Sense of control and diabetes mellitus among U.S. adults: a cross-sectional analysis.
Little is known about the influence of psychosocial factors on diabetes mellitus. The aim of this study was to improve understanding of the association between two psychosocial factors- sense of control and social support- and diabetes mellitus. The authors analyzed data from 2,592 U.S. households in the 1995 survey of the Aging, Status, and the Sense of Control study. Logistic regression analyses were conducted to examine whether sense of personal control and social support were associated with DM and whether gender, race, and Hispanic ethnicity modified these associations. After adjusting for age, obesity, and socioeconomic position, a one point increase in sense of control (i.e., a stronger sense of control) was associated a significant reduction in risk of diabetes mellitus (odds ratio = 0.67, 95% confidence interval: 0.47, 0.95). A weak social support system was associated with a non-significant risk of diabetes (odds ratio = 1.32, 95% confidence interval: 0.93, 1.89). No effect modification was detected. Sense of control deserves greater attention as a predictor of diabetes mellitus. Further studies of the contribution of psychosocial factors to diabetes mellitus should assess the temporal nature of this relationship.


Utility of the Oncotype DX® Prostate Cancer Assay in Clinical Practice for Treatment Selection in Men Newly Diagnosed with Prostate Cancer: A Retrospective Chart Review Analysis.
The 17-gene Oncotype DX® prostate cancer assay (Genomic Health Inc., Redwood City, California) is a validated, biopsy based gene expression assay that reports the Genomic Prostate Score. Combined with clinical risk features, Genomic Prostate Score provides an individualized estimation of disease aggressiveness at diagnosis. With this retrospective chart review we assessed the impact of incorporating the Oncotype DX Genomic Prostate Score on treatment recommendations and decisions for men with newly diagnosed low risk prostate cancer in community urology practices. A total of 24 urologists who ordered the Oncotype DX prostate cancer assay soon after launch (May 2013) were invited to participate in the study. Clinicopathological data, Genomic Prostate Score results and treatment related information were retrieved from medical records. Data also were collected for a pre-Genomic Prostate Score baseline group diagnosed from May 2012 to April 2013. Descriptive analyses were performed to evaluate the proportion of men for whom active surveillance was recommended and used before and after the availability of Genomic Prostate Score. Overall 15 physicians contributing 211 patients (Genomic Prostate Score group 124, baseline group 87) participated in the chart review. Patients in the Genomic Prostate Score and baseline groups had comparable risk based on traditional clinical pathological features, with 82% with NCCN® very low or low risk disease. With Genomic Prostate Score the relative increase in active surveillance recommended was 22% (baseline 50% and Genomic Prostate Score 61%, absolute increase of 11%) and the relative increase in use of active surveillance was 56% (baseline 43% and Genomic Prostate Score 67%, absolute increase of 24%). Treatment recommendations for active surveillance were directionally consistent with assay reported risk. Genomic Prostate Score testing was associated with greater physician recommendation of and use of active surveillance in community clinical practices.


[Comparative estimation of effectiveness of nonsteroidal anti-inflammatory drugs used for postoperative pain management].
A comparative analysis of the analgetic and side effects of Ketonal, Ketoral and Diklogen was performed during treatment of 64 patients. Ketonal was found to have more pronounced analgetic effect and minimal side effects.


Electrodiagnosis of peripheral neuropathy.
Electrodiagnostic studies are an important component of the evaluation of patients with suspected peripheral nerve disorders. The pattern of findings and the features that are seen on the motor and sensory nerve conduction studies and needle electromyography can help to identify the type of neuropathy, define the underlying pathophysiology (axonal or demyelinating), and ultimately help to narrow the list of possible causes. This article reviews the electrodiagnostic approach to and interpretation of findings in patients with peripheral neuropathies.


Slipping through the door: HIV entry into the nucleus.
HIV infection of non-dividing cellular targets like macrophages requires successful passage of the viral preintegration complex (PIC) across an intact nuclear envelope. Unique but redundant nuclear import signals reside within the HIV integrase, matrix, and Vpr proteins as well as the 'DNA flap'; these signals appear to facilitate PIC transport through the limiting nuclear pores. We discuss recent studies that have advanced our understanding of this key step in the HIV life cycle.


Decreased L-carnitine transport in mechanically overloaded rat hearts.
The transport of L[14C] carnitine was studied in rat hearts with a three-month-old aorto-caval fistula. Tissue TG content was determined in order to assess the state of FFA utilization. The hearts were perfused with a bicarbonate buffer containing 11 mM glucose and variable concentrations (10-200 microM) of L[14C] carnitine. In some experiments, the active component of carnitine transport was suppressed by the adjunction of 0.05 mM mersalyl acid. The subtraction of passive from total transport allowed us to reconstruct the saturation curves of the net active transport of L-carnitine. Our results suggest that at physiological carnitine concentration (50 microM) the uptake of L-carnitine is significantly depressed in mechanically overloaded hearts. These changes are not related to alterations of coronary perfusion, since coronary flow rates (ml/min/g dry wt) are quite comparable in both groups tested. According to the Lineweaver-Burk analysis of the kinetics of saturable transport, the affinity of the membrane carrier for L-carnitine is considerably diminished in the overloaded hearts (Km[carnitine] 125 instead of 83 microM). The alterations of the kinetics of carnitine transport do not seems to be related to the decrease of the transmembrane gradient of sodium: the intracellular sodium content of the hypertrophied, but non-failing, hearts is quite similar to that of control hearts. In addition, carnitine deficiency does not lead to TG accumulation, at least under in situ conditions.


Targeting Cell Senescence for the Treatment of Age-Related Bone Loss.
We review cell senescence in the context of age-related bone loss by broadly discussing aging mechanisms in bone, currently known inducers and markers of senescence, the senescence-associated secretory phenotype (SASP), and the emerging roles of senescence in bone homeostasis and pathology. Cellular senescence is a state of irreversible cell cycle arrest induced by insults or stressors including telomere attrition, oxidative stress, DNA damage, oncogene activation, and other intrinsic or extrinsic triggers and there is mounting evidence for the role of senescence in aging bone. Cellular aging also instigates a SASP that exerts detrimental paracrine and likely systemic effects. With aging, multiple cell types in the bone microenvironment become senescent, with osteocytes and myeloid cells as primary contributors to the SASP. Targeting undesired senescent cells may be a favorable strategy to promote bone anabolic and anti-resorptive functions in aging bone, with the possibility of improving bone quality and function with normal aging and/or disease.


Calcaneal tumors and tumor-like conditions.
Approximately 3% of osseous tumors occur in the foot and ankle. Solitary bone cysts, chondroblastoma, intraosseous lipoma, osteoid osteoma, chondrosarcoma, and Ewing's sarcoma seem to have a predilection for the calcaneus. Biopsy is often a crucial step in management. Tumor-like conditions, such as cysts, reactive lesions, and osteomyelitis, must be considered during evaluation. Treatment is often observation or curettage of benign lesions and resection or amputation for malignancies.


Validation of 24-hour trough concentration as a proxy for intensive pharmacokinetic measurements for a combined oral contraceptive pill containing desogestrel.
To confirm that 24-hour steady-state trough measurements (C24) are high-quality proxies for gold standard pharmacokinetic measurements (area under the curve [AUC]) of a combined oral contraceptive pill (COCP). We conducted a 12-sample, 24-hour pharmacokinetic study in healthy reproductive-age females taking a COCP containing 0.15-mg desogestrel (DSG) and 30-μg ethinyl estradiol (EE). As DSG is a pro-drug for etonogestrel (ENG), we calculated correlations between steady-state C24 and 24-hour AUC values for both ENG and EE. Among 19 participants at steady state, C24 measurements were highly correlated with AUC for both ENG (r = 0.93; 95% CI 0.83-0.98) and EE (r = 0.87; 95% CI 0.68-0.95). Steady-state 24-hour trough concentrations are high-quality proxies for gold standard pharmacokinetics of a DSG-containing COCP. Use of single-time trough concentration measurements at steady state provides excellent surrogate results for gold standard AUC values for both DSG and EE among COCP users. These findings support that large studies exploring interindividual variability in COCP pharmacokinetics can avoid the time- and resource-intensive costs associated with measuring AUC. Clinicaltrials.gov, NCT05002738.


ATP-induced synaptic potentiation in hippocampal slices.
The purpose of this study was to investigate the influence of different adenosine triphosphate (ATP) concentrations (ranging from 400 nM to 250 microM) on hippocampal potentials recorded from pyramidal neurons. ATP applied at a concentration of 400 nM induced a 100% increase in the size of the population spike (potentiation). The potential started to increase 30-60 s after ATP application, reached a maximum after 20 min, and remained potentiated for longer than 1.5 h. Washing the slices with fresh Ringer solution did not reverse the effect. ATP applied at a concentration of 50-150 microM, temporarily depressed the potential. This depression, however, was transient, as the potential gradually recovered by itself and reached a value higher than that observed before ATP application. ATP applied at the concentration of 250 microM caused a long-lasting depression of the potential. The potential was not restored by washing the slices, but recovered after addition of 0.7 microM 3,4-diaminopyridine. These data show a concentration-dependent mode of ATP action on hippocampal neurons and suggest a role for ATP in regulating synaptic efficiency.


Staff shortage affects care for families of seriously ill children.
THERE IS a 'worrying shortage' of children's nurses to care for seriously ill children, a charity has found.


Guided pedicle screw insertion: techniques and training.
In spinal fusion surgery, the accuracy with which screws are inserted in the pedicle has a direct effect on the surgical outcome. Accurate placement generally involves considerable judgmental skills that have been developed through a lengthy training process. Because the impact of misaligning one or more pedicle screws can directly affect patient safety, a number of navigational and trajectory verification approaches have been described and evaluated in the literature to provide some degree of guidance to the surgeon. To provide a concise review to justify the need and explore the current state of developing navigational or trajectory verification techniques for ensuring proper pedicle screw insertion along with simulation methods for better educating the surgical trainees. Recent literature review. To justify the need to develop new methods for optimizing pedicle screw paths, we first reviewed some of the recent publications relating to the statistical outcomes for different types of navigation along with the conventional freehand (unassisted) screw insertion. Second, because of the importance of providing improved training in the skill of accurate screw insertion, the training aspects of relevant techniques are considered. The third part is devoted to the description of specific navigational assist methods or trajectory verification techniques and these include computer-assisted navigation, three-dimensional simulations, and also electric impedance and optical and ultrasonic image-guided methods. This article presents an overview of the need and the current status of the guidance methods available for improving the surgical outcomes in spinal fusion procedures. It also describes educational aids that have the potential for reducing the training process.


New molecular settings to support in vivo anti-malarial assays.
Quantitative real-time PCR (qPCR) is now commonly used as a method to confirm diagnosis of malaria and to differentiate recrudescence from re-infection, especially in clinical trials and in reference laboratories where precise quantification is critical. Although anti-malarial drug discovery is based on in vivo murine efficacy models, use of molecular analysis has been limited. The aim of this study was to develop qPCR as a valid methodology to support pre-clinical anti-malarial models by using filter papers to maintain material for qPCR and to compare this with traditional methods. FTA technology (Whatman) is a rapid and safe method for extracting nucleic acids from blood. Peripheral blood samples from mice infected with Plasmodium berghei, P. yoelii, or P. falciparum were kept as frozen samples or as spots on FTA cards. The extracted genetic material from both types of samples was assessed for quantification by qPCR using sets of specific primers specifically designed for Plasmodium 18S rRNA, LDH, and CytB genes. The optimal conditions for nucleic acid extraction from FTA cards and qPCR amplification were set up, and were confirmed to be suitable for parasite quantification using DNA as template after storage at room temperature for as long as 26 months in the case of P. berghei samples and 52 months for P. falciparum and P. yoelii. The quality of DNA extracted from the FTA cards for gene sequencing and microsatellite amplification was also assessed. This is the first study to report the suitability of FTA cards and qPCR assay to quantify parasite load in samples from in vivo efficacy models to support the drug discovery process.


Toxic Risk Assessment of Arsenic in Males Through Drinking Water in Tharparkar Region of Sindh, Pakistan.
Humans are exposed to arsenic (As) through air, drinking water, and food. The arsenic (As) hazardous quotient was calculated on the basis of its concentration in drinking water of different origin and scalp hair of male subjects (n = 313), residents of different exposed and non-exposed areas of Sindh, Pakistan. The total As was determined in water and scalp hair samples, while As species were determined in water samples by advance extraction methodologies. The total As concentrations in drinking water of less-exposed (LE) and high-exposed (HE) areas was found to be 2.63 to 4.46 and 52 to 235, fold higher than the permissible limit, respectively, than recommended by World Health Organization (2004) for drinking water. While the levels of As in drinking water of non-exposed (NE) areas was within the permissible limit. The resulted data indicated that the dominant species was As(+5) in groundwater samples. The levels of As in scalp hair samples of male subjects of two age groups (18-30 and 31-50 years), belonging to NE, LE, and HE areas, ranged from 0.26 to 0.69, 0.58 to 1.34, and 15.6 to 60.9 μg/g, respectively. A significant correlation between As levels in drinking water and scalp hair was observed in HE area (r = 0.86-0.90, p < 0.001) as compared to those subjects belonging to LE area. A toxicity risk assessment was calculated as hazard quotient (HQ), which indicates that the study subjects of HE area have significantly higher values of HQ than LE. The population of As exposed areas is at high risk of non-carcinogenic and carcinogenesis effects.


Context isn't everything: Search performance is influenced by the nature of the task but not the background.
AbstractIt has been demonstrated in the literature that cues in the environment that are predictive of how a task ought to be performed can influence performance. In an extension of this general notion, Cosman and Vecera (Journal of Experimental Psychology: Human Perception and Performance, 39(3), 836-848, 2013) reported that simply performing singleton and feature search tasks when irrelevant scenes were displayed in the background automatically modulated the search strategies adopted by participants when these scenes were reinstated at a later time. While intriguing, this result was also somewhat surprising given that an adaptive system (like the human brain) should disregard irrelevant information so task competencies generalize across environments. To investigate this issue further, we replicated the experimental procedures of Cosman and Vecera, while varying whether the test phase was either a singleton search (Experiments 1 and 3) or a feature search (Experiment 2) task. While it was observed that the nature of the search task varied whether a color singleton distractor influenced performance, there was no evidence that background scenes modulated the search strategies adopted by participants, contrasting the results of Cosman and Vecera. Overall, the findings here support the conclusion that the visual system prioritizes task-relevant information while disregarding irrelevant background information.


Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates.
Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect.


13C NMR evidence of the failure of human erythrocytes to metabolize ascorbate and dehydroascorbate to lactate.
13C-NMR spectroscopy was used to record time courses of the metabolism of [1-(13)C]-L-ascorbic acid (AA) and [2-(13)C]-L-ascorbic acid and their dehydro-counterparts (DHAA) by human erythrocytes. Under a range of experimental conditions, but most notably in the absence of glucose in the incubation medium, no (13)C-NMR signal for lactate emerged during any of the 5 h time courses. The NMR resonances that did emerge over time were assigned to diketogulonic (DKG) acid and CO(2). Only very minor resonances from degradation products of DKG appeared from samples that contained physiologically high concentrations of DHAA. These results are in contrast with those in a recent report that lactate is derived from AA in human erythrocytes. However, an explanation for this possible artifact is given.


Directional tuning of complex cells in area 17 of the feline visual cortex.
1. Directional tuning for motion of a field of static visual noise and for motion of bar stimuli against the same stationary noise field as background was compared in eighty-four deep-layer complex cells recorded from area 17 of cats, lightly anaesthetized with N(2)O/O(2) supplemented with pentobarbitone. Detailed comparisons of monocular tuning for the dominant eye receptive field were made for seventy-two cells. Interocular, and stimulus-dependent ocular dominance differences are reported elsewhere (Hammond, 1978c, and in preparation).2. Directional bias for preferred and opposite directions of motion was enhanced with moving noise fields, compared with moving bar stimuli. Two thirds of cells directionally biased for bars, were directionally selective for noise (33/49); ten of these showed suppression of firing to noise moving in the ;null' direction. An additional twenty-three cells were directionally selective for bar stimuli and for noise, nine with suppression of firing in the null direction.3. A majority of cells (52/62) showed significant differences in preferred directions for bar stimuli and for noise; in an exceptional case, tuning for the two classes of stimuli was orthogonal. Tuning for bar stimuli was usually sharper than for noise. In cells asymmetrically tuned for bar stimuli, tuning was broader for the flank of the tuning curve closest to the preferred direction for noise. Ten cells showed similar tuning for bars and noise; tuning for the remaining ten cells was rather variable or poorly defined.22/62 cells showed bimodal directional tuning to noise, with depression of sensitivity over the range of directions to which the cell responded well with a moving bar stimulus.4. Cells were frequently more responsive to noise-field motion than to bar motion. Cells with large receptive fields showed greater sensitivity to noise than those with small fields, and were relatively more sensitive to noise than to bar stimuli.5. The results are interpreted as evidence that the directional and orientational sensitivity of complex cells are mediated by different mechanisms.


Militarizing politics of recognition through the Invictus Games: post-heroic exalting of the armed forces.
The Invictus Games is an international sporting competition involving military veterans who have become either wounded, injured or sick during their service. Having become a prominent event in the public sphere of participating nations that are drawn from Western security alliances, this article outlines results from a thematic analysis of Australian media surrounding the 2018 Sydney Games. While reporting of the Games included the use of cultural frames that reflect traditional symbolic relationships between sport and war, the data reveal new military-civilian discourses drawn from identity politics and focused on cultural recognition. These discourses emerge through the Invictus Games by (1) disability providing a cultural basis to demand greater respect for contemporary veterans and military service; and (2) empowerment narratives of rehabilitation being symbolically connected to participants' reengagement with their former military identity. Institutional problems central to rising political activism amongst contemporary veterans did not feature in the media coverage. It is argued that the Invictus Games illustrates the need for sociology to conceive of militarization in more multidimensional ways, appreciating both the prominence of a civilian-military gap in contemporary culture and how various social actors in Defense utilize post-heroic narratives in seeking to redress this cultural divide.


Primary chemotherapeutic management of unresectable and metastatic hepatoblastoma in children: report of four cases.
Four children presenting with unresectable hepatoblastomas and one with metastatic disease are reported. Following initial biopsy all were treated with chemotherapy which included Adriamycin. Three of the four children showed a significant reduction in tumor size, and in two, delayed resection of the primary lesion was possible. Chemotherapy including Adriamycin represents effective initial cytoreductive therapy for childhood hepatoblastoma, thereby reducing the morbidity and mortality associated with the extensive hepatic resection usually required for an untreated lesion.


Docosahexaenoic acid is potent against the growth of mature stages of Plasmodium falciparum; inhibition of hematin polymerization a possible target.
The present study investigates the potential effect of externally added unsaturated fatty acids on P. falciparum growth. Our results indicate that polyunsaturated fatty acids (PUFAs) inhibit the growth of Plasmodium in proportional to their degree of unsaturation. At higher concentration the PUFA Docosahexaenoic acid (DHA) induces pyknotic nuclei in infected erythrocytes. When Plasmodium stages were treated transiently with DHA, the ring stage culture recovered from the drug effect and parasitemia was increased post DHA removal with delayed growth of 12 h, compared to untreated control. Schizont stage treated culture displayed a 36 h delay in growth to infect fresh erythrocytes signifying its recovery is less than the ring stage. However the trophozoite stage failed to recover and showed a decrease in parasitemia, similar to that of continuous treated culture. PUFAs inhibited β- hematin polymerization by binding to free heme derived from hemoglobin degradation. Digestive vacuole neutral lipid bodies, which are pivotal for β- hematin polymerization, decreased and subsequently abrogated with increasing concentration of DHA in trophozoite stage treated culture. Our study concludes that DHA interacts with heme monomers and inhibits the β- hematin polymerization and growth of mature stages i.e., trophozoite and schizont stages of plasmodium.


Dissecting the smell of fear from conspecific and heterospecific prey: investigating the processes that induce anti-predator defenses.
Prey use chemical cues from predation events to obtain information about predation risk to alter their phenotypes. Though we know how many prey respond to predators, we still have a poor understanding of the processes and chemical cues involved during a predation event. We examined how gray treefrog tadpoles (Hyla versicolor) altered their behavior and morphology when raised with cues from different stages of predator attack, predators fed different amounts of prey, and predators consuming different combinations of treefrog tadpoles or snails (Helisoma trivolvis). We found that starved predators and predators fed snails induced no defensive responses whereas tadpoles exposed to a predator consuming gray treefrogs induced greater hiding, lower activity, and relatively deeper tails. We also found that the tadpoles did not respond to crushed, chewed, or digested conspecifics, but they did respond to consumed (i.e., chewed plus digested) conspecifics. When we increased the treefrog biomass consumed by predators, tadpoles frequently increased their defenses when only tadpoles were consumed and always increased their defenses when the total diet biomass was held constant via the inclusion of snails. When predators experienced temporal variation in diet composition, including cues from snails to cause additional digestive cues or chemical noise, there was no effect on tadpole phenotypes. Our results suggest that amphibian prey rely on cues from both chewing and digestion of conspecifics and that the presence of cues from digested heterospecifics play little or no role in adding chemical noise or increased digestive enzymes and by-products that could potentially interfere with induced defenses.


Patient information ahead of thyroid surgery. Guidelines of the French Society of Oto-Rhino-Laryngology and Head and Neck Surgery (SFORL).
The authors present the guidelines of the French Society of Oto-Rhino-Laryngology and Head and Neck Surgery (SFORL) on patient information ahead of thyroid surgery. A multidisciplinary medical team was tasked with a scientific literature review on this topic. The texts retrieved were analyzed by an independent committee. A joint meeting drew up the final guidelines. The strength of the recommendations (grade A, B or C) was based on levels of evidence. It is recommended that the results of preoperative exploration and the indications for surgery should be explained to the patient. Patients should be informed as to the type of surgery, surgical objectives, risks and consequences. It is mandatory to obtain the patient's written consent before surgery. Appropriate medical information is a critical step in patient management.


Enhanced exopolysaccharide production by multi metal tolerant Klebsiella variicolaSMHMZ46 isolated from mines area and application in metal bioremediation.
The current study aimed to enhance exopolysaccharide production by Klebsiella variicolaSMHMZ46 isolated from the Zawar mines area in Udaipur, Rajasthan, India, by optimizing the medium with OFAT and a central composite design. The trial including sucrose (9.5%), casein hydrolysate (3%), and NaCl (0.5%) yielded the maximum EPS production as indicated by applying the CCD-RSM biostatistical program. The composition of exopolysaccharides produced by Klebsiella variicolaSMHMZ46 culture was characterized. Growth under Pb(II), Cd(II), and Ni(II) metal amended conditions induced EPS production relative to control. TLC was used for identifying the sugar residues of EPS, in addition to determination of both total carbohydrate and protein contents. According to FT-IR analysis, EPS can interact with metal ions via their functional chemical groups, thereby supporting their bioremediation potential. The metal removal efficiency of bacteria and their produced EPS in broth individually spiked with Pb(II), Ni(II), and Cd(II) was 99.18%, 97.60%, and 98.20%, respectively, and powdered EPS from contaminated water was 85.76%, 72.40%, and 71.53%, respectively. According to FEG-SEM observations, the surface morphology of EPS becomes rough, demonstrating sharp bumps after metal binding. A FEG-SEM analysis of the structure of EPS was performed; the surface structure of EPS (with metal) was more rigid than that of control EPS (without metal). The interaction between the EPS system and Pb(II) ions was investigated using FEG-SEM coupled with energy dispersive X-ray spectra, and a strong peak of C, O, and Pb elements was observed, indicating successful Pb adsorption. These findings suggest that EPS from Klebsiella variicolaSMHMZ46 has a good metal adsorbing nature and could be a promising biosorbent for metal bioremediation of contaminated water.


Femtosecond Laser Induced Phase Transformation of TiO2 with Exposed Reactive Facets for Improved Photoelectrochemistry Performance.
Titanium dioxide (TiO2) is one of the most promising candidates for photoelectrochemistry applications. For a high photoelectrochemistry performance, the control of crystal structure and crystal facet is essential. The phase transformation of TiO2 is conventionally achieved by thermal annealing. Here, we report an approach for selective phase transformation of TiO2 containing exposed reactive facets with improved photoelectrochemistry performance. After femtosecond laser processing, TiO2 nanotubes with exposed reactive anatase {010} facets are prepared, and they have a maximum photocurrent density more than 5 times that of pure anatase. Additionally, this strategy can induce phase transformation in a selective area, which shows the advantages of patterning processing. Our method constructs a promising strategy for preparing functional nanomaterials with high performances and functionality.


Karyologically identified homozygous tw18 embryos: extrauterine growth properties and transformation by SV40.
A method for identifying individual embryos from crosses segregating homozygous t lethals using the marker chromosome Rb7 is described and applied to the tw18 haplotype. In contrast to wild-type and heterozygous littermates, homozygous tw18/tw18 6 and 8 day embryos have very limited growth potentialities in vitro. When transplanted under the testis capsule, homozygous tw18 embryos (3, 6 and 7 day) produce teratomas at a much lower efficiency than heterozygous and wild-type embryos, and the rare teratomas thus obtained have limited growth potentialities when cultured in vitro. Upon transformation with SV40, however, permanent lines of cells of mesodermal origin, capable of myoblastic or adipocytic differentiation, have been obtained. This shows that the effect of the mutation on cell growth can be overcome by SV40 transformation.


Combination of pioglitazone and dendritic cell to optimize efficacy of immune cell therapy in CT26 tumor models.
The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway. Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis. In vitro results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed. Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.


Profound structural alterations of the extracellular collagen matrix in postischemic dysfunctional ("stunned") but viable myocardium.
Ultrastructural studies of the extracellular collagen matrix were made on the "stunned" myocardium using scanning, conventional and high voltage transmission electron microscopy and light microscopy. Regional myocardial dysfunction was produced by 12 sequential 5 minute occlusions of the left anterior descending coronary artery, separated by 10 minute intervals of reperfusion. A final 90 minute reperfusion period documented persistent myocardial dysfunction. At the end of the final reperfusion period, the percent systolic shortening, measured by sonomicrometers, was depressed significantly to 35 +/- 9% of baseline. The heart was then perfusion fixed, and samples were taken from both control and stunned areas. No changes associated with irreversible cellular damage were noted in the stunned region. However, scanning electron microscopy of the stunned area showed that the extracellular collagen matrix underwent profound structural changes. Collagen cables were roughened, uncoiled and discontinuous. Linear grooves on the surface of the myocytes were frequently seen, indicating complete loss of collagen cables. The usual dense collagen weave surrounding myocytes became patchy or absent. Myocyte to myocyte struts were sparse and frequently absent, with remnant nodular or nublike structures indicative of breakage. High voltage electron microscopy of the stunned area showed that the collagen struts were discontinuous and vacuolated with rounded tips. Light microscopy of silver-stained sections of the stunned tissue demonstrated large patchy areas that were devoid of silver, indicating absence of the collagen matrix. There was a progressive increase in percent systolic bulging during each sequential coronary occlusion, suggesting increasing myocardial compliance. These results indicate that the myocardial collagen matrix is severely damaged from reversible ischemic cell injury. The greater myocardial compliance and less effective contractile effort in the stunned myocardium might be explained on a structural basis: disruption of the mechanical coupling function provided by the extracellular collagen matrix.


Low diagnostic yield in follow-up MR imaging in patients with spontaneous intracerebral hemorrhage with a negative initial MRI.
Follow-up MRI/MRA is historically obtained as outpatient when patients with a spontaneous intracerebral hemorrhage (ICH) have an initial MRI/MRA that is negative for an underlying structural lesion. However, the utility of repeating MR imaging in a delayed fashion remains uncertain. We retrospectively reviewed 396 patients with spontaneous ICH admitted at our institution between 2015 and 2017 and selected those whose initial MRI/MRA was negative for an underlying structural lesion and those who underwent follow-up MR imaging in a delayed fashion. A total of 113 patients met the study criteria. The average age of those with negative follow-up MRI/MRA was 65.0 ± 12.6 (IQR: 55.0-74.0) years old. None of the 113 patients with a negative inpatient MRI/MRA had an underlying structural lesion on follow-up MRI/MRA (0%, 95% CI 0.0-0.032, p < 0.001). The mean time of the follow-up imaging from the initial study was 105.7 days (median: 62 days; IQR: 42.5-100.5). Of the 113, 83 (73.5%) underwent follow-up MRI with and without gadolinium, while 30 (26.5%) patients did not receive gadolinium. Delayed follow-up MRI in patients with a negative initial MRI/MRA for workup of spontaneous ICH was not diagnostic in any of the patients included in the study. Our study suggests that a routine follow-up MRI for this patient population is not necessary.


Effect of statins on amyloidosis in the rodent models of Alzheimer's disease: Evidence from the preclinical meta-analysis.
Previous studies have shown contrasting results in determining efficacy of statins against amyloid beta accumulation. The aim of this study was to assess the impact of statin in AD. We searched PubMed and Embase for relevant preclinical studies. A meta-analysis of the statin's efficacy on amyloidosis and cognitive impairment was performed. Also, stratified analysis was performed on several covariates including the type of statin used, gender and age of rodents and duration of statin therapy, to account for the reported heterogeneity in the results obtained. The study protocol was registered in PROSPERO (CRD42018102557). 17 studies including 22 comparisons, containing a sample size of 446 rodents, participated in the meta-analysis of statin's effect on overall Aβ deposition. Although the effect of statin on overall Aβ deposition was found to be protective (p < 0.00001) but as we categorized the efficacy of statin on different Aβ species (soluble and insoluble Aβ40/42) and Aβ plaque load, we found that significance in the protection decreased. A stratified meta-analysis demonstrated a significant role in the duration of statin supplements and rodent's age on the heterogeneity of the results. Statin administered to rodents for the longest duration (>6 months) and younger rodents (<6 months of age) demonstrated significant efficacy of statin on Aβ deposition. Statin showed reduction in Aβ level but stratified analysis revealed that this effect of statin was dependent on rodent's age and duration of the treatment.


Comparing survival and treatment response of patients with acquired T790M mutation second-line osimertinib versus sequential treatment of chemotherapy followed by osimertinib: A real-world study.
To investigate the survival benefit with first/second generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and osimertinib in different treatment sequences. We retrospectively screened 3807 patients diagnosed with cancer between 2013 and 2019 at Kaohsiung Chang Gung Memorial Hospital. In total, 76 patients with EGFR T790M mutation who received osimertinib after re-biopsy or liquid biopsy were enrolled for the analysis. The median progression-free survival (PFS), median overall survival (OS), and median OS2 of the 76 patients were 11.93, 66.53, and 29.57 months, respectively. A significant difference was observed in the disease control rate between those who received osimertinib treatment after chemotherapy (group A) and those who received osimertinib immediately following EGFR-TKI therapy (group B) (34 [94.4%] vs. 31 [77.5%], p = 0.036). In addition, chronic obstructive pulmonary disease tended to be a poor prognostic factor for PFS and OS. This real-world analysis revealed that previous chemotherapy could affect the treatment outcomes of patients with non-small cell lung cancer treated with osimertinib. Osimertinib treatment following first/second generation EGFR-TKI treatment or chemotherapy resulted in improved survival benefit.


Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesions.
We aimed to evaluate the safety and technical success of an easy-to-use technique that applies underwater cap suction pseudopolyp formation to facilitate the resection of flat lesions or those at the appendiceal orifice or ileocecal valve. We retrospectively analyzed a register of consecutive cap suction underwater endoscopic mucosal resection (CAP-UEMR) procedures performed at two centers between September 2020 and December 2021. Procedures were performed using a cone-shaped cap, extending 7 mm from the endoscope tip, to suction the lesion while submerged underwater, followed by underwater snare resection. Our primary end point was technical success, defined as macroscopic complete resection. We treated 83 lesions (median size 20 mm; interquartile range [IQR] 15-30 mm) with CAP-UEMR: 64 depressed or flat lesions (18 previously manipulated, 9 with difficult access), 11 from the appendix, and 8 from the ileocecal valve. Technical success was 100 %. There were seven intraprocedural bleedings and two delayed bleedings, all managed endoscopically. No perforations or other complications occurred. Among the 64 lesions with follow-up colonoscopy, only one recurrence was detected, which was treated endoscopically. CAP-UEMR was a safe and effective technique for removing nonpolypoid colorectal lesions, including those arising from the appendiceal orifice or ileocecal valve.


Smoking in Saudi Arabia and its relation to coronary artery disease.
The health hazards related to smoking are well known. Smoking is a recognized risk factor for coronary artery disease (CAD). Despite rejection of smoking by the Saudi community, we are still seeing smokers in our population. This study is designed to determine the prevalence of smoking in the Kingdom of Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of the Coronary Artery Disease In Saudis (CADIS) study. This health survey was conducted by collecting data regarding smoking status among adult Saudis aged between 30 and 70 years of both sexes in KSA over a five year period from 1995 up to 2000. The study sample was of normal distribution and representative of all regions of KSA. The data were analyzed to provide the prevalence of smoking and its relation with CAD. The total number of subjects was 17,350, and current smokers were 2217; accordingly the overall prevalence of smoking among Saudis was 12.8%. Males (1555) were significantly smoking more than females (662) with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more prevalent among Saudis living in urban, northern, western, and eastern regions compared to other regions of KSA. Smokers are more likely to develop CAD compared to non-smokers (P < 0.0001). Smoking is a prevalent health problem among Saudis that requires intervention for eradication. We found clear association between cigarettes smoking and CAD particularly among males. Persistent education of the health hazards related to smoking is recommended particularly at early age in-order to prevent initiation of smoking.


Identification of a new alpha-2-macroglobulin: Multi-spectroscopic and isothermal titration calorimetry study.
A α2M homologue was isolated from sheep (Ovis aries) blood plasma, using a simple two-step procedure, ammonium sulphate fractionation and gel filtration chromatography. Sheep α2M was found to be a large tetrameric glycoprotein of 630 kDa with monomeric subunit of 133 kDa each. Each subunit of sheep α2M was found to be made up of two fragments of 102 and 31 kDa respectively. The proteinase inhibitor from sheep was found to have Stokes radius of 79Ǻ, which makes it much more compact than its human homologue. It entraps only 1 mol of trypsin per mole of inhibitor, like its caprine counterpart. The use of isothermal titration calorimetry has become gold standard for exploring thermodynamics of binding interactions. In this study, binding interaction of trypsin with alpha-2-macroglobulin is studied using ITC. The thermodynamic signatures--enthalpy change (ΔH), entropy change (ΔS) and Gibb's free energy change (ΔG), along with number of binding sites (N) and affinity constant (K) are explored for α2M-trypsin binding for the first time for any known α2M molecule. The thermodynamics of proteinase-antiproteinase association suggests that trypsin-α2M interaction is enthalpy driven event.


Effects of Montelukast on free radical production in whole blood and isolated human polymorphonuclear neutrophils (PMNs) in asthmatic children.
Montelukast is a highly selective leukotriene-receptor antagonist (LTRA). It is widely used in the treatment of bronchial asthma, primarily as an adjunct to corticosteroids. Reactive oxygen species (ROSs) play an important role in the pathogenesis of asthma and oxidative stress contributing to the initiation and worsening of inflammatory respiratory disorders, such as asthma. Antioxidant drugs may have a role in minimizing or preventing damage in asthmatic children. The aim of this study was to assess the antioxidant effect of montelukast on the production of free radicals in the whole blood and polymorphonuclear neutrophils (PMNs) in asthmatic children. A group of 48 (38 males and 10 females), apparently healthy asthmatic children were recruited with ages ranging between 6 and 14 years. In asthmatic children, base line (premedication) and post medication free radicals activity in the whole blood and polymorphonuclear neutrophils (PMNs) was determined by measuring chemiluminescence (CL) response through chemiluminescence luminometer. Free radical productions were significantly decreased in the whole blood, when stimulated with Phorbol Myristate Acetate (p < 0.04) and Opsonised Zymosan (p < 0.05). The free radicals were also significantly decreased in isolated polymorphonuclear neutrophils (PMNs) when stimulated with Opsonised Zymosan (p < 0.05) after the post medication treatment of montelukast in asthmatic children. Montelukast decreased the reactive oxygen species production, both in the whole blood as well as isolated PMNs in asthmatic children.


New Alkaloids from Aconitum stapfianum.
Nineteen alkaloids, including a new C19-diterpenoid alkaloid stapfianine A (1) and a new benzamide derivative stapfianine B (2) were isolated from the roots of Aconitum stapfianum. Their structures were established on the basis of extensive spectroscopic analyses (IR, HRESIMS, 1D and 2D NMR).


A client-binding site of Cdc37.
The molecular chaperone Hsp90 is distinct from Hsp70 and chaperonin in that client proteins are apparently restricted to a subset of proteins categorized as cellular signaling molecules. Among these, many specific protein kinases require the assistance of Hsp90 and its co-chaperone Cdc37/p50 for their biogenesis. A series of Cdc37 deletion mutants revealed that all mutants capable of binding Raf-1 possess amino acid residues between 181 and 200. The 20-residue region is sufficient and, in particular, a five-residue segment (residue 191-195) is essential for binding to Raf-1. These five residues are present in one alpha helix (residues 184-199) in the middle of Cdc37, which is unexpectedly nested within the Hsp90-interacting domain of Cdc37, which was recently determined by crystallography, but does not seem to contribute to direct contact with Hsp90. Furthermore, an N-terminally truncated mutant of Cdc37 composed of residues 181-378 was shown to bind the N-terminal portion of Raf-1 (subdomains I-IV). This mutant can bind not only other Hsp90 client protein kinases, Akt1, Aurora B and Cdk4, but also Cdc2 and Cdk2, which to date have not been shown to physically interact with Cdc37. These results suggest that a region of Cdc37 other than the client-binding site may be responsible for discriminating client protein kinases from others.


Prenatal lorazepam exposure: 4. Persistent alterations in pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake after prenatal lorazepam exposure.
Prenatal benzodiazepine exposure is associated with behavioral and neurochemical alterations in the early postnatal period. To determine the persistence of these effects, we evaluated pentylenetetrazole-induced seizure threshold and GABA-dependent chloride uptake in mice at 6 and 12 months of age after prenatal lorazepam exposure. Seizure threshhold was reduced after acute lorazepam pretreatment in mice exposed to lorazepam prenatally, compared to control groups, at 6 and 12 months of age. Maximal GABA-dependent chloride uptake was also reduced in exposed mice at 6 and 12 months of age. These data indicate that behavioral and neurochemical alterations persist well into maturity after prenatal lorazepam exposure.


Parenteral systems for statin delivery: a review.
The oral route of drug administration is the most common and convenient route for dosing statin drugs, and, in fact, most medications, because of ease of drug delivery, patient compliance, and cost-effectiveness. However, the oral administration of statin drugs has disadvantages such as hepatic first-pass metabolism and degradation within the gastrointestinal tract that limit their overall bioavailability. This review introduces several diverse non-oral delivery methods for the administration of statins. These alternative delivery systems and routes of administration are varied and are capable of improving the bioavailability and therapeutic efficacy of statin drugs.


Hyperpolarized [1-13 C]pyruvate combined with the hyperinsulinaemic euglycaemic and hypoglycaemic clamp technique in skeletal muscle in a large animal model.
What is the central question of this study? Is it possible to combine the hyperpolarized magnetic resonance technique and the hyperinsulinaemic clamp method in order to evaluate skeletal muscle metabolism in a large animal model? What is the main finding and its importance? The logistical set-up is possible, and we found substantial increments in glucose infusion rates representing skeletal muscle glucose uptake but no differences in ratios of [1-13 C]lactate to [1-13 C]pyruvate, [1-13 C]alanine to [1-13 C]pyruvate, and 13 C-bicarbonate to [1-13 C]pyruvate, implying that the hyperpolarization technique might not be optimal for detecting effects of insulin in skeletal muscle of anaesthetized animals, which is of significance for future studies. In skeletal muscle, glucose metabolism is tightly regulated by the reciprocal relationship between insulin and adrenaline, with pyruvate being at the intersection of both pathways. Hyperpolarized magnetic resonance (hMR) is a new approach to gain insights into these pathways, and human trials involving hMR and skeletal muscle metabolism are imminent. We aimed to combine the hyperinsulinaemic clamp technique and hMR in a large animal model resembling human physiology. Fifteen anaesthetized pigs were randomized to saline (control group), hyperinsulinaemic euglycaemic clamp technique (HE group) or hyperinsulinaemic hypoglycaemic clamp technique (HH group). Skeletal muscle metabolism was evaluated by hyperpolarized [1-13 C]pyruvate injection and hMR at baseline and after intervention. The glucose infusion rate per kilogram increased by a statistically significant amount in the HE and HH groups (P < 0.001). Hyperpolarized magnetic resonance showed no statistically significant changes in metabolite ratios: [1-13 C]lactate to [1-13 C]pyruvate in the HH group versus control group (P = 0.19); and 13 C-bicarbonate to [1-13 C]pyruvate ratio in the HE group versus the control group (P = 0.12). We found evidence of profound increments in glucose infusion rates representing skeletal muscle glucose uptake, but interestingly, no signs of significant changes in aerobic and anaerobic metabolism using hMR. These results imply that hyperpolarized [1-13 C]pyruvate might not be optimally suited to detect effects of insulin in anaesthetized resting skeletal muscle, which is of significance for future studies.


Future directions in phosphodiesterase drug discovery.
Research on phosphodiesterases both in academic labs and in the pharmaceutical industry has remained steady over the past 35 years. Although there have been some clinical successes, they have been clustered around just a couple of PDE isoforms, and disproportionate to the huge investment put forth against what seem like very druggable targets. This review attempts to uncover the reasons for the lack of productivity in PDE drug discovery, and summarizes the current hot areas of research. In addition, new insights gathered about structure-function relationships are highlighted, in particular those relating to enzyme regulation. Lastly, novel strategies for targeting the activation or inactivation of selected PDEs are proposed that may allow for a more targeted approach for PDE modulation.


Risk factors associated to bovine brucellosis seroprevalence in the eastern region of Paraguay.
In Paraguay, whose main economic activity is cattle raising, bovine brucellosis is an endemic disease. Between May 2019 and October 2020, a national prevalence survey was implemented by the Paraguayan Veterinary Services. In the frame of that survey, a cross-sectional study was conducted in the eastern region of Paraguay to identify the risk factors that could be associated with brucellosis-positive farms and to estimate the bovine brucellosis seroprevalence and farmers' awareness about the disease. A questionnaire was administered to farmers to collect data on potential risk factors for bovine brucellosis as well as awareness on the disease. A logistic regression model was used to identify the risk factors associated with a farm brucellosis positive status. Blood samples were collected from 2551 cattle on 133 farms. The overall apparent seroprevalence was 27.8 % (95 % CI: 20.4-36.3 %) at the farm level, and 5.5 % (95 % CI: 4.7-6.5 %) at the animal level. Among 18 potential risk factors, four were associated with a farm brucellosis positive status. Farm size was associated with a higher risk of positive status in medium (20-80 cows) and large farms (>80 cows), compared with small farms (<20 cows). Barn disinfection had a protective effect on the risk of positive status. Conversely, presence of dogs and not incinerating/burying aborted material increased this risk. Even if 89 % of the farmers acknowledged being aware of the bovine brucellosis transmission to humans, only 46% of these farmers declared using protective gloves during calving or when handling abortions. The findings of this study emphasize the importance of implementing biosecurity measures and proper disposal of aborted material to control the disease. Therefore, to control the disease in Paraguay, vaccination campaigns should be accompanied by awareness campaigns addressing good farm management practices to minimize the risk of introduction and maintenance of brucellosis as well as the risk of human infection.


Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome.
DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle. We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2, CDC20, AURKA, AURKB and TPX2). The M-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI -27.127779 to -2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI -72.922115 to -1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI -69.189259 to -0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation. As 5mC immunoexpression increases, the expressions of POLH (r=-0.816; r2 =0.665; p=0.000), POLQ (r=-0.790; r2=0.624; p=0.001), PCNA (r=-0.635; r2=0.403; p=0.020), POLK (r=-0.633; r2=0.400; p=0.036 and REV1 (r=-0.578; r2=0.334; p=0.049) decrease. Our results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.


Endogenous electric currents might guide rostral migration of neuroblasts.
Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 μA/cm(2), average field strength of ∼3 mV/mm) along the rostral migration path in adult mouse brain. Electric fields of similar strength direct migration of neuroblasts from the SVZ in culture and in brain slices. The purinergic receptor P2Y1 mediates this migration. The results indicate that naturally occurring electric currents serve as a new guidance mechanism for rostral neuronal migration.


Decisions in complex clinical situations: Prevalence and factors associated in general public.
Many studies have focused on advanced directives. However, the type of treatment that citizens would choose in critical health situations and whether their decision varies with their sociodemographic characteristics and their experiences of life both within and outside the family context, are unknown. This study analyzes the factors associated with choosing or refusing life support treatment in hypothetical situations of differing clinical complexity. This transversal descriptive study was carried out by questionnaires given to 1051 participants from primary care centres. The Life Support Preferences Questionnaire (LSPQ) used to assess preferences of life-sustaining treatment, describes six scenarios with different prognoses. Analysis of the sociodemographic characteristics and life experiences of the subjects led to the following findings. In situations of very severe prognosis, treatment is mostly rejected. When there is chance of recovery, treatment is mostly accepted, especially in the least aggressive cases and when deciding for another person. A greater propensity to reject treatment was observed among subjects over 55 years, those in poor health and those who had observed a terminal illness in a family member. Practising Catholics are more likely to accept treatment in all medical situations described. Preferences for life support treatment are linked to sociodemographic characteristics and life experiences of patients. Physicians should bear in mind these characteristics when confronted with critical clinical situations, involving difficult decisions.


Normal distribution and denervation changes of neurotransmitter related enzymes in cholinergic neurones.
1. The activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were assayed in adult pigeon ciliary ganglia, in the post-synaptic ciliary and choroid nerves, and in ciliary nerve iris terminals isolated from control birds and from animals from which the oculomotor nerve was previously transected. Enzyme activity levels were also measured in the iris terminals after surgical section of the ciliary nerves. From differences in enzyme activity between control and 3-day denervated tissues, the localization of CAT and AChE in pre- and post-synaptic elements of the ganglia and at the iris neuromuscular junctions was estimated. The fate of the preganglionic nerve terminals after denervation was investigated by electron microscopic examination of ganglia after surgical section of the oculomotor nerve.2. The CAT activity in the ganglion was distributed as follows: 60% in presynaptic elements, 31% in cell somas, and 9% in intraganglionic post-synaptic axons; in the iris junctions, 98% of the activity was present in the ciliary nerve terminals. For AChE: 20% was present in the preganglionic terminals, 69% in ganglion cell somas and the remaining 11% in post-ganglionic axons; at the neuromuscular iris junctions, 20% was found in the ciliary nerve terminals and 80% in the iris striated muscle.3. The first changes in the fine structure of the nerve terminals were observed 14 hr after surgery, and by 24 hr marked alteration of the synaptic structure were clearly recognized. No preganglionic endings were found in 3 day-old denervated ganglia.4. There was a positive correlation between CAT activity in the control iris nerve terminals and in ganglia. After denervation, when the activity of the enzyme decreased in ganglion cell somas, there was a corresponding decrease in the post-synaptic nerves. These two findings suggest that CAT slow axoplasmic transport is related to its perikarial concentration.5. There was a 60% reduction of CAT activity in the post-synaptic elements, assayed in the 10-day denervated ganglia, which was accompanied by a 30% decrease in activity in the iris nerve terminals. Similarly, post-synaptic AChE decreased approximately 30% in the ganglion and approximately 30% in the iris 10 days after section of the oculomotor nerve. At the same time, CAT activity also decreased in the nerve trunks, 70% at the ciliary nerve and 40% at the choroid; for AChE there were smaller changes.6. In contrast to CAT and AChE, there were no differences in ganglionic protein content, or lactate dehydrogenase (LDH), co-enzyme A (CoA) and monoamine oxidase (MAO) levels between short-term (3 days) and long-term (10 days) denervated ganglia.7. The later decrease of CAT and AChE activity in the cell somas, axons and nerve terminals after long-term preganglionic transection suggests that the activity of these enzymes is regulated across the synapses. It is postulated that the AChE regulation is part of a general ;trophic interaction' between neurones, but that the trans-synaptic modulation of CAT is specific for cholinergic cells.


Mechanism of dielectric barrier plasma technology to improve the quantity and quality of short chain fatty acids in anaerobic fermentation of cyanobacteria.
The recycling of high value carbon resources from cyanobacteria has become a research hotspot. This work investigated the possibility of dielectric barrier discharge (DBD) plasma pretreatment to improve the anaerobic fermentation performance of cyanobacteria. The maximum accumulations of short-chain fatty acids (SCFAs) and acetic acid in DBD group were 3.30 and 1.49 times of that in control group. The physical effects of DBD plasma and the oxidative stress response of cyanobacteria cells could improve the solubilization of cyanobacteria polymer. The destruction of humus by DBD plasma can reduce the negative impact of humus on the early stage of anaerobic fermentation, thus facilitating the rapid start of anaerobic fermentation. The contents of Bacteroidetes, Firmicutes and Chloroflexi in DBD group were higher than those in control group, while the content of Proteobacteria was on the contrary, which was conducive to the hydrolysis and acidification process. The decrease of Methanosaeta sp. and Methanosarcina sp. abundance in DBD group might be another reason for the increase of acetic acid ratio. Under the joint action of plasma chemical oxidation and microbial degradation, the degradation effect of microcystin-LR in the anaerobic fermentation supernatant of DBD group was better than that of the control group, which was conducive to the recycling of cyanobacteria anaerobic fermentation supernatant. Therefore, DBD pretreatment was conductive to recycling valuable carbon source from cyanobacteria and can be further developed as a potential new pretreatment technology.


No evidence of association between subclinical thyroid disorders and common carotid intima medial thickness or atherosclerotic plaque.
Increased carotid artery intima-media thickness (IMT) and the presence of plaques have been shown to be predictors of cardiovascular disease. The cardiovascular risk in patients with overt thyroid diseases is related to increased risk of atherosclerosis, but there has been no clear evidence about subclinical disorders. We have assessed whether subclinical thyroid dysfunction is associated with arterial thickening and plaque. The SardiNIA study is a population-based survey on the Italian island of Sardinia. We reviewed data from 5815 subjects (aged 14-102 years), none of whom had overt hyperthyroidism or hypothyroidism or was taking thyroid medication. Serum thyrotropin (TSH), free thyroxine, together with carotid ultrasound IMT and the presence of common carotid plaques were analysed in all subjects. Possible association of IMT and carotid plaques with thyroid parameters was evaluated by univariate and multivariate analyses. IMT was significantly associated with age, sex, smoking, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol, pulse pressure (PP), history of arterial hypertension, diabetes, and previous cardiovascular events (p = 0.001 or lower, R(2) = 0.47). Carotid plaques were predicted by age, sex, LDL, PP, history of diabetes, previous cardiovascular events, and the use of statins (p = 0.029 or lower). Thyroid hormone was not predictive of carotid atherosclerosis when adjusted for confounders. Thyroid hormone is not associated with increased IMT or with the presence of carotid artery plaque. Our data do not support the idea that treating subclinical disorders might help to prevent arterial remodelling or carotid atherosclerosis.


Induced Pluripotent Stem Cells Reveal Common Neurodevelopmental Genome Deprograming in Schizophrenia.
Schizophrenia is a neurodevelopmental disorder characterized by complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain is established during gestation, long before clinical manifestation of the disease. Over 200 genes and even greater numbers of single nucleotide polymorphisms and copy number variations have been linked with schizophrenia. How does altered function of such a variety of genes lead to schizophrenia? We propose that the protein products of these altered genes converge on a common neurodevelopmental pathway responsible for the development of brain neural circuit and neurotransmitter systems. The results of a multichanneled investigation using induced pluripotent stem cell (iPSCs)- and embryonic stem cell (ESCs)-derived neuronal committed cells (NCCs) indicate an early (preneuronal) developmental-genomic etiology of schizophrenia and that the dysregulated developmental gene networks are common to genetically unrelated cases of schizophrenia. The results support a "watershed" mechanism in which mutations within diverse signaling pathways affect the common pan-ontogenic mechanism, integrative nuclear (n)FGFR1 signaling (INFS). Dysregulation of INFS in schizophrenia NCCs deconstructs coordinated gene networks and leads to formation of new networks by the dysregulated genes. This genome deprograming affects critical gene programs and pathways for neural development and functions. Studies show that the genomic deprograming reflect an altered nFGFR1-genome interactions and deregulation of miRNA genes by nFGFR1. In addition, changes in chromatin topology imposed by nFGFR1 may play a role in coordinate gene dysregulation in schizophrenia.


The relationship between cataract type and glare disability as measured by the Miller-Nadler glare tester.
Cataract patients were tested for glare disability using the Miller-Nadler glare tester. Predicted outdoor visual acuity was then compared with the actual outdoor visual acuity. The Miller-Nadler glare test scores predicted actual outdoor visual impairment to within one Snellen line in 46.7% of the eyes, underestimated actual outdoor visual impairment by more than one Snellen line in 31.5% of the eyes, and overestimated outdoor visual impairment by more than one Snellen line in 21.7% of the eyes. Overall, 64.1% of the eyes had outdoor vision which was more closely predicted by their glare scores than by their indoor Snellen acuity. When the cataractous eyes were divided into three categories, eyes with pure nuclear sclerosis, eyes with nuclear sclerosis and posterior subcapsular opacities, and eyes with all other cataractous combinations, predictability differences were observed. Although we found that actual outdoor visual acuities were not precisely predicted by disability glare scores in a substantial proportion of our subjects, the glare scores were considerably more predictive than indoor Snellen acuity. Further development and field testing of glare testing devices as predictors of outdoor visual impairment is necessary.


Emergent renal dysfunction with colistin pharmacotherapy.
To evaluate the association between the administration of intravenous (IV) colistin and the emergence of renal dysfunction. A retrospective medical record review. A tertiary care academic medical center. A total of 174 critically ill patients who received at least one dose of IV colistin between 2004 and 2007. The primary outcome was development of renal dysfunction, defined as an increase in serum creatinine of 50% or more during therapy or the initiation of renal replacement therapy (RRT), in patients who received at least one dose of colistin and were not already on RRT. The severity of renal dysfunction was further categorized by the RIFLE criteria. Demographic and clinical characteristics were analyzed by logistic regression for association with new renal dysfunction. A total of 174 patients were evaluated for renal dysfunction. Of these patients, 84 (48%) experienced renal dysfunction on colistin. On multivariate analysis, age in years (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05) and receipt of concurrent nephrotoxin(s) (OR 3.35, 95% CI 1.34-8.36) significantly increased the risk of developing renal dysfunction. In this critically ill population, renal dysfunction occurred frequently and was associated with older age and receipt of nephrotoxins.


The cardiorenal anaemia syndrome in systolic heart failure: prevalence, clinical correlates, and long-term survival.
We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes. We studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was all-cause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. The prevalence of CRA syndrome was 21.1%. Age (P < 0.001), body mass index (P< 0.001), diabetes (P =< 0.001), ischaemic aetiology (P< 0.006), left ventricular ejection fraction (P= 0.018), and treatment with renin-angiotensin system inhibitors (P< 0.001) were independently related to CRA syndrome. During a median follow-up of 3.7 years, the primary outcome occurred in 404 patients (42.5%). Compared with patients with preserved renal function and normal haemoglobin (Hb) levels, those with CRA syndrome had a significantly increased risk for the primary outcome; the univariate and multivariate-adjusted HRs were 4.04 (CI: 3.11-5.24; P< 0.0001) and 2.22 (CI: 1.64-2.98; P< 0.0001), respectively. Three-year UHT-free survival was 86 and 47%, respectively. Among patients with renal dysfunction, the adjusted HR for the primary outcome increased by 17% (CI: 8-26; P= 0.0001) for each 1g/dL decrease below an Hb value of 13.0 g/dL. Heart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF.


Use of a robotic device to measure age-related decline in finger proprioception.
Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p < 0.05); proprioceptive reaction time was 78 % longer in older adults compared to young adults (p < 0.01). When visual feedback was provided in addition to proprioception, these age-related differences were no longer apparent. No difference between dominant and non-dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception.


Novel synthesis of siligraphene/tungstates (g-SiC/AWO) with promoted transportation of photogenerated charge carriers via direct Z-scheme heterojunctions.
We developed here the efficient photocatalysts for the removal of high concentrations of tetracycline under visible light by immobilizing the AWO (A = Ag, Bi, Na) nanocrystals on the surface of siligraphene (g-SiC) nanosheets. The g-SiC/AWO composites was synthesized by magnesiothermic synthesis of g-SiC and sonochemical immobilization of tungstates. These new heterojunctions of g-SiC/tungstates show superior photocatalytic activities in the degradation of high concentrations of tetracycline and 97, 98, and 94% of tetracycline were removed by using low amounts of g-SiC/Ag2WO4, g-SiC/Bi2WO6, and g-SiC/Na2WO4 catalysts, respectively. Based on band structures, the band gaps reduce and the photocatalytic activities were extremely enhanced due to the shortening of electron transfer distance through the Z-scheme mechanism. Also, the graphenic structure of g-SiC is another parameter that was effective in improving photocatalytic performance by increasing the electron transfer and decreasing the rate of electron-hole recombination. Furthermore, the π back-bonding of g-SiC with metal atoms increases the electron-hole separation to enhance the photocatalytic activity. Interestingly, g-SiC composites (g-SiC/AWO) showed much higher photocatalytic properties compared to graphene composites (gr/AWO) and can remove the tetracycline even at dark by producing the oxygenated radicals via adsorption of oxygen on the positive charge of Si atoms in siligraphene structure.


Evaluation of HIV and highly active antiretroviral therapy on the natural history of human papillomavirus infection and cervical cytopathologic findings in HIV-positive and high-risk HIV-negative women.
The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous intraepithelial lesions (SILs). Longitudinal cytopathologic and HPV DNA results were analyzed using multistate models. States of cervical SIL were defined as absent, present, and treatment; HPV states were defined as negative or positive. Demographic variables and markers of sexual activity were considered predictors. Results were calculated on the basis of transition probabilities and reported as hazard ratios (HRs). The CWHS followed 750 HIV-positive and 323 HIV-negative women during 1993-2002. A total of 467 and 456 women were included in the longitudinal cervical cytopathologic and HPV DNA analyses, respectively. HIV-positive women had increased prevalence (46.6% vs 28.7%; P < .0001), increased acquisition (HR, 2.3; P = .03), and decreased clearance (HR, 0.4; P < .001) of oncogenic HPV as compared to HIV-negative women. Oncogenic HPV infection predicted progression of cervical dysplasia from normal to abnormal SIL (HR, 2.8; P = .002). Among HIV-positive participants, HAART increased the likelihood of regression (from present to absent) of cervical SIL (HR, 3.3; P = .02) and increased the clearance of oncogenic HPV types other than HPV-16 or HPV-18 (HR, 2.2; P = .01). This analysis demonstrated beneficial effects of HAART on cervical SIL in HIV-positive women.


Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.
Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented.


BRACETS: Bimodal repository of auscultation coupled with electrical impedance thoracic signals.
Respiratory diseases are among the most significant causes of morbidity and mortality worldwide, causing substantial strain on society and health systems. Over the last few decades, there has been increasing interest in the automatic analysis of respiratory sounds and electrical impedance tomography (EIT). Nevertheless, no publicly available databases with both respiratory sound and EIT data are available. In this work, we have assembled the first open-access bimodal database focusing on the differential diagnosis of respiratory diseases (BRACETS: Bimodal Repository of Auscultation Coupled with Electrical Impedance Thoracic Signals). It includes simultaneous recordings of single and multi-channel respiratory sounds and EIT. Furthermore, we have proposed several machine learning-based baseline systems for automatically classifying respiratory diseases in six distinct evaluation tasks using respiratory sound and EIT (A1, A2, A3, B1, B2, B3). These tasks included classifying respiratory diseases at sample and subject levels. The performance of the classification models was evaluated using a 5-fold cross-validation scheme (with subject isolation between folds). The resulting database consists of 1097 respiratory sounds and 795 EIT recordings acquired from 78 adult subjects in two countries (Portugal and Greece). In the task of automatically classifying respiratory diseases, the baseline classification models have achieved the following average balanced accuracy: Task A1 - 77.9±13.1%; Task A2 - 51.6±9.7%; Task A3 - 38.6±13.1%; Task B1 - 90.0±22.4%; Task B2 - 61.4±11.8%; Task B3 - 50.8±10.6%. The creation of this database and its public release will aid the research community in developing automated methodologies to assess and monitor respiratory function, and it might serve as a benchmark in the field of digital medicine for managing respiratory diseases. Moreover, it could pave the way for creating multi-modal robust approaches for that same purpose.


The frequency of heterologous synapsis increases with aging in Robertsonian heterozygous male mice.
The house mouse is characterised by highly variable chromosome number due to the presence of Robertsonian (Rb) chromosomes. During meiosis in Rb heterozygotes, intricated chromosomal figures are produced, and many unsynapsed regions are present during the first prophase, triggering a meiotic silencing of unsynapsed chromatin (MSUC) in a similar mode to the sex chromosome inactivation. The presence of unsynapsed chromosome regions is associated with impaired spermatogenesis. Interestingly, in male mice carrying multiple Rb trivalents, the frequency of germ cell death, defective tubules, and altered sperm morphology decreases during aging. Here, we studied whether synapsis of trivalent chromosomes and MSUC are involved in this improvement. By immunocytochemistry, we analysed the frequency of unsynapsed chromosomes and of those positive to γH2AX (a marker of MSUC) labelling in spermatocytes of 3-, 5- and 7-month-old Rb heterozygotes. With aging, we observed a decrease of the frequency of unsynapsed chromosomes, of spermatocytes bearing them and of trivalents carrying γH2AX-negative unsynapsed regions. Our quantitative results show that both synapsis and MSUC processes are better accomplished during male aging, partially accounting for the improvement of spermatogenesis.


An activated factor VII variant with enhanced tissue factor-independent activity speeds wound healing in a mouse hemophilia B model.
Essentials Disorders of hemostasis can lead to delayed and defective wound healing. In hemophilia B (HB) mice, 7 days of Factor (F)IX or VIIa are needed to normalize wound healing. One dose of a highly active FVIIa variant (DVQ) restored normal wound closure time in HB mice. Coagulation factors with enhanced activity may acquire biological effects not due to hemostasis. Introduction We have previously reported that hemophilia B (HB) mice have delayed healing of cutaneous wounds and alterations in wound histology. Administration of a single dose of either factor IX or recombinant activated FVII (rFVIIa) (NovoSeven) prior to wounding did not improve wound closure time or histology. The FVIIa analog DVQ (V158D, E296V and M298Q mutations) was designed to have higher tissue factor-independent activity than rVIIa. We hypothesized that a single dose of DVQ would be more effective in restoring wound healing in HB mice. Methods Cutaneous punch wounds were made on the backs of HB and wild-type mice, and the time to wound closure was monitored. HB mice were treated with a dose of rFVIIa (10 mg kg(-1) ) or DVQ (1 mg kg(-1) ) that corrected the tail bleeding time. Skin samples were taken at various time points after wounding, fixed, and stained, and the histology was examined. Results As previously reported, wound closure times in HB mice given one dose of rFVIIa were not improved over those in untreated HB mice. Surprisingly, healing times in HB mice treated with an equally hemostatic dose of DVQ were normalized to that in wild-type mice. However, DVQ did not correct all histologic abnormalities in HB mice. Conclusions As the doses of DVQ and rFVIIa were chosen to support comparable levels of hemostasis, our data suggest that the improved healing seen with DVQ is not solely attributable to its hemostatic activity. It is possible that the improved wound healing arises through the effect of DVQ on cell signaling mechanisms.


Effect of epinephrine on end-tidal carbon dioxide monitoring during CPR.
End-tidal carbon dioxide (ETCO2) has been shown to correlate with coronary perfusion pressure (CPP) during CPR and has been proposed as a useful noninvasive monitor of CPR efficacy. The effects of therapeutic epinephrine dosing on ETCO2 and CPP in six dogs were examined. Ventricular fibrillation was induced and left untreated for five minutes before CPR was initiated. After five minutes of CPR, epinephrine 0.045 mg/kg IV was administered. CPP and ETCO2 were compared immediately before and two minutes after epinephrine administration. There was a significant increase in CPP from 12.2 +/- 9.6 to 26.8 +/- 7.1 mm Hg (P = .006) after epinephrine. This was accompanied by a significant decrease in ETCO2 from 8.2 +/- 2.9 to 3.8 +/- 2.0 mm Hg (P = .01). These data indicate that after epinephrine administration, caution must be exercised in using ETCO2 as an indicator of CPP.


Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat.
Ghrelin is a gut peptide that is secreted from the stomach and stimulates food intake. There are ghrelin receptors throughout the gut and intracerebroventricular ghrelin has been shown to increase gastric acid secretion. The aim of the present study was to examine the effects of peripherally administered ghrelin on gastric emptying of a non-nutrient and nutrient liquid, as well as, basal and pentagastrin-stimulated gastric acid secretion in awake rats. In addition, gastric contractility was studied in vitro. Rats equipped with a gastric fistula were subjected to an intravenous infusion of ghrelin (10-500 pmol kg(-1) min(-1)) during saline or pentagastrin (90 pmol kg(-1) min(-1)) infusion. After administration of polyethylene glycol (PEG) 4000 with 51Cr as radioactive marker, or a liquid nutrient with (51)Cr, gastric retention was measured after a 20-min infusion of ghrelin (500 pmol kg(-1) min(-1)). In vitro isometric contractions of segments of rat gastric fundus were studied (10(-9) to 10(-6) M). Ghrelin had no effect on basal acid secretion, but at 500 pmol kg(-1) min(-1) ghrelin significantly decreased pentagastrin-stimulated acid secretion. Ghrelin had no effect on gastric emptying of the nutrient liquid, but significantly increased gastric emptying of the non-nutrient liquid. Ghrelin contracted fundus muscle strips dose-dependently (pD2 of 6.93+/-0.7). Ghrelin IV decreased plasma orexin A concentrations and increased plasma somatostatin concentrations. Plasma gastrin concentrations were unchanged during ghrelin infusion. Thus, ghrelin seems to not only effect food intake but also gastric motor and secretory function indicating a multifunctional role for ghrelin in energy homeostasis.


Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer.
Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances.


Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients.
Interindividual variability in dosage requirements of the calcineurin inhibitor immunosuppressive agents cyclosporine and tacrolimus after liver transplantation may result from differences in the CYP3A activity of the liver graft. Early postoperative erythromycin breath test (ERMBT) is an in vivo measure of graft CYP3A activity. This study evaluates the usefulness of an early postoperative ERMBT in predicting early morbidity in liver transplant recipients. In 26 liver transplant recipients, ERMBT was performed within 2 hr after transplantation. Main end points were the occurrence of cyclosporine and tacrolimus nephrotoxicity, episodes of early graft rejection, early graft function, and graft survival. Cyclosporine and tacrolimus nephrotoxicity were associated with low postoperative ERMBT values (mean 0.63%+/-0.25% 14C/hr vs. 1.35%+/-0.84% 14C/hr, P=0.02). No significant association between early graft rejection and ERMBT values was demonstrated. There was a significant inverse correlation between postoperative ERMBT values and the time to normalization of international normalized ratio as a measure of early graft function (r=-0.78, P<0.001). Graft loss was associated with low postoperative ERMBT values (0.21%+/-0.15% 14C/hr vs. 1.09%+/-0.72% 14C/hr, P=0.002). An early postoperative ERMBT may be useful in predicting the development of cyclosporine and tacrolimus nephrotoxicity, severe graft dysfunction, or even graft loss in liver transplant recipients when calcineurin inhibitors are administered according to protocols. Whether ERMBT results may be used to individualize dosage of calcineurin inhibitors needs to be explored.


Valve proteoglycan content and glycosaminoglycan fine structure are unique to microstructure, mechanical load and age: Relevance to an age-specific tissue-engineered heart valve.
This study characterized valve proteoglycan and glycosaminoglycan composition during development and aging. This knowledge is important for the development of age-specific tissue-engineered heart valves as well as treatments for age-specific valvulopathies. Aortic valves and mitral valves from first-third trimester, 6-week, 6-month and 6-year-old pigs were examined using immunohistochemistry for versican, biglycan, decorin and hyaluronan, as well as elastin and fibrillin. The fine structure of glycosaminoglycans was examined by fluorophore-assisted carbohydrate electrophoresis. Decorin expression was strongest in the 6-year-old valves, particularly in the aortic valve spongiosa. The quantity of iduronate was also highest in the 6-year-old valves. The central tensile-loading region of the anterior mitral leaflet demonstrated reduced glycosaminoglycan content, chain length and hydration and a larger fraction of 4-sulfated iduronate and lower fraction of 6-sulfation. With age, the anterior leaflet center showed a further increase in 4-sulfated iduronate and decrease in 6-sulfation. In contrast, the anterior leaflet free edge showed decreased iduronate and 4-sulfated glucuronate content with age. The young aortic valve was similar to the mitral valve free edge with a higher concentration of glycosaminoglycans and 6-rather than 4-sulfation, but aged to resemble the mitral anterior leaflet center, with an increase in 4-sulfated iduronate content and a decrease in the 6-sulfation fraction. Elastin and fibrillin often co-localized with the proteoglycans studied, but elastin co-localized most specifically with versican. In conclusion, composition and fine structure changes in valve proteoglycans and glycosaminoglycans with age are complex and distinct within valve type, histological layers and regions of different mechanical loading.


Improved synthesis of chalconoid-like compounds under ultrasound irradiation.
Claisen-Schmidt condensation of various substituted acetophenones with cinnamaldehyde catalyzed by KF-Al2O3 results chalconoid-like compounds, (2E,4E)-1,5-diarylpenta-2,4-dien-1-ones, in 67-92% yields in 5-60 min under ultrasound irradiation.


Processing of acoustic temporal patterns in barn owls and echolocating bats: similar mechanisms for the generation of neural place representations of auditory space.
Evidence for 'coincidence detection' or temporal summation mechanisms of temporal-pattern processing is presented for interaural-phase comparison in the barn owl's brainstem and echo delay sensitivity in the auditory cortex of the echolocating bat Myotis lucifugus. In each system, temporal tuning is correlated with the synchronous arrival of excitatory inputs from different acoustic events. Input coincidence is achieved by differences in neural transmission delay that counterbalance acoustic time disparities. Neural transmission delays are spatially organized, thus producing a topographic representation of acoustic time disparity.


Prions and haemophilia: assessment of risk.
Based on information accumulated to date, it is still difficult to assess the risk of Creutzfeldt-Jakob disease (CJD) and blood transfusion with any degree of confidence. However, it is reasonable to conclude that CJD is produced by a transmittable agent which is probably contained in low titer in the blood of infected people and animals. From the present clinical and epidemiological studies, transmission by blood or blood products appears to be a rare or non-existent cause of current and past cases of CJD in humans. Since blood products are necessary to prevent the immediate risk of death or significant morbidity in many clinical conditions, therapeutic decisions should be made after consideration of the known risk in these situations vs the theoretical long-term risk of the rare occurrence of CJD.


Arthroscopic Dissection of the Distal Semimembranosus Tendon: An Anatomical Perspective on Posteromedial Instability and Ramp Lesions.
Ramp lesions are increasingly recognized as a hallmark of posteromedial knee instability. Although the precise mechanisms through which these lesions occur is not completely understood, the distal semimembranosus complex has been implicated in their pathogenesis due to its attachment to the posterior horn of the medial meniscus (PHMM). Arthroscopic dissection of the distal semimembranosus tendon, and the application of traction to it, results in posterior translation of the PHMM and stretching of the meniscocapsular region. This demonstrates a mechanism through which ramp lesions can occur. Furthermore, the subsequent open dissection highlights the complex anatomical relationships of the distal semimembranosus tendon complex, particularly its tensioning effect on the posterior oblique ligament. The clinical relevance of this is that when a ramp lesion occurs, it is likely to be part of a spectrum of posteromedial injury and it should be considered a hallmark of posteromedial instability rather than an isolated meniscocapsular injury.


Map-fingerprint-dot changes in the corneal epithelial basement membrane following radial keratotomy.
Corneal epithelial opacities similar to those seen in corneal epithelial basement membrane dystrophy were seen in 33 of 71 eyes following radial keratotomy. These changes were clinically indistinguishable from those seen in map-fingerprint-dot dystrophy with map type changes seen most often. Basement membrane changes tended to be transient (persisting less than 3 months in 75.3% of eyes) and not usually visually significant. However, three eyes had changes which persisted for 12 months. Most eyes with basement membrane changes had involvement of less than one-half quadrant of the corneal (68%). Involvement of two or more quadrants occurred in 9.4% of eyes with these changes. One eye had visually significant changes which persisted for 3 months. There were no episodes of recurrent erosion.


[Observation on effects of Zhiling Capsule in treating 400 patients with various types of cancer in mid-ad-vanced stage].
To observe the efficacy of Zhiling Capsule (ZLC) in improving symptoms and quality of life (QOL) in patients with various types of cancer in mid-advanced stage. A multi-centre randomized and controlled trial was conducted. Four hundred patients with mid-advanced cancer were assigned to two groups: the treatment group (300 cases) treated with ZLC and the control group (100 cases) with Pingxiao Capsule (PXC), both were given orally for two weeks. Clinical symptoms, QOL, weight and adverse reactions were observed before and after treatment. Improving rate of symptom, increasing rates of QOL and weight in the treatment group were all higher than those in the control group (P<0.05); and no obvious adverse reaction was observed in the two groups. ZLC could alleviate the qi-yin deficiency syndrome and pain syndrome and improve QOL in patients with various types of cancer in mid-advanced stage.