Pre-whitened matched filter and convolutional neural network based model observer performance for mass lesion detection in non-contrast breast CT.
Mathematical model observers have been shown to reasonably predict human observer performance and are useful when human observer studies are infeasible. Recently, convolutional neural networks (CNNs) have also been used as substitutes for human observers, and studies have shown their utility as an optimal observer. In this study, a CNN model observer is compared to the pre-whitened matched filter (PWMF) model observer in detecting simulated mass lesions inserted into 253 acquired breast computed tomography (bCT) images from patients imaged at our institution. To compare CNN and PWMF model observers for detecting signal-known-exactly (SKE) location-known-exactly (LKE) simulated lesions in bCT images with real anatomical backgrounds, and to use these model observers collectively to optimize parameters and understand trends in performance with breast CT. Spherical lesions with different diameters (1, 3, 5, 9 mm) were mathematically inserted into reconstructed patient bCT image data sets to mimic 3D mass lesions in the breast. 2D images were generated by extracting the center slice along the axial dimension or by slice averaging across adjacent slices to model thicker sections (0.4, 1.2, 2.0, 6.0, 12.4, 20.4 mm). The role of breast density was retrospectively studied using the range of breast densities intrinsic to the patient bCT data sets. In addition, mass lesions were mathematically inserted into Gaussian images matched to the mean and noise power spectrum of the bCT images to better understand the performance of the CNN in the context of a known ideal observer (the PWMF). The simulated Gaussian and bCT images were divided into training and testing data sets. Each training data set consisted of 91 600 images, and each testing data set consisted of 96 000 images. A CNN and PWMF was trained on the Gaussian training images, and a different CNN and PWMF was trained on the bCT training images. The trained model observers were tested, and receiver operating characteristic (ROC) curve analysis was used to evaluate detection performance. The area under the ROC curve (AUC) was the primary performance metric used to compare the model observers. In the Gaussian background, the CNN performed essentially identically to the PWMF across lesion sizes and section thicknesses. In the bCT background, the CNN outperformed the PWMF across lesion size, breast density, and most section thicknesses. These findings suggest that there are higher-order features in bCT images that are harnessed by the CNN observer but are inaccessible to the PWMF. The CNN performed equivalently to the ideal observer in Gaussian textures. In bCT background, the CNN captures more diagnostic information than the PWMF and may be a more pertinent observer when conducting optimal performance studies in breast CT images.


Common and Uncommon Benign Pancreatic Lesions Mimicking Malignancy: Imaging Update and Review.
There is a broad range of inflammatory, pseudotumoral, and benign lesions that may masquerade as pancreatic malignancies, often representing a challenge to the radiologist. Unawareness of these entities can lead to inadequate differential diagnoses or misdiagnosis, with important prognostic and therapeutic consequences. The purpose of this article is to revisit a spectrum of lesions, varying from common to exceedingly rare nonmalignant, that may mimic malignant pancreatic neoplasms on imaging, identifying relevant features that may contribute to reaching the correct diagnosis. Representative cases include focal fatty replacement, intrapancreatic accessory spleen, pancreatic lobulation, lipoma, autoimmune pancreatitis, focal pancreatitis, eosinophilic pancreatitis, groove pancreatitis, hemangioma, intrapancreatic aneurysm, tuberculosis, and Castleman's disease.


Combined action of interferons and transforming growth factor beta on the proliferation of human fibroblasts.
The effects of interferons (IFNs) and transforming growth factor-beta (TGF-beta) used alone and in combination on the multiplication of human embryonic diploid fibroblasts were studied. The experimental conditions were standardized and medium containing 2% of a single batch of fetal calf serum, which was almost minimal dose required for good the cell attachment and growth, was used. The observed effects were dose related. IFNs (types alpha, beta, or gamma) at concentration of 1 to 100 U/ml or TGF-beta at concentration of 0.1 to 1.0 ng/ml stimulated the cell multiplication by 20 to 25% when compared to the control cultures incubated without the factors. At higher doses both IFNs (10(2) to 10(5) U/ml) or TGF-beta (1 to 10 ng/ml) inhibited the proliferation of the cells. The antimitogenic action of IFNs and TGF-beta was synergistic. We suggest that IFNs as well as TGF-beta are bifunctional growth regulators although their antimitotic action dominates over their possible growth stimulatory activity. The latter action may be a secondary phenomenon due to interaction of IFNs or TGF-beta with other factors present in cell culture. We have shown that epidermal growth factor (EGF) may increase the growth stimulatory action of low doses of IFN-gamma or TGF-beta.


A comparative study on nasal packing after septoplasty: does it matter in terms of patient comfort, bleeding, and crust or synechia formation?
This study aims to compare pain, bleeding, nasal obstruction, crust and synechia formation, and anesthesia-related morbidity in patients with and without use of nasal packs after septoplasty. A total of 66 patients (32 women, 34 men; mean age 24 years; range 18 to 48 years) who underwent Cottle's septoplasty under general anesthesia were randomly allocated to three groups in this prospective cohort. Telfa nasal packs were used in sutures + telfa group (n=22) and Merocell nasal packs in merocel alone group (n=22). No packs were administered in sutures alone group (n=22). Three groups were compared in terms of nasal obstruction, bleeding, pain, crust and synechia formation, as well as the amount of secretion, the need for oropharyngeal airway, the presence of laryngospasm, and effort for nasal breathing after anesthesia. The amount of bleeding was higher with lower degree of nasal obstruction in sutures alone group. Pain and secretion were more remarkable in merocel alone group. After the first week, these differences were unable to be differentiated among the groups. There were no differences between three groups with respect to crust and synechia formation two weeks after septal surgery. Nasal packs can be more useful in patients who suffer from bleeding-related morbidity, while septoplasty applied without nasal packs can be more suitable in patients with obstructive sleep apnea. The use of nasal packs in septoplasty should be determined on an individualized basis with respect to the characteristics of each patient.


Adenoviral inhibition of AT1a receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat.
Brain and peripheral renin-angiotensin systems are important in blood pressure maintenance. Circulating ANG II stimulates brain RAS to contribute to the increase mean arterial pressure (MAP). This mechanism has not been fully clarified, so it was hypothesized that reducing angiotensin type 1a (AT(1a)) receptors (AT(1a)Rs) in the paraventricular nucleus (PVN) would diminish intravenous ANG II-induced increases in MAP. Adenoviruses (Ad) encoding AT(1a) small hairpin RNA (shRNA) or Ad-LacZ (marker gene) were injected into the PVN [1 × 10(9) plaque-forming units/ml, bilateral (200 nl/site)] of male Sprague-Dawley rats instrumented with radiotelemetry transmitters for MAP and heart rate measurements and with venous catheters for drug administration. No differences in weight gain or basal MAP were observed. ANG II (30 ng·kg(-1)·min(-1) iv, 15 μl/min for 60 min) was administered 3, 7, 10, and 14 days after PVN Ad injection to increase blood pressure. ANG II-induced elevations in MAP were significantly reduced in PVN Ad-AT(1a) shRNA rats compared with Ad-LacZ rats (32 ± 6 vs. 8 ± 9 mmHg at 7 days, 35 ± 6 vs. 10 ± 6 mmHg at 10 days, and 32 ± 2 vs. 1 ± 5 mmHg at 14 days; P < 0.05). These observations were confirmed by acute administration of losartan (20 nmol/l, 100 nl/site) in the PVN prior to short-term infusion of ANG II; the ANG II-pressor response was attenuated by 69%. In contrast, PVN Ad-AT(1a) shRNA treatment did not influence phenylephrine-induced increases in blood pressure (30 μg·kg(-1)·min(-1) iv, 15 μl/min for 30 min). Importantly, PVN Ad-AT(1a) shRNA did not alter superior mesenteric arterial contractility to ANG II or norepinephrine; ACh-induced arterial relaxation was also unaltered. β-Galactosidase staining revealed PVN Ad transduction, and Western blot analyses revealed significant reductions of PVN AT(1) protein. In conclusion, PVN-localized AT(1)Rs are critical for short-term circulating ANG II-mediated elevations of blood pressure. A sustained suppression of AT(1a)R expression by single administration of shRNA can interfere with short-term actions of ANG II.


Structure and activity of a chimeric interleukin-8-melanoma-growth-stimulatory-activity protein.
A 72-amino-acid chimeric protein, Chi1, was constructed from the N-terminal part of interleukin 8, IL-8-(1-53), and the C-terminal part of melanoma growth stimulatory activity, MGSA-(54-72). Chi1 protein showed receptor-binding specificity and biological activity similar, but not identical to IL-8 and decidedly different from MGSA. The structure of Chi1 was determined in solution by two-dimensional NMR and molecular-dynamics calculations. The structure resembled the structures of MGSA and IL-8 closely, containing a triple-stranded beta-sheet in the IL-8 part and an amphipathic alpha-helix in the MGSA part. Chi1 formed dimers at millimolar concentrations via the first strand from the N-terminus, analogous to IL-8 and MGSA. In contrast to the latter molecules, however, the alpha-helix of Chi1 did not pack against the beta-sheet part, but was an independent structural element. This structural difference could be explained mainly by the modulation of hydrophobic interactions between the helix and the rest of the protein in Chi1 as compared to IL-8 and MGSA. It is concluded that tight helix packing is not required for receptor binding and biological activity of Chi1.


Aesthetic properties of pictorial perception.
The present study assessed the dynamic person-object relationship in pictorial perception as associated with a high-level experience like the aesthetic. A series of experiments was designed to gain insight into the complexities of self-world interactions involving the perceptual experience, which is the basis of artistic communication. Participants were asked to produce line drawings, which were then ranked by a larger group of participants as to whether they conveyed expressive contents. This resulted in considerable agreement among the judges. In addition, the factor structure of the semantic differential responses was determined. The results indicated that considerable semantic space existed between them. A theory of a linkage between affective and cognitive processes in perceptual experience is proposed.


Populations with constant immigration.
"We consider a Leslie-type model of a one-sex (female) population of natives with constant immigration. The fertility and mortality schedule of the natives may be below or above replacement level. Immigrants retain their fertility and mortality, their children adopt the fertility and mortality of the natives. It is shown how this model may be written in a homogeneous form (without additive term) with a Leslie-type matrix. Reproductive values of individuals in each age group are discussed in terms of a left eigenvector of this matrix. The homogeneous form of our projection model permits the transformation into a Markov chain with transient and recurrent states. The Markov chain is the basis for the definition of genealogies, which incorporate immigration. It is shown that genealogies describe the life histories of individuals in a population with immigration. We calculate absorption times of the Markov chain and relate them to genealogies. This extends the theory originally designed for closed populations to populations with immigration." (SUMMARY IN FRE)


Design and development of portal for biological database in agriculture.
The application of novel and modern techniques in genetic engineering and genomics has resulted in information explosion in genomics. Three major genome databases under International Nucleotide Sequence Database collaboration NCBI, DDBJ and EMBL have been providing a convenient platform for submission of sequences which they share among themselves. Many institutes in India under Indian Council of Agricultural Research have scientists working on biotechnology and bioinformatics research. The various studies conducted by them, generate massive data related to biological information of plants, animals, insects, microbes and fisheries. These scientists are dependent on NCBI, EMBL, DDBJ and other portals for their sequence submissions, analysis and other data mining tasks. Due to various limitations imposed on these sites and the poor connectivity problem prevents them to conduct their studies on these open domain databases. The valued information generated by them needs to be shared by the scientific communities to eliminate the duplication of efforts and expedite their knowledge extended towards new findings. A secured common submission portal system with user-friendly interfaces, integrated help and error checking facilities has been developed in such a way that the database at the backend consists of a union of the items available on the above mentioned databases. Standard database management concepts have been employed for their systematic storage management. Extensive hardware resources in the form of high performance computing facility are being installed for deployment of this portal. http://cabindb.iasri.res.in:8080/sequence_portal/


Molecular cloning and expression of Rickettsia prowazekii genes for three outer membrane proteins in Escherichia coli.
Rickettsia prowazekii (virulent Breinl strain) random genomic DNA fragments were cloned in the lambda gt11 expression vector by using non-palindromic adaptors. Several immunoreactive clones were selected after screening 20,000 individual recombinant plaques with human convalescent serum. Some recombinants expressed complete 60 kDa polypeptide, and others expressed beta-galactosidase fusion polypeptides containing different epitopes of 134 kDa protein of the R. prowazekii outer membrane (OM). Amplified genomic library was screened with monospecific antibodies directed against abundant 31 kDa and 29.5 kDa OM proteins (OMPs). Several recombinant clones expressing full or part of 29.5 kDa polypeptide, and none expressing 31 kDa polypeptide were revealed. The serum of a patient convalescing from epidemic typhus did not react in Western blot with recombinant 29.5 kDa protein.


p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance.
Mammalian tRNA synthetases form a macromolecular complex with three nonenzyme factors: p43, p38, and p18. Here we introduced a mutation within the mouse p38 gene to understand its functional significance for the formation of the multi-tRNA synthetase complex. The complex was completely disintegrated by the deficiency of p38. In addition, the protein levels and catalytic activities of the component enzymes and cofactors were severely decreased. A partial truncation of the p38 polypeptide separated the associated components into different subdomains. The mutant mice showed lethality within 2 days of birth. Thus, this work provides the first evidence, to our knowledge, that p38 is essential for the structural integrity of the multi-tRNA synthetase complex and mouse viability.


Multifunctional nanoparticles co-delivering EZH2 siRNA and etoposide for synergistic therapy of orthotopic non-small-cell lung tumor.
Malignant proliferation and metastasis in non-small cell lung carcinoma (NSCLC) are great challenges for effective clinical treatment through conventional chemotherapy. The combinational therapy strategy of RNA interfering (RNAi) technology and chemotherapeutic agents have been reported to be promising for effective cancer therapy. In this study, based on multifunctional nanoparticles (NPs), the simultaneous delivery of etoposide (ETP) and anti-Enhancer of Zeste Homologue 2 (EZH2) siRNA for the effective treatment of orthotopic lung tumor was achieved. The NPs exhibited pH/redox dual sensitivity verified by particle size changes, morphological changes, and in vitro release of drugs. Confocal microscopy analysis confirmed that the NPs exhibited endosomal escape property and on-demand intracellular drug release behavior, which can protect siRNA from degradation and facilitate the chemotherapeutic effect respectively. In vitro tumor cell motility study demonstrated that EZH2 siRNA loaded in NPs can decrease the migration and invasion capabilities of tumor cells by downregulating the expression of EZH2 mRNA and protein. In particular, an antiproliferation study revealed that the co-delivery of siRNA and ETP in the multifunctional NPs can induce a synergistic therapeutic effect on NSCLC. In vivo targeting evaluation showed that cRGDyC-PEG modification on NPs exhibited a low distribution in normal organs and an obvious accumulation in orthotopic lung tumor. Furthermore, targeted NPs co-delivering siRNA and ETP showed superior inhibition on tumor growth and metastasis and produced minimal systemic toxicity. These findings indicated that multifunctional NPs can be utilized as a co-delivery system, and that the combination of EZH2 siRNA and ETP can effectively treat NSCLC.


Australia's Better Access initiative: an evaluation.
Australia's Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule (Better Access) initiative involves a series of Medicare Benefits Schedule (MBS) item numbers which offer a rebate for selected services delivered by eligible clinicians. There has been considerable debate about the appropriateness and effectiveness of Better Access, much of which has been based on limited evidence. The current paper contributes to this debate by presenting the findings of a study which profiled the clinical and treatment characteristics of Better Access patients and examined the outcomes of their care. We approached a stratified random sample of providers who had billed for at least 100 occasions of service under the Better Access item numbers in 2008 (509 clinical psychologists, 640 registered psychologists, 1280 GPs) and invited them to participate. Those who agreed were asked to recruit 5-10 Better Access patients according to a specific protocol. We collected data that enabled us to profile providers, patients and sessions. We also collected pre- and post-treatment patient outcome data, using the Kessler-10 (K-10) and the Depression Anxiety Stress Scales (DASS-21). In total, 883 patients were recruited into the study (289 by 41 clinical psychologists, 317 by 49 registered psychologists and 277 by 39 GPs). More than 90% of participating patients had diagnoses of depression and/or anxiety (compared with 13% of the general population). More than 80% were experiencing high or very high levels of psychological distress (compared with 10% of the general population). Around half of all participating patients had no previous history of mental health care. Patients experienced statistically significant improvements in average K-10 and DASS-21 scores from pre- to post-treatment. The findings suggest that Better Access is playing an important part in meeting the community's previously unmet need for mental health care.


Acute-phase protein detection and quantification in gingival crevicular fluid by direct and indirect immunodot.
The development of an assay for markers of active periodontitis, obtained directly from gingival crevicular fluid (GCF) and simply quantified, would be of great importance to the dental practitioner. The purpose of this study was to evaluate direct and indirect immunodot techniques as to their potential in easily quantifying acute-phase proteins within periodontally diseased and healthy site GCF. Indirect immunodots (GCF eluates dotted onto nitrocellulose membrane) using monoclonal antibodies and a radioactive isotope label were used to identify and establish relative amounts of C-reactive protein (CRP) and alpha-2-macroglobulin (A2M) in 2 diseased and 2 healthy sites in 24 periodontitis patients. Periodontally diseased sites were found to contain significantly lower concentrations of A2M than healthy sites (p less than 0.001), but CRP levels did not vary significantly between healthy and diseased locations. Using a direct immunodot assay (GCF absorbed directly into nitrocellulose membrane strips), A2M levels quantified with radioactive isotopes at healthy and diseased sites could be correlated with A2M levels determined by enzyme-linked antibody-colormetric probes at those same sites. Such a direct sampling and quantification system shows promise for future "in-office" diagnostic methodology.


Polychlorinated biphenyls in Spanish adults: determinants of serum concentrations.
Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). The concentration of total PCBs was 459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.


A Tin Analogue of Carbenoid: Isolation and Reactivity of a Lithium Bis(imidazolin-2-imino)stannylenoid.
The lithium bis(imino)stannylenoid (NIPr)2 Sn(Li)Cl (1; NIPr=bis(2,6-diisopropylphenyl)imidazolin-2-imino) was prepared by the reaction of LiNIPr with 0.5 equiv of SnCl2 ⋅diox (diox=1,4-dioxane) and the ambiphilic character of the compound was demonstrated by investigations into its reactivity. Treatment of 1 with I2 or MeI yielded the oxidative addition products (NIPr)2 SnI2 and (NIPr)2 Sn(Me)I, respectively. In contrast, the reaction of 1 with one equivalent of Me3 SiCl resulted in the formation of Me3 SiNIPr and the chlorostannylene dimer [NIPrSnCl]2 . Moreover, the substitution reaction of compound 1 with MeLi led to the formation of the methyl-substituted stannate (NIPr)2 Sn(Li)Me.


The pentatricopeptide repeat MTSF1 protein stabilizes the nad4 mRNA in Arabidopsis mitochondria.
Gene expression in plant mitochondria involves a complex collaboration of transcription initiation and termination, as well as subsequent mRNA processing to produce mature mRNAs. In this study, we describe the function of the Arabidopsis mitochondrial stability factor 1 (MTSF1) gene and show that it encodes a pentatricopeptide repeat protein essential for the 3'-processing of mitochondrial nad4 mRNA and its stability. The nad4 mRNA is highly destabilized in Arabidopsis mtsf1 mutant plants, which consequently accumulates low amounts of a truncated form of respiratory complex I. Biochemical and genetic analyses demonstrated that MTSF1 binds with high affinity to the last 20 nucleotides of nad4 mRNA. Our data support a model for MTSF1 functioning in which its association with the last nucleotides of the nad4 3' untranslated region stabilizes nad4 mRNA. Additionally, strict conservation of the MTSF1-binding sites strongly suggests that the protective function of MTSF1 on nad4 mRNA is conserved in dicots. These results demonstrate that the mRNA stabilization process initially identified in plastids, whereby proteins bound to RNA extremities constitute barriers to exoribonuclease progression occur in plant mitochondria to protect and concomitantly define the 3' end of mature mitochondrial mRNAs. Our study also reveals that short RNA molecules corresponding to pentatricopeptide repeat-binding sites accumulate also in plant mitochondria.


THE IMMEDIATE AND LONG-TERM EFFECTS OF KINESIOTAPE® ON BALANCE AND FUNCTIONAL PERFORMANCE.
The application of Kinesio Tex® tape (KT) results, in theory, in the improvement of muscle contractibility by supporting weakened muscles. The effect of KT on muscle strength has been investigated by numerous researchers who have theorized that KT facilitates an immediate increase in muscle strength by generating a concentric pull on the fascia. The effect of KT on balance and functional performance has been controversial because of the inconsistencies of tension and direction of pull required during application of KT and whether its use on healthy individuals provides therapeutic benefits. The purpose of the present study was to investigate the immediate and long-term effects of the prescribed application (for facilitation) of KT when applied to the dominant lower extremity of healthy individuals. The hypothesis was that balance and functional performance would improve with the prescribed application of KT versus the sham application. Pretest-posttest repeated measures control group design. Seventeen healthy subjects (9 males; 8 females) ranging from 18-35 years of age (mean age 23.3 ± 0.72), volunteered to participate in this study. KT was applied to the gastrocnemius of the participant's dominant leg using a prescribed application to facilitate muscle performance for the experimental group versus a sham application for the control group. The Biodex Balance System and four hop tests were utilized to assess balance, proprioception, and functional performance beginning on the first day including pre- and immediately post-KT application measurements. Subsequent measurements were performed 24, 72, and 120 hours after tape application. Repeated measures ANOVA's were performed for each individual dependent variable. There were no significant differences for main and interaction effects between KT and sham groups for the balance and four hop tests. The results of the present study did not indicate any significant differences in balance and functional performance when KT was applied to the gastrocnemius muscle of the lower extremity. Level 1- Randomized Clinical Trial.


Competition in general practice: prescriptions to the elderly in a list patient system.
Income motivation among general practitioners (GPs) is frequently discussed in the health economics literature. The question addressed in the present study on reimbursement drugs and addictive drugs is whether increased competition among GPs, which is part of a declared health policy to improve efficiency, contributes to more prescriptions for the elderly. The dataset comprises registered data of all prescribed drugs dispensed at pharmacies from the Norwegian Prescription Database merged with data on GPs. In choosing a method, particular attention is given to the fact that patients tend to be attracted to GPs who fit their preferences. Hence, we treat the composition of the patient list as endogenous. The results indicate that the stronger competition a GP faces, the more drugs are prescribed, which implies that GPs' prescription style may conflict with their role as gatekeepers, and even worse, it may be a hazard to patients' health.


Inhibitory effect of caerulein on salivary secretion in man.
Previous works have documented that pentagastrin has a stimulatory effect on salivary secretion. In this paper, we have studied the action of caerulein, a peptide that has an active gastrin-like terminal tetrapeptide, on salivary secretion in man. Our data documented that caerulein and pentagastrin have similar excitatory effect on gastric secretion in man, but different actions on salivary flow. Caerulein, at increasing doses, inhibits salivary flow, but not the secretion of amylase; this effect is statistically significant at 0.5 micrograms/kg/h which is the same dose that maximally stimulates gastric secretion. The inhibitory effect of caerulein was not reversed by previous injection of papaverin.


Brain blood flow in the dementias: SPECT with histopathologic correlation.
Single photon emission computed tomography (SPECT) of regional cerebral blood flow (RCBF) has been employed experimentally in the assessment of patients with dementia. The standard with which the SPECT diagnosis has been compared previously has been the initial clinical diagnosis. Recognizing that histopathologic diagnosis would be a more reliable standard, the authors compared SPECT diagnoses and clinical diagnoses with histopathologic diagnoses in a series of 18 patients who had been referred by the Alzheimer Disease Research Center. SPECT RCBF studies were carried out prospectively in 15 patients with an inhaled xenon-133 SPECT technique and in three patients with technetium-99m hexamethyl-propylene-amine oxime and triple-camera-scanner SPECT. When compared with histopathologic diagnosis, clinical diagnosis was correct in 15 of 18 patients; visual scanning diagnosis, in 13 of 18; and Xe-133-SPECT diagnosis based on quantitative ratios in regions of interest, in 14 of 15 (13 of 13 with Alzheimer disease).


Institutional review board barriers and solutions encountered in the Collaboration Among Pharmacists and Physicians to Improve Outcomes Now Study: a national multicenter practice-based implementation trial.
To categorize institutional review board (IRB) challenges and solutions encountered in a multicenter practice-based research network (PBRN) study and to assess the impact of IRB requirements on the willingness of individual principal investigators (PIs) to participate in future PBRN studies. Descriptive analysis of IRB challenges and solutions encountered in the Collaboration Among Pharmacists and Physicians to Improve Outcomes Now (CAPTION) trial, a multicenter prospective cluster-randomized study conducted by the National Interdisciplinary Primary Care PBRN, and a correlational analysis from a survey of individual site PIs. IRB barriers encountered and solutions were categorized for study sites. A survey of study-site PIs was conducted with a correlational analysis assessing the impact of various IRB requirements and the willingness of individual PIs to participate in future PBRN studies; of 31 study sites participating in the CAPTION study, 28 study-site PIs were surveyed. IRBs posed a number of challenges including bias regarding the source of the application, issues regarding study design, study instruments, access to patient records, study procedures, Spanish-only speaking subjects, role of clinic physicians, interdepartmental concerns, and updates at continuing review. Responses from the PI survey (21 of 28 PIs surveyed [75% response rate]) indicated that the willingness of an individual to serve as a PI in the future was inversely related to the perceived difficulty of obtaining initial (rS = -0.599, p=0.004) and continuing (rS = -0.464, p=0.034) IRB approval. Significant time and resources were required to address various challenges associated with IRB approval, which had a negative impact on an individual PI's willingness to participate in future PBRN projects. A revision of current rules and regulations regarding the protection of human subjects for practice-based studies, improvement in IRB processes, and support from coordinating centers may decrease the burden associated with IRB approval and increase participation in practice-based research.


Sex Difference in Global Burden of Major Depressive Disorder: Findings From the Global Burden of Disease Study 2019.
Globally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs). Global and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden. Sex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10-24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P < 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P < 0.001; standardized β = 0.300, P < 0.001). Although some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD.


Exploring experiences and needs of spousal carers of people with behavioural variant frontotemporal dementia (bvFTD) including those with familial FTD (fFTD): a qualitative study.
Carers of people with frontotemporal dementia (FTD) experience greater challenges than carers of people with other dementias due to the younger age of onset and the challenging presentation of symptoms. The aim of the present study was to explore experiences of spousal carers of people with bvFTD, including those with the familial form of the disease (fFTD). Fourteen qualitative interviews were analysed using an inductive approach to Thematic Analysis to understand experiences of spousal carers of people with bvFTD including those with fFTD. Five main themes were identified including: a) The "Constant Battle" - A journey toward an FTD diagnosis, b) Shock, Relief and Fear - Challenges persist post diagnosis, c) The "Life Altering" impact - The loss of the spousal relationship and shifting roles, d) Adapting, Managing Symptoms and Receiving Carer Support, e) Lack of General Knowledge - Barriers to support. Healthcare professionals should be educated on the initial presentations of FTD, to enable carers and families receive timely diagnosis and appropriate support. Future research should investigate the impact of fFTD on carers and families, to explore positive or meaningful experiences in caring, as well as theory-driven research to identify helpful coping strategies for carers of people with FTD.


Overexpression of beta 1,4N-acetylgalactosaminyl- transferase mRNA as a molecular marker for various types of cancers.
To determine GalNAcT mRNA expression in human carcinoma cell lines and primary tumor tissues. Assessment of the potential use of GalNAcT mRNA as a molecular marker for detection of metastatic cancer cells in the peripheral blood of patients with hepatocellular carcinoma. We investigated GalNAcT mRNA expression in various human cancer cell lines and primary cancer tissues using RT-PCR assay for GalNAcT mRNA. The expression of GalNAcT mRNA was detected in 25 of 26 cancer cell lines tested and in the majority of primary tumors from different organs: 8 of 10 colon cancers, 9 of 9 breast cancers, 11 of 12 esophageal cancers, 14 of 14 gastric cancers, 4 of 18 pancreatic cancers, 6 of 12 biliary tract cancers, 17 of 18 hepatocellular carcinomas and 13 of 14 lung cancers. Semi-quantitative analysis with duplex RT-PCR showed that the amount of the GalNAcT mRNA was enhanced in cancer tissues as compared to the surrounding cancer-free tissues. Blood specimens of 5 of 14 patients with hepatocellular carcinoma were positive for GalNAcT mRNA, all of whom developed recurrent disease in less than 24 months. Peripheral blood samples of 30 normal subjects were negative for GalNAcT mRNA. Our results suggest that the RT-PCR assay for GalNAcT mRNA could be a potentially useful molecular marker for detecting cancer dissemination in blood circulation of patients with malignancy.


The endocannabinoid system as a target for the treatment of cannabis dependence.
The endocannabinoid system modulates neurotransmission at inhibitory and excitatory synapses in brain regions relevant to the regulation of pain, emotion, motivation, and cognition. This signaling system is engaged by the active component of cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), which exerts its pharmacological effects by activation of G protein-coupled type-1 (CB1) and type-2 (CB2) cannabinoid receptors. During frequent cannabis use a series of poorly understood neuroplastic changes occur, which lead to the development of dependence. Abstinence in cannabinoid-dependent individuals elicits withdrawal symptoms that promote relapse into drug use, suggesting that pharmacological strategies aimed at alleviating cannabis withdrawal might prevent relapse and reduce dependence. Cannabinoid replacement therapy and CB1 receptor antagonism are two potential treatments for cannabis dependence that are currently under investigation. However, abuse liability and adverse side-effects may limit the scope of each of these approaches. A potential alternative stems from the recognition that (i) frequent cannabis use may cause an adaptive down-regulation of brain endocannabinoid signaling, and (ii) that genetic traits that favor hyperactivity of the endocannabinoid system in humans may decrease susceptibility to cannabis dependence. These findings suggest in turn that pharmacological agents that elevate brain levels of the endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol (2-AG), might alleviate cannabis withdrawal and dependence. One such agent, the fatty-acid amide hydrolase (FAAH) inhibitor URB597, selectively increases anandamide levels in the brain of rodents and primates. Preclinical studies show that URB597 produces analgesic, anxiolytic-like and antidepressant-like effects in rodents, which are not accompanied by overt signs of abuse liability. In this article, we review evidence suggesting that (i) cannabis influences brain endocannabinoid signaling and (ii) FAAH inhibitors such as URB597 might offer a possible therapeutic avenue for the treatment of cannabis withdrawal.


Immune insulitis and antibodies to nucleic acids induced with streptozotocin in mice.
Streptozotocin (STZ), a known beta cell toxin, given in a single injection of either a high (100 mg/kg body weight) or a low dose (60 mg/kg body weight) to young (45 days old) CD-I mice induced permanent hyperglycaemia which led to insulin-dependent diabetes (IDD). Further study, however, revealed that the course of the disease was strikingly different between the groups. The average latent period of the high-dose group (n = 20) before the development of hyperglycaemia was only 3 days while that of the low-dose group was 7 weeks (n = 30). Islets of pancreas in the high-dose group showed extensive acute necrosis of the islets with only two out of 20 showing limited mononuclear cell infiltration. In contrast, 20 out of 30 mice in the low-dose group had 45% of their islets heavily infiltrated with mononuclear cells (P less than 0.001). In addition, the deposition of IgG was found in 40% of the islets in 23 out of 30 mice in the low-dose group, in contrast to only two out of 20 in the high-dose group (P less than 0.005). The incidence of antibody to nucleic acids, polyadenylic-polyuridylic acid, polyinosinic-polycytidylic acid, single-stranded DNA and anti-nuclear antibody was significantly higher in the low-dose group as compared to the high-dose group or controls (P less than 0.01). Since the findings in the low-dose group are similar to pathological and serological changes reported in man with recent-onset IDD, this model should be of value in the study of the pathogenesis of this disease.


Organic resolution function and effects of platinum nanoparticles on bacteria and organic matter.
Rapid progress has been made in terms of metal nanoparticles studied in numerous fields. Metal nanoparticles have also been used in medical research, and antibacterial properties and anticancer effects have been reported. However, the underlying mechanism responsible for these effects has not been fully elucidated. Therefore, the present study focused on platinum nanoparticles (PtNPs) and examined their antibacterial properties and functional potential for decomposing organic matter, considering potential applications in the dental field. PtNPs were allowed to react with dental-related bacteria (Streptococcus mutans; Enterococcus faecalis, caries; Porphyromonas gingivalis, and endodontic and periodontal lesions). Antibacterial properties were evaluated by measuring colony formation. In addition, PtNPs were allowed to react with albumin and lipopolysaccharides (LPSs), and the functional potential to decompose organic matter was evaluated. All evaluations were performed in vitro. Colony formation in all bacterial species was completely suppressed by PtNPs at concentrations of >5 ppm. The addition of PtNPs at concentrations of >10 ppm significantly increased fragmentation and decomposition. The addition of PtNPs at concentrations of >125 pico/mL to 1 EU/mL LPS resulted in significant amounts of decomposition and elimination. The results revealed that PtNPs had antibacterial effects against dental-related bacteria and proteolytic potential to decompose proteins and LPS, an inflammatory factor associated with periodontal disease. Therefore, the use and application of PtNPs in periodontal and endodontic treatment is considered promising.


An Analytical Model of Interlaminar Fracture of Polymer Composite Reinforced by Carbon Fibres Grafted with Carbon Nanotubes.
An analytical model was developed to study the interlaminar fracture behaviour of polymer composite reinforced by carbon fibres grafted with carbon nanotubes. Delamination properties, such as load with displacement or crack (R-curve) and toughness with crack (GR-curve), can be obtained from this model. The bridging laws presented, based on the CNT pullout mechanism (CNT pullout from polymer matrix) and the CNT sword-in-sheath mechanism (CNT breakage), were incorporated into the proposed analytical model to investigate the influence of the structure of CNT growth onto CFs (CNT@CFs) on delamination properties. The numerical results showed that different toughening mechanisms led to different features of GR-curves, R-curves, and load with displacement curves. Parametric study demonstrated that strengthening the CNT@CF interface resulted in significant improvement in toughness. Further, it was found that elastic deformation of CNTs played an important role in the toughness improvement in the CNT sword-in-sheath mechanism, but no such role was evident in the CNT pullout mechanism.


Experience of communication among cervical cancer patients in Kenya.
Communication influences patient disclosure, treatment adherence, and outcome, adaptation to illness, and bereavement. Different cancer patients and caregivers communicate their various experiences in unique ways. These distinctive experiences are necessary to be told, because it empowers both the teller and everyone who hears and shares that experience. However, there is little research documenting the experiences of cervical cancer patients and caregivers in Kenya and the rest of Africa. This study therefore sought to assess the communication experience among cervical cancer patients and their caregivers. This study was a qualitative study employing the phenomenological method to obtain data from cervical patients and caregivers. It was carried out in Uasin Gishu County, Kenya, where a range of in-depth interviews were held with eight patients and eight caregivers purposively sampled. Data from the interviews were analysed thematically and presented in narrative form using paraphrases and quotations. Ethical issues such as informed consent, confidentiality and official authorisation were observed at all levels. To enrich this study, hermeneutic theory, which explains more about the individual's experience, was used. The findings of the study indicated that communication is therapeutic, although most of the patients and the caregivers were reluctant to talk about their illness. The findings of this study will be of interest to scholars, policy-makers and caregivers of terminally ill patients.


Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.
Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005, 0.004, respectively). I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.


Application of pharmacologically induced transcriptomic profiles to interrogate PI3K-Akt-mTOR pathway activity associated with cancer patient prognosis.
The PI3K-Akt-mTOR signaling pathway has been identified as a key driver of carcinogenesis in several cancer types. As such, a major area of focus in cancer biology is the development of genomic biomarkers that can measure the activity level of the PI3K-Akt-mTOR pathway. In this study, we systematically estimate PI3K-Akt-mTOR pathway activity in breast primary tumor samples using transcriptomic profiles derived from drug treatment in MCF7 cell lines. We demonstrate that gene expression profiles derived from chemically-induced protein inhibition allows us to measure PI3K-Akt-mTOR pathway activity in patient tumor samples. With this approach, we predict prognosis and response to chemotherapy in cancer patients, and screen for potential pharmacological modulators of PI3K-Akt-mTOR pathway inhibitors.


A Feature Extraction Method Based on Differential Entropy and Linear Discriminant Analysis for Emotion Recognition.
Feature extraction of electroencephalography (EEG) signals plays a significant role in the wearable computing field. Due to the practical applications of EEG emotion calculation, researchers often use edge calculation to reduce data transmission times, however, as EEG involves a large amount of data, determining how to effectively extract features and reduce the amount of calculation is still the focus of abundant research. Researchers have proposed many EEG feature extraction methods. However, these methods have problems such as high time complexity and insufficient precision. The main purpose of this paper is to introduce an innovative method for obtaining reliable distinguishing features from EEG signals. This feature extraction method combines differential entropy with Linear Discriminant Analysis (LDA) that can be applied in feature extraction of emotional EEG signals. We use a three-category sentiment EEG dataset to conduct experiments. The experimental results show that the proposed feature extraction method can significantly improve the performance of the EEG classification: Compared with the result of the original dataset, the average accuracy increases by 68%, which is 7% higher than the result obtained when only using differential entropy in feature extraction. The total execution time shows that the proposed method has a lower time complexity.


The needle and the damage done: musculoskeletal and vascular complications associated with injected drug use.
Injected drug use is associated with a wide range of medical complications which are predominantly musculoskeletal and vascular in nature. Illicit drug use is increasing worldwide. Patients with complications of injected drug use often present in a non-specific manner without a reliable clinical history. Musculoskeletal complications are typically infective in aetiology and may vary widely in severity from mild to life-threatening. A multimodal imaging approach is often required for both diagnostic imaging and image-guided sampling. Plain radiographs are often an important initial test, for example in identifying retained needles from injection. Ultrasound and CT play important roles in the assessment of complex soft tissue complications and MRI is the imaging modality of choice for bone and joint disorders. Vascular complications may be venous or arterial in nature and usually occur locally at the injection site. These complications may be related to direct injury to the vessel wall by a needle, or secondary to local infection and inflammation. A multimodal imaging strategy is also often required in the assessment of these vascular complications, typically involving a combination of ultrasound and CT. Familiarity with the multimodal imaging features of the complications related to injected drug use is crucially important as they may be rapidly progressive and life-threatening and require timely diagnosis.


Functional analysis of the UL24 protein of suid herpesvirus 1.
The UL24 homologous genes are conserved in alphaherpesviruses. However, the proximity of the UL24 gene and the UL23 gene encoding for thymidine kinase (TK) in the genome of suid herpesvirus 1 (SuHV-1) makes it difficult to mutate UL24 without affecting the expression of the TK gene, and thus functional studies of the UL24 gene have lagged behind. In this study, CRISPR/Cas9 and homologous recombination were adopted to generate UL24 and TK mutant viruses. Deletion of either the UL24 or the TK gene resulted in significantly reduced SuHV-1 replication and spread capacity in Vero cells. However, UL24-deleted virus still maintained a certain degree of lethality in mice, while TK-deleted viruses completely lost their lethality in mice. Similarly, neurovirulence of UL24-deleted virus in mice was not significantly affected compared to parental virus. In comparison, infection with the TK-deleted viruses resulted in significantly reduced neurovirulence and complete loss of lethality. In addition, and for the first time, viral UL24 protein was found to be expressed late during SuHV-1 infection; enhanced green fluorescence protein (eGFP) labeled UL24 protein was shown to be localized in the nucleus via heterologous expression. In conclusion, the UL24 gene of SuHV-1 encodes a nuclear-localized viral protein and acts as a minor virulence-associated factor compared to the TK gene.


Molecular analysis and long-term follow-up of patients with different forms of 6-pyruvoyl-tetrahydropterin synthase deficiency.
The outcome of 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, the most common form of tetrahydrobiopterin (BH4) deficiency, depends on factors such as severity of the disease, type of mutation, time of diagnosis, and mode of treatment. We investigated five patients from four different families, four of them presenting with the severe form of PTPS deficiency and one with the mild peripheral form. In this study, missense (L26F, T67M, P87L, V124L, D136G, D136V) and nonsense (R15-16ins) mutations were detected by reverse transcriptase polymerase chain reaction and sequence analysis. Two patients with the severe form were compound heterozygotes (T67M/P87L and D136G/R15-16ins), two siblings were homozygous for the D136V mutation, and in the patient with the mild form, heterozygous L26F/V124L mutations were present. Two patients are on combined therapy with L-dopa/carbidopa/5-hydroxytryptophan plus BH4, the siblings are on monotherapy with BH4, and the patient with the mild form is now off treatment, presenting with normal plasma phenylalanine levels. Long-term follow-up shows that the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency benefits from treatment started in the first months of life and that the phenotype may change with age. Additionally, depending on the type of mutations, prenatal damage to the fetus may multiply the clinical abnormalities and thus worsen the prognosis of the disease. In patients initially diagnosed with the mild peripheral form of the disease, therapy with tetrahydrobiopterin should be stopped after some time to test whether hyperphenylalaninaemia was only a transient condition.


Demonstration of loss of attenuation and extended field persistence of a live avian metapneumovirus vaccine.
A live A type avian metapneumovirus (AMPV) vaccine which had been shown to be highly protective and short lived in experimental conditions was found to persist for longer periods in the field and to be associated with disease. Previously other factors such as possible secondary pathogens and management considerations had made it impossible to conclude whether the observed disease was a result of an increase in the vaccine virulence. In this study, an AMPV was isolated from poults on a farm which had been vaccinated with the same live A type vaccine. Full sequencing of the isolate, the vaccine and the vaccine progenitor confirmed its vaccine origin and further showed that generation of the vaccine had only involved nine substitutions of which three coded for amino acid changes. The isolated virus was inoculated into 1-day-old turkey poults in disease secure isolators and shown to cause disease with a severity similar to that caused by virulent field virus. Only two coding mutations were associated with this reversion to virulence.


Home Non-Invasive Ventilation in COPD: A Global Systematic Review.
Uncertainty remains around the benefit of home non-invasive ventilation (NIV) for stable chronic obstructive pulmonary disease (COPD) patients and those with a recent exacerbation (post-hospital). The aim of this systematic review was to: (1) update the evidence base with studies published in any language, including Chinese language studies not indexed in standard medical databases, and (2) explore the impact of additional studies on the evidence base. Standard systematic review methodology was used for identifying and appraising studies. Randomized controlled trials (RCTs) and non-randomized studies reporting mortality, hospitalizations, exacerbations, quality of life, adverse events, or adherence were included. Random effects meta-analysis was undertaken for mortality and hospitalizations, with studies sub-grouped by population and study design. Sensitivity analysis was performed to explore the effect of including studies from Western and non-Western countries. A total of 103 studies were included, substantially more than in previous reviews. There was no significant effect on mortality for the stable population. There was a benefit from NIV for the post-hospital population based on non-randomized studies, or RCTs from non-Western countries. There was a small but significant reduction in hospital admissions (1-2/year) with NIV across all sub-groups, and a variable reduction in duration of stay with greater reductions in studies from China. The evidence base on home NIV is considerably larger than previously presented. While NIV may reduce hospital admissions and improve quality of life, there is still little evidence of a reduction in mortality, regardless of country. Individual participant data analysis may clarify which patients would benefit most from NIV.


Eustachian valve endocarditis: a rare complication of automatic implantable cardioverter defibrillator placement.
Eustachian valve (EV) endocarditis is extremely rare and often difficult to diagnose. An extensive review of the English literature has shown no report of EV endocarditis as a complication of the automatic implantable cardioverter defibrillator (AICD). A rare case is reported following AICD placement that was diagnosed by clinical findings of sepsis and positive blood cultures, and supported (using transesophageal echocardiography) by the presence of vegetations attached to the EV. Previously reported cases of EV endocarditis are reviewed, and its significance discussed in the setting of an increased use of AICD.


Generation of Spin Defects by Ion Implantation in Hexagonal Boron Nitride.
Optically addressable spin defects in wide-band-gap semiconductors as promising systems for quantum information and sensing applications have recently attracted increased attention. Spin defects in two-dimensional materials are expected to show superiority in quantum sensing due to their atomic thickness. Here, we demonstrate that an ensemble of negatively charged boron vacancies (VB -) with good spin properties in hexagonal boron nitride (hBN) can be generated by ion implantation. We carry out optically detected magnetic resonance measurements at room temperature to characterize the spin properties of ensembles of VB - defects, showing a zero-field splitting frequency of ∼3.47 GHz. We compare the photoluminescence intensity and spin properties of VB - defects generated using different implantation parameters, such as fluence, energy, and ion species. With the use of the proper parameters, we can successfully create VB - defects with a high probability. Our results provide a simple and practicable method to create spin defects in hBN, which is of great significance for realizing integrated hBN-based devices.


Endoluminal ultraflex stent for palliative treatment of malignant rectosigmoidal obstruction.
Rectosigmoidal obstruction due to a malignant tumor usually requires emergency surgical treatment, and colostomy is usually inevitable. This report describes our experience with the use of endoluminal self-expanding metallic stents in the treatment for rectosigmoidal obstruction in patients with unresectable recurrent colorectal cancer or intra-abdominal dissemination. A total of 5 cases were included (4 male and 1 female) with a mean age of 70.8 (range, 63-80) years. A self-expanding noncovered Ultraflex, 10 cm in length and 22 mm in diameter, was emplaced at the site of the obstruction under both endoscopic and fluoroscopic guidance. Each patient had a recurrent malignancy (colorectal cancer, 3; ovarian cancer, 1; gastric cancer, 1). No subsequent surgery was planned due to ascites or extensive intra-abdominal dissemination. There was no mortality related to the procedure. Immediate decompression with symptomatic relief was achieved. One stent later became obstructed due to tumor ingrowth, and in two cases there was intermittent bleeding from the tumor and these were treated by argon plasma coagulation (APC) endoscopically. The use of self-expanding Ultraflex stent provides good palliation for unresectable advanced tumors that cause left colonic obstruction.


Crystallization and preliminary X-ray analysis of a U2AF65 variant in complex with a polypyrimidine-tract analogue by use of protein engineering.
The large subunit of the essential pre-mRNA splicing factor U2 auxiliary factor (U2AF65) binds the polypyrimidine tract near the 3' splice site of pre-mRNA introns and directs the association of the U2 small nuclear ribonucleoprotein particle (U2 snRNP) of the spliceosome with the pre-mRNA. Protein engineering, in which the flexible linker region connecting tandem RNA-recognition motifs (RRMs) within the U2AF65 RNA-binding domain was partially deleted, allowed successful crystallization of the protein-nucleic acid complex. Cocrystals of a U2AF65 variant with a deoxyuridine dodecamer diffract X-rays to 2.9 angstroms resolution and contain one complex per asymmetric unit.


The neuA/flmD gene cluster of Helicobacter pylori is involved in flagellar biosynthesis and flagellin glycosylation.
Helicobacter pylori possesses a gene (HP0326/JHP309) homologous to neuA of other bacteria, encoding a cytidyl monophosphate-N-acetylneuraminic acid synthetase-homologous enzyme in its N-terminal portion. We analysed the function of this gene, which is controlled by a flagellar class 2 sigma(54) promoter, in flagellar biosynthesis. HP0326/JHP309 actually represents a bicistronic operon consisting of a neuA and a flmD-like putative glycosyl transferase gene. An isogenic flmD mutant synthesized basal bodies but no filaments, was non-motile, and expressed severely reduced amounts of a FlaA flagellin of reduced molecular mass. FlaA flagellin was found to be glycosylated in its exported form within the flagellar filament, but not inside the cytoplasm. Glycosylated FlaA was not detectable in the flmD mutant. Together with other genes in the H. pylori genome, a proposed function of the neuA/flmD gene products could be to provide a pathway for glycosylation of flagellin and other extracytoplasmic molecules during type III secretion.


An enantiospecific route towards taiwaniaquinoids. First synthesis of (-)-taiwaniaquinone H and (-)-dichroanone.
A new methodology for the enantiospecific synthesis of taiwaniaquinoids, based on a thermal 6pi electrocyclization, is reported. Under this procedure, 4a-methylhexahydrofluorene terpenoids bearing an A/B trans-configuration has been prepared for the first time. This methodology also makes it feasible to synthesize taiwaniaquinoids with an A/B cis-configuration and 4a-methyltetrahydrofluorene terpenoids. Accordingly, the first synthesis of (-)-taiwaniaquinone G, (-)-taiwaniaquinone H and (-)-dichroanone has been achieved.


Reversed-Polarity Synthesis of Diaryl Ketones through Palladium-Catalyzed Direct Arylation of 2-Aryl-1,3-dithianes.
An umpolung approach to the synthesis of diaryl ketones has been developed based on in situ generation of acyl anion equivalents and their catalytic arylation. This method entails the base promoted palladium catalyzed direct C-H arylation of 2 The resulting 2,2-diaryl-1,3-dithianes with aryl bromides. Use of MN(SiMe3)2 (M=Li, Na) base results in reversible deprotonation of the weakly acidic dithiane. In the presence of a Pd(NiXantphos)-based catalyst and aryl bromide, cross-coupling of the metallated 2-aryl-1,3-dithiane takes place under mild conditions (2 h at rt) with yields as high as 96%. The resulting 2,2-diaryl-1,3-dithianes were converted into diaryl ketones by either molecular iodine, N-bromo succinimide (NBS) or Selectfluor in the presence of water. The dithiane arylation/hydrolysis can be performed in a one-pot procedure to yield a good to excellent yields. This method is suitable for rapid and large-scale synthesis of diaryl ketones. A one-pot preparation of anti-cholesterol drug fenofibrate (TriCor®) has been achieved on 10.0 mmol scale in 86% yield.


The relation of interleukin-6, tumor necrosis factor-alpha, IL-2, and IL-2 receptor levels to cellular rejection, allograft dysfunction, and clinical events early after cardiac transplantation.
Immunoregulatory cytokines have been implicated in the pathophysiology of graft dysfunction after heart transplantation (HTx). In 15 consecutive patients undergoing HTx we prospectively determined levels of interleukin-6 (IL-6), tumor-necrosis-factor-alpha (TNF-alpha), interleukin-2 (IL-2), and soluble-interleukin-2-receptor (sIL-2-R) at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first three months after HTx. Blood was taken from the pulmonary arterial line. IL-6-levels correlated positively with hemodynamic and echocardiographic parameters of pump dysfunction--namely, pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, heart rate--and negatively with isovolumic relaxation time and stroke volume independent of the degree of cellular rejection as classified by the ISHLT criteria. A similar pattern was found for TNF-alpha- and sIL-2-R, while IL-2 correlated negatively with left and right heart filling pressures and positively with fractional shortening. In the three patients who died of sepsis or multiorgan failure within the study period IL-6-, TNF-alpha, and sIL-2-R-levels were elevated and IL-2-levels were suppressed compared with the 12 patients with a stable clinical course. IL-6 and sIL-2-R correlated positively while IL-6 and IL-2 correlated negatively. In this pilot study, a cytokine pattern with elevated levels of IL-6, TNF-alpha, and sIL-2-R as well as suppressed levels of IL-2 in the early period after HTx corresponds to impaired hemodynamics independent of cellular rejection and may indicate an unfavorable prognosis. These cytokines may therefore be useful for monitoring and warrant further study.


Lack of MHC class I complex expression has no effect on spread and control of cytomegalovirus infection in vivo.
It has been claimed that MHC class I proteins serve as receptors for murine cytomegalovirus (MCMV) and that this interaction is the most important mechanism for virus entry in most cells. This claim is based on the observation that the MHC haplotype contributes to the susceptibility to cytomegalovirus (CMV) infection in vivo. Results from in vitro studies support the concept that stable expression of correctly folded MHC class I molecules contributes to infection, since the individual properties of MHC class I alleles, the availability of beta 2-microglobulin (beta 2m) and also the degree of peptide charging of the MHC class I heavy chain beta 2m heterodimers determined the infection phenotype of cell lines. To assess the biological relevance of proper MHC class I expression we investigated CMV infection in beta 2m-deficient mice which fail to express ternary MHC class I complexes and lack peripheral CD8+ T lymphocytes. We found that organ virus titres and virus clearance kinetics were not altered in beta 2m mutant mice. In addition, there was no indication of diminished virus propagation in beta 2m-/- embryonic fibroblasts. beta 2m-/- mice suffered from the lack of CD8+ T lymphocytes that was partially compensated for by the function of CD4+ T lymphocytes. An organ-specific anti-virus function of natural killer (NK) cells was observed, independent from the beta 2m deletion. The immune control unique for salivary gland infection was maintained. From the data presented here, we confirm the role of MHC class I molecules in the immune surveillance of CMV infection but question the biological impact of correct MHC class I complexes for productive infection.


Ethanol Attenuates Histiotrophic Nutrition Pathways and Alters the Intracellular Redox Environment and Thiol Proteome during Rat Organogenesis.
Ethanol (EtOH) is a reactive oxygen-generating teratogen involved in the etiology of structural and functional developmental defects. Embryonic nutrition, redox environment, and changes in the thiol proteome following EtOH exposures (1.56.0 mg/ml) were studied in rat whole embryo culture. Glutathione (GSH) and cysteine (Cys) concentrations with their respective intracellular redox potentials (Eh) were determined using high-performance liquid chromatography. EtOH reduced GSH and Cys concentrations in embryo (EMB) and visceral yolk sac (VYS) tissues, and also in yolk sac and amniotic fluids. These changes produced greater oxidation as indicated by increasingly positive Eh values. EtOH reduced histiotrophic nutrition pathway activities as measured by the clearance of fluorescin isothiocyanate (FITC)-albumin from culture media. A significant decrease in total FITC clearance was observed at all concentrations, reaching approximately 50% at the highest dose. EtOH-induced changes to the thiol proteome were measured in EMBs and VYSs using isotope-coded affinity tags. Decreased concentrations for specific proteins from cytoskeletal dynamics and endocytosis pathways (α-actinin, α-tubulin, cubilin, and actin-related protein 2); nuclear translocation (Ran and RanBP1); and maintenance of receptor-mediated endocytosis (cubilin) were observed. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis also identified a decrease in ribosomal proteins in both EMB and VYS. Results show that EtOH interferes with nutrient uptake to reduce availability of amino acids and micronutrients required by the conceptus. Intracellular antioxidants such as GSH and Cys are depleted following EtOH and Eh values increase. Thiol proteome analysis in the EMB and VYS show selectively altered actin/cytoskeleton, endocytosis, ribosome biogenesis and function, nuclear transport, and stress-related responses.


[Chronic granulomatous disease: the surgical aspects].
Chronic granulomatous disease is characterized by recurrent infections that have an aggressive course in spite of medical treatment. Surgery is necessary, starting early in life, to treat the infections episodes. We present four patients affected by recurrent infections episodes needing a variety of treatments, who were finally diagnosed with chronic granulomatous disease. Our aim is to emphasize the importance of clinical suspicion in order to make an early accurate diagnosis, and to underline the role of surgery in the resolution of the infection spells that occur along the file of the pediatric patients affected by this disease.


Addition of benzyl ethers to alkynes: a metal-free synthesis of 1H-isochromenes.
Bromotrimethylsilane (TMSBr)-promoted intramolecular cyclization of (o-arylethynyl)benzyl ethers to form 1H-isochromenes at room temperature is reported. Further studies indicated that vinyl carbocations are the reaction intermediates which are stabilized by the conjugated aryl groups. Thus, O-addition of benzyl ethers/tetrahydropyrans to alkynes was achieved under metal-free, acidic conditions. These reaction conditions were compatible with an alkynyl Prins reaction; therefore, 1H-isochromenes were produced directly from alkynyl benzaldehydes and alkynyl alcohols using a one-pot procedure.


Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.
Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient's quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.


Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss).
In order to study the immunomodulatory effects of decaffeinated green tea extract on rainbow trout, a study with a 30-day feeding trial was conducted. Commercial diets with graded levels of decaffeinated green tea extract, 20 mg (T1), 100 mg (T2), 500 mg (T3) per kg feed were prepared. 120 rainbow trout (35 ± 3 g) were randomly assigned to 4 groups in triplicates and fed one of the 3 experimental diets formulated or control diet. After feeding trial, 12 fish from each group were sampled for analysis of some immunological parameters. Remaining fish were injected with 0.5 ml of chicken red blood cell (C-RBC) suspension (2%) intraperitoneally on days 5 and 15 after feeding trial. Results of the current study showed that the inclusion of 20 mg kg-1 green tea (T1) in fish diet enhanced the serum bactericidal activity against Yersinia ruckeri, while significant elevation of lysozyme activity was shown in T2 group. Anti-trypsin activity due to α1-antiprotease was significantly higher in T1 and T2 groups while peroxidase content showed significant increase in all treatment groups compared to control group. Hemagglutination antibody titer against C-RBC was significantly higher in fish administered with 100 mg kg(-1) green tea (T2). Our findings showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout.


Treatment Experiences in Adults Born With Cleft Lip and/or Palate: A Whole of Life Survey in the United Kingdom.
Adults with cleft lip and/or palate (CL/P) may report dissatisfaction with aesthetic and/or functional outcomes and express desire for further treatment. Although medical intervention can improve quality of life, surgical procedures require complex decision-making and can invoke psychological distress. The aim of this study was to gain a better understanding of ongoing treatment-related support needs by examining self-reported treatment experiences of a sample of adults born with CL/P. An online, mixed-methods survey was designed by the Cleft Lip and Palate Association in collaboration with the Centre for Appearance Research at the University of the West of England. A total of 207 eligible responses were received. Qualitative data were analyzed using inductive content analysis, while quantitative data were analyzed using descriptive statistics. Although participants were satisfied with surgical and dental/orthodontic outcomes overall, many reported ongoing difficulties. Some stated they would seek further treatment while others felt conflicted about risks and benefits. Some had refused treatment, citing treatment fatigue, anxiety, and/or concerns that treatment would be unsuccessful. More than 40% of participants were unaware of their entitlement to cleft-related treatment provided by the National Health Service, and many others had experienced difficulties accessing care. Although advances in health care may offer opportunities for adults to improve their quality of life, treatment decisions should be weighed with the support of a clinical psychologist where available. Guidance for young adults considering future treatment is also recommended. Finally, training and resources for local practitioners may improve general awareness of CL/P services and increase access to specialist care for adults with ongoing CL/P-related concerns.


Formation of epoxide and quinone protein adducts in B6C3F1 mice treated with naphthalene, sulfate conjugate of 1,4-dihydroxynaphthalene and 1,4-naphthoquinone.
Naphthalene (NA) is metabolically activated to the reactive intermediates, naphthalene oxide (NO) and naphthoquinones. To investigate the role of circulating reactive metabolites in NA toxicity, the half-life of NO was examined. The in vitro half-life of NO in both whole blood and plasma was 10 min. Detectable levels of NO were seen in perfusate leaving the isolated perfused liver of B6C3F1 mice infused with 10 mumol/h NA. Identification of protein sulfhydryl adducts in NA-exposed mice (50 and 100 mg/kg, IP, 24 h) revealed a predominance of quinone adducts in liver, lung, kidney, red blood cells and brain. The epoxide adduct predominated in plasma protein. Administration of the sulfate conjugate of 1,4-dihydroxynaphthalene (NHQS) (100 mg/kg) resulted in formation of naphthoquinone protein sulfhydryl adducts in lung, liver and kidney. Administration of 1,4-naphthoquinone (NQ) (5 mg/kg) produced NQ adducts in liver, lung, kidney, plasma and brain.


Vestibular modulation of somatosensory perception.
Functional imaging studies show that vestibular and somatosensory projections overlap in the human brain. However, it remains unclear whether and how vestibular inputs affect somatosensory function. To address this issue, we studied the effects of left caloric vestibular stimulation (CVS) on detection of near-threshold somatosensory stimuli delivered to the left and right hands of healthy volunteers. To investigate whether these effects were somatosensory specific, or supramodal, we also tested CVS modulation of visual contrast detection. Signal detection analyses showed increased somatosensory perceptual sensitivity immediately after CVS, both ipsilaterally and contralaterally. No statistically reliable effects on visual contrast sensitivity were found. These findings suggest that vestibular stimulation has a specific facilitatory effect on somatosensory detection, distinct from non-specific arousal and spatial attentional effects of CVS. Thus, the overlap in brain activations for vestibular and somatosensory inputs is not simply an anatomical curiosity, but may reflect a functional cross-modal perceptual interaction.


Antimicrobial and antioxidant activity of catechin-3-o-rhamnoside isolated from the stem bark of Lannea kerstingii Engl. and K. Krause (Anacardiaceae).
Various epidemiological researches have shown that consumption of vegetables and fruits are essential to maintain health and prevent diseases but the emergence of more and more drug resistance bacteria has led to high mortality. Thus the study of the antimicrobial and antioxidant activities of a flavonoid (Catechin-3-o-rhamnoside) isolated for the first time from Lannea kerstingii. Catechin-3-o-rhamnoside was isolated using dry vacuum liquid chromatography. It was characterized using 1H-NMR, 13C-NMR and 2D NMR spectra. The antimicrobial activity was determined using agar diffusion and broth dilution method. Antioxidant activity was determined through reaction of the compound with DPPH radical. The compound was active against, Methicillin Resistant Staphylococcus aureus, S. aureus, B. subtilis, E. coli, K. pneumoniae, S. typhi, S. dysentariae, C. albicans and C. tropicalis with zone of inhibition ranging from 22.0±0.1 to 35.0±0.2mm and inactive against vancomycin resistant enterococci, Proteus mirabilis and C. ulcerans. The MIC ranged from 6.25 to 12.5μg/ml while the MBC/MFC ranged from 12.5 to 50.0μg/ml. The compound showed a high radical scavenging activity with EC50 of 46.87µg/ml. These results show a potential lead drug for resistant bacteria and natural antioxidants.


Improved Adhesion Performance of Soy Protein-Based Adhesives with a Larch Tannin-Based Resin.
This study aimed to improve the bonding strength and water resistance of soy protein-based adhesives (SPAs) by modifying with larch tannin-based resins (TRs). This is especially important because of their eco-beneficial effects. The TR was characterized by Fourier Transform Infrared (FTIR) and Thermogravimetric/Derivative Thermogravimetric (TG/DTG) in order to demonstrate the formation of the self-crosslinking structure. Rheological properties, fracture morphology, solubility, and crosslinking density were characterized in detail. Three-ply poplar plywood was fabricated and the wet shear strength was measured. The experimental data showed that the addition of TR improved the moisture uptake, residual rate, and shear strength of SPA. This improvement was attributed to the crosslink reactions of TR with the relevant active functional groups of the side chains of soy protein molecules. The crosslinking structure joined with the TR self-crosslinking structure to form an interpenetrating network, which promoted a uniform and compact cured structure. The 5 wt % TR additions in the SPA was found to yield optimum results by improving the wet shear strength of the plywood by 105.4% to 1.13 MPa, which meets the interior-use plywood requirement. Therefore, the larch tannin could be applied in the modification of soy protein adhesive.


Asymmetric Corneal Flattening Effect After Small Incision Cataract Surgery.
To determine whether the flattening effect of corneal incisions differs between the right and left eye. A retrospective study of preoperative and postoperative corneal astigmatism was performed for patients who had bilateral cataract surgery by a right-handed surgeon. The change in corneal astigmatism was attributed to the 2.2-mm phacoemulsification incision, and the incisional flattening effect was calculated. The incisions were grouped by position on the eye and whether they were performed on the preoperative steep corneal meridian. A total of 1,298 eyes of 649 patients were evaluated. The flattening effect of temporal 2.2-mm incisions performed on the preoperative corneal steep meridian was different for right eyes (0.53 diopters [D]) and left eyes (0.34 D) (P = .017). The flattening effect of superior 2.2-mm incisions performed on the preoperative corneal steep meridian was equivalent in the two eyes. The flattening effect of a corneal incision may depend on whether it has been performed on the right or the left eye. [J Refract Surg. 2016;32(9):598-603.].


[Alzheimer's disease. Considerations for its clinical diagnosis].
This paper present features for identifying, on a clinical basis, the syndromatic complex "primary degenerative dementia of Alzheimer's disease type". Data are included which aid in the identification among the broad picture of dementia disorders. Information is presented about the most recent histopathological findings, the study proceedings and therapeutic trends.


High incidence of thrombotic complications early after liver transplantation for familial amyloidotic polyneuropathy.
Early thrombotic complications are critical causes of in-hospital morbidity after orthotopic liver transplantation (OLT), potentially culminating in graft loss. The aim of this study was to retrospectively analyse these complications, trying to identify associated independent risk factors. This retrospective analysis included 223 OLTs performed on 213 patients, in a 30-month period. Eighty-six OLTs were performed on familial amyloidotic polyneuropathy (FAP) patients. Preoperative details (primary diagnosis and Child-Turcotte-Pugh classification, when applicable), surgical features (including type of arterial reconstruction), postoperative variables and outcome were analysed. The observation period ended 30 days post-OLT, until discharge or in-hospital death. Early thrombotic complications were diagnosed in 16 cases (7.2%), affecting mainly FAP patients (n = 12). Hepatic artery thrombosis (HAT) was the most frequent early thrombotic event (n = 12): incidence in FAP patients 11.6% (n = 10) versus incidence in non FAP patients 1.5% (n = 2), P = 0.001. By logistic regression analysis, FAP turned out to be an independent risk factor for early thrombotic complications, and specifically for HAT. The type of arterial reconstruction and other analysed surgical and medical factors did not influence early HAT occurrence. In conclusion, FAP was identified in this study as an independent risk factor for early HAT, a new datum not yet described in the literature.


Brain metastases from apocrine carcinoma of the scalp: case report.
Apocrine carcinoma is an extremely rare malignant neoplasm that occurs most frequently in the axilla. Although it usually shows an indolent clinical course, it often metastasizes to regional lymph nodes and sometimes to lungs or bones. However, a literature search did not reveal any report describing the detailed clinical course of brain metastases from apocrine carcinoma. We report a case of a 54-year-old male who suffered from multiple brain metastases from apocrine carcinoma that had originated in the scalp 6 years before. The brain metastases appeared in spite of several regimens of chemotherapy for lung metastases for two years. The tumor in the right frontal lobe was successfully operated. However, the small tumor in the right occipital lobe was not cured by gamma knife surgery, and eventually required second operation. The operation had contributed to his neurologically independent life for about one year until he died for gradual progression of lung metastases. To our knowledge this is the first reported case of metastatic brain tumor from apocrine carcinoma.


Holmium Oxide Glass Wavelength Standards.
Holmium oxide glass has been used as a wavelength standard for over four decades. These standards have shown insignificant spectral variation from batch to batch and from one manufacturer to another. The National Institute of Standards and Technology (NIST) has certified and recertified holmium oxide glass samples for over four decades. Over this period of time there has been no recorded instance of a spectral shift of the certified bands for any of the samples measured. Moreover, these samples are known to be robust and relatively insensitive to a normal range of temperature and humidity. Based on the extensive experience that NIST has with this material and its long-term stability, NIST will no longer recommend the recertification of these standards. Furthermore, traceability may be established either through the supplier or by the end user without the need for NIST involvement.


Intake of phytosterols from natural sources and risk of cardiovascular disease in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) population.
Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk. The study included 35,597 Dutch men and women, participating in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) study. At baseline, intakes of naturally occurring PSs were estimated with a validated food frequency questionnaire and non-fasting blood lipids were measured. Occurrence of CVD, coronary heart disease (CHD) and myocardial infarction (MI) was determined through linkage with registries. The average energy-adjusted PS intake at baseline was 296 mg/d (range: 83-966 mg/d). During 12.2 years of follow-up, 3047 CVD cases (8.6%) were documented. After adjustment for confounders, PS intake was not associated with risk of CVD, CHD or MI (p-value trend > 0.05); hazard ratios ranged from 0.90-0.99 for CVD, from 0.83-0.90 for CHD and from 0.80-0.95 for MI risk across quintiles of PS intake and were almost all non-significant. Higher PS intake was associated with lower total cholesterol (-0.06 mmol/l per 50 mg/d; p-value = 0.038) and lower LDL-C (-0.07 mmol/l; p-value = 0.007), particularly among men. In mediation analysis, LDL-C did not materially affect the association between PS intake and CVD risk. In this population with a relatively narrow range of low naturally occurring PS intakes, intake of PS was not associated with reduced CVD risk despite lower LDL-C concentrations in men.


Arthroscopy of the proximal interphalangeal joints of the finger.
Cadaveric studies were carried out to evaluate the technique, portals and possible indications for arthroscopy of the proximal interphalangeal joints of the finger. We suggest horizontal placement of the hand instead of using a traction tower, as it is important to be able to flex the joint freely. The recommended arthroscopic portals are either between the central slip and the lateral bands of the extensor mechanism or between the lateral band and the collateral ligament. A blunt technique of introduction is used to avoid iatrogenic cartilage damage and possible digital nerve injury.


The biology of imaging.
On the cave wall, a discrete but stunning silhouette runs across the uneven surface. Standing still for more than 45 000 years, this is a witness to the ever-enduring need of mankind to image the world around us. The biological world that feeds us is a primary source of inspiration but also an essential element to creating the imaging systems we use every day. But once obscured by the technological jargon and the thunderstorm of numbers and algorithms, those origins fade away into the background. This small piece is about a few marvellous little stories about the biology of imaging, not the debate about the origin of vision and the eye but rather about plants and animals that open the world to new dimensions of biological imaging to fully image the biological world. An eye for an eye. This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 2)'.


Measuring Temporal and Spatial Variability of Red Blood Cell Velocity in Human Retinal Vessels.
The retinal circulation regulates blood flow through various internal and external factors; however, it is unclear how locally these factors act within the retinal microcirculation. We measured the temporal and spatial variability of blood velocity in small retinal vessels using a dual-beam adaptive optics scanning laser ophthalmoscope. In young healthy subjects (n = 3), temporal blood velocity variability was measured in a local vascular region consisting of an arteriole, capillary, and venule repeatedly over 2 days. Data consisted of 10 imaging periods separated into two sessions: (1) five 6-minute image acquisition periods with 30-minute breaks, and (2) five 6-minute image acquisition periods with 10-minute breaks. In another group of young healthy subjects (n = 5), spatial distribution of velocity variability was measured by imaging three capillary segments during three 2-minute conditions: (1) baseline imaging condition (no flicker), (2) full-field flicker, and (3) no flicker condition again. Blood velocities were measurable in all subjects with a reliability of about 2%. The coefficient of variation (CV) was used as an estimate of the physiological variability of each vessel. Over 2 days, the average CV in arterioles was 7% (±2%); in capillaries, it was 19% (±6%); and, in venules, it was 8% (±2%). During flicker stimulation, the average capillary CV was 16% during baseline, 15% during flicker stimulation, and 18% after flicker stimulation. Capillaries in the human retina exhibit spatial and temporal variations in blood velocity. This inherent variation in blood velocity places limits on studying the vascular regulation of individual capillaries, and the study presented here serves as a foundation for future endeavors.


In mice transgenic for IGF1 under keratin-14 promoter, lifespan is decreased and the rates of aging and thymus involution are accelerated.
IGF1 signaling is supposedly a key lifespan determinant in metazoans. However, controversial lifespan data were obtained with different means used to modify IGF1 or its receptor (IGF1R) expression in mice. The emerging puzzle lacks pieces of evidence needed to construct a coherent picture. We add to the available evidence by using the Gompertz model (GM), with account for the artifactual component of the Strehler-Mildvan correlation between its parameters, to compare the survival patterns of female FVB/N and FVB/N-derived K14/mIGF1 mice. In K14/mIGF1 vs. FVB/N mice, the rate of aging (γ) is markedly increased without concomitant changes in the initial mortality (μ0). In published cases where IGF1 signaling was altered by modifying liver or muscle IGF1 or whole body IGF1R expression, lifespan changes are attributable to μ0. The accelerated aging and associated tumor yield in K14/mIGF1 mice are consistent with the finding that the age-associated decreases in thymus weight and serum thymulin are accelerated in K14/mIGF1 mice. Our results underscore the importance of accounting for the mathematical artifacts of data fitting to GM in attempts to resolve discrepancies in survival data and to differentiate the contributions of the initial mortality and the rate of aging to changes in lifespan.


Potentiation of acetazolamide induced ectrodactyly in SWV and C57BL/6J mice by cadmium sulfate.
CdSO4 and acetazolamide each induce postaxial ectrodactyly in rodents when administered at a critical time in forelimb development. C57BL/6J mice are extremely sensitive to the teratogenic action of both agents, whereas SWV mice are relatively resistant. Additionally, both of these agents can inhibit carbonic anhydrase. In the present study administration of CdSO4 and acetazolamide in combination to either strain of mice potentiates the incidence of forelimb ectrodactyly. These results, in combination with the aforementioned similarities of teratogenesis, suggest a common mechanism of teratogenesis.


Advances in the use of hydroxyurea.
Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD. Hydroxyurea has proven clinical efficacy for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. Salutary effects on hematological parameters include increases in fetal hemoglobin (HbF), hemoglobin, and MCV; also significant decreases occur in WBC, ANC, reticulocytes, LDH, and bilirubin. Treatment with hydroxyurea is usually considered for patients with recurrent vaso-occlusive events, but additional indications for treatment may include laboratory markers of disease severity and evidence of chronic organ dysfunction. Ten years ago, the US Food and Drug Administration approved hydroxyurea for adult patients with clinically severe SCD; however, its use in children remains off-label. Despite the large body of evidence regarding its efficacy and safety, hydroxyurea is currently prescribed only sparingly for patients with SCD and therefore has only limited effectiveness for this disorder; barriers to its use need to be identified and overcome.


Robust and Fast Scene Recognition in Robotics Through the Automatic Identification of Meaningful Images.
Scene recognition is still a very important topic in many fields, and that is definitely the case in robotics. Nevertheless, this task is view-dependent, which implies the existence of preferable directions when recognizing a particular scene. Both in human and computer vision-based classification, this actually often turns out to be biased. In our case, instead of trying to improve the generalization capability for different view directions, we have opted for the development of a system capable of filtering out noisy or meaningless images while, on the contrary, retaining those views from which is likely feasible that the correct identification of the scene can be made. Our proposal works with a heuristic metric based on the detection of key points in 3D meshes (Harris 3D). This metric is later used to build a model that combines a Minimum Spanning Tree and a Support Vector Machine (SVM). We have performed an extensive number of experiments through which we have addressed (a) the search for efficient visual descriptors, (b) the analysis of the extent to which our heuristic metric resembles the human criteria for relevance and, finally, (c) the experimental validation of our complete proposal. In the experiments, we have used both a public image database and images collected at our research center.


[Method of obtaining optical sectioning by grating spatial filter].
Based on the theory of digital spatial filter, we have developed a new method for obtaining optical sectioning by using a grating structured light in a conventional microscope. Theoretical derivation of technology was presented in the paper. In order to remove the unwanted grid pattern superimposed, we have changed the FFTs spectrum of image and have found a method better than the original linear method. Lastly we have explained how to realize the method as well as its advantage and disadvantage.


Fiber optic based system for polarization sensitive spectroscopy of semiconductor quantum structures.
We describe an optical fiber based setup for performing polarization resolved magneto-optical spectroscopy measurements under low temperatures ( approximately 4 K) and high magnetic fields ( approximately 8 T). The measurements are performed in a windowless helium Dewar. Circularly polarized light is produced inside the Dewar by inserting the polarizing elements between the fiber end and the sample. Photoconductivity spectra of a GaAs/AlGaAs multiquantum-well sample have been measured over the photon energy range of 1.5-1.7 eV in left and right circularly polarized light under crossed magnetic and electric fields. It is shown that reversing the direction of magnetic field produces the same spectral changes as caused by changing the direction of circular polarization with the optical components.