pronounced in people with hearing impairment. Recent advances in AI have allowed to synthesize photorealistic talking faces from a speech recording and a still image of a person's face in an end-to-end manner. However, it has remained unknown whether such facial animations improve speech-in-noise comprehension. Here we consider facial animations produced by a recently introduced generative adversarial network (GAN), and show that humans cannot distinguish between the synthesized and the natural videos. Importantly, we then show that the end-to-end synthesized videos significantly aid humans in understanding speech in noise, although the natural facial motions yield a yet higher audiovisual benefit. We further find that an audiovisual speech recognizer (AVSR) benefits from the synthesized facial animations as well. Our results suggest that synthesizing facial motions from speech can be used to aid speech comprehension in difficult listening environments.


Message framing and perinatal decisions.
The purpose of this study was to explore the effect of information framing on parental decisions about resuscitation of extremely premature infants. Secondary outcomes focused on elucidating the impact of other variables on treatment choices and determining whether those effects would take precedence over any framing effects. This confidential survey study was administered to adult volunteers via the Internet. The surveys depicted a hypothetical vignette of a threatened delivery at gestational age of 23 weeks, with prognostic outcome information framed as either survival with lack of disability (positive frame) or chance of dying and likelihood of disability among survivors (negative frame). Participants were randomly assigned to receive either the positively or negatively framed vignette. They were then asked to choose whether they would prefer resuscitation or comfort care. After completing the survey vignette, participants were directed to a questionnaire designed to test the secondary hypothesis and to explore possible factors associated with treatment decisions. A total of 146 subjects received prognostic information framed as survival data and 146 subjects received prognostic information framed as mortality data. Overall, 24% of the sample population chose comfort care and 76% chose resuscitation. A strong trend was detected toward a framing effect on treatment preference; respondents for whom prognosis was framed as survival data were more likely to elect resuscitation. This framing effect was significant in a multivariate analysis controlling for religiousness, parental status, and beliefs regarding the sanctity of life. Of these covariates, only religiousness modified susceptibility to framing; participants who were not highly religious were significantly more likely to be influenced to opt for resuscitation by the positive frame than were participants who were highly religious. Framing bias may compromise efforts to approach prenatal counseling in a nondirective manner. This is especially true for subsets of participants who are not highly religious.


Genetic variance in blood pressure.
The National Heart and Lung Institute Twin Study has examined 514 white adult male twin sets aged 42-56 with respect to blood pressure. The data were analyzed by a method of Christian et al. which eliminates possible biases in estimated genetic variances that could result from different total variances in MZ and DZ twins. Results of the test for the presence of genetic variance indicate that both systolic and diastolic blood pressure are to a considerable extent genetically controlled with an estimated heritability of 0.8 for systolic and 0.6 for diastolic pressure. Although these findings are at variance with some previous reports, it is thought that much of the discrepancy results from application of different analytic techniques, not in the data themselves. The application of these findings to our understanding of hypertension epidemiology and community hypertension control programs are discussed.


Molecular Structure and Properties of Sulfur-Containing High Refractive Index Polymer Optical Materials.
High refractive index polymers (HRIPs) are widely used in lenses, waveguide, antireflective layer and encapsulators, especially the advanced fields of augmented/virtual reality (AR / VR) holographic technology and photoresist for chip manufacturing. In order to meet the needs of different applications, the development of HRIPs focuses not only on the increase in refractive index but also on the balance of other properties. Sulfur-containing high refractive index polymers have received extensive attention from researchers due to their excellent properties. In recent years, not only ultrahigh refractive index sulfur-containing polymers have been continuously developed, but also low dispersion, low birefringence, high transparency, good mechanical properties, and machinability have been studied. The design of HRIPs is generally based on formulas and existing experience. In fact, molecular structure and properties are closely related. Mastering the structure-property relationship helps researchers to develop high refractive index polymer materials with balanced properties. This review briefly introduces the preparation methods of sulfur-containing high refractive index polymers, and summarizes the structure-property relationship between the sulfur-containing molecular structure and optical properties, mechanical properties, thermal properties, etc. Finally, the important role of synergistic effect in the synthesis of HRIPs and the prospect of future research on HRIPs are proposed.


Clonal Dissemination of Plasmid-Mediated Carbapenem and Colistin Resistance in Refugees Living in Overcrowded Camps in North Lebanon.
Carbapenem and colistin-resistant bacteria represent a global public health problem. Refugees carrying these bacteria and living in inadequate shelters can spread these microorganisms. The aim of this study was to investigate the intestinal carriage of these bacteria in Syrian refugees in Lebanon. Between June and July 2019, 250 rectal swabs were collected from two refugee camps in North Lebanon. Swabs were cultured on different selective media. Antibiotic susceptibility testing was performed using the disk diffusion method. Carbapenemase-encoding genes and mcr genes were investigated using real-time polymerase chain reaction (RT-PCR) and standard polymerase chain reaction (PCR). Epidemiological relatedness was studied using multilocus sequence typing (MLST). From 250 rectal swabs, 16 carbapenem-resistant, 5 colistin-resistant, and 4 colistin and carbapenem-resistant Enterobacteriaceae were isolated. The isolates exhibited multidrug-resistant phenotypes. Seven Klebsiella pneumoniae isolates harboured the blaOXA-48 gene, and in addition four K. pneumoniae had mutations in the two component systems pmrA/pmrB, phoP/phoQ and co-harboured the blaNDM-1 gene. Moreover, the blaNDM-1 gene was detected in six Escherichia coli and three Enterobacter cloacae isolates. The remaining five E. coli isolates harboured the mcr-1 gene. MLST results showed several sequence types, with a remarkable clonal dissemination. An urgent strategy needs to be adopted in order to avoid the spread of such resistance in highly crowded underserved communities.


[Economics, health, and health care].
Since the seventies the growing of sanitary expenses has become the first worry for our authorities and the seeking of solutions has brought the presence of economists to solve the health problems. Therefore the health economy studies the production and distribution of health and sanitary attention in two senses: one like a discipline (usually located in universities and publications in the area of economy) and another one to the resolution of health problems and care, favouring interdisciplinary cooperation and its application to management. When speaking about the relation ship between economy and health, it is necessary to consider three areas: first that of basic concepts in economy: demand, offer, elasticity, market faults and state intervention in economy. The second aspect goes to the specific characteristics of sanitary care from economic perspective and the application of economic concepts to health field. And finally the third one is the field of the most important techniques of economic evaluation for sanitary programs and the analysis of sanitary systems reforms in some countries.


Nonclassical protein secretion by Bacillus subtilis in the stationary phase is not due to cell lysis.
The carboxylesterase Est55 has been cloned and expressed in Bacillus subtilis strains. Est55, which lacks a classical, cleavable N-terminal signal sequence, was found to be secreted during the stationary phase of growth such that there is more Est55 in the medium than inside the cells. Several cytoplasmic proteins were also secreted in large amounts during late stationary phase, indicating that secretion in B. subtilis is not unique to Est55. These proteins, which all have defined cytoplasmic functions, include GroEL, DnaK, enolase, pyruvate dehydrogenase subunits PdhB and PdhD, and SodA. The release of Est55 and those proteins into the growth medium is not due to gross cell lysis, a conclusion that is supported by several lines of evidence: constant cell density and secretion in the presence of chloramphenicol, constant viability count, the absence of EF-Tu and SecA in the culture medium, and the lack of effect of autolysin-deficient mutants. The shedding of these proteins by membrane vesicles into the medium is minimal. More importantly, we have identified a hydrophobic α-helical domain within enolase that contributes to its secretion. Thus, upon the genetic deletion or replacement of a potential membrane-embedding domain, the secretion of plasmid gene-encoded mutant enolase is totally blocked, while the wild-type chromosomal enolase is secreted normally in the same cultures during the stationary phase, indicating differential specificity. We conclude that the secretion of Est55 and several cytoplasmic proteins without signal peptides in B. subtilis is a general phenomenon and is not a consequence of cell lysis or membrane shedding; instead, their secretion is through a process(es) in which protein domain structure plays a contributing factor.


Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.
In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications.


Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia.
Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia. Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination. PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels. In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.


Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo.
Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC's capital, Kinshasa, to inform additional prevention efforts. We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as "exposed" and "unexposed," respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.


A pedunculated left ventricular hemangioma initially misdiagnosed as thrombus in a woman with atypical chest pain.
The incidence of cardiac masses increased as echocardiography is becoming increasingly popular. Benign tumors of the heart constitute about 72% of all primary cardiac neoplasms and hemangioma accounts for 5-10% of benign cardiac tumors. Cardiac hemangiomas are generally asymptomatic and diagnosed incidentally during echocardiography or magnetic resonance imaging (MRI). We reported a 52-year-old woman presented with atypical chest pain and exertional dyspnea. The echocardiographic examination revealed a hyperechoic round mass in the left ventricle. With an initial diagnosis of left ventricular thrombus, the patient underwent cardiac MRI. The mass was found compatible with cardiac hemangioma. It was removed surgically and histopathologic evaluation identified a cardiac hemangioma. As reports of cardiac hemangioma are extremely rare and cardiac masses are mostly thought to be thrombi or myxomas (being the most common primary cardiac tumor), such hemangioma cases warrant attention as possibility of hemangioma should also be kept in mind.


Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction.
Caloric restriction (CR) has positive effects on health and longevity. CR in mammals implements time-restricted (TR) feeding, a short period of feeding followed by prolonged fasting. Periodic fasting, in the form of TR or mealtime, improves metabolism without reduction in caloric intake. In order to understand the relative contribution of reduced food intake and periodic fasting to the health benefits of CR, we compared physiological and metabolic changes induced by CR and TR (without reduced food intake) in mice. CR significantly reduced blood glucose and insulin around the clock, improved glucose tolerance, and increased insulin sensitivity (IS). TR reduced blood insulin and increased insulin sensitivity, but in contrast to CR, TR did not improve glucose homeostasis. Liver expression of circadian clock genes was affected by both diets while the mRNA expression of glucose metabolism genes was significantly induced by CR, and not by TR, which is in agreement with the minor effect of TR on glucose metabolism. Thus, periodic fasting contributes to some metabolic benefits of CR, but TR is metabolically different from CR. This difference might contribute to differential effects of CR and TR on longevity.


Accuracy and Predictability of PANC-3 Scoring System over APACHE II in Acute Pancreatitis: A Prospective Study.
Acute Pancreatitis (AP) is one of the common conditions encountered in the emergency room. The course of the disease ranges from mild form to severe acute form. Most of these episodes are mild and spontaneously subsiding within 3 to 5 days. In contrast, Severe Acute Pancreatitis (SAP) occurring in around 15-20% of all cases, mortality can range between 10 to 85% across various centres and countries. In such a situation we need an indicator which can predict the outcome of an attack, as severe or mild, as early as possible and such an indicator should be sensitive and specific enough to trust upon. PANC-3 scoring is such a scoring system in predicting the outcome of an attack of AP. To assess the accuracy and predictability of PANC-3 scoring system over APACHE II in predicting severity in an attack of AP. This prospective study was conducted on 82 patients admitted with the diagnosis of pancreatitis. Investigations to evaluate PANC-3 and APACHE II were done on all the patients and the PANC-3 and APACHE II score was calculated. PANC-3 score has a sensitivity of 82.6% and specificity of 77.9%, the test had a Positive Predictive Value (PPV) of 0.59 and Negative Predictive Value (NPV) of 0.92. Sensitivity of APACHE II in predicting SAP was 91.3% and specificity was 96.6% with PPV of 0.91, NPV was 0.96. Our study shows that PANC-3 can be used to predict the severity of pancreatitis as efficiently as APACHE II. The interpretation of PANC-3 does not need expertise and can be applied at the time of admission which is an advantage when compared to classical scoring systems.


The influence of salt intake on the metabolic acidosis of chronic renal failure;.
The influence of dietary salt on the levels of plasma bicarbonate and on the characteristics of bicarbonate reabsorption was studied in experimental chronic renal failure. Chronic renal failure was produced in rats by sequential partial nephrectomies. The control group received a diet constant in salt content throughout the progression of renal failure; the other group (PRNa), at each stage of renal failure, received salt intake reduced in direct proportion to the fall in glomerular filtration rate (GFR). In the steady state, the quantities of urinary sodium closely approximated intake in obth groups of animals. The adaptive increased natriuresis per nephron exhibited by the control animals was prevented in the PRNa animals. The PRNa group had (a) higher plasma bicarbonate levels, (b) increased bicarbonate thresholds, and (c) increased maximal tubular reabsorptive capacity for bicarbonate. As renal failure progresses, dietary salt can become a determining factor of the levels at which plasma bicarbonate is maintained. Proportional reduction of dietary salt results in bicarbonate conservation in rats with experimental progressive renal failure.