Patients with migraine prefer zolmitriptan orally disintegrating tablet to sumatriptan conventional oral tablet.
The Zolmitriptan Evaluation versus Sumatriptan Trial (ZEST) assessed patient preference for 2.5 mg zolmitriptan orally disintegrating tablet (ODT) or 50 mg sumatriptan conventional tablet in 218 patients with significant migraine disability. Significantly more patients preferred zolmitriptan ODT to sumatriptan conventional tablet (60.1% vs 39.9%; p = 0.0130). In terms of efficacy, significantly more patients considered zolmitriptan ODT to be an effective migraine treatment than sumatriptan conventional tablet (77% vs 63%; p = 0.0063). When asked about specific formulation attributes, significantly more patients selected zolmitriptan ODT as the least disruptive therapy (83.6% vs 16.4%), the easiest to take (85.5% vs 14.5%), the most convenient to take (86.1% vs 13.9%), and the one which enabled them to maintain an active lifestyle (65.5% vs 34.5%), compared with the sumatriptan conventional tablet (all comparisons p < 0.001). Zolmitriptan ODT is a convenient and beneficial alternative to conventional tablets and is preferred to sumatriptan conventional tablets by migraineurs.


Theory of the photoacoustic effect in condensed matter.
The basic equations governing the photoacoustic effect in condensed matter are derived based on themoelastic considerations. A general solution is given for the case when the pulsed light beam is used as the activation source. Some special cases where thermal diffusion is negligible are discussed.


New Drugs 2019, part 1.
This article reviews seven drugs recently approved by the FDA, including indications, precautions, adverse reactions, and nursing considerations.


Rhodium-Catalyzed ortho-Amidations in the Preparation of Thiadiazine 1-Oxides.
Rhodium-catalyzed ortho-amidations of sulfoximines lead to key intermediates for the preparation of thiadiazine 1-oxides. Following a straightforward protocol, a variety of synthetically valuable compounds can be obtained, thus circumventing common multistep approaches towards potentially bioactive products.


[Radiosensitivity of malignant melanoma].
Based on case histories of 67 patients with malignant melanomas (14 primary tumors and 53 metastases to the lymph nodes) who underwent sole irradiation, the correlation between the total dose needed for a local healing and the period of treatment has been investigated. It appeared that excessively high doses are not necessary for healing. A dose of about 5500 rd in 35 days is regarded as sufficient. In long-term treatment, however, the total dose has to be increased more than, for example, with squamous cell carcinoma.


HBO's the weight of the nation for kids. Opportunities for school nurses.
The Weight of the Nation for Kids film series highlights youth who take a lead role in making healthy changes in their schools and communities. School nurses can combat childhood obesity in their schools and communities by implementing an initiative based on the film series along with resources from the National Institutes of Health to support healthy eating and regular physical activity in youth.


Reactive Hybrid of Polyhedral Oligomeric Silsesquioxane (POSS) and Sulfur as a Building Block for Self-Healing Materials.
This work demonstrates a new reactive and functional hybrid (S-MMA-POSS) of polyhedral oligomeric silsesquioxane (POSS) and sulfur prepared with a direct reaction between a multifunctional methacrylated POSS compound (MMA-POSS) and elemental sulfur (S8 ) through the "inverse vulcanization" process. S-MMA-POSS is an effective building block for imparting self-healing ability to the corresponding thermally crosslinked POSS-containing nanocomposites through a self-curing reaction and co-curing reaction with conventional thermosetting resins. Moreover, S-MMA-POSS is also a useful precursor for preparation of materials with high transparency in mid-infrared region.


The potential of mesenchymal stem cells for neural repair.
Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair.


Towards a close computed tomography monitoring approach for screen detected subsolid pulmonary nodules?
Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3%) SSNs in 234 participants were detected during the trial. 147 (63%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5%) participants available for analysis. The median follow-up time was 95 months (range 20-110 months). 33 (28%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes.


Fungistatic and bacteriostatic activities of alkamides from Heliopsis longipes roots: affinin and reduced amides.
This work demonstrates the fungistatic and bacteriostatic activities of affinin, the main alkamide of Heliopsis longipes (Gray) Blake (Asteraceae) roots and two alkamides obtained by catalytic reduction of affinin: N-isobutyl-2E-decenamide and N-isobutyl-decanamide. The bioactivity was tested against Rhizoctonia solani groups AG3 and AG5, Sclerotium rolfsii, Sclerotium cepivorum, Fusarium sp., Vertcillium sp., phytopathogenic fungi; Phytophthora infestans, a phytopathogenic Chromista; Saccharomyces cerevisiae, a nonphytopathogenic ascomycete; and Escherichia coli, Erwinia carotovora, and Bacillus subtilis, bacteria. Affinin, being the primary component of the lipidic fraction, is expected to be responsible for the fungitoxic activity observed in roots of this plant species. Four of the assayed fungi showed an important sensitivity to the presence of affinin: S. rolfsii, S. cepivorum, P. infestans, and R. solani AG-3 and AG-5, displaying a growth inhibition of 100%. S. cerevisiaeshowed a similar growth inhibition with affinin. None of the alkamides obtained by catalytic reduction of affinin showed a fungitoxic activity. Affinin had a definite negative effect on the growth of E. coli and B. subtilis, but E. carotovora carotovora was not sensitive to the highest dose of affinin assayed. N-Isobutyl-2E-decenamide displayed a higher bacteriostatic activity against E. coli and E. carotovora carotovora. In both cases, this alkamide was more potent than affinin. On the other hand, only N-isobutyl-decanamide displayed a significant activity on the growth of B. subtilis.


Prevalence and molecular characterization of Cryptosporidium species in poultry in Bangladesh.
Cryptosporidium is an opportunistic parasite that has been reported in >30 avian hosts worldwide, however, there is no information regarding Cryptosporidium spp. in poultry in Bangladesh. Accordingly, we investigated the prevalence of Cryptosporidium spp. in poultry at open live bird markets in Bangladesh. A total of 197 samples were randomly collected from poultry at open live bird markets in Bangladesh and screened for the detection of Cryptosporidium. Initial microscopic examination revealed Cryptosporidium spp. was observed in 19.8% (39/197) of the poultry specimens. Subsequent nested PCR targeting the 18S rRNA gene revealed that 15.7% (31/197) of the samples were Cryptosporidium positive. Of these 31 samples, 17 were Cryptosporidium baileyi (8.7%), 12 were Cryptosporidium meleagridis (6.0%), and 2 were Cryptosporidium parvum (1.0%). Nucleotide sequence analysis of the GP60 gene of the C. meleagridis revealed that two subtypes (IIIbA21G1R1 and IIIbA23G1R1), which were found in broiler, native and sonali chickens and a pigeon, matched those previously reported in humans and poultry. We identified two novel subtypes (IIIbA21G2R1 and IIIbA20G2R1) in sonali chickens, a broiler chicken and a layer chicken. We also amplified the GP60 gene of C. parvum and found two subtypes (IIaA11G2R1 and IIaA13G2R1) in a sonali and a broiler chicken that were previously reported in calf. These findings suggest that poultry can be a source of cryptosporidial infections for humans and animals in Bangladesh. This is the first molecular investigation of Cryptosporidium genotypes and subtypes in poultry at open live bird markets in Bangladesh.


Fresh Cut Versus Stored Cut Paraffin-embedded Tissue: Effect on Immunohistochemical Staining for Common Breast Cancer Markers.
The proper handling of unstained paraffin slides for immunohistochemistry has been a matter of debate, with several studies demonstrating loss of antigenicity with prolonged storage at room temperature, 4°C and -20°C. The purpose of this study was to determine whether long-term storage of unstained slides at -80°C would impact the staining intensity and expression distribution of markers used to molecularly subtype breast cancer specimens [estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), epidermal growth factor receptor (EGFR), and Ki67]. The staining pattern of previously unstained breast tumor slides (n=39 to 64) stored at -80°C for a minimum of 9.93 years (avg., 12.8 y) was compared with the staining pattern of fresh cut slides from the same tumors. The Allred scoring method was used to score ER (0 to 2, negative; 3 to 8, positive), CK5 (≥4, positive), and EGFR (≥4, positive). ASCO/CAP guidelines were used to assess HER2 (0/1+, 2+, or 3+). Ki67 scores were determined based on the proportion of cells stained of any intensity, with 20% staining used as a cut-off. Agreement was assessed using concordance rates and chance-corrected agreement statistics. The chance-corrected agreements were as follows: 0.94 (38/39) for ER, 0.92 (53/55) for CK5, 0.87 (61/64) for EGFR, 0.86 (37/39) for HER2, and 0.67 (46/54) for Ki67. Long-term storage of cut unstained slides at -80°C does not significantly impact the scoring interpretation of ER, CK5, EGFR, and HER2.


Joint Transcriptomic and Metabolomic Analyses Reveal Changes in the Primary Metabolism and Imbalances in the Subgenome Orchestration in the Bread Wheat Molecular Response to Fusarium graminearum.
Fusarium head blight is a prevalent disease of bread wheat (Triticum aestivum L.), which leads to considerable losses in yield and quality. Quantitative resistance to the causative fungus Fusarium graminearum is poorly understood. We integrated transcriptomics and metabolomics data to dissect the molecular response to the fungus and its main virulence factor, the toxin deoxynivalenol in near-isogenic lines segregating for two resistance quantitative trait loci, Fhb1 and Qfhs.ifa-5A. The data sets portrait rearrangements in the primary metabolism and the translational machinery to counter the fungus and the effects of the toxin and highlight distinct changes in the metabolism of glutamate in lines carrying Qfhs.ifa-5A. These observations are possibly due to the activity of two amino acid permeases located in the quantitative trait locus confidence interval, which may contribute to increased pathogen endurance. Mapping to the highly resolved region of Fhb1 reduced the list of candidates to few genes that are specifically expressed in presence of the quantitative trait loci and in response to the pathogen, which include a receptor-like protein kinase, a protein kinase, and an E3 ubiquitin-protein ligase. On a genome-scale level, the individual subgenomes of hexaploid wheat contribute differentially to defense. In particular, the D subgenome exhibited a pronounced response to the pathogen and contributed significantly to the overall defense response.


Production of biochar from tropical fruit tree residues and ecofriendly applications - A review.
Environmental contamination is considered a major issue with the growing urbanization and industrialization. In this context, the scientific society is engaged in searching for a sustainable, safe, and eco-friendly solution. Sustainable materials such as biochar play an important role in environmental contamination. It has some specific properties such as micropores which increase the surface area to bind the pollutants. This review endeavors to analyze the potential of fruit wastes especially tropical fruit tree residues as potential candidates for producing highly efficient biochar materials. The review discusses various aspects of biochar production viz. pyrolysis, torrefaction, hydrothermal carbonization, and gasification. In addition, it discusses biochar use as an adsorbent, wastewater treatment, catalyst, energy storage, carbon sequestration and animal feed. The review put forward a critical discussion about key aspects of applying biochar to the environment.


Contrast media for angiography: effect on renal function.
A total of 125 patients with severe peripheral vascular disease were examined with translumbar aortography. The mean dose of contrast medium injected was 65 ml of Angio Conray (containing 31.2 g of iodine). Forty patients were pretreated with mannitol, and 32 received furosemide. Thirty-eight patients (30%) had diabetes and, presumably, diabetic nephropathy. Eleven of them had significant azotemia (creatinine values greater than or equal to 4 mg/dl). Administration of contrast material did not significantly reduce renal function in any patient group. We conclude that acute renal failure following the injection of contrast material is uncommon, is reversible, and almost always occurs when avoidable complicating factors are present.


Determination of Agrin and Related Proteins Levels as a Function of Age in Human Hearts.
Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of proliferation. Agrin based therapies have proven successful at inducing repair in animal models of cardiac injury, however whether similar pathways exist in the human heart is unknown. Right ventricular (RV) biopsies were collected from 40 patients undergoing surgery for congenital heart disease and the expression of agrin and associated proteins was investigated. Agrin transcripts were found in all samples and their levels were significantly negatively correlated to age (p = 0.026), as were laminin transcripts (p = 0.023), whereas no such correlation was found for the other proteins analyzed. No significant correlations for any of the proteins were found when grouping patients by their gender or pathology. Immunohistochemistry and western blots to detect and localize agrin and the other proteins under analysis in RV tissue, confirmed their presence in patients of all ages. We show that agrin is progressively downregulated with age in human RV tissue but not as dramatically as has been demonstrated in mice; highlighting both similarities and differences to findings in rodents. Our results lay the groundwork for future studies exploring the potential of agrin-based therapies in the repair of damaged human hearts.


The mitotic checkpoint in cancer and aging: what have mice taught us?
The spindle assembly checkpoint is a cellular surveillance mechanism that functions to ensure faithful chromosome segregation during mitosis. Failure of this checkpoint can result in aneuploidy, a state of having abnormal numbers of chromosomes. Most human cancers consist of aneuploid cells, but it is unclear if the aneuploidy is a cause or a consequence of tumorigenesis. Over recent years, mouse models for spindle assembly checkpoint failure have been generated to investigate the biological relevance of the different spindle assembly checkpoint genes and the pathologies associated with chromosome number instability. Most of these models exhibit susceptibility to carcinogenesis. Moreover, one model has led to the identification of the spindle checkpoint protein BubR1 as a regulator of the normal aging process.


Synergizing Cobalt Ruthenium Alloy with Chromium Oxyhydroxide for Highly Efficient Electrocatalytic Water Splitting.
Constructing a coupling interface of multicomponents with different functions is of considerable importance for designing an advanced bifunctional water splitting electrode. Particularly, designing and developing alloy/oxyhydroxide-integrated electrodes have emerged as a tendency yet remain a considerable challenge. In this work, a novel 3D nanostructure electrocatalyst assembled from CoRu nanoalloy and CrOOH nanosheets (denoted as CoRu-CrOOH/NF) was directly grown on nickel foam via a successive hydrothermal method. The unique synergy in CoRu-CrOOH/NF heterostructures is not only conducive to strengthening charge transfer capability and accelerating the reaction kinetics but also favors the redistribution of charge within the interface, thus improving the electrocatalytic performance. In view of the above-mentioned points, the resultant CoRu-CrOOH/NF displays outstanding catalytic performance with overpotentials of 26 and 272 mV at 10 mA cm-2 for hydrogen evolution reaction (HER) and 50 mA cm-2 for oxygen evolution reaction (OER). Remarkably, the symmetrical two-electrode cell using CoRu-CrOOH/NF only acquires 1.47 V at 10 mA cm-2 in 1.0 M KOH, which is superior to many other state-of-the-art overall water-splitting electrocatalysts. This holistic work provides a new insight to designing alloy/oxyhydroxide-integrated electrodes for high-efficiency overall water splitting.


Resistant Ventricular Arrhythmia and the Role of Overdrive Pacing in the Suppression of the Electrical Storm.
Ventricular arrhythmia storm is a state of cardiac instability characterized by multiple ventricular arrhythmias or multiple ICD therapies within a 24-hour duration. Management of this life-threatening state depends on the reversal of the cause besides either electrical or medical management of the arrhythmia. We report a case of a 54-year-old male who underwent a percutaneous coronary intervention following massive acute myocardial infarction. Afterwards, he developed frequent life-threatening ventricular arrhythmias that required multiple shocks and antiarrhythmic medications. Despite all these interventions, it was very difficult to control the electrical instability, but after overdrive ventricular pacing, the storm subsided and within a few days the case was stabilized. Overdrive pacing is an easy temporary modality to control the resistant arrhythmia following myocardial infarction.


Nanoparticles Stokes radius assessment through permeability coefficient determination within a new stratified epithelium on-chip model.
Tissue barrier permeability plays a crucial role in determining the selective transport of substances across epithelial tissues, including drugs, cosmetic substances, and chemicals. The ability of these substances to cross through tissue barriers affects their absorption into the bloodstream and ultimately their effectiveness. Therefore, the determination of their permeability on these type of tissue barriers represents a useful tool for pharmaceutical and cosmetic industries as well as for toxicological studies.In this regard, microfluidic devices and organ-on-chip technologies are becoming more important to generate reliable data. We have designed and performed an alternative new stratified epithelia-on-chip model that allows to correlate the Stokes radius and the diffusion of molecules and/or nanoformulations through the in vitro generated barrier and establish a system suitable for the analysis of diffusion through stratified epithelium. Thus, extrapolating from experimental data we can predict the Stokes radius for unknown fluorescent labelled particles within a molecular size range, such as gold nanoparticles.


Molecular clues to pathogenesis in prion diseases.
The infectious agent of the transmissible spongiform encephalopathies (TSE) resembles a virus in that it propagates in vivo and has distinct strains. However, compelling evidence strongly suggests that a posttranslational structural alteration in a glycoprotein PrPC (the normal, cellular isoform of the so-called prion protein) is responsible for pathogenesis of these diseases. According to this hypothesis-now close to being generally accepted-iatrogen, sporadic and familial forms of TSE would have the same molecular mechanism: the conversion of PrPC into a protease-resistant isoform PrPSc kinetically behaves as an autocatalytic process which, combined with the high turnover rate of the normal isoform, may endow the system with bistability properties and subsequent threshold behavior between normal and pathogenic steady-states. Normal prion protein seems to be necessary for long-term survival of Purkinje neurons, regulation of circadian rhythms and, more controversially, for normal synaptic function. At least part of the pathology might be due to the unavailability of normal isoform rather than to the accumulation of PrPSc. NMR structure of the normal mouse prion protein reveals a short, unexpected beta-sheet which might be a nucleation site for the conformational transition between PrPC and PrPSc. Prion diseases may challenge the edged distinction that we use to make between informational (DNA) and functional (proteins) macromolecules. Pathogenic mechanism of prions might also be involved in other proteins to achieve and pass on their conformation. Hence, structural inheritance at the molecular level might be the missing link for the understanding of the structural inheritance processes featured at the cellular level. Moreover, evolutionary paradigm postulating a primitive RNA world is weakened by the mechanism of prion diseases.


Does the tibial and sural nerve transection model represent sympathetically independent pain?
Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.


The health professionals' perspectives of support needs of adult head and neck cancer survivors and their families: a Delphi study.
The aim was to identify the views of Australian and New Zealand health professionals regarding the support needs of people with head and neck cancer (HNC) and their families and current gaps in service delivery. A modified Delphi process assessed support needs of people with HNC following acute medical management. A systematic review of the literature was used to develop items relevant to seven key concepts underpinning the psychological experience of living with HNC. A panel of 105 health professionals was invited to participate in two questionnaire rounds. Of the potential panellists, 50 (48%) completed round 1, and of these, 39 (78%) completed round 2. Following two rounds, there was consensus agreement on the concepts uncertainty and waiting, disruption to daily life and fear of recurrence. The concepts the diminished self, making sense of and managing the experience, sharing the burden and finding a path did not achieve consensus. There were no differences in responses according to gender, organization type or location. Medical professionals had significantly higher agreement for the concept uncertainty and waiting compared to allied health professionals, and professionals with five years' or more experience had significantly higher agreement than those with less experience. Health professionals agreed that many psychosocial support needs of HNC survivors and families are not being met and that they experience difficulties in meeting these needs. Findings may inform evidence-based treatment programs for HNC survivors and their families to promote psychological resilience and quality of life in this vulnerable population.


The history of lupus erythematosus. From Hippocrates to Osler.
Hippocrates (460-375 BC) was the first to describe cutaneous ulcers under the heading of herpes esthiomenos. From what we can tell, Herbernus of Tours was the first to apply the term lupus to a skin disease in 916 AD. Following this, a number of terms including lupus, noli me tangere, and herpes esthiomenos were used to describe cutaneous ulcers. Willan (1757-1812) expanded the classification of skin diseases using the term herpes for vesicular diseases and lupus for destructive and ulcerative diseases of the face. The first clear description of lupus erythematosus was by Biett and was reported by his student Cazenave under the term erythema centrifugum in 1833. In 1846 Hebra, under the name of Seborrhea Congestiva described disc-shaped patches and introduced the butterfly simile for the malar rash. In 1851 Cazenave renamed erythema centrifugum, calling it lupus erythematosus and gave a classic description of discoid lupus erythematosus. In 1872 Kaposi subdivided lupus into the discoid and systemic forms and introduced the concept of systemic disease with a potentially fatal outcome. Hutchinson alluded to the photosensitive nature of the rash and may have provided the earliest description of what is now called annular subacute cutaneous lupus. In 1894 Payne used quinine in the treatment of patients with LE and postulated the presence of a vascular disturbance. In 1902, Sequira and Balean published a large series of patients with discoid and systemic LE and provided clinical and pathologic details of a young woman who died of glomerulonephritis. In 1904, Jadassohn published an exhaustive review of discoid and systemic LE, including clinical features and pathologic findings. Between 1895 and 1904 Sir William Osler published 29 cases of what was termed the erythema group of diseases. Perhaps his major contribution was to show that skin diseases could be accompanied by a variety of systemic manifestations. In retrospect most of his patients suffered from diseases other than SLE and it was only in his 1904 paper that two cases with SLE were described. He did not acknowledge this diagnosis in his cases and we share the viewpoint that his contribution to the study of SLE has been overemphasized.


A case of Noonan's syndrome with numerous cardiac abnormalities.
To report a case of Noonan's syndrome in a patient with numerous cardiac abnormalities. We present a case report of a patient with Noonan's syndrome, including clinical, laboratory, and radiologic findings, and discuss the characteristic features of this condition. A 19-year-old male patient had most of the typical clinical findings of Noonan's syndrome-dysmorphic face, short stature, ear abnormalities, cryptorchidism, webbed neck, and high palate. In addition, mitral valve prolapse, secondary mitral insufficiency, left ventricular hypertrophy, and secondary tricuspid insufficiency were diagnosed. Although some cardiac abnormalities have been reported in patients with this syndrome, a case with numerous cardiac abnormalities has not been described previously. Noonan's syndrome is a rare disorder with characteristic clinical features and cardiac abnormalities. Although previously reported cases have described cardiovascular anomalies, on review of the literature we found no other case with numerous cardiac abnormalities.


Effect of stress and sampling site on metabolite concentration in rat plasma.
The effect of mild stress on various plasma metabolites in the rat has been studied. Mild stress resulted in significant decreases in liver size and glycogen content, as well as in an increase of blood glucose. In addition, plasma lactate, insulin, glycerol and urea, as well as a number of amino acids were altered by stress. These data indicate that minimal stress can have major effects upon the composition of blood, and suggest the need for strict precautions on the handling of animals during blood sampling. The site of blood extraction--tail tip vs. neck--was also found to have a significant effect on plasma lactate, glucose and urea concentrations. In stressed animals the differences between tail- and neck blood composition were increased.


β-asarone and levodopa co-administration protects against 6-hydroxydopamine-induced damage in parkinsonian rat mesencephalon by regulating autophagy: down-expression Beclin-1 and light chain 3B and up-expression P62.
In this study, we investigated Beclin-1, light chain (LC)3B, and p62 expression in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats after β-asarone and levodopa (l-dopa) co-administration. Unilateral 6-OHDA injection into the medial forebrain bundle was used to create the models, except in sham-operated rats. Rats were divided into eight groups: sham-operated group; 6-OHDA model group; madopar group (75 mg/kg, per os (p.o.)); l-dopa group (60 mg/kg, p.o.); β-asarone group (15 mg/kg, p.o.); β-asarone + l-dopa co-administered group (15 mg/kg + 60 mg/kg, p.o.); 3-methyladenine group (500 nmol, intraperitoneal injection); and rapamycin group (1 mg/kg, intraperitoneal injection). Then, Beclin-1, LC3B, and p62 expression in the mesencephalon were detected. The mesencephalon was also observed by transmission electron microscope. The results showed that Beclin-1 and LC3B expression decreased and that p62 expression increased significantly in the madopar, l-dopa, β-asarone, and co-administered groups when compared with the 6-OHDA model. Beclin-1 and LC3B expression in the β-asarone and co-administered groups were less than in the madopar or l-dopa groups, whereas p62 expression in the β-asarone and co-administered groups was higher than in the madopar or l-dopa groups. In addition, a significant decrease in autophagosome was exhibited in the β-asarone and co-administered groups when compared with the 6-OHDA group. Our findings indicate that Beclin-1 and LC3B expression decreased, whereas p62 expression increased after co-administration treatment. In sum, all data suggest that the co-administration of β-asarone and l-dopa may contribute to the treatment of 6-OHDA-induced damage in rats by inhibiting autophagy activity.


Attitudes towards suicidal behaviour and associated factors among nursing professionals: A quantitative study.
WHAT IS KNOWN ON THE SUBJECT?: Self-confident health professionals with positive and understanding attitudes can take better care of people with suicidal behaviour, but the factors associated with these attitudes are not known. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The majority of nursing professionals had no experience or training in mental health or suicide. They were less self-confident and had more negative attitudes. Nurses and nursing assistants who worked before in mental health services were more understanding with people with suicidal behaviour. Nurses and nursing assistants who were working in prehospital services were less self-confident to taking care of people with suicidal behaviour. Some members of the nursing team had already seriously considered committing suicide. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The practicing, support and training in mental health may improve the nurses' attitudes and emotional competencies. It is important to know why few nurses had suicide-related training, despite the relevance of this issue. Training in mental health or suicide need to include attitudinal and emotional competencies. It is important to offer emotional support to emergency nursing professionals. Background The attitudes towards suicide of emergency nurses may affect the care provided. However, the factors associated with these attitudes remain unclear. Objective To investigate attitudes towards suicidal behaviour and associated factors among nursing professionals working in emergency settings. Methods A cross-sectional observational study including 28 nurses and 118 who were nursing assistants employed at two emergency services in Brazil was conducted. Data were collected in 2015 using a self-administered sociodemographic questionnaire and the Suicide Behavior Attitude Questionnaire (SBAQ). Results The majority of participants reported having no experience or training in mental health or suicide. They reported more negative feelings towards the patient and a lower self-perception of professional competence regarding suicidal behaviours, and these attitudes seemed to reinforce each other. Nurses who worked in mental health services reported less moralistic/judgemental attitudes. Working in prehospital services was associated with having a lower self-perception of professional competence. There were professionals who reported thinking seriously about committing suicide. Conclusion When combined with support and training, practicing mental health nursing may serve as an opportunity to develop favourable attitudes and emotional competences, and these issues need to be addressed in suicide education strategies.


Kinetic modelling of cytochrome c adsorption on SBA-15.
The adsorption capacity of mesoporous silicate (MPS) materials as an adsorbent for protein adsorption from the aqueous phase and the mechanism of the adsorption processes by comparative analyses of the applicability of five kinetic transfer models, pseudo-first-order model, pseudo-second-order model, Elovich kinetic model, Bangham's equation model, and intraparticle diffusion model, were investigated. A mixture of tetraethyl orthosilicate (TEOS) and triblock copolymer as a template was stirred, hydrothermally treated to form the mesoporous SBA-15 structure, and heat-treated at 550°C to form the MPS material, SBA-15. The synthesized SBA-15 was immersed in a phosphate buffered saline (PBS) solution containing cytochrome c for 2, 48, and 120 hours at 4°C. The TEM observations of proteins on/in mesoporous SBA-15 revealed the protein behaviors. The holes of the MPS materials were observed to overlap those of the stained proteins for the first 2 hours of immersion. The stained proteins were observed between primary particles and partly inside the mesoporous channels in the MPS material when it had been immersed for 48 hours. For MPS when it had been immersed for 120 hours, stained proteins were observed in almost all meso-scale channels of MPS. The time profiles for adsorption of proteins can be described well by Bangham's equation model and the intraparticle diffusion model. The Bangham's equation model is based on the assumption that pore diffusion was the only rate controlling step during adsorption, whose contribution to the overall mechanism of cytochrome c adsorption on SBA-15 should not be neglected. The kinetic curves obtained from the experiment for cytochrome c adsorption on SBA-15 could show the three steps: the initial rapid increase of the adsorbed amount of cytochrome c, the second gradual increase, and the final equilibrium stage. These three adsorption steps can be interpreted well by the multi-linearity of the intraparticle diffusion model, proving the significant role of intraparticle diffusion as one of the rate controlling mechanisms.


New paradigms in cell adaptation: decades of discoveries on the CrRLK1L receptor kinase signalling network.
Receptor-like kinases (RLKs), which constitute the largest receptor family in plants, are essential for perceiving and relaying information about various environmental stimuli. Tremendous progress has been made in the past few decades towards elucidating the mechanisms of action of several RLKs, with emerging paradigms pointing to their roles in cell adaptations. Among these paradigms, Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) proteins and their rapid alkalinization factor (RALF) peptide ligands have attracted much interest. In particular, FERONIA (FER) is a CrRLK1L protein that participates in a wide array of physiological processes associated with RALF signalling, including cell growth and monitoring cell wall integrity, RNA and energy metabolism, and phytohormone and stress responses. Here, we analyse FER in the context of CrRLK1L members and their ligands in multiple species. The FER working model raises many questions about the role of CrRLK1L signalling networks during cell adaptation. For example, how do CrRLK1Ls recognize various RALF peptides from different organisms to initiate specific phosphorylation signal cascades? How do RALF-FER complexes achieve their specific, sometimes opposite, functions in different cell types? Here, we summarize recent major findings and highlight future perspectives in the field of CrRLK1L signalling networks.


Dosage and duration of tamoxifen treatment for mastalgia: a controlled trial.
A controlled trial has been conducted in which 60 women with mastalgia were randomly allocated to receive tamoxifen at a dosage of either 10 mg or 20 mg daily for either 3 or 6 months. All eligible patients had self-rated moderate or severe mastalgia present for at least 6 months, for which no specific therapy had been given for the previous 3 months. End points of the study were pain control, measured by linear analogue scales, relapse rate and side-effects. Pain relief was achieved in 90 per cent of those receiving 10 mg daily and 86 per cent of those given 20 mg daily. The relapse rate was also similar for both dosages, being 48 per cent and 39 per cent respectively and usually occurred within 2-3 months of discontinuing treatment. However, side-effects were reported less frequently among those receiving 10 mg daily (21 per cent versus 64 per cent; chi 2 = 11.1, P less than 0.001). Prolongation of treatment from 3 months to 6 months did not materially improve the response rate (85 per cent versus 90 per cent). Side-effects were similar, as was the relapse rate among the patients receiving the two durations of treatment. The agent proved to be significantly more effective in the relief of cyclical rather than non-cyclical pain (94 per cent versus 56 per cent). Use of tamoxifen for the treatment of mastalgia is still experimental. Nevertheless, for the majority of women with mastalgia, pain relief can be achieved using tamoxifen 10 mg daily, given for a 3-month course. As almost half these patients will develop relapse of breast pain it may be necessary to give longer courses of therapy, although the safety of this more protracted treatment has yet to be determined.


From 2,5-Diformyl-1,4-dihydropyrrolo[3,2-b]pyrroles to Quadrupolar, Centrosymmetric Two-Photon-Absorbing A-D-A Dyes.
An original approach has been developed for the insertion of formyl substituents at positions 2 and 5 of 1,4-dihydropyrrolo[3,2-b]pyrroles by conversion of thiazol-2-yl substituents. The synthetic utility of these formyl groups was investigated, and a series of centrosymmetric A-π-D-π-A frameworks were constructed. The two-photon absorption of the quadrupolar pyrrolo[3,2-b]pyrrole possessing two dicyanovinylidene flanking groups is attributed to an S0 → (S1) → S4 transition which has a large TPA cross-section (1300 GM) for a molecule of this size.


Inflammation-Sensitive Myosin-X Functionally Supports Leukocyte Extravasation by Cdc42-Mediated ICAM-1-Rich Endothelial Filopodia Formation.
Leukocyte transendothelial migration is key to inflammation. Leukocytes first start rolling over the inflamed endothelium, followed by firmly adhering to it. Under inflammatory conditions, endothelial cells express small finger-like protrusions that stick out into the lumen. The function and regulation of these structures are unclear. We present evidence that these ICAM-1- and F-actin-rich endothelial finger-like protrusions are filopodia and function as adhesive structures for leukocytes to transit from rolling to crawling but are dispensable for diapedesis. Mechanistically, these structures require the motor function of myosin-X, activity of the small GTPase Cdc42, and p21-activated kinase 4. Moreover, myosin-X expression is under control of TNF-α-mediated c-Jun N-terminal kinase activity and is upregulated in human atherosclerotic regions. To our knowledge, this is the first study to identify that regulation of endothelial filopodia is crucial for leukocyte extravasation, in particular for the initiation of leukocyte adhesion under flow conditions.


Unveiling Angiotensin II and Losartan-Induced Gene Regulatory Networks Using Human Urine-Derived Podocytes.
Podocytes are highly specialized cells that play a pivotal role in the blood filtration process in the glomeruli of the kidney, and their dysfunction leads to renal diseases. For this reason, the study and application of this cell type is of great importance in the field of regenerative medicine. Hypertension is mainly regulated by the renin-angiotensin-aldosterone system (RAAS), with its main mediator being angiotensin II (ANG II). Elevated ANG II levels lead to a pro-fibrotic, inflammatory, and hypertrophic milieu that induces apoptosis in podocytes. The activation of RAAS is critical for the pathogenesis of podocyte injury; as such, to prevent podocyte damage, patients with hypertension are administered drugs that modulate RAAS signaling. A prime example is the orally active, non-peptide, selective angiotensin-II-type I receptor (AGTR1) blocker losartan. Here, we demonstrate that SIX2-positive urine-derived renal progenitor cells (UdRPCs) and their immortalized counterpart (UM51-hTERT) can be directly differentiated into mature podocytes. These podocytes show activation of RAAS after stimulation with ANG II, resulting in ANG II-dependent upregulation of the expression of the angiotensin-II-type I receptor, AGTR1, and the downregulated expression of the angiotensin-II-type II receptor 2 (AGTR2). The stimulation of podocytes with losartan counteracts ANG II-dependent changes, resulting in a dependent favoring of the specific receptor from AGTR1 to AGTR2. Transcriptome analysis revealed 94 losartan-induced genes associated with diverse biological processes and pathways such as vascular smooth muscle contraction, the oxytocin signaling pathway, renin secretion, and ECM-receptor interaction. Co-stimulation with losartan and ANG II induced the exclusive expression of 106 genes associated with DNA methylation or demethylation, cell differentiation, the developmental process, response to muscle stretch, and calcium ion transmembrane transport. These findings highlight the usefulness of UdRPC-derived podocytes in studying the RAAS pathway and nephrotoxicity in various kidney diseases.


Bispecific antibody pretargeting of radionuclides for immuno single-photon emission computed tomography and immuno positron emission tomography molecular imaging: an update.
Molecular imaging is intended to localize disease based on distinct molecular/functional characteristics. Much of today's interest in molecular imaging is attributed to the increased acceptance and role of 18F-flurodeoxyglucose (18F-FDG) imaging in a variety of tumors. The clinical acceptance of 18F-FDG has stimulated research for other positron emission tomography (PET) agents with improved specificity to aid in tumor detection and assessment. In this regard, a number of highly specific antibodies have been described for different cancers. Although scintigraphic imaging with antibodies in the past was helpful in patient management, most antibody-based imaging products have not been able to compete successfully with the sensitivity afforded by 18F-FDG-PET, especially when used in combination with computed tomography. Recently, however, significant advances have been made in reengineering antibodies to improve their targeting properties. Herein, we describe progress being made in using a bispecific antibody pretargeting method for immuno-single-photon emission computed tomography and immunoPET applications, as contrasted to directly radiolabeled antibodies. This approach not only significantly enhances tumor/nontumor ratios but also provides high signal intensity in the tumor, making it possible to visualize micrometastases of colonic cancer as small as 0.1 to 0.2 mm in diameter using an anti-carcinoembryonic antigen bispecific antibody, whereas FDG failed to localize these lesions in a nude mouse model. Early detection of micrometastatic non-Hodgkin's lymphoma is also possible using an anti-CD20-based bispecific antibody pretargeting procedure. Thus, this bispecific antibody pretargeting procedure may contribute to tumor detection and could also contribute to the detection of other diseases having distinct antigen targets and suitably specific antibodies.


Semimembranosus tendonitis after total knee arthroplasty: good outcome after surgery in 6 patients.
More than 700 total knee arthroplasties were performed in our Department between 1992-2000. 6 patients developed pain on the postero-medial aspect of the knee, within 1 year of surgery. The pain increased during walking and especially on rising from a chair. All patients were women with good knee motion and good alignment of the implanted prosthesis. We found no signs of low-grade infection. Injection of 1% Xylocaine relieved pain for a short time in all patients. They were all treated with excision of the reflected portion of the semimembranosus tendon which was not cut during the arthroplasty. Pain was completely relieved in 5 cases and improvement occurred in 1.


Investigation of TF-binding lectins from dietary sources and SRL on proliferation and cell cycle progression in human colon HT29 and SW620 cells.
TF antigen binding lectins from dietary sources PNA, ACA, ABL, JAC, and SRL from Sclerotium rolfsii have been reported to induce diverse effects on cancer cell proliferation by different mechanisms. This study aimed to compare effects of these lectins on growth and cell cycle progression in colon cancer HT29 and SW620 cells. As reported SRL, ABL, and JAC inhibited while PNA and ACA increased cell proliferation. ABL and JAC treated HT29 cells showed increased cell population in G0/G1 phase. PNA, ACA, ABL, and JAC increased SW620 cell population in S and decreased in G2/M phase. In contrast, SRL and JAC increased hypodiploid population in both the cells. PNA and ACA reduced whereas SRL and ABL diminished cell cyclin D1 expression. SRL, PNA, and ACA also reduced cellular cyclin D3 level while SRL, ABL, and JAC reduced cyclin E levels. ABL decreased CDK5 levels while SRL and ACA completely abolished CDK5 expression. All the lectins completely abolished cyclin D2 expression. These results not only confirms growth regulatory effects of TF-binding lectins but also indicates different effects of these lectins on cell growth is associated with regulation on expression of cell cycle associated proteins in G1-S phase and on cell cycle progression.


Transient dispersion of an initial point pollutant concentration in wetland flows.
Initial point pollutant transport in wetland flows acts as a typical form in various applications. Accurate determination of the basic characteristics for dispersion fundamentally supports the predication of pollutant transport especially in the transient stage. This work analytically studies the transient dispersion of an initial point pollutant concentration in wetland flows through the phase average technique and the method of concentration moments. The characteristics including the vertical mass distribution, longitudinal displacement, dispersivity, skewness, and kurtosis corresponding to the zeroth- to fourth-order concentration moments are accurately illustrated in their full-time dependance for the first time. Present results show to be distinctive from those of initial uniform concentration in the transient dispersion process. The temporal evolutions of the five characteristics are all dependent of the initial point release position. The results further demonstrate that the timescale 3.0 as measured by the skewness, rather than 0.5 as measured by the dispersivity, should be characterized as the transient period for the dispersion of initial point concentration in comparison with that of initial uniform. Furthermore, the longitudinally distributed mean concentration is as well analyzed through the Hermite polynomials. The results imply that strict criteria for environmental and ecological implications should be established by further accounting for the five characteristics.


Antigenotoxicity and Cytotoxic Potentials of Metabiotics Extracted from Isolated Probiotic, Lactobacillus rhamnosus MD 14 on Caco-2 and HT-29 Human Colon Cancer Cells.
Probiotics, the beneficial bacteria produce active metabolites which could probably mimic their anticancer effect and prevent the risk associated with live bacteria. Thus, the study was designed to isolate effective lactic acid bacteria (LAB) and monitor anticancerous potential of their metabiotic extracts. Probiotics were isolated from different sources and their cell free supernatants (CFS) were screened for antigenotoxic and cytotoxic potentials using SOS Chromo Test and MTT assay on Caco-2 and HT-29 cells. Organic extracts of CFS were prepared and dissolved in different solvents. The isolate with most effective metabiotic extract in terms of cytotoxicity was classified for probiotic and phylogenetic characters and the metabiotic extract was characterized physiochemically. Among 60 isolated LAB, CFS of only 10 isolates showed antigenotoxicity more than 30% and four exhibited 70-80% cytotoxicity. Further, organic extracts of these four CFS dissolved in carboxymethyl cellulose showed 80-90% cytotoxicity. Interestingly, the most effective isolate was found to possess probiotic attributes and phylogenetic characterization revealed it to be Lactobacillus rhamnosus MD 14. Physiochemical characterization of its metabiotic extract indicated the presence of heat sensitive organic acids and proteins. To conclude, metabiotics produced by isolated probiotic L. rhamnosus MD 14 exhibited both antigenotoxic and cytotoxic potential against colon cancer.


Development of clinical criteria for the evaluation of indirect restorations.
To propose the development and validation of criteria for evaluating the clinical performance of indirect restorations, considering the variables related to the operator, material, and/or patient. The experimental design of this study was divided into three stages. Stage 1: development of the new criteria items by specialists in Prosthodontics. Step 2: creation of the criteria, named UERJ criteria, with the description of the parameters that indicate the quality of the restoration, the possible associated complications, and a detailed description of each classification. As well as the development of a form of variables. Step 3: validation of the UERJ criteria. Cohen's Kappa statistic registered for both intra- and inter-examiner agreements a coefficient >0.91 with a p-value <0.0001. The validity of the UERJ criteria was evaluated by tests of sensitivity (0.96) and specificity (0.91) and had a satisfactory accuracy (92.7%), a positive (10.99), and negative (0.05) likelihood ratio and high values predictive variables, with positive (PPV) 0.84 (high specificity) and negative (VPN) 0.98 (high sensitivity), with a confidence interval of 95%. The UERJ criteria is a valid instrument for evaluating the clinical performance of indirect restorations. The UERJ criteria, developed exclusively for the analysis of indirect restorations, elucidates the details necessary to identify the causes of failures and complications of these restorations.


Effects of Titanium Layer Oxygen Scavenging on the High-k/InGaAs Interface.
One of the main challenges in the path to incorporating InGaAs based metal-oxide-semiconductor structures in nanoelectronics is the passivation of high-k/InGaAs interfaces. Here, the oxygen scavenging effect of thin Ti layers on high-k/InGaAs gate stacks was studied. Electrical measurements and synchrotron X-ray photoelectron spectroscopy measurements, with in situ metal deposition, were used. Oxygen removal from the InGaAs native oxide surface layer remotely through interposed Al2O3 and HfO2 layers observed. Synchrotron X-ray photoelectron spectroscopy has revealed a decrease in the intensity of InOx features relative to In in InGaAs after Ti deposition. The signal ratio decreases further after annealing. In addition, Ti 2p spectra clearly show oxidation of the thin Ti layer in the ultrahigh vacuum XPS environment. Using capacitance-voltage and conductance-voltage measurements, Pt/Ti/Al2O3/InGaAs and Pt/Al2O3/InGaAs capacitors were characterized both before and after annealing. It was found that the remote oxygen scavenging from the oxide/semiconductor interface using a thin Ti layer can influence the density of interface traps in the high-k/InGaAs interface.


Predicting cubitus varus in supracondylar fractures of the humerus by Baumann's angles in post reduction X-rays.
The present study presents the technique to predict cubitus varus by post reduction Affected Side and Normal Side Baumann's angle difference (ASBA and NSBA) respectively. It intends to correlate the Baumann's angle to the final carrying angle of the injured elbow and presents the relevant mathematical clinical rule along with its prediction test characteristics. Total 57 patients of 6.5+/-1.67 yrs, 22 were males and 8 females with 19/30 having left side injury. Isolated closed supracondylar fractures of humerus up to 5 days duration included and previous trauma, pathological fracture, other injury, elbow disease were excluded .30/57 completed >1 year follow-up. The Mean NSBA was 74.4+/-4.14 masculine. The mean normal side carrying angles (NSCA) were 9.56 +/- 2.2 masculine. The NSCA IQR (Inter Quartile Range) was 8.8-10 masculine. The ASBA was 79.9+/-9.1 masculine and affected side carrying angles (ASCA) was 0.20+/-8.7 masculine. The ASCA was best predicted by the difference between ASBA-NSBA (ASCA=3.87-0.65(ASBA- NSBA; F=15.91). At a cut off of 8.8 masculine (the lower limit of IQR for NSCA), a value >0 masculine for ASBA- NSBA was 80% predictive of cubitus varus. With pre test probability of varus at 70%, sensitivity was 0.94 and specificity 0.42. A prediction rule to predict the final carrying angle from ASBA NSBA difference is presented with a positive predictive value 0.80, specificity of 0.42, and sensitivity of 0.94 at a pre test probability of 0.70.When the diagnosis of cubitus varus is ASCA<8.8 masculine (Lower limit of the IQR for NSCA). If affected side Baumann's Angle - Normal Side Baumann's Angle is equal to or greater than 0 then there was 80% probability of having cubitus varus.


Long-term survival analysis in metastatic melanoma: serum S100B is an independent prognostic marker and superior to LDH.
The prognosis of metastatic melanoma is poor. The purpose of this study was to perform a long-term survival analysis on patients with advanced melanoma to determine clinical and laboratory prognostic factors for treatment outcome and long-term survival. The prognostic importance of S100B serum levels on overall survival compared to lactate dehydrogenase (LDH) was evaluated. The medical records of 105 AJCC (American Joint Committee on Cancer) stage IV melanoma patients from 1994 to 2001 were analyzed retrospectively. Median time to progression and overall survival were assessed. Univariate and multivariate analysis were performed to determine prognostic factors. 86 (81.9%) of the 105 patients died during the observation period. In univariate analysis, pre-therapeutic LDH and S100B levels in serum samples (p = 0.01 and p = 0.002, respectively), tumor stage (AJCC IVa-IVc, p = 0.005), and response to the firstline therapy (p < 0.001) were found to be significant prognostic markers. However, in the multivariate analysis, pre-therapeutic S100B serum levels (p = 0.005, odds ratio (OR): 2.22, confidence interval (CI): 1.22-4.1) as well as presence of brain metastases (p = 0.009, OR: 5.08, CI: 1.51-17.05) were the only independent prognostic factors for overall survival. In metastatic melanoma, S100B is a strong prognostic factor for overall and long-term survival, and superior to LDH.


Murine macrophages cultured with IL-4 acquire a phenotype similar to that of epithelioid cells from granulomatous inflammation.
Epithelioid cells (ECs) found in granulomas are thought to derive from mononuclear phagocytes. Although GM-CSF and/or IL-4 are known to promote cell differentiation their role in the development of ECs has never been demonstrated. Here we showed that mouse macrophages treated exclusively with recombinant IL-4 (rIL-4) differentiate into epithelioid-like cells. Macrophages cultivated with rIL-4 presented a fried-egg shape, and ultrastructural studies revealed membrane interdigitations, cytoplasmic vesicles, prominent Golgi complex, and rough endoplasmic reticulum. Compared with controls, rIL-4 treated cells displayed increased expression of MHC class II molecules and of Migration Inhibitory Factor-Related Protein-14. Whereas mannose receptor-mediated phagocytosis was increased, Fcgamma-receptor mediated phagocytosis and the production of nitric oxide were decreased in treated cultures. All these features overlap those reported for ECs from granulomatous lesions. In conclusion, treatment of mouse peritoneal macrophages with rIL-4 drives their in vitro differentiation to an epithelioid phenotype and provides a tool to investigate the biology of ECs.


Race-related disparities in 5-year cognitive level and change in untrained ACTIVE participants.
The current study examined a 5-year cognitive change in untrained African American and White participants from the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study. Five-year trajectories of memory, reasoning, visual processing speed/useful field of view, digit-symbol substitution, and vocabulary were investigated. Education, health, gender, age, and retest/practice effects were controlled for, and a missing data pattern mixture approach was used to adjust for dropout effects. After considering age, education, health, and gender, being African American uniquely explained 2% to 7% of the variance in cognitive performance. There were virtually no significant race differences in the rates of change. Race-related results in the current study are consistent with previous research suggesting that social advantage factors such as education have a stronger influence on the level of performance than the rate of change. The small remaining effects of being African American on performance levels likely reflect uncontrolled variation in factors like literacy and financial advantage.


[Aneurysm of the abdominal aorta associated with an ectopic pelvic kidney and abnormal vascularisation: a case report].
Renal malformations during surgery for repair of an abdominal aortic aneurysm are a rare occurrence that can create technical problems during the operation in terms of preservation of renal parenchyma and vascularisation. A case of abdominal aortic aneurysmectomy associated with an ectopic pelvic kidney is presented. Preoperative diagnosis is necessary in order to plan the surgical technique to be employed in each anatomical variant encountered.


Fluorescent GTP-sensing in aqueous solution of physiological pH.
A new water-soluble imidazolium anthracene derivative not only differentiates two structurally similar compounds GTP and ATP but also acts as potential fluorescent chemosensors (as a quencher and an enhancer, respectively) for GTP and ATP in 100% aqueous solution (pH = 7.4, 10 mM HEPES).


Long-term complications of diabetes and co-morbidities contributing to atherosclerosis in diabetic population of Mirpur, Azad Kashmir.
To ascertain the prevalence of diabetes mellitus and its chronic complications along with co-morbidities contributing to atherosclerosis in the diabetic population of Mirpur, Azad Kashmir. The cross-sectional study and was carried out at the Divisional Headquarter Hospital, Mirpur, Azad Kashmir, between January and August 2012. The patients selected were established diabetics. Data was collected through special questionnaire. SPSS version 14 was used to analyse the data. A total 3602 patients were interviewed initially. Of them 318 were diabetics; the prevalence rate being 8.83%. Of the 318 study subjects, 24 (7.3%) had a history of stroke; 4 (1.3%) had history of transient ischaemic attack; 17 (5.3%) had history of myocardial infarction; 27 (8.5%) and had a history of angina. Foot ulcers were present in 22 (6.9%) and 3 (0.9%) had an amputation. Diabetic retinopathy was found in 95 (29.9%), diabetic nephropathy in 25 (7.9%) and diabetic neuropathy in 126 (39.6%). Co-morbid hypertension was found in 153 (48.1%) of cases whereas co-morbid hypercholesterolaemia was found in 66 (20.8%) and 56.9% had family history of diabetes mellitus. Overall, 34 (10.7%) were smokers. Diabetes is responsible for significant morbidity and mortality. Co-morbidities like hypertension and hypercholesterolaemia must be aggressively treated to prevent coronary heart disease.


Hb F-Jiangsu, the first gamma chain variant with a valine----methionine substitution: alpha 2A gamma 2 134(H12)Val----Met.
During a survey of cord blood samples of healthy Chinese babies an A gamma variant was detected by its partial separation from normal A gamma in a high performance liquid chromatographic experiment. Structural analysis of the isolated A gamma X chain identified a Val----Met substitution at position A gamma 134; this substitution created a rather unique Met-Met sequence. The ratio of A gamma X to A gamma was about 2 to 3; thus, Hb F with this variant A gamma chain appears to have approximately normal stability.


[Dnmt2 is the Most Evolutionary Conserved and Enigmatic Cytosine DNA Methyltransferase in Eukaryotes].
Dnmt2 is the most strongly conserved cytosine DNA methyltransferase in eukaryotes. It has been found in all organisms possessing methyltransferases of the Dnmt1 and Dnmt3 families, whereas in many others Dnmt2 is the sole cytosine DNA methyltransferase. The Dnmt2 molecule contains all conserved motifs of cytosine DNA methyltransferases. It forms 3D complexes with DNA very similar to those of bacterial DNA methyltransferases and performs cytosine methylation by a catalytic mechanism common to all cytosine DNA methyltransferases. Catalytic activity of the purified Dnmt2 with DNA substrates is very low and could hardly be detected in direct biochemical assays. Dnmt2 is the sole cytosine DNA methyltransferase in Drosophila and other dipteran insects. Its overexpression as a transgene leads to DNA hypermethylation in all sequence contexts and to an extended life span. On the contrary, a null-mutation of the Dnmt2 gene leads to a diminished life span, though no evident anomalies in development are observed. Dnmt2 is also the sole cytosine DNA methyltransferase in several protists. Similar to Drosophila these protists have a very low level of DNA methylation. Some limited genome compartments, such as transposable sequences, are probably the methylation targets in these organisms. Dnmt2 does not participate in genome methylation in mammals, but seems to be an RNA methyltransferase modifying the 38th cytosine residue in anticodon loop of certain tRNAs. This modification enhances stability of tRNAs, especially in stressful conditions. Dnmt2 is the only enzyme known to perform RNA methylation by a catalytic mechanism characteristic of DNA methyltransferases. The Dnmt2 activity has been shown in mice to be necessary for paramutation establishment, though the precise mechanisms of its participation in this form of epigenetic heredity are unknown. It seems likely, that either of the two Dnmt2 activities could become a predominant one during the evolution of different species. The high level of the Dnmt2 evolutionary conservation proves its activity to have a significant adaptive value in natural environment.


Cost-effectiveness of vaccination against herpes zoster.
Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN.


Neuropilin-1 and VEGF correlate with somatostatin expression and microvessel density in ovarian tumours.
Vascular endothelial growth factor (VEGF), is an angiogenic growth factor, expressed more highly in malignant than benign ovarian tumours. Neuropilin-1, which can act as a VEGF receptor has been shown to be associated with tumour angiogenesis in some cancer systems. Somatostatin (SST), a potentially anti-angiogenic factor, acts via somatostatin receptors that are expressed in ovarian cancer. We used immunohistochemistry to demonstrate expression of Neuropilin-1 in 63 malignant and 35 benign ovarian tumours and compared it to VEGF, Flt, Flk, SST expression and tumour microvessel density (MVD). Neuropilin-1 was expressed in 34/63 malignant and 22/35 benign lesions. VEGF, Flt, Flk and SST were expressed more highly in the epithelium of malignant and the vessels of benign lesions. VEGF expression correlated with SST expression in the epithelium (p<0.001) and the vessels (p<0.001), this co-expression was confirmed by dual immunostaining. The MVD for malignant lesions was higher than benign (p<0.001) and positively correlated to epithelial VEGF expression (p=0.001) and negatively correlated to vascular VEGF expression (p=0.025). These results show that Neuropilin-1 is expressed in ovarian tumours and also show that VEGF and SST are co-expressed in the same tissue compartments raising the intriguing possibility that SST may be important in angiogenesis in ovarian cancer.


A new operative technique for restorative proctocolectomy: the endorectal pull-through combined with a double-stapled ileo-anal anastomosis.
In children, restorative proctocolectomy is usually accomplished by a rectal mucosectomy followed by a hand-sewn ileo-anal anastomosis+/-ileal pouch. In certain patients, a hand-sewn anastomosis can be technically difficult. This led us to develop a new technique that combines endorectal mucosectomy with a double-stapled ileo-anal anastomosis. After colectomy, an ileal J-pouch is constructed. The head of the circular stapler is placed in the apex of the pouch and secured. An endorectal mucosectomy is completed from the abdomen to approximately 1.5 cm above the dentate line. The rectal mucosal/submucosal tube is everted onto the perineum. A transverse stapler is positioned 1.5 cm above the dentate line on the perineum and fired. The circular stapler is inserted transanally and the trocar advanced through the transverse staple line until the head and anvil are mated and then fired. A loop ileostomy is constructed. Thirteen patients, with a mean age of 12.3 years, have undergone endorectal mucosectomy with a double-stapled anastomosis without major complication. The operative time averaged 280+/-70 minutes. The mean 24-hour stool frequency, with 9 months' follow-up, was 6.8+/-3.2, of which 1+/-0.7 were at night. The combination of endorectal mucosectomy with a double-stapled anastomosis is a new approach for patients requiring restorative proctocolectomy. In our early experience, this technique was completed with a low complication rate and excellent functional results.


Minimally invasive groin dissection.
Melanoma of the lower extremity with a positive sentinel lymph node biopsy (SLNB) mandates a groin dissection. This procedure has been associated with numerous complications; therefore we devised a modified approach. All patients presenting with lower extremity melanomas that met criteria for SLNB had this procedure performed through an incision in the inguino-femoral region. In the event of a positive SLND, this same incision was used for the minimally invasive groin dissection (MIGD). A lighted retractor was used to improve visualization and a Ligasure (Valley-lab) was used to prevent seroma formation. Twenty patients met criteria for this investigation and five underwent MIGD. All patients tolerated the procedure well. There was no incidence of flap necrosis nor wound dehiscence. There was one case of seroma and cellulitis, one seroma, and one patient with lymphedema. All patients preferred the MIGD incision over traditional incisions. This new algorithm utilizing MIGD is well tolerated in patients. Complications appear to be minimal and patient satisfaction superior to traditional groin dissection.


Rhino-Orbital Mucormycosis After COVID-19 Recovery: A Case Report.
The pandemic caused by SARS-CoV-2 remains a health care concern, despite vaccination programs. Mucormycosis, especially rhino-orbital-mucormycosis, has been described as a severe complication of COVID-19. Although it has been described mostly in India and other developing countries, few cases in the western world have also been described. We present a case of rhino-orbito-mucormycosis after recovery from severe COVID-19 in Portugal. A 75-year-old diabetic and obese man presented with right proptosis associated with right eye pain and low vision one month after recovery from severe COVID-19. Considering the most probable etiology for this clinical picture, anti-fungal therapy with liposomal amphotericin B was promptly initiated, followed by endoscopic sinus debridement. However, due to persistent and progressive infection, and after a multidisciplinary revision of the case, orbital exenteration was performed. One year after surgery, the patient is stable, without clinical or imagological signs of relapse of the disease. Although the evolution of the pandemic, along with vaccination programs, led to a lower incidence of severe COVID-19 disease, there are still patients presenting with severe COVID-19, requiring intensive care and at risk for serious complications. This case illustrates the importance of being aware of the development of post-COVID-19 mucormycosis and the need for close surveillance of patients recovering from severe COVID-19. COVID-19 prompt diagnosis and multidisciplinary approach are essential for a timely intervention achieving better survival while minimizing morbidity.


Influence of cold water immersion on heat debt and substrate utilization in males varying in body composition: a retrospective analysis.
The present article is a retrospective analysis of previously published data. This analysis examined the effect of immersion in 18, 22 and 26 degrees C cold water, on heat debt (kJ), substrate utilization [i.e., R (respiratory exchange ratio) calculated using indirect calorimetry], and aerobic metabolic rate (i.e., VO2 (oxygen consumption) 1 # min(-1)] in 24 male volunteers (20-35 years) given a preexposure meal (60.2 g carbohydrate, 12.0 g protein, and 2.8 g fat at 60 min prior to the experimental trial) and examined during 90 min of immersion to the first thoracic vertebrae. Body composition was determined via underwater densitometry. Subjects were divided with respect to high body fat (HF; 18-22%, n = 12) or low body fat (LF; 8-12%, n = 12) and randomly assigned to one of three water temperatures. Body heat debt and R did not differ between the LF or HF groups, between temperatures, or across time. Percent calories utilized indicated that for these experimental conditions the predominant substrate utilized between the LF and HF groups across time was derived from carbohydrate. In addition, VO2 was greater (p = .0004) in the LF than HF group, and the latter was greater (p = .0013) in the 18 degrees C group versus the 26 degrees C group and increased across time (p = .0001); that is, VO2 after 5 min of immersion was less than at 60 and 90 min, and values obtained after 30 min of immersion were less than those at 90 min of immersion. Based on these data, it appears that the LF group would expend more calories (308.9 vs. 199.9 kcal, respectively) and more likely derive these calories from a carbohydrate source than the HF group during 90 min of cold water immersion. It would appear beneficial to consider a feeding supplement for the low-fat individual if immersion was in a more thermal stressful environment or extended for a protracted period of time.


Diagnosis of Lung Adenocarcinoma with Clear Cell Features in Pleural Effusion: Cytomorphologic Features, Immunocytochemical Studies, and Differential Diagnosis.
Clear cell adenocarcinoma (CCA) of the lungs is no longer referred to as a subtype in recent classifications of lung adenocarcinoma. Like signet ring features, clear cell features are regarded as cytological features rather than histological subtypes. Additionally, in serous fluids, adenocarcinoma metastasis with clear cell features is a diagnostic challenging entity due to other tumors that come to mindfirst during the differential diagnosis. Here we report a case, diagnosed as CCA of lung metastasis in pleural fluid and evaluated its differential diagnosis.


Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.
Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single 'turnover' parameter, a single 'exchange' parameter and a single 'delay' parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained.


Randomized clinical trial of HIV treatment adherence counseling interventions for people living with HIV and limited health literacy.
Limited health literacy is a known barrier to medication adherence among people living with HIV. Adherence improvement interventions are urgently needed for this vulnerable population. This study tested the efficacy of a pictograph-guided adherence skills-building counseling intervention for limited literacy adults living with HIV. Men and women living with HIV and receiving antiretroviral therapy (N = 446) who scored <90% correct on a test of functional health literacy were partitioned into marginal and lower literacy groups and randomly allocated to 1 of 3 adherence-counseling conditions: (1) pictograph-guided adherence counseling, (2) standard adherence counseling, or (3) general health improvement counseling. Participants were followed for 9 months postintervention with unannounced pill count adherence and blood plasma viral load as primary end points. Preliminary analyses demonstrated the integrity of the trial and >90% of participants were retained. Generalized estimating equations showed significant interactions between counseling conditions and levels of participant health literacy across outcomes. Participants with marginal health literacy in the pictograph-guided and standard-counseling conditions demonstrated greater adherence and undetectable HIV viral loads compared with general health counseling. In contrast and contrary to hypotheses, participants with lower health literacy skills in the general health improvement counseling demonstrated greater adherence compared with the 2 adherence counseling conditions. Patients with marginal literacy skills benefit from adherence counseling regardless of pictographic tailoring, and patients with lower literacy skills may require more intensive or provider-directed interventions.


Organisation of the tectorotundal and SP/IPS-rotundal projections in the chick.
The organisation of the neural projections from the optic tectum and pretectal nuclei complex, n. subpretectalis / n. interstitio-pretecto-subpretectalis (SP/IPS), to the nucleus rotundus (Rt) in chicks was studied by using retrograde tracing techniques. After the injection of fluorescent retrograde tracers, rhodamine-conjugated latex microspheres, fluorescein-conjugated latex microspheres, True Blue, Fluoro-Gold, or rhodamine B isothiocyanate, into different regions of Rt and its middorsal extension, the nucleus triangularis (T), the distribution of retrogradely labelled neuronal cell bodies in the tectum and pretectal nuclei was assessed. Both the ipsilateral and contralateral tectorotundal projections were found to be organised topographically in as much as different sublaminas of the stratum griseum centrale (SGC) project in an orderly manner to Rt and T. The deepest stratum of SGC overlapping into the stratum album centrale projects to T. Deep SGC projects to the dorsal Rt and superficial SGC to the ventral Rt. A band running through the centre of Rt receives input from the central sublamina of SGC, and the caudal central Rt receives input from a deeper sublamina than does the rostral central Rt. The SP/IPS projects to the ipsilateral Rt only and the projection order is dorsal SP to dorsal Rt, ventral SP to ventral Rt and middle SP to the central band of Rt. The neurones in IPS and the nucleus of the tractus tectothalamicus project to T. Thus, Rt and T receive topographically both tecto- (excitatory) and SP/IPS- (inhibitory) projections. The possible functional implications for parallel information processing in these projections are discussed.


Semantic Negative Priming From an Ignored Single-Prime Depends Critically on Prime-Mask Inter-Stimulus Interval and Working Memory Capacity.
The aim of this study is to examine the link between working memory capacity and the ability to exert cognitive control. Here, participants with either high or low working memory capacity (WMC) performed a semantic negative priming (NP) task as a measure of cognitive control. They were required to ignore a single prime word followed by a pattern mask appearing immediately or after a delay. The prime could be semantically related or unrelated to an upcoming target word where a forced-choice categorization was required. Each type of mask (immediate vs. delayed) appeared randomly from trial to trial. Results demonstrated that, when the ignored prime was immediately followed by the mask, neither of the groups (high or low WMC) showed reliable NP. In clear contrast, when the mask onset was delayed responses latencies were reliably slower for semantically related trials than for unrelated trials (semantic NP), but only for the high WMC group. The present results clearly demonstrate that semantic NP from single ignored primes depends on both the masking pattern that follows the prime (immediate vs. delayed mask), and on working memory capacity.


[Pathophysiological and clinical implications of AT(1)/AT(2) angiotensin II receptors in heart failure and coronary and renal failure].
The octapeptide angiotensin II (Ang II), the potent effector molecule of the renin-angiotensin-aldosterone system (RAAS), is involved in the control of blood pressure, cardiac and vascular function as well as sodium and water homeostasis. Because Ang II has also been implicated in the pathophysiology of cardiovascular diseases and renal failure, it has been of increasing interest to inhibit the RAAS at the level of its enzymes such as renin and angiotensin-converting enzyme (ACE) and receptors. At least two subtypes of angiotensin receptors have been identified: AT(1) and AT(2). The AT(1 )receptor mediates all of the known actions of Ang II in the cardiovascular system, such as vasoconstriction, increasing cardiac contractility and renal tubular sodium reabsorption, as well as vascular and cardiac hypertrophy. In contrast, less is known regarding the function of the AT(2) receptor. Evidence suggests that the AT(2) receptor inhibits cell proliferation and induces differentiation, apoptosis and regeneration. The AT(2) receptor has been shown to reverse AT(1) receptor-mediated hypertrophy, suggesting that these receptors exert opposing effects in the cardiovascular system. While renin and ACE inhibitors block the RAAS at the enzymatic level, AT receptor antagonists specifically inhibit the RAAS at the receptor site. AT(1 )receptor antagonists induce a dose-dependent blockade of Ang II-induced effects, resulting in a reduction in blood pressure, cardiac and vascular hypertrophy, proteinuria and glomerular sclerosis. It is postulated that AT(1) receptor antagonists may provide end-organ protection by blocking Ang II via the AT(1) receptor, yet leaving the AT(2) receptor unopposed. These substances have been shown to decrease morbidity and mortality of patients with heart failure and renal disease associated with diabetes.


Breast cancer highlights: key findings from the San Antonio Breast Cancer Symposium: a U.S. perspective.
The San Antonio Breast Cancer Symposium has become one of the leading forums for communication of important discoveries in breast cancer research. Over the past couple of years, seminal, practice-changing results have been presented at this meeting. The aromatase inhibitors represent the most effective endocrine interventions for postmenopausal women with hormone receptor-positive breast cancer. Their introduction into the adjuvant therapy of primary breast cancer was prompted by evidence from the ATAC trial. Progress in adjuvant chemotherapy included the introduction to taxanes, and more recently, the demonstration that the dose-dense administration of paclitaxel in association with doxorubicin and cyclophosphamide resulted in significant improvements in relapse-free and overall survival rates. Molecular targets have become accepted as rational targets, and targeted therapies are proceeding through clinical trials. The success of trastuzumab elicited much excitement, but a number of theoretical and practical hurdles must be overcome before other molecularly targeted agents are incorporated into standard therapy of primary and metastatic breast cancer.


Bacteria from Animals as a Pool of Antimicrobial Resistance Genes.
Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.


Psychiatric manifestations of normal-pressure hydrocephalus: a short review and unusual case.
Normal-pressure hydrocephalus (NPH) is a common cause of potentially reversible dementia. It can present with psychiatric manifestations that may hinder its diagnosis. A 68-year-old man presented with a paranoid psychosis and mild cognitive impairment, but not neurological signs or classic "triad." Gait disturbance and urinary incontinence developed later in the course of illness after the diagnosis of NPH had already been made on computed tomographic (CT) scanning. A lumbo-peritoneal shunt was performed, followed by full remission of psychotic symptoms, as well as considerable improvement in functioning, continence, and gait. This case demonstrates the need to consider NPH when older patients present with psychotic symptoms, particularly in the presence of cognitive impairment, gait disturbance, or incontinence. The decision whether to perform a shunting operation is often difficult, because selection of patients with good prognosis is still inaccurate. CT scanning of the brain is an important investigation in older patients presenting with both functional and organic disorders.


Rod outer segment retinol dehydrogenase: substrate specificity and role in phototransduction.
The reaction catalyzed by all-trans-retinol dehydrogenase of rod outer segments completes the quenching of photoactivated rhodopsin and initiates the cycle of reactions leading to regeneration of visual pigment. The goal of this study was to determine the kinetic parameters of the dehydrogenase at physiological levels of bleaching, to investigate its specificity, and to determine its possible role in modulating phototransduction. Reduction of all-trans-retinal could be measured after bleaching < 0.15% rhodopsin. Kinetic parameters for the forward reaction determined with endogenous all-trans-retinal were Km = 1.1 microM; Vmax = 7 nmol/min/mg rhodopsin. The low enzymatic activity suggests that at high bleach rates, all-trans-retinal could accumulate, increasing the steady state level of bleaching intermediates or promoting formation of pseudophotoproducts. Active pseudophotoproducts, which stimulate Gt activation and opsin phosphorylation by rhodopsin kinase, are formed with opsin and all-trans-retinal as well as retinal analogues lacking the 13 methyl or the terminal two carbons of the polyene chain. Addition of all-trans-retinol, NADP, and [32P]ATP to rod outer segments increased rhodopsin phosphorylation. Kinetic parameters for the reverse reaction determined with exogenous all-trans-retinol were Km = 10 microM; Vmax = 11 nmol/min/mg rhodopsin. Our results support the hypothesis that all-trans-retinol dehydrogenase could influence the phototransduction cascade, including activities of Gt, rhodopsin kinase, and binding of arrestin, by impeding the recycling of rhodopsin at high bleach levels.


Alignment of library services with the research lifecycle.
This study sought to understand the needs of biomedical researchers related to the research lifecycle and the present state of library support for biomedical research. Qualitative interview data were collected from biomedical researchers who were asked to describe their research activities from identifying a problem to measuring the impact of their findings. Health sciences library leaders were surveyed about the services that they currently provide or plan to provide in supporting biomedical research. Library services were strongest at the beginning and end of the research lifecycle but were weaker in the conducting phase of research. Co-occurrence of codes from the qualitative data suggests that library services are on the fringe of rather than integrated into the research lifecycle. Findings from this study suggest that tradition-based service models of health sciences libraries are insufficient to meet the needs of biomedical researchers. Investments by libraries in services that integrate with the conducting phase of research are needed for libraries to remain relevant in their support of the research lifecycle.


Paraoxonase 1 (PON1) activity in serum, follicular fluid and seminal plasma of sheep.
This work aimed to describe the activity of paraoxonase 1 (PON1) in serum, follicular fluid and seminal plasma of sheep. Average serum PON1 activity was 286.8 ± 96.2 U/ml in females and 237.6 ± 18.9 U/ml in males. There was a positive correlation between PON1 activity in serum and follicular fluid in females, being twice higher in serum than in follicular fluid (148.8 ± 15.7 U/ml). PON1 activity in males' serum was 10-fold higher than in seminal plasma (21.18 ± 14.2 U/ml), and there was no correlation between PON1 activity in both compartments. Finally, this work suggests that PON1 activity of in sheep is higher compared to other mammalian species, and there is an association between PON1 in serum and follicular fluid only.


The increase in alcohol consumption among women: a phenomenon related to accessibility or stress? A general population study.
This population survey of Norwegian women (N = 3997) and their husbands explore the relative importance of accessibility and stress variables in explaining the level of women's alcohol consumption. Among the accessibility-variables, population density and husbands' alcohol consumption have a significant impact on the women's consumption. Employment among women is not significantly related to their alcohol use when controlling for the husbands' consumption. Stress variables (work stress, nervousness) have no significant influence on consumption when controlling for accessibility variables. The findings show that the increase in women's consumption of alcohol is more specifically related to accessibility, variables with a close relationship to lifestyle, rather than to general accessibility to alcoholic beverages.


The lymphatic vasculature: recent progress and paradigms.
The field of lymphatic research has been recently invigorated by the identification of genes and mechanisms that control various aspects of lymphatic development. We are beginning to understand how, starting from a subgroup of embryonic venous endothelial cells, the whole lymphatic system forms in a stepwise manner. The generation of genetically engineered mice with defects in different steps of the lymphangiogenic program has provided models that are increasing our understanding of the lymphatic system in health and disease. This knowledge, in turn, should lead to the development of better diagnostic methods and treatments of lymphatic disorders and tumor metastasis.


[Incidence of refractive errors with corrective aids subsequent selection].
This study follows the occurrence of refractive errors in population and the possible selection of the appropriate type of corrective aids. Objective measurement and subsequent determination of the subjective refraction of the eye is on essential act in opotmetric practice. The file represented by 615 patients (1230 eyes) is divided according to the refractive error of myopia, hyperopia and as a control group are listed emetropic clients. The results of objective and subjective values of refraction are compared and statistically processed. The study included 615 respondents. To determine the objective refraction the autorefraktokeratometer with Placido disc was used and the values of spherical and astigmatic correction components, including the axis were recorded. These measurements were subsequently verified and tested subjectively using the trial lenses and the projection optotype to the normal investigative distance of 5 meters. After this the appropriate corrective aids were then recommended. Group I consists of 123 men and 195 women with myopia (n = 635) of clients with an average age 39 +/- 18,9 years. Objective refraction - sphere: -2,57 +/- 2,46 D, cylinder: -1,1 +/- 1,01 D, axis of: 100 degrees +/- 53,16 degrees. Subjective results are as follows--the value of sphere: -2,28 +/- 2,33 D, cylinder -0,63 +/- 0,80 D, axis of: 99,8 degrees +/- 56,64 degrees. Group II is represented hyperopic clients and consists of 67 men and 107 women (n = 348). The average age is 58,84 +/- 16,73 years. Objective refraction has values - sphere: +2,81 +/- 2,21 D, cylinder: -1,0 +/- 0,94 D; axis 95 degree +/- 45,4 degrees. Subsequent determination of subjective refraction has the following results - sphere: +2,28 +/- 2,06 D; cylinder: -0,49 +/- 0,85 D, axis of: 95,9 degrees +/- 46,4 degrees. Group III consists from emetropes whose final minimum viasual acuity was Vmin = 1,0 (5/5) or better. Overall, this control group is represented 52 males and 71 females (n = 247). The average age was 43 +/- 18,73 years. Objective refraction - sphere: +0,32 +/- 0,45 D; cylinder: -0,51 +/- 0,28 D, axis of: 94,7 degrees +/- 57,5 degrees. Values of objective refraction take higher values than the subsequent execution of the subjective examination of the refractive error and recommendation of the appropriate type of corrective aids. This all is in examined groups and in the individual components of refractive errors. It also confirmed the hypothesis that the population outweighs with-the-rule astigmatism, the deployment of resources according to the literature ranges from 90 degrees +/- 10 degrees. The values observed correction of refractive errors are then derived also offer the most common prescription ranges and products for the correction of given ametropia. In the selection and design corrective aids, we are often limited. Our task is then to manufacture high quality, functional and aesthetic corrective aids, you need to connect knowledge from the fields of optics, optometry and ophthalmology. Faster visual rehabilitation simplifies clients' rapid return to everyday life.


Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox.
Cancer formation is a highly regulated and complex process, largely dependent on its microenvironment. This complexity highlights the need for developing novel target-based therapies depending on cancer phenotype and genotype. Autophagy, a catabolic process, removes damaged and defective cellular materials through lysosomes. It is activated in response to stress conditions such as nutrient deprivation, hypoxia, and oxidative stress. Oxidative stress is induced by excess reactive oxygen species (ROS) that are multifaceted molecules that drive several pathophysiological conditions, including cancer. Moreover, autophagy also plays a dual role, initially inhibiting tumor formation but promoting tumor progression during advanced stages. Mounting evidence has suggested an intricate crosstalk between autophagy and ROS where they can either suppress cancer formation or promote disease etiology. This review highlights the regulatory roles of autophagy and ROS from tumor induction to metastasis. We also discuss the therapeutic strategies that have been devised so far to combat cancer. Based on the review, we finally present some gap areas that could be targeted and may provide a basis for cancer suppression.