Phylogenetic assessment of culture collection strains of Thiobacillus thioparus, and definitive 16S rRNA gene sequences for T. thioparus, T. denitrificans, and Halothiobacillus neapolitanus.
The 16S rRNA gene sequences of 12 strains of Thiobacillus thioparus held by different culture collections have been compared. A definitive sequence for the reference type strain (Starkey; ATCC 8158(T)) was obtained. The sequences for four examples of the Starkey type strain were essentially identical, confirming their sustained identity after passage through different laboratories. One strain (NCIMB 8454) was reassigned as a strain of Halothiobacillus neapolitanus, and a second (NCIMB 8349) was a species of Thermithiobacillus. These two strains have been renamed in their catalog by the National Collection of Industrial and Marine Bacteria. The 16S rRNA gene sequence of the type strain of Halothiobacillus neapolitanus (NCIMB 8539(T)) was determined and used to confirm the identity of other culture collection strains of this species. The reference sequences for the type strains of Thiobacillus thioparus and Halothiobacillus neapolitanus have been added to the online List of Prokaryotic Names with Standing in Nomenclature. Comparison of the 16S rRNA gene sequences available for strains of Thiobacillus denitrificans indicated that the sequence for the type strain (NCIMB 9548(T)) should always be used as the reference sequence for new and existing isolates.


Astrocytes in the pathophysiology of neuroinfection.
Key homeostasis providing cells in the central nervous system (CNS) are astrocytes, which belong to the class of cells known as atroglia, a highly heterogeneous type of neuroglia and a prominent element of the brain defence. Diseases evolve due to altered homeostatic state, associated with pathology-induced astroglia remodelling represented by reactive astrocytes, astroglial atrophy and astrodegeneration. These features are hallmarks of most infectious insults, mediated by bacteria, protozoa and viruses; they are also prominent in the systemic infection. The COVID-19 pandemic revived the focus into neurotropic viruses such as SARS-CoV2 (Coronaviridae) but also the Flaviviridae viruses including tick-borne encephalitis (TBEV) and Zika virus (ZIKV) causing the epidemic in South America prior to COVID-19. Astrocytes provide a key response to neurotropic infections in the CNS. Astrocytes form a parenchymal part of the blood-brain barrier, the site of virus entry into the CNS. Astrocytes exhibit aerobic glycolysis, a form of metabolism characteristic of highly morphologically plastic cells, like cancer cells, hence a suitable milieu for multiplication of infectious agent, including viral particles. However, why the protection afforded by astrocytes fails in some circumstances is an open question to be studied in the future.


A stable Cerberus tris(maloNHC) and its coinage metal complexes.
The first trisanionic Cerberus-type maloNHC has been generated and coordinated to two different coinage metals (Au(i) and Ag(i)). The resulting triszwitterionic metal complexes have been characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The molecular structures of the new metal complexes reveal an average AuAu and AgAg separation of 20.89 and 21.03 Å respectively, the longest distances reported to date for any related Cerberus-type NHCs.


Prevalence of osteoporosis in patients with chronic kidney disease (stages 3-5) in comparison with age- and sex-matched controls: A study from Kashmir Valley Tertiary Care Center.
Chronic kidney disease (CKD) is associated with a range of metabolic bone diseases. Fracture rates are higher in CKD patients than age-matched controls throughout all the five stages of CKD. Dialysis patients have 4 times as many hip fractures as expected for their age. CKD forms an independent risk factor for osteoporosis, even in the absence of traditional risk factors. This study was carried out at the nephrology unit in a tertiary care center of Kashmir to know the prevalence of osteoporosis in CKD patients having glomerular filtration rate (GFR) <60 mL/min (stages 3-5). Among the 151 cases studied, the average estimated GFR was 16.78 ± 10.714 mL/min. There were 98 males (64.9%) and 53 females (35.1%). Their mean age was 51.01 ± 14.138 years. Osteoporosis based on femoral neck T-Score was seen in 31 patients (31.6%) while 43 patients (28.5%) had osteoporosis at L1, L2 lumbar vertebrae. The prevalence of osteoporosis based on femoral neck T-Score as well as osteopenia was highest in stage-5 CKD. In our study, the body mass index (BMI) had a positive correlation with osteoporosis; low BMI patients were at higher risk for osteoporosis (P = 0.014). In the Kashmir valley, the prevalence of osteoporosis was 31.8% in CKD patients against 22% in controls. Thus, CKD forms an important risk factor for osteoporosis even in the absence of traditional risk factors. We recommend early screening, detection, and management of osteoporosis to reduce the burden of morbidity and mortality in this subset of patients.


Assessing physician attitudes and perceptions of Alzheimer's disease across Europe.
Given the important role that physicians play in clinical care, disease advocacy, national health policy making and clinical research, the IMPACT survey sought to assess the attitudes and perceptions of physicians in 3 general categories: diagnosis and treatment of Alzheimer's disease (AD); caregivers and families of patients with AD; and the role of government in dealing with this disease and its consequences. Survey respondents comprised a total of 250 generalists and 250 specialists (neurologists, geriatricians, neuro-psychiatrists, psychiatrists and psychogeriatricians) from France, Germany, Italy, Spain and the United Kingdom. Physicians were aged 25 to 69 years, in practice for between 5 and 30 years and currently spending more than 50% of their time in direct patient care. Results showed that a sizable majority of physicians throughout Europe, specialists and generalists alike, agree that: 1) AD is underdiagnosed and undertreated; 2) patients and families are not prepared to recognise the early symptoms of the disease; 3) early treatment can help to slow the progression of the disease; and 4) more effective treatments are needed. Attitudes were statistically significantly different between some groups of physicians regarding disclosure of the diagnosis of AD, the benefits of lifestyle modification, and the value of AD-specific medication in patients whose symptoms are worsening. Differences in attitudes and perceptions of AD between specialists and generalists were limited; differences between countries were more common and of greater magnitude, particularly with respect to barriers to the use of prescription medications.


Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors.
Stimulation of histamine H1 receptors initiates the hydrolysis of phosphatidylinositides and results in the production of inositol (1, 4,5)-triphosphate and intracellular Ca2+ mobilization. Although the mechanism for signal transduction via the H1 recptor has been extensively investigated, little is known about the correlation between the sensitivity of histamine-induced Ca2+ mobilization and the density of H1 receptors in cultured cells. Cytosolic free Ca2+ concentration ([Ca2+]i) after stimulation by histamine was monitored in single CHO and rat C6-glioma cells stably expressed with H1 receptors and astrocytoma 1321N1 cells using the Ca2+-sensitive dye Indo-1 and dynamic single cell imaging techniques (ACAS 570 laser cytometer). Both of the H1 receptor-expressed CHO cells and C6-glioma cells were over 10 times more sensitive to histamine than astrocytoma 1321N1 cells in which H1 receptors were naturally present. The density of H1 receptors in the transfected cells was also more than 10-fold that of 1321N1 cells. In addition, inhibition of intracellular Ca2+-ATPase by thapsigargin elicited an increase in [Ca2+]i in H1 receptor-overexpessed cells and astrocytoma 1321N1 cells with similar sensitivity. These data suggest that the sensitivity of Ca2+ mobilization by histamine in these cells was correlatively augmented with the increase in the density of H1 receptors.


Estimating the Number of Civilian Casualties in Modern Armed Conflicts-A Systematic Review.
Objective: To examine the possibility of estimating the number of civilian casualties in modern armed conflicts. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using PubMed, Scopus, and Web of Science search engines. The outcome was analyzed using a qualitative inductive thematic analysis. The scientific evidence of selected article was assessed, using the Health Evidence Quality Assessment Tool. Findings: The review of 66 included articles in this study indicates that with an increasing number of public health emergencies and the lack of vital elements of life such as water and food, emerging armed conflicts seem to be inevitable. In contrast to military-led cross-border traditional wars, modern armed conflicts affect internally on local communities and take civilian lives. Consequently, the measures and tools used in traditional military-led cross-border wars to adequately tally wounded and dead for many decades under the mandates of the International Humanitarian Law, is insufficient for modern warfare. While casualty counting during modern conflicts is deficient due to organizational, political or strategic reasons, the international organizations responsible for collecting such data (the International Federation of Red Cross and Red Crescent and International Institute of Humanitarian Law) face difficulties to access the conflict scene, resulting in under-reported, unreliable or no-reported data. Conclusion: There are challenges in estimating and counting the number of civilian casualties in modern warfare. Although the global need for such data is evident, the risks and barriers to obtaining such data should be recognized, and the need for new international involvement in future armed conflicts should be emphasized.


Zero Lower Bound and negative interest rates: Choices for monetary policy in the UK.
There have been relatively few analyses of the policy context and consequences of a Zero Lower Bound (ZLB) for nominal interest rates. This paper sets out monetary policy alternatives, including negative interest rates, a revision of the inflation target, and rendering unconventional policy instruments such as QE conventional (permanent). Following extensive discussion of policy options, we set out a model that explores the impacts of the real policy rate on economic growth, employment and inflation, with particular attention to the British economy. We use a Time-Varying Structural Vector Auto-regressive (TVSVAR) Model where the sources of time variation are both the coefficients and variance-covariance matrix of the innovations. It was found that real rates have significant implications for real growth, the labour market and price stability even when monetary policy was constrained at the ZLB in nominal terms. The study additionally applies a discrete break in the data to focus on the Post-Global Financial Crisis and ZLB period. This indicates that the effectiveness of real rates did not diminish and this has important implications in terms of a policy approach which seeks to exploit real negative rates.


[Characteristics of ion selective electrodes with hetero-poly anion sites].
Drug ion-selective electrodes made with hetero-poly anion as exchange site exhibit better performances than the respective electrodes of conventional tetraphenylboron type, yielding low detection limits and fast responses. Functions of propantheline, berberine, dibazol, thiamine, streptomycin, moroxydine, tetracycline, oxytetracycline, doxycycline, erythromycin, carbetapentane, benzydamine, tetramisole and trifluoperazine electrodes are reported. The electrodes can be used in potentiometric determinations of the respective drugs in aqueous solutions, urine and mixture of water and organic solvents.


Effect of vitamin D₃ overdose and calcium supplementation in experimental nephrolithiasis model.
There is little information in the literature relating supplementary oral usage of vitamin D and calcium to the development of kidney stones. To evaluate the effect of high dose, 200 IU of vitamin D3 (V) with calcium supplementation (Ca). Experimental model consists of insertion of pellets into the bladder of rats. V was administered for 30 days with or without Ca. The rats were divided in 6 groups: 1. Sham, 2. Pellets control; 3. V control; 4. Pellets + V; 5. Pellets + Ca and 6. Pellets + Ca + V. 50% and 17% decreases bladder stones formation in groups 5 and 6, p < 0.005 comparing with the group 2 were observed. There was no hypercalcemia or hypercalciuria in all groups. We observed a significant decrease in calciuria in group 6 (p = 0.03). The administration of the V associated with Ca significantly decreased the formation of stones and caused a significant reduction in urinary calcium, suggesting a protection in the lithogenic pathophysiology.


Secondary hydrogen isotope effects on the structure and stability of cation-pi complexes (cation = Li(+), Na(+), K(+) and pi = acetylene, ethylene, benzene).
Secondary hydrogen isotope effects on the geometries, electronic wave functions and binding energies of cation-pi complexes (cation = Li(+), Na(+), K(+) and pi = acetylene, ethylene, benzene) are investigated with NEO/HF and NEO/MP2 methods. These methods determine both electronic and nuclear wave functions simultaneously. Our results show that an increase of the hydrogen nuclear mass leads to the elongation of the cation-pi bond distance and the decrease in its binding energy. An explanation to this behavior is given in terms of the changes in the pi-molecule electronic structure and electrostatic potential induced by isotopic substitutions.


Interannual variability in net ecosystem carbon production in a rain-fed maize ecosystem and its climatic and biotic controls during 2005-2018.
Interannual variability (IAV) in net ecosystem carbon production (NEP) plays an important role in the processes of the carbon cycle, but the long-term trends in NEP and the climatic and biotic control of IAV in NEP still remain unclear in agroecosystems. We investigated interannual variability in NEP, expressed as annual values and anomalies, and its climatic and biotic controls using an eddy-covariance dataset for 2005-2018 for rain-fed spring maize in northeastern China. Average annual NEP was 270±31 g C m-2yr -1, with no significant changes over time. The effects on interannual variability in NEP of gross ecosystem productivity (GEP) that was mainly controlled by soil water content (SWC) and leaf area index (LAI), were more than those of respiration (RE) that was controlled by temperature and LAI. Further, maximum daily NEP (NEPmax) that was dominated by summer vapor pressure deficit explained the largest fraction of annual anomalies in NEP, followed by carbon dioxide uptake period (CUP) that was defined by the beginning date (BDOY) and the end date (EDOY) of CUP. The variability in BDOY was mainly determined by spring precipitation and the effective accumulated temperature, and the variability in EDOY was determined by autumn precipitation, SWC and LAI. NEP may decrease with declining precipitation in the future due to decreasing GEP, NEPmax, or CUP, and irrigation and residues cover may be useful in efforts to maintain current NEP levels. Our results indicate that interannual variability in NEP in agroecosystems may be more sensitive to changes in water conditions (such as precipitation, SWC and VPD) induced by climate changes, while temperature may be an important indirect factor when VPD is dominated.


Evolutionarily Conserved Proline Residues Impede the Misfolding of the Mouse Prion Protein by Destabilizing an Aggregation-competent Partially Unfolded Form.
The misfolding of the prion protein has been linked to several neurodegenerative diseases. Despite extensive studies, the mechanism of the misfolding process remains poorly understood. The present study structurally delineates the role of the conserved proline residues present in the structured C-terminal domain of the mouse prion protein (moPrP) in the misfolding process. It is shown that mutation of these Pro residues to Ala leads to destabilization of the native (N) state, and also to rapid misfolding. Using hydrogen-deuterium exchange (HDX) studies coupled with mass spectrometry (MS), it has been shown that the N state of moPrP is in rapid equilibrium with a partially unfolded form (PUF2*) at pH 4. It has been shown that the Pro to Ala mutations make PUF2* energetically more accessible from the N state by stabilizing it relative to the unfolded (U) state. The apparent rate constant of misfolding is found to be linearly proportional to the extent to which PUF2* is populated in equilibrium with the N state, strongly indicating that misfolding commences from PUF2*. It has also been shown that the Pro residues restrict the boundary of the structural core of the misfolded oligomers. Overall, this study highlights how the conserved proline residues control misfolding of the prion protein by modulating the stability of the partially unfolded form from which misfolding commences.


Preliminary experience using S1-alar iliac fixation with navigation: technical note.
Traditional iliac screws and S2-alar iliac (S2-AI) screws are common methods used for pelvic fixation, and many surgeons advocate pelvic fixation for long-segment fixation to the sacrum. However, in patients without severe deformities and only degenerative conditions, many surgeons may choose S1 screws only. Moreover, even with S2-AI screws, there is more muscular dissection than with using S1 screws, and the rod connection can be cumbersome in both S2-AI fixation and placing iliac screws. Using a surgical video, artist's illustration, and intraoperative photographs, the authors describe the S1-AI screw fixation technique that allows for single-screw sacral and iliac fixation, requires less distal dissection of the sacrum, allows for easier rod connection, and may be an option in degenerative conditions needing pelvic fixation. However, this is a preliminary feasibility study, and in long fusion constructs, this type of fixation has only been used in conjunction with L5-S1 anterior lumbar interbody fusion (ALIF), and there are no long-term data on the use of this screw fixation technique without ALIF. In short-segment revision fusions, this technique may be considered for salvage in cases of large halos in the sacrum from loosened S1 screw fixation.


Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus.
In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This is due primarily to a reduction in the transcriptional activity of TFIIIC, a transcription factor which binds in a sequence specific manner to the internal promoter of pol III genes. Using gel retardation assays, we have shown previously that inhibition of pol III transcription by poliovirus is correlated with disappearance of a transcriptionally active form of TFIIIC (complex I) concomitant with the appearance of a faster mobility, transcriptionally inactive form of TFIIIC (complex III). We show here that a poliovirus with a point mutation in the proteinase 3C (3Cpro) region failed to produce complex III and is limited in its ability to inhibit pol III transcription compared with the wild-type virus. Incubation of purified 3Cpro, expressed in Escherichia coli, with transcriptionally active TFIIIC (complex I) in vitro resulted in generation of the transcriptionally inactive complex III form of TFIIIC. In an in vitro transcription assay, treatment of the complex I form of TFIIIC with 3Cpro almost completely inhibited pol III transcription. Finally expression of the 3Cpro gene in transfected HeLa cells resulted in significant inhibition of pol III-mediated transcription. The results presented here suggest that proteolysis of the transcriptionally active form of TFIIIC by poliovirus 3Cpro is a mechanism by which poliovirus inhibits host cell RNA pol III transcription.


Vaginal ecosystem modeling of growth patterns of anaerobic bacteria in microaerophilic conditions.
The human vagina constitutes a complex ecosystem created through relationships established between host mucosa and bacterial communities. In this ecosystem, classically defined bacterial aerobes and anaerobes thrive as communities in the microaerophilic environment. Levels of CO2 and O2 present in the vaginal lumen are impacted by both the ecosystem's physiology and the behavior and health of the human host. Study of such complex relationships requires controlled and reproducible causational approaches that are not possible in the human host that, until recently, was the only place these bacterial communities thrived. To address this need we have utilized our ex vivo human vaginal mucosa culture system to support controlled, reproducible colonization by vaginal bacterial communities (VBC) collected from healthy, asymptomatic donors. Parallel vaginal epithelial cells (VEC)-VBC co-cultures were exposed to two different atmospheric conditions to study the impact of CO2 concentrations upon the anaerobic bacteria associated with dysbiosis and inflammation. Our data suggest that in the context of transplanted VBC, increased CO2 favored specific lactobacilli species defined as microaerophiles when grown as monocultures. In preliminary studies, the observed community changes also led to shifts in host VEC phenotypes with significant changes in the host transcriptome, including altered expression of select molecular transporter genes. These findings support the need for additional study of the environmental changes associated with behavior and health upon the symbiotic and adversarial relationships that are formed in microbial communities present in the human vaginal ecosystem.


Energy transfer-mediated white light emission from Nile red-doped 9,10-diphenylanthracene nanoaggregates upon excitation with near UV light.
The low cost, ease of preparation, colour tunability and wide application range garnered huge research interest on organic light emitting diode materials (OLED). The development of white light-emitting organic diode materials is mostly targeted for this. Anthracene derivatives have recently emerged as low-cost and efficient blue light-emitting diodes. However, developing efficient organic diode materials that cover the entire visible spectrum is very challenging. Herein, we demonstrated that Nile red (NR)-doped 9,10-diphenylanthracene (DPA) nanoaggregates provided strong white light emission upon excitation with near UV light. The dual emissions of the DPA nanoaggregates covering the blue and green regions were exploited and combined with the controlled red emission of the properly doped NR dye to cover the full visible spectrum, rendering white light emission with a quantum yield of >0.4. The fluorescence spectra of the DPA nanoaggregates doped with NR at various concentrations were monitored and their CIE coordinates were followed to evaluate the proper doping ratio for equal-energy white-light emission. Concurrent time-resolved emission studies provided mechanistic insights into the energy transfer from the exciton and excimer states of DPA to NR. It was revealed that the energy transfer from the singlet excitonic state of DPA followed the diffusion-assisted resonance energy transfer (RET) model. On the other hand, the excimer state showed negligible diffusion and energy transfer from this state found to follow the single-step Förster resonance energy transfer mechanism. The observation of efficient white light emission in the doped DPA nanoaggregates was proposed to have prospective applications in OLED devices, given the fact that triplet excitons may be exploited for emission through the efficient triplet-triplet annihilation contribution to fluorescence enhancement.


Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering.
This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wavelet transform, which localizes distinctive spike features, with superparamagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods.


Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center.
Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first- or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Evaluation of the efficacy and tolerance of mitotane in CD patients. Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5 ± 8.9 mg/l, with a mean daily dose of 2.6 ± 1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P<0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), P=0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.


Severe Alcoholic Hepatitis Effectively Treated with Vitamin E as an Add-on to Corticosteroids.
A 49-year-old woman with a history of heavy alcohol drinking was admitted to our hospital due to jaundice and abdominal distention. A blood test showed leukophilia, mild hypoalbuminemia, hyperbilirubinemia, hepatobiliary injury and coagulopathy. Image studies showed an extremely enlarged fatty liver and splenomegaly. The Japan alcoholic hepatitis score and Maddrey's discriminant function were 10 and 54 points, respectively. We diagnosed her with severe alcoholic hepatitis and treated her with corticosteroids, but her liver function did not improve. We therefore administered the vitamin E product tochopheryl acetate (150 mg/day) as an add-on therapy, after which her leukophilia, liver enzymes and coagulopathy improved immediately.


Ear as an alternative sampling site for GSR analysis following shotgun discharge.
Detection of GSR particles potentially indicates that a person fired a gun or somehow involved to a shooting event. GSR on the shooter's hand, face, and clothing may disappear within hours and with sweat secretion, washing or cleaning to remove evidences. Due to its anatomical properties, ears are relatively protected; therefore, we aimed to identify GSR particles on ears, to compare its anatomical parts of ears, and compare ears with common GSR sampling sites, based on firing frequency. A 12-gauge semi-automatic shotgun was used. In the 4-week study, one shot in the first week, two consecutive shots in second week, three shots in third week, and five shots in fourth week were fired by six participants. Samples were taken from MAE, CA, and AAECA of both ears and common GSR sampling sites. The characteristic 3-component structure (Pb/Sb/Ba) of the samples was analyzed by SEM/EDX. Right CA was the most suitable area for sampling, which might be attributed to posture of body during targeting. Right ear was the most suitable area to take samples from CA or MAE in 3-shot group. Besides, left AAECA in 1- and 2-shot groups and the left MAE in 5-shot group were the most suitable areas for GSR sampling. In conclusion, ear seems to be a valuable alternative for detection of GSR particles, due to its complex anatomical structure potentially preventing loss of GSR with daily cleaning. Findings suggested that crime scene investigation teams and criminal laboratory staff should consider ear as a valuable alternative for GSR detection.


Macrophage antiviral activity: extrinsic versus intrinsic activity.
Peritoneal exudate cells from strains of mice both resistant and susceptible to challenge with mouse hepatitis virus strain JHM were examined for extrinsic and intrinsic antiviral activity. Thioglycolate-elicited and resident peritoneal cells from uninfected mice were able to suppress viral growth in a permissive cell. The active cell in both populations is an adherent, radiation-resistant, Thy-1.2 antigen- and Ia antigen-negative cell. The suppression of virus replication was not related to nonspecific cellular cytotoxicity directed against the permissive host cell, and no interferon was detected. The expression of extrinsic antiviral activity was not related to the ability of the host to resist mouse hepatitis virus infection by virtue of either age or genetic background. The expression of intrinsic antiviral activity, on the other hand, correlated with the ability of the host to resist virus challenge, indicating a characteristic distinction between these two in vitro mechanisms of macrophage-mediated antiviral activity with regard to host resistance to viral infection. Further, the ability of a macrophage to support viral replication itself was independent of the ability of the macrophage to suppress virus growth in another cell.


Mary S. Easton Center of Alzheimer's Disease Research at UCLA: advancing the therapeutic imperative.
The Mary S. Easton Center for Alzheimer's Disease Research (UCLA-Easton Alzheimer's Center) is committed to the "therapeutic imperative" and is devoted to finding new treatments for Alzheimer's disease (AD) and to developing technologies (biomarkers) to advance that goal. The UCLA-Easton Alzheimer's Center has a continuum of research and research-related activities including basic/foundational studies of peptide interactions; translational studies in transgenic animals and other animal models of AD; clinical research to define the phenotype of AD, characterize familial AD, develop biomarkers, and advance clinical trials; health services and outcomes research; and active education, dissemination, and recruitment activities. The UCLAEaston Alzheimer's Center is supported by the National Institutes on Aging, the State of California, and generous donors who share our commitment to developing new therapies for AD. The naming donor (Jim Easton) provided substantial funds to endow the center and to support projects in AD drug discovery and biomarker development. The Sidell-Kagan Foundation supports the Katherine and Benjamin Kagan Alzheimer's Treatment Development Program, and the Deane F. Johnson Alzheimer's Research Foundation supports the Deane F. Johnson Center for Neurotherapeutics at UCLA. The John Douglas French Alzheimer's Research Foundation provides grants to junior investigators in critical periods of their academic development. The UCLA-Easton Alzheimer's Center partners with community organizations including the Alzheimer's Association California Southland Chapter and the Leeza Gibbons memory Foundation. Collaboration with pharmaceutical companies, biotechnology companies, and device companies is critical to developing new therapeutics for AD and these collaborations are embraced in the mission of the UCLA-Easton Alzheimer's Center. The Center supports excellent senior 3 investigators and serves as an incubator for new scientists, agents, models, technologies and concepts that will significantly influence the future of AD treatment and AD research.


Impulsivity in Adolescent Bipolar Disorder.
Increased impulsivity has been demonstrated to be a trait feature of adults with bipolar disorder (BD), yet impulsivity has received little study in adolescents with BD. Thus, it is unknown whether it is a trait feature that is present early in the course of the disorder. We tested the hypotheses that self-reported impulsiveness is increased in adolescents with BD, and that it is present during euthymia, supporting impulsiveness as an early trait feature of the disorder. Impulsiveness was assessed in 23 adolescents with BD and 23 healthy comparison (HC) adolescents using the self-report measure of impulsivity, the Barratt Impulsiveness Scale (BIS), comprised by attentional, motor and nonplanning subscale scores. Effects of subscale scores and associations of scores with mood state and course features were explored. Total and subscale BIS scores were significantly higher in adolescents with BD than HC adolescents. Total, attentional and motor subscale BIS scores were also significantly higher in the subset of adolescents with BD who were euthymic, compared to HC adolescents. Adolescents with BD with rapid-cycling and chronic mood symptoms had significantly higher total and motor subscale BIS scores than adolescents with BD without these course features. These results suggest increased self-reported impulsiveness is a trait feature of adolescents with BD. Elevated impulsivity may be especially prominent in adolescents with rapid-cycling and chronic symptoms.


The effect of hitch-hiking on genes linked to a balanced polymorphism in a subdivided population.
The effect of multi-allelic balancing selection on nucleotide diversity at linked neutral sites was investigated by simulations of subdivided populations. The motivation is to understand the behaviour of self-recognition systems such as the MHC and plant self-incompatibility. For neutral sites, two types of subdivision are present: (1) into demes (connected by migration), and (2) into classes defined by different functional alleles at the selected locus (connected by recombination). Previous theoretical studies of each type of subdivision separately have shown that each increases diversity, and decreases the relative frequencies of low-frequency variants, at neutral sites or loci. We show here that the two types of subdivision act non-additively when sampling is at the whole population level, and that subdivision produces some non-intuitive results. For instance, in highly subdivided populations, genetic diversity at neutral sites may decrease with tighter linkage to a selected locus or site. Another conclusion is that, if there is population subdivision, balancing selection leads to decreased expected FST values for neutral sites linked to the selected locus. Finally, we show that the ability to detect balancing selection by its effects on linked variation, using tests such as Tajima's D, is reduced when genes in a subdivided population are sampled from the total population, rather than within demes.


Effect of two types of composite resin on oral bacterial plaque. "In vitro qualitative and quantitative study".
160 specimens of composite (80 chemical and 80 light cured) were prepared in teflon mold 4 mm x 2.5 mm in dimension. Plaque samples were collected using absorbent paper points from 20 normal persons and 20 persons with cervical carious teeth. The samples were inoculated in TSB containing both types of composites. Duplicate cultures were done for aerobic and anaerobic incubations at 37 degrees C. There was no effect of both types of composite on the quality of the isolated organisms from normal group or patient group. Chemical and light cured composite increased significantly the count of aerobic bacterial plaque from normal group. While they decreased the count of aerobic bacterial plaque from patient group and also the anaerobic bacterial plaque from both normal and patient group.


Effect of trauma on the mental health of Palestinian children and mothers in the Gaza Strip.
A cross-sectional study was conducted among 286 Palestinian children 9-18 years of age and their mothers in the Gaza Strip. Traumatic events recollected by children living in areas of conflict, the prevalence of post-traumatic stress reactions and the relationship between children's and mothers' mental health were investigated. The Gaza Traumatic Events Checklist, Impact of Event Scale (IES) and General Health Questionnaire (GHQ) were used to measure outcome. Children experienced on average four traumatic events; one-third reported significant post-traumatic stress reactions. IES scores were higher among girls and mothers' GHQ scores significantly predicted children's IES scores.


Natural evolution of patent ductus arteriosus in the extremely preterm infant.
The persistence of the patent ductus arteriosus (PDA) is frequently encountered in very preterm infants. Neither preventive nor curative treatments of PDA have been shown to improve the outcome of these infants. Since no consensus on optimal treatment of PDA is established, we evaluated the rate of spontaneous PDA closure in infants born before 28 weeks of gestation. We studied a retrospective cohort of 103 infants (gestational age 24-27 weeks) admitted to our neonatal intensive care unit from 1 June 2008 to 31 July 2010. Maternal and neonatal characteristics were collected. The PDA was defined by the persistence of ductal patency after 72 h and was followed up by regular echocardiography. Twelve infants died within the first 72 h and were excluded from the analysis. Among 91 infants analysed, 8 (9%) closed their ductus arteriosus before 72 h and the ductus could not be determined patent in 13. Of the 70 infants with a PDA still persistent, one underwent surgical ligation and echocardiography showed spontaneous closure in 51 (73%) of them. In the remaining 18 infants, the date of PDA closure could not be determined either because of their death (n=11) or due to discharge (n=7). Overall, a spontaneous closure of the ductus arteriosus was observed in 59 of the 91 infants. We have to question whether exposure to the risks of therapeutic interventions targeted for ductal closure is warranted since a PDA closes spontaneously in at least 73% of infants born before 28 weeks.


Cortical morphological changes in chronic migraine in a Taiwanese cohort: Surface- and voxel-based analyses.
Previous voxel- or surface-based morphometric analysis studies have revealed alterations in cortical structure in patients with chronic migraine, yet with inconsistent results. The discrepancies may be derived partly from the sample heterogeneity. Employing both methods in a clinically homogenous group may provide a clearer view. Structural MRI data from 30 prevention-naïve patients with chronic migraine without medication overuse headache or a history of major depression and 30 healthy controls were analyzed. Vertex-wise (surface-based) or voxel-wise (voxel-based) linear models were applied, after controlling for age and gender, to investigate between-group differences. Averaged cortical thicknesses and volumes from regions showing group differences were correlated with parameters related to clinical profiles. Surface-based morphometry showed significantly thinner cortices in the bilateral insular cortex, caudal middle frontal gyrus, precentral gyrus, and parietal lobes in patients with chronic migraine relative to healthy controls. Additionally, the number of migraine days in the month preceding MRI examination was correlated negatively with right insular cortical thickness. Voxel-based morphometry (VBM) did not show any group differences or clinical correlations. Patients with chronic migraine without medication overuse headache, major depression, or prior preventive treatment had reduced cortical thickness in regions within the pain-processing network. Compared to voxel-based morphometry, surface-based morphometry analysis may be more sensitive to subtle structural differences between healthy controls and patients with chronic migraine.


Sucrose-induced receptor kinase SIRK1 regulates a plasma membrane aquaporin in Arabidopsis.
The transmembrane receptor kinase family is the largest protein kinase family in Arabidopsis, and it contains the highest fraction of proteins with yet uncharacterized functions. Here, we present functions of SIRK1, a receptor kinase that was previously identified with rapid transient phosphorylation after sucrose resupply to sucrose-starved seedlings. SIRK1 was found to be an active kinase with increasing activity in the presence of an external sucrose supply. In sirk1 T-DNA insertional mutants, the sucrose-induced phosphorylation patterns of several membrane proteins were strongly reduced; in particular, pore-gating phosphorylation sites in aquaporins were affected. SIRK1-GFP fusions were found to directly interact with aquaporins in affinity pull-down experiments on microsomal membrane vesicles. Furthermore, protoplast swelling assays of sirk1 mutants and SIRK1-GFP expressing lines confirmed a direct functional interaction of receptor kinase SIRK1 and aquaporins as substrates for phosphorylation. A lack of SIRK1 expression resulted in the failure of mutant protoplasts to control water channel activity upon changes in external sucrose concentrations. We propose that SIRK1 is involved in the regulation of sucrose-specific osmotic responses through direct interaction with and activation of an aquaporin via phosphorylation and that the duration of this response is controlled by phosphorylation-dependent receptor internalization.


Dietary Polyacetylenic Oxylipins Falcarinol and Falcarindiol Prevent Inflammation and Colorectal Neoplastic Transformation: A Mechanistic and Dose-Response Study in A Rat Model.
Falcarinol (FaOH) and falcarindiol (FaDOH) are cytotoxic and anti-inflammatory polyacetylenic oxylipins, which are commonly found in the carrot family (Apiaceae). FaOH and FaDOH have previously demonstrated a chemopreventive effect on precursor lesions of colorectal cancer (CRC) in azoxymethane (AOM)-induced rats. The purpose of the present study was to elucidate possible mechanisms of action for the preventive effect of FaOH and FaDOH on colorectal precancerous lesions and to determine how this effect was dependent on dose. Gene expression studies performed by RT-qPCR of selected cancer biomarkers in tissue from biopsies of neoplastic tissue revealed that FaOH and FaDOH downregulated NF-κβ and its downstream inflammatory markers TNFα, IL-6, and COX-2. The dose-dependent anti-neoplastic effect of FaOH and FaDOH in AOM-induced rats was investigated in groups of 20 rats receiving a standard rat diet (SRD) supplemented with 0.16, 0.48, 1.4, 7 or 35 µg FaOH and FaDOH g-1 feed in the ratio 1:1 and 20 rats were controls receiving only SRD. Analysis of aberrant crypt foci (ACF) showed that the average number of small ACF (<7 crypts) and large ACF (>7 crypts) decreased with increasing dose of FaOH and FaDOH and that this inhibitory effect on early neoplastic formation of ACF was dose-dependent, which was also the case for the total number of macroscopic neoplasms. The CRC protective effects of apiaceous vegetables are mainly due to the inhibitory effect of FaOH and FaDOH on NF-κB and its downstream inflammatory markers, especially COX-2.


Guidelines for the management of people with foot health problems related to rheumatoid arthritis: a survey of their use in podiatry practice.
In the last decade there has been a significant expansion in the body of knowledge on the effects of rheumatoid arthritis (RA) on the foot and the management of these problems. Aligned with this has been the development of specialist clinical roles for podiatrists. However, despite being recommended by national guidelines, specialist podiatrists are scarce. In order to inform non-specialist podiatrists of the appropriate interventions for these foot problems, management guidelines have been developed and disseminated by a group of specialist podiatrists. The aim of this survey was to investigate the use of these guidelines in clinical practice. Following ethical approval an online questionnaire survey was carried out. The questions were formulated from a focus group and comprised fixed response and open response questions. The survey underwent cognitive testing with two podiatrists before being finalised. An inductive approach using thematic analysis was used with the qualitative data. 245 questionnaires were completed (128-non-specialist working in the private sector, 101 non-specialists working in the NHS and 16 specialist podiatrists). Overall, 97% of the non-specialists (n = 222) had not heard of the guidelines. The non-specialists identified other influences on their management of people with RA, such as their undergraduate training and professional body branch meetings. Three main themes emerged from the qualitative data: (i) the benefits of the foot health management guidelines, (ii) the barriers to the use of guidelines generally and (iii) the features of useable clinical guidelines. This study has revealed some crucial information about podiatrists' level of engagement with the foot health management guidelines and the use of guidelines in general. Specifically, the non-specialist podiatrists were less likely to use the foot health management guidelines than the specialist podiatrists. The positive aspects were that for the specialist practitioners, the guidelines helped them to identify their professional development needs and for the few non-specialists that did use them, they enabled appropriate referral to the rheumatology team for foot health management. The barriers to their use included a lack of understanding of the risk associated with managing people with RA and that guidelines can be too long and detailed for use in clinical practice. Suggestions are made for improving the implementation of foot health guidelines.


Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance.
Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI. Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT. The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period. This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.


Longitudinal evaluation of iron concentration and atrophy in the dentate nuclei in friedreich ataxia.
Friedreich ataxia is a recessively inherited, progressive neurological disease characterized by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of abnormalities in these structures. Using in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n = 20) and healthy controls (n = 18) over a 2-year period. The longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Specifically, atrophy was maximal in individuals early in the disease course, whereas the rate of iron concentration increased with disease progression. Progressive dentate nucleus abnormalities are evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a 2-year period highlight the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool. © 2019 International Parkinson and Movement Disorder Society.


Royal Jelly Promotes Ovarian Follicles Growth and Increases Steroid Hormones in Immature Rats.
Royal jelly (RJ) is a complementary diet widely prescribed by traditional medicine specialists for treatment of infertility. The aim of present study was to evaluate the effects of RJ on a set of reproductive parameters in immature female rats. In this experimental study, thirty two immature female rats (30-35 g) were divided into four groups (n=8/group): three experimental groups and one control. The experimental groups received 100, 200 and 400 mg/kg/body weight doses of RJ daily for 14 days, and the control group received 0.5 ml distilled water interaperitonealy (i.p). The treated rats were sacrificed and their ovaries were dissected for histological examination. The serum levels of ovarian hormones, nitric oxide (NO) and ferric reducing antioxidant power (FRAP) were evaluated, and the ratios of the ovarian and uterine weight to body weight were calculated. One-way ANOVA was used for data analysis. The body weights were significantly different (P=0.002) among the rat groups, with an increase in all RJ treated animals. Uterine and ovarian weights and the serum levels of progesterone (P=0.013) and estradiol (P=0.004) were significantly increased in experimental groups compared to the control group. In addition, a significant increase in the number of mature follicles and corpora lutea (P=0.007) was seen in RJ recipients compared to the controls. A significant increase in the serum levels of FRAP (P=0.009) and a significant decrease in NO level (P=0.013) were also observed. RJ promotes folliculogensis and increases ovarian hormones. This product can be considered as a natural growth stimulator for immature female animals.


How an mRNA capping enzyme reads distinct RNA polymerase II and Spt5 CTD phosphorylation codes.
Interactions between RNA guanylyltransferase (GTase) and the C-terminal domain (CTD) repeats of RNA polymerase II (Pol2) and elongation factor Spt5 are thought to orchestrate cotranscriptional capping of nascent mRNAs. The crystal structure of a fission yeast GTase•Pol2 CTD complex reveals a unique docking site on the nucleotidyl transferase domain for an 8-amino-acid Pol2 CTD segment, S5PPSYSPTS5P, bracketed by two Ser5-PO4 marks. Analysis of GTase mutations that disrupt the Pol2 CTD interface shows that at least one of the two Ser5-PO4-binding sites is required for cell viability and that each site is important for cell growth at 37°C. Fission yeast GTase binds the Spt5 CTD at a separate docking site in the OB-fold domain that captures the Trp4 residue of the Spt5 nonapeptide repeat T(1)PAW(4)NSGSK. A disruptive mutation in the Spt5 CTD-binding site of GTase is synthetically lethal with mutations in the Pol2 CTD-binding site, signifying that the Spt5 and Pol2 CTDs cooperate to recruit capping enzyme in vivo. CTD phosphorylation has opposite effects on the interaction of GTase with Pol2 (Ser5-PO4 is required for binding) versus Spt5 (Thr1-PO4 inhibits binding). We propose that the state of Thr1 phosphorylation comprises a binary "Spt5 CTD code" that is read by capping enzyme independent of and parallel to its response to the state of the Pol2 CTD.


Nonparametric estimation of the incubation period of AIDS based on a prevalent cohort with unknown infection times.
Estimation of the incubation period distribution of human immunodeficiency virus based on prevalent cohorts of subjects, already infected at the time of recruitment, is complicated by the absence of information on the original times of infection. Here, we overcome this difficulty by using a prior distribution for the infection times, based on external data. Our estimate is nonparametric, but uses smoothness assumptions to avoid instability. The method is illustrated on two prevalent cohorts from San Francisco, separately and combined. The estimates produced agree with other published estimates of the incubation period distribution.


CD5-Positive Intravascular Large B-Cell Lymphoma in a Patient with Wilson's Disease: Case Report and Review of the Literature.
Intravascular large B-cell lymphoma (IVLBCL) is a rare extra-nodal B-cell lymphoma that proliferates within small/intermediate blood vessels and capillaries while sparing large blood vessels and organ parenchyma. Clinical presentation is highly variable and may include B symptoms, neurological deficits, and/or cutaneous findings. The diagnosis of IVLBCL is difficult due to multiorgan involvement and nonspecific symptoms. We describe the case of a 68-year-old male who presented with progressive weakness, confusion, and falls. He had a past medical history of liver cirrhosis secondary to Wilson's disease. Physical exam and laboratory results revealed a lethargic man with jaundice, hepatic encephalopathy, and abnormal liver/kidney function tests. He expired after a short hospital course in the setting of hepatic and renal failure. Postmortem examination revealed large neoplastic lymphoid cells involving multiple organ blood vessels; however skin and neurologic involvement was absent. The neoplastic cells demonstrated B-cells positive for CD5, rendering a diagnosis of IVLBCL. Our case represents the occurrence of IVLBCL with CD5-positivity in a patient with Wilson's disease, diagnosed at autopsy demonstrating the challenging nature of diagnosing IVLBCL.


Perception of runway image shape and approach angle magnitude by pilots in simulated night landing approaches.
One cue for visual judgments of glidepath angle has been referred to as form ratio. Form ratio is defined as the ratio of vertical height of the runway to width of the far end in the runway retinal image. The ability of pilots to judge form ratios was compared with the ability to judge approach angles in the nighttime "black hole" situation in two experiments. Responses in both static and dynamic simulated approach conditions indicated a general tendency to overestimate form ratios and approach angles less than 3 degrees. Intersubject and intrasubject variability of form ratio and approach angle responses were comparable. These findings (i) do not support the utility of form ratio judgments as an aid in selecting approach angle, (ii) add to the empirical evidence of visual illusions and the danger of reliance on visual information for judgment of approach angle in the nighttime "black hole" situation where only runway light are visible, and (iii) point to variability in perception of approach angle as an important part of the problem.


Placebo Response in Fragile X-associated Tremor/Ataxia Syndrome.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder characterized by intention tremor, cerebellar ataxia, and executive dysfunction in carriers of a CGG repeat expansion premutation (55-200 repeats) in the fragile X mental retardation 1 (FMR1) gene. Given reports of poor insight in FXTAS, we postulated that patients with FXTAS would be less likely to exhibit placebo response. To analyze placebo response from the first randomized controlled trial in FXTAS that evaluated cognitive and motor outcomes after 1 year of treatment with memantine. Data from the placebo arm of the first randomized controlled trial in FXTAS were analyzed. There were 2 coprimary outcomes. Based on studies in Parkinson's disease, placebo responders were defined as individuals with an improvement of at least 50% in the coprimary outcomes. Improvements of 20% and 30% served as secondary cutoff values based on the suggested magnitude of placebo response in other movement disorders. A total of 36 participants in the placebo group completed baseline and follow-up evaluations. The average age was 66 ± 7 years, and 60% were men. Average CGG repeat size was 86 ± 18. A total of 19 participants had stage 3 disease. Only 1 patient showed 50% improvement in both coprimary outcomes. At 30% and 20% improvement, there were 2 and 3 patients showing placebo response in the coprimary outcomes, respectively. Patients with FXTAS exhibited low rates of placebo response in a randomized controlled trial. Further studies on the relationship between baseline insight and placebo responsivity are applicable to FXTAS and other disorders exhibiting cognitive impairment.


Value of D-dimer and C reactive protein in predicting inhospital death in acute aortic dissection.
To evaluate the role of D-dimer and C reactive protein (CRP) in predicting inhospital death in acute aortic dissection (AD). A single-centre prospective study. University hospital in China. 114 patients with acute AD. Admission D-dimer and CRP concentrations were assayed. To observe the association of D-dimer and CRP with inhospital death. Increased levels of plasma D-dimer (9.84±3.53 vs. 4.28±1.99, P < 0.001), CRP (14.08±2.81 vs. 11.18±1.85, P < 0.001) and aortic diameter (45.2±9.5 vs. 40.3±6.0, p = 0.007) were found in dead patients compared with those survived. Moreover, plasma D-dimer concentrations in type A were higher than that in type B (6.51±4.11 vs. 4.87±2.29, p = 0.013). Plasma D-dimer concentrations had positive correlations with CRP levels (r=0.527, P < 0.001) and aortic diameter (r=0.227, p = 0.015), and had negative correlations with the type of AD (r=-0.232, p = 0.013) and the time from onset (r=-0.264, p = 0.005). D-dimer and CRP levels and the type of AD were strongly associated with inhospital mortality. The OR and 95% CI were 3.272, 1.638 to 6.535; 2.322, 1.134 to 4.757; and 0.126, 0.019 to 0.853, respectively. Furthermore, the sensitivity and specificity of D-dimer ≥5.67 μg/mL in predicting inhospital death in acute AD were 90.3% and 75.9% (95% CI 0.85 to 0.96), respectively. Moreover, the sensitivity and specificity of CRP levels ≥11.21 mg/L were 100% and 54.2%, respectively (95% CI 0.74 to 0.89). D-dimer ≥5.67 μg/mL, CRP ≥11.21 mg/L and type A acute AD were important risk factors and independently associated with acute AD inhospital death.


Features Associated With Quality of Life Impairment in Hidradenitis Suppurativa Patients.
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with an adverse impact on patients' quality of life (QoL). Objectives: To quantify QoL impairment in patients in Germany suffering from HS and to identify the parameters associated with QoL impairment. Methods: A non-interventional, cross-sectional, mono-centric study with 500 HS patients. QoL data (measured using the Dermatology Life Quality Index; DLQI) and demographic, anamnestic, clinical, and blood parameters were collected. All patients were examined by dermatologists that documented the skin alterations. QoL data from 462 HS patients were available and evaluated. Results: The mean (± standard deviation) DLQI score of HS patients was 13.18 ± 7.99. Approximately 40% and 20% of HS patients declared very large and extremely large QoL impairment, respectively. The degree of QoL disturbance correlated with the severity of skin alterations, blood leucocyte count and, in particular, with anogenital localization and the presence of nodules and fistulas. Furthermore, QoL impairment was associated with specific comorbidities, such as adiposity and back pain, but not with HS family history. QoL impairment was not influenced by whether or not the patients had undergone resection surgery or antibiotic treatment but was more severe in HS patients that had undergone abscess lancing compared to patients without such treatment in the past. Limitations: It was a mono-centric study and most data were obtained from self-administered patient questionnaires. The association of QoL with type of treatment was analyzed for abscess lancing, resection surgery, and antibiotic treatment. Further therapeutic modalities recommended in the guidelines were not investigated. Conclusion: A profound impairment in QoL was present in patients with HS, and this was higher than that observed in other studied dermatoses. The degree of impairment correlated with the extent of cutaneous and some extra-cutaneous alterations. Surgical and conventional medicamentous therapies of HS were not associated with long-lasting reduction of QoL impairment. Our data support the implementation of patient-reported outcome measures for the assessment of therapy responses.


[Eosinophils in peripheral blood and nasal mucus, in asthmatic and healthy subjects].
600 subjects were studied, chosen at random, between 1 and 55 years old, 300 asthmatic and the rest apparently healthy. Of 300 asthmatic patients, the average concentration of eosinophils in peripheral blood was of 615.93/mm3 (p = 0.000004, R = 2.13), the asthmatic patients with levels of eosinophils over a 400/mm3 presented: more severe asthma per month and made use of hospital services more often, (p = 0.00001, R = 3.56). In 195 patients were detected eosinophils in nasal mucus with an average concentration of 10.54% (p = 0.04, R = 0.70). The incidence and prevalence of asthma seem favored by the lact of predictive sensors. In the study, the blood and nasal eosinophils, in high levels were identified in subjects at high risk, consequently its use is proposed to diagnose and follow up, with the goal of applying measures in the balanced phase of the health-illness chain.


Phenotypic screening for pharmaceuticals using tissue constructs.
Compounds can be screened for pharmaceutical activity either by detecting interactions with specified target molecules such as receptors or enzymes (molecular screening) or observing effects on the structure or physiological activities of cells or tissues (phenotypic screening). Screening at the molecular level has been greatly enhanced by fluorescence methods. Especially the combination of confocal detection with measurements of the amplitudes and time courses of fluorescence fluctuations have reduced sample volumes to < microliters and have increased throughputs to >100000 compounds per day. Screening at the molecular level, however, does not provide information about the effects of test compounds on cellular functions. Phenotypic screening, although much slower than molecular screening, does provide information about effects on cell or tissue structure or function and therefore can be used to eliminate at an early stage compounds that are toxic or do not produce the desired cellular response. Tissue constructs reconstituted using cells of specified types and defined extracellular matrix components provide test systems for detecting the effects of test compounds on cellular mechanical functions such as the development of contractile force and on cell and matrix structure and stiffness. For example, constructs based on vascular smooth muscle cells provide information about effects on cellular contractile force that can be used to identify agents that control blood pressure. Tissue constructs that mimic skeletal, smooth and heart muscles and connective tissues have been produced and can be used to study mechanical and structural responses to active compounds.


The role of Tyr605 and Ala607 of thimet oligopeptidase and Tyr606 and Gly608 of neurolysin in substrate hydrolysis and inhibitor binding.
The physicochemical properties of TOP (thimet oligopeptidase) and NEL (neurolysin) and their hydrolytic activities towards the FRET (fluorescence resonance energy transfer) peptide series Abz-GFSXFRQ-EDDnp [where Abz is o-aminobenzoyl; X=Ala, Ile, Leu, Phe, Tyr, Trp, Ser, Gln, Glu, His, Arg or Pro; and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine] were compared with those of site-mutated analogues. Mutations at Tyr605 and Ala607 in TOP and at Tyr606 and Gly608 in NEL did not affect the overall folding of the two peptidases, as indicated by their thermal stability, CD analysis and the pH-dependence of the intrinsic fluorescence of the protein. The kinetic parameters for the hydrolysis of substrates with systematic variations at position P1 showed that Tyr605 and Tyr606 of TOP and NEL respectively, played a role in subsite S1. Ala607 of TOP and Gly608 of NEL contributed to the flexibility of the loops formed by residues 600-612 (GHLAGGYDGQYYG; one-letter amino acid codes used) in NEL and 599-611 (GHLAGGYDAQYYG; one-letter amino acid codes used) in TOP contributing to the distinct substrate specificities, particularly with an isoleucine residue at P1. TOP Y605A was inhibited less efficiently by JA-2 {N-[1-(R,S)-carboxy-3-phenylpropyl]Ala-Aib-Tyr-p-aminobenzoate}, which suggested that the aromatic ring of Tyr605 was an important anchor for its interaction with wild-type TOP. The hydroxy groups of Tyr605 and Tyr606 did not contribute to the pH-activity profiles, since the pKs obtained in the assays of mutants TOP Y605F and NEL Y606F were similar to those of wild-type peptidases. However, the pH-kcat/Km dependence curve of TOP Y605A differed from that of wild-type TOP and from TOP Y606F. These results provide insights into the residues involved in the substrate specificities of TOP and NEL and how they select cytosolic peptides for hydrolysis.


Blockchain Technology Projects to Provide Telemedical Services: Systematic Review.
One of the most promising health care development areas is introducing telemedicine services and creating solutions based on blockchain technology. The study of systems combining both these domains indicates the ongoing expansion of digital technologies in this market segment. This paper aims to review the feasibility of blockchain technology for telemedicine. The authors identified relevant studies via systematic searches of databases including PubMed, Scopus, Web of Science, IEEE Xplore, and Google Scholar. The suitability of each for inclusion in this review was assessed independently. Owing to the lack of publications, available blockchain-based tokens were discovered via conventional web search engines (Google, Yahoo, and Yandex). Of the 40 discovered projects, only 18 met the selection criteria. The 5 most prevalent features of the available solutions (N=18) were medical data access (14/18, 78%), medical service processing (14/18, 78%), diagnostic support (10/18, 56%), payment transactions (10/18, 56%), and fundraising for telemedical instrument development (5/18, 28%). These different features (eg, medical data access, medical service processing, epidemiology reporting, diagnostic support, and treatment support) allow us to discuss the possibilities for integration of blockchain technology into telemedicine and health care on different levels. In this area, a wide range of tasks can be identified that could be accomplished based on digital technologies using blockchains.


Risk communication planning for the aftermath of a plague bioattack.
We create an influence diagram of how a plague bioattack could unfold and then use it to identify factors shaping infection risks in many possible scenarios. The influence diagram and associated explanations provide a compact reference that allows risk communicators to identify key messages for pre-event preparation and testing. It can also be used to answer specific questions in whatever unique situations arise, considering both the conditions of the attack and the properties of the attacked populations. The influence diagram allows a quick, visual check of the factors that must be covered when evaluating audience information needs. The documentation provides content for explaining the resultant advice. We show how these tools can help in preparing for crises and responding to them.


The DRESS syndrome: the great clinical mimicker.
The life-threatening DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is characterized by the presence of at least three of the following findings: fever, exanthema, eosinophilia, atypical circulating lymphocytes, lymphadenopathy, and hepatitis. This syndrome is difficult to diagnose, as many of its clinical features mimic those found with other serious systemic disorders. This idiosyncratic reaction occurs most commonly after exposure to drugs such as allopurinol, sulfonamides, and aromatic anticonvulsants such as phenytoin, phenobarbital, and carbamazepine. We describe a 44-year-old woman who was brought to the emergency department with new-onset hemorrhagic stroke. She was admitted to the intensive care unit where she received supportive care that included clonidine and hydralazine for blood pressure control and phenytoin for seizure prophylaxis. On hospital day 21, the patient developed signs and symptoms of severe sepsis. Despite receipt of broad-spectrum antibiotics (vancomycin and piperacillin-tazobactam) and supportive care, the patient's clinical condition worsened with progressive jaundice, severe oliguria, and labile blood pressures. All cultures revealed no growth, and her chest radiograph remained clear. Several days after the onset of her fever, the patient developed several hematologic abnormalities including thrombocytopenia, with schistocytes present on a peripheral smear. She also had an elevated lactate dehydrogenase level. A provisional diagnosis of thrombotic thrombocytopenic purpura was made; however, the patient then developed severe facial edema, nearly global erythroderma, and severe exfoliative dermatitis. A punch biopsy of the skin was compatible with the DRESS syndrome. Phenytoin, vancomycin, and piperacillin-tazobactam were discontinued, and the patient was started on systemic corticosteroids, with rapid resolution of her fever and eosinophilia and progressive improvement in her skin rash and multiorgan system dysfunction. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of DRESS syndrome and treatment with phenytoin. Clinicians should have a high index of suspicion for the DRESS syndrome in patients being treated with aromatic anticonvulsants who develop a sepsis-like syndrome. Furthermore, considering the potential severe effects associated with phenytoin, the risks and benefits should be carefully evaluated before using this agent for seizure prophylaxis.


Bacteriology of abscesses of the central nervous system: a multicentre prospective study.
Pus from 46 patients with abscesses of the central nervous system (CNS) was examined for bacteria; bacteria were found in all patients. Streptococci were isolated from 36 patients and most isolates were Streptococcus milleri, Lancefield Group F, Ottens and Winkler type O III. Staphylococci were isolated from nine patients, organisms of the bacteroides group from 11, Proteus spp from seven, Klebsiella aerogenes from one, and Haemophilus aphrophilus from one. Pure cultures predominated over mixed cultures. Streptococci were isolated from abscesses of all types, and at all sites, but members of the Enterobacteriaceae and of the bacteroides group were isolated, in mixed cultures, principally from abscesses of the temporal lobe secondary to infection of the middle ear. Staphylococci predominated in abscesses that followed accidental or surgical trauma. Compared with fully sensitive control organisms, microbes infecting half the patients were resistant to penicillin. The prognosis of abscess of the CNS is grave, and the microbiological findings have important consequences for treatment. Prompt inoculation of specimens to culture plates and prompt incubation are mandatory if bacteria are to be cultured. Inhibitors of antimicrobial agents should be added to culture media if antibiotics have been administered. Provided that the site of the abscess and the antecedent history are ascertainable, the neurosurgeon should be able to start appropriate treatment while awaiting the results of culture.


The equine cervical spine: comparing MRI and contrast-enhanced CT images with anatomic slices in the sagittal, dorsal, and transverse plane.
The impact of cervical pathology on performance is of great importance to the horse industry. Accurate diagnosis of cervical disease with imaging modalities, including computed tomography (CT) and magnetic resonance imaging (MRI), requires thorough appreciation of normal cervical anatomy. (1) To describe in detail the anatomy of the equine cervical spine by comparing anatomical sections with corresponding MR and contrast-enhanced CT images in the sagittal, dorsal, and transverse plane. (2) To discuss the ability of MR and contrast-enhanced CT imaging to visualize anatomical structures in the cervical spine. Three cervical spines of young adults (3-8 years), collected immediately after humane euthanasia, were used. The spine was stabilized on a frame in a natural flexed position with an angle of 20°. MR and contrast-enhanced CT imaging was performed within six hours after euthanasia. Anatomical sections of 1 cm were made in the sagittal, dorsal, and transverse plane and compared with corresponding CT and MR images. The intervertebral disk thickness, facet joint angle, sagittal dural space diameter and ventromedial facet joint projection were quantified. The anatomic location of clinically important structures including the facet joints, spinal cord, cervical nerve roots and intervertebral disks were reliably identified in the anatomical sections and their corresponding MR images. Contrast-enhanced CT images depicted all osseous borders, whereas MR images were superior for soft tissue structures. This study enhances our understanding of normal cervical spine anatomy and the diagnostic usefulness of cervical MRI and contrast-enhanced CT in the horse.


Effects of combined α-galactosidase and xylanase supplementation on nutrient digestibility and growth performance in growing pigs.
Two experiments were conducted to investigate the effect of combined supplementation of α-galactosidase and xylanase on nutrient digestibility and growth performance in growing pigs. Experiment 1 had a 2 × 2 Latin square design, where eight barrows (45.0 ± 0.52 kg body weight [BW]) were fitted with a simple T-cannula in the distal ileum and received a basal diet without or with supplementation of α-galactosidase (12 U/kg diet) and xylanase (15 AXC/kg diet) within two periods of 10 d. The apparent ileal digestibility (AID) and apparent total tract digestibility of nutrients, pH, viscosity of digesta and digestive enzyme activities were assessed. In Experiment 2, a total of 432 growing pigs (initial BW 44.7 ± 0.66 kg) were allocated to four treatments. Diets were based on corn and soybean meal and had a normal or reduced nutrient level (reduced by 0.42 kJ digestible energy [DE] per kg and 0.8% crude protein). Both diets were offered without or with supplementation of α-galactosidase and xylanase. The growth performance was assessed within a 43-d feeding period, where at the end, biochemical serum indices were estimated. In Experiment 1, the enzyme-supplemented diet had a greater contents of DE and DE/gross energy ratio (p < 0.05), and a higher AID of Arg, raffinose, stachyose and arabinoxylan (p < 0.05). In Experiment 2, the low nutrient level caused lower daily gain (p < 0.05), which was partially compensated by enzyme addition. Enzyme addition also increased the serum concentration of Lys (p < 0.05). Moreover, it appears that the tested enzyme supplementation could increase dietary DE, serum total amino acid concentrations and decrease serum urea nitrogen.


Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden.
The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 0.10; 95% CI, -0.08 to 0.28; P = .27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = -0.36; 95% CI, -0.34 to 0.09; P = .25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.


Radiation-induced PGE2 sustains human glioma cells growth and survival through EGF signaling.
Glioblastoma Multiforme (GBM) is the most common brain cancer in adults. Radiotherapy (RT) is the most effective post-operative treatment for the patients even though GBM is one of the most radio-resistant tumors. Dead or dying cells within the tumor are thought to promote resistance to treatment through mechanisms that are very poorly understood. We have evaluated the role of Prostaglandin E2 (PGE2), a versatile bioactive lipid, in GBM radio-resistance. We used an in vitro approach using 3D primary cultures derived from representative GBM patients. We show that irradiated glioma cells produced and released PGE2 in important quantities independently of the induction of cell death. We demonstrate that the addition of PGE2 enhances cell survival and proliferation though its ability to trans-activate the Epithelial Growth Factor receptor (EGFR) and to activate β-catenin. Indeed, PGE2 can substitute for EGF to promote primary cultures survival and growth in vitro and the effect is likely to occur though the Prostaglandin E2 receptor EP2.


Reasons for patient's delay in diagnosis of breast carcinoma in Pakistan.
Delay in diagnosis of breast cancer is associated with a poorer survival and a pivotal contribution to this delayed diagnosis comes from patient delay in presenting at a clinic. Reasons involved must be evaluated in order to decrease this reducible delay. i) To evaluate the reasons for patient delay in diagnosis of breast cancer; ii) to investigate any association with other variables. A 6 month cross sectional study (from July 2012 to Dec 2012), was carried out in Surgical and Oncology Units of Civil Hospital, Karachi. A total of 100 females diagnosed with breast cancer of any histological type were interviewed after informed consent and relevant data were collected. Due ethical clearance was obtained. Mean age was 47.5±12.1 years with a range from 25-77 years. Mean duration of delay was 5.13±4.8 months, from shortest 1 month to longest 36 months. Duration of delay was observed to be no delay (<1 month) in 28%, short delay (1-3 months) in 30% and long delay (>3 months) in 42% of patients. Considering the symptoms as "harmless" (39%) was the most frequent reason of delay followed by "temporary" (20%) and the "use of traditional methods" (12%). Most common reason for later approaches was an increase in the size of the lump (41%). Statistically significant association (p-value <0.05) of longer patient delay was obtained with being single, being illiterate, painless breast lump as the first symptom, negative family history of breast cancer and vague attribution of the symptoms. Significant delay in approach to health care facility was observed in our study due to variable reasons given by women. Sufficient awareness regarding breast cancer, its symptoms and favorable effects of a timely diagnosis on prognosis must be imparted to our general population.


Mechanisms of animal navigation in odor plumes.
Chemical signals mediate many of life's processes. For organisms that use these signals to orient and navigate in their environment, where and when these cues are encountered is crucial in determining behavioral responses. In air and water, fluid mechanics impinge directly upon the distribution of odorous molecules in time and space. Animals frequently employ behavioral mechanisms that allow them to take advantage of both chemical and fluid dynamic information in order to move toward the source. In turbulent plumes, where odor is patchily distributed, animals are exposed to a highly intermittent signal. The most detailed studies that have attempted to measure fluid dynamic conditions, odor plume structure, and resultant orientation behavior have involved moths, crabs, and lobsters. The behavioral mechanisms employed by these organisms are different but generally integrate some form of chemically modulated orientation (chemotaxis) with a visual or mechanical assessment of flow conditions in order to steer up-current or upwind (rheo- or anemo-taxis, respectively). Across-stream turns are another conspicuous feature of odor-modulated tracks of a variety of organisms in different fluid conditions. In some cases, turning is initiated by detection of the lateral edges of a well-defined plume (crabs), whereas in other animals turning appears to be steered according to an internally generated program modulated by odor contacts (moth counterturning). Other organisms such as birds and fish may use similar mechanisms, but the experimental data for these organisms is not yet as convincing. The behavioral strategies employed by a variety of animals result in orientation responses that are appropriate for the dispersed, intermittent plumes dictated by the fluid-mechanical conditions in the environments that these different macroscopic organisms inhabit.


Inducible synthesis of collagenase and other neutral metalloproteinases by cells of aortic origin.
In view of the possible link between collagenase and the formation of aortic aneurysms we have determined whether cells within the aorta are able to synthesize this enzyme. Explanted cells obtained from fragments of lapine abdominal aorta secreted little or no collagenase. Two related metalloproteinases, gelatinase and stromelysin, were also produced at very low levels. Treatment with purified human monocyte interleukin-1 beta, partially purified lapine, synovial IL-1 or phorbol myristate acetate strongly induced the synthesis of all these enzymes. These activators also increased synthesis of prostaglandin E2. The identity of collagenase was confirmed by detection of the characteristic TCA and TCB breakdown fragments of collagen and by demonstration of collagenase mRNA within activated aortic cells. Unactivated aortic cells contained no detectable collagenase mRNA, suggesting a pretranslational level of regulation. Aortic cells thus possess the ability to express several neutral metalloproteinases and, if a sufficient inflammatory stimulus was present, they might do so in arteries undergoing aneurysmal degeneration.


A fluid-structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems.
Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment and strain-induced flow of interstitial fluid is believed to be the primary mediator of mechanical stimuli to bone cells in vivo. In vitro investigations have shown that bone cells produce important biochemical signals in response to fluid flow applied using parallel-plate flow chamber (PPFC) systems. However, the exact mechanical stimulus experienced by the cells within these systems remains unclear. To fully understand this behaviour represents a most challenging multi-physics problem involving the interaction between deformable cellular structures and adjacent fluid flows. In this study, we use a fluid-structure interaction computational approach to investigate the nature of the mechanical stimulus being applied to a single osteoblast cell under fluid flow within a PPFC system. The analysis decouples the contribution of pressure and shear stress on cellular deformation and for the first time highlights that cell strain under flow is dominated by the pressure in the PPFC system rather than the applied shear stress. Furthermore, it was found that strains imparted on the cell membrane were relatively low whereas significant strain amplification occurred at the cell-substrate interface. These results suggest that strain transfer through focal attachments at the base of the cell are the primary mediators of mechanical signals to the cell under flow in a PPFC system. Such information is vital in order to correctly interpret biological responses of bone cells under in vitro stimulation and elucidate the mechanisms associated with mechanotransduction in vivo.


Reduction of severity of pruritus after elective caesarean section under spinal anaesthesia with subarachnoid morphine: a randomised comparison of prophylactic granisetron and ondansetron.
The incidence of pruritus after elective caesarean section under spinal anaesthesia with subarachnoid morphine may be 60-100%, and is a common cause of maternal dissatisfaction. Ondansetron has been shown to reduce pruritus but the effect is short-lived. The objective of this randomized double-blind trial was to evaluate the anti-pruritic efficacy of granisetron compared with ondansetron. Eighty ASA I or II women undergoing elective caesarean section received spinal anaesthesia with 0.5% hyperbaric bupivacaine 10 mg, fentanyl 25 microg and preservative-free morphine 150 microg. After delivery of the baby and clamping of the umbilical cord, they were randomised to receive granisetron 3mg i.v. (group G) or ondansetron 8 mg i.v. (group O). The two groups were similar for age, gestational age, height and weight. According to visual analogue pruritus scores, patients in group G experienced less pruritus at 8h (P=0.003) and 24h (P=0.01). Fewer patients in group G (n=8) than group O (n=18) required rescue anti-pruritic medication (P=0.03). Satisfaction scores were also higher in group G than in group O (P=0.03). There was no difference in overall incidence of pruritus, nausea and vomiting, and visual analogue pain scores between the two groups. Administration of granisetron 3mg i.v. reduces the severity of pruritus and the use of rescue anti-pruritic medication, and improves satisfaction but does not reduce the overall incidence of pruritus in women who have received subarachnoid morphine 150 microg compared to ondansetron 8 mg i.v.


Two-stage ligament reconstruction with remnant preservation as treatment of knee dislocation.
The purpose of this study was to evaluate the clinical outcomes of two-stage reconstruction (peripheral reconstruction in phase I and central anterior cruciate ligament (ACL) / posterior cruciate ligament (PCL) reconstruction in phase II) with remnant preservation for patients with knee dislocation. A total of 70 patients (10 IIIM, 17 IIIL, and 43 IV) with knee dislocation were randomly divided into the remnant-preserved group and the simple reconstruction group. Patients underwent two-stage reconstruction, including the reconstruction of collateral ligament in phase I and the reconstruction of ACL/PCL in phase II (12 weeks after phase I). Grafts were harvested from the semitendinosus and gracilis tendons from both lower limbs. After the surgery, the joint flexion and extension, bone tunnel and ligament healing, and joint stability were evaluated. After the surgery, the lateral stability recovered in all patients, and X-ray revealed a good position of bone tunnel. Follow-up was performed at 12 months postoperatively and ranged from 24 to 91 months. At the final follow-up, knee flexion angle, IKDC, Lysholm, and Tegner scores were all higher in both groups compared to the preoperative period. Notably, the remnant-preserved group showed superior results in these parameters compared to the simple reconstruction group. There was statistical significance between the two groups in terms of the Lachman test. The knee function was well recovered after two-stage ligament reconstruction with remnant preservation.


GP experience and understandings of providing follow-up care in prostate cancer survivors in England.
Survival times for prostate cancer have increased substantially, meaning more survivors will be discharged to General Practitioners' (GP) services. The detection of recurrence and monitoring of symptoms and long-term side-effects in prostate cancer survivors requires the active involvement of GPs in their follow-up care. In order to address this, the transition and discharge from hospital to primary care must be managed effectively. The objective of this study was to examine the preparedness, concerns and experiences of GPs in relation to their role in providing follow-up care to prostate cancer survivors. Purposive sampling was used to recruit GPs with experience in providing care to prostate cancer survivors. Twenty semi-structured telephone interviews were conducted with GPs across England. The interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Participants described their current role in the follow-up pathway, a number of challenges and barriers in assuming this role, and potential ways to resolve these and improve their involvement. They expressed a range of views about their preparedness and willingness to take over follow-up care after discharge for this group of patients. GPs had reservations about workload, lack of resources, expertise and deficiencies in communication with hospitals. Findings from this study suggest that GPs will be ready to take over the follow-up care of prostate cancer survivors if better information, additional training and adequate resources are provided and communication lines with hospital specialists are clear. Understanding the issues faced by GPs and overcoming identified barriers to providing follow-up care to prostate cancer survivors will provide the insight necessary to make the process of transferring care from secondary to primary teams a more straightforward task for all stakeholders.


Future Financing Scenarios for Iran's Healthcare System.
The financing function within a health system is considered inherently complex, so it is of utmost importance to design a suitable future for this system given uncertainties and complexities of the environment. With regard to the current and future complicated conditions, health system financing is also likely to succeed if it can anticipate the impacts of effective factors in the future and further plan appropriate interventions ahead of time. Thus, the purpose of this study was to develop scenarios for the health system financing in Iran. This mixed-design research of exploratory future studies type was conducted using the scenario method. In this respect, the key variables were evaluated using a questionnaire from two aspects of importance and uncertainty as well as formation of a future studies group (focus group). Finally, sensitivity analysis was carried out through cross-impact balance (CIB) analysis using the Scenario Wizard (Version 4.31) software. A total of 25 factors were selected based on the type and the position of the variables (driving force, bi-dimensional, risk, secondary leverage or modifiable-to-secondary leverage) over the diameter of the MICMAC chart. Considering the degree of significance and uncertainty, eight variables including all four driving force variables (oil sales and economic blockade, leadership and advocacy, bureaucracy and corruption, and possibility of using information technology in providing services), as well as the variables of resource sustainability, natural disasters, regional security, and specialization culture were chosen. Then, five variables were finalized as the key changes that would create the scenario based on sensitivity analysis and final expert opinions. According to the defined conditions, 270 scenarios were developed, of which fourteen scenarios were identified as poorly adaptable and five cases as highly adaptable. The best scenario identified in this study based on the degree of adaptation included the use of massive technology and oil sales, mediocre economic conditions with high probability of occurrence, strong leadership and advocacy, high regional security, as well as bureaucracy and low corruption with medium probability of occurrence.


Utility of Line Probe Assay for the Early Detection of Multidrug-Resistant Pulmonary Tuberculosis.
Despite endorsement of the line probe assay (LPA) for the diagnosis of drug-resistant pulmonary tuberculosis patients, there is limited data available on the performance of LPAs in India, especially from high burden states like Maharashtra, for the early diagnosis and detection of drug resistance, in order to initiate timely and appropriate treatment. To evaluate the utility of the line probe assay (LPA) for the early diagnosis of drug-resistant pulmonary tuberculosis as compared to the 'Gold standard' 1% proportion method (PM). A total of 687 patients suspected of pulmonary tuberculosis were screened. One hundred samples (95 sputum and 5 BAL), positive for Acid Fast Bacilli (AFB) by Ziehl Neelson (ZN) smears, were included in the study. Digested and decontaminated specimens were subjected directly to the LPA (Genotype MTBDR@ plus assay) and were processed in parallel using the conventional culture on the Lowenstein-Jensen (LJ) medium followed by drug susceptibility testing (DST) using the PM. All the 100 samples gave interpretable results on LPA with a turnaround time of 24-48 hours as opposed to six to eight weeks taken by the 1% proportion method. Sensitivity for the detection of rifampicin, isoniazid, and multidrug resistance (MDR) was 98.1, 92.1, and 95%, respectively, with a specificity of 97.8% for rifampicin and 98.33% for MDR detection. It also had the additional advantage of allowing a study of mutation patterns. High performance characteristics and a short turnaround time makes LPA an excellent diagnostic tool, for an early and accurate diagnosis, in a high MDR- TB-prevalent region, as reflected from our data.