Compliance and persistence with Alzheimer's disease treatment: a retrospective analysis of multiregional hospital databases in Thailand.
Aims: Due to the lack of studies evaluating compliance or persistence with Alzheimer's Disease (AD) treatment outside High-Income Countries (HICs), this study aimed to assess compliance, persistence, and factors associated with non-compliance and non-persistence by utilizing existing "real-world" information from multiregional hospital databases in Thailand.Materials and methods: Study subjects were retrospectively identified from databases of five hospitals located in different regions across Thailand. AD patients aged ≥60 years who were newly-prescribed with donepezil, galantamine, rivastigmine, or memantine between 2013 and 2017 were eligible for analysis. The Medication Possession Ratio (MPR) was used as a proxy for compliance, while the Kaplan-Meier survival analysis was employed to estimate persistence. Logistic and Cox regressions were used to assess determinants of non-compliance and non-persistence, adjusted for age and gender.Results: Among 698 eligible patients, mean (SD) MPR was 0.83 (0.25), with 70.3% of the patients compliant to the treatment (having MPR ≥ 0.80). Half of the patients discontinued their treatment (having a treatment gap >30 days) within 177 days with a 1-year persistence probability of 21.1%. The patients treated in the university-affiliated hospital were more likely to be both non-compliant (OR = 1.71; 95% CI = 1.21-2.42) and non-persistent (HR = 1.33; 95% CI = 1.12-1.58). In addition, non-compliance was higher for those prescribed with single AD treatment (OR = 2.52; 95% CI = 1.35-4.69), while non-persistence was higher for those unable to reimburse for AD treatment (HR = 1.34; 95% CI = 1.11-1.62).Limitations: By using retrospective databases, a difficulty in validating whether the medications are actually taken after being refilled may over-estimate the levels of compliance and persistence. Meanwhile, possible random coding errors may under-estimate the strength of association findings.Conclusions: This study reveals the situation of compliance and persistence on AD treatment for the first time outside HICs. The determinants of non-compliance and non-persistence underline key areas for improvement.


Combined central and peripheral myelinopathy.
We studied clinical, electrophysiologic, and nerve biopsy findings in two men with evidence of severe central and peripheral demyelinating disease. These patients may be rare examples of MS with associated severe, chronic, clinically evident peripheral demyelinating neuropathy. Alternatively, they may be cases of some other form of combined central-peripheral myelinopathy or fortuitous coincidence of MS with idiopathic inflammatory-demyelinating neuropathy. There have been only five other reports of clinically evident combined central-peripheral myelinopathy, but there have also been reports of only electrophysiologic or nerve biopsy evidence (without clinical manifestation) of peripheral neuropathy in MS patients.


Portopulmonary hypertension in children: a rare but potentially lethal and under-recognized disease.
Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary arterial hypertension (PAH). Very little is known about this process in pediatric patients but prognosis is generally poor. We review our institutional experience and report on five patients with pediatric PoPH. The median age of PoPH diagnosis was six years and PAH was 14 years. PAH diagnosis was made by echocardiogram in all patients, four of whom also had cardiac catheterization. The median mean pulmonary artery pressure (mPAP) was 48.5 mmHg (interquartile range [IQR] = 46-60) with a median pulmonary vascular resistance index (PVRi) of 9 WU*M2 (IQR = 8-22). All were acute pulmonary vasodilator testing non-responsive. All patients received targeted therapies. Three of five patients (60%) died despite an evidence-based approach to care. Of those who died, timing from the PoPH diagnosis to death ranged from three days to three years. Based upon our limited experience, PoPH is a disorder with significant mortality in childhood and challenges in treatment. Future research, focused on screening and early targeted treatment strategies, may alter the current dismal prognosis for these children.


Structural domains within the 3' untranslated region of Turnip crinkle virus.
The genomes of positive-strand RNA viruses undergo conformational shifts that complicate efforts to equate structures with function. We have initiated a detailed analysis of secondary and tertiary elements within the 3' end of Turnip crinkle virus (TCV) that are required for viral accumulation in vivo. MPGAfold, a massively parallel genetic algorithm, suggested the presence of five hairpins (H4a, H4b, and previously identified hairpins H4, H5, and Pr) and one H-type pseudoknot (Psi(3)) within the 3'-terminal 194 nucleotides (nt). In vivo compensatory mutagenesis analyses confirmed the existence of H4a, H4b, Psi(3) and a second pseudoknot (Psi(2)) previously identified in a TCV satellite RNA. In-line structure probing of the 194-nt fragment supported the coexistence of H4, H4a, H4b, Psi(3) and a pseudoknot that connects H5 and the 3' end (Psi(1)). Stepwise replacements of TCV elements with the comparable elements from Cardamine chlorotic fleck virus indicated that the complete 142-nt 3' end, and subsets containing Psi(3), H4a, and H4b or Psi(3), H4a, H4b, H5, and Psi(2), form functional domains for virus accumulation in vivo. A new 3-D molecular modeling protocol (RNA2D3D) predicted that H4a, H4b, H5, Psi(3), and Psi(2) are capable of simultaneous existence and bears some resemblance to a tRNA. The related Japanese iris necrotic ring virus does not have comparable domains. These results provide a framework for determining how interconnected elements participate in processes that require 3' untranslated region sequences such as translation and replication.


[Bronchial casts associated with pulmonary lymphatic anomalies].
We report a case of a patient who presented with bronchial moulds. The classic causes, particularly bronchopulmonary aspergillosis could not be found. The pulmonary radiology and CT of thorax revealed an alveolar syndrome. Lymphography and lymphoscintigraphy showed evidence of lymphatic anomalies including the non-visualisation of the thoracic canal. In the absence of evidence for other diseases, we would suggest that these anomalies were responsible for the symptomatology.


PH-cycling model to verify the efficacy of fluoride-releasing materials in enamel demineralization.
The current study proposes a pH-cycling model to verify the dose-response relationship of fluoride-releasing materials in their ability to reduce in vitro demineralization. Sixty bovine enamel blocks (4 x 3 x 3 mm) were selected, using baseline surface microhardness (SMH1) evaluations at different distances from the enamel sectioned border (150, 300, 450 and 600 microm). Specimens (n=48) were prepared with Z100, Fluroshield and Vitremer at the standard powder/liquid ratio and at a 1/4 diluted-powder/liquid ratio. The 12 remaining specimens were used as a control group. The specimens were submitted to a pH-cycling model with high cariogenic challenge. After pH-cycling, final surface microhardness (SMH2) was assessed to calculate the percentage change of surface microhardness (%SMHc). Next, the fluoride present in enamel (microg F/mm3) and in pH-cycling solutions (microg F) was measured. Cross-sectional microhardness was done to calculate the mineral content (deltaZ). Data from %SMHc, deltaZ and microg F were analyzed by analysis of variance (p < 0.05), while microg F/mm3 analysis was done using the Kruskal-Wallis test. The results showed a correlation between %SMHc and microg F/mm3 (r3 = 0.4129; p < 0.0001), %SMHc and microg F (r2 = 0.4932; p < 0.0001), deltaZ and microg F/mm3 (r3 = 0.4573; p < 0.0001), micorg F/mm3 and microg F (r2 = 0.3029; p < 0.0001) and between deltaZ and microg F (r2 = 0.5276; p < 0.0001). The pH-cycling model allowed the in vitro verification of the dose-response relationship of fluoride-releasing materials in the demineralization of enamel.


Nano-Magnetic Resonance Imaging (Nano-MRI) Gives Personalized Medicine a New Perspective.
This paper reviews some of the major and most recent advances in nanoscale-magnetic resonance imaging (nano-MRI) for personalized medicine (PM). Nano-MRI may drastically expand the capabilities of the traditional magnetic resonance images (MRI), down to the nanometer scale and possibly, in the near future, at the atomic scale. Nano-MRI is potentially able to observe structures which cannot be seen using today's molecular imaging, with sensitivities of many billions of times better than MRI as currently used in hospitals, for example. The paper briefly reports on the foremost research themes in nano-MRI.


[Sweet's syndrome in patient with refractory anemia during recombinant human granulocyte colony stimulating factor therapy].
We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.


Acoustic characteristics of Mandarin esophageal speech.
The present study attempted to investigate the acoustic characteristics of Mandarin laryngeal and esophageal speech. Eight normal laryngeal and seven esophageal speakers participated in the acoustic experiments. Results from acoustic analyses of syllables /ma/and /ba/ indicated that, F0, intensity, and signal-to-noise ratio of laryngeal speech were significantly higher than those of esophageal speech. However, opposite results were found for vowel duration, jitter, and shimmer. Mean F0, intensity, and word per minute in reading were greater but number of pauses was smaller in laryngeal speech than those in esophageal speech. Similar patterns of F0 contours and vowel duration as a function of tone were found between laryngeal and esophageal speakers. Long-time spectra analysis indicated that higher first and second formant frequencies were associated with esophageal speech than that with normal laryngeal speech.


The Relationship between Smoking and Sublingual Varices in the Elderly.
We investigated the existence of any connection between smoking and sublingual varices (SLV) in the older population. This case-control study was conducted in 2019 on adults > 65 years old at Kahrizak Charity Nursing Home, Alborz, Iran. We conducted clinical examination and inspection of 222 elderly patients. Both the case group and control group contained the same number of patients (n = 111). SLV were classified as grade 0 (few or none visible) and grade 1 (moderate or severe). The case group included patients with SLV and the control group consisted of those older adults without SLV and who were matched with the case group based on age, gender, blood pressure, denture wearing, and varicose veins in their legs. Cigarette smoking habits were investigated in both groups. Smokers were considered those who smoked at least one cigarette per day for more than six months. Chi-square and odds ratio (OR) were used to statistically analyze the exposure of participants to smoking in both groups. Among 222 participants, 21.6% and 5.4% were smokers in the case and control groups, respectively. The results of our data analysis revealed that SLV were significantly associated with smoking (p < 0.001, OR = 4). Elderly patients with SLV are more likely to be cigarette smokers. Therefore, cigarette smoking cessation programs are recommended for older adults in society.


Ru-Catalyzed Cross-Dehydrogenative Coupling between Primary Alcohols to Guerbet Alcohol Derivatives: with Relevance for Fragrance Synthesis.
A simple method has been developed for the cross dehydrogenative coupling between two different primary alcohols using readily available RuCl2(PPh3)3 as a precatalyst through the borrowing-hydrogen approach. The present methodology is applicable to a large variety of alcohol derivatives including long chain aliphatic alcohols and heteroaryl alcohols. In addition, the methodology was applied in a straightforward protocol to synthesize commercially available fragrances such as Rosaphen and Cyclamenaldehyde in good yields.


Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults: analysis of the variable heavy chain repertoire.
Streptococcus pneumoniae is a leading cause of morbidity and mortality in both developed and developing countries. The current pneumococcal polysaccharide (PPS) vaccine is highly effective in young adults; however, vaccine efficacy is dramatically decreased in the elderly population. We hypothesized that the decreased vaccine efficacy in the elderly results from altered variable gene family usage. We have characterized the immunoglobulin G gene usage of the antibody response to PPS4 and PPS14 in 20 young and 20 elderly adults. The variable heavy (V(H)) gene repertoire of human peripheral B cells was amplified by using PCR. A total of 364 heavy chain sequences with specificity for PPS4 and 305 heavy chain sequences for PPS14 were analyzed from young adults. In addition, a total of 325 sequences for PPS4 and 291 sequences for PPS14 were obtained from elderly adults. Complete sequence identity, somatic mutation frequencies, and V(H) gene usage was determined in response to PPS4 and PPS14. In all volunteers, the immune response to both polysaccharides consisted predominantly of heavy chains belonging to the V(H)3 gene family. There were significant differences in the variable gene repertoire between young and elderly adults. Somatic mutation occurred more frequently in sequences derived from young compared to elderly derived sequences. With aging, a loss of oligoclonality was noted in response to PPS4 and PPS14 compared to young adults. The observed differences in V(H) repertoire, somatic mutation, and loss of oligoclonality may contribute to decreased vaccine efficacy in the elderly.


Defining herpes simplex genes involved in neurovirulence and neuroinvasiveness.
In this discussion, strategies for physically mapping HSV gene functions associated with significant biologic effects are presented and discussed. They represent an application of molecular biological technologies to complex biologic systems, and are a beginning step in understanding the fundamental basis of herpetic disease. Future studies will involve precise identification of relevant genes, and studies of the important properties of products encoded by these genes.


Mixed Methods in Prostate Cancer Prevention and Service Utilization Planning: Combining Focus Groups, Survey Research, and Community Engagement.
This article reports on the use of sequential and integrated mixed-methods approach in a focused population and small-area analysis. The study framework integrates focus groups, survey research, and community engagement strategies in a search for evidence related to prostate cancer screening services utilization as a component of cancer prevention planning in a marginalized African American community in the United States. Research and data analysis methods are synthesized by aggregation, configuration, and interpretive analysis. The results of synthesis show that qualitative and quantitative data validate and complement each other in advancing our knowledge of population characteristics, variable associations, the complex context in which variables exist, and the best options for prevention and service planning. Synthesis of findings and interpretive analysis provided two important explanations which seemed inexplicable in regression outputs: (a) Focus group data on the limitations of the church as an educational source explain the negative association between preferred educational channels and screening behavior found in quantitative analysis. (b) Focus group data on unwelcoming provider environments explain the inconsistent relationship between knowledge of local sites and screening services utilization found in quantitative analysis. The findings suggest that planners, evaluators, and scientists should grow their planning and evaluation evidence from the community they serve.


Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells.
Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose-dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA-treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.


Ultrahigh-Capacity Lithium-Oxygen Batteries Enabled by Dry-Pressed Holey Graphene Air Cathodes.
Lithium-oxygen (Li-O2) batteries have the highest theoretical energy density of all the Li-based energy storage systems, but many challenges prevent them from practical use. A major obstacle is the sluggish performance of the air cathode, where both oxygen reduction (discharge) and oxygen evolution (charge) reactions occur. Recently, there have been significant advances in the development of graphene-based air cathode materials with a large surface area and catalytically active for both oxygen reduction and evolution reactions, especially with additional catalysts or dopants. However, most studies reported so far have examined air cathodes with a limited areal mass loading rarely exceeding 1 mg/cm2. Despite the high gravimetric capacity values achieved, the actual (areal) capacities of those batteries were far from sufficient for practical applications. Here, we present the fabrication, performance, and mechanistic investigations of high-mass-loading (up to 10 mg/cm2) graphene-based air electrodes for high-performance Li-O2 batteries. Such air electrodes could be easily prepared within minutes under solvent-free and binder-free conditions by compression-molding holey graphene materials because of their unique dry compressibility associated with in-plane holes on the graphene sheet. Li-O2 batteries with high air cathode mass loadings thus prepared exhibited excellent gravimetric capacity as well as ultrahigh areal capacity (as high as ∼40 mAh/cm2). The batteries were also cycled at a high curtailing areal capacity (2 mAh/cm2) and showed a better cycling stability for ultrathick cathodes than their thinner counterparts. Detailed post-mortem analyses of the electrodes clearly revealed the battery failure mechanisms under both primary and secondary modes, arising from the oxygen diffusion blockage and the catalytic site deactivation, respectively. These results strongly suggest that the dry-pressed holey graphene electrodes are a highly viable architectural platform for high-capacity, high-performance air cathodes in Li-O2 batteries of practical significance.


The science of lipidology impacts underwriting and improves mortality.
Substantial change in how we think about lipids and atherosclerosis is on the afoot. Discoveries in lipidology are changing the relative importance of commonly used lipid markers, and indentifying new lipid markers for premature disease, new targets for treatment, and new treatment regimens. These advances in lipid science will definitely change clinical practice. They will also force life insurance medical directors to write new underwriting guidelines and consider new testing paradigms. At a minimum, the new science of lipidology offers an opportunity for alert medical directors to substantially improve risk classification and selection.


Ultrastructural alterations in blood vessels of the white matter after experimental spinal cord trauma.
The ultrastructure of the microvasculature of the white matter of the spinal cord was studied after experimentally induced trauma in the cat. Immediately after the induction of trauma, disruption of endothelial cell junctions, increased pinocytotic activity in endothelial cells, and perivascular edema were seen in the blood vessels at the site of injury, but not in those of adjacent segments. However, within 2 hours of injury, the blood vessels of the white matter of the rostral and caudal segments also showed evidence of increased endothelial cell pinocytotic activity and perivascular edema, but disruption of endothelial junctions was not seen. It is therefore concluded that vasogenic edema occurs in the white matter at the site of injury soon after trauma and is due both to leakage from vessels with damaged endothelial cell junctions and also to increased transvesicular transport. By contrast, vasogenic edema develops only after a lapse of time in segments rostral and caudal to the site of injury, and probably results from increased transvesicular transport. A possible role for neurogenic chemical mediators in the genesis of the perivascular edema is discussed.


Selective microbial genomic DNA isolation using restriction endonucleases.
To improve the metagenomic analysis of complex microbiomes, we have repurposed restriction endonucleases as methyl specific DNA binding proteins. As an example, we use DpnI immobilized on magnetic beads. The ten minute extraction technique allows specific binding of genomes containing the DpnI Gm6ATC motif common in the genomic DNA of many bacteria including γ-proteobacteria. Using synthetic genome mixtures, we demonstrate 80% recovery of Escherichia coli genomic DNA even when only femtogram quantities are spiked into 10 µg of human DNA background. Binding is very specific with less than 0.5% of human DNA bound. Next Generation Sequencing of input and enriched synthetic mixtures results in over 100-fold enrichment of target genomes relative to human and plant DNA. We also show comparable enrichment when sequencing complex microbiomes such as those from creek water and human saliva. The technique can be broadened to other restriction enzymes allowing for the selective enrichment of trace and unculturable organisms from complex microbiomes and the stratification of organisms according to restriction enzyme enrichment.


The first aminoacylase-catalyzed enantioselective synthesis of aromatic beta-amino acids.
The first aminoacylase-catalyzed enantioselective synthesis of aromatic beta-amino acids is reported. The presence of an N-chloroacetyl group as acyl group in the substrate as well as the use of porcine kidney acylase I as a suitable enzyme component are prerequisites for this resolution process whereby optically active beta-amino acids are formed with high enantioselectivities of >98% ee.


Photocatalytic hydrogen evolution from FeMoS-based biomimetic chalcogels.
The naturally abundant elements used to catalyze photochemical processes in biology have inspired many research efforts into artificial analogues capable of proton reduction or water oxidation under solar illumination. Most biomimetic systems are isolated molecular units, lacking the protective encapsulation afforded by a protein's tertiary structure. As such, advances in biomimetic catalysis must also be driven by the controlled integration of molecular catalysts into larger superstructures. Here, we present porous chalcogenide framework materials that contain biomimetic catalyst groups immobilized in a chalcogenide network. The chalcogels are formed via metathesis reaction between the clusters [Mo(2)Fe(6)S(8)(SPh)(3)Cl(6)](3-) and [Sn(2)S(6)](4-) in solution, yielding an extended, porous framework structure with strong optical absorption, high surface area (up to 150 m(2)/g), and excellent aqueous stability. Using [Ru(bpy)(3)](2+) as the light-harvesting antenna, the chalcogels are capable of photocatalytically producing hydrogen from mixed aqueous solutions and are stable under constant illumination over a period of at least 3 weeks. We also present improved hydrogen yields in the context of the energy landscape of the chalcogels.


HIV RNA testing in the context of nonoccupational postexposure prophylaxis.
The specificity and positive predictive value of human immunodeficiency virus (HIV) RNA assays have not been evaluated in the setting of postexposure prophylaxis (PEP). Plasma from subjects enrolled in a nonoccupational PEP study was tested with 2 branched-chain DNA (bDNA) assays, 2 polymerase chain reaction (PCR) assays, and a transcription-mediated amplification (TMA) assay. Assay specificity and positive predictive value were determined for subjects who remained negative for HIV antibody for >or=3 months. In 329 subjects examined, the lowest specificities (90.1%-93.7%) were seen for bDNA testing performed in real time. The highest specificities were seen with batched bDNA version 3.0 (99.1%), standard PCR (99.4%), ultrasensitive PCR (100%), and TMA (99.6%) testing. Only the 2 assays with the highest specificities had positive predictive values >40%. For the bDNA assays, increasing the cutoff point at which a test is called positive (e.g., from 50 copies/mL to 500 copies/mL for version 3.0) increased both specificity and positive predictive values to 100%. The positive predictive value of HIV RNA assays in individuals presenting for PEP is unacceptably low for bDNA-based testing and possibly acceptable for PCR- and TMA-based testing. Routine use of HIV RNA assays in such individuals is not recommended.


Micro LC/MS in drug analysis and metabolism studies.
LC/MS has become a routine research tool in some laboratories. Although no single approach to LC/MS presently is without limitations, each approach offers encouraging results and prompts continued improvements. The remaining hurdles appear to be the introduction of total LC effluent into the MS, increased sensitivity, and the ability to analyze higher molecular weight, polar molecules. The micro LC/MS results discussed in this paper offer an opportunity for significantly increased sensitivity by allowing total micro LC effluent introduction into the MS. It remains to be seen whether the development of micro LC column and equipment technology will allow practical micro LC/MS. It may someday provide improved separation of drugs, metabolites, and their conjugates from high levels of endogenous materials in reasonable time periods. Currently, the impressive efficiencies demonstrated for micro LC columns involve mixtures containing low molecular weight solutes that are perhaps more amenable to GC analysis. The analyst routinely involved with problem solving must deal with complex mixtures composed of components with large concentration differences. The future of micro LC, and hence micro LC/MS, will depend upon how well the technique helps solve problems. We believe the future is bright for micro LC/MS. The techniques may require some fine tuning of operating procedures, just as with capillary GC/MS, but certainly the potential for increased efficiency and sensitivity is worth the effort. Currently we are testing a new micro LC/MS DLI probe wherein the exit of the micro column is within 1 cm of the MS ion source [82]. The micro LC column is contained within the DLI probe and should offer the lowest dead volume and the least extracolumn effects yet achieved by LC/MS. Initial testing of this new probe is under way, and experimental results will be reported subsequently. The analytical potential of micro LC/MS is receiving considerable interest. Practical micro LC performance can provide increased capabilities to all types of LC/MS reported to date, and perhaps offer new insight into alternative methods of LC/MS not yet reported. We look forward to learning of these breakthroughs as they become available.


Isolation and expression analysis of Alzheimer's disease-related gene xb51 in zebrafish.
XB51 protein is known to interact with the amino-terminal of the X11L protein and to be involved in Abeta40 generation, a hallmark of Alzheimer's disease. In this study, we isolated a zebrafish xb51 homologue and analyzed its spatio-temporal expression pattern during early brain development. The xb51 transcript was first detected in the forebrain at 22 hr post-fertilization. Expression of xb51 in the brain persisted by 36 hpf and became more complex in the brain after 48 hpf. The detailed expression domain of xb51 in the dorsal telencephalon was defined by several molecular markers: emx1, dlx2, lim1, islet1, neurod4/zath3, ngn1, her4, and elavl3/huC. The location of xb51-expressing cells was restricted in a subset of cells positive for elavl3/huC and acetylated alpha-tubulin, markers of differentiating and/or differentiated neurons. Together, these results suggest that xb51 may be required for maturation and maintenance of xb51-expressing neurons in the forebrain.


Surgery for scoliosis in Duchenne muscular dystrophy.
Scoliosis in people with Duchenne muscular dystrophy is usually progressive and treated with surgery. However, it is unclear whether the existing evidence is sufficiently scientifically rigorous to support a recommendation for spinal surgery for most people with Duchenne muscular dystrophy and scoliosis. This is an updated review and an updated search was undertaken in which no new studies were found. To determine the effectiveness and safety of spinal surgery in people with Duchenne muscular dystrophy with scoliosis. We intended to test whether spinal surgery is effective in increasing survival, improving respiratory function, improving quality of life and overall functioning; and whether spinal surgery is associated with severe adverse effects. We searched the specialized registers of the Cochrane Neuromuscular Disease Group (31 July 2012), MEDLINE (January 1966 to July 2012), EMBASE (January 1947 to July 2012), CENTRAL (2012, Issue 7 in the Cochrane Library), CINAHL Plus(January 1937 to July 2012), Proquest Dissertation and Thesis Database (January 1980 to July 2012), and the National Institute of Health Clinical Trials Database (July 2012). No language restrictions were imposed. We planned to include controlled clinical trials using random or quasi-random allocation of treatment evaluating all forms of spinal surgery for scoliosis in people with Duchenne muscular dystrophy in the review. The control interventions would have been no treatment, non-operative treatment, or a different form of spinal surgery. Two authors independently examined the search results and evaluated the study characteristics against inclusion criteria to decide which ones would be included in the review. On searching, 47 studies were relevant but none met the inclusion criteria for the review, because they were not clinical trials but prospective or retrospective reviews of case series. Since there were no randomized controlled clinical trials available to evaluate the effectiveness of scoliosis surgery in people with Duchenne muscular dystrophy, no evidence-based recommendation can be made for clinical practice. People with scoliosis should be informed about the uncertainty of benefits and potential risks of surgery for scoliosis. Randomized controlled trials are needed to investigate the effectiveness of scoliosis surgery, in terms of quality of life, functional status, respiratory function and life expectancy.


Multiresonant spinor dynamics in a Bose-Einstein condensate.
We analyze the spinor dynamics of a 87Rb F=2 condensate initially prepared in the m(F) = 0 Zeeman sublevel. We show that this dynamics, characterized by the creation of correlated atomic pairs in m(F) = +/-1, presents an intriguing multiresonant magnetic-field dependence induced by the trap inhomogeneity. This dependence is directly linked to the most unstable Bogoliubov spin excitations of the initial m(F) = 0 condensate, showing that, in general, even a qualitative understanding of the pair-creation efficiency in a spinor condensate requires a careful consideration of the confinement.


PetC1 is the major Rieske iron-sulfur protein in the cytochrome b6f complex of Synechocystis sp. PCC 6803.
Many of the completely sequenced cyanobacterial genomes contain a gene family that encodes for putative Rieske iron-sulfur proteins. The Rieske protein is one of the large subunits of the cytochrome bc-type complexes involved in respiratory and photosynthetic electron transfer. In contrast to all other subunits of this complex that are encoded by single genes, the genome of the cyanobacterium Synechocystis PCC 6803 contains three petC genes, all encoding potential Rieske subunits. Most interestingly, any of the petC genes can be deleted individually without altering the Synechocystis phenotype dramatically. In contrast, double deletion experiments revealed that petC1 and petC2 cannot be deleted in combination, whereas petC3 can be deleted together with any of the other two petC genes. Further results suggest a different physiological function for each of the Rieske proteins. Whereas PetC2 can partly replace the dominating Rieske isoform PetC1, PetC3 is unable to functionally replace either PetC1 or PetC2 and may have a special function involving a special donor with a lower redox potential than plastoquinone. A predominant role of PetC1, which is (partly) different from PetC2, is suggested by the mutational analysis and a detailed characterization of the electron transfer reactions in the mutant strains.


The antiplasmodial activity of isolates from Ajuga remota.
Ajuga remota is the most frequently used medicinal herb for malaria treatment in Kenya. Its two known isolates ajugarin-1 (1) and ergosterol-5,8-endoperoxide (3) and a new isolate 8-O-acetylharpagide (2) were evaluated for their in vitro antiplasmodial activity. Ajugarin-1 was moderately active, with an IC(50) of 23.0 +/- 3.0 microM, as compared to chloroquine (IC(50) = 0.041 +/- 0.003 microM) against the chloroquine-sensitive (FCA 20/GHA) strain of Plasmodium falciparum. Ergosterol-5,8-endoperoxide was about 3x as potent (IC(50) = 8.2 +/- 1.1 microM), while 8-O-acetylharpagide, whose structure was established by spectroscopic evidence, was inactive. Both ajugarin-1 and ergosterol-5,8-endoperoxide did not exhibit cytotoxicity against A431 (skin carcinoma) cell line, but 8-O-acetylharpagide was significantly cytotoxic. This iridoid glucoside, which has been formerly isolated from Ajuga decumbens, was identified in A. remota for the first time.


Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.
Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions.


[Treatment of severe botulism with 3,4-diaminopyridine]].
The specific treatments of botulism with serotherapy and with guanidine are of debatable efficacy. We report a case of nutritional toxin B botulism successfully treated with 3,4-diaminopyridine. Following a meal, a 69 year-old woman consulted for digestive disorders followed by damage to several cranial pairs, autonomous nervous system and ventilation command, motivating mechanical ventilation on tracheal intubation. Administration of symptomatic treatment with 3,4-diaminopyridine led to progressive improvement, although the diagnosis of toxin B botulism was confirmed. Administration of 3,4-diaminopyridine, the efficacy of which had been suggested by the review of experimental literature, led to rapid and clear improvement, probably due to its potentiating effect on acetylcholine release in the neuromuscular junction.


[Cross-over studies].
Randomized, parallel group clinical trials often require large groups of patients; this is expensive and takes time. A randomized cross-over trial can be an efficient and more affordable alternative. A cross-over design can be used to study chronic disorders in which treatments have temporary effects. Participants receive all treatments in consecutive periods and outcomes are measured after every period. In general, only a quarter of the total group size is needed for cross-over studies compared with parallel group studies. Results can be affected by period-effects and carry-over-effects, which can be prevented through randomization and a wash-out period of sufficient length. The dropping-out of participants has more negative consequences for cross-over studies than for parallel group studies.


[Fever-shivers reaction and standard platelet concentrates transfusion: a prospective study].
Fever-shivers reaction (FSR) is the most frequent transfusion immediate incident related to platelet transfusions. The aim of our prospective study was to assess the frequency of the different immediate incidents, especially the frequency and the causes of the FSR, observed during the transfusion of standard platelet concentrates (SPC). For each FSR, analysis of causes included: a bacterial culture of the implicated SPC, a blood culture and HLA antibody screening (lymphocytotoxicity assay) among the patients. In the study period, 34 patients were followed during 74 transfusions. Ten immediate incidents were noted; FSR: N = 8, erythema-urticaria: N = 1 and nausea-vomit: N = 1. The FSR was observed in 6 patients who received 56 SPC. Analysis of causes of this reaction revealed that: HLA antibodies were present in one patient; bacterial contamination was not found neither among the patients nor in the implicated SPC, and the risk of the FSR occurrence rose with increased storage time of the SPC transfused. Indeed, a significant difference was noted between the mean age of the SPC implicated in the FSR and the mean age of those not implicated (P = 0,0028). In conclusion, the FSR is a frequent incident observed during SPC transfusions. In the majority of cases, the cause of this reaction was not identified. Further studies will be necessary to better understand the physiological mechanisms of the FSR.


Phosphoinositide 3-kinase/AKT signaling can promote AIB1 stability independently of GSK3 phosphorylation.
The transcriptional coactivator AIB1 is an oncogene overexpressed in different types of tumors, including breast cancer. Although the subcellular compartimentalization of AIB1 seems to be intimately linked to abnormal proliferation, the molecular mechanisms that regulate its subcellular distribution are not well defined. Here, we report that the nuclear accumulation and half-life of AIB1 vary between cancer cell lines. Using these differences as an experimental model, our results reveal that alterations to the Akt signaling pathway and nuclear export determine the stability of AIB1 and nuclear content of this coactivator. Moreover, our results show that AIB1 is degraded in the nucleus by the proteasome in an ubiquitin-dependent manner. However, this process does not require phosphorylation by GSK3, thereby revealing an alternative mechanism for regulating the turnover of AIB1. We define a new region at the carboxy terminus of AIB1 that is required for proteasome-dependent transcriptional activation and is preceded by a PEST domain that is required for adequate protein turnover. Based on differences in Akt signaling and the subcellular distribution of AIB1 between different cell lines, our results suggest that dysregulation of nuclear shuttling and proteasomal degradation may modulate the oncogenic potential of AIB1.


Influence of external and covert food stimuli on insulin secretion in obese and normal persons.
Exposure to food produces an increase in insulin secretion that is more pronounced in obese than in normal persons. We sought to replicate this finding as well as to determine whether insulin secretion could be influenced by thoughts about food and eating. Normal and obese subjects were presented in counterbalanced order with an external food stimulus or instructions to think about food and eating. Levels of insulin, salivary output, and hunger ratings were obtained prior to and immediately following stimulus presentation. All subjects displayed higher insulin levels following stimulus presentation, with the values for the obese higher than for normals. Although the insulin secretion of the obese was greater in response to the covert as opposed to the external stimulus, the difference was not significant. Salivary output following stimulus presentation was higher for the obese than normals, with hunger ratings increasing in both groups. These data support an expanded role of insulin as an appetite-inducing mechanism.


Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells.
The chicken anemia virus protein apoptin induces a p53-independent, Bcl-2-insensitive type of apoptosis in various human tumor cells. Here, we show that, in vitro, apoptin fails to induce programmed cell death in normal lymphoid, dermal, epidermal, endothelial, and smooth-muscle cells. However, when normal cells are transformed they become susceptible to apoptosis by apoptin. Long-term expression of apoptin in normal human fibroblasts revealed that apoptin has no toxic or transforming activity in these cells. In normal cells, apoptin was found predominantly in the cytoplasm, whereas in transformed and malignant cells it was located in the nucleus, suggesting that the localization of apoptin is related to its activity. These properties make apoptin a potential agent for the treatment of a large number of tumors, also those lacking p53 and/or overexpressing Bcl-2.


Laminin-511-derived recombinant fragment and Rho kinase inhibitor Y-27632 facilitate serial cultivation of keratinocytes differentiated from human embryonic stem cells.
Keratinocytes derived from pluripotent stem cells have a short proliferative lifespan under conventional culture conditions that are optimized for keratinocytes. Recently, a Rho kinase inhibitor, Y-27632, had been used as a standard supplement for culture medium in which the proliferative lifespan of postnatal keratinocytes was markedly expanded. In addition, recombinant human laminin-511 was demonstrated to be an adhesive ligand for promoting proliferation of cultured epidermal keratinocytes. Based on this knowledge, efficacies of Y-27632 and a laminin511-derived recombinant fragment, known as laminin-511 E8 fragment (LN-511-E8), were evaluated for establishing cultivation methods of keratinocyte differentiated from human embryonic stem cells (hESC). Differentiated cells from hESCs, which were established with clinical grade in previous study, were seeded onto culture dishes coated with LN-511-E8 and co-cultured with a mouse feeder layer in serum-free medium supplemented with Y-27632. Before serial cultivation, hESC-derived keratinocytes were separated from other differentiated cells by trypsinization. The isolated hESC-derived keratinocytes were used for evaluating clonogenicity, gene expression analysis for keratinocyte markers, potency of terminal differentiation by air-lifting culture, and long-term proliferation activity by serial cultivation. Moreover, efficacies of Y-27632, LN-511-E8, and mouse feeder layer were evaluated on proliferation of hESC-derived keratinocytes. hESC-derived keratinocytes with activity of clonal growth were successfully isolated by trypsinization and exhibited potency of differentiation to form stratified epidermal equivalents with expressions of progenitor and differentiation markers of epidermal keratinocyte. Y-27632 and LN-511-E8 were required for maintaining the proliferative activity of the hESC-derived keratinocytes in serially cultivation using mouse feeder layer with stable doubling time during logarithmic growth phase. These results indicate the utility of Y-27632 and LN-511-E8 for serial cultivation of hESC-derived keratinocytes, which have a potential for fabricating allogeneic cellular products in clinical situations for regeneration of stratified epithelial tissues.


Resistance mechanism development to the topoisomerase-I inhibitor Hoechst 33342 by Leishmania donovani.
The bisbenzimidazole compound Hoechst 33342 (Ho342) has been identified as a specific Topoisomerase-I (Topo-I) inhibitor in mammalian cells. More recently, we have reported the ability of Ho342 to target L. donovani Topo-I, leading to parasite growth inhibition in vitro by mechanisms involving DNA breakage and apoptosis-like phenomenon. As the Ho342 lead molecule (2,5'-Bi-1H-benzimidazole) can be used as a starting structure for derivative compounds more effective against Leishmania, defining the Ho342 resistance mechanism(s) in Leishmania represents an important strategic tool. In the present study, we selected resistant parasites to Ho342 (LdRHo.300). While we observed an increase of the Topo-I gene expression correlated by a higher Topo-I DNA relaxation activity, the Topo-I genes (LdTOP1A and LdTOP1B) sequencing did not reveal any mutation for the resistant parasites. Moreover, our results on Ho342 cellular accumulation suggested the presence of a potential energy-dependent Ho342 transporter in the wild-type parasite, and that an alteration of this transporter has occurred in LdRHo.300, leading to an altered drug accumulation. Collectively, Ho342 resistance characterization provided results supporting that the resistance developed by LdRHo.300 involves complex mechanisms, most likely dominated by an altered drug accumulation, providing new insight in the Ho342 resistance mechanisms.


Community acquired Pseudomonas pneumonia in an immune competent host.
Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia in immune-competent hosts. It is commonly seen in patients with structural lung abnormality such as cystic fibrosis or in immune compromised hosts. Here, the authors report a case of community-acquired Pseudomonas pneumonia in a 26-year old healthy man who presented with 8-week history of malaise and cough.


Effect of aging on cardiac function during cold stress in humans.
To determine whether skin surface cooling increases left ventricular preload and contractility to a greater extent in older compared with young adults we studied 11 young (28 +/- 2 yr; means +/- SE) and 11 older (64 +/- 3 yr) adults during normothermia (35 degrees C water perfused through a tube-lined suit) and cooling (15 degrees C water perfused for 20 min) using standard and tissue Doppler echocardiography. Cooling significantly decreased skin surface temperature in young (Delta2.8 +/- 0.3 degrees C) and older (Delta3.0 +/- 0.3 degrees C) adults and increased rate-pressure product, an index of myocardial oxygen demand, in older (6,932 +/- 445 to 7,622 +/- 499 mmHg x beats/min for normothermia and cooling, respectively), but not young (7,085 +/- 438 to 7,297 +/- 438 mmHg x beats/min) adults. Increases in blood pressure (systolic and mean blood pressure) during cooling were greater (P < 0.05) in older than in young adults. Cooling increased preload in older (left ventricular end-diastolic volume from 106 +/- 7 to 126 +/- 9 ml and left ventricular internal diameter in diastole from 4.69 +/- 0.12 to 4.95 +/- 0.14 cm; both P < 0.01), but not young adults (left ventricular end-diastolic volume from 107 +/- 7 to 111 +/- 7 ml and left ventricular internal diameter in diastole from 4.70 +/- 0.10 to 4.78 +/- 0.10 cm). Indices of left ventricular contractility (ejection fraction, myocardial acceleration during isovolumic contraction, and peak systolic mitral annulus velocity) were unchanged during cooling in both young and older adults. Collectively, these data indicate that cooling increases left ventricular preload, without affecting left ventricular contractility in older but not young adults. Greater increases in preload and afterload during cooling in older adults contribute to greater increases in indices of myocardial oxygen demand and may help explain the increased risk of cardiovascular events in cold weather.


Intravenous metoclopramide versus dexketoprofen trometamol versus metoclopramide+ dexketoprofen trometamol in acute migraine attack in the emergency department: A randomized double-blind controlled trial.
The objective of this study was to determine the analgesic efficacy and safety of intravenous, single-dose metoclopramide versus dexketoprofen trometamol versus metoclopramide+ dexketoprofen trometamol in patients presenting with acute migraine attack to the emergency department (ED). This single-center, randomized, double-blind study was conducted in a tertiary care ED. Eligible patients met the migraine criteria of the International Headache Society were randomized to receive 10 mg intravenous metoclopramide, 50 mg intravenous dexketoprofen trometamol, or 50 mg dexketoprofen trometamol +10 mg metoclopramide. Visual analogue scale (VAS) was used for pain measurement at baseline, after 15 and 30 min. The primary outcome measure was the changes in the VAS scores at the 15th and 30th minutes of treatment. The secondary outcome measures were the presence of adverse effects and the requirement of rescue medicine. Patients (n = 150) were randomized into 3 groups with similar VAS scores at baseline. While there was no significant difference between metoclopramide and dexketoprofen trometamol in reducing pain at the 15th and 30th minute (p = 0.618 and p = 0.862, respectively) and between metoclopramide and metoclopramide + dexketoprofen trometamol at the 15th minute (p = 0.074), metoclopramide + dexketoprofen trometamol was superior to both metoclopramide [mean difference: -13.2 mm (95% CI -23.1 to -3.3)] and dexketoprofen trometamol [mean difference: -11.02 mm (95% CI -20.9 to -1.1)] at the 30th min (p = 0.006 and p = 0.025 respectively). The rescue drug was required by 3 patients (6%) were in metoclopramide group, 4 patients (8%) in dexketoprofen trometamol group and one patient (2%) in the metoclopramide + dexketoprofen trometamol group. No side effects were observed in subjects in three treatment groups. No significant difference in VAS was found between three treatment groups at the 15th minute, but metoclopramide + dexketoprofen trometamol was superior to both metoclopramide and dexketoprofen trometamol at the 30th min.


Anti-parasitic drug discovery against Babesia microti by natural compounds: an extensive computational drug design approach.
Tick-borne Babesiosis is a parasitic infection caused by Babesia microti that can infect both animals and humans and may spread by tick, blood transfusions, and organ transplantation. The current therapeutic options for B. microti are limited, and drug resistance is a concern. This study proposes using computational drug design approaches to find and design an effective drug against B. microti. The study investigated the potentiality of nine natural compounds against the pathogenic human B. microti parasite and identified Vasicinone and Evodiamine as the most promising drugs. The ligand structures were optimized using density functional theory, molecular docking, molecular dynamics simulations, quantum mechanics such as HOMO-LUMO, drug-likeness and theoretical absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetics characteristics performed. The results showed that Vasicinone (-8.6 kcal/mol and -7.8 kcal/mol) and Evodiamine (-8.7 kcal/mol and -8.5 kcal/mol) had the highest binding energy and anti-parasitic activity against B. microti lactate dehydrogenase and B. microti lactate dehydrogenase apo form. The strongest binding energy was reported by Vasicinone and Evodiamine; the compounds were evaluated through molecular dynamics simulation at 100 ns, and their stability when they form complexes with the targeted receptors was determined. Finally, the pkCSM web server is employed to predict the ADMET qualities of specific molecules, which can help prevent negative effects that arise from taking the treatment. The SwissADME web server is used to assess the Lipinski rule of five and drug-likeness properties including topological polar surface area and bioavailability. The Lipinski rule is used to estimate significant drug-likeness. The theoretical pharmacokinetics analysis and drug-likeness of the selected compounds are confirmed to be accepted by the Lipinski rule and have better ADMET features. Thus, to confirm their experimental value, these mentioned molecules should be suggested to carry out in wet lab, pre-clinical, and clinical levels.


Comparative analysis of calcified soft tissues revealed shared deregulated pathways.
Calcification of soft tissues is a common age-related pathology that primarily occurs within vascular tissue. The mechanisms underlying pathological calcification in humans and tissue specificity of the process is still poorly understood. Previous studies examined calcified tissues on one to one basis, thus preventing comparison of deregulated pathways across tissues. This study aimed to establish common and tissue-specific changes associated with calcification in aorta, artery tibial, coronary artery and pituitary gland in subjects from the Genotype-Tissue Expression (GTEx) dataset using its RNA sequencing and histological data. We used publicly available data from the GTEx database https://gtexportal.org/home/aboutGTEx. All GTEx tissue samples were derived by the GTEx consorcium from deceased donors, with age from 20 to 79, both men and women. GTEx study authorization was obtained via next-of-kin consent for the collection and banking of de-identified tissue samples for scientific research. Hematoxylin and eosin (H&E) staining of arteries were manually graded based on the presence of calcification on a scale from zero to four, where zero designates absence of calcification and four designates severe calcification. Samples with fat contamination and mislabeled tissues were excluded, which left 430 aorta, 595 artery tibial, 124 coronary artery, and 283 pituitary samples for downstream gene expression analysis. Transcript levels of protein-coding genes were associated with calcification grade using sex, age bracket and cause of death as covariates, and tested for pathway enrichment using gene set enrichment analysis. We identified calcification deposits in 28 (6.5%) aortas, 121 (20%), artery tibials, 54 (43%), coronary arteries, and 24 (8%) pituitary glands of GTEx subjects. We observed an age-dependent increase in incidence of calcification in all vascular tissues, but not in pituitary. Subjects with calcification in the artery tibial were significantly more likely to have calcification in the coronary artery (OR = 2.56, p = 6.3e-07). Markers of calcification previously established in preclinical and in vitro studies, e.g., BMP2 and RUNX2, were deregulated in the calcified tibial and coronary arteries, confirming the relevance of these genes to human pathology. Differentially expressed genes associated with calcification poorly overlapped across tissues suggesting tissue-specific nuances in mechanisms of calcification. Nevertheless, calcified arteries unanimously down-regulated pathways of intracellular transport and up-regulated inflammatory pathways suggesting these as universal targets for pathological calcification. In particular, PD-1 and PD-L1 genes were up-regulated in calcified tissues but not in the blood of the same subjects, suggesting that localized inflammation contributes to pathological calcification. Pathological calcification is a prevalent disease of aging that shares little changes in expression in individual genes across tissues. However, our analysis suggests that it potentially can be targeted by alleviating local inflammation of soft tissues.


Optimizing imaging in the pediatric trauma patient, part 1: head and neck trauma.
Trauma is the leading cause of death in the pediatric population and is among the most common reasons for ED visits by children. Imaging is an important tool for the diagnosis and management of pediatric trauma, but there are risks associated with exposure to ionizing radiation. In pediatric head and neck injuries, clinical findings and clinical decision tools can help inform selection of the most appropriate imaging modalities for the trauma patient, while also reducing unnecessary radiation exposure. This supplement reviews evidence-based recommendations for imaging decisions and interpretations in skull fractures, traumatic brain injuries, abusive head trauma, cervical spine injuries, and facial bone fractures. Examples demonstrating imaging modalities and specific findings for the types of injuries are also provided.


Problems and perspectives of diagnostic imaging: the pineal region.
In 1970 the state of the art in neuroradiological diagnosis was considered satisfactory enough, if not almost perfect, by the people working in this field. But when a few years later Computerized Tomography appeared, a new impressive standard in neuroradiological resolution was achieved, moreover with a non-invasive method. In the '80 further improvement was brought by several striking new diagnostic technologies, such as Magnetic Resonance, Positron Emission Tomography and Single Photon Emission Computed Tomography which allow the physician to achieve a new standard in non-invasive high resolution neuro-imaging which was simply unbelievable a few years ago. A new era is now beginning in the neuro-radiological sciences in which the new techniques surely allow the diagnosis towards disease previously escaping the neuro-radiological observation.


Surgical treatment of isolated type II superior labrum anterior-posterior (SLAP) lesions: repair versus biceps tenodesis.
It is still unclear which patients with isolated type II superior labrum anterior-posterior (SLAP) lesions benefit from either superior labral repair or biceps tenodesis. This study evaluates the indications and outcomes of patients with isolated type II SLAP lesions who have undergone either procedure. A retrospective analysis was performed of patients who had surgery for an isolated type II SLAP lesion between 2008 and 2011. There were 25 patients: 15 underwent biceps tenodesis, with a mean follow-up of 31 months (range, 26-43 months), and 10 underwent SLAP repair, with a mean follow-up of 35 months (range, 25-52 months). The mean age was 47 years (range, 30-59 years) in the tenodesis group and 31 years (range, 21-43 years) in the repair group. At latest follow-up, both groups showed significant improvements in subjective shoulder value and pain score. No difference was observed in American Shoulder and Elbow Surgeons score (93.0 vs 93.5, P = .45), patient satisfaction (93% vs 90%, P = .45), or return to preinjury sporting level (73% vs 60%, P = .66). Analysis of the indications for treatment showed that in the large majority, tenodesis was performed in older patients (>35 years) and patients who showed degenerative or frayed labrums whereas SLAP repairs were performed in younger and more active patients with healthy-appearing labral tissue. There was only 1 failure in the tenodesis group, and in the SLAP repair group, there were 2 cases of postoperative stiffness; all were treated nonoperatively. In this study, we show that both biceps tenodesis and SLAP repair can provide good to excellent results if performed in appropriately selected patients with isolated type II SLAP lesions.


[The impact of unilateral diaphragmatic paralysis on sleep-disordered breathing: a scoping review].
Unilateral diaphragm paralysis (UDP) may potentially worsen sleep-disordered breathing (SDB). Unilateral diaphragm paralysis has been associated with proximal brachial plexus blockade, such as interscalene and supraclavicular block. The impact of UDP in patients with SDB is not known in this context. The objectives of this scoping review were to explore the associations between UDP and worsening SDB severity, oxygenation, and pulmonary function. A systematic search was developed, peer-reviewed, and applied to Embase, Medline, CINAHL, and Cochrane databases to include studies involving adult patients (≥ 18 yr) with SDB, where the effects of UDP on SDB severity, oxygenation, and pulmonary function were examined. Six studies (n = 100 patients) with UDP and SDB were included. The sample population was derived exclusively from respirology-sleep clinics, and none were surgical patients. Compared with control (no UDP), UDP was associated with an increased respiratory disturbance index, most pronounced during rapid eye movement (REM) sleep and supine sleep. Supine and REM sleep were associated with obstructive and mixed (both obstructive and central) events, respectively. Compared with control, UDP was associated with a lower mean and minimum oxygen saturation and arterial oxygen tension during all sleep stages and in all body positions. The majority of UDP patients were found to have clinically significant reductions in mean forced expiratory volume in one second and forced vital capacity values, consistent with restrictive ventilatory pattern. We observed an association between UDP and increasing SDB severity, particularly during REM sleep and while sleeping in the supine position. Although we identified weaknesses in study design and lack of perioperative data, anesthesiologists should be aware of this association when considering proximal brachial plexus blockade in patients with SDB.


Gene analysis for longitudinal family data using random-effects models.
We have extended our recently developed 2-step approach for gene-based analysis to the family design and to the analysis of rare variants. The goal of this approach is to study the joint effect of multiple single-nucleotide polymorphisms that belong to a gene. First, the information in a gene is summarized by 2 variables, namely the empirical Bayes estimate capturing common variation and the number of rare variants. By using random effects for the common variants, our approach acknowledges the within-gene correlations. In the second step, the 2 summaries were included as covariates in linear mixed models. To test the null hypothesis of no association, a multivariate Wald test was applied. We analyzed the simulated data sets to assess the performance of the method. Then we applied the method to the real data set and identified a significant association between FRMD4B and diastolic blood pressure (p-value = 8.3 × 10(-12)).


Visual feature tuning of superior colliculus neural reafferent responses after fixational microsaccades.
The primate superior colliculus (SC) is causally involved in microsaccade generation. Moreover, visually responsive SC neurons across this structure's topographic map, even at peripheral eccentricities much larger than the tiny microsaccade amplitudes, exhibit significant modulations of evoked response sensitivity when stimuli appear perimicrosaccadically. However, during natural viewing, visual stimuli are normally stably present in the environment and are only shifted on the retina by eye movements. Here we investigated this scenario for the case of microsaccades, asking whether and how SC neurons respond to microsaccade-induced image jitter. We recorded neural activity from two male rhesus macaque monkeys. Within the response field (RF) of a neuron, there was a stable stimulus consisting of a grating of one of three possible spatial frequencies. The grating was stable on the display, but microsaccades periodically jittered the retinotopic RF location over it. We observed clear short-latency visual reafferent responses after microsaccades. These responses were weaker, but earlier (relative to new fixation onset after microsaccade end), than responses to sudden stimulus onsets without microsaccades. The reafferent responses clearly depended on microsaccade amplitude as well as microsaccade direction relative to grating orientation. Our results indicate that one way for microsaccades to influence vision is through modulating how the spatio-temporal landscape of SC visual neural activity represents stable stimuli in the environment. Such representation depends on the specific pattern of temporal luminance modulations expected from the relative relationship between eye movement vector (size and direction) on one hand and spatial visual pattern layout on the other.NEW & NOTEWORTHY Despite being diminutive, microsaccades still jitter retinal images. We investigated how such jitter affects superior colliculus (SC) activity. We found that SC neurons exhibit short-latency visual reafferent bursts after microsaccades. These bursts reflect not only the spatial luminance profiles of visual patterns but also how such profiles are shifted by eye movement size and direction. These results indicate that the SC continuously represents visual patterns, even as they are jittered by the smallest possible saccades.


[Cytological observation and DNA methylation analysis of two new cytoplasmic male sterile lines of maize during microsporogenesis].
Cytoplasmic male sterility (CMS) is a widespread phenomenon in higher plants and has been applied in the commercial production of hybrid seeds. Two CMS lines A1 and A2 of maize were obtained previously by a transgenic experiment. In this study, we conducted cytological observation of developmental microspores with CMS line A1, A2 and their maintainer line (18 red) using paraffin section technology. We also analyzed DNA methylation levels at different developmental stages using high performance liquid chromatography (HPLC). Our results showed that the pollen abortion of A1 and A2 mainly happened from the tetrad stage to the middle of mononuclear stage. Another abortive phenomenon found in CMS line A2 occurred at the pollen mother cell stage. The DNA methylation level of leaf increased rapidly from the seedling stage to the shooting stage in 18 red, while it remained constant in A1 and A2. For the tassel, the DNA methylation levels in 18 red increased gradually during the anther development, while a peak of DNA methylation level occurred in A1 and A2 at the tetrad stage, corresponding to the abortion period of microspore. This result suggested that the level of DNA methylation in the tassels is associated with the pollen abortion characteristics in CMS lines. In summary, our results implied a connection between pollen abortion and epigenetic regulation in maize CMS.


Capsaicin affects macrophage anti-inflammatory activity via the MAPK and NF-κB signaling pathways.
Capsaicin, the main constituent in chili, is an extremely spicy vanillin alkaloid and is found in several Capsicum species in China. Traditionally, it has been used to treat inflammatory diseases such as allergic rhinitis, neuralgia after shingles, refractory female urethral syndrome, spontaneous recalcitrant anal pruritus, and solid tumors. Constant stimulation of the body by inflammatory factors can lead to chronic inflammation. Capsaicin possesses anti-inflammatory activity; however, the underlying mechanism is unknown. We investigated the effect of capsaicin on the secretion of macrophage inflammatory factors in a lipopolysaccharide-induced inflammation model using 56 healthy, SPF grade, BALB/c mice. To this end, mice peritoneal macrophages were isolated and stimulated with lipopolysaccharide (1 μg/mL) and capsaicin (25, 50, 75, or 100 μg/mL) for 24 h. At all concentrations tested, capsaicin significantly promoted the phagocytosis of neutral red dye by macrophages. Furthermore, the gene expression and secretion of inflammatory cytokines significantly increased after induction with lipopolysaccharide (P<0.01); the interleukin (IL)-6 level was 204 μg/mL, tumor necrosis factor (TNF)-α level was 860 μg/mL, and nitric oxide (NO) level was 19.8 μg/mL. However, the treatment with capsaicin reduced their levels (P<0.01) and protein expression of lipopolysaccharide-induced extracellular signal-related kinase 1/2 and p65 (P<0.05). Overall, capsaicin reduced the secretion of inflammatory cytokines (P<0.01), interleukins, TNF-α (P<0.01), and NO by inhibiting the nuclear factor-kappa B and microtubule-associated protein kinase signaling pathways, and thereby reduced lipopolysaccharide-induced inflammatory response in macrophages.


Outcomes of a trial of an age-friendly dining initiative: Dining Co.
With the rise of age-friendly cities and communities, increasing attention is being paid to coproducing age-friendly guidelines with older people and community stakeholders. Little is known however about age-friendly guidelines for dining establishments. A three-stage study to develop general and contextualised requirements for an age-friendly dining experience was conducted in the City of Onkaparinga, South Australia. The first stage involved older people in co-designing aspects of an age-friendly dining experience. Subsequently, the second and third stage coproduced, trialed and evaluated age-friendly initiatives with two dining venues. Through co-design, seven domains of an age-friendly dining experience were identified (Menu, Affordability, Dementia Awareness, Venue, Feeling Welcome, Special Offerings and Assistance), alongside an overarching desire for a 'meaningful' dining experience. Differences in health and socioeconomic status of diners underpinned the differences needed to ensure an age-friendly dining experience and highlight the importance of contextualisation for the local population. The trial demonstrated positive outcomes for both older diners and venues. The environment, value and logistics of dining out are important to older people when making choices about dining in the community. The elements of an age-friendly dining experience presented in this study are a useful starting point for contextualisation to other local settings.


Xenoantigen-Dependent Complement-Mediated Neutralization of Lymphocytic Choriomeningitis Virus Glycoprotein-Pseudotyped Vesicular Stomatitis Virus in Human Serum.
Neutralization by antibodies and complement limits the effective dose and thus the therapeutic efficacy of oncolytic viruses after systemic application. We and others previously showed that pseudotyping of oncolytic rhabdoviruses such as maraba virus and vesicular stomatitis virus (VSV) with the lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) results in only a weak induction of neutralizing antibodies. Moreover, LCMV-GP-pseudotyped VSV (VSV-GP) was significantly more stable in normal human serum (NHS) than VSV. Here, we demonstrate that depending on the cell line used for virus production, VSV-GP showed different complement sensitivities in nonimmune NHS. The NHS-mediated titer reduction of VSV-GP was dependent on activation of the classical complement pathway, mainly by natural IgM antibodies against xenoantigens such as galactose-α-(1,3)-galactose (α-Gal) or N-glycolylneuraminic acid (Neu5Gc) expressed on nonhuman production cell lines. VSV-GP produced on human cell lines was stable in NHS. However, VSV-GP generated in transduced human cells expressing α-Gal became sensitive to NHS. Furthermore, GP-specific antibodies induced complement-mediated neutralization of VSV-GP independently of the producer cell line, suggesting that complement regulatory proteins potentially acquired by the virus during the budding process are not sufficient to rescue the virus from antibody-dependent complement-mediated lysis. Thus, our study points to the importance of a careful selection of cell lines for viral vector production for clinical use.IMPORTANCE Systemic application aims to deliver oncolytic viruses to tumors as well as to metastatic lesions. However, we found that xenoantigens incorporated onto the viral surface from nonhuman production cell lines are recognized by natural antibodies in human serum and that the virus is thereby inactivated by complement lysis. Hence, to maximize the effective dose, careful selection of cell lines for virus production is crucial.


Low uptake affinity cultivars with biochar to tackle Cd-tainted rice--A field study over four rice seasons in Hunan, China.
Biochar is becoming an environmentally friendly material for remediation of heavy metal contaminated soils and improving food safety. A field trial over four rice seasons was conducted to investigate the use of biochar and low Cd accumulating cultivars on Cd uptake in a heavy metal contaminated soil. Wheat straw derived biochar was applied at 0, 20 and 40 t ha(-1). Two rice cultivars with differing Cd accumulation abilities were selected in each season. The results showed that both biochar and low Cd affinity cultivars significantly reduced rice grain Cd accumulation. Biochar had no significant effect the first season but thereafter consistently reduced rice grain Cd by a maximum of 61, 86 and 57% over the next three seasons. Zn accumulation in the rice grains was not decreased by biochar application, although available soil Zn was sharply reduced (35-91%). Indica conventional rice cultivars had much lower Cd, but higher Zn and lower Cd/Zn ratios in the grain than indica hybrid cultivars. Biochar was more effective for mitigating grain Cd accumulation in low Cd affinity cultivars than in high affinity cultivars. Soil pH was sustainably increased (up to nearly 1 unit) while available Cd significantly decreased by a maximum of 85% after biochar addition. The translocation of Cd from rice roots to shoots was reduced from 20 to 80% by biochar. Low uptake affinity cultivars combined with biochar reduced late rice grain Cd concentration and Cd/Zn ratios by 69-80% and 72-80%, respectively. It indicated that the management of combining biochar and low Cd affinity cultivars should be an efficient way to remediate Cd contaminated rice paddies and reduce health risk associated with consuming rice from these soils.


A study of chromosomal aberrations in miners exposed to diesel exhausts.
A study was made of chromosome aberrations in cultured lymphocytes from a group of 14 miners exposed to diesel exhausts and a reference group of office employees and construction workers. No increased frequency of chromosomal aberrations was observed. The frequency of chromosomal aberrations (both gaps and breaks) was, however, found to be associated with smoking.


Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.
Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.


The Value of Injection Therapy with Botulinum Toxin in Pain Treatment of Primary Chronic Anal Fissures Compared to Anal Dilation, and Local Nifedipine in Combination with Lidocaine.
Introduction: Anal fissure is a longitudinal tear of the mucosa of the anal canal extending from the outer anal orifice in the direction of the dentate line of the inner anal opening. Fissures are divided into primary and secondary, and acute or chronic. Besides minimal rectal bleeding, itching and soiling, primary chronic anal fissures (PCAF) manifest with anal pain as theirs main determinant. It is described as the most troubling symptom. Aim: To compare the effect of injection therapy with botulinum toxin A (ITBT) vs. anal dilation (AD), and local nifedipine with lidocaine (LNL) in pain treatment of PCAF. Materials and Methods: This controlled retrospective prospective longitudinal study covered 94 patients, divided in 3 groups. The first was treated with ITBT, the second with AD and third using LNL (31, 33 and 30 patients respectively). Clostridium botulinum toxin A was used, dissolved with saline to concentration of 200 U/ml. The solution was applied to both sides of PCAF at dose of 40U. Modified technique of AD was done using 3 fingers of a single hand, progressively introduced into the anal canal, followed by gradual lateral distraction during 1 min. LNL therapy was conducted using nifedipine (0.3%) with lidocaine (1.5%) ointment, applied twice daily for 3 weeks. To measure pain, a visual analog scale (VAS) was used. The follow-up period was 12 weeks with checkup at week 4. Results: The median age of participants was 46.6±13.9 years (50 males vs. 44 females). The type of therapy had a significantly different effect on pain at week 4 (p=0.0003). Severe pain was present in only 2 ITBT patients, 16 AD, and 6 LNL patients. Post hoc analyses showed different pain disappearance time by week 12 (p <0.0001). The mean time was shortest in ITBT group (6.1±1.5 weeks). Anal pain intensity significantly differed among the 3 groups (Fisher exact, p=0.002). Namely, 71% in ITBT group rated the pain as weakest (VAS score 1) compared to 18.2% in AD and 30% of patients in LNL group. The overall pain reduction significance was in favor of ITBT, due to the differences between the ITBT and AD groups (p=0.00024) and ITBT compared to LNL group (p=0.018). Conclusion: ITBT is superior to AD and LNL in reducing pain in PCAF.


Early delivery following chronic and acute ambient temperature exposure: a comprehensive survival approach.
Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery. We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002-2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season. Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7-9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0-1.6 for 2°C vs 11.6°C] and 10-4 days before delivery (RR: 1.6, 95% CI: 1.1-2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05-3.8) or 20-26 weeks after conception (RR: 2.9, 95% CI: 1.2-6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth. In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births.


Linear instability in Rayleigh-stable Taylor-Couette flow.
Rayleigh's stability criterion describes the inviscid stability of rotating fluid flows. Despite the limitations of the criterion due to the assumptions used, it has been widely viewed as a general stability barrier in various rapidly rotating flows. However, contrary to previous belief, a linear instability is identified in Rayleigh-stable Taylor-Couette flow. The instability is found in cyclonic rapid rotation regime, for almost the entire range of the radius ratio of the cylinders.


Clinical features of adult moyamoya disease with special reference to the diagnosis.
Fifteen years of experience with adult moyamoya disease (MMD) in a single department were analyzed to describe the clinical features and to clarify the existence of the disease entity of adult MMD with special reference to its diagnosis. This study included 348 patients treated between 1996 and 2010. Male to female ratio was 128 to 220 with mean age of 39 years. The presence of neurological symptoms and signs during childhood and mean Suzuki stage according to the age were evaluated. Adult MMD was differentiated from other diseases, such as vasculitis, by comparing the laboratory data including common markers and specific markers for such diseases between 22 adult MMD and 21 atherosclerotic disease (ASD) patients. Conventional angiographic data were analyzed to detect progression in 52 unilateral adult MMD patients over a mean follow-up duration of 4.8 years. Only one of 128 patients (0.8%) aged over 40 years showed childhood symptoms and signs. The distribution of the mean Suzuki stage between patients aged 40 years and under and over 40 years was similar. Laboratory tests differentiating the other diseases with the same phenotype with MMD revealed no difference between adult MMD and ASD. The progression of unilateral MMD to bilateral MMD occurred in 6 of 52 patients (11.5%). Adult MMD is not a syndrome, but a distinct disease entity with significant progression of unilateral MMD to bilateral MMD. Diagnostic and therapeutic strategies should be different from pediatric cases when considering adult MMD.


Near-exact non-relativistic ionization energies for many-electron atoms.
Electron-electron interactions and correlations form the basis of difficulties encountered in the theoretical solution of problems dealing with multi-electron systems. Accurate treatment of the electron-electron problem is likely to unravel some nice physical properties of matter embedded in the interaction. In an effort to tackle this many-body problem, a symmetry-dependent all-electron potential generalized for an n-electron atom is suggested in this study. The symmetry dependence in the proposed potential hinges on an empirically determined angular momentum-dependent partitioning fraction for the electron-electron interaction. With the potential, all atoms are treated in the same way regardless of whether they are open or closed shell using their system specific information. The non-relativistic ground-state ionization potentials for atoms with up to 103 electrons generated using the all-electron potential are in reasonable agreement with the existing experimental and theoretical data. The effects of higher-order non-relativistic interactions as well as the finite nuclear mass of the atoms are also analysed.


Variations in Low Intensity Shockwave Treatment Protocols for Erectile Dysfunction: A Review of the Literature and Guide to Offering Treatment.
Low-intensity shockwave therapy (LiSWT) for erectile dysfunction (ED) continues to gain popularity in both clinical practice and the academic literature. The majority of trials and meta-analysis studies have shown LiSWT to be low risk with a trend toward positive improvements in International Index of Erectile Function (IIEF) scores. However, there is still debate over the clinical utility of LiSWT and there is no agreed upon optimal treatment protocol. In this review article we summarize published meta-analysis studies of LiSWT for ED, and review the treatment protocols from randomized sham-control trials published in the last 10 years. We found the most common device settings were an energy of 0.09 mJ/mm² and a frequency of 5 Hz. Shock number and location varied, but the most common protocol was 1,500 shocks per session, with 900 shocks to the penis (shaft, base, or hilum) and 600 shocks to the proximal corpora/crura. Protocols ranged from 4 to 12 treatment sessions. We also describe our institutional experience with LiSWT, including patient counseling and treatment protocol.


Ovarian conservation is associated with better survival in young patients with T1N0M0 cervical adenocarcinoma: a population-based study.
Ovarian conservation is controversial in patients with cervical adenocarcinoma due to the risk of ovarian metastasis. The aim of this study is to evaluate the association of ovarian conservation with survival outcomes in young patients with T1N0M0 cervical adenocarcinoma. Women who were 45 years of age or younger with T1N0M0 cervical adenocarcinoma from 1988 to 2013 recorded in the Surveillance, Epidemiology, and End Results (SEER) database were included. Propensity score weighting was used to balance the intragroup differences. Cause-specific survival (CSS) and overall survival (OS) were compared using Kaplan-Meier estimates. A multivariate Cox model was used to adjust for covariates including propensity score. A stratified analysis was then conducted. Totally, 1090 (79.7%) patients underwent oophorectomy and 278 (20.3%) patients whose ovaries were preserved were identified. Patients with preserved ovaries were younger, with a lower T classification and less likely to undergo pelvic lymphadenectomy (all p < 0.05). After propensity weighting, ovarian conservation group had better cause-specific survival (CSS) (5-year 98.8 versus 97.1%, 10-year 98.0 versus 95.2%, p = 0.0370) and overall survival (OS) (5-year 98.8 versus 97.1%, 10-year 96.5 versus 93.5%, p = 0.0025). After adjustment, the CSS benefit of ovarian conservation was marginally significant (p = 0.051) and OS benefit was still significant (p = 0.006). Stratified analysis showed that the CSS benefit was found in T1b classification (HR, 0.23; 95% CI 0.06-0.89, p = 0.033) and histological grade > 1 (HR 0.12; 95% CI 0.02-0.87; p = 0.035). Among young women with T1N0M0 cervical adenocarcinoma, ovarian conservation is associated with better survival.


An improved correlation method for determining the period of a torsion pendulum.
Considering variation of environment temperature and unhomogeneity of background gravitational field, an improved correlation method was proposed to determine the variational period of a torsion pendulum with high precision. The result of processing experimental data shows that the uncertainty of determining the period with this method has been improved about twofolds than traditional correlation method, which is significant for the determination of gravitational constant with time-of-swing method.


Arthroscopic resection of wrist ganglia.
The arthroscopic resection of synovial cysts of the wrist is a simple technique which is comfortable for the patient. We report on a series of 96 patients with dorsal synovial cysts (75 women, 21 men). All patients had undergone preliminary treatment which had been unsuccessful. We operated on 32 patients with a volar cyst (27 women, five men). All the patients were operated on as outpatients under local regional anaesthesia. For the dorsal cysts, after having precisely located the cyst, it is then resected after having inserted a shaver directly through the wall of the cyst starting with the capsule. For the volar cysts the arthroscope was inserted through a 3-4 portal and the shaver was inserted through a 1-2 radiocarpal portal. In all cases, there was no immobilisation and a range of motion was started the same day. For the dorsal cysts, our average follow-up was 34 months (range 12-46 months). There were no complications. We had four recurrences. For the palmar cysts, our average follow-up was 26 months (range 12-39 months). There have been no recurrences to date.


Long-term controlled release of PLGA microparticles containing antidepressant mirtazapine.
The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.2%, yield 79.7%). Interaction between organic solvent effect and effect of PVA concentration was revealed. The prepared samples released the drug for 5 days with kinetics very close to that of zero order (R(2 )= 0.9549 - 0.9816). According to the correlations, the drug was probably released by a combination of diffusion and surface erosion, enhanced by polymer swelling and chain relaxation.


Design and Implementation of a Dual-Region Self-Referencing Fiber-Optic Surface Plasmon Resonance Biosensor.
The need for self-referencing is extremely important in the field of biosensing. In this manuscript, we report on the study, design, and validation of a dual-region self-referencing fiber-optic surface plasmon resonance biosensor. One region is intended to measure and monitor the binding events of the biological sample under test, while the other one is designed to be used as a reference channel to compensate for external factors, such as bulk refractive index modifications and temperature oscillations, that can negatively affect the biomolecular interaction measurement. Two different configurations for the biosensor probe are presented and investigated here, both theoretically and experimentally. First, the theoretical performance of the proposed biosensor probes, in terms of surface plasmon resonance wavelength shift, was simulated using a numerical model. Afterward, they were experimentally validated in sucrose-water solutions and showed a response to refractive index and temperature changes with sensitivities up to 2000 nm/RIU and 1.559 nm/°C, respectively. Finally, an aptamer-based bioassay and a high-resolution melting assay were successfully implemented on the two proposed configurations, demonstrating the feasibility of analyzing the binding events and measuring other external signal modifications simultaneously using the same biosensor probe.


Evaluation of thermographic imaging of the limbs of healthy dogs.
To describe a thermographic imaging protocol, identify normal thermographic patterns (ie, color map reflecting the skin temperature distribution) for various regions of interest (ROIs) of dog limbs, and evaluate effects of clipping the coat on thermographic patterns and limb temperature in healthy dogs. 10 healthy dogs. Each dog was thermographically evaluated in the same room (ambient temperature, 21 degrees C) via ROIs that included cranial and caudal views of the body, full lateral body views, full views of the limbs, and views of various limb regions. After initial imaging, the coat was clipped on the forelimbs and hind limbs only. Each dog was then evaluated 15 and 60 minutes and 24 hours after clipping by use of the same protocol. For each ROI within a category (intact coat and each time point after clipping), mean temperatures were similar among the 10 dogs. Pairwise comparisons for 15 and 60 minutes and 24 hours established patterns of temperature stabilization among the 3 time points. Temperatures did not differ significantly between the left and right limbs. There was a mean success rate of 75% for use of image pattern analysis for recognition of similar thermographic patterns in the forelimbs and hind limbs. Thermography can be a viable, noninvasive imaging modality that provides consistent images with reproducible thermal patterns in ROIs examined in healthy dogs. Although the coat had a predictable influence to decrease the mean temperature, thermal patterns remained fairly consistent after the coat was clipped.


Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis.
Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11'-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunA-tunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.


Color improves "visual" acuity via sound.
Visual-to-auditory sensory substitution devices (SSDs) convey visual information via sound, with the primary goal of making visual information accessible to blind and visually impaired individuals. We developed the EyeMusic SSD, which transforms shape, location, and color information into musical notes. We tested the "visual" acuity of 23 individuals (13 blind and 10 blindfolded sighted) on the Snellen tumbling-E test, with the EyeMusic. Participants were asked to determine the orientation of the letter "E." The test was repeated twice: in one test, the letter "E" was drawn with a single color (white), and in the other test, with two colors (red and white). In the latter case, the vertical line in the letter, when upright, was drawn in red, with the three horizontal lines drawn in white. We found no significant differences in performance between the blind and the sighted groups. We found a significant effect of the added color on the "visual" acuity. The highest acuity participants reached in the monochromatic test was 20/800, whereas with the added color, acuity doubled to 20/400. We conclude that color improves "visual" acuity via sound.


Immune Microenvironment Change and Involvement of Circular RNAs in TIL Cells of Recurrent Nasopharyngeal Carcinoma.
Nasopharyngeal carcinoma is a malignant tumor that is highly prevalent in southern China and the Southeast Asian belt. Recent studies have shown that the T cells play important regulatory roles in tumorigenesis and progression. We test TIL cell of recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. We found that T cell change in recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. Based on GEO database, we selected differently expressed circRNAs in nasopharyngeal carcinoma tissues. qRTPCR show that some circRNAs also highly expressed in TIL cells. In conclusion, immune microenvironment changed in recurrent nasopharyngeal carcinoma. There is involvement of circular RNAs in this progress, with should be researched further.