Clinically silent Paget disease of male nipple.
Male breast cancer constitutes less than 1% of all breast cancer cases. Special types, such as Paget disease of the breast, are extremely rare. To our knowledge there are less than 50 cases of Paget disease of male breast described in world medical literature. Authors present pathologically proven but clinically silent case of Paget disease of the nipple in an 86-year old male with breast cancer. Literature data suggest that the prognosis of male Paget cancer is worse than in "ordinary" male breast cancer. Therefore, the histologic diagnosis of Paget disease, even in an asymptomatic male patient, may have negative prognostic value.


National chest week to raise public awareness.
Respiratory disease is responsible for the loss of more working days than any other single cause in this country according to the Chest, Heart and Stroke Association.


Bilateral lung transplantation in asymmetric thorax: case reports.
Suppurative lung diseases, such as cystic fibrosis and bronchiectasis, when diffuse and associated with important functional loss, can be treated with bilateral lung transplantation with good results. These diseases are frequently associated with previous lung resections presenting an asymmetric thorax, thus making lung extraction difficult and generating disproportion between the graft and the pleural cavity. To treat this condition, pneumonectomy and single lung transplantation is a feasible option; however, there are associated comorbidities and an invariable need for extracorporeal circulation. Described herein are 2 patients with an asymmetric thorax, treated with bilateral transplantation and lung volume reduction with lobectomy.


Test-dependent relationship of the antidepressant and analgesic effects of amitriptyline.
Antidepressants have been found to be of value in the treatment of pain of various etiologies. Nevertheless, the data are conflicting as it is often difficult to distinguish between the analgesic and antidepressant action. The analgesic effect of acutely administered amitriptyline at doses of 2.5, 5, 10, 20 and 40 mg/kg was investigated in four nociceptive tests involving physical (hot plate and tail flick tests), or noxious chemical stimuli (acetic acid and formalin tests). Relationships were established between the analgesic actions and the antidepressant effect of acutely administered amitriptyline at doses of 2.5, 5, 10 and 20 mg/kg in the forced swimming test. The results demonstrated a relationship between the antidepressant effect and the analgesic action in the tail flick test, but not in the hot plate, acetic acid and formalin tests. Thus, the type of noxious stimulus may be a determining factor in the relationship between these two pharmacological actions.


[The treatment of Eubacterium suis infections in boars].
The main habitat of Eubacterium suis (E. suis) is the preputial diverticulum of male pigs. E. suis can be transmitted from boars to sows at the time of mating, and ascending urinary tract infections (cystitis and pyelonephritis) in sows may develop. In this paper different methods of treatment were investigated to eliminate E. suis from the diverticulum of carrier boars (n = 33). Local therapy and feed medication were administered separately or in combination. For local instillation into the preputial sac penicillin, penicillin/streptomycin or enrofloxacin were used, while medicated feed contained enrofloxacin. None of the treatments resulted in boars, which were persistently free from E. suis. Also additional hygiene measures as washing of boars and disinfection of pens could not improve the results. At the latest 18 days after treatment E. suis could be detected again in the preputial diverticulum of all boars. Short duration of action of antibiotics in the preputial sac as well as re-colonisation of the diverticulum by contaminated pens are discussed. In herds in which urinary tract infections are troublesome it is worthwhile using artificial insemination to prevent transmission of E. suis to the sow. Treatment of unspecific urinary tract infections in sows may be also important, because alterations of bladder mucosa due to other bacteria may support the colonisation of E. suis.


Reversibility of the changes induced by n-3 fatty acids in mouse plasma, liver and blood cell lipids.
The changes induced by dietary n-3 fatty acids (FA) in the lipids and FA of plasma, liver and blood cells, and their reversibility, was studied in mice given a diet containing 9% fish oil (FO) for 2 weeks and then returned to, and kept for another 2 weeks on, the usual standard lab chow diet. In plasma, the concentrations of phospholipids (PL), mostly phosphatidylcholine (PC), triacylglycerols (TG), cholesterol and cholesterol esters (CE) decreased rapidly after starting the FO diet, and remained low from day 3 onwards. This decrease was concomitant with a remarkable reduction in the n-6 FA, especially 18:2n-6, not compensated for by the relative enrichment in n-3 FA induced by FO. In liver, TG and CE decreased and PL slightly increased, all of them showing reduced n-6/n-3 ratios. Sphingomyelin, which lacks polyunsaturated FA other than small amounts of 18:2 and 24:2n-6, showed altered ratios between its very long chain monoenes and saturates. In the washout phase, the most rapid event was an immediate increase in 18:2n-6 and after a few days in 20:4n-6 in plasma and liver, where most of the lipid and FA changes were reversed completely in about 10 days. In the case of blood cells even 2 weeks were insufficient for a reversal to the initial n-6/n-3 ratios. The lipid class responsible for this lack of reversibility was phosphatidylethanolamine, PC having returned to the initial fatty acid composition during the stated period.


Effect of continuous feeding on maternal protein metabolism and fetal growth in the rat.
Accelerated maternal catabolism ensures adequate fetal growth in the postabsorptive pregnant mammal during late gestation. However, the relative importance of maternal stores and diet in supplying nutrient requirements to the fetus is unknown. We have measured rates of protein synthesis and breakdown in maternal and fetal tissues during continuous intravenous feeding on days 17 and 20 in the rat, using leucine tracer infusions. Nutrient solutions supplying 180 and 250 kcal.kg-1.day-1 were tested. Changes in fetal size were measured in these rats and in rats maintained on ad libitum chow feeding. In comparison to previous results in the postabsorptive rat, leucine flux from endogenous sources into plasma was significantly suppressed, with only 12-20% of circulating leucine derived from maternal tissues. Muscle protein catabolism (previously described on day 20 of gestation) was abolished with continuous feeding. Fetal growth rate averaged 46%/day on day 17 of gestation in all groups but was reduced to 12%/day on day 20 in the rats intravenously fed 180 kcal.kg-1.day-1 and 22%/day in the rats fed 250 kcal.kg-1.day-1. Fetal growth on day 20 in the rats fed rat chow ad libitum was unaffected. We conclude that by decreasing the maternal contribution to circulating nutrients, continuous intravenous feeding may adversely affect fetal growth in late pregnancy. The findings in the current study underline the physiological importance of maternal-fetal nutrient exchange.


Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation.
To study the effect of age on the physiological threshold asymmetries for the motor evoked potential (MEP) and silent period (SP) following transcranial magnetic stimulation. We studied 63 right-handed subjects and 13 young left-handed subjects (19-39 years). The right-handers were classified into three age groups; 22 young (20-38 years), 20 middle-aged (40-58 years) and 21 old (61-82 years) subjects. We measured the MEP thresholds at rest and during voluntary contraction (VC), and the SP thresholds from the right and left abductor pollicis brevis (APB) muscles. We also measured the side to side differences of the F wave persistency and the F wave/M wave amplitude ratio from the same muscles. Among young subjects, all of the MEP and SP thresholds for the right APB were significantly lower than those for the left APB in the right-handers, and the reverse was true in the left-handers. The results in the middle-aged right-handers were similar to those in the young right-handers, but in the old right-handers, none of the thresholds were different between the two sides. We did not find any asymmetries of the F wave in the subjects of any age group. We speculate that the age-dependent threshold asymmetries are preferentially related to functional asymmetries at the cortical level.


Mitochondrial genome of Phalantus geniculatus (Hemiptera: Reduviidae): trnT duplication and phylogenetic implications.
Reduviidae is the second largest family of Heteroptera and most of them are important natural enemies of agricultural and forest pests. Most of the sequenced mitochondrial (mt) genomes in this family have the typical gene arrangement of insects and encode 37 coding genes (13 protein-coding genes, 22 tRNA genes and two rRNA genes). In the present study, we sequenced the mt genome of Phalantus geniculatus from the subfamily Peiratinae through high-throughput sequencing and encountered the duplication of tRNA genes for the first time in this subfamily. We identified 23 tRNA genes, including 22 tRNAs commonly found in insect mt genomes and an extra trnT (trnT2), which has high sequence similarity (96.9%) to trnT1. The presence of a "pseudo-trnP" in the non-coding region between trnT1 and trnT2 supports the hypothesis that the presence of an extra trnT can be explained by the tandem duplication-random loss (TDRL) model. Phylogenetic results inferred from mt genome sequences supported a sister relationship between Phymatinae and the remaining sampled subfamilies, as well as a paraphyletic Reduviinae. The present study highlights the utility of mt genomes in the phylogenetic study of Reduviidae based on the large scale taxon sampling in the future.


Cochlear implant placement: round window approach.
The indications for cochlear implantation continue to extend to patients with increased levels of residual hearing. Single-sided deafness and tinnitus are currently under various clinical trials as even further expansion of the application of cochlear implant device and programming technology is underway. This video details a round window and hearing preservation approach for cochlear implant placement, and incorporates the most recent advances in surgical technique. The video can be found here: http://youtu.be/bDqkbboXrU4 .


Co-occurrence of citrinin and ochratoxin A in rice in Asia and its implications for human health.
Citrinin (CIT) and ochratoxin A (OTA) are nephrotoxic mycotoxins, produced by several Aspergillus and Penicillium species and their co-occurrence in rice may cause health effects in humans. Rice is an important food crop worldwide and is a major staple food in Asia which may be invaded by CIT and OTA producing fungal spores in the field, during harvest and storage. Humans are exposed to these mycotoxins through ingestion of contaminated rice and other food commodities. Yet, data on the combined presence to these food contaminants are still insufficient to estimate human exposure in Asia. This review describes the prevalence of CIT and OTA in rice in Asia and its implications on human health, which may help in establishing and carrying out proper management strategies against mould development on rice. From the health point of view, combined exposition of CIT and OTA should be a public concern as both are nephrotoxic and long-term exposure can pose detrimental health effects. Thus, it is necessary for local farmers and food factories to implement strict measures and to improve methods for rice preservation during the distribution to consumers, particularly in the markets. Moreover, regular surveys for CIT and OTA occurrence in rice and human biomonitoring are recommended to reduce the health effects in Asian population. © 2017 Society of Chemical Industry.


Zinc deficiency-induced trace element concentration and localization changes in the central nervous system of albino rat during postnatal development. II. Atomic absorption spectrophotometric examinations.
The changes in the zinc and copper concentrations in the central nervous system (spinal cord, cerebellum, cerebrum, hippocampus, corpus striatum) of albino rat were studied by atomic absorption spectrophotometry in a state of zinc deficiency induced experimentally during the first 30 days of postnatal ontogenesis. It was found that in these structures the zinc deficiency is able to influence the changes and tendencies in the trace element content essentially only in an area undergoing intensive development in the given period, or which is sensitive to unsatisfactory dietary influences. The results lead to the assumption that the state of zinc deficiency is accompanied by a change in the distribution of the trace element content within the cells.


The grape-derived polyphenol resveratrol differentially affects epidermal and platelet-derived growth factor signaling in human liver myofibroblasts.
The grape-derived polyphenol resveratrol is anti-proliferative for human liver myofibroblasts, which may be beneficial for the treatment of liver fibrosis. However, its mechanism of action is ill understood. Here, we have studied how resveratrol interfered with signaling pathways used by epidermal or platelet-derived growth factors to induce the proliferation of these cells. We found that resveratrol inhibited epidermal growth factor or platelet-derived growth factor-induced DNA synthesis. Resveratrol did not, however, decrease epidermal growth factor receptor autophosphorylation or activation of extracellular regulated kinases, but strongly inhibited the phosphorylation of Akt and of its substrate forkhead related transcription factor. This suggested that resveratrol inhibited epidermal growth factor-induced mitogenic signaling through inhibition of the phosphatidylinositol 3-kinase /Akt pathway. The phosphatidylinositol 3-kinase inhibitor LY 294002, also, inhibited epidermal growth factor-dependent DNA synthesis and Akt phosphorylation but did not decrease extracellular regulated kinases phosphorylation. In contrast, resveratrol inhibited platelet-derived growth factor-stimulated receptor autophosphorylation and every subsequent signaling step. Resveratrol did not directly inhibit phosphatidylinositol 3-kinase activity measured on immunoprecipitates from epidermal growth factor-stimulated myofibroblasts, but it strongly reduced the autophosphorylation of the phosphatidylinositol 3-kinase downstream target phospho-inositide-dependent kinase-1 that phosphorylates Akt. We, thus, show that resveratrol has growth factor-specific effects: it inhibits platelet-derived growth factor signaling via reduced receptor activation, whereas it reduces epidermal growth factor-dependent DNA synthesis via inhibition of the phosphatidylinositol 3-kinase/Akt pathway, possibly through inhibition of phospho-inositide-dependent kinase-1 activity.


[Measurement of coaxial position in lens implants].
Intraocular lens implantation occasionally causes binocular diplopia resistant to prismatic correction. Present methods of examination cannot determine the cause of this incurable diplopia. Therefore, a new method based on keratometry has been invented to allow qualitative and quantitative analysis of biomicroscopically undetectable decentration of intraocular lens implants producing asthenopic complaints. The present study investigates the type and frequency of intraocular lens decentration relative to the visual axis.


Protein S activity in patients with heredofamilial protein S deficiency and in patients with juvenile venous thrombosis. Results of a functional method.
Using an ACL 300R coagulometer (Instrumentation Laboratory) we assessed the clinical usefulness of a new method to measure PS activity (PS:Act), based on the prolongation of prothrombin time of a mixture of diluted plasma sample, PS depleted plasma previously incubated with Protac for protein C activation, bovine thromboplastin and calcium ions. The results were compared with those from immunological assays. PS:Act was measured in 42 apparently healthy subjects, in 12 patients with hereditary PS deficiency (HPSD group) diagnosed on the basis of immunologic tests and in 48 patients with episodes of juvenile venous thromboembolism at least three months prior to testing (JVTE group). All the HPSD patients had PS:Act below the normal range (less than 62%). In JVTE group 9 patients (18.7%) showed abnormal results for PS:Act, 4 (8.3%) had low levels of free PS:Ag; all patients had normal total PS:Ag levels. Levels of antiphospholipid antibodies (immunologic test) were normal in the 9 JVTE patients with low PS:Act. When all the results were considered together (n = 102), the correlation coefficient between PS:Act and free PS:Ag was 0.78 (p less than 0.01).


Acetate recognition by 2,6-bis(2-benzimidazolyl)pyridine.
2,6-Bis(2-benzimidazolyl)pyridine, bbp, a simple tridentate ligand, is employed as a receptor for the recognition of anions. The binding of anionic guest species with bbp can be studied in short duration using UV/vis spectroscopy, fluorescence spectroscopy and (1)H NMR techniques at very low concentrations. The results obtained from the above spectroscopic techniques indicate that 2,6-bis(2-benzimidazolyl)pyridine is an efficient anion receptor providing chemical shift and optical modification based signals for the detection of acetate ions.


Finite temperature mott transition in hubbard model on anisotropic triangular lattice.
We investigate the Hubbard model on the anisotropic triangular lattice by means of the cellular dynamical mean-field theory. The phase diagram determined in the Hubbard interaction versus temperature plane shows novel reentrant behavior in the Mott transition due to the competition between Fermi-liquid formation and magnetic correlations under geometrical frustration. We demonstrate that the reentrant behavior is characteristic of the Mott transition with intermediate geometrical frustration and indeed consistent with recent experimental results of organic materials.


Diffusion weighted MR imaging in acute stroke: the SGH experience.
Cerebrovascular accident (CVA) is a leading cause of death and disability in many countries. Diffusion-weighted (DW) magnetic resonance (MR) imaging has been reported to be useful in the detection of acute strokes and as an investigative tool evaluating the therapeutic effects of neuroprotective and thrombolytic agents. The objectives of this study are to share our experience using the commercially available isotropic DW scan in imaging of acute stroke, assess its usefulness over conventional T2-weighted (T2W) scans in a busy clinical radiology unit and highlight it pitfalls. We found the rapid sub-minute DW technique well suited for ill and restless stroke patients and superior to T2W scans in many ways. It was highly sensitive to acute ischaemic lesions, made lesions easily identifiable and readily differentiated the acute lesion from a background of multiple chronic infarcts. However, there are potential pitfalls in the evaluation of small hyperacute posterior fossa strokes and venous infarcts. The major strength of this MR technique lies in its ability to diagnose hyperacute strokes and thence the potential for therapeutic thrombolysis, but unfortunately patients qualifying for the "therapeutic window" were a minority. More efforts need to be focused on public education in order for this powerful imaging modality to find its true value and contribute to viability of an effective thrombolytic programme.


[Professional confidentiality of the physician].
Summarizing it is to be mentioned that, concerning the professional secrecy, the principle is held that the physician is allowed to speak as much as it is necessary and he must be silent as far as it is possible. The physician is entitled to reveal but not obliged to do so as far as he has been exonerated from the professional secrecy or as far as the revelation is necessary for the protection of a higher legal proceeding. This is taken into consideration also for evidence in judicial proceedings. Apart from legal informational obligations at first, however, not the physician but the patient defines the breadth of allowable infringements. Only when the professional secrecy collides with the legal matters of third persons the physician himself gets into compulsions of decision. Taking into consideration the criminal law the maintenance as well as the infringement of the professional secrecy remain without consequences for the physician, if the translegal critical state is present. In such cases, however, he should endeavour to keep the dangers which brings his silence for others as insignificant as possible.


[Hiatal hernia. Symptoms, diagnosis and therapy].
Forty-eight patients with a mean age of 53 years were treated for hiatal hernia at the University of Würzburg Department of Surgery between 1983 and 1989. The cohort was subdivided according to type of herniation, age and sex, and symptoms. Conservative treatment sufficed in 22%, but the majority (78%) underwent surgery. Nissen's fundoplication predominated (48%); other methods used were gastropexy (17%), antrectomy with Roux's Y-gastrojejunostomy (6%) and Angelchik's prosthesis (6%). Intra- and postoperative complications included 5 splenectomies following iatrogenic trauma to the spleen, 2 cases of subphrenic abscess, and 2 with pleural effusions. The extensive discussion stresses the various operative treatment procedures and their respective advantages and drawbacks.


Ocular injuries from automobile batteries.
The incidence of eye injuries related to automobile batteries has sharply increased, currently comprising nearly 1% of all unscheduled eye visits to one medical center. A series of 93 cases obtained over 81/2 years was reviewed and follow-up information obtained. While two thirds of the injuries were relatively minor, 10% (9) of the patients sustained permanent ocular damage or required hospitalization. All of the severe injuries and the majority of the other injuries were caused by battery explosions. Not only should the inherent danger of the lead-acid storage battery be reduced, but the public must be alerted to the hazard.


Linking microstructure and nanochemistry in human dental tissues.
Mineralized dental tissues and dental pulp were characterized using advanced analytical transmission electron microscopy (TEM) methods. Quantitative X-ray energy dispersive spectroscopy was employed to determine the Ca/P and Mg/P concentration ratios. Significantly lower Ca/P concentration ratios were measured in peritubular dentine compared to intertubular dentine, which is accompanied by higher and variable Mg/P concentration ratios. There is strong evidence that magnesium is partially substituting calcium in the hydroxyapatite structure. Electron energy-loss near-edge structures (ELNES) of C-K and O-K from enamel and dentine are noticeably different. We observe a strong influence of beam damage on mineralized dental tissues and dental pulp, causing changes of the composition and consequently also differences in the ELNES. In this article, the importance of TEM sample preparation and specimen damage through electron irradiation is demonstrated.


Salmonella and Campylobacter contamination of broiler chicken carcasses and scald tank water: the influence of water pH.
Scalding at 50 degrees +/- 0.5 degrees C, in water maintained at pH 9.0 +/- 0.2 by the addition of sodium hydroxide, had no effect on the incidence of salmonella or campylobacter contamination of chicken carcasses. There were significant reductions, however, in the numbers of these organisms in the water itself.


Occurrence, Seasonal Variation and Risk Assessment of Antibiotics in the Surface Water of North China.
In this study, the occurrence, seasonal, and spatial variations of four classes antibiotics were investigated in the surface water of North China. Water samples were taken from 24 sampling sites along rivers in May and August and antibiotics in water samples were detected by SPE-UPLC-MS/MS. The occurrence of all antibiotics except for FLO in May were higher than in August. The mean concentrations of four classes antibiotics detected in May and August were in the following order respectively: quinolones (421.23 ng/L) > tetracyclines (28.37 ng/L) > amphenicols (20.38 ng/L) > sulfonamides (5.79 ng/L) and amphenicols (284.36 ng/L) > quinolones (15.74 ng/L) > tetracyclines (3.05 ng/L) > sulfonamides (0.20 ng/L). The results showed that quinolones and amphenicols were dominant antibiotics among four classes antibiotics. To explore the source of antibiotics from the fish ponds nearby, antibiotic concentration data, which was investigated in the sediment, fish feed and fish revealed a direct relationship between the main antibiotics and fish farms along the rivers. Risk assessment data indicated enrofloxacin and florfenicol could cause higher safety risks to aquatic organisms compared to other antibiotics.


Overexpression of Sirtuin2 prevents high glucose-induced vascular endothelial cell injury by regulating the p53 and NF-κB signaling pathways.
To investigate the potential role and underlying mechanism of Sirtuin2 (SIRT2) in regulating high glucose (HG)-induced vascular endothelial cell injury by using human umbilical vein endothelial cells (HUVECs). SIRT2 mRNA and protein expression levels were decreased in HG-treated HUVECs. SIRT2 overexpression increased viability, decreased apoptosis and reduced levels of reactive oxygen species in HG-treated HUVECs. SIRT2 overexpression decreased TNF-α expression (146.5 ± 22.8 pg TNF-α ml-1) relative to that in the empty vector group (263.5 ± 18.5 pg TNF-α ml-1) and decreased MCP-1 expression (63.8 ± 9.85 pg MCP-1 ml-1) relative to that in the empty vector group (105.8 ± 8.5 pg MCP-1 ml-1). SIRT2 overexpression decreased the acetylation of p53 by 33% and decreased the acetylation of NF-κB p65 by 58% in HG-treated HUVECs. SIRT2 prevents HG-induced vascular endothelial cell injury through suppressing the p53 and NF-κB signaling pathways.


The development of immunological relationship between mother and fetus under physiological and pathological conditions.
On the basis of results of our research and review of literature, the complex of immuno logical influences, operating during the development of the human fetus, were evaluated. It is obvious that during the early stages of pregnancy the conceptus is protected by non-specific mechanisms, i.e. hormonally (HCG, progesterone) and by certain properties of the trophoblast (barrier function, immunologically inert surface). Specific immunological tolerance is formed by gradual penetration of trophoblast particles and later by penetration of fetal blood cells into maternal circulation. Thus a specific suppression of maternal T lymphocytes against fetal antigens develops, other immunological functions being intact. - Following a strong antigenic stimulus (e.g. Rh-D), isoimmunization of the mother and serious risk for the fetus occur. Immunological causes of abortion could not be unequivocally proved in recurrent abortions. The explanation of the origin of EPH-gestosis on the basis of toxic action of immunocomplexes is highly probable, however the laboratory and experimental proof is still lacking.


A review of the nutritional value of legumes and their effects on obesity and its related co-morbidities.
Since the 1970s, the proportion of overweight and obese people in the United States has grown at an alarming rate. An awareness of the consequences of obesity on the health and well-being of individuals is evident in the plethora of strategic plans at the local and national levels, most of which have largely fallen short of their goals. If interventions continue to be unsuccessful, it is estimated that approximately three of four Americans will be overweight or obese by 2020. Prevention of excess weight gain can be accomplished with relatively small changes in lifestyle behaviours to control body weight. Small sustainable changes are perhaps better than efforts to achieve larger changes that cannot be sustained. Legumes can be a valuable food by which the needs of the undernourished or under-served populations could be met. They can be incorporated into meat products, such as sausages and burgers, to lower the energy density of these foods while providing important nutrients. Replacing energy-dense foods with legumes has been shown to have beneficial effects on the prevention and management of obesity and related disorders, such as cardiovascular disease, diabetes and the metabolic syndrome. This review explores the nutritional value and obesity-related health benefits of legume consumption while focusing on pulses.


Three distinct open-pore morphologies from a single particle-filled polymer blend.
Ternary mixtures composed of polyisobutylene (PIB), polyethylene oxide (PEO), and silica particles yield three distinct open-pore morphologies depending on the mixture composition: (1) pendular network (particles bonded together by menisci of PEO); (2) capillary aggregate network (particles and PEO form a combined phase with strongly solid-like properties which forms a percolating network); (3) cocontinuous morphology (silica and the PEO form a highly viscous combined phase which retards interfacial tension-driven coarsening). Remarkably, interfacial tension plays altogether different roles in stabilizing these three morphologies: stabilizing the first, not affecting the second, and destabilizing the last. The first two of these morphologies appear to be generalizable to other systems, e.g. to oil/water/particle mixtures. In all three cases, the pores do not collapse even after flow, i.e. all three porous morphologies are amenable to processing.


Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts.
The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH and PGE2, but no significant effects could be observed in other clonal lines.


Added value of pretreatment (18)F-FDG PET/CT for staging of advanced gastric cancer: Comparison with contrast-enhanced MDCT.
To evaluate the added clinical value of pretreatment (18)F-FDG PET/CT compared with conventional contrast-enhanced multidetector-row CT (CECT) alone for staging of advanced gastric cancer We studied 106 patients with locally advanced gastric cancer who underwent pretreatment CECT and (18)F-FDG PET/CT. Two experienced reviewers assessed the diagnostic performance of both CECT alone and the combination of CECT and (18)F-FDG PET/CT for the primary tumor, regional lymph node metastasis (N) and distant metastasis (M), rating their diagnostic confidence with a 5-point scoring system for each location. The two methods were compared using receiver operating characteristic (ROC) curve analysis for histopathologic findings, imaging, and clinical follow-up as the reference standards. Among the 106 patients, 96 primary tumors (90.6%) were detected by CECT, while 101 (95.3%) were clearly identified by (18)F-FDG PET/CT (p=0.074). Patient-based areas under the ROC curves for CECT alone versus the combination of CECT and (18)F-FDG PET/CT for diagnosis of N stage, peritoneal dissemination, liver metastasis, distant lymph node metastasis, bone metastasis, metastasis at other sites and overall M stage were 0.787 vs. 0.858 (p=0.13), 0.866 vs. 0.878 (p=0.31), 0.998 vs. 1.0 (p=0.36), 0.744 vs. 0.865 (p=0.049), 0.786 vs. 0.998 (p=0.034), 0.944 vs. 0.984 (p=0.34), and 0.889 vs. 0.912 (p=0.21), respectively. The diagnostic performance of primary tumor detection and NM staging was not influenced by the histologic subtype. Adding (18)F-FDG PET/CT to CECT provides better diagnostic accuracy for detection of distant lymph node metastasis and bone metastasis in patients with untreated advanced gastric cancer.


Recognizing the long-term sequelae of burns as a chronic medical condition.
As medicine continues to advance, many individuals are living longer with injuries previously considered life threatening. These individuals often face numerous long-term physical and psychological sequelae associated with their injury that persist through the course of their lives. Recently, other injury populations have begun to think of their condition as "chronic". Using data collected from the Burn Model System National Database, a framework for the reconsideration of burn injury as a chronic condition is proposed.


Management of essential thrombocythemia: implications of the medical research council primary thrombocythemia 1 trial.
There has been a dearth of prospective randomized studies in essential (or primary) thrombocythemia (ET). To date, only two reports have been published. Cortelazzo et al reported the first study in 1995. The second is the Medical Research Council Primary Thrombocythemia 1 trial (MRC PT-1), the results and implications of which are the subject of this article.


Phenolic profiles of nectar and honey of Quillaja saponaria Mol. (Quillajaceae) as potential chemical markers.
Quillaja saponaria Mol. (Quillajaceae) is one of the most important melliferous species in Chile, mainly as a source of monofloral honey. Honey made by A. mellifera presents biological activity against pathogens and antioxidant capacity associated with the presence of phenolic compounds deriving from the nectar, as a result of bee honey foraging. The aim of this study was to identify and quantify the phenolic compounds from the floral nectar of Q. saponaria and the honey made in apiaries in the central zone, and compare the composition of the chromatographic profiles of nectar and honey to known phenolic compounds. The results obtained by HPLC-DAD (high-performance liquid chromatography with diode-array detection) showed a similar profile of phenolic compounds, in which gallic acid, myricetin, rutin, quercetin and naringenin were identified. The phenolic compounds detected could be used as a reference for future studies for determining potential chemical markers of this honey, complementing the present identification of honeys by determining their botanical origin. The identification of bioindicators of the floral origins for honey of this species could provide added value to honey commercialization by certifying the botanical origin of their chemical features and biological attributes.


3D structures and ligand specificities of nuclear xenobiotic receptors CAR, PXR and VDR.
The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantly available, providing valuable insights into the ligand-binding specificity as well as the activation mechanisms. The ligand-binding site of PXR is large and flexible, whereas those of CAR and VDR are compact and rigid, respectively. In general, the ligand profiles of the receptors are in agreement with the LBD structures. The crystal structures have greatly helped us to understand the promiscuity and/or specificity of CAR, PXR and VDR.


On the properties of a bundle of flexible actin filaments in an optical trap.
We establish the statistical mechanics framework for a bundle of Nf living and uncrosslinked actin filaments in a supercritical solution of free monomers pressing against a mobile wall. The filaments are anchored normally to a fixed planar surface at one of their ends and, because of their limited flexibility, they grow almost parallel to each other. Their growing ends hit a moving obstacle, depicted as a second planar wall, parallel to the previous one and subjected to a harmonic compressive force. The force constant is denoted as the trap strength while the distance between the two walls as the trap length to make contact with the experimental optical trap apparatus. For an ideal solution of reactive filaments and free monomers at fixed free monomer chemical potential μ1, we obtain the general expression for the grand potential from which we derive averages and distributions of relevant physical quantities, namely, the obstacle position, the bundle polymerization force, and the number of filaments in direct contact with the wall. The grafted living filaments are modeled as discrete Wormlike chains, with F-actin persistence length ℓp, subject to discrete contour length variations ±d (the monomer size) to model single monomer (de)polymerization steps. Rigid filaments (ℓp = ∞), either isolated or in bundles, all provide average values of the stalling force in agreement with Hill's predictions Fs (H)=NfkBTln(ρ1/ρ1c)/d, independent of the average trap length. Here ρ1 is the density of free monomers in the solution and ρ1c its critical value at which the filament does not grow nor shrink in the absence of external forces. Flexible filaments (ℓp < ∞) instead, for values of the trap strength suitable to prevent their lateral escape, provide an average bundle force and an average trap length slightly larger than the corresponding rigid cases (few percents). Still the stalling force remains nearly independent on the average trap length, but results from the product of two strongly L-dependent contributions: the fraction of touching filaments ∝〈L〉(O.T.) (2) and the single filament buckling force ∝〈L〉(O.T.) (-2).


First-principles study on thermodynamic properties and phase transitions in TiS(2).
Structural and vibrational properties of TiS(2) with the CdI(2) structure have been studied to high pressures from density functional calculations with the local density approximation (LDA). The calculated axial compressibility of the CdI(2)-type phase agrees well with experimental data and is typical of layered transition-metal dichalcogenides. The obtained phonon dispersions show a good correspondence with available experiments. A phonon anomaly is revealed at 0 GPa, but is much reduced at 20 GPa. The thermodynamic properties of this phase were also calculated at high pressures and high temperatures using the quasi-harmonic approximation. Our LDA study on the pressure-induced phase transition sequence predicts that the CdI(2)-type TiS(2), the phase stable at ambient conditions, should transform to the cotunnite phase at 15.1 GPa, then to a tetragonal phase (I4/mmm) at 45.0 GPa. The tetragonal phase remains stable to at least 500 GPa. The existence of the tetragonal phase at high pressures is consistent with our previous findings in NiS(2) (Yu and Ross 2010 J. Phys.: Condens. Matter 22 235401). The cotunnite phase, although only stable in a narrow pressure range between 15.1 and 45.0 GPa, displays the formation of a compact S network between 100 and 200 GPa, which is evidenced by a kink in the variation of unit cell lengths with pressure. The electron density analysis in cotunnite shows that valence electrons are delocalized from Ti atoms and concentrated near the S network.


Effects of third-generation aromatase inhibitors on bone.
Low oestradiol levels in women are associated with decreased bone mineral density (BMD) and increased fracture risk. The third-generation aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane) are used in the treatment of early and advanced breast cancer and act by substantially reducing oestrogen synthesis in postmenopausal women. However, due to their mechanism of action, there is concern regarding the long-term effects of these agents on bone, particularly when used in the adjuvant setting. In this paper, the currently available data on the effects of the third-generation AIs on markers of bone turnover, BMD, and fracture risk are reviewed, with the emphasis on results in the adjuvant treatment of early breast cancer. These data suggest that both the steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs appear to affect bone turnover. Conclusions regarding any clinically relevant differences between these agents are difficult to make, and further data are awaited from long-term adjuvant use of these three agents in ongoing clinical studies. Postmenopausal women are at increased risk of osteoporosis and fracture, and the increasing use of AIs in the adjuvant treatment of postmenopausal breast cancer patients will require appropriate consideration of fracture risk, with the use of anti-osteoporotic therapies, if necessary.


A multistage neural network for color constancy and color induction.
A biologically-based multistage neural network is presented which produces color constant responses to a variety of color stimuli. The network takes advantage of several mechanisms in the human visual system, including retinal adaptation, spectral opponency, and spectrally-specific long-range inhibition. This last stage is a novel mechanism based on cells which have been described in cortical area V4. All stages include nonlinear response functions. The model emulates human performance in several psychophysical paradigms designed to test color constancy and color induction. We measured the amount of constancy achieved with both natural and artificial simulated illuminants, using homogeneous grey backgrounds and more complex backgrounds, such as Mondrians. On average, the model performs as well or better than the average human color constancy performance under similar conditions. The network simulation also displays color induction and assimilation behavior consistent with human perceptual data.


Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure.
To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism. Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye. Visual acuity testing, cycloplegic refraction, slit-lamp biomicroscopy, and ophthalmoscopy were done on every patient. Corneal topography was obtained in 40 cooperative patients. External photographs of the midface were taken in 45 children. The degree of slanting of the palpebral fissures was evaluated based on the photographs. The statistical analysis tool used was repeated measures analysis of variance. Patients in whom photographic analysis was not available were excluded from the part of the statistical analysis dealing with eyelid slant. Palpebral fissure slant (P =.013) and gender (P =.0005) were highly correlated with the obliquity of cylinder axis. There was a possible correlation between gender and eyelid slant (P =.0594), with females having slightly larger degrees of upward palpebral fissure slanting and male more downward slanting of their fissures compared to published angles in an age-matched population. We found a statistically significant correlation between the degree of total astigmatism and a larger abnormal slant (P =.0192) and between the axis and magnitude of corneal astigmatism and abnormal slant (P =.0092). Higher degrees of eyelid slant (> 8 degrees or < -4 degrees ) increased the risk of high cylinder magnitude (> 3.00 D) by an odds ratio of 4.17 (95% CI: 1.03, 19.95). Children with astigmatism with large degrees of slanting of their palpebral fissures are at higher risk for high astigmatism (> 3.00 D). The axis of the astigmatism is highly correlated with the slanting of the palpebral fissure.


Role of eicosanoids in regulation of macrophage phagocytic functions by platelet-activating factor during endotoxic shock.
We studied the role of eicosanoids in the regulation of macrophage phagocytic functions by products secreted in heterogeneous populations of macrophages and platelet-activating factor during endotoxic shock. Phagocytic activity depended on the metabolism of arachidonic acid in target macrophages and the ratio between its cyclooxygenase and lipoxygenase metabolites produced by heterogeneous populations of macrophages and affecting target cells. The regulatory effect of platelet-activating factor on phagocytosis was related to its interaction with products of the arachidonic acid cascade. Depending on the quantitative ratio of eicosanoids, platelet-activating factor produced various effects on phagocytic functions of heterogeneous macrophage populations.


[Molecular epidemiological analysis of Pseudomonas aeruginosa by pulsed-field gel electrophoresis].
In order to see the nosocomial infection by Pseudomonas aeruginosa (P. aeruginosa) in the Akita University Hospital, we analyzed the serotype and genotype for 150 strains isolated from various clinical specimens from 1994 to 1996. One hundred strains chosen at random were divided into 11 serotypes by serotyping and into 50 genotypes by pulsed-field gel electrophoresis of Spe I-digested P. aeruginosa genomic DNAs. Serotype E strains, most common, gave 17 genome patterns. Fifty strains separated periodically in certain wards had further 7 genome patterns. The strains isolated from one patient with different times or with different serotypes showed the same stable genotype. Genome patterns were inconsistent with susceptibility to antimicrobial agents. Both drug-susceptible and -resistant strains were found in strains with the same genome pattern. The genome pattern was identical, even though the susceptibility was different due to isolation time or storage. This suggested that the multidrug-resistant strains of P. aeruginosa expanded in the hospital were not derived from one original strain.


Influence of filter ventilation on the chemical composition of cigarette mainstream smoke.
Total yields of cigarette smoke constituents are greatly influenced by smoking behaviour, the tobacco blend as well as a variety of cigarette design parameters. Thereby, filter ventilation, i.e. diluting the smoke by providing a zone of microscopic holes around the circumference of the filter is one method to reduce the yield of 'tar' and other smoke compounds. However, little is known how these design variations influence the combustion conditions, and therefore, the overall chemical pattern of the smoke. In this paper single photon ionization-time-of-flight mass spectrometry (SPI-TOFMS) is used to characterize and compare cigarettes on a puff-by-puff basis, which differ only in filter ventilation magnitude. The research cigarettes investigated were made from Virginia tobacco and featured filter ventilations of 0% (no ventilation), 35%, and 70%. The cigarettes were smoked under two different puffing regimes, one using the puffing parameters of the conventional International Organization for Standardization (ISO) smoking regime and a more intense smoking condition. Results show that every variation entails a change of the chemical pattern, whereby, in general, cigarettes with 0% filter ventilation as well as the intense smoking regime lead to a more complete combustion compared to the ISO smoking conditions and the high ventilated cigarettes. Changes in the overall patterns can also be observed during the smoking for individual puffs. Some substances dominate the first puff, some species are more pronounced in the middle puffs, whereas others are preferably formed in the last puffs. This demonstrates the high complexity of the occurring processes. Results might help to understand the formation and decomposition reactions taking place when a cigarette is smoked and offer scope for targeted reduction strategies for specific toxicants or groups of toxicants in the smoke.


Characteristic single glucosinolates from Moringa oleifera: Induction of detoxifying enzymes and lack of genotoxic activity in various model systems.
Leaves of Moringa oleifera are used by tribes as biological cancer medicine. Scientific investigations with M. oleifera conducted so far have almost exclusively used total plant extracts. Studies on the activity of single compounds are missing. Therefore, the biological effects of the two main aromatic multi-glycosylated glucosinolates of M. oleifera were investigated in the present study. The cytotoxic effects of M. oleifera glucosinolates were identified for HepG2 cells (NRU assay), for V79-MZ cells (HPRT assay, SCE assay), and for two Salmonella typhimurium strains (Ames test). Genotoxic effects of these glucosinolates were not observed (Ames test, HPRT assay, and SCE assay). Reporter gene assays revealed a significant increase in the ARE-dependent promoter activity of NQO1 and GPx2 indicating an activation of the Nrf2 pathway by M. oleifera glucosinolates. Since both enzymes can also be induced via activation of the AhR, plasmids containing promoters of both enzymes mutated in the respective binding sites (pGL3enh-hNQO1-ARE, pGL3enh-hNQO1-XRE, pGL3bas-hGPX2-mutARE, pGL3bas-hGPX2-mutXRE) were transfected. Analyses revealed that the majority of the stimulating effects was mediated by the ARE motif, whereas the XRE motif played only a minor role. The stimulating effects of M. oleifera glucosinolates could be demonstrated both at the transcriptional (reporter gene assay, real time-PCR) and translational levels (enzyme activity) making them interesting compounds for further investigation.


Medication administration by caregiving youth: An inside look at how adolescents manage medications for family members.
Children take on the role of family caregiver throughout the world. No prior published research exists surrounding the particular circumstances of the task of medication administration and management by these youth, which was explored in this study. A series of focus groups were conducted using semi-structured interviews of 28 previously identified caregiving youth ages 12-19 years old who live in the United States. Data analysis followed guidelines of conventional content analysis. The following categories emerged about youth caregivers handling medications: 1) tasks involve organizational and administrative responsibilities; 2) youth have varying degrees of knowledge pertaining to these medications; 3) most share responsibility with other family members; 4) they lack formal education about their responsibilities; 5) multiple challenges exist relating to this task; 6) managing medications is associated with emotional responses; and 7) possible safety issues exist. These responsibilities represent a unique hardship and merit support and research from the medical, healthcare, legislative, and public health communities, among others.


Use of Corticosteroids in the Treatment of Patients With Diabetic Macular Edema Who Have a Suboptimal Response to Anti-VEGF: Recommendations of an Expert Panel.
Guidance on the use of corticosteroids in the treatment of diabetic macular edema (DME) is lacking. This study aimed to develop a clinically recommended treatment paradigm for DME with emphasis on the role of corticosteroids. An expert panel of nine retinal specialists in the United States developed consensus recommendations for DME treatment through a modified Delphi process. The panelists typically use intravitreal injections of vascular endothelial growth factor (VEGF) antagonists as first-line treatment of DME and switch patients with an inadequate response to anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or better because of edema after three to six monthly injections, or a less-than-50% reduction in excess macular thickness after three to four monthly injections) to intravitreal corticosteroid treatment. Intravitreal corticosteroids have a potentially useful role in the treatment of patients with DME who have an inadequate response to intravitreal anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:291-301.].


Photoconduction in amorphous organic solids.
Herein, we focus on the principles of photoconduction in random semiconductors-the key processes being optical generation of charge carriers and their subsequent transport. This is not an overview of the current work in this area, but rather a highlight of elementary processes, their involvement in modern devices and a summary of recent developments and achievements. Experimental results and models are discussed briefly to visualize the mechanism of optical charge generation in pure and doped organic solids. We show current limits of models based on the Onsager theory of charge generation. After the introduction of experimental techniques to characterize charge transport, the hopping concept for transport in organic semiconductors is outlined. The peculiarities of the transport of excitons and charges in disorderd organic semiconductors are highlighted. Finally, a short discussion of ultrafast transport and single chain transport completes the review.


Medicinal and veterinary plants of El Caurel (Galicia, northwest Spain).
A study of the medicinal and veterinary plants popularly used in El Caurel region (Lugo province, northwest Spain) and their relationships is reported. We obtained data for 85 species belonging to 31 families of vascular plants. Their vernacular names, properties, preparations, mode and popular uses are presented.


GENETIC VARIATION AND COVARIATION IN RESPONSES TO HOST PLANTS BY ALSOPHILA POMETARIA (LEPIDOPTERA: GEOMETRIDAE).
Progeny of uncommon parthenogenetic genotypes of the polyphagous geometric Alsophila pometaria were reared on four host plant species representing the same genus, different confamilial genera, and different families. On the supposition that uncommon asexual genotypes have arisen recently from the sympatric sexual population, they may be viewed as a representation of variation in the sexual population that has been captured by parthenogenesis. In both the laboratory and the field, significant effects of genotype, host, and their interaction were found for survival. Live weight displayed significant effects of genotype, host, and genotype x host interaction in the laboratory, and significant main effects in the field. The broad heritability of live weight within hosts was significantly greater than zero in all cases, ranging from 0.18 to 0.33. Heritability values in the field were similar to those in the laboratory. Genetic correlations between weight attained on pairs of host plants, calculated from uncorrected family means, were all positive and many were statistically significant. When the data were corrected for differences in generalized vigor by taking the deviations from genotype means on a standard host plant, one of nine genetic correlations was significant and positive, and one was significant and negative. Within their limits of precision, these data suggest that genetic factors enhancing performance on one host do not generally have strong antagonistic pleiotropic effects on performance on the other hosts in this population. The relevance of these observations to the evolution of resource specialization in general and host specialization by phytophagous insects in particular is discussed. The common assumption that trade-offs in efficiency of utilization cause the evolution of specialized resource use requires more empirical evidence than seems to exist.


[Colostomy as a cause of deviation colitis in a blind-ended bowel segment].
Two women aged 63 and 53 who had undergone colostomy for faecal incontinence, presented a few months later complaining of anal blood and mucous loss. On sigmoidoscopy, a previously healthy section of colorectum seemed to be inflamed. Local treatment with hydrocortisone and mesalazine and oral prednisolone did not relieve the symptoms. Subsequently the affected part of the colon was resected upon which the anal blood and mucous loss stopped. After a deviating stoma procedure, the colonic segment diverted from the faecal stream can develop signs of non-specific inflammation. The risk of colitis following the creation of a stoma is 0-50%. On systematic endoscopy 3-36 months following deviation, the risk of findings corresponding to deviation colitis is 50-100%. Symptoms are usually mild but can be so devastating that continuity of the faecal stream has to be restored or further resection is warranted.


[Shortage of supported housing for patients with mental disorder and substance abuse].
Some patients with comorbidity of severe mental illness and substance abuse--often called patients with dual diagnosis--are in need of supported housing. The extent of this need was one of the aspects of a survey conducted by the Norwegian Board of Health in 1999. Findings concerning housing from one part of the survey, which included inpatients in psychiatric hospitals and clinics, are presented in this paper. The survey was performed as a cross-sectional study of 310 dually diagnosed inpatients in Norwegian psychiatric institutions on 27 January 1999. Their housing at the time of admission, planned housing at discharge and ideal housing in the opinion of the clinician who knew the patient best--mainly a psychiatrist--were registered. At admission, 3% were living in supported housing, while such housing was planned for 10% on discharge. However, clinicians evaluated that 43% ideally were in need of supported housing, most of them with support at daytime, but a substantial number needed support night and day. The need for supported housing for patients with dual diagnosis is of significant magnitude and represents a challenge for communities as well as psychiatric services.


Cutaneous alternariosis and regional lymphadenitis during allogeneic BMT.
Alternariosis, a fungal infection resembling aspergillosis, has been described in immunocompromized and immunocompetent hosts. We report a case of cutaneous alternariosis that occurred during neutropenia in an allogeneic BMT patient receiving antifungal prophylaxis with fluconazole. Therapy required surgical excision and iv amphotericin B. Awareness of this entity may help in early diagnosis and successful therapy.


Photolytic changes in lens proteins.
Many of the age related and cataractous changes that occur in the human lens may be due to some photolytic process. These include either the direct photolysis of lens protein or photosensitized reactions involving 3-OH Kyn glucoside. The extent to which these photochemical reactions play a role is determined by the level of lens oxygen and the presence of quenchers endogenous to the lens.


[Clinical evaluation of donor renal artery reconstruction in kidney transplantation].
This retrospective study describes the experience of arterial reconstruction of donor kidney in our institute since 1982. Of total 56 living related kidney transplantations 15 required renal arterial reconstruction or ligation of donor kidneys. Renal arterial reconstruction was employed for 11 cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric artery graft interposition [3], other [1], while simple ligation was employed for 4. Bench surgery with microsurgical techniques was employed for the repair. Elective surgery was done for preoperatively defined multiple renal arteries [10] and aneurysm [1], while imperative surgery for intraoperatively detected accessory arteries [2] and surgical injuries [2]. Postoperative patency of arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy. The mean total ischemic time of reconstructed cases was 135 min., while that of ligated ones was 67 min. None of them required hemodialysis due to acute tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11 reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%). Two failure attempts of arterial reconstruction cases were all imperative ones. Postoperative GFR of the graft was well preserved in all cases. We conclude that (1) Ligation and imperative surgery tend to be associated with renal infarction, although it does not affect GFR. (2) Renal artery reconstruction was highly successful in preserving renal mass (or normal cortical image), albeit longer ischemic time than simple ligation. (3) Considering importance of preserved nephron mass in clinical renal transplantation every attempt should be made to repair the donor arterial anomalies when expected (elective) or found (imperative). (4) Thorough preoperative evaluation of donor renal arteries is mandatory.


An empirical predictive model for the spring emergence of Thecodiplosis japonensis (Diptera: Cecidomyiidae): model construction and validation on the basis of 25 years of field observation data.
The reliability of the empirical phenology model proposed by Nam et al. (2013) was tested using spring emergence data of Thecodiplosis japonensis Uchida et Inouye (Diptera: Cecidomyiidae) from 1986 to 2011 in Yeongcheon, Korea. First, the lower developmental threshold temperature (LDT) was estimated using spring emergence of T. japonensis and field temperatures. Then a degree-day model to predict spring emergence of T. japonensis was constructed, based on LDTs estimated from field observations and laboratory temperature-dependent development data. Based on field observations, the estimated LDT value for postdiapause development of T. japonensis was 6.1 degrees C, only 0.2 degrees C higher than that estimated from laboratory data. The explanatory power of the empirical degree-day model constructed on the basis of LDT from field observations was 87.2%, similar to the 87.0% of a degree-day model based on laboratory data, suggesting that both models had similar explanatory power. Furthermore, the predictions of median date of emergence in both models were only five days earlier than the observed median date in 2011. These results show that the empirical phenology model based on field observations is a reliable method for predicting the phenology of insects.


Prospective associations of vitamin D status with β-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status.
Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer β-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of β-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis.


Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare skin-tropic hematological malignancy of uncertain pathogenesis and poor prognosis. We examined 118 BPDCN cases for cytomorphology, MYC locus rearrangement, and MYC expression. Sixty-two (53%) and 41 (35%) cases showed the classic and immunoblastoid cytomorphology, respectively. Forty-one (38%) MYC+BPDCN (positive for rearrangement and expression) and 59 (54%) MYC-BPDCN (both negative) cases were identified. Immunoblastoid cytomorphology was significantly associated with MYC+BPDCN. All examined MYC+BPDCNs were negative for MYB/MYBL1 rearrangement (0/36). Clinically, MYC+BPDCN showed older onset, poorer outcome, and localized skin tumors more commonly than MYC-BPDCN. MYC was demonstrated by expression profiling as one of the clearest discriminators between CAL-1 (MYC+BPDCN) and PMDC05 (MYC-BPDCN) cell lines, and its shRNA knockdown suppressed CAL-1 viability. Inhibitors for bromodomain and extra-terminal protein (BETis), and aurora kinases (AKis) inhibited CAL-1 growth more effectively than PMDC05. We further showed that a BCL2 inhibitor was effective in both CAL-1 and PMDC05, indicating that this inhibitor can be used to treat MYC-BPDCN, to which BETis and AKis are probably less effective. Our data will provide a rationale for the development of new treatment strategies for patients with BPDCN, in accordance with precision medicine.


Diabetes risk evaluation and microalbuminuria (DREAM) studies: ten years of participatory research with a First Nation's home and community model for type 2 diabetes care in Northern Saskatchewan.
To review the DREAM studies and the role of participatory research using a Home and Community Care model in treating First Nations diabetes. Population survey, pilot and prospective randomized trial Review documented history of these studies since inception. Collation of all data from the DREAM studies from 1998 to the present, including interviews with all providers and many of the participants. The DREAM studies were a participatory process providing a needs assessment and became the foundation for this First Nation's Home and Community Care team involvement in providing community-based chronic-disease management. The findings motivated the community to find a process that would lead to needed changes. This participatory research enabled a culturally tailored algorithm of evidence-based management of hypertension and disease management strategies for people with diabetes. These studies demonstrated that in this community the Home and Community Care team could work together with primary care physicians and specialists to prevent the complications of diabetes. The DREAM studies demonstrated in the first controlled trial that with participatory research a systems change is possible; a chronic-disease management model utilizing a trained multidisciplinary Home and Community Care team and informed patients can lead to lower blood pressure in a Canadian First Nations population with diabetes.


Follow-up CT of moderately complex cystic lesions of the kidney (Bosniak category IIF).
The purpose of this study is to show the use of follow-up CT studies in the management of moderately complex cystic lesions of the kidney (Bosniak category IIF). The CT scans of 42 moderately complex cystic renal masses (Bosniak category IIF) with follow-up examinations for 2 years or greater or with pathology correlation (n = 3) were retrospectively analyzed by the authors in consensus. The complexity of each lesion was assessed on the basis of the number and appearance of the septa, wall thickness, interface with the kidney parenchyma, presence and amount of calcification, and contrast enhancement characteristics. Lesion size was measured in two dimensions. Follow-up examinations were evaluated for any interval change. The average size of the lesions was 3.9 x 3.6 cm, and the average follow-up time was 5.8 years (range, 2 years-18 years 4 months; median, 5.0 years). Eighteen lesions had fewer than five septa, 16 lesions had between five and nine septa, and eight lesions had more than nine septa. In 39 lesions, the wall or septa or both were slightly thickened, and in a single lesion, the wall and septa were hairline thin. The two remaining lesions were of uniformly high attenuation and completely intrarenal. Forty-one lesions had a sharp interface with the kidney, whereas one had an indistinct interface. Twenty lesions contained calcium. Enhancement was not shown in any lesions except for minimal enhancement of smooth walls or septa of some lesions. Follow-up examinations showed that three lesions had developed more calcification, one lesion had increased in overall size but appeared less complex, and three lesions had decreased in size. In addition, two lesions had become more complex and developed thicker septa, and these lesions proved to be cystic neoplasms. Follow-up CT studies are an effective way of managing patients with moderately complex cystic lesions of the kidney (Bosniak category IIF) because the absence of change supports benignity and progression indicates neoplasm.


Imaging of musculoskeletal soft tissue infections.
Prompt and appropriate imaging work-up of the various musculoskeletal soft tissue infections aids early diagnosis and treatment and decreases the risk of complications resulting from misdiagnosis or delayed diagnosis. The signs and symptoms of musculoskeletal soft tissue infections can be nonspecific, making it clinically difficult to distinguish between disease processes and the extent of disease. Magnetic resonance imaging (MRI) is the imaging modality of choice in the evaluation of soft tissue infections. Computed tomography (CT), ultrasound, radiography and nuclear medicine studies are considered ancillary. This manuscript illustrates representative images of superficial and deep soft tissue infections such as infectious cellulitis, superficial and deep fasciitis, including the necrotizing fasciitis, pyomyositis/soft tissue abscess, septic bursitis and tenosynovitis on different imaging modalities, with emphasis on MRI. Typical histopathologic findings of soft tissue infections are also presented. The imaging approach described in the manuscript is based on relevant literature and authors' personal experience and everyday practice.


Calcifying epithelial odontogenic tumour or Pindborg's tumour: features and behaviour in relation to a case.
The calcifying epithelial odontogenic tumour (CEOT) or Pindborg's tumour is a rare benign odontogenic neoplasm composed of epithelioid cells, amorphous amyloid-like substance and calcifications. Its clinical and radiographical pictures are not characteristic depending upon the site, size and developmental stages in a range of its composition degeneration. A case of calcifying epithelial odontogenic tumour in the mandible is presented and the main aspects of the research about this tumour, such as the pathogenesis, histological features, developmental stages, malignancy, recurrence rate, differential diagnosis and therapeutic aspects are discussed.


Nurse-led ranibizumab intravitreal injections in wet age-related macular degeneration: a literature review.
Aim The aim of this literature review was to explore the development of the role of specialist ophthalmic nurses in delivering ranibizumab intravitreal injections to patients with wet age-related macular degeneration (AMD), and to evaluate their contribution to reducing capacity pressures in medical retina services, while maintaining safe and effective standards of care. Method A systematic literature search was undertaken to identify relevant articles published between January 2000 and June 2015. A search of electronic databases was undertaken, and selected relevant journals were searched manually. A free text and subject heading search strategy was conducted, in which the abstracts of publications identified for review were assessed for relevance. Inclusion criteria were: nurses delivering ranibizumab intravitreal treatment; studies performed in the UK and other countries; and patients with AMD, diabetic macular oedema or central retinal vein occlusion receiving nurse-led ranibizumab (Lucentis) intravitreal treatment. Findings Five studies were identified from the literature search, which audited a total of 31,303 injections delivered by nurse practitioners between January 2007 and November 2013. The visual outcomes and the rate of complications from intravitreal injections delivered by trained ophthalmic nurse practitioners were comparable to intravitreal injections delivered by ophthalmologists. Four of the five studies reported increased patient satisfaction, patients consenting to nurse-delivered intravitreal injections, favourable pain experience, and absence of complaints. Conclusion Practice innovation is an example of a quality, innovation, productivity and prevention process. Role expansion, in which specialist ophthalmic nurses deliver intravitreal injections, has been shown to be economical, safe and effective. It enables timely delivery of the service, thereby preventing irreversible blindness for individuals with wet AMD.


The ultrastructure of the rabbit submandibular gland.
The secretory granules of the terminal and pre-terminal tracts of the rabbit submandibular gland display distinct features, while the cell morphology is quite similar. Among these cells, some smaller ones presenting an highly dilated endoplasmic reticulum have been identified in the pre-terminal tracts. Some hypothesis have been formulated concerning the function of these cells.


Identification of cDNAs encoding two subtypes of vitamin D receptor in flounder, Paralichthys olivaceus.
cDNAs encoding two subtypes of the vitamin D receptor (VDR) are cloned from a teleost (flounder, Paralichthys olivaceus). This is the first report of VDR subtypes in fish. Flounder VDR (fVDR) a and b share 86% identity at the amino acid level. With human (h), rat, mouse, quail, and Xenopus VDRs, fVDRa shares 72%, 71%, 71%, 69%, and 71% identity, and fVDRb shares 70%, 69%, 69%, 67%, and 68% identity, respectively. The peptide sequences of the DNA-binding domain (DBD) and hormone-binding domain (HBD) of both subtypes have particularly high homology to those of the tetrapods; e.g. 92% identity for DBP and 74% for HBD between fVDRa and hVDR. In an evolutionary tree constructed with peptide sequences of VDRs and related members of the nuclear receptor superfamily, fVDRa and b are more closely related to each other than to other molecules, and situated in the cluster of VDRs at a position which corresponds well with the evolutional position of fish in the vertebrates. Additional independent genome duplication which is thought to have occurred in ray-finned fish phylogeny may explain the existence of two subtypes of VDR in flounder.


Recent advances in the role of supramolecular hydrogels in drug delivery.
Supramolecular hydrogels, formed by noncovalent crosslinking of polymeric chains in water, constitute an interesting class of materials that can be developed specifically for drug delivery and biomedical applications. The biocompatibility, stimuli responsiveness to various external factors, and powerful functionalization capacity of these polymeric networks make them attractive candidates for novel advanced dosage form design. This review summarizes the significance of supramolecular hydrogels in various biomedical and drug delivery applications. The recent advancement of these hydrogels as potential advanced drug delivery systems (for gene, protein, anticancer and other drugs) is discussed. The importance of these hydrogels in biomedical applications, particularly in tissue engineering, biosensing, cell-culture research and wound treatment is briefly described. The use of supramolecular hydrogels in drug delivery is still in very early stages. However, the potential of such a system is undeniably important and very promising. A number of recent studies have been conducted, which mainly focus on the use of cyclodextrin-based host-guest complex as well as other supramolecular motifs to form supramolecular hydrogels for delivery of various classes of drugs, therapeutic agents, proteins and genes. However, there are still plenty of opportunities for further development in this area for drug delivery and other biomedical applications.


The variation in anti-ENA characteristics between different ethnic populations with systemic lupus erythematosus over a 10-year period.
To assess how anti-ENA characteristics change in patients with systemic lupus erythematosus from different ethnic backgrounds over a 10-year period follow-up study. There were 61 patients, of whom 37 were Caucasian, 12 were Asian and 12 were Afro-Caribbean. At the first available bleed 12/37 (32%) Caucasians were anti-ENA positive compared to 6/12 (50%) Asians and 9/12 (75%) of Afro-Caribbeans (Chi-squared P=0.01 for Caucasian vs Afro-Caribbean) and these proportions remained essentially unchanged after 10 y of follow-up. However, over the 10 y of follow-up anti-ENA patterns did change, with anti-Ro being the commonest antibody pattern to emerge and anti-Ro/La the commonest antibody pattern to disappear. There were 20/37(54%) Caucasians, 1/12(8%) Afro-Caribbeans and 5/12(42%) Asians who remained negative for anti-ENA throughout the 10-year follow-up (Chi-squared P=0.03 for Caucasian vs Afro-Caribbean). Anti-ENA were more commonly found in the Afro-Caribbean than the Caucasian population. The commonest patterns of anti-ENA differ between ethnic groups and, over a 10-year period, anti-ENA patterns in individual patients changed in a significant number of individuals. However, Caucasians were more likely to remain anti-ENA negative over 10 y of follow-up than Afro-Caribbeans.


[Copy number variation is a new form of genomic diversity].
This is a short review of recently described copy number variation of some segments of DNA. The origin of this phenomenon, the localization of these segments and their possible role in regulation of gene expression are discussed. The copy number variation should be regarded as a new form of genomic diversity.


Anomalous renal arteries and its clinical implications.
Often, the accessory renal arteries are observed near the hilum. Presence of anomalous accessory renal arteries may be associated with other underlying renal pathological conditions. We detected anomalous pattern of the renal arteries, in a 51 year old male cadaver, during routine undergraduate teaching program, in the department of Anatomy. The left renal artery originated at the level of the second lumbar vertebra and gave off two branches and each branch bifurcated into two branches which were destined to supply the suprarenal gland and the left kidney. However, the right renal artery displayed an early extra-renal division into two branches. The upper branch was found traversing to the upper pole, whereas the lower branch reached renal hilum by passing posterior to the renal pelvis. Anatomical description of this anomalous pattern of renal vasculature is presented in this case report, highlighting its clinical implications (Fig. 2, Ref. 10). Full Text (Free, PDF) www.bmj.sk.


Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood eosinophils and neutrophils.
Intercellular adhesion molecule 3 (ICAM-3) is highly expressed on human granulocytes, including eosinophils and neutrophils, but the functions of ICAM-3 in these cells are not well understood. Our studies test the hypothesis that ICAM-3 regulates granulocyte apoptosis. Intercellular adhesion molecule 3 was activated by a mAb that recognizes an ICAM-3 epitope that binds its ligand, CD11a/CD18. In some experiments with eosinophils, recombinant human IL-5 or GM-CSF was added to mimic in vivo antiapoptotic conditions. Staining with annexin V-fluorescein isothiocyanate and propidium iodide identified apoptotic cells. Binding of ICAM-3 increased apoptosis of both eosinophils (18 and 48 hours) and neutrophils (18 hours). At 18 hours, eosinophil apoptosis increased from 31.4% +/- 3.5 SE (IgG control) to 45.2% +/- 3.8 SE (anti-ICAM-3), and neutrophil apoptosis increased from 48% +/- 4.1 SE (IgG control) to 55.3% +/- 4.5 SE (anti-ICAM-3). At 48 hours, eosinophil apoptosis increased 2-fold under baseline conditions and also in the presence of recombinant human IL-5 or GM-CSF. In both eosinophils and neutrophils, incubation with a blocking antibody against CD18 integrins blunted ICAM-3-induced apoptosis. In eosinophils, blocking peptides for caspases 8 and 9, proteases critical to apoptosis, also decreased ICAM-3-induced apoptosis to control levels. Through its effect on eosinophil and neutrophil apoptosis, ICAM-3 may be an important anti-inflammatory molecule that can oppose the proinflammatory effects of IL-5 and GM-CSF. These findings provide a mechanism for apoptotic clearance of eosinophils and neutrophils involved in allergic inflammation that, unlike necrosis, does not cause nonspecific tissue injury.


p53 linear diffusion along DNA requires its C terminus.
In cells, sequence-specific transcription factors must search through an entire genome to find their target sites in promoters. Such sites may be identified by using one-dimensional (linear diffusion) and/or three-dimensional (association/dissociation) mechanisms. We show here that wild-type p53 possesses the ability to linearly diffuse on DNA. p53 lacking its C terminus is incapable of such sliding along DNA, while the isolated C terminus of p53 is even more effective than the full-length protein at one-dimensional linear diffusion. Importantly, neither acetylation-mimicking mutations nor phosphorylation of residues within the C terminus stimulates linear diffusion by p53. Supporting these in vitro observations, we found that C-terminally deleted p53 (p53Delta30) expressed at physiological levels is deficient in binding to and transactivating downstream promoters in vivo. Therefore, our data show that the C terminus is a positive regulator of DNA binding in vivo and in vitro, and indicate that the mechanism may involve linear diffusion.


Cross-column prediction of gas-chromatographic retention of polychlorinated biphenyls by artificial neural networks.
In this paper, we build a multiple-column retention model able to predict the behaviour of polychlorinated biphenyls (PCBs) in capillary gas-chromatography (GC) within a wide range of separation conditions. To this end, GC retention is related to both chemical structure of PCBs, encoded by selected theoretical molecular descriptors, and the kind of stationary phase, represented by the relative retention time (RRT) of a suitable small number of analytes. The model was generated using the retention data of 70 PCBs extracted from the pool of the 209 possible congeners collected on 17 different capillary columns featured by non-polar or moderately polar stationary phases, reported in the literature. Multilinear regression combined with genetic algorithm variable selection was preliminarily applied to generate a four-dimensional quantitative structure-retention relationship (QSRR) for each of the 17 columns, based on theoretical molecular descriptors extracted from the large set provided by the software Dragon. 33 molecular descriptors obtained by merging the non-common descriptors of various single-column QSRRs, combined with RRTs values of the less and the most retained PCB, were considered as the starting independent variables of the multiple-column retention model. A multi-layer artificial neural network (ANN), optimised on a validation set extracted from the calibration data, was applied to generate the multi-column retention model. The influence of starting inputs on the network output was evaluated by a sensitivity analysis and model complexity was reduced through a step-wise elimination of redundant molecular descriptors, while RRTs of further PCBs were included to improve description of the stationary phase. Nine molecular descriptors and RRTs of eight selected PCBs are considered as the independent variables of the final ANN-based model, whose predictive performance was tested on the 139 PCBs excluded from calibration and on six external columns and/or temperature programs.


[Prenatal ultrasonic diagnosis of skeletal malformations].
Two cases of skeleton malformations found by ultrasonic diagnostics are described. One was osteogenesis imperfecta and other achondroplasia. The possibility of malformation was postulated in 36th gestation week in the first case, and in 37th gestation week in the second. The authors discuss on malformations and their early diagnosis.


Transport proteins of the ABC family and multidrug resistance of tumor cells.
Some new data concerning the role of transport proteins of the ABC family in multidrug resistance (MDR) of human tumor cells, and problems connected with regulation of these proteins are considered. MDR is a complex phenomenon that may be caused simultaneously by several mechanisms functioning in one and the same cell. Among them there may be the alterations of activity of several transport proteins. Activation of these proteins may be associated with alterations of activities of different cell protective systems and of the signal transduction pathways involved in regulation of proliferation, differentiation, and apoptosis. Clinical significance of multifactor MDR is discussed.


[Clear-cell tumor of the lung].
An observation of a clear-cell lung tumour in a girl of 14 is described. The segment of the right lung with the tumour, 3 cm in diameter, was removed during the operation. Histologically, the tumour node consisted of clear cells with a number of thin-walled vessels and rare branching tubular structures lined with monolayer epithelium. Glycogen but no lipids or argyrophilic neurosecretory granules were found in the cytoplasm of tumour cells. The neoplasm is considered to be a hamartoma.


Advanced Imaging Techniques of the Skull Base.
Although conventional imaging can depict the anatomy of the head and neck with exquisite detail, it often falls short in its ability to characterize tissue physiology and abnormality; this is especially seen in the posttherapy setting where benign posttreatment changes and recurrent tumors can show intense postcontrast enhancement and similar features on conventional imaging. Advanced imaging can evaluate tissue physiology and, along with conventional imaging, provide a more accurate assessment of the skull base. This article describes the technical details and clinical applications of different advanced imaging techniques with a primary focus on diffusion-weighted imaging.


The ICF Core Sets for hearing loss: researcher perspective, Part II: Linking outcome measures to the International Classification of Functioning, Disability and Health (ICF).
To link outcome measures used in audiological research to the ICF classification and thereby describe audiological research from the ICF perspective. Through a peer-reviewed or a joint linking procedure, link outcome measures to the ICF classification system using standardized ICF linking rules. Additional linking rules were developed in combination with the established rules to overcome difficulties when connecting audiological data to ICF. Absolute and relative frequencies of ICF categories were reported. The identified outcome measures from the previous study (Part I) constituted the empirical material. In total, 285 ICF categories were identified. The most prevalent categories were related to listening, hearing functions, auditory perceptions, emotions and the physical environment, such as noise and hearing aids. Categories related to communication showed lower relative frequencies, as did categories related to the social and attitudinal environment. Based on the linked outcome measures, communication as a research topic is subordinated to other research topics. The same conclusion can be drawn for research targeting the social and attitudinal environment of adults with HL. Difficulties in the linking procedure were highlighted and discussed, and suggestions for future revisions of the ICF from the audiological perspective were described.


Highly active analogs of 1alpha,25-dihydroxyvitamin D(3) that resist metabolism through C-24 oxidation and C-3 epimerization pathways.
The secosteroid hormone 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] is metabolized in its target tissues through modifications of both the side chain and the A-ring. The C-24 oxidation pathway, the main side chain modification pathway is initiated by hydroxylation at C-24 of the side chain and leads to the formation of the end product, calcitroic acid. The C-23 and C-26 oxidation pathways, the minor side chain modification pathways are initiated by hydroxylations at C-23 and C-26 of the side chain and lead to the formation of the end product, calcitriol lactone. The C-3 epimerization pathway, the newly discovered A-ring modification pathway is initiated by epimerization of the hydroxyl group at C-3 of the A-ring to form 1alpha,25(OH)(2)-3-epi-D(3). A rational design for the synthesis of potent analogs of 1alpha,25(OH)(2)D(3) is developed based on the knowledge of the various metabolic pathways of 1alpha,25(OH)(2)D(3). Structural modifications around the C-20 position, such as C-20 epimerization or introduction of the 16-double bond affect the configuration of the side chain. This results in the arrest of the C-24 hydroxylation initiated cascade of side chain modifications at the C-24 oxo stage, thus producing the stable C-24 oxo metabolites which are as active as their parent analogs. To prevent C-23 and C-24 hydroxylations, cis or trans double bonds, or a triple bond are incorporated in between C-23 and C-24. To prevent C-26 hydroxylation, the hydrogens on these carbons are replaced with fluorines. Furthermore, testing the metabolic fate of the various analogs with modifications of the A-ring, it was found that the rate of C-3 epimerization of 5,6-trans or 19-nor analogs is decreased to a significant extent. Assembly of all these protective structural modifications in single molecules has then produced the most active vitamin D(3) analogs 1alpha,25(OH)(2)-16,23-E-diene-26,27-hexafluoro-19-nor-D(3) (Ro 25-9022), 1alpha,25(OH)(2)-16,23-Z-diene-26,27-hexafluoro-19-nor-D(3) (Ro 26-2198), and 1alpha,25(OH)(2)-16-ene-23-yne-26,27-hexafluoro-19-nor-D(3) (Ro 25-6760), as indicated by their antiproliferative activities.


Epidemiology of Respiratory Syncytial Virus-related Hospitalizations and the Influence of Viral Coinfections in Southern Austria in a 7-year Period.
The aim of this study was to determine the respiratory syncytial virus (RSV) epidemiology and to analyze the influence of risk factors and coinfections over the last years. Retrospectively all infants, children and adolescents hospitalized due to respiratory disease with positive RSV test [hospitalized for RSV infection (RSV-H)] between January 1, 2009, and December 31, 2015, at a tertiary care center in the southern part of Austria were included for analysis. Patients were all identified by a search via International Classification of Diseases and Related Health Problems, 10th Edition codes, and all medical data were collected from the local electronic databases called openMedocs. RSV tests had to prove true infection case definition. During a 7-year study period, 745 infants, children and adolescents exhibited RSV-H. Main diagnosis was bronchiolitis (70%). Nearly half of all cases (44%) were born during the first half of the RSV season (November-January), and seasonal peak of RSV-H was in January. Predominant underlying condition was history of prematurity in 15% followed by neurologic impairment (3.5%) and hemodynamically significant congenital heart disease (2.95%). Age ≤2 months and underlying conditions/morbidities were associated with more severe disease. The majority of cases (96%) had an age below 24 months, and 91% below 12 months. Viral coinfection (most common influenza virus, adenovirus and rhinovirus) was diagnosed in 37 cases (5%) resulting in a more severe course of disease. Main risk factors of coinfection were siblings and crowding. Mortality was 0.27% (2/745). Both children had coinfection with influenza A virus and were multihandicapped (15 and 20 years of age, respectively). Prematurity and underlying morbidities play a marked role in RSV-H. Viral coinfections aggravated disease with death in 2 multihandicapped adolescents.


Contributions of basal and post-prandial hyperglycaemia to micro- and macrovascular complications in people with type 2 diabetes.
People with Type 2 diabetes mellitus are at high risk of cardiovascular disease and microvascular complications. A number of epidemiological studies have shown a strong relationship between the prevalence of vascular complications and raised levels of plasma glucose and glycated haemoglobin (HbA(1c)). Accumulating evidence supports the superior independent prognostic importance of the post-challenge glucose level, measured either 1 or 2 h after a glucose load. Thus, data from studies conducted in Europe, the USA, and particularly the Pacific rim and South Asia suggest that 2-h glucose is a better predictor of cardiovascular and all-cause mortality than pre-breakfast glucose, both in people with diabetes and those with pre-diabetic impaired glucose tolerance (IGT). Pathophysiological studies suggest that post-prandial rises in hyperglycaemia can trigger endothelial damage through multiple mechanisms, including increased oxidative stress and the increased expression of atherogenic circulating adhesion molecules and inflammatory cytokines that induce and regulate cell recruitment, migration, growth, and proliferation. Optimal pharmacological control of meal-time glucose levels can help to lower the HbA(1c) and thus may reduce the incidence of vascular complications in many people with diabetes. Moreover, emerging evidence suggests that reducing meal-time hyperglycaemia may delay the progression from pre-diabetic states toward overt diabetes. This review (based on MEDLINE searches, 1980-2005) examines the evidence linking the microvascular and macrovascular complications of diabetes and glycaemic control, assesses the relative contributions of basal and meal-time concentrations, and considers the implications for optimal treatment for people with Type 2 diabetes or with prediabetic IGT.


Current strategies to streamline pharmacotherapy for older adults.
Although the term "personalized medicine" has been associated in many cases with pharmacogenomics, its definition embraces the use of specific biomarkers and covariates to help in the selection of medical treatments and procedures which are best for each patient. While several efforts have been performed for the tailored selection of therapies and dosing regimens in the general population, developing personalized medicine initiatives for elderly patients remains understudied. The personalized drug therapy for older patients requires the consideration of anatomical, physiological and functional alterations in a multimorbid setting requiring multiple medications. The present review focuses on currently employed qualitative and quantitative precision medicine approaches for elderly patients and discusses some of the associated challenges and limitations. Furthermore, the use of and confidence in physiologically-based approaches for optimal dose selection in this understudied yet clinically important patient population will be highlighted and discussed.


Recurrent necrotizing fasciitis of the vulva. A case report.
Necrotizing fasciitis most often occurs in the context of prior trauma or surgery. Predisposing medical conditions include diabetes mellitus, arteriosclerosis, obesity, hypertension and prior irradiation. De novo occurrence in the vulva, in the absence of prior injury, surgery or irradiation, has been reported rarely. Necrotizing fasciitis of the vulva in the diabetic patient may have an insidious onset but requires an early diagnosis and aggressive surgical episode of fasciitis occurred in an obese, diabetic woman. Aggressive, wide excision of all infected vulvar, mons and thigh tissue, followed by aggressive medical and surgical postoperative care, resulted in minimal morbidity. Prompt recognition and aggressive care are required to treat this condition.


The role of ocular torsion on the etiology of A and V patterns.
Theoretically, the torsion of the globe produced by primary oblique overaction results in a vertical displacement of the insertions of the horizontal recti and a horizontal displacement of the insertions of the vertical recti. This should alter the vectors of the forces exerted on the globe by the rectus muscles so that the horizontal recti become partial elevators or depressors and the vertical recti become increasing abductors or adductors. This change in force vectors tends to enhance the A or V pattern that results from oblique dysfunction. I propose that the etiology of A and V patterns is the result of a complex interplay between all of the extraocular muscles and present a clinical series to suggest the validity of that theory.