Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia.
Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34(+) enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 microg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils > or = 0.5 x 10(9)/l and platelets > or = 20 x 10(9)/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan-Meier estimate of survival was 83.9% (95% CI, 70.1-95.2%) with a median follow-up duration of 33.5 (6-44) months. CD34(+)-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients.


Ribonucleotide reduction and the possible role of cobalamin in evolution.
The biological pathways of ribonucleotide reduction are briefly reviewed. The hypothesis is presented that reduction of ribonucleoside triphosphates to their deoxynucleotide analogs through the mediation of vitamin B12 or a similar corrinoid preceded and was necessary for the subsequent development of a DNA-type genome. There are two known biological systems for ribonucleotide reduction: (1) The ribonucleoside diphosphate reduction system which utilizes a nonheme iron ribonucleotide reductase enzyme, thioredoxin and its reductase, and NADPH. This enzyme complex is found in most bacteria, some higher organisms, and in all animals. (2) The ribonucleoside triphosphate reduction system which utilizes adenosyl cobalamin, ribonucleotide reductase and either thioredoxin or a disulfhydryl compound. The cobalamin-dependent reductase is restricted to a few species of bacteria and blue-gree algae. This system is considered more primitive than the iron reductase one based on their differences in distribution, components, and products.


58,000 dalton intermediate filament proteins of neuronal and nonneuronal origin in the goldfish visual pathway.
A group of proteins in the goldfish optic nerve with a molecular weight of 58K daltons was analyzed by two-dimensional gel electrophoresis. Results show that the proteins are differentially phosphorylated and found exclusively in a cytoskeletal-enriched fraction. The proteins from this fraction can be reconstituted into typical intermediate filament structures, as shown by electron microscopy. Two components which are of neuronal origin are transported within the slow phase of transport. The 58K proteins are the most abundant proteins in the optic nerve, and they are distinct from actin and tubulin. It was concluded that they are intermediate filament proteins. Cytoskeletal preparations of rat spinal cord, rat optic nerve, and goldfish optic nerve were compared by one-dimensional gel electrophoresis. The rat spinal cord contains glial fibrillary acidic protein (GFAP), and the rat optic nerve contains vimentin and GFAP, in addition to the neurofilament triplet. A typical mammalian neurofilament triplet is not detected in the goldfish optic nerve, while the major cytoskeletal constituent is a 58K band which coelectrophoreses with vimentin in the rat optic nerve by one-dimensional gel electrophoresis.


Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity.
Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.


A common spatial factor analysis model for measured neighborhood-level characteristics: The Multi-Ethnic Study of Atherosclerosis.
The purpose of this study was to reduce the dimensionality of a set of neighborhood-level variables collected on participants in the Multi-Ethnic Study of Atherosclerosis (MESA) while appropriately accounting for the spatial structure of the data. A common spatial factor analysis model in the Bayesian setting was utilized in order to properly characterize dependencies in the data. Results suggest that use of the spatial factor model can result in more precise estimation of factor scores, improved insight into the spatial patterns in the data, and the ability to more accurately assess associations between the neighborhood environment and health outcomes.


Electroacupuncture pretreatment promotes angiogenesis via hypoxia-inducible factor 1α and vascular endothelial growth factor in a rat model of chronic myocardial ischemia.
Electroacupuncture (EA) pretreatment appears useful in the treatment of chronic myocardial ischemia (CMI). The goal of this study was to investigate the effect of EA preconditioning on the regulation of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) proteins in a CMI model of vascular regeneration. A CMI model was established by subcutaneous injection of isoprinosine hydrochloride (ISO) for 14 days in 45 Wistar rats, which had been randomly divided into a model group (n = 15), a CMI group pretreated with sham EA for 21 days (CMI + Sham group, n = 15) and a CMI group pretreated with verum EA for 21 days (CMI + EA, n = 15) prior to modeling. An additional 15 Wistar rats received 0.9% sodium chloride via intraperitoneal injection for 14 consecutive days (control group). Serum levels of VEGF and HIF-1α were measured by ELISA, while protein expression of VEGF and HIF-1α in the area of myocardial infarction was measured by Western blotting. The area of myocardial infarction and fibrosis of the myocardial tissue in the study groups were visualized by hematoxylin-eosin (HE) staining and Masson staining, respectively. EA pretreatment improved cardiac function by regulating left ventricular end-diastolic diameter and left ventricular end-systolic diameter, left ventricular ejection fraction and the ST segment voltage of the electrocardiogram. EA pretreatment promoted vascular regeneration by increasing serum levels of VEGF and HIF-1α and by increasing protein expression of HIF-1α and VEGF in the infarcted region of the myocardium, leading to a reduction in the area of myocardial infarction on HE staining and reduction of myocardial fibrosis on Masson staining. EA pretreatment promotes protein expression of HIF-1α and VEGF in areas of ischemic myocardium, which may represent useful biomarkers for coronary collateral establishment and offer potential targets for therapeutic angiogenesis in patients with CMI.


Understanding ploidy complex and geographic origin of the Buchloe dactyloides genome using cytoplasmic and nuclear marker systems.
Characterizing and inferring the buffalograss [Buchloe dactyloides (Nutt.) Engelm.] genome organization and its relationship to geographic distribution are among the purposes of the buffalograss breeding and genetics program. This buffalograss study was initiated to: (1) better understand the buffalograss ploidy complex using various marker systems representing nuclear and organelle genomes; (2) determine whether the geographic distribution was related to nuclear and organelle genome variation; and (3) compare the genetic structure of accessions with different ploidy levels. The 20 buffalograss genotypes (15 individuals from each genotype) that were studied included diploid, tetraploid, pentaploid, and hexaploid using nuclear (intersimple sequence repeat (ISSRs), simple sequence repeat (SSRs), sequence related amplified polymorphism (SRAPs), and random amplified polymorphic DNA (RAPDs)) and cytoplasmic markers (mtDNA and cpDNA). There was a significant correlation between the ploidy levels and number of alleles detected using nuclear DNA (ISSR, SSR, and SRAP, r = 0.39, 0.39, and 0.41, P<0.05, respectively), but no significant correlation was detected when mitochondrial (r = 0.17, P<0.05) and chloroplast (r = 0.11, P < 0.05) DNA data sets were used. The geographic distribution of buffalograss was not correlated with nuclear and organelle genome variation for the genotypes studied. Among the total populations sampled, regression analysis indicated that geographic distance could not explain genetic differences between accessions. However, genetic distances of those populations from the southern portion of buffalograss adaptation were significantly correlated with geographic distance (r= 0.48, P<0.05). This result supports the hypothesis that genetic relationship among buffalograss populations cannot be estimated based only on geographic proximity.


Competition between photobleaching and fluorescence increase of photosensitizing porphyrins and tetrasulphonated chloroaluminiumphthalocyanine.
The time-dependent fluorescence changes of photosensitizing porphyrins and tetrasulphonated chloroaluminiumphthalocyanine (A1C1SPc) were measured at different intracellular sites using video-enhanced microscopy and image processing. To obtain variations in intracellular fluorescence intensity, different radiant exposures of a Kr+ laser-pumped dye laser were delivered via a 600 microns plastic-clad silica fibre connected to the microscope. During irradiation, competition between photobleaching and fluorescence increase of the different dyes was observed. The porphyrins normally showed photobleaching, which was dependent on the sensitizer and its specific accumulation within the cell. Photobleaching was less pronounced for hydrophilic uroporphyrin than for more hydrophobic dyes. In contrast with an almost exponential decrease in porphyrin fluorescence with increasing light dose, the fluorescence intensity of A1C1SPc significantly increased at the beginning of irradiation, and could be correlated with intracellular deaggregation.


Relationship between perceived stress, stress coping strategies, and clinical status in patients with rheumatoid arthritis.
Coping with a chronic disease such as rheumatoid arthritis (RA) involves significant changes in life and promotes stressful situations. The inability to cope with stress can contribute to the lack of effectiveness of therapy. The aim of this study was to evaluate the relationship between perceived stress, coping strategies, and the clinical status of RA patients determined by C-reactive protein (CRP) and Disease Activity Score (DAS28). 165 subjects were studied, 84 of them had RA and the rest were controls. Standardised questionnaires were used: the Inventory for the Measurement of Coping Strategies (Mini-COPE) and the Perceived Stress Scale (PSS-10). A self-administered questionnaire was used to collect sociodemographic data. The blood levels of protein CRP and cortisol were determined. DAS28 was obtained from medical records. The study was cross-sectional. The mean severity of perceived stress PSS-10 was not significantly different between the control and study groups. RA patients most often used coping strategies such as active coping, planning, and acceptance. Compared to the control group, they used the strategy of turning to religion significantly more often (1.8 vs 1.4; p = 0.012). Women with RA who had higher cortisol levels were more likely to use positive reevaluation, seeking emotional support and instrumental support, as well as the denial strategy. In men with RA, high stress was associated with twice as high CRP levels compared to patients with low stress (p = 0.038). As the levels of CRP protein levels (p = 0.009) and the DAS28 index (p = 0.005) increased, patients were more likely to use a denial strategy.


An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse.
Deciphering the mechanisms that govern skeletal muscle plasticity is essential to understand its pathophysiological processes, including age-related sarcopenia. The voltage-gated calcium channel CaV1.1 has a central role in excitation-contraction coupling (ECC), raising the possibility that it may also initiate the adaptive response to changes during muscle activity. Here, we revealed the existence of a gene transcription switch of the CaV1.1 β subunit (CaVβ1) that is dependent on the innervation state of the muscle in mice. In a mouse model of sciatic denervation, we showed increased expression of an embryonic isoform of the subunit that we called CaVβ1E. CaVβ1E boosts downstream growth differentiation factor 5 (GDF5) signaling to counteract muscle loss after denervation in mice. We further reported that aged mouse muscle expressed lower quantity of CaVβ1E compared with young muscle, displaying an altered GDF5-dependent response to denervation. Conversely, CaVβ1E overexpression improved mass wasting in aging muscle in mice by increasing GDF5 expression. We also identified the human CaVβ1E analogous and show a correlation between CaVβ1E expression in human muscles and age-related muscle mass decline. These results suggest that strategies targeting CaVβ1E or GDF5 might be effective in reducing muscle mass loss in aging.


The ion implantation-induced properties of one-dimensional nanomaterials.
Nowadays, ion implantation is an extensively used technique for material modification. Using this method, we can tailor the properties of target materials, including morphological, mechanical, electronic, and optical properties. All of these modifications impel nanomaterials to be a more useful application to fabricate more high-performance nanomaterial-based devices. Ion implantation is an accurate and controlled doping method for one-dimensional nanomaterials. In this article, we review recent research on ion implantation-induced effects in one-dimensional nanostructure, such as nanowires, nanotubes, and nanobelts. In addition, the optical property of single cadmium sulfide nanobelt implanted by N+ ions has been researched.


Impact of the fungus Balansia henningsiana on Panicum agrostoides: frequency of infection, plant growth and reproduction, and resistance to pests.
The impact of the systemic fungus Balansia henningsiana (Clavicipitaceae) on the grass Panicum agrostoides was examined in field and greenhouse studies comparing infected and uninfected plants. Approximately one-half of all plants in three populations located in southern Indiana were infected. In field samples and greenhouse studies infected plants were significantly heavier than uninfected plants and produced significantly more tillers. Infection tended to suppress flowering but occasional asymptomatic tillers on infected plants produced healthy inflorescences. Although infected plants produced fewer inflorescences than uninfected plants as a proportion of total tillers, absolute numbers of inflorescences were similar in the two groups. Because other grasses infected by different species of Balansia and related fungi often are more resistant to insect damage, pest damage was quantified in one population. No differences between infected and uninfected plants were detected in levels of herbivory but infected plants had significantly less damage by the common leaf spot fungus Alternaria triticina. The results suggest that there is no selective disadvantage for plants infected by B. henningsiana.


Impact of androgen deprivation therapy on sexual function.
Many patients with prostate cancer for whom androgen deprivation therapy (ADT) is indicated are young and desire to remain sexually active. In such patients, the side effects of androgen therapy on sexual function can be a source of serious reduction in overall quality of life. Providing the appropriate treatment options in this patient population is therefore essential. Nevertheless, treating such patients is challenging and an understanding of the underlying mechanisms of sexual physiology and pathophysiology is crucial to optimal patient care. In this paper, we reviewed what was known regarding the effects of ADT on sexual function in animal models and we also provided a detailed review on the effects of ADT on sexual health in humans and its treatment.


Decalcification of teeth in a microwave oven.
The effects of microwave radiation in reducing decalcification time were evaluated by measuring rates of calcium removal from samples of rat and cat teeth in 0.1 mol l-1 EDTA. In some cases, 3% glutaraldehyde was added to the decalcifying solution. Test specimens were placed in a microwave oven at 39 +/- 2 degrees C for repeated periods of 1-2 h. Control specimens were placed in a conventional oven at 39 degrees C for the same times or held at room temperature. The calcium removed during each treatment was measured using an atomic absorption spectrophotometer. There was no consistent difference between the results obtained with microwave radiation as compared with heating in a conventional oven, although in both cases decalcification was slightly faster than at room temperature. These results are attributed to thermal effects. No evidence for non-thermal effects of micro-radiation was found.


A junction-dependent mechanism drives murine mammary cell intercalation for ductal elongation.
The luminal epithelium of the mammary gland is organized into monolayers; however, it originates from multilayered terminal end buds (TEBs) during development. Although apoptosis provides a plausible mechanism for cavitation of the ductal lumen, it doesn't account for ductal elongation behind TEBs. Spatial calculations in mice suggest that most TEB cells integrate into the outermost luminal layer to generate elongation. We developed a quantitative cell culture assay that models intercalation into epithelial monolayers. We found that tight junction proteins play a key role in this process. ZO-1 puncta form at the new cellular interface and resolve into a new boundary as intercalation proceeds. Deleting ZO-1 suppresses intercalation both in culture and in cells transplanted into mammary glands via intraductal injection. Cytoskeletal rearrangements at the interface are critical for intercalation. These data identify luminal cell rearrangements necessary for mammary development and suggest a mechanism for integration of cells into an existing monolayer.


A tribute to Jean Lindenmann, co-discoverer of interferon (1924-2015).
In 1957, the discovery of interferon was reported by Isaacs and Lindenmann in the prestigious journal Proceedings of the Royal Society (1957) [1,2]. This discovery was definitely one of the scientific landmarks in cell biology of the past century. It was the result of an initially unplanned and amazingly creative collaboration with Alick Isaacs that lasted from July 1956 to June 1957 at Mill Hill in London. Jean Lindenmann died in Zürich on January 15, 2015, at the age of 90, after having survived Alick Isaacs (1921-1967) for almost five decades.


[The preparation and the in vitro release of OANO-1 microspheres].
To prepare OANO-1 microspheres and test their release in vitro. OANO-1 microspheres were made by W/O/W-liquid drying process. The surface morphology of the microspheres was observed by SEM. The mean diameter and the size distribution of microspheres, the drug loading and the incorporation efficiency were examined. The release of OANO-1 microspheres in vitro was examined by small cup method. The accumulated release percent of OANO-1 microspheres was examined. The OANO-1 microspheres were regular in their morphology. The average particle size was 8.59 microm with over 90% of the microspheres being in the range of 1-12 microm. The drug loading and the incorporation efficiency were 48.39% and 19.32% respectively. The accumulated release percent of OANO-1 microspheres was 78.4% after 108 h. The release half-life t1/2 was 40.8 h and Higuchi equation was Y = 0.1326 X - 0.4782, r = 0.9951. The preparation of OANO-1 microspheres was well. The release in vitro of OANO-1 microspheres showed significant sustained release.


Two Ribosomes Are Better Than One... Sometimes.
In this issue of Molecular Cell, Meydan and Guydosh present an elegant and rigorous addition to the exciting investigation of the roles played by ribosome collisions in eukaryotic translation and cellular homeostasis.


Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial.
Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. Clinical Trials.gov NCT01607060, registered 24 May 2012.


Influence of coralline hydroxyapatite used as an ocular implant on the dose distribution of external beam photon radiation therapy.
Coralline hydroxyapatite spheres are used as buried integrated ocular implants after enucleation or evisceration surgery. Because such implants are used after surgery for intraocular malignancy and because some patients may require postoperative radiation therapy for orbital tumor recurrence, the radiation attenuation characteristics of the implant are of interest. The authors evaluated the attenuation and scattering properties of coralline hydroxyapatite implants using a 4 MV photon beam and film dosimetry. Optical density analyses indicate that coralline hydroxyapatite implants have no significant influence on the attenuation or scattering properties of the photon beam. As such, there is no basis for concern that such implants might adversely affect external beam photon irradiation.


Complete nucleotide sequence of RNA 3 from alfalfa mosaic virus, strain S.
We report the sequence of RNA 3 from strain S of Alfalfa mosaic virus (2,055 nucleotides). This RNA codes for a 32.4 kd protein (P3) and for the 24 kd coat protein (P4). The largest part of the sequence was established using RNA sequencing methods. The completion of the sequence in the region coding for P3 was achieved with cloned cDNA synthesized after priming at internal sites of RNA 3. Comparison of the RNA sequences coding P3 and P4 proteins in strain S with those reported in the literature for strain 425 revealed a higher amino acid substitution rate (3%) for P3 than for P4 (congruent to 1%) despite a similar average base substitution of 3-4% in these regions. In P3, two out of nine amino acid changes occur in hydrophilic regions. The amino acid changes in P4 do not modify the local hydrophilicity distribution. The intercistronic region displays a low degree of base substitution (2%) when compared with the untranslated 3'-end region (3.6%) or the 5'-end leader region (8%), the average substitution rate being 3.2%.


Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period.
Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy.


Decreased susceptibility of Malassezia furfur to UV light by synthesis of tryptophane derivatives.
Recently, tryptophane (Trp)-dependent synthesis of pigments and fluorochromes in Malassezia furfur was described. The possible significance of this metabolic pathway for the microorganism remains to be explored. Since the upper parts of the human epidermis are a natural habitat of M. furfur, increased exposure to UV light may be hazardous. Five reference strains and one wild type strain of M. furfur were grown on m-Dixon agar, in which the nitrogen source peptone had been substituted either by pigment-inducing tryptophane or arginine. The yeast cells thus obtained were harvested after 6 days, washed with physiological saline and inoculated on to the modified Dixon medium. Immediately after inoculation, the yeast cells were irradiated with UVA (100, 150 and 200 Jcm-2, single dose) or UVB (100, 500, 1000, 1500, 2000 mJcm-2, single dose; 500, 1500, 2500 mJcm-2 cumulative dose). Irrespective of the primary nitrogen source (Trp or Arg), unexposed controls showed nearly identical cell yield after 5 days. In the case of irradiation, however, growth reduction of cells cultured on Trp was lesser than that of cells fed with arginine. High significance (p < 0.0001) was found especially with the upper UVA and UVB doses. Differences were also found among the individual test strains, the wild strain being most sensitive. One strain (CBS 6094) failed to produce pigment on Trp medium, and there were no differences in the growth behavior of subcultures of this strain fed with either arginine or tryptophane under irradiation. In conclusion, synthesis of pigments and fluorochromes by M. furfur implies the generation of potent UV filters in the UVA and UVB spectrum.


Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.
Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects.


Factors that potentially influence successful weight loss for adults with intellectual disabilities: A qualitative comparison.
People with intellectual disabilities are more at risk of obesity than the general population. Emerging literature indicates that multicomponent interventions are most effective, however, individual results are variable and little research exists as to why this is the case. Focus groups were conducted to explore lived experiences between two groups of adults with intellectual disabilities; an overweight group (n = 6) and a group identified as successful in losing weight (n = 6). Similarities and differences were explored across four domains. Transcripts were produced and analysed using Theoretical Thematic Analysis. Similarities included service centre supports, basic food knowledge and issues restricting independence. The successful weight loss group had also internalised health messages, engaged with external reinforcement programmes, responded to positive feedback and demonstrated healthier dietary habits. Weight management interventions would benefit from understanding the influence that internalisation of health messages, effective reinforcement systems and positive feedback can have on supporting the adoption of healthier habits.


Possible interferon response in a child with measles encephalitis during immunosuppression.
A 4-yr-old boy with acute lymphoblastic leukaemia in remission developed an encephalopathy following an attenuated measles infection. He was treated with interferon and further deterioration was halted. Three weeks after interferon treatment was stopped, leukaemic blast cells reappeared in his peripheral blood and he died shortly thereafter. Aspects of diagnosis and treatment of this syndrome are discussed now that the presumptive clinical diagnosis is made more frequently.


Bifenthrin induces developmental immunotoxicity and vascular malformation during zebrafish embryogenesis.
Bifenthrin is a synthesized pyrethroid insecticide which is frequently used in the farmland to eradicate insects. Bifenthrin mainly disrupts sodium ion channel inducing neurotoxicity in the target insects. It also exerts toxic effects such as hormone dysregulation, hepatotoxicity and immunotoxicity in other vertebrates. However, there is no evidence of the acute-toxicity associated embryogenesis and organogenesis of bifenthrin in zebrafish. Here we first demonstrated that bifenthrin induced acute-toxicity accompanying inflammatory response and physiological degradations resulting in loss of embryogenesis and vascular development in zebrafish embryos. We found that bifenthrin increased intestinal ROS accumulation and the inflammatory genes including tnfa, il6, il8 and ptgs2b, thereby increasing embryo mortality. Moreover, bifenthrin disrupted angiogenesis by down-regulation of VEGF receptors in embryos. Not only in the zebrafish, bifenthrin also decreased cell viability and hampered vascular formation of HUVECs. Collectively, bifenthrin induced developmental toxicity, inflammatory cell death and anti-angiogenesis during embryogenesis.


Use of cover and the need to breathe: the effects of hypoxia on vulnerability of dwarf gouramis to predatory snakeheads.
The behavior of dwarf gouramis (Colisa lalia, Pisces, Belontiidae) and their vulnerability to predation by snakeheads (Channa micropeltes, Pisces, Channidae) were observed at four dissolved oxygen concentrations. When the oxygen level was near saturation (8 ppm) or only moderately reduced (3 ppm), the gouramis rarely breathed air and spent most of their time in a patch of artificial vegetation. At extremely low oxygen concentrations (1 and 0 ppm) the gouramis increased their air-breathing frequency and spent less time in cover. Gouramis were more likely to be captured by the snakeheads when out of the vegetation, and thus were caught more quickly at lower oxygen levels, even though their air-breathing frequency declined and use of cover increased in the presence of the predators. These results indicate that dissolved oxygen concentration, which varies considerably in many fish habitats, can affect use of cover and risk of predation in fishes.


Identification of the novel allele, HLA-DRB1*08:03:12, in a Chinese cord blood donor.
HLA-DRB1*08:03:12 differs from HLA-DRB1*08:03:02 by a single nucleotide substitution at position 702C>T.


Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study.
Cardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH. Twenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed. Increased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed. We found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies.


Thioridazine inhibits gene expression control of the cell wall signaling pathway (CWI) in the human pathogenic fungus Paracoccidioides brasiliensis.
Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), the most common systemic mycosis in Latin America. PCM treatment involves a long-term chemotherapeutic approach and relapses occur at an alarming frequency. Moreover, the emergence of strains with increased drug-resistance phenotypes puts constant pressure on the necessity to develop new alternatives to treat systemic mycoses. In this work, we show that the phenothiazine (PTZ) derivative thioridazine (TR) inhibits in vitro growth of P. brasiliensis yeasts at micromolar concentrations. We employed microarray hybridization to examine how TR affects gene expression in this fungus, identifying ~1800 genes that were modulated in response to this drug. Dataset evaluation showed that TR inhibits the expression of genes that control the onset of the cell wall integrity (CWI) response, hampering production of all major structural polysaccharides of the fungal cell wall (chitin, α-glucan and β-glucan). Although TR and other PTZs have been shown to display antimicrobial activity by various mechanisms, inhibition of CWI signaling has not yet been reported for these drugs. Thus, TR may provide a novel approach to treat fungal infections by targeting cell wall biogenesis.


Students' Perspectives and Concerns for the 2020 to 2021 Radiation Oncology Interview Season.
Recently, the Coalition for Physician Accountability Work Group on Medical Students in the Class of 2021 recommended limiting visiting medical student rotations, conducting virtual residency interviews, and delaying the standard application timeline owing to the ongoing corona virus disease 2019 (COVID-19) pandemic. These changes create both challenges and opportunities for medical students and radiation oncology residency programs. We conducted a comprehensive needs assessment to prepare for a virtual recruitment season, including a focus group of senior medical students seeking careers in oncology. A single 1.5-hour focus group was conducted with 10 third- and fourth-year medical students using Zoom videoconferencing software. Participants shared opinions relating to visibility of residency programs, virtual clerkship experiences, expectations for program websites, and remote interviews. The focus group recording was transcribed and analyzed independently by 3 authors. Participants' statements were abstracted into themes via inductive content analysis. Inductive content analysis of the focus group transcript identified several potential challenges surrounding virtual recruitment, including learning the culture of a program and/or city, obtaining accurate information about training programs, and uncertainty surrounding the best way to present themselves during a virtual interview season. In the present environment, the focus group participants anticipate relying more on departmental websites and telecommunications because in-person interactions will be limited. In addition, students perceived that the educational yield of a virtual clerkship would be low, particularly if an in-person rotation had already been completed at another institution. With the COVID-19 crisis limiting visiting student rotations and programs transitioning to hosting remote interviews, we recommend programs focus resources toward portraying the culture of their program and city, accurately depicting program information, and offering virtual electives or virtual interaction to increase applicant exposure to residency program culture.


Prevalence and clinicopathologic findings of conjunctival epithelial neoplasia in pterygia.
To study the prevalence of conjunctival neoplasia in clinically diagnosed pterygia and the clinicopathologic characteristics of conjunctival tissues obtained from pterygium excision. Prospective, observational case series. From February through August 2007, consecutive subjects indicated for pterygium excision were enrolled from an outpatient eye clinic of King Chulalongkorn Memorial Hospital, Bangkok, Thailand, and from the eye camp at the 6th Station of the Thai Red Cross Society, Aranyaprathet District, Sa Kaeo, Thailand. A total of 498 eyes from 482 subjects were studied. The mean age of the subjects was 56.5 ± 11.7 years. The male-to-female ratio was 3:7. Clinical data were gathered, including age, sex, occupation, family history, and medical history. Pterygia were clinically graded as mild, intermediate, or fleshy. Tissues from surgical fields were fixed in formalin and processed using standard pathology laboratory methods. Histopathologic results were examined in a masked fashion by 3 pathologists. Ninety-one percent of tissue was from primary pterygia. Most lesions were classified as intermediate grade (45.2%). Histopathologic results showed that 4 eyes had conjunctival intraepithelial neoplasia. Two eyes had minimal cellular atypia at the conjunctival epithelium. Two eyes had complex choristoma. For the subjects who had conjunctival epithelial neoplasia, the mean age was 57.0 ± 8.0 years, 44.4% were male, and none had a history of carcinoma in other organs or any history of herpes virus, human papilloma virus, or human immunodeficiency virus infections. The prevalence of conjunctival epithelial neoplasia in clinically diagnosed pterygia is approximately 1.8%. Because the clinical characteristics of subjects who have conjunctival epithelial neoplasia apparently did not differ from those without, tissue pathologic examination may be required to diagnose the condition.


Reversal of oligohydramnios with subtotal immersion: a report of five cases.
The purpose was to summarize five cases where subtotal immersion was associated with an increase in the amniotic fluid index. Five women with oligohydramnios, as defined by an amniotic fluid index < 8 cm, who underwent subtotal (shoulder-deep) immersion therapy are described. The mean pretreatment amniotic fluid index was 4.9 +/- 3 cm. After immersion therapy was instituted, the amniotic fluid index increased an average of 6 +/- 2.2 cm. In three subjects whose immersion therapy was discontinued, the amniotic fluid index fell an average of 4.7 cm. Subtotal immersion may help reverse oligohydramnios stemming from uteroplacental insufficiency.


BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts.
Adult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone formation. Osteocytes or osteoblasts express receptor activator of nuclear factor κ-B ligand (Rankl) or osteoprotegerin (Opg) to promote or inhibit osteoclastogenesis, respectively. Bone morphogenetic protein (BMP) is a potent bone inducer, but its major role in adult bone is to induce osteocytes to upregulate sclerostin (Sost) and increase the Rankl/Opg expression ratio, resulting in promotion of osteoclastogenesis. However, the precise effect of BMP-target gene(s) in osteoblasts on the Rankl/Opg expression ratio remains unclear. In the present study, we identified atonal homolog 8 (Atoh8), which is directly upregulated by the BMP-Smad1 axis in osteoblasts. In vivo, Atoh8 was detected in osteoblasts but not osteocytes in adult mice. Although global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton, the bone volume was decreased and osteoclasts were increased in the adult phase. Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow cells. Atoh8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio, while Runx2 knockdown normalized the Rankl/Opg expression ratio. Moreover, Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression ratio. These results suggest that bone remodeling is regulated elaborately by BMP signaling; while BMP primarily promotes bone resorption, it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts, suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.


Heart rate and blood pressure response and metabolic changes in the sheep fetus following reduction of uterine blood flow.
The cardiovascular and metabolic responses during acute fetal hypoxia were studied in 7 pregnant sheep near term. Complete reduction of uterine flow (UBF) for 180 s was performed in 13 experiments by inflating a balloon positioned in the maternal aorta. Fetal heart rate (FHR), systolic and diastolic blood pressure (BP) and fetal arterial oxygen saturation (SO2) were measured continuously. Blood samples were taken at short intervals and analyzed for pH, PCO2, PO2, SO2, base excess and lactate. Following the reduction of UBF, FHR began to rise after 4.7 +/- 14.4 (SD)s and fell after 31.3 s paralleled by the rise of the BP after 23.2 +/- 8.2 (SD)s. The fall of FHR was not related to the SO2 at control, but to the decline of the SO2 by 10-15%. There was no critical limit of SO2 at which the FHR started to fall and the BP began to rise. The rise of the FHR after UBF had been released was significantly correlated to the rise of SO2. Lactate production during hypoxia was related to the slope of the SO2 decline, i.e., to the fetal O2 consumption. The total metabolic response during hypoxia and recovery given by the pH area was correlated to the SO2 at control. No correlation between dip area of FHR and PH area could be established.


Carcinogenic bioassay of the herbicide, 2,4,5-trichlorophenoxyethanol (TCPE) with different 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) content in Swiss mice.
The carcinogenic effect of a herbicide trichlorophenoxyethanol (TCPE) was investigated. The substance always contains 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) as a trace contaminant. Outbred Swiss-H/Riop mice were treated for 1 year with different doses of the various admixtures of the two compounds and those of dioxin alone to determine whether their carcinogenic effects are dose-dependent. Observation time after TCPE treatment was 1 and 2 years. The maximum tolerable dose of TCPE (70 mg/kg) with a dioxin concentration of 7.10(-6) mg/kg doubled the number of liver tumours as compared to the controls. The occurrence of liver tumours decreased at the administration of lower doses of the two compounds. No change in tumour frequency could be detected when the level of dioxin as a trace contaminant was raised, either (10 ppm). According to our preliminary results, dioxin has a more toxic than carcinogenic effect. The use of TCPE as a herbicide in accordance with the proper factory regulations and the consumption of products treated with it does not seem to bear a carcinogenic risk for the consumer.


Recurrent pulmonary thromboembolism after initiating fibrinolytic therapy: a therapeutic dilemma.
A patient had pulmonary thromboembolism that was treated with streptokinase. Although an adequate thrombolytic state was achieved, pulmonary thromboemboli recurred. This patient then responded to conventional anticoagulation therapy.


Standing with assistance of a tilt table in intensive care: a survey of Australian physiotherapy practice.
Although tilt tables are used by physiotherapists to reintroduce patients to the vertical position, no quantitative evidence is available regarding their use within intensive care units (ICUs) of Australian hospitals. The purpose of this study was to evaluate the use of tilt tables in physiotherapy management of patients in ICUs across Australia. Ninety-nine physiotherapists working in Australian public ICUs were contacted via mail and asked to complete a questionnaire regarding their use of tilt tables in practice. Reasons for the use of the tilt table, contraindications, commonly used adjuncts, monitoring, and outcome measures were also investigated. Eighty-six questionnaires were returned (87% response). The tilt table was used by 58 physiotherapists (67.4%). The most common reasons for inclusion of tilt table treatment were to: facilitate weight bearing (94.8% of those who tilt); prevent muscle contractures (86%); improve lower limb strength (81%); and increase arousal (70%). The tilt table was most frequently applied to patients with neurological conditions (63.8%) and during long-term ICU stay (43.1%). Techniques often combined with tilt table treatment included upper limb exercises (93.1%) and breathing exercises (86.2%). Standing with assistance of the tilt table is used by the majority of physiotherapists working in Australian ICUs. A moderate level of agreement is demonstrated by physiotherapists regarding indications to commence tilt table treatment and adjunct modalities combined with standing with assistance of the tilt table.


Artificial Intelligence decision-making tools based on comprehensive two-dimensional gas chromatography data: the challenge of quantitative volatilomics in food quality assessment.
Effective investigation of food volatilome by comprehensive two-dimensional gas chromatography with parallel detection by mass spectrometry and flame ionization detector (GC×GC-MS/FID) gives access to valuable information related to industrial quality. However, without accurate quantitative data, results transferability over time and across laboratories is prevented. The study applies quantitative volatilomics by multiple headspace solid phase microextraction (MHS-SPME) to a large selection of hazelnut samples (Corylus avellana L. n = 207) representing the top-quality selection of interest for the confectionery industry. By untargeted and targeted fingerprinting, performant classification models validate the role of chemical patterns strongly correlated to quality parameters (i.e., botanical/geographical origin, post-harvest practices, storage time and conditions). By quantification of marker analytes, Artificial Intelligence (AI) tools are derived: the augmented smelling based on sensomics with blueprint related to key-aroma compounds and spoilage odorant; decision-makers for rancidity level and storage quality; origin tracers. By reliable quantification AI can be applied with confidence and could be the driver for industrial strategies.


[Isolation of DNA fraction bound to the axial structure of metaphase chromosomes and studies of renaturation].
Mitotic chromosomes of L cells (metaphase plates) were dehistonized by centrifugation through a layer of 2 M NaCl and then treated with restriction endonuclease EcoRI and HindIII. Alternatively, they were pretreated with EcoRI endonuclease. The DNA remaining attached to the axial structure of the chromosomes was isolated and investigated in renaturation experiments. It was found to be enriched in reiterated base sequences belonging to the satellite and to abundant intermediate repeats.


Normal variations of the superior vena cava and azygos venous system depiction by CT scan in the adult Thai population.
Identification of normal variations to the thoracic central venous system anatomy is essential in radiological intervention and cardiothoracic surgery to prevent complications. To estimate the prevalence and pattern of normal variations of superior vena cava (SVC) and azygos venous system as well as factors associated with normal variations of SVC. Venous-phase chest CT of 1336 patients were retrospectively reviewed. Age, sex, and underlying disease were recorded. SVC diameter and cross-sectional area were measured to evaluate for associations with normal variations. The prevalence of normal anatomical variations of SVC and azygos venous system were 0.3% and 1.5%, respectively. Duplicated SVC was the most common variations. The most common variation for the azygos venous system was the connection between the hemiazygos and accessory hemiazygos veins draining into the left brachiocephalic vein (12/1336 cases, 0.9%). The median (interquartile range [IQR]) cross-sectional area compared between normal SVC (297.2 mm2) and duplicated SVC (223.5 mm2) showed a statistically significant difference (P = 0.033). This study determined the prevalence of rare normal variations of the azygos venous system, a connection between the hemiazygos and accessory hemiazygos veins draining into the left brachiocephalic vein. The prevalence of normal variations of the SVC and azygos venous system in the adult Thai population was similar with that of previous publications. Cross-sectional area was the only factor with a significant association with SVC variations.


Modeling Huntington׳s disease with patient-derived neurons.
Huntington׳s Disease (HD) is a fatal neurodegenerative disorder caused by expanded polyglutamine repeats in the Huntingtin (HTT) gene. While the gene was identified over two decades ago, it remains poorly understood why mutant HTT (mtHTT) is initially toxic to striatal medium spiny neurons (MSNs). Models of HD using non-neuronal human patient cells and rodents exhibit some characteristic HD phenotypes. While these current models have contributed to the field, they are limited in disease manifestation and may vary in their response to treatments. As such, human HD patient MSNs for disease modeling could greatly expand the current understanding of HD and facilitate the search for a successful treatment. It is now possible to use pluripotent stem cells, which can generate any tissue type in the body, to study and potentially treat HD. This review covers disease modeling in vitro and, via chimeric animal generation, in vivo using human HD patient MSNs differentiated from embryonic stem cells or induced pluripotent stem cells. This includes an overview of the differentiation of pluripotent cells into MSNs, the established phenotypes found in cell-based models and transplantation studies using these cells. This review not only outlines the advancements in the rapidly progressing field of HD modeling using neurons derived from human pluripotent cells, but also it highlights several remaining controversial issues such as the 'ideal' series of pluripotent lines, the optimal cell types to use and the study of a primarily adult-onset disease in a developmental model. This article is part of a Special Issue entitled SI: Exploiting human neurons.


MicroRNAs in oral lichen planus and potential miRNA-mRNA pathogenesis with essential cytokines: a review.
Oral lichen planus (OLP) is a potentially premalignant condition with unknown pathogenesis. Immune and inflammatory factors are thought to play important roles in the development of OLP, and cytokines, such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, can act as critical players in the immunopathogenesis of OLP. MicroRNAs (miRNAs) are closely correlated with cytokines in various inflammation-related diseases. In patients with OLP, miRNA-146a and miRNA-155 are increased in peripheral blood mononuclear cells, and numerous miRNAs have been shown to exhibit altered expression profiles in lesions. Although the microRNA-messenger RNA (miRNA-mRNA) network is thought to be involved in the development of OLP, in-depth studies are lacking. Here, we summarize current data on the mechanisms of action of miRNAs regulating typical cytokines in OLP, including interleukin (IL)-10, IL-17, IL-22, IFN-γ, and TNF-α, to study the genetic basis of the pathogenesis of OLP and to provide prospects of therapy.


Pyrrospirones A and B, apoptosis inducers in HL-60 cells, from an endophytic fungus, Neonectria ramulariae Wollenw KS-246.
Pyrrospirones A and B have been isolated from unpolished rice cultures of the endophytic fungus Neonectria ramulariae Wollenw KS-246. Their absolute stereostructures (1 and 2) were elucidated through spectroscopic methods using 1D and 2D NMR techniques and chemical transformations, including the modified Mosher's method. The compounds exhibited cytotoxicity and induced apoptosis in human promyelocytic leukemia HL-60 cells.


Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas.
Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors. The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma. We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up. Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P < 0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P < 0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P < 0.05). The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.


Intervention to reduce the use of unsafe abbreviations in a teaching hospital.
To determine the effectiveness of a two-phase intervention designed to reduce the use of unsafe abbreviations. An observational prospective study was conducted at the King Khalid University Hospital in Riyadh, Saudi Arabia during May-September 2009. A list of unsafe abbreviations was formulated based on the recommendations of the Institute for Safe Medication Practices. The first 7000 medication orders written at the beginning of each period were collected. Phase one of the intervention involved educating health care professionals about the dangers of using unsafe abbreviations. In the second phase of the intervention, a policy was approved that prohibited the use of unsafe abbreviations hospital-wide. Then, another educational campaign targeted toward prescribers was organized. Descriptive statistics are used in this paper to present the results. At baseline, we identified 1980 medication abbreviations used in 7000 medication orders (28.3%). Three months after phase one of the intervention, the number of abbreviations found in 7000 medication orders had decreased to 1489 (21.3%). Six months later, after phase two of the intervention, the number of abbreviations used had decreased to 710 (10%). During this phase, the use of all abbreviations had declined relative to the baseline and phase one use levels. The decrease in the use of abbreviations was statistically significant in all three periods (P < 0.001). The implementation of a complex intervention program reduced the use of unsafe abbreviations by 65%.


Immunohistochemical search for viral and bacterial antigens in Crohn's disease.
Recent studies show that diseased intestinal tissues of patients with Crohn's disease (CD) contain obstructed lymphatics, granulomas, and tertiary lymphoid organs, representing responses to persistent antigen. Forty-seven tissue sections from 28 CD patients and 20 tissue sections from 17 control patients were studied. Tissues were immunostained with antibody directed against adenovirus, Epstein-Barr virus, herpes simplex virus I, parvovirus B19, Listeria monocytogenes, Escherichia coli, Clostridium perfringens, and Mycobacterium avium subspecies paratuberculosis. There was no evidence of adenovirus, Epstein-Barr virus, parvovirus B19, or M. avium subsp. paratuberculosis in the tissues. Clostridia were positively stained in the mucus of 18.5% of CD patients versus 35.3% of controls and in the tissue of 11.1% of CD patients but in no controls. Immunoreactivity to listeria antibody occurred in the mucus of 3.7% of CD patients and in 5.9% of controls while it occurred in the tissue of 37.0% of CD patients and 29.4% of controls. E. coli occurred in the mucus of 48.1% CD and 64.7% controls and in the tissue of 18.5% and 5.9% respectively. Of the agents demonstrated in this search, none was located in granulomas or inflamed lymphatics. Finding the common gut microbes, E. coli and clostridia, in the mucus of patients and controls was not unexpected. The minor focal staining of E. coli and clostridia does not suggest a primary role for these pathogens in CD. Positive staining for listeria in patients and controls may very well represent cross reactivity rather than specific identification.


Late-fall satellite-based soil moisture observations show clear connections to subsequent spring streamflow.
Because runoff production is more efficient over wetter soils, and because soil moisture has an intrinsic memory, soil moisture information can potentially contribute to the accuracy of streamflow predictions at seasonal leads. In this work, we use surface (0-5 cm) soil moisture retrievals obtained with the National Aeronautics and Space Administration's Soil Moisture Active Passive satellite instrument in conjunction with streamflow measurements taken within 236 intermediate-scale (2000-10,000 km2) unregulated river basins in the conterminous United States to show that late-fall satellite-based surface soil moisture estimates are indeed strongly connected to subsequent springtime streamflow. We thus show that the satellite-based soil moisture retrievals, all by themselves, have the potential to produce skillful seasonal streamflow predictions several months in advance. In poorly instrumented regions, they could perform better than reanalysis soil moisture products in this regard.


"Right-to-Try" experimental drugs: an overview.
The "Right-to-Try" experimental drugs act passed by Donald Trump in 2018 provides an opportunity of early access to experimental drugs for the treatment of life-threatening diseases and a potential boon to many young and under-capitalized biotechnology or pharmaceutical companies. The pros and cons of experimental drugs, including a number of "cutting edge" scientific, clinical, and a number of synergistic approaches such as artificial intelligence, machine learning, big data, data refineries, electronic health records, data driven clinical decisions and risk mitigation are reviewed.


Development of a SYBR safe technique for the sensitive detection of DNA in cesium chloride density gradients for stable isotope probing assays.
SYBR safe, a fluorescent nucleic acid stain, was evaluated as a replacement for ethidium bromide (EtBr) in cesium chloride (CsCl) density gradients for DNA stable isotope probing (DNA-SIP) assays. The separation of 12C- and 13C-labelled DNA using SYBR safe gave similar results to those obtained using EtBr with pure cultures and environmental samples exposed to a 13C-labelled substrate, while the detection limit of DNA was enhanced by the use of SYBR safe by at least 5 times. The results demonstrated that SYBR safe is a safe, sensitive and effective alternative to the use of ethidium bromide in CsCl density gradients for DNA-SIP assays.


Positive and general psychopathology associated with specific gray matter reductions in inferior temporal regions in patients with schizophrenia.
Schizophrenia is a complex disorder that affects perception, cognition, and emotion causing symptoms such as delusions, hallucinations, and suspiciousness. Schizophrenia is also associated with structural cortical abnormalities including lower gray matter (GM) concentration, GM volume, and cortical thickness relative to healthy control individuals. However, the association between GM measures and symptom dimensions in schizophrenia is still not well understood. Here, we applied parallel independent component analysis (pICA), a higher-order statistical approach that identifies covarying patterns within two (or more) data modalities simultaneously, to link covarying brain networks of GM concentration with covarying linear combinations of the positive and negative syndrome scale (PANSS). In a large sample of patients with schizophrenia (n = 337) the association between these two data modalities was investigated. The pICA revealed a distinct PANSS profile characterized by increased delusional symptoms, suspiciousness, hallucinations, and anxiety, that was associated with a pattern of lower GM concentration in inferior temporal gyri and fusiform gyri and higher GM concentration in the sensorimotor cortex. GM alterations replicate previous findings; additionally, applying a multivariate technique, we were able to map a very specific symptom profile onto these GM alterations extending our understanding of cortical abnormalities associated with schizophrenia. Techniques like parallel ICA can reveal linked patterns of alterations across different data modalities that can help to identify biologically-informed phenotypes which might help to improve future treatment targets.


Biochemical characterization of hydroquinone hydroxylase from Phanerochaete chrysosporium.
The white-rot fungus Phanerochaete chrysosporium can degrade lignin polymers using extracellular, non-specific, one-electron oxidizing enzymes. This results in the formation of guaiacyl (G), syringyl (S), and hydroxyphenyl (H) units, such as vanillic acid, syringic acid, and p-hydroxybenzoic acid (p-HBA) and the corresponding aldehydes, which are further metabolized intracellularly. Therefore, the aim of this study was to identify proteins involved in the hydroxylation of H-unit fragments such as p-HBA and its decarboxylated product hydroquinone (HQ) in P. chrysosporium. A flavoprotein monooxygenase (FPMO), PcFPMO2, was identified and its activity was characterized. Recombinant PcFPMO2 with an N-terminal polyhistidine tag was produced in Escherichia coli and purified. In the presence of NADPH, PcFPMO2 used six phenolic compounds as substrates. PcFPMO2 catalyzed the hydroxylation of the H-unit fragments such as p-HBA and HQ, and the G-unit derivative methoxyhydroquinone (MHQ). The highest catalytic efficiency (kcat/Km) was observed with HQ, indicating that PcFPMO2 could be involved in HQ hydroxylation in vivo. Additionally, PcFPMO2 converted MHQ to 3-, 5-, and 6-methoxy-1,2,4-trihydroxybenzene (3-, 5-, and 6-MTHB), respectively, suggesting that PcFPMO2 might partially be involved in MHQ degradation, following aromatic ring fission, via three MTHBs. FPMOs are divided into eight groups (groups A to H). This is the first study to show MHQ hydroxylase activity of a FPMO-group A superfamily member. These findings highlight the unique substrate spectrum of PcFPMO2, making it an attractive candidate for biotechnological applications.


Gender differences in mood stabilizer medications prescribed to Veterans with serious mental illness.
Mood stabilizer medications (MSMs) can induce significant weight gain and other metabolic side effects. Research suggests that women are more susceptible to psychotropic medication-induced metabolic side effects than men. We examined gender differences in the likelihood of receiving an MSM with a lower liability for weight gain using data from the U.S. Department of Veterans Affairs (VA) healthcare system. We identified 3823 VA patients with a schizophrenia or bipolar disorder diagnosis who initiated treatment with a MSM between 10/2006 and 9/2011. We used multivariable logistic regression analysis to examine gender differences in the likelihood of incident prescription of MSMs with low versus medium/high metabolic risk, adjusting for fiscal year of prescribing and demographic, mental health, and physical health characteristics. Overall, 47% of women were prescribed a low metabolic risk MSM compared to 26% of men (p<0.0001). In multivariable analysis, women were 2.19 times as likely as men to be prescribed a low metabolic risk MSM (95% CI: 1.84-2.60, p<0.0001). Several demographic and clinical covariates were also independently related to prescribing of MSMs by level of metabolic risk. This study used retrospective administrative data collected from a VA healthcare system database, which does not allow us to understand the context in which MSM treatment decisions were made. Prescribing choices for MSMs by VA mental health prescribers and female Veterans may reflect a growing awareness of the potential adverse health consequences of these treatments in women.


Effects of estradiol benzoate and castration on LH in experimental hyperprolactinemia.
Female rats of the Wistar strain were rendered hyperprolactinemic by grafting one additional pituitary gland under the right kidney capsule at various ages (5 days group A; 30 days group B and 90 days group C). Age matched animals were sham operated to serve as controls. Plasma levels of PRL and LH were measured by specific double antibody RIA. Basal preoperative PRL levels were increased rapidly after grafting, reaching values over 100 ng/ml, in front of the 20 ng/ml showed by sham operated controls. Plasma LH levels were significantly decreased in all hyperprolactinemic groups as compared to controls. After Estradiol Benzoate (EB) administration all control rats showed an increase in PRL levels in a pulsatile manner with higher values found in the afternoon. PRL response in transplanted rats was less evident and with absence of pulsatility. LH responses to EB in control animals showed a biphasic pattern, with a negative feed-back in the first hours followed by a positive effect at 31 or 55 h after the injection. This pattern of response started in the control rats from group A at 19 days of age. Before that, only the negative feed-back effect was present. In grafted animals from the same group no positive feed-back effect could be detected at any time studied. In group B, a reduction in the positive feed-back effect, more evident after 90 days of hyperprolactinemia was detected. Animals of group C on the contrary showed an increased positive feed-back effect 40 days after grafting. Eight days after castration a reduction in PRL levels was detected in all groups, together with an increase in LH values. PRL values after ovariectomy were less reduced in grafted animals, and these rats also showed a less marked LH increase. This effect is more evident in group B. All these data seem to point out that hyperprolactinemia is capable of modifying the feed-back system between E2 and LH, and that the age at which hyperprolactinemia starts has a profound effect.


Optimal escapement in stage-structured fisheries with environmental stochasticity.
Stage-structured population models are commonly used to understand fish population dynamics and additionally for stock assessment. Unfortunately, there is little theory on the optimal harvest of stage-structured populations, especially in the presence of stochastic fluctuations. In this paper, we find closed form optimal equilibrium escapement policies for a three-dimensional, discrete-time, stage-structured population model with linear growth, post-harvest nonlinear recruitment, and stage-specific pricing and extend the analytic results to structured populations with environmental stochasticity. When only fishing reproductive adults, stochasticity does not affect optimal escapement policies. However, when harvesting immature fish, the addition of stochasticity can increase or decrease optimal escapement depending on the second and third derivative of the recruitment function. For logistic recruitment, stochasticity reduces optimal immature escapement by a multiplicative factor of one over one plus the variance of the environmental noise. Using hard clam, Mercenaria mercenaria, as an example and assuming Beverton-Holt recruitment, we show that optimal fishing of hard clam targets the immature stage class exclusively and that environmental stochasticity increases optimal escapement for low discount rates and decreases optimal escapement for high discount rates.


Postictal diffusion tensor imaging.
The objective of the study was to investigate postictal diffusion tensor imaging (DTI) in focal epilepsy. DTI and statistical parametric mapping (SPM) were used to examine objectively the diffusion properties of the brains of 18 patients with intractable focal epilepsy both postictally and interictally and to compare them with 27 normal controls scanned twice. Three sets of statistical tests were performed on each patient's fractional anisotropy and mean diffusivity data: interictal versus controls, postictal versus controls and a third "difference analysis" to test for significant changes in comparison with the differences noted between the two sets of control scans. Thirteen of the 18 patients (72%) had significant increases in mean diffusivity in the interictal scan. No decreases in mean diffusivity were detected. The difference analysis detected significant relative decreases in mean diffusivity postictally in nine patients (50%). These changes were focal in seven patients. In six of these, the site of the epileptic focus was known and co-localized with the diffusivity change in three. No significant changes in anisotropy were noted between the post- and interictal states. The postictal decrease in diffusivity probably reflects cellular swelling in the area of seizure onset and possibly areas of seizure spread. Postictal diffusivity changes appear complex and dynamic and timing after the seizure may be critical. Anisotropy measures appear less sensitive to these changes. Further systematic studies are needed and correlation with outcome after epilepsy surgery will determine the role of postictal diffusion measures in the presurgical evaluation of epilepsy patients.


Mixed gonadal dysgenesis, pathogensis, and management.
Fourteen patients with Mixed Gonadal Dysgenesis who presented as infants or children are discussed. Gonadal asymmetry, and/or sex chromosomal mosaicism, as well as retained Mullerian Ducts characterize the anomaly. The dysgenetic testis may occur as the result of a cascade of development mishaps stemming from abnormalities of H-Y antigen expression or function that lead to abnormal differentiation of the indifferent urogenital ridge and, in turn, to aberrant production of Mullerian inhibiting Substance and testosterone. The latter two cause retention of Mullerian ducts and incomplete masculinization of the external genitalia. Absence of a second X chromosome may lead to the formation of a streak ovary, in which the dysgenetic testis may invoke formation of hilar and medullary cords. Neoplastic transformation, so characteristic of this group of patients, may result from unprotected germ cells and abnormally high and prolonged gonadotropin stimulation. Gonadoblastoma and seminoma-dysgerminomas are the tumors found in the gonads with the risk exceeding 50% as the third decade is approached. Laterality of the gonads in this anomaly remains an enigma. The gonads should be removed at birth if possible and the external genitalia repaired soon thereafter. These patients should be raised as females. The risk of neoplastic transformations must be considered at all stages of management.


Study on the mechanism of biochar loaded typical microalgae Chlorella removal of cadmium.
Coconut shell activated carbon (Csac) is one of the most widely used materials to remove cadmium (Cd) from contaminated water. A large diversity of microorganisms exists in various aquatic systems and may aid Cd removal by Csac. In this study, we explored the reactions of Csac with microalgae (Chlorella) in Cd-containing media. The results of scanning electron microscope (SEM) imaging, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), superconducting pulse-Fourier transform nuclear magnetic resonance (pulse-FT NMR) and X-ray photoelectron spectroscopy (XPS) indicated that Chlorella could adhere in the micropores of Csac formed Csac@Chlorella composite adsorbent loading Chlorella. Furthermore, the composite adsorbent surface had abundant functional groups such -COOH, -OH and C-O-C, which served as active sites during the adsorption process. Compared with Csac, Csac@Chlorella had an enhanced Cd adsorption capacity evidently. The results showed that pH 8, 0.2 g Csac, OD680 of 0.1 for Chlorella were optimal conditions for maximum Cd adsorption capacity within one hour contact time. Furthermore, the Cd adsorption process was well described by the pseudo-second-order and Langmuir adsorption isotherm models. The models revealed that the adsorption process was mainly based on chemical adsorption of a single molecular layer, accompanied by electrostatic attraction, complexation and intracellular adsorption, amongst other parameters. Collectively, the findings illustrate that the microalgae (Chlorella)-Csac-Cd interaction is complex and will thus have immense interest to a broad range of biological, environmental, and geoscience communities.


Reductive dechlorination of chlorobiphenylols by rats.
Dechlorinated products were isolated from the urine of rats that were administered chlorobiphenylols, the primary hydroxylated metabolites of PCB in mammals. The mechanism of chlorine loss from chlorobiphenylols is different from the mechanism of dechlorination via arene oxides whereby concomitant hydroxylation is always observed.


The origin of monocyte-macrophage heterogeneity: possible alternatives.
The heterogeneity of the monocyte-macrophage population may be explained by several alternatives. In the present study we summarize our data and other studies concerning the variability and instability in the expression of markers and functions by monocytes and macrophages as well as the analysis of cloned populations of macrophages. We suggest the hypothesis that most macrophage heterogeneity may be due to reversible changes in a multifunctional population.


Behavioral and anatomical consequences of small intrastriatal injections of kainic acid in the rat.
The effects of bilateral injections of kainic acid into the anteromedial neostriatal region were examined behaviorally and anatomically in two groups of rats. Behaviorally, kainic acid injections resulted in a severe impairment of delayed alternation retention, while the ability for visual discrimination remained unaffected. Anatomically it was found that axons traversing the injected area remain able to transport horseradish peroxidase. Furthermore, histological examinations of the injected regions revealed a heavy loss of neurons and a decrease of histochemical staining for specific acetylcholinesterase. Silver impregnation showed slightly disorganized, but continuous, axons in bundles of the capsula interna. On the other hand, the axonal network throughout the neuropil of the injected area was markedly diminished. No conspicuous change was found in myelin staining or in the intensity or catecholamine fluorescence. The anatomical results suggest that kainic acid appears to affect only perikarya of the neostriatum and the axons originating from these perikarya, whereas passing axons seem to remain intact. Thus, the observed behavioral impairment must be attributed to changes in the neostriatum itself. It is concluded that the neostriatum has 'complex' or 'cognitive' functions and that some mental symptoms in Huntington's chorea may be attributed to a dysfunction of this part of the brain.


Hyaluronan synthase 3 promotes plaque inflammation and atheroprogression.
Hyaluronan (HA) is a prominent component of the provisional extracellular matrix (ECM) present in the neointima of atherosclerotic plaques. Here the role of HA synthase 3 (HAS3) in atheroprogression was studied. It is demonstrated here that HAS isoenzymes 1, -2 and -3 are expressed in human atherosclerotic plaques of the carotid artery. In Apolipoprotein E (Apoe)-deficient mice Has3 expression is increased early during lesion formation when macrophages enter atherosclerotic plaques. Importantly, HAS3 expression in vascular smooth muscle cells (VSMC) was found to be regulated by interleukin 1 β (IL-1β) in an NFkB dependent manner and blocking antibodies to IL-1β abrogate Has3 expression in VSMC by activated macrophages. Has3/Apoe double deficient mice developed less atherosclerosis characterized by decreased Th1-cell responses, decreased IL-12 release, and decreased macrophage-driven inflammation. Inhibition of HAS3-dependent synthesis of HA dampens systemic Th1 cell polarization and reduces plaque inflammation. These data suggest that HAS3 might be a promising therapeutic target in atherosclerosis. Moreover, because HAS3 is regulated by IL-1β, our results suggest that therapeutic anti-IL-1β antibodies, recently tested in human clinical trials (CANTOS), may exert their beneficial effects on inflammation in post-myocardial infarction patients in part via effects on HAS3. TOC categorybasic study TOC subcategoryarteriosclerosis.


Evaluation of pH and calcium ion release at the simulated external root resorption cavities of teeth obturated with bioceramic sealer.
The purpose of this study was to evaluate pH and calcium ion release at the outer dentin surface of simulated external root resorption cavities after root canals obturated with bioceramic root canal sealer compared with those medicated with calcium hydroxide. Sixty extracted human single-rooted teeth were selected and instrumented. External root resorption cavities were prepared at the lingual surface of the root. The teeth were randomly divided into three groups: (1) Bioceramic sealer group, canals were obturated with gutta-percha and BioRoot sealer; (2) Calcium hydroxide group, canals were medicated with UltraCal XS; (3) Control group, canals were left empty. Thirty specimens were used for evaluation of pH at 7, 14, and 28 days (n = 10 per group) and the other 30 specimens were used for evaluation of calcium ion diffusion at 28 days (n = 10 per group). Calcium hydroxide group showed the highest median pH value at all time points (7, 14, and 28 days). Both calcium hydroxide and bioceramic sealer groups showed significantly higher median pH values compared with control (p < .001). Comparing within groups, both bioceramic sealer group and calcium hydroxide group showed significantly decreased median pH over time, while the median pH of the control did not show any significant difference among Days 7, 14, and 28. Both calcium hydroxide and bioceramic sealer groups had significantly higher calcium ion release than control. Notably, bioceramic sealer group showed significantly higher calcium ion release than the calcium hydroxide group (p < .01). Root canals obturated with gutta-percha and bioceramic sealer showed high calcium ion levels at the simulated external root resorption cavities but did not show an extended period of alkaline pH.


An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release.
The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1beta-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1beta-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains.


Postmenopausal women with minimal trauma fractures are unapprised of the existence of low bone mass or osteoporosis.
To explore barriers to medical care for osteoporosis following a minimal trauma fracture (MTF). MTFs occur from a fall while in a seated, recumbent or standing position; during normal walking, or from a height less than 4 feet. Prospective study and focus groups of women with MTF performed in Chicago from June to December of 2003. Study protocol approved by Institutional Review Board (IRB) and all participants signed consent forms. Focus groups were audiotaped and transcribed, transcripts analyzed using Atlas.ti. Survey results analyzed with SPSS 11.5. Twenty nine participants recruited with average age of 74+/-16 years. MTF occurred at the mean age of 61+/-8 years, with fifteen (15/29) reporting more that one prior MTF. The age distribution was 40-49 years 2 (2/29) participants, 50-59 years 2 (2/29), 60-69 years 6 (6/29), 70-79 years 10 (10/29), 80 and above 9 (9/29). Most participants (21/29, 70%) reported knowledge about osteoporosis obtained from written media. Osteoporotic fractures were rated on a single item Likert Scale (1=not important to 5=most important) as 2.5 (compared with breast cancer 2.3, and myocardial infarction 2.8). Half (16/29) had osteoporosis counseling with their PCP and 9 were receiving medications for bone loss. We observed a positive correlation between osteoporosis counseling and BMD testing (r=0.6, p<0.001), and a trend toward osteoporosis treatment (r=0.372, p=0.09). Half of the participants had reported the occurrence of MTF to their PCP (14/29), however this did not lead to counseling, BMD testing (r=0.07, p=0.78), or treatment (r=-0.14, p=0.53). None of the women believed that low BMD or osteoporosis had contributed to their fracture. Women studied believed that they were "too young" (12/29) to have osteoporosis. Women are not receiving adequate information about osteoporosis; they remain unaware of the connection between MTFs and osteoporosis. Post-menopausal women with MTF do not identify osteoporosis as a cause for the fracture, may exhibit ageism and thereby fail to seek adequate medical care.


Sonographic finding of papillary thyroid carcinoma with nodular fasciitis-like stroma.
Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is an extremely rare variant of papillary thyroid carcinoma characterized by prominent stromal cell proliferation. To our knowledge, sonographic findings of PTS-NFS have not been reported. Here, we report a case of PTC-NFS that presented as a homogenous and hypoechoic mass in the peripheral portion of the left thyroid gland on sonography in a 35-year-old pregnant woman.


Local management in primary breast cancer. Our experience of 331 cases.
The peroperative exploration of axillary content gave wrong result from the stage of axillary nodes in every fourth case compared with the final result of axillary evacuation. There were no locoregional recurrences in stage I-patients irradiated after mastectomy. In postoperatively irradiated stage II-patients there were locoregional recurrences in 2.5% of cases, which was 1/8 of recurrences of patients not irradiated postoperatively.


Biosensor-surface plasmon resonance methods for quantitative analysis of biomolecular interactions.
The surface plasmon resonance (SPR) biosensor method has emerged as a very flexible and powerful approach for detecting a wide diversity of biomolecular interactions. SPR monitors molecular interactions in real time and provides significant advantages over optical or calorimetric methods for systems with strong binding and low spectroscopic signals or reaction heats. The SPR method simultaneously provides kinetic and equilibrium characterization of the interactions of biomolecules. Such information is essential for development of a full understanding of molecular recognition as well as for areas such as the design of receptor-targeted therapeutics. This article presents basic, practical procedures for conducting SPR experiments. Initial preparation of the SPR instrument, sensor chips, and samples are described. This is followed by suggestions for experimental design, data analysis, and presentation. Steady-state and kinetic studies of some small molecule-DNA complexes are used to illustrate the capability of this technique. Examples of the agreement between biosensor-SPR and solution studies are presented.


The efficacy of the adjunct use of subgingival air-polishing therapy with erythritol powder compared to conventional debridement alone during initial non-surgical periodontal therapy.
To assess the efficacy of the adjunct use of a subgingival erythritol powder air-polishing device (EPAP) in comparison to conventional subgingival instrumentation alone during initial non-surgical periodontal therapy. Twenty-one patients with generalized Stages 2 and 3 grade B periodontitis were included in this single centre, single blinded, split-mouth, randomized clinical trial. Teeth on the control side were treated with conventional hand and ultrasonic instrumentation, while those on the contralateral test side was treated using EPAP as adjunct to conventional subgingival instrumentation with hand and ultrasonic instruments. Three months after initial instrumentation, persisting pockets of ≥4 mm were re-treated, in both control and test sides, again with the respective treatment approach-subgingival instrumentation alone on control, and subgingival instrumentation + EPAP on test side. Clinical parameters such as probing pocket depth (PPD), bleeding on probing, and relative attachment level were recorded at baseline and 3 and 6 months following the initial instrumentation. Subgingival plaque samples were collected at baseline, immediately post surgery, as well as at 1 week, 1 month, 3 months, and 6 months after initial instrumentation. In the test group after 6 months, a significantly larger number of initially deep pockets (PPD ≥ 5.5 mm) were reduced to shallow (PPD ≤ 3.4 mm), and a larger attachment gain was observed. No statistically significant microbiological differences could be found between test and control group. The results of the present study indicate that the adjunct use of subgingival airflow therapy with EPAP during initial non-surgical periodontal therapy might be beneficial in initially deep pockets (PPD ≥ 5.5 mm).


Statistical moments in pharmacokinetics.
Statistical moments are parameters that describe the characteristics of the time courses of plasma concentration (area, mean residence time, and variance of residence time) and of the urinary excretion rate that follow administration of a single dose of a drug. The relationship between the moments of a time-course curve and pharmacokinetic profiles of drug disposition, i.e., absorption, distribution, metabolism, and excretion, is described. The moments are related to the extent and rate of bioavailability, and it is shown that they can be effectively applied to the deconvolution operation.


Preventive strategies for atrial fibrillation after cardiac surgery in Nordic countries.
Atrial fibrillation is a common arrhythmia after cardiac surgery. It increases morbidity, length of hospital stay, and costs of operative treatment. Beta-blockers, sotalol, amiodarone, corticosteroids, and biatrial pacing have been shown to be efficient in the prevention of postoperative atrial fibrillation. The aim of this study was to find out how widely different prophylactic strategies for postoperative atrial fibrillation are used in Scandinavian countries. An online link for a questionnaire was emailed to (214) cardiac surgeons in Finland, Sweden, Norway, Denmark, and Estonia to assess the use of prophylactic methods for postoperative atrial fibrillation. A total of 97 surgeons responded to the survey. Oral beta-blockers were routinely used for atrial fibrillation prophylaxis by 62% of responders. The main reasons for nonuse of beta-blockers were that responders were unconvinced of the evidence of benefit or they preferred some alternative prophylaxis. Intravenous beta-blockers were used frequently by 6% of responders. Amiodarone was used for prophylaxis by 18% of responders. Nonusers were unconvinced of its efficacy, were afraid of its complications, or found its use too cumbersome. Other prophylactic atrial fibrillation strategies that were used are as follows: sotalol by 2%, magnesium by 17%, corticosteroids by 1%, and atrial pacing by 11% of respondents. There is still widely varying implementation of strategies for atrial fibrillation prophylaxis among Scandinavian cardiac surgeons. Lack of confidence in the efficacy of these approaches is the main rationale for nonimplementation.


Invasive breast cancer following bilateral subcutaneous mastectomy in a BRCA2 mutation carrier: a case report and review of the literature.
Primary prevention of breast cancer through prophylactic mastectomy can reduce the risk of malignancy in high-risk individuals. No type of mastectomy completely removes all breast tissue, but a subcutaneous mastectomy leaves more tissue in situ than does a simple mastectomy. We report a case of invasive breast cancer in a BRCA2-positive woman 33 years after bilateral subcutaneous mastectomy. To our knowledge, only one case of primary breast cancer after prophylactic mastectomy in a BRCA1-positive patient has been reported in the literature and none in BRCA2-positive individuals. Careful documentation and long follow-up is essential to fully assess the benefits and risks of preventive surgical procedures in BRCA1 and BRCA2 mutation carriers.


DNA polymorphism and molecular pathology of the human globin gene clusters.
In the past few years there has been intensive study of the human globin genes. This study has provided important insights into normal gene structure and function and the nature of molecular defects leading to a set of inherited diseases. In turn, this information forms the basis for rational design of specific tests for prenatal diagnosis of particular forms of beta-thalassemia. Several areas demand further investigation. First, we need to know more about the region within the beta-gene cluster in which recombination appears to be more frequent than in areas surrounding it. This will provide new insights into the evolution of a segment of the genome and aid in explaining how particular mutations are dispersed to numerous chromosome types. Second, study of additional beta-thalassemia genes from human populations not previously studied will provide new gene defects, some of which may yield further clues about RNA transcription and processing. In addition, some (e.g., the coding region substitutions that affect RNA processing) may allow identification of new mechanisms of gene dysfunction. Third, we need further refinement of prenatal diagnostic tests so that early, accurate, and simplified assessment of pregnancies at risk can be accomplished widely, particularly in those geographic regions where beta-thalassemia is especially prevalent.