Translating 'dementia friends' programme to undergraduate medical and nursing practice: a qualitative exploration.
Dementia awareness is a key priority of medical and nursing pre-registration education. The 'dementia friends' programme is an internationally recognised and accredited dementia awareness workshop that is led by a trained facilitator. While this programme has been associated with positive outcomes, few studies have examined how medical and nursing students apply their learning in practice after the workshop. The aim of his study was to explore how nursing and medical students apply the dementia friend's programme into practice when caring for people living with dementia. Seven focus-group interviews were conducted with 36 nursing students and 14 medical students at one university in Northern Ireland (n = 50), following 'the dementia friends programme. Interview guides were co-designed alongside people living with dementia. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Ethical approval was granted for this study. Four themes emerged: 'reframing dementia', which highlighted how the education had enabled students to actively empower and support people living with dementia in practice; 'dementia friendly design', which focused on how students had modified their clinical environments when providing care for people living with dementia, 'creative communication', which considered how students had used their education to adapt their verbal and non-verbal communication with people living with dementia and 'realities of advanced dementia' which contemplated how students believed their dementia education could be improved within their current curriculum. The Dementia Friends programme has actively supported nursing and medical students to improve the lives of people with dementia in their care through environmental adaptions and creative approaches to communication. This study provides an evidence base that supports the provision of 'a dementia friends programme to healthcare professional students. The study also highlights how this education can actively influence how nursing and medical students support people living with dementia in their practice in the months and years after education.


Insulation Cork Boards-Environmental Life Cycle Assessment of an Organic Construction Material.
Envelope insulation is a relevant technical solution to cut energy consumption and reduce environmental impacts in buildings. Insulation Cork Boards (ICB) are a natural thermal insulation material whose production promotes the recycling of agricultural waste. The aim of this paper is to determine and evaluate the environmental impacts of the production, use, and end-of-life processing of ICB. A "cradle-to-cradle" environmental Life Cycle Assessment (LCA) was performed according to International LCA standards and the European standards on the environmental evaluation of buildings. These results were based on site-specific data and resulted from a consistent methodology, fully described in the paper for each life cycle stage: Cork oak tree growth, ICB production, and end-of-life processing-modeling of the carbon flows (i.e., uptakes and emissions), including sensitivity analysis of this procedure; at the production stage-the modeling of energy processes and a sensitivity analysis of the allocation procedures; during building operation-the expected service life of ICB; an analysis concerning the need to consider the thermal diffusivity of ICB in the comparison of the performance of insulation materials. This paper presents the up-to-date "cradle-to-cradle" environmental performance of ICB for the environmental categories and life-cycle stages defined in European standards.


Localization of the mandibular neurovascular bundle using dental magnetic resonance imaging.
To assess the reliability of a commercially available 3D-MPR MRI program for the jaws for imaging the mandibular neurovascular bundle. A gradient echo sequence (TR: 49 ms/TE: 6.3 ms/flip angle: 25 degrees/excitations: 3) with a spectral fat suppression pre-impulse and a voxel size of 0.9 x 0.9 x 0.8 mm was designed. Cross-sectional and panoramic reconstruction of the whole mandible were performed from the axial scans using Easy Vision (Philips, Best, The Netherlands) software package. The ability of differentiate the mandibular neurovascular bundle was assessed in 11 patients. The mandibular neurovascular bundle was clearly visualized in all cases. Dental MRI is a possible alternative to plain films or CT for patients requiring surgery near the mandibular canal.


Ultrastructural analysis of acute lymphoblastic cells: peanut lectin binding correlates with degree of differentiation of the leukemic cells.
Peanut agglutinin (PNA) has been shown to bind selectively to immature cells. Bone marrow cells from some children having acute lymphocytic leukemia (ALL) bind PNA while cells from other ALL patients do not bind, the significance being that the patients whose cells bind PNA have a poorer prognosis than those not binding PNA. In the present study, PNA was conjugated to horseradish peroxidase and the two cell types were compared. Cells binding PNA are immature compared with the non-PNA-binding cells.


Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses.
Bath application of the inhibitors of phospholipases, nordihydroguaiaretic acid (NDGA) and p-bromo-phenacyl bromide (BPB), to the rat hippocampal slices suppressed long-term potentiation (LTP) in Schaffer/commissural-CA1 pyramidal synapses. On the other hand, neither of the two inhibitors suppressed LTP in mossy fiber-CA3 pyramidal cell synapses. BPB did not suppress phosphatidylinositol-specific phospholipase C (PI-PLC) activity of the slices. These results suggested that the mechanisms of LTP were quite different in the CA1 and CA3 subfields of rat hippocampus: in CA1, the involvement of an arachidonate metabolism was strongly suggested, whereas in CA3, an arachidonic acid cascade may not be necessary for LTP.


Influence of plasma calcium and vitamin D on bone collagen. Effects on lysine hydroxylation and crosslink formation.
In chick bone collagen the degree of lysine hydroxylation and the magnitude of the crosslink ratio dihydroxylysinonorleucine/hydroxylysinonorleucine were both found to be inversely related to the concentration of plasma calcium. Lysine hydroxylation was also affected by a second factor related to vitamin D status.


Enhancing the Photocatalytic Activity of Zirconium-Based Metal-Organic Frameworks Through the Formation of Mixed-Valence Centers.
Despite the desirability of metal-organic frameworks (MOFs) as heterogeneous photocatalysts, current strategies available to enhance the performance of MOF photocatalysts are complicated and expensive. Herein, a simple strategy is presented for improving the activity of MOF photocatalysts by regulating the atomic interface structure of the metal active sites on the MOF. In this study, MOF (PCN-222) is hybridized with cellulose acetate (CA@PCN-222) through an optimized atomic interface strategy, which lowers the average valence state of Zr ions. The electronic metal-support interaction mechanism of CA@PCN-222 is revealed by evaluating the photocatalytic CO2 reduction reaction (CO2 RR). The experimental results suggested that the electron migration efficiency at the atomic interface of the MOFs strongly coupled with cellulose is significantly improved. In particular, the CO2 RR to formate activity of CA@PCN-222 photocatalyst greatly increased from 778.2 to 2816.0 µmol g-1 compared with pristine PCN-222 without cellulose acetate. The findings suggest that the strongly coupled metal-ligand moiety at the atomic interface of MOFs may play a synergistic role in heterogeneous catalysts.


Age determination of adult individuals by three-dimensional modelling of canines.
Accurate age determination is fundamental in both forensic medicine and anthropology. Many methods that relate dental characteristics to adult age have been proposed, but there is still no simple and reliable method that does not damage the study material. The aim of this work was to propose a relevant and practical technique for determining age in adults that could be used in both living and deceased individuals. The sample was composed of 210 CT scans from individuals aged from 15 to 85 years old, with four healthy canines present in the mouth. The 840 canines were modelled using Mimics® 10.01 software. The pulp volume/total volume ratio ×100 was determined for each tooth. Seven mathematical models, corresponding to all possible real situations, were determined by the weighted least squares method and ranked in order of relative performance. The adequacy of the seven models to the data was very high with the regressions proposed (0.915 < R (2) adjusted < 0.964). Ranked in order of performance, the maxillary model was the most powerful of the seven models for age determination, followed by the 4 canines model, the 13 model and the 23 model.


Knockdown of lncRNA MFI2-AS1 inhibits lipopolysaccharide-induced osteoarthritis progression by miR-130a-3p/TCF4.
Long noncoding RNA melanotransferrin antisense RNA (MFI2-AS1) plays a vital role in the development of multiple diseases. This study aimed to investigate the effect of this lncRNA on osteoarthritis progression and explore the interaction among MFI2-AS1, microRNA (miR)-130a-3p and transcription factor 4 (TCF4). Forty-six knee osteoarthritis tissues and 28 normal samples were collected. Human chondrocytes C28/I2 cells treated by lipopolysaccharide (LPS) were used as the model of osteoarthritis. The expression levels of MFI2-AS1, miR-130a-3p and TCF4 were detected by quantitative real-time polymerase chain reaction or western blot. LPS-induced chondrocytes injury was investigated by cell viability, apoptosis, inflammatory response and extracellular matrix degradation using MTT, flow cytometry, enzyme-linked immunosorbent assay and western blot. The target association between miR-130a-3p and MFI2-AS1 or TCF4 was confirmed by luciferase reporter assay and RNA immunoprecipitation. MFI2-AS1 expression was increased in osteoarthritis tissues and LPS-treated C28/I2 cells. Silence of MFI2-AS1 attenuated LPS-induced viability suppression, apoptosis production, inflammatory response and extracellular matrix degradation. MFI2-AS1 was validated as a decoy of miR-130a-3p and TCF4 was confirmed as a target of miR-130a-3p. miR-130a-3p overexpression inhibited LPS-induced cell injury in C28/I2 cells by decreasing TCF4 expression. Moreover, knockdown of MFI2-AS1 alleviated LPS-induced cell injury in C28/I2 cells by mediating miR-130a-3p and TCF4. Knockdown of MFI2-AS1 increased cell viability but suppressed apoptosis, inflammatory response and extracellular matrix degradation in LPS-treated chondrocytes by increasing miR-130a-3p and decreasing TCF4, indicating a novel target for the treatment of osteoarthritis.


Isolation of viable Toxoplasma gondii cysts from brain samples for oral infection.
A method was developed to separate contaminant-free viable Toxoplasma gondii cysts from brain samples of infected mice for molecular biology studies and reinfection. The mice brains were homogenized and washed with phosphate buffered saline (PBS) Tween 80 prior to fractionation using 19-22% dextran solution. Finally, the supernatant was purified by two-step membrane filtration (100-160 microm and < 10 microm) to obtain pure T. gondii cyst. The isolates were analyzed through microscopic observation, qPCR and by reinfection of new batch of mice. T. gondii cysts were best isolated with 21% dextran solution and two step filtration. The method was observed not to disrupt the integrity of the cysts containing bradyzoites. In addition, the isolated cysts in the filtrate were found to be contaminant-free, viable and able to infect healthy mice when introduced orally; which, mimics the natural infectivity pathway.


Global myocardial ischemia in the newborn, juvenile, and adult isolated isovolumic rabbit heart. Age-related differences in systolic function, diastolic stiffness, coronary resistance, myocardial oxygen consumption, and extracellular pH.
Controversy persists over the relative tolerance of the immature myocardium to global ischemia. Thus, we evaluated the physiologic effects of 30, 60, and 180 minutes of global ischemia in an isolated, isovolumic rabbit heart model, at 3 different ages: newborns (less than 1 week of age) (n = 36), juveniles (4 to 6 weeks old) (n = 36), and adults (5 to 7 months old) (n = 36). Following 30 and 60 minutes of ischemia, respectively, adults recovered 87 +/- 4% (mean +/- SEM) and 90 +/- 7% of baseline systolic function, and juveniles recovered 91 +/- 10% and 85 +/- 8%. In contrast, newborns recovered only 27 +/- 6% and 28 +/- 4% of baseline systolic function (p less than 0.05 compared to adults and juveniles). During ischemia, newborn hearts became stiff more rapidly, reaching 361 +/- 46% of baseline stiffness by 60 minutes, whereas adults and juveniles were at 122 +/- 33% and 92 +/- 18% of baseline stiffness (p less than 0.05 newborns compared to adults and juveniles). With reperfusion after 60 minutes of ischemia, the work efficiency of the newborn heart deteriorated to 39 +/- 7% of baseline, compared with 95 +/- 7% and 91 +/- 7% of baseline efficiency in the adult and juvenile hearts (p less than 0.05, newborns compared to adults and juveniles). The ratio of tissue wet-to-dry weights were similar in all age groups after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Upregulation of MTOR, RPS6KB1, and EIF4EBP1 in the whole blood samples of Iranian patients with multiple sclerosis compared to healthy controls.
Various genetic and epigenetic mechanisms have been suggested to play roles as the underlying pathophysiology of Multiple Sclerosis (MS). Changes in different parts of the mTOR signaling pathway are among the potential suggested mechanisms based on the specific roles of this pathway in CNS. MTOR, RPS6KB1, and EIFEBP1 genes are among important genes in the mTOR pathway, responsible for the proper function of acting proteins in this signaling pathway. This study aimed to investigate the relative expression levels of these genes in the blood samples of relapsing-remitting MS (RRMS) patients compared to healthy controls. In this case-control study blood samples were collected from 30 newly diagnosed RRMS patients and 30 age and sex-matched healthy controls. mRNA level of MTOR, RPS6KB1, and EIFEBP1 genes were assessed using Real-Time PCR. The expression of MTOR, RPS6KB1, and EIF4EBP1 genes was up regulated in MS patients compared to healthy controls (p < 0.001 for all mentioned genes). Considering gender differences, expression of the mentioned genes was increased among female patients (all P < 0.001). However, no statistically significant changes were observed among male patients. Based on the receiver operating characteristic, MTOR gene had the highest diagnostic value followed by EIF4EBP1 and RPS6KB1 genes in differentiating RRMS patients from controls. In conclusion, we found the simultaneous upregulation of MTOR, RPS6KB1, and EIF4EBP1 genes among RRMS patients. MTOR showed to have the highest diagnostic value compared to other 2 genes in differentiating RRMS patients. Further studies evaluating the importance of these findings from pharmacological and prognostic perspectives are necessary.


[Thyroid and hepatitis C].
Autoimmune thyroid diseases are complex diseases that develop as a result of interactions between genetic, epigenetic and environmental factors. IFNa therapy of chronic HCV infection is associated with subclinical or clinical thyroiditis, while the relationship between thyroiditis and virus C infection is still debated.


SAP102 contributes to hyperalgesia formation in the cancer induced bone pain rat model by anchoring NMDA receptors.
The pathogenesis of cancer induced bone pain (CIBP) is extremely complex, and glutamate receptor dysfunction plays an important role in the formation of CIBP. Synapse-associated protein 102 (SAP102) anchors glutamate receptors in the postsynaptic membrane. However, its effect on hyperalgesia formation in CIBP has not been clarified. This study investigated the role of SAP102 in the formation of hyperalgesia in rats with CIBP SAP102 is present in spinal dorsal horn neurons, but not in astrocytes or microglia. NMDAR-NR2B is localized with neurons. In addition, SAP102 and NMDAR-NR2B expression levels in spinal dorsal horn tissues were detected by Western blot and co-immunoprecipitation. Intrathecal injection of lentiviral vector of RNAi to knockdown SAP102 expression in the spinal dorsal horn significantly attenuated abnormal mechanic pain when compared to non-coding lentiviral vector. These findings indicate that SAP102 can anchor NMDA receptors to affect hyperalgesia formation in bone cancer pain.


Influence of common genetic variants on childhood kidney outcomes.
Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood. We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFRcreat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels. We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10(-3)) and with a lower eGFR (P value 4.0 × 10(-4)) in children. The genetic risk score was not associated with microalbuminuria. Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.


More phylogenetically diverse polycultures inconsistently suppress insect herbivore populations.
Because the diet of many herbivorous insects is restricted to closely related taxa with similar chemistry, intercropping with diverse plant communities may reduce both pest populations and reliance on chemical pesticides in agroecosystems. We tested whether the effectiveness of intercropping against herbivorous insects depends on the phylogenetic relatedness of neighboring crops, using butternut squash (Cucurbita moschata) as a focal crop species in a series of different intercropping combinations. We found that increased phylogenetic divergence of neighboring plants could reduce abundance of herbivorous insects, but the effect was only detectable mid-season. In addition, we tested two hypothesized mechanisms for a negative association between phylogenetic distance of neighboring plants and reduced herbivore populations: one, we tested using Y-tube olfactometer and choice cage trials whether diverse volatile cues impede host-plant location by the dominant pest of butternut squash in our experiment, striped cucumber beetle Acalymma vittatum. Two, we recorded predator and parasitoid abundance relative to crop phylodiversity to test whether diverse crops support larger natural-enemy populations that can better control pest species. Our results, however, did not support either hypothesis. Striped cucumber beetles preferentially oriented toward non-host-plant volatiles, and predator populations more often decreased with phylodiversity than increased. Thus, the mechanisms driving associations in the field between phylogenetic divergence and herbivore populations remain unclear.


Effects of opioid peptides administered in conscious rats on the changes in blood adrenaline levels caused by immobilization stress.
Effects of several opioid peptides administered in the lateral cerebroventricle on the changes in blood adrenaline (AD) levels were examined at 10, 20 and 30 min after the start of immobilization in conscious rats. beta-Endorphin, (D-Ala2)-Met-enkephalinamide, morphiceptin and (D-Ala2, D-Leu5)-enkephalinamide produced significantly lower elevations of AD than the control, and the effect was enhanced by naloxone. The effect of dynorphin, however, was almost the same as that of the control.


Number of sampling movements and manual stiffness judgments.
It has been suggested that when using posteroanterior pressure to assess the stiffness of the spine, no more than two or three oscillations should be used. This study sought to examine this clinical impression by investigating the effect of the number of sampling movements on stiffness perception. Perceptual study using a mechanical device to provide stiffness stimuli, with university staff and students as judges. University psychophysics laboratory. In part 1, subjects were directed to sample the stimuli a prescribed number of times (either 1, 2, 3, 4 or 5 pushes), whereas in part 2, subjects were free to choose the number of sampling movements. Measures of interstimulus discriminability and bias. An inverted-U relationship between the number of directed sampling movements and stiffness discriminability was found, with three cycles providing best discriminability. When subjects were given a choice, most chose to use three cycles. The number of sampling movements had no effect on bias. This study confirms the hypothesis under investigation and suggests that therapists will be maximally sensitive when using three testing cycles of posteroanterior pressure to assess stiffness.


A computationally efficient QRS detection algorithm for wearable ECG sensors.
In this paper we present a novel Dual-Slope QRS detection algorithm with low computational complexity, suitable for wearable ECG devices. The Dual-Slope algorithm calculates the slopes on both sides of a peak in the ECG signal; And based on these slopes, three criterions are developed for simultaneously checking 1)Steepness 2)Shape and 3)Height of the signal, to locate the QRS complex. The algorithm, evaluated against MIT/BIH Arrhythmia Database, achieves a very high detection rate of 99.45%, a sensitivity of 99.82% and a positive prediction of 99.63%.


Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells.
Human folate-binding proteins (FBPs) are single chain glycoproteins that contain a high affinity binding site for folates and methotrexate and occur in a soluble or membrane-associated form. The membrane-associated FBP is involved in the uptake of physiologic folates and methotrexate. In this study, human FBP cDNA clones were isolated from human malignant nasopharyngeal carcinoma (KB) cell and placental cDNA libraries by means of oligonucleotide probes derived from determined internal amino acid sequences. The longest cDNA nucleotide sequence is 1126 base pairs and encodes a polypeptide that contains 257 amino acid residues (calculated molecular mass = 29,817). The deduced amino acid sequence is 80% homologous to a bovine soluble FBP, is greater than 99% homologous to the reported partial amino acid sequence of the human soluble FBP, contains three potential N-linked glycosylation sites, and has hydrophobic amino- and carboxylterminal regions which are consistent with a signal peptide and a potential membrane-anchoring domain, respectively. On Northern blot analysis, radiolabeled cDNA probes hybridize to a single 1100-base pair mRNA species that is expressed to a variable degree in human KB cells, placenta, brain, and epithelial mRNA but is not detectable in human liver mRNA. In vitro translation of RNA transcripts from the FBP cDNA inserts yields a 30-kDa and a 42-kDa polypeptide in the absence and presence of microsomal membranes, respectively.


Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats.
The phenotypic alteration of interstitial fibroblasts into 'myofibroblasts', acquiring characteristics of both fibroblasts and smooth muscle cells is a key event in the formation of tubulointerstitial fibrosis. The up-regulation of the early growth response gene 1 (Egr-1) preceded the increased interstitial expression of alpha-smooth muscle actin (alphaSMA), a marker of phenotypic changes, in obstructed kidney, a model of interstitial fibrosis. To target Egr-1 expression in the interstitium of obstructed kidneys, we introduced a DNA enzyme for Egr-1 (ED5) or scrambled DNA (SCR) into interstitial fibroblasts by electroporation-mediated gene transfer. Northern blot analysis confirmed an increase in the cortical mRNA expression of Egr-1 in the obstructed kidneys from untreated or SCR-treated rats, while ED5 transfection blocked Egr-1 expression with a concomitant reduction in TGF-beta, alphaSMA and type I collagen mRNA expression. Consequently, ED5 inhibited interstitial fibrosis. In conclusion, electroporation-mediated retrograde gene transfer can be an ideal vehicle into interstitial fibroblasts, and molecular intervention of Egr-1 in the interstitium may become a new therapeutic strategy for interstitial fibrosis.


Delayed onset of luteinization as a cause of infertility.
Two groups of infertility patients with regular cycles and apparently normal ovarian function were studied. In group I (n = 28) the infertility could be explained satisfactorily either by tubal occlusion or by infertility of the husband, or the women became pregnant within a few months. In group II (n = 32) no explanation was found for the infertility. Significantly fewer ovulation stigmata were present at laparoscopy in group II than in group I (P less than 0.05). In group I the basal body temperature (BBT) (P less than 0.001) and the plasma progesterone concentrations (P less than 0.05) were significantly elevated on the 1st day following the luteinizing hormone (LH) peak. In group II, THE BBT was slightly elevated on the 1st day following the LH peak (P less than 0.05), but the increase in the plasma progesterone concentrations occurred only on the 2nd day following the LH peak. In four women the onset of the BBT rise followed a normal LH peak with delays respectively, of 3, 4, 4, and 5 days, and in two women no LH peak occurred immediately prior to the onset of the BBT rise. The datings of the endometrial biopsies in these patients were in phase with the onset of the BBT rise but not with the LH peak. It is concluded that anovulation with in situ luteinization may be a rather frequent cause of infertility in regularly cycling women. A hypothesis about the mechanism of anovulation with in situ luteinization is proposed.


Human mesenchymal stem cells respond differentially to platelet preparations and synthesize hyaluronic acid in nucleus pulposus extracellular matrix.
In recent years, autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have been used as treatments for disc-related pain. A better understanding of the effects of leukocyte-rich (LR) versus leukocyte poor (LP-) PRP on bone marrow derived human mesenchymal stem/progenitor cells (hMSCs) is likely to improve future research studies, clinical practice and care for patients with chronic discogenic back pain. The primary aim of this study is to determine the effects of LR-PRP and LP-PRP on the proliferation and migration of hMSCs in pig nucleus pulposus (NP) extracellular matrix (ECM). The secondary aim is to characterize hMSC-dependent expression of the matrix remodeling enzymes metalloproteinases MMP-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinases TIMP-2, and to determine whether transplanted hMSCs can synthesize hyaluronic acid (HA). Controlled laboratory study. Bone marrow-derived culture expanded hMSCs were seeded onto pig NP and cultured with LR-PRP, LP-PRP or serum/platelet releasate (PR). The same conditions without hMSCs were used as controls. hMSC proliferation, migration and dispersion was assessed via fluorescent microscopy, while HA synthesis, MMP-2, MMP-3, MMP-9, and TIMP-2 protein levels were assessed via enzyme linked immunosorbent assay. All funding was provided by a 501c(3) research foundation and does not have any commercial or sponsorship interests. LP-PRP and PR cultures resulted in higher hMSC proliferation, migration, dispersion, and MMP-2 expression. LP-PRP cultures resulted in the highest HA production. LR-PRP cultures resulted in lower hMSC proliferation, negligible migration and dispersion, increased MMP-9 expression and lower HA production. Human bone marrow-derived hMSCs seeded onto pig NP ECM are capable of synthesizing HA, indicating a transition towards a NP cell phenotype. This process was most enhanced by LP-PRP and marked by increased hMSC proliferation, MMP-2 production, HA synthesis and reduced MMP-9 levels. LP-PRP and PR, with or without hMSCs, may provide better outcomes than LR-PRP in lab investigations and clinical trials for discogenic pain. Bone marrow-derived hMSCs may hold promise as a treatment for disc degeneration.


Nerve induced responses and force-velocity relations of regenerated detrusor muscle after subtotal cystectomy in the rat.
To study the pharmacological and mechanical properties of newly developed detrusor muscle after subtotal cystectomy, to explore if the regenerated detrusor has characteristics similar to the normal bladder base, from which it regenerated, or to the normal bladder body which it replaces. Partial cystectomy was performed in female rats. Fifteen weeks later, detrusor strips were cut from supratrigonal and equatorial segments. Unoperated rats served as controls. Responses to field stimulation were obtained in the absence and presence of scopolamine, prazosin, and P2X1 blockade. Dose-response curves were obtained for carbachol, alpha,beta-methylene-ATP, and phenylephrine. Force-velocity data were obtained on maximally activated chemically skinned preparations. Maximal contractile response to field stimulation was 60% of that to high-K+ with no difference between strips from control and cystectomy bladders. Prazosin had no effect. Scopolamine decreased maximal response of supratrigonal strips to 62 +/- 6 (controls) and 61 +/- 4% (operated) of that without blocker. For equatorial strips the decrease was to 81 +/- 5 (controls) and 58 +/- 8% (operated). Frequency-response relations were obtained during blockade with scopolamine, alpha,beta-methylene-ATP, and prazosin. Supratrigonal strips showed a pronounced additional inhibition up to 40 Hz. Equatorial strips from controls were completely inhibited at all frequencies. Equatorial strips from operated bladders were inhibited up to 20 Hz but not at 40 and 60 Hz. Carbachol EC(50) values were similar in all groups. Maximum response to phenylephrine was 10-20% of high-K+ response. Maximal shortening velocity (Vmax) was similar in control supratrigonal and equatorial strips, but was significantly lower in the operated bladders. (1): A regional difference exists in pharmacological properties of control detrusor, with a considerable contractile response to stimulation remaining in the supratrigonal muscle after simultaneous cholinergic, adrenergic, and purinergic blockade. (2): The new detrusor was functionally well innervated with no supersensitivity to muscarinic stimulation. (3): The newly formed bladder body had pharmacological properties specific for the supratrigonal segment from which it had developed. (4): There was no regional difference in force-velocity characteristics of the control detrusor. (5): The lowered Vmax in the newly formed bladder might thus be related to growth and regeneration of muscle cells.


Chronic pulmonary thromboendarterectomy complicated by antithrombin III deficiency and antiphospholipid syndrome.
Pulmonary thromboendarterectomy was performed on two patients with chronic pulmonary thromboembolism showing thrombotic tendency. Patient 1 was a 25-year-old male with the disease complicated by congenital antithrombin III deficiency. Patient 2 was a 21-year-old male with the disease complicated by antiphospholipid syndrome. Both patients were admitted to the center upon showing dyspnea. Lung perfusion scintigraphy revealed multiple defects in the right and left lungs. Pulmonary arteriography showed occlusion and stenosis from lobar to segmental arteries. Cardiac catheterization showed marked pulmonary hypertension. Pulmonary angioscopy confirmed the presence of organized thrombi while an intravascular ultrasound revealed a thickening of the pulmonary arterial walls in both lungs. After the insertion of an inferior vena cava filter in each patient, surgery was performed. Following a median sternotomy, a cardiopulmonary bypass was utilized to induce deep hypothermia at a pharyngeal temperature of 16 degrees C, after which a thromboendarterectomy of the bilateral pulmonary arteries was performed under intermittent circulatory arrest. A large amount of organized thrombi was extracted from these arteries. After surgery, both patients showed good postoperative outcome with improved blood flow in both lungs, reduced pulmonary arterial pressure and increased cardiac output.


Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes: The involvement of peroxisome proliferator-activated receptor-γ and dipeptidyl peptidase-4.
This research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium (EACA) tubers in a type 2 diabetes model. The tubers were processed and sequentially extracted in hexane followed by ethylacetate, using a Soxhlet apparatus, and subjected to gas chromatography-mass spectrometry (GC-MS). The acute toxicity of EACA was investigated in albino Wistar rats. An antihyperglycaemic study was carried out using high-fat diet (pelletized diet and margarine in the ratio of 10:1 and 20% fructose solution) and streptozotocin-induced hyperglycaemic Wistar rats. The effects of the extract (150, 300 and 600 mg/kg) on blood glucose level, insulin, peroxisome proliferator-activated receptor-γ (PPAR-γ) and dipeptidyl peptidase-4 (DPP-4) were evaluated using enzyme-linked immunosorbent assay. The oral median lethal dose in Wistar rats was estimated to be > 5000 mg/kg. Treatment with EACA at all doses significantly reduced the fasting blood glucose levels, compared to the hyperglycaemic control, and over time. Administration of EACA increased the serum insulin and PPAR-γ levels while decreasing DPP-4 levels. GC-MS analysis revealed the presence of 13 compounds, with isothiazole and isoxazolidine covering total area of 24.6% and 22.69%, respectively. The findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-γ level and decreasing DPP-4 activity.


Structural insights into biosynthesis of resorcinolic lipids by a type III polyketide synthase in Neurospora crassa.
Microbial type III polyketide synthases (PKSs) have revealed remarkable mechanistic as well as functional versatility. Recently, a type III PKS homolog from Azotobacter has been implicated in the biosynthesis of resorcinolic lipids, thus adding a new functional significance to this class of proteins. Here, we report the structural and mutational investigations of a novel type III PKS protein from Neurospora crassa involved in the biosynthesis of resorcinolic metabolites by utilizing long chain fatty acyl-CoAs. The structure revealed a long hydrophobic tunnel responsible for its fatty acyl chain length specificity resembling that of PKS18, a mycobacterial type III PKS. Structure-based mutational studies to block the tunnel not only altered the fatty acyl chain specificity but also resulted in change of cyclization pattern affecting the product profile. This first structural characterization of a resorcinolic lipid synthase provides insights into the coordinated functioning of cyclization and a substrate-binding pocket, which shows mechanistic intricacy underlying type III PKS catalysis.


Synthesis and mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling.
A series of anilinonicotinyl linked pyrazolo[1,5-a]pyrimidine conjugates (6a-x) were synthesized and evaluated for their antiproliferative activity. Some of these conjugates exhibited promising cytotoxic effects in the MCF-7 cell line and among these 6a and 6c exhibited significant effects, apart from G2/M cell cycle arrest. Interestingly they showed profound effects on cyclin D1, Bcl-2 and survivin proteins that regulate breast cancer cell proliferation. Moreover, ER alpha protein expression was studied to understand regulatory role of these conjugates on estrogen activity in estrogen positive breast cancer cells like MCF-7 and compounds 6a and 6c reduced their activity.


Controlled clinical trial of cadralazine as a second-step drug in the treatment of hypertension.
The antihypertensive efficacy of a new long-lasting vasodilator, cadralazine, and the diuretic chlorthalidone have been compared in hypertensive patients receiving concurrent treatment with atenolol. After a 4-week run-in period with atenolol alone 100 mg/day, two groups of 10 patients whose diastolic blood pressure exceeded 100 mm Hg were given for a period of 65 days either cadralazine 15 mg/day or chlorthalidone 25 mg/day, according to a randomized, double-blind, between-patients design. Compared to atenolol alone, both cadralazine and chlorthalidone induced a statistically and clinically significant decrease in blood pressure. The antihypertensive effect did not differ significantly between groups. Good compensation of the atenolol-induced decrease in heart rate was obtained with cadralazine, whereas during atenolol + chlorthalidone treatment at times the standing heart rate was significantly lower than during treatment with atenolol + cadralazine. Side-effects, many of which were already present during atenolol treatment, occurred with a similar frequency in both groups. It is concluded that atenolol + cadralazine and atenolol + chlorthalidone are equally well tolerated, acceptable and effective in the treatment of hypertension, but that further studies are warranted to explore the potential haemodynamic advantages of the cadralazine + atenolol combination.


[Eosinophilic esophagitis in the adult--clinical, endoscopic, pH-metric, and manometric findings].
Eosinophilic esophagitis (EE) is a condition characterized by dysphagia and frequent food impaction in young adults. The aim of our study was to evaluate the clinical aspects, endoscopic features, pH-metric and motility disorders in EE. Adult patients with EE were prospectivity included. Endoscopy with biopsy, stationary esophageal manometry, and 24-hour pH-metry were performed. We analyzed the duration of disease, allergies, blood peripheral eosinophilia, prevalence of dysphagia, number of food impaction episodes, and complications during the endoscopic procedure. Eleven male patients with a mean age of 35 years were followed. Endoscopy showed esophageal disorders in all cases: 5 esophageal felinizations, mucosal abnormalities in 4 cases, distal rings in 3 cases, and 2 esophageal stenoses. In two cases mucosal tearing during the endoscopic procedure was described. In 6 patients the manometric study showed motor disorders affecting the esophageal body, 5 of them displaying hypomotility. Two patients showed pathological gastroesophageal reflux during pH-monitoring. Blood peripheral eosinophilia was detected in 3 patients. Although endoscopic abnormalities are frequently found, they do not usually explain dysphagia and food impaction episodes in EE. Ineffective esophageal peristalsis is the most prevalent manometric disorder associated with this entity, although it is not clearly related to symptom worsening either.


Classifying risk level of gastric cancer: Evaluation of questionnaire-based prediction model.
This study aimed at evaluating the efficacy of the questionnaire-based prediction model in an independent prospective cohort. A cluster-randomized controlled trial was conducted in Changsha, Harbin, Luoshan, and Sheyang in eastern China in 2015-2017. A total of 182 villages/communities were regarded as clusters, and allocated to screening arm or control arm randomly. Face-to-face interview through a questionnaire interview, including of relevant risk factors of gastric cancer, was administered for each subject. Participants were further classified into high-risk or low-risk groups based on their exposure to risk factors. All participants were followed up until December 31, 2019. Cumulative incidence rates from gastric cancer between high-risk and low-risk groups were calculated and compared using the log-rank test. Cox proportional hazard regression models were applied to estimate hazard ratio (HR) and 95% confidence interval (95% CI). Totally, 89,914 residents were recruited with a mean follow-up of 3.47 years. And 42,015 (46.73%) individuals were classified into high-risk group and 47,899 (53.27%) subjects were categorized into low-risk group. Gastric cancer was diagnosed in 131 participants, of which 91 were in high-risk group. Compared with the low-risk participants, high-risk individuals were more likely to develop gastric cancer (adjusted HR=2.15, 95% CI, 1.23-3.76). The sensitivity of the questionnaire-based model was estimated at 61.82% (95% CI, 47.71-74.28) in a general population. Our questionnaire-based model is effective at identifying high-risk individuals for gastric cancer.


Towards Building Comprehensive Legal Frameworks for Corporate Accountability in Food Governance.
Given the failures of the UN Food Systems Summit and Food and Agriculture Organization (FAO) to tackle the problems related to the corporate capture of food governance, this article calls for developing comprehensive legal frameworks for corporate accountability in food governance. In doing so, the authors identify key regulatory elements that need to be taken into account in food governance discussions. Their recommendations are borrowed from the guidance developed in the context of the negotiations for an International Legally Binding Instrument on TNCs and other Businesses with Respect to Human Rights, as well as in the WHO Framework Convention on Tobacco Control, the WHO Framework of Engagement with Non-State Actors, and the WHO Financial Regulations and Financial Rules.


Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.
DNA polymerase ζ (Polζ) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 Å) and without DNA (4.1 Å). Polζ displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31' Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein-protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Polζ's role in TLS and provide a framework for new cancer therapeutics.


[Operative access routes in reconstructive vascular surgery of arteries. Part 1: neck and torso].
Exact knowledge of the topographical anatomy of the arterial vascular system is the basis for all access routes. This article describes the most important assess routes in the neck and torso regions and gives an overview of the basic principles of the surgical technique with respect to suture material, suture technique, anastomotic technique and the atraumatic preparation of the anastomosis region. The article makes no claims to completeness because this would overstretch the limits but refers in particular to the references listed.


Collagen-like antimicrobial peptides.
Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016.


The Minimal Clinically Important Difference of the Anterior Skull Base Nasal Inventory-12.
The minimal clinically important difference (MCID) is defined as the smallest change in health-related quality of life (QOL) that patients consider meaningful. The MCID is essential for determining clinically significant changes, rather than simply statistically significant changes, in QOL scores. The Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific sinonasal QOL instrument, has emerged as a standard instrument for assessing QOL in patients who have undergone endonasal transsphenoidal surgery. To determine the MCID for the ASK Nasal-12. Distribution- and anchor-based methods were used to determine the MCID for the ASK Nasal-12 based on raw data from a multicenter prospective QOL study of 218 patients. Two distribution-based statistical methods, the one-half standard deviation method and the effect-size method, both yielded MCIDs of 0.37 (medium effect). The first anchor-based method, using the 2-wk postoperative overall nasal functioning item as the anchor, yielded an MCID of 0.31. The second anchor-based method, using the 2-wk postoperative Short Form Health Survey 8 bodily pain item as the anchor, yielded an MCID of 0.29. The largest MCID obtained for the ASK Nasal-12 using 4 statistical methods 2 wk postoperatively was 0.37. This information provides clinicians with an essential context for determining the clinical significance of changes in QOL scores after interventions. Our results will help clinicians better interpret QOL scores and design future studies that are powered to detect meaningful QOL changes.


Preservation of within-compound associations after blocked preexposure to two compound flavors.
Three experiments investigated the extinction of the within-compound A↔X association established when two compound flavors, AX and BX, are preexposed in blocks (i.e., AX, AX, AX, ... BX, BX, BX). In Experiment 1, a group of rats received preexposure to a block of AX trials followed by a second block of BX trials (AX-BX), while a second group received blocked preexposure to the same stimuli in the opposite order (BX-AX). Subsequently, flavor A was paired with lithium chloride. This conditioning resulted in a similar reduction of consumption of flavor X in both groups. In Experiment 2 four groups of rats received blocked preexposure to AX-BX, AX-B, A-BX, or A-X. After aversive conditioning of X, consumption of A and B was significantly lower for the groups which received these flavors paired with X than for the groups for which these flavors were presented isolated. In Experiment 3 a group of rats was preexposed to a block of SaltX presentations followed by a block of BX presentations (SaltX-BX), and a second group received blocked preexposure to (BX-SaltX). After subsequent sodium depletion, consumption of X was high and similar for the SaltX-BX and for the BX-SaltX groups. These results indicate that the within-compound association established in the first block of a blocked preexposure is not extinguished when the preexposure phase is concluded.


Airway complications after pulmonary transplantation.
Airway healing was identified initially as one of the fundamental limitations of pulmonary transplantation. Recent experience suggests that this is no longer the case. A series of 67 pulmonary transplants (27 heart-lung, 31 single-lung, 9 double-lung) in 66 patients surviving more than 14 days was reviewed with reference to airway complications. There were 75 anastomoses at risk in two groups as defined by anastomotic location: 47 anastomoses in 38 patients in a bronchial group and 28 anastomoses in 28 patients in a tracheal group. A total of 10 airway complications developed (stenosis in 5 patients [4 bronchial group, 1 tracheal group] and dehiscence in 5 patients [1 bronchial group, 4 tracheal group]) causing two airway-related deaths (2 of 67) in the series. However, no significant correlation could be identified with either ischemic interval, suture technique, type of wrap, preoperative or postoperative steroid therapy, or date of first rejection episode. Airway complications are no longer a major limitation of pulmonary transplantation. Satisfactory airway healing can occur in both the presence of steroid therapy and the absence of an omental or pericardial wrap.


Chromosome location of the ribosomal RNA genes in Triturus vulgaris meridionalis (Amphibia, Urodela). II. Intraspecific variability in number and position of the chromosome loci for 18S + 28S ribosomal RNA.
Ribosomal genes have been localized on mitotic and lampbrush chromosomes of 20 specimens of Triturus vulgaris meridionalis by in situ hybridization with 3H 18S + 28S rRNA. The results may be summarized as follows: 1) each individual shows positive in situ hybridization at the nucleolus organizing region (NOR) on chromosome XI; 2) in addition, many specimens exhibit a positive reaction in chromosomal sites other than the NOR (additional ribosomal sites); 3) the chromosomal distribution of the additional sites appears to be identical in different tissues from the same specimen and to follow a specific individual pattern; 4) the additional ribosomal sites are preferentially found at the telomeric, centromeric or C-band regions of the chromosomes involved.


Bis-Naphthalene Cleft with Aggregation-Induced Emission Properties through Lone-Pair⋅⋅⋅π Interactions.
A rigid molecular cleft shows unique aggregation-induced emission (AIE) by restricting the motion of aldehyde through intermolecular lone pair⋅⋅⋅π interactions, which are tuned by side chains. This AIE luminogen was demonstrated to work as a fluorescent sensor for aniline and an optical chirality sensor for chiral amine.


Purification and characterization of an extracellular keratinolytic protease from a new isolate of Aspergillus parasiticus.
Keratinolytic proteases find extensive applications both in environmental biotechnology and pharmaceutical industries. An extracellular keratinolytic protease was purified and characterized from the fungus, Aspergillus parasiticus, isolated from poultry soil. The enzyme was purified to homogeneity by acetone and ammonium sulfate precipitations followed by CM-Sepharose column chromatography. The molecular mass of the enzyme was 36kDa as judged by SDS-PAGE. The purified keratinase had a pH optimum of 7.0 and temperature optimum of 50(o)C. The enzyme hydrolyzed the substrate azocasein and the Km and Vmax of the purified keratinase were found to be 1.04mg/ml and 3463.34Units/min/mg protein, respectively. The enzyme showed increased activity in the presence of reducing agents. The enzyme was found to be glycosylated. According to the inhibition profiles obtained with the various protease inhibitors, it was confirmed that the purified keratinase belongs to the serine protease type. The purified enzyme activity was enhanced by calcium, magnesium and manganese ions and partially inhibited by cadmium, copper and zinc ions. The purified enzyme showed increased activity with nonionic detergents and urea.


Right hemothorax: An unusual presentation of a Barrett's ulcer perforation.
Despite improvements in detection and surgical techniques perforation of the esophagus are lifethreatening. In this case report a rare presentation esophageal perforation due to Barrett's ulceration into an aortic vessel is described. We report a 42 year old man with known Barrett's esophagus presenting with abdominal pain. Further investigations showed an active intrathoracal hemorrhage due to esophageal perforation at exactly the same site of the known Barret's ulcer one year before. Thoracotomy with evacuation of blood was performed and an aortic branch as bleeding focus was found. Hemothorax due to esophageal perforation of a benign Barrett's ulcer is rare. The diagnosis of aortoesophageal fistula's can be complicated and its presentation is frequently unspecific and is simply confused with other disorders. Acute thoracotomy is necessary and choice of closure depends on the cause and size of the perforation. This case illustrates the need for maintaining a wide-ranging view of potential casus of hemothorax. The key to survival in patients with aorto-esophageal fistula is maintaining awareness of the condition to allow early diagnosis and operative management of this treatable lesion.


Intracellular Ca2+ mediates lipoxygenase-induced proliferation of U-373 MG human astrocytoma cells.
The role of intracellular Ca2+ in the regulation of tumor cell proliferation by products of arachidonic acid (AA) metabolism was investigated using U-373 MG human astrocytoma cells. Treatment with nordihydroguaiaretic acid (NDGA), a lipoxygenase (LOX) inhibitor, or caffeic acid (CA), a specific 5-LOX inhibitor, suppressed proliferation of the tumor cells in a dose-dependent manner. However, indomethacin (Indo), a cyclooxygenase (COX) inhibitor, did not significantly alter proliferation of the tumor cells. At anti-proliferative concentrations, NDGA and CA significantly inhibited intracellular Ca2+ release induced by carbachol, a known intracellular Ca2+ agonist in the tumor cells. Exogenous administration of leukotriene B4 (LTB4), an AA metabolite of LOX pathway, enhanced proliferation of the tumor cells in a concentration-dependent fashion. In addition, LTB4 induced intracellular Ca2+ release. Intracellular Ca2+ inhibitors, such as an intracellular Ca2+ chelator (BAPTA) and intracellular Ca(2+)-release inhibitors (dantrolene and TMB-8), significantly blocked the LTB4-induced enhancement of cell proliferation and intracellular Ca2+ release. These results suggest that LOX activity may be critical for cell proliferation of the human astrocytoma cells and that intracellular Ca2+ may play a major role in the mechanism of action of LOX.


Comparison of monoclonal antibodies AUA1 and BER EP4 with anti-CEA for detecting carcinoma cells in serous effusions and distinguishing them from mesothelial cells.
Commercially available monoclonal antibodies AUA1, BER EP4 and carcinoembryonic antigen (CEA) were applied to cell blocks from 95 serous effusions. AUA1 and BER EP4 were reactive with 89% of effusions known to contain carcinoma cells, and anti-CEA with 71%. They also reacted with cells in two effusions from patients with malignant disease which were regarded as negative on conventional cytological examination of Papanicolaou-stained smears. They were negative in all but one of the benign effusions. Using all three antibodies, 95% of effusions containing carcinoma cells were detected. Use of these antibodies could improve the cytological diagnosis of serous effusions.


Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2 and p53 immunoexpression.
The aims of this study were twofold: (i) to determine the occurrence frequency of apocrine carcinoma of the breast (ApBCa) in Turkish breast cancer (BCa) patients; and (ii) to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), gross cystic disease protein-15 (GCDFP-15), c-erbB-2, and p53 in these cases. Six hundred and twenty-six cases of BCa were studied immunohistochemically (streptoavidin-biotin horseradish peroxidase method). The results of ApBCa were compared with those of invasive ductal carcinoma not otherwise specified type (IDC-NOS) cases of similar grade. Thirteen cases of ApBCa were encountered, accounting for 2.1% of all BCa cases. Immunohistochemically, ApBCa positivity was as follows: GCDFP-15 (100%), ER (39%), PR (8%), AR (54%), p53 (39%), and c-erbB-2 (85%). In the IDC-NOS group, GCDFP-15* was expressed in less than 50% of the tumors. The occurrence frequencies of the other markers were as follows: ER (69%), PR (69%)*, AR (46%), c-erbB-2 (0%)*, and p53 (31%), (*) indicating significant differences between the two groups. For Turkish BCa patients, (i) the occurrence rate of ApBCa (2.1%) was high; and (ii) the following combination would allow for an immunohistochemical identification of ApBCa: GCDFP-15(+), c-erbB-2(+), and PR(-).


[The Treatment Exit Options for Uveitis (TOFU) Registry: Involving Patients in the Generation of Evidence].
Uveitis comprises a group of rare diseases characterised by intraocular inflammation which may cause vision impairment and blindness and mostly affects people of working age. Non-infectious uveitis involving the posterior pole or the entire eye is often treated with different immunomodulating or disease-modifying anti-rheumatic drugs (DMARDs). However, the evidence on long-term management strategies and reduction/termination of treatment is limited. To help develop treatment exit strategies for patients with quiescent uveitis on long-term DMARD treatment, the Treatment Exit Options for Non-infectious Uveitis registry was initiated by the German ophthalmological society. A key aspect of the registry is active participation of patients (patient-reported outcomes, PROs). In a pilot study involving members of patient organizations, a combination of questionnaires covering vision- and general health-related quality of life, adherence to treatment, productivity and effects of treatment were evaluated. As the pilot study showed coverage of relevant patient-related aspects of the disease and its effect on daily life, the evaluated questionnaires were implemented in the registry's patient module. The registry including the patient module uses the electronic data capture (EDC) software REDCap (Version 9, Vanderbilt University, USA). By involving patients in both conceptualization and ongoing data collection, the TOFU registry emphasizes the patients' perspectives, and the inclusion of patient-relevant evidence for such as the development of guidelines and treatment recommendations is ensured.


Quantitation of phosphopeptides using affinity chromatography and stable isotope labeling.
Reversible phosphorylation of proteins represents an important component of cellular signaling pathways. The isolation of phosphoproteins in complex mixtures and the determination of the level of phosphorylation have been and remain a major challenge. It has prompted the development of several strategies, including immobilized metal affinity capture to enrich for phosphorylated peptides. An improved methodology was published (Ficarro, et al., Nature Biotechnology 2002, 20, 301-305) that showed increased selectivity through esterification of amino acid side chain carboxylic groups of enzymatically digested peptides. This method was applied for relative quantitation of phosphopeptides in conjunction with the use of stable isotope labeling. The merits and limits of the approach are discussed and its application to the analysis of the effects of serum starvation on in vitro cultured human lung cells is presented.


So2Sat POP - A Curated Benchmark Data Set for Population Estimation from Space on a Continental Scale.
Obtaining a dynamic population distribution is key to many decision-making processes such as urban planning, disaster management and most importantly helping the government to better allocate socio-technical supply. For the aspiration of these objectives, good population data is essential. The traditional method of collecting population data through the census is expensive and tedious. In recent years, statistical and machine learning methods have been developed to estimate population distribution. Most of the methods use data sets that are either developed on a small scale or not publicly available yet. Thus, the development and evaluation of new methods become challenging. We fill this gap by providing a comprehensive data set for population estimation in 98 European cities. The data set comprises a digital elevation model, local climate zone, land use proportions, nighttime lights in combination with multi-spectral Sentinel-2 imagery, and data from the Open Street Map initiative. We anticipate that it would be a valuable addition to the research community for the development of sophisticated approaches in the field of population estimation.


Parent-Therapist Partnership Survey: Parent Feedback and Psychometric Properties.
Parents of children with disabilities are an important part of their child's special education team. However, parents often have limited involvement in school-based therapies that are provided as part of a child's Individualized Education Program. The field lacks tools to assess the domain and extent of parent needs for optimal engagement in their child's special education therapies. Study one assessed the Parent-Therapist Partnership Survey's (PTPS) (formerly known as the Needs of Parents Questionnaire -School-Based Therapy Version) measure's clarity, fit, and comprehensiveness. Study two assessed the factor structure and internal consistency. Two factors emerged - Need to Be an Informed, Engaged Member of Their Child's Team, and Need for Support and Guidance. Internal consistency was 0.93 for the overall scale. The PTPS can serve as a powerful measure to better identify opportunities to engage parents in school therapeutic goals while improving parent-provider collaboration in school-based therapies.


Super-CHO-A cell line capable of autocrine growth under fully defined protein-free conditions.
Chinese Hamster Ovary (CHO) cells are widely used for the large scale production of recombinant biopharmaceuticals. Growth of the CHO-K1 cell line has been demonstrated in serum-free medium containing insulin, transferrin and selenium. In an attempt to get autocrine growth in protein-free medium, DNA coding for insulin and transferrin production was transfected into CHO-K1 cells. Transferrin was expressed well, with clones secreting approximately 1000 ng/10(6) cells/24h. Insulin was poorly expressed, with rates peaking at 5 ng/10(6) cells/24h. Characterisation of the secreted insulin indicated that the CHO cells were incompletely processing the insulin molecule. Site-directed mutagenesis was used to introduce a furin (prohormone converting enzyme) recognition sequence into the insulin molecule, allowing the production of active insulin. However, the levels were still too low to support autocrine growth. Further investigations revealed insulin degrading activity (presumably due to the presence of insulin degrading enzymes) in the cytoplasm of CHO cells. To overcome these problems insulin-like growth factor I (instead of insulin) was transfected into the cells. IGF-1 was completely processed and expressed at rates greater than 500 ng/10(6)cells/24h. In this paper we report autonomous growth of the transfected CHO-K1 cell line expressing transferrin and IGF-1 in protein-free medium without the addition of exogenous growth factors. Growth rates and final cell densities of these cells were identical to that of the parent cell line CHO-K1 growing in insulin, transferrin, and selenium supplemented serum-free media.


An unusual cause of pleural effusion, urinothorax in a child with urinary stone disease.
The association of obstructive uropathy with ascites has been known since 1863 and with pleural effusion since 1954. Urinothorax is a rare complication of blunt renal trauma, ureteral instrumentation or ureteral surgery. Leakage from the urinary tract may cause urinoma, retroperitoneal collection of fluid, which can lead to urinothorax. This case report describes a child with a massive right-sided pleural effusion that was caused by same-sided renal calculi. The effusion disappeared within a few days after adequate urinary drainage had been established.


The prevalence of simple renal and hepatic cysts detected by spiral computed tomography.
To provide a definitive evaluation of the prevalence of simple renal and hepatic cysts using spiral computed tomography (CT). Contrast-enhanced abdominal CT studies from 617 patients (295 women, 322 men) attending for investigations unrelated to renal or hepatic pathology were included. The number of renal cysts, their location and the diameter of the largest cyst were recorded. Hepatic cysts were recorded as being either present or absent. Two hundred and fifty-four patients (41%) were found to have simple renal cysts and 110 patients were found to have simple hepatic cysts (18%). Both renal and hepatic cysts became more common with age. Renal cysts were significantly more common at all ages in men (p=0.001), and increased in both size (p=0.02) and number (p<0.05) with age. A major discrepancy has, until now, existed between autopsy prevalence of renal cysts and prevalence as reported by in-vivo third-generation CT or sonography studies. Using newer spiral CT machines, we have generated prevalence data closer to post-mortem findings. We have also shown a significant, but age dependent, association between the presence of simple hepatic and simple renal cysts (p=0.001)


The influence of climate change, green innovation, and aspects of green dynamic capabilities as an approach to achieving sustainable development.
Green dynamic capability is acquiring significant traction among academics, practitioners, and policymakers; however, its relationship to green innovation, climate change, and sustainable development remains unclear. This study aims to identify green innovation within the context of developing nations to cover this void. Utilizing dynamic capability and stakeholder theory, this research illuminated the significance of green dynamic capability for sustainable development. Using a two-wave research methodology, the sample for this study was comprised of organizations from the Pakistani public sector. This investigation compiled data from 342 top and middle-level employees from the ministry of climate change, the ministry of agriculture, and the capital development authority (CDA). Using SEM SMART-PLS-path modeling to test hypotheses and investigate the model's causal links. Green innovation mediates the positive relationship between green dynamic capabilities and sustainable development, as indicated by the findings. However, neither green dynamic capabilities nor the relationship between green innovation and sustainable development is moderated by climate change. The findings of the study suggest strategies for government organizations to use green innovation in environmental literature. In addition, organizations will collaborate to develop strategies to combat climate change.


Effects of 25OHD concentrations on chances of pregnancy and pregnancy outcomes: a cohort study in healthy Danish women.
Plasma 25-hydroxyvitamin D (P-25OHD) concentrations may affect pregnancy outcomes. To elucidate this further, we studied the effects of pre-conception P-25OHD concentrations on chances for pregnancy as well as the effects of P-25OHD during pregnancy on the risk of miscarriage, birth weight and length, Apgar score and head circumference. Moreover, we studied whether pregnancy and breastfeeding patterns affect maternal P-25OHD concentrations. A total of 153 healthy Caucasian women with pregnancy plans were followed with measurements performed before pregnancy, at pregnancy weeks 11±2, 22±1 and 35±2 as well as 15±7, 129±12 and 280±15 days postpartum. Furthermore, 75 non-pregnant, age-matched women were followed in parallel as controls. The 203 women were aged 29 (25-35) years. At baseline, median P-25OHD was 59 nmol/l. Of these women, 31% had P-25OHD <50 nmol/l, whereas 12% had levels above 80 nmol/l. Within ∼6 months after inclusion, 63% conceived. P-25OHD was not associated with chances of conceiving or overall risk of miscarriage. However, women with a miscarriage in their second trimester (n=3) had lower P-25OHD concentrations at measurements performed in the first trimester compared with women without a miscarriage (P=0.03). P-25OHD before or during pregnancy was not associated with gestational length or infant parameters. Adjustments for possible confounders did not change the result. During pregnancy, P-25OHD changed significant over time, but similar changes occurred within the control group, indicating no effect of pregnancy per se (P=0.59). Overall, P-25OHD did not differ according to length of breastfeeding at 2 weeks, and 4 and 9 months postpartum, although women breastfeeding for >9 months had lower P-25OHD levels at the last visit compared with the controls. P-25OHD concentrations did not affect fertility or pregnancy outcomes, although low P-25OHD may be associated with an increased risk of late miscarriage.


Online measurement of learning temporal statistical structure in categorization tasks.
The ability to grasp relevant patterns from a continuous stream of environmental information is called statistical learning. Although the representations that emerge during visual statistical learning (VSL) are well characterized, little is known about how they are formed. We developed a sensitive behavioral design to characterize the VSL trajectory during ongoing task performance. In sequential categorization tasks, we assessed two previously identified VSL markers: priming of the second predictable image in a pair manifested by a reduced reaction time (RT) and greater accuracy, and the anticipatory effect on the first image revealed by a longer RT. First, in Experiment 1A, we used an adapted paradigm and replicated these VSL markers; however, they appeared to be confounded by motor learning. Next, in Experiment 1B, we confirmed the confounding influence of motor learning. To assess VSL without motor learning, in Experiment 2 we (1) simplified the categorization task, (2) raised the number of subjects and image repetitions, and (3) increased the number of single unpaired images. Using linear mixed-effect modeling and estimated marginal means of linear trends, we found that the RT curves differed significantly between predictable paired and control single images. Further, the VSL curve fitted a logarithmic model, suggesting a rapid learning process. These results suggest that our paradigm in Experiment 2 seems to be a viable online tool to monitor the behavioral correlates of unsupervised implicit VSL.


Interpersonal relations and nurses' job satisfaction through knowledge and usage of relational skills.
Many interpersonal labor disputes stem from the lack of communication skills and the relational problems in the interactions between health professionals. A qualitative study was conducted in a Spanish hospital in order to get to know how the communicative interaction between hospital nurses is like in relation to the nurses' interpersonal interaction and communication skills developed in their working relationships. Twenty-one hospital nurses between 29 and 55 years old, working in different wards, were interviewed. Open-ended interview discourses were transcribed verbatim and analyzed using qualitative content analysis. The following four key themes were analyzed: communication and sender; communication and awareness of who has the problem; non-verbal communication; communication and recipient. The results of this study highlight the need to broaden nurses' relational-communication skills in order to increase job satisfaction.


New glutarimide antibiotics, S-632-B1 and B2. II. Isolation, physico-chemical properties and chemical structure.
Antifungal antibiotics S-632-A1,A2,B1 and B2 were extracted with ethyl acetate from the filtered broth of Streptomyces hygroscopicus S-632 and isolated through a combination of conventional and reversed-phase silica gel column chromatography. On the basis of the spectral data, S-632-B1 and B2 were found to be new members of the glutarimide family of antibiotics. The chemical structures of these components were elucidated as two stereo-isomers of 3-(5,7-dimethyl-8,9-epoxy-2-hydroxy-4-oxo-6-decenyl)glutarimide.


Protocol to perform dynamic microfluidic single-cell cultivation of C. glutamicum.
Here, we present a protocol for the design, fabrication, and usage of a polydimethylsiloxane (PDMS)-based chip for dynamic microfluidic single-cell cultivation of Corynebacterium glutamicum. We describe steps for flow profile establishment and biological preparation. We then detail time-lapse imaging to observe reactions of C. glutamicum to repeated environmental changes in the range of seconds. This system can be adapted to other organisms with a cell wall and soluble non-gaseous environmental factors like nutrients. For complete details on the use and execution of this protocol, please refer to Täuber et al..1.


Nerve, plexus and spinal cord: possible targets for non-invasive neuromagnetic measurements in man.
Somatosensory evoked neuromagnetic fields are recorded from peripheral nerves in the upper arm, from plexus brachialis at the ventral and dorsal thorax and from the dorsal horn of the cervical spinal cord ('P13m') at the upper lateral neck. Some perspectives for clinical applications are suggested.


Synchronous and metachronous colon lesions in squamous cell carcinoma of the anal canal.
The charts of 79 patients with a histologic diagnosis of squamous cell carcinoma of the anal canal were reviewed to determine the incidence of synchronous and/or metachronous colon lesions. Forty-six patients underwent an adequate preoperative evaluation of the colon and rectum. Ten patients underwent colonoscopy, 33 patients underwent a barium enema, and three patients underwent colonoscopy and a barium enema. In this group six adenomatous polyps and three hyperplastic polyps were discovered. An adenocarcinoma of the sigmoid colon was found in another patient six months prior to the diagnosis of a squamous cell carcinoma of the anal canal. Twenty-three patients had follow-up evaluation of the large bowel for metachronous lesions following treatment of the squamous cell carcinoma of the anal canal. Ten patients underwent colonoscopy, three patients had a barium enema, and ten autopsies were available for analysis. In this group metachronous lesions consisted of two adenomatous polyps and one hyperplastic polyp.


Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours.
Since its discovery in the early 1990s the deleted in colorectal cancer (DCC) gene, located on chromosome 18q21, has been proposed as a tumour suppressor gene as its loss is implicated in the majority of advanced colorectal and many other cancers. DCC belongs to the family of netrin 1 receptors, which function as dependence receptors as they control survival or apoptosis depending on ligand binding. However, the role of DCC as a tumour suppressor remains controversial because of the rarity of DCC-specific mutations and the presence of other tumour suppressor genes in the same chromosomal region. Here we show that in a mouse model of mammary carcinoma based on somatic inactivation of p53, additional loss of DCC promotes metastasis formation without affecting the primary tumour phenotype. Furthermore, we demonstrate that in cell cultures derived from p53-deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumour cells lacking DCC. Consistent with this idea, in vivo tumour-cell survival is enhanced by DCC loss. Together, our data support the function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells.


Tetanic stimulation recruits vesicles from reserve pool via a cAMP-mediated process in Drosophila synapses.
At Drosophila neuromuscular junctions, there are two synaptic vesicle pools, namely the exo/endo cycling pool (ECP) and the reserve pool (RP). We studied the recruitment process from RP using a fluorescent dye, FMI-43. During high-frequency nerve stimulation, vesicles in RP were recruited for release, and endocytosed vesicles were incorporated into both pools, whereas with low-frequency stimulation, vesicles were incorporated into and released from ECP. Release of vesicles from RP was detected electrophysiologically after emptying vesicles in the ECP of transmitter by a H+ pump inhibitor. Recruitment from RP was depressed by inhibitors of steps in the cAMP/PKA cascade and enhanced by their activators. In rutabaga (rut) with low cAMP levels, mobilization of vesicles from RP during tetanic stimulation was depressed, while it was enhanced in dunce (dnc) with high cAMP levels.


Methodological issues in measuring subjective well-being and quality-of-life: Applications to assessment of affect in older, chronically and cognitively impaired, ethnically diverse groups using the Feeling Tone Questionnaire.
Quality of life assessment includes measurement of positive affect. Methods artifacts associated with positively and negatively worded items can manifest as negative items loading on a second factor, despite the conceptual view that the items are measuring one underlying latent construct. Negatively worded items may elicit biased responses. Additionally, item-level response bias across ethnically diverse groups may compromise group comparisons. The aim was to illustrate methodological approaches to examining method factors and measurement equivalence in an affect measure with 9 positively and 7 negatively worded items: The Feeling Tone Questionnaire (FTQ). The sample included 4,960 non-Hispanic White, 1,144 non-Hispanic Black, and 517 Hispanic community and institutional residents receiving long-term supportive services. The mean age was 82 (s.d.=11.0); 73% were female. Two thirds were cognitively impaired. Methods effects were assessed using confirmatory factor analyses (CFA), and reliability with McDonald's omega and item response theory (IRT) generated estimates. Measurement equivalence was examined using IRT-based Wald tests. Methods effects associated with negatively worded items were observed; these provided little IRT information, and as a composite evidenced lower reliability. Both 13 and 9 item positive affect scales performed well in terms of model fit, reliability, IRT information, and evidenced little differential item functioning of high magnitude or impact. Both CFA and IRT approaches provided complementary methodological information about scale performance. The 9-item affect scale based on the FTQ can be recommended as a brief quality-of-life measure among frail and cognitively impaired individuals in palliative and long-term care settings.


Extra-articular resection for bone sarcomas involving the hip joint.
The aim of this study was to determine the oncologic, functional, and clinical outcomes after the extra-articular resection and limb-salvage reconstruction of the hip joint. A retrospective study of 34 patients who underwent extra-articular resection of the hip joint for bone sarcomas between 1996 and 2016 was conducted. The primary tumor site was pelvis in 26 patients (76%) and femur in eight (24%). The surgical margins achieved were clear in 31 (91%) patients, and seven (21%) patients developed local recurrence; mostly occurring in pelvic tumors (n = 6). The 3-year overall survival was 63% with a median follow-up of 38 months (range, 5-219), which showed no statistical difference in tumor location. The most common complication was deep infection (n = 7) and dislocation (n = 7), mostly seen in pelvic tumors. Implant failure was seen in two patients with pelvic tumors, while no failure was noted in patients with femoral tumors. The median Musculoskeletal Tumour Society score was 69%; 67% for pelvic tumors and 73% for femoral tumors (P = .535). Despite complex surgery, extra-articular resection of the hip joint can achieve oncologically and functionally acceptable outcomes. While tumors of the pelvis are associated with a higher incidence of infection and local recurrence after resection, resection of tumors involving the femur are well tolerated.


Unscheduled DNA synthesis in various types of cells of the mouse brain in vivo.
Very low incorporation of 3H-thymidine (TdR) into neurons and non-proliferating glial and endothelial cells in various brain areas of the adult mouse after 3H-TdR injection and subsequent X-irradiation of the head with 45 Gy has been demonstrated autoradiographically after exposure times of 250 days. In accordance with biochemical studies this incorporation of 3H-TdR represents DNA repair synthesis or UDS (unscheduled DNA synthesis). However, 3H-TdR incorporation into nuclear DNA of non-proliferating cells in the brain was not only found in X-irradiated but also in sham-irradiated mice. This suggests that spontaneous UDS also occurs. Up to now spontaneous UDS has been shown only in HeLa cells in vitro. Nearly all the various types of brain cells tested exhibited UDS after X-irradiation as well as spontaneous UDS. After correcting the mean grain numbers per nucleus not only for background but also for beta-self-absorption, substantial differences became apparent in the extent of UDS between the individual types of cells. After X-irradiation, UDS was highest in Purkinje cells and hippocampal granular cells but comparable UDS was also found in endothelial cells, regardless of the different brain areas studied. The extent of spontaneous UDS is also quite different in the various cell types, being highest in neurons of different sites and considerably lower in endothelial and glial cells.


Silver nanomaterials released from commercial textiles have minimal impacts on soil microbial communities at environmentally relevant concentrations.
Silver nanomaterials (Ag NMs) have been used in a variety of commercial products to take advantage of their antimicrobial properties. However, there are concerns that these AgNMs can be released during/after use and enter wastewater streams, potentially impacting aquatic systems or accumulating in wastewater biosolids. Biosolids, which are a residual of wastewater treatment processes, have been found to contain AgNMs and are frequently used as agricultural fertilizer. Since the function of soil microbial communities is imperative to nutrient cycling and agricultural productivity, it is important to characterize and assess the effects that silver nanomaterials could have in agricultural soils. In this study agricultural soil was amended with pristine engineered (PVP-coated or uncoated AgNMs), aged silver (sulphidized or released from textiles) nanomaterials, and ionic silver to determine the fate and toxicity over the course of three months. Exposures were carried out at various environmentally relevant concentrations (1 and 10 mg Ag/kg soil) representing between 30 to over 800 years of equivalent biosolid loadings. Over thirteen different methodologies and measures were used throughout this study to assess for potential effects of the silver nanomaterials on soil, including microbial community composition, average well colour development (AWCD) and enzymatic activity. Overall, the AgNM exposures did not exhibit significant toxic effects to the soil microbial communities in terms of density, activity, function and diversity. However, the positive ionic silver treatment (100 mg Ag/kg soil) resulted in suppression to microbial activity while also resulting in significantly higher populations of Frankia alni (nitrogen-fixer) and Arenimonas malthae (phytopathogen) as compared to the negative control (p < 0.05, Tukey HSD) which warrants further investigation.


An evaluation of the usefulness of mycophenolate mofetil in pemphigus.
Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. We found that MMF permitted a reduction in prednisolone dosage without disease relapse.


Anterior and posterior hip osteoarthritis: prevalence and potential value of CT compared to radiographs.
To determine the added value of computed tomography (CT) to identify severe hip osteoarthritis (OA). A retrospective query of all cases of hip or knee arthroplasty planning CTs between January 2018 and March 2022 was performed. Age, sex, and symptoms were collected from the medical record. CTs were evaluated for the degree of osteoarthritis and classified using an adapted Kellgren-Lawrence (KL) grading system in the anterior, posterior, superior, and superomedial hip. Frontal hip or pelvis radiographs within 1 year of the CT were also graded. There were 265 eligible hips in 178 subjects, age 66 ± 11 (range 31-93) years, with 85/178 (48%) males and 93/178 (52%) females, and 127/265 (48%) right and 138/265 (52%) left hips. The posterior hip joint was the most common location for grade 2/3 OA (20%), followed by superior hip joint (14%). Anterior or posterior grade 2/3 OA occurred concurrently with superior or superomedial grade 2/3 OA in 32/68 (47%) of hips. Grade 2/3 OA was detected on CT more commonly than on XR both in the superior (14 vs 8.6%, P = 0.0016) and superomedial (8.7 vs 4.8%, P = 0.016) hip joint. Of the 71 symptomatic hips, 22 (31%) hips demonstrated either anterior and/or posterior grade 2/3 OA on CT, and 9 (9/22, 41%) of these hips had superior or superomedial grade 0/1 OA. CT may be warranted when the patient has pain suggestive of osteoarthritis not detected on radiographs.


Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies.
Selective degeneration of the smallest fibers (papillo-macular bundle) of the human optic nerve occurs in a large number of optic neuropathies characterized primarily by loss of central vision. The pathophysiology that underlies this peculiar pattern of cell involvement probably reflects different forms of genetic and acquired mitochondrial dysfunction. Maternally inherited Leber's hereditary optic neuropathy (LHON), dominant optic atrophy (Kjer disease), the optic atrophy of Leigh's syndrome, Friedreich ataxia and a variety of other conditions are examples of inherited mitochondrial disorders with different etiologies. Tobacco-alcohol amblyopia (TAA), the Cuban epidemic of optic neuropathy (CEON) and other dietary (Vitamins B, folate deficiencies) optic neuropathies, as well as toxic optic neuropathies such as due to chloramphenicol, ethambutol, or more rarely to carbon monoxide, methanol and cyanide are probably all related forms of acquired mitochondrial dysfunction. Biochemical and cellular studies in LHON point to a partial defect of respiratory chain function that may generate either an ATP synthesis defect and/or a chronic increase of oxidative stress. Histopathological studies in LHON cases and a rat model mimicking CEON revealed a selective loss of retinal ganglion cells (RGCs) and the corresponding axons, particularly in the temporal-central part of the optic nerve. Anatomical peculiarities of optic nerve axons, such as the asymmetric pattern of myelination, may have functional implications on energy dependence and distribution of mitochondrial populations in the different sections of the nerve. Histological evidence suggests impaired axonal transport of mitochondria in LHON and in the CEON-like rat model, indicating a possible common pathophysiology for this category of optic neuropathies. Histological evidence of myelin pathology in LHON also suggests a role for oxidative stress, possibly affecting the oligodendrocytes of the optic nerves.


Eye injuries in the National Hockey League from 2010 to 2018: an analysis of injury rates, mechanisms, and the National Hockey League visor policy.
We aim to assess the efficacy of widespread visor adoption by assessing eye injury rates during the 2010-2018 seasons. We also compare injury rates, missed games, and financial losses to previously reported data in order to track progress over time. Lastly, we characterize the mechanism and type of eye injuries sustained by National Hockey League (NHL) players to examine risk areas within NHL games. We performed a retrospective review of NHL player injuries using official NHL team reports, ProSportsTransactions, and TSN Sports. All NHL players who suffered an eye injury from 2010 to 2018 were included; 31 injuries matched this criterion. Trends in injuries, missed games, and financial losses over time were analyzed using Pearson's correlation coefficients. Wilcoxon-Mann-Whitney tests were performed to compare our data with eye injury data. Fisher's exact test was performed to assess significance between mechanism and type of eye injury and outcome. There were 31 total eye injuries causing 233 missed games and a total of US$8 951 000 in financial losses across the 2010-2018 seasons. There was a strong decrease in the number of eye injuries (r = -0.83, p = 0.01) and a moderate decrease in number of missed games (r = -0.62, p = 0.09). Injuries due to direct puck strikes contributed to over US$6.5 million in financial losses and led to significantly more missed games compared with stick injuries (14.6 vs 4.3). We tangibly demonstrate the financial and physical effects of recent safety interventions and indicate areas for improved safety in the NHL.


A novel general and efficient technique for dissociating antigen in circulating immune complexes.
Circulating immune complexes (CICs) are produced during the immune response. It is more clinically important to establish a general and efficient CICs dissociation technique for the detection of antigens for CICs other than the detection of free antigens in the serum. Polyethylene glycol (PEG) two-precipitation separation and glycine-HCl as a buffer system were employed to develop a general and efficient buffer dissociation technique to separate CICs from serum and dissociate antigens from CICs. The measurement value of new PEG two-precipitation separation technique was higher than traditional PEG precipitation separation technique. There were slight differences in the dissociation conditions of HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC as compared to HBsAg-IC. The detection of antigens in HBsAg-IC, HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC with this technique was superior to that with HCl Dissociation, Trypsin Digestion or Immune Complex Transfer technique. PEG two-precipitation dissociation technique may reduce macromolecular protein and the adhesion of free antigens during the co-precipitation, which increases the efficiency of separation and precipitation of CICs. This technique also avoids the damage of reagents to antigens, assuring the repeatability, reliability and validity. Thus, this technique is application in samples negative or positive for free antigens.


Computed tomography of aortoiliac atherosclerosis.
Twenty-three patients with atherosclerotic peripheral vascular disease underwent angiography and CT of the aortoiliac segment within a 72-hour interval. Examinations were evaluated for depiction of disease in the aortic and iliac segments in five categories: stenosis, plaque morphology, vascular ectasia, calcification, and other pathologic conditions. Angiography and CT were equally accurate in their depiction of the degree of aortic stenosis or occlusion and in identification of aortic ectasia. Angiography proved superior to CT in the display of plaque morphology in 57% of aortic lesions and 74% of iliac abnormalities. Angiography also showed clear superiority over CT in quantification of iliac stenosis in 75% of patients with abnormalities, as well as in identification of iliac ectasia. CT detected both intimal calcification and incidental disease or congenital abnormalities better than angiography, including an unsuspected chronic contained aortic rupture. Overall, CT compared favorably with angiography in the identification of all types of aortic disease but major disadvantages of CT were evident in the iliac segment because of vessel tortuosity or heavy calcification. CT cannot replace arteriography in detecting atherosclerotic disease of the aortoiliac segment but can help to clarify angiographic findings in selected groups of patients.


Marginal Micro-leakage of Self-etch and All-in One Adhesives to Primary Teeth, with Mechanical or Chemo-Mechanical Caries Removal.
Chemo-mechanical caries removal is an effective alternative to the traditional rotary drilling method. One of the factors that can influence micro-leakage is the method of caries removal. To compare the micro-leakage of resin composite in primary dentition using self-etch and all-in one adhesives following conventional and chemo-mechanical caries removal. Sixty extracted human primary anterior teeth with class III carious lesions were collected. The selected teeth were divided randomly into two groups each consisting of 30 teeth. In group1 carious lesions were removed using Carisolv multi mix gel. In group 2, caries was removed using round steel burs in a slow-speed hand piece. Then, the specimens in each group were randomly divided into two subgroups (A and B) of 15 and treated by either Clearfil SE Bond (CSEB) or Scotch bond. All prepared cavities were filled with a resin composite (Estellite). All the specimens were stored in distilled water at 37ºC for 24 hours and then thermocycled in 5ºC and 55ºC water with a dwell time of 20 seconds for 1500 cycles. The specimens were immersed in 1% methylene blue solution for 24 hours, removed, washed and sectioned mesiodistally. The sectioned splits were examined under a stereomicroscope to determine the micro-leakage scores. The data were analyzed using Kruskal-Wallis Test in SPSS version 21. There were no significant differences between micro-leakage scores among the four groups (p = 0.127). Score 0 of micro-leakage was detected for 60% of the specimens in group 1-A (Carisolv + CSEB), 73% of the group 2-A (hand piece + CSEB), 80% of the group 1-B (Carisolv + Scotch bond), and 93% of the group 2-B in which caries was removed using hand piece and bonded with Scotch bond . Although caries removal using hand piece bur along with using Scotch bond adhesive performed less micro-leakage, it would seems that the use of Carisolv doesn't adversely affect the micro-leakage of composite restorations while using self-etch or all-in one adhesives.


Environmental control of Vibrio spp. abundance and community structure in tropical waters.
We measured Vibrio spp. distribution and community profile in the tropical estuary of Port Klang and coastal water of Port Dickson, Malaysia. Vibrio spp. abundance ranged from 15 to 2395 colony forming units mL-1, and was driven by salinity and chlorophyll a (Chl a) concentration. However, the effect of salinity was pronounced only when salinity was <20 ppt. A total of 27 Vibrio spp. were identified, and theVibrio spp. community at Port Dickson was more diverse (H' = 1.94 ± 0.21). However species composition between Port Dickson and Port Klang were similar. Two frequently occurring Vibrio spp. were V. owensii and V. rotiferianus, which exhibited relatively higher growth rates (ANCOVA: F > 4.338, P < 0.05). Co-culture experiments between fast- and slow-growing Vibrio spp. revealed that fast-growing Vibrio spp. (r-strategists) were overwhelmed by slower-growing Vibrio spp. (K-strategists) when nutrient conditions were set towards oligotrophy. In response to resource availability, the intrinsic growth strategy of each Vibrio spp. determined its occurrence and the development of Vibrio spp. community composition.


Origins of extreme boundary lubrication by phosphatidylcholine liposomes.
Phosphatidylcholine (PC) vesicles have been shown to have remarkable boundary lubricating properties under physiologically-high pressures. Here we carry out a systematic study, using a surface force balance, of the normal and shear (frictional) forces between two opposing surfaces bearing different PC vesicles across water, to elucidate the origin of these properties. Small unilamellar vesicles (SUVs, diameters < 100 nm) of the symmetric saturated diacyl PCs DMPC (C(14)), DPPC (C(16)) and DSPC (C(18)) attached to mica surfaces were studied in their solid-ordered (SO) phase on the surface. Overall liposome lubrication ability improves markedly with increasing acyl chain length, and correlates strongly with the liposomes' structural integrity on the substrate surface: DSPC-SUVs were stable on the surface, and provided extremely efficient lubrication (friction coefficient μ ≈ 10(-4)) at room temperature at pressures up to at least 18 MPa. DMPC-SUVs ruptured following adsorption, providing poor high-pressure lubrication, while DPPC-SUVs behavior was intermediate between the two. These results can be well understood in terms of the hydration-lubrication paradigm, but suggest that an earlier conjecture, that highly-efficient lubrication by PC-SUVs depended simply on their being in the SO rather than in the liquid-disordered phase, should be more nuanced. Our results indicate that the resistance of the SUVs to mechanical deformation and rupture is the dominant factor in determining their overall boundary lubrication efficiency in our system.