[Effects of simulated acid rains on Cd, Cu and Zn release and their form transformation in polluted soils].
The release and form transformation of Cd, Cu, and Zn in polluted red soil and yellow red soil affected by simulated acid rains were studied through batch equilibrium experiments. The results showed that the release of test heavy metals increased significantly with decreasing pH value of simulated acid rain. Their release amount was negatively correlated to the pH value of acid rains. In polluted red soil and yellow red soil, Cd existed mainly in exchangeable form, and Cu in organically bound and Mn oxide-occluded forms. Zn existed mainly in residual and exchangeable forms in polluted red soil, and in residual and organically bound forms in polluted yellow red soil. To some extents, the release of Cd, Cu and Zn and the chemical forms of Cd and Zn in test soils were affected by soil organic matter content and CEC. The release amount of bio-available Cd and Cu in polluted red soil and yellow red soil was increased greatly with the increasing acidity of simulated acid rains, but the transformation of Zn from stable to bio-available form was not obvious.


Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes.
To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K(+), Ca(2+), Na(+), Mg(2+) and SO4(2-) decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L(-1)) and a long nano-TiO2 deposition time (48 h), the concentration of Na(+) decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L(-1), respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO4(2-) decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L(-1), respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials.


A self-determination approach to the understanding of the impact of physical activity on depressive symptoms.
The purpose was to test a new motivational sequence. It was hypothesized that more autonomous forms of motivation would predict the intensity of physical activity (PA), which in turn, would predict depressive symptoms. In order to evaluate self-determined motivation, the Self-Determination Index (SDI) was used. Because the reasons that can lead a person to engage in walking, moderate PA, or vigorous PA may be different, 3 independent self-determination indexes were measured (SDIWalking, SDIModerate, and SDIVigorous). It was also measured the metabolic equivalent of task values (METs) for walking, moderate, and vigorous PA, as well as the depressive symptoms. The sample consisted of 357 college students whose ages ranged from 18 to 29 years. Structural equation modeling was used to test the hypothesized model. The indices of fit showed that the revised model fits the data reasonably well: S-Bχ2(11) = 14.83, p = .190; χ2 /df = 1.35; *comparative fit index = .99; *root mean square error of approximation = .03, 90% CI [.000, .068]; standardised root mean square residual = .03. It was found that vigorous PA is the only intensity that predicts depressive symptoms. In other words, SDIV-predicted vigorous PA (measured as METS V), which subsequently predicted less depressive symptoms (SDIV → METS V → Depressive symptoms). Further research should investigate the effects of vigorous PA on depressive symptoms.


[A biological study of inbred Weiser-Maples guinea pigs--urinalysis, hematological and blood-chemical values and organ weights].
Urinalysis, hematological and blood chemical examinations and measurement of organ weights were carried out for the purpose of collecting background data on Weiser-Maples (WM) which was established as an inbred strain of guinea pigs. The results were compared with those for the commercial guinea pigs, Std: Hartley (H). In addition, the measurement methods for urinary specific gravity and whether centrifugation of urine influences the results of urinalysis or not were examined. The specific gravity values calculated from the volume and weight of urine were highly correlated with those from the refraction rate. The results of urinalysis of the supernatant of centrifuged urine were similar to those of urine not centrifuged, but the results suggested that the use of the supernatant provided a more accurate measurement of urine in guinea pigs. The positive rate for urinary protein was higher in the WM strain (38.9%) than in the H strain (0%). Although the WM strain showed higher or lower values than the H strain in some items of hematological and blood chemical examinations and organ weights, we could not regard them as characteristic of the WM strain.


Role of Metabolic Reprogramming of Long non-coding RNA in Clear Cell Renal Cell Carcinoma.
Renal cell carcinoma (RCC), one of the most frequent cancers, is a "classical" malignancy characterized by metabolic reprogramming. Clear cell renal cell carcinoma (ccRCC) is its most common histopathological subtype. Long-stranded non-coding ribonucleic acids (LncRNAs) are regulatory RNA molecules with limited protein-coding capacity and evolutionary conservation. Recent studies have revealed that lncRNAs can broadly regulate the metabolic reprogramming of ccRCC and its malignant transformation. However, there are few studies on lncRNAs regulating the metabolism of ccRCC, and the specific mechanisms are unknown. Therefore, this paper summarizes the regulatory mechanisms of lncRNAs in the metabolism of ccRCC, especially in the pathways of glycolysis, mitochondrial function, glutamine and lipid metabolism, cellular mechanisms, interactions with other molecules, specific scientific and clinic implications and applications to provide a basis for early clinical diagnosis, prediction and treatment. We also discuss the clinical application and challenges of targeting lncRNAs in ccRCC metabolism.


The effect of intestinal reperfusion on renal function and perfusion.
This study examines the effect of intestinal reperfusion injury (IIR) on renal blood flow and relates this temporally to changes in renal ATP levels and renal tubular function. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IIR). Renal blood flow was measured with radiolabeled microspheres and a Doppler flow probe. Renal dysfunction was quantitated by measuring inulin clearance and fractional excretion of sodium (FENa) in the isolated perfused organ. Renal tissue ATP levels were measured using a luciferase-luciferin assay. Sham-operated animals served as controls (SHAM). Renal blood flow was reduced by > 80% in the animals sustaining IIR when compared to baseline measurements (P < 0.05) or SHAM (P < 0.05). Temporally this reduction in renal blood flow was associated with a 25% reduction in tissue ATP levels (P < 0.05). The kidneys of animals sustaining IIR had a significantly greater FENa than did those of controls. These data support the notion that IIR is associated with a profound reduction in renal blood flow which is temporally related to reduced renal tissue ATP levels and renal tubular dysfunction.


Iatrogenic conjunctival entrapment of cilium and scleral ulceration after subtenon steroid injection.
To report the presence of an asymptomatic cilium in the subconjunctival area and an adjacent sterile scleral ulcer, together as a complication of subtenon injection of steroids, and the resolution of the ulcer despite the in situ cilium. Medical management of a 51-year-old man, who was a known case of ankylosing spondylitis, with a 3-mm scleral ulcer located in the inferior palpebral area with one adjacent fully embedded cilium at the probable site of subtenon injection given for suspected acute iridocyclitis. On altering the medication, the ulcer resolved completely. This occurred despite the in situ cilium, which did not act as a nidus for infection or inflammation. The presence of cilia did not adversely affect the outcome of treatment of the adjacent ulcer. Therefore, if there is no exposure of the entrapped cilium through the conjunctiva, as was in this case, conservative management of the ulcer and not trying to remove the cilium seems to be a good alternative as opposed to reports in literature, which warrant its removal in most cases.


Experimental assessment of three electrosurgical tissue-sealing devices in a porcine model.
Three electrosurgical tissue-sealing devices (EnSeal ETSDRC-01, LigaSure LS1500 and Thunderbeat TB-0535PC) were compared regarding sealing time (ST), maximum working temperature (WTmax) and the total (MTZtotal) as well as the collateral microscopic thermal injury zone (MTZcollat) using laparoscopic handpieces 5 mm in diameter on four types of tissue (liver, mesentery, cross striated muscle and spleen) in an in vivo porcine model. LigaSure had the lowest mean ST in spleen, mesentery, muscle and liver, followed by Thunderbeat and EnSeal with significant differences between all types of tissues and devices. The significantly lowest mean WTmax was obtained for EnSeal in mesentery, muscle and liver. LigaSure and EnSeal operated at the lowest temperature in spleen without a significant difference between them. Thunderbeat produced significantly higher temperature peaks in all cases. The lowest mean MTZtotal was caused by LigaSure and EnSeal in spleen, mesentery and muscle without significant differences between them, followed by the significantly higher values of Thunderbeat. Nevertheless, Thunderbeat produced the significantly lowest mean MTZtotal in the liver. EnSeal produced the lowest mean MTZcollat in the liver, followed by LigaSure and Thunderbeat showing significant differences. EnSeal and LigaSure produced the lowest mean MTZcollat in the spleen, mesentery and muscle without significant differences between them, followed by the significantly higher values of Thunderbeat. Based on the results of this study, Thunderbeat seems to be more invasive to tissue integrity (even without the activation of the ultrasonic scissor function) than EnSeal or LigaSure, that operate at lower temperatures and were found to cause negligible collateral thermal damage.


MIMO Radar Accurate 3-D Imaging and Motion Parameter Estimation for Target with Complex Motions.
In this paper, three-dimensional (3-D) multiple-input multiple-output (MIMO) radar accurate localization and imaging method with motion parameter estimation is proposed for targets with complex motions. To characterize the target accurately, a multi-dimensional signal model is established including the parameters on target 3-D position, translation velocity, and rotating angular velocity. For simplicity, the signal model is transformed into three-joint two-dimensional (2-D) parametric models by analyzing the motion characteristics. Then a gridless method based on atomic norm optimization is proposed to improve precision and simultaneously avoid basis mismatch in traditional compressive sensing (CS) techniques. Once the covariance matrix is obtained by solving the corresponding semi-definite program (SDP), estimating signal parameters via rotational invariance techniques (ESPRIT) can be used to estimate the positions, then motion parameters can be obtained by Least Square (LS) method, accordingly. Afterwards, pairing correction is carried out to remove registration errors by setting judgment conditions according to resolution performance analysis, to improve the accuracy. In this way, high-precision imaging can be realized without a spectral search process, and any slight changes of target posture can be detected accurately. Simulation results show that proposed method can realize accurate localization and imaging with motion parameter estimated efficiently.


Nature-inspired topographies on hydroxyapatite surfaces regulate stem cells behaviour.
Surface topography is one of the key factors in regulating interactions between materials and cells. While topographies presented to cells in vivo are non-symmetrical and in complex shapes, current fabrication techniques are limited to replicate these complex geometries. In this study, we developed a microcasting technique and successfully produced imprinted hydroxyapatite (HAp) surfaces with nature-inspired (honeycomb, pillars, and isolated islands) topographies. The in vitro biological performance of the developed non-symmetrical topographies was evaluated using adipose-derived stem cells (ADSCs). We demonstrated that ADSCs cultured on all HAp surfaces, except honeycomb patterns, presented well-defined stress fibers and expressed focal adhesion protein (paxillin) molecules. Isolated islands topographies significantly promoted osteogenic differentiation of ADSCs with increased alkaline phosphatase activity and upregulation of key osteogenic markers, compared to the other topographies and the control unmodified (flat) HAp surface. In contrast, honeycomb topographies hampered the ability of the ADSCs to proliferate and differentiate to the osteogenic lineage. This work presents a facile technique to imprint nature-derived topographies on the surface of bioceramics which opens up opportunities for the development of bioresponsive interfaces in tissue engineering and regenerative medicine.


Early adversities accelerate epigenetic aging into adulthood: a 10-year, within-subject analysis.
Longitudinal studies are needed to clarify whether early adversities are associated with advanced methylation age or if they actually accelerate methylation aging. This study test whether different dimensions of childhood adversity accelerate biological aging from childhood to adulthood, and, if so, via which mechanisms. 381 participants provided one blood sample in childhood (average age 15.0; SD = 2.3) and another in young adulthood (average age 23.1; SD = 2.8). Participants and their parents provided a median of 6 childhood assessments (total = 1,950 childhood observations), reporting exposures to different types of adversity dimensions (i.e. threat, material deprivation, loss, unpredictability). The blood samples were assayed to estimate DNA methylation age in both childhood and adulthood and also change in methylation age across this period. Cross-sectional associations between the childhood adversity dimensions and childhood measures of methylation age were non-significant. In contrast, multiple adversity dimensions were associated with accelerated within-person change in methylation age from adolescence to young adulthood. These associations attenuated in model testing all dimensions at the same time. Accelerated aging increased with increasing number of childhood adversities: Individuals with highest number of adversities experienced 2+ additional years of methylation aging compared to those with no exposure to childhood adversities. The association between total childhood adversity exposure and accelerated aging was partially explained by childhood depressive symptoms, but not anxiety or behavioral symptoms. Early adversities accelerate epigenetic aging long after they occur, in proportion to the total number of such experiences, and in a manner consistent with a shared effect that crosses multiple early dimensions of risk.


The intrastromal corneal ring segments: Intacs.
Although evolution of the intrastromal corneal ring technology will unquestionably continue, the ICRS in its current design is remarkably safe and offers several potential advantages, including preservation of the central cornea, reversibility and adjustability. The approval of this technology by the FDA has added a potentially unique procedure to the refractive surgeon's surgical inventory.


Catecholamine secretion from the rabbit adrenal gland is not modulated by a mechanism involving beta-adrenoceptors.
The possibility that catecholamine secretion from the rabbit adrenal gland is subject to modulation by a mechanism involving beta-adrenoceptors was investigated in an isolated perfused preparation of the gland. The adrenal catecholamine stores were radiolabelled with 3H-adrenaline and subsequently efflux of radioactivity was elicited by stimulation of an attached branch of the splanchnic nerve. The efflux of radioactivity evoked by nerve stimulation (1 min at 5 Hz) was not altered by isoprenaline (0.1 microM), metroprolol (0.1 microM) or (+/-)-propranolol (1 microM). Stimulation-induced efflux was reduced in the presence of a higher concentration of (+/-)-propranolol (10 microM); however, it was also reduced by (+)-propranolol (10 microM). These findings do not support the existence in the rabbit adrenal gland of a mechanism involving beta-adrenoceptors through which catecholamine secretion may be modulated.


A Process-Based Model for Bioturbation-Induced Mixing.
Bioturbation refers to the transport processes carried out by living organisms and their physical effects on soils and sediments. It is widely recognized as an important mixing mechanism, particularly at the sediment-water interface in many natural systems. In order to quantify its impact on mixing, we propose a process-based model based on simple assumptions about organism burrowing behavior. Specifically, we consider burrowing events to be stochastic but memoryless, leading to exponential inter-burrow waiting times and depths. We then explore the impact of two different transport mechanisms on the vertical concentration distributions predicted by the model for a conservative (inert) tracer. We compare the results of our model to experimental data from a recent laboratory study of bioturbation by the freshwater oligochaete worm Lumbriculus variegatus, and find good quantitative agreement.


MeCP2 deficiency downregulates specific nuclear proteins that could be partially recovered by valproic acid in vitro.
MeCP2, the major causative factor of Rett syndrome and related phenotypes including autism, is a two-face nuclear modulator acting via transcriptional and chromatin remodeling mechanisms. This study investigated the expression of several nuclear proteins and their dependence on MeCP2 dose and presence of the Rett causative R306C mutation. To this end, we developed in vitro models representing MeCP2 deficiency induced by siRNAs, and cells expressing the R306C mutation. Using an extended antibody microarray validated by specific assays, revealed that MeCP2 dose was correlated with specific nuclear proteins profiles including the BRM/SNF2 component of SWI/SNF complex, PRMT1 methyl transferase and HDAC2. Furthermore, while exposing the MeCP2 knock-down system to therapeutic concentrations of valproic acid (VPA), a known HDACs inhibitor, we observed a partial restoration of MeCP2 expression levels. Exposure to VPA also increased the levels of BRM, as well as of BDNF, an important co-factor in MeCP2-mediated pathway. Our findings provide additional evidence of diverse mechanisms of MeCP2 function as transcriptional repressor and activator of specific genes. As it has been recently demonstrated that post-natal restoration of MeCP2 deficiency may reverse neurological defects in a mouse model of Rett syndrome, we suggest to study the restorative effect of HDAC inhibitors in MeCP2-deficient mouse model.


Posttraumatic Lymphedema after Open Fractures of the Lower Extremity-A Retrospective Cohort Analysis.
Secondary lymphedema is a very common clinical issue with millions of patients suffering from pain, recurrent skin infections, and the constant need for a decongestive therapy. Well-established as a consequence of oncologic procedures, secondary lymphedema is also a well-known phenomenon after trauma. However, precise epidemiological data of lymphedema progress upon severe extremity injuries are still missing. In the present work, we analyzed a patient cohort of 94 individuals who suffered open fractures of the lower extremity and soft tissue injury, of 2nd and 3rd grade according to Tscherne classification, between 2013 and 2019. Typical symptoms of lymphedema have been obtained via interviews and patient medical records in a retrospective cohort analysis. Of all patients, 55% showed symptoms of secondary lymphedema and 14% reported recurrent skin infections, indicating severe lymphedema. Furthermore, comparing patients with and without lymphedema, additional parameters, such as obesity, total number of surgeries, infections, and compartment syndrome, related to lymphedema progress could be identified. According to these data, posttraumatic secondary lymphedema has a highly underestimated clinical prevalence. Further prospective studies are needed to validate this first observation and to identify high-risk groups in order to improve patient's health care.


Unexpected co-detection of promastigote and amastigote Leishmania forms in a human cutaneous lesion: implications for leishmaniasis physiopathology and treatment.
Cutaneous leishmaniasis pathogenicity depends on the survival and replication of the parasitic protozoa in the form of non-motile amastigotes inside macrophages. Here, we report the unprecedented observation of both Leishmania major amastigote and promastigote forms (the latter is normally detected only in the mid gut of the insect vector or in vitro culture) in a cutaneous lesion of a 6-year-old boy. This finding suggests that modifications of the skin lesion environment, such as maceration and changes in pH or temperature, could promote the in situ transformation of Leishmania amastigotes into promastigotes. This observation raises questions about the physiopathology of cutaneous leishmaniasis and the influence of micro-environmental changes on the efficiency of topical treatments.


[Report of a case: large tonsillolith in palatine tonsil].
A 69-year-old woman presented with a one-year history of dysphagia and a hard overgrowth of the right palatine tonsil visible in oral examination. Computerized Tomography scan showed a big calcified lesion inside the tonsil not seen in a pharyngoscopy. Tonsillectomy was performed and a giant tonsillolith was found inside the resected piece. The calculus was 3 x 2 x 2.3 cm and with an irregular-pyramidal shape. Normal tonsillar tissue with many colonies of Actionomyces inside the tonsillar crypts was the definitive pathological feature.


Ultrafast decay of electronically excited singlet cytosine via a pi,pi* to n(O),pi* state switch.
Singlet fluorescence lifetimes of adenosine, cytidine, guanosine, and thymidine, determined by femtosecond pump-probe spectroscopy (Pecourt, J.-M. L.; Peon, J.; Kohler, B. J. Am. Chem. Soc. 2000, 122, 9348. Pecourt, J.-M. L.; Peon, J.; Kohler, B. J. Am. Chem. Soc. 2001, 123, 10370), show that the excited states produced by 263 nm light in these nucleosides decay in the subpicosecond range (290-720 fs). Ultrafast radiationless decay to the ground state greatly reduces the probability of photochemical damage. In this work we present a theoretical study of isolated cytosine, the chromophore of cytidine. The experimental lifetime of 720 fs indicates that there must be an ultrafast decay channel for this species. We have documented the possible decay channels and approximate energetics, using a valence-bond derived analysis to rationalize the structural details of the paths. The mechanism favored by our calculations and the experimental data involves (1) a two-mode decay coordinate composed of initial bond length inversion followed by internal vibrational energy redistribution (IVR) to populate a carbon pyramidalization mode, (2) a state switch between the pi,pi* and nO,pi* (excitation from oxygen lone pair) excited states, and (3) decay to the ground state through a conical intersention. A second decay path through the nN,pi* state (excitation from the nitrogen lone pair), with a higher barrier, involves out-of-plane bending of the amino substituent.


A Clustering Method of Case-Involved News by Combining Topic Network and Multi-Head Attention Mechanism.
Finding the news of same case from the large numbers of case-involved news is an important basis for public opinion analysis. Existing text clustering methods usually based on topic models which only use topic and case infomation as the global features of documents, so distinguishing between different cases with similar types remains a challenge. The contents of documents contain rich local features. Taking into account the internal features of news, the information of cases and the contributions provided by different topics, we propose a clustering method of case-involved news, which combines topic network and multi-head attention mechanism. Using case information and topic information to construct a topic network, then extracting the global features by graph convolution network, thus realizing the combination of case information and topic information. At the same time, the local features are extracted by multi-head attention mechanism. Finally, the fusion of global features and local features is realized by variational auto-encoder, and the learned latent representations are used for clustering. The experiments show that the proposed method significantly outperforms the state-of-the-art unsupervised clustering methods.


Phorbol esters down-regulate transcription and translation of the CD4 gene.
This study investigated the effects of PMA on biosynthesis and transcription of the CD4 molecule and gene in order to define mechanisms resulting in reduced cell surface expression of the CD4 molecule after treatment with PMA. Cells treated with PMA showed reduced biosynthesis of the CD4 molecule but not of class I HLA molecules. Furthermore, PMA treatment resulted in reduced steady-state levels of CD4 mRNA and inhibition of the relative rate of transcription of the CD4 gene. Cells expressing transfected CD4 cDNA gene products modulated in response to PMA, however, re-expressed CD4 earlier than cells expressing the product of the wild-type CD4 gene. These data suggest that the cell surface expression of the CD4 molecule is probably down-regulated at the level of the protein, as well as the gene, and that inhibition of transcription may affect the kinetics of CD4 expression. These observations provide further insight into the mechanisms by which HIV affects expression of CD4.


A case of hilar bile duct cancer with intestinal Behçet's disease.
We encountered a hilar bile duct cancer patient with intestinal Behçet's disease who manifested various symptoms during a short period in the acute stage after liver resection. Under a diagnosis of hilar bile duct cancer, a 52-year-old Japanese male was referred and admitted to our hospital. Hepatectomy and resection of the extrahepatic bile duct were performed. During the postoperative course, a large number of painful aphthous ulcers developed in the oral mucosa, along with a genital ulcer. A deep excavation-type ulcer was confirmed by colonoscopy in the ileum on the orifice side. We administered colchicine and mesalazine. Thereafter, the patient was treated at the outpatient clinic. Recurrent localized hilar bile duct cancer developed, and the patient died about 8 months after surgery. We present the clinical details of this rare case of hilar bile duct cancer with intestinal Behçet's disease.


POSH misexpression induces caspase-dependent cell death in Drosophila.
POSH (Plenty of SH3 domains) is a scaffold for signaling proteins regulating cell survival. Specifically, POSH promotes assembly of a complex including Rac GTPase, mixed lineage kinase (MLK), MKK7, and Jun kinase (JNK). In Drosophila, genetic analysis implicated POSH in Tak1-dependent innate immune response, in part through regulation of JNK signaling. Homologs of the POSH signaling complex components, MLK and MKK7, are essential in Drosophila embryonic dorsal closure. Using a gain-of-function approach, we tested whether POSH plays a role in this process. Ectopic expression of POSH in the embryo causes dorsal closure defects due to apoptosis of the amnioserosa, but ectodermal JNK signaling is normal. Phenotypic consequences of POSH expression were found to be dependent on Drosophila Nc, the caspase-9 homolog, but only partially on Tak1 and not at all on Slpr and Hep. These results suggest that POSH may use different signaling complexes to promote cell death in distinct contexts.


Chromosomal Location of Genes Encoding Barley (1-->3, 1-->4)-beta-Glucan 4-Glucanohydrolases.
Preparations of DNA from wheat (Triticum aestivum, cv Chinese Spring), barley (Hordeum vulgare, cv Betzes) and six euplasmic wheat-barley addition lines were digested to completion with restriction endonucleases and the products probed by Southern blot analysis using a cDNA-encoding barley (1-->3, 1-->4)-beta-glucanase isoenzyme II. It is shown that one of the barley (1-->3, 1-->4)-beta-glucanase genes is located on chromosome 1.


Responses to depression in unipolar depressed patients: an investigation of Nolen-Hoeksema's response styles theory.
The response styles theory suggests that rumination in response to depressed mood exacerbates and prolongs depression, while distraction ameliorates and shortens it. Gender differences in response styles are said to contribute to the observed gender differences in the prevalence of unipolar depression. While empirical support for the theory has been found from a variety of non-clinical studies, its generalizability to clinically depressed patient populations remains unclear. A cohort of 52 unipolar depressed in-patients was assessed with the Response Styles Questionnaire during in-patient stay (T1) and 4 weeks after discharge (T2). The patients were followed up 4 months after discharge (T3). Clinical assessment included the SCAN-PSE-10. Moderate and statistically significant retest-stabilities for rumination and distraction were found, comparable for patients with stable and changing depression status from T1 to T2. A cross-sectional diagnosis of a major depressive episode was associated with rumination, while gender was not. Post-discharge baseline rumination (T2), adjusted for concurrent depression, predicted follow-up levels of depression (T3), and, in patients who were non-remitted at post-discharge baseline, it predicted presence of a major depressive episode at follow-up (T3). Results on distraction were more ambiguous. Our results suggest that rumination is likely to have a deteriorating impact on the course of clinical episodes of depression in unipolar depressed patients. Larger longitudinal patient studies are needed to validate these findings.


Parent perspectives of health related quality of life for adolescents with bladder exstrophy-epispadias as measured by the child health questionnaire-parent form 50.
Few groups have examined health related quality of life for adolescents with bladder exstrophy-epispadias. We studied parent reported health related quality of life for adolescents with bladder exstrophy-epispadias using the Child Health Questionnaire-Parent Form 50. We recruited 11 to 17-year-old participants with bladder exstrophy-epispadias and their parents. Parents served as proxy respondents for the adolescents by self-administering a validated generic health related quality of life instrument, the Child Health Questionnaire-Parent Form 50. We collected urinary incontinence, catheterization status, and medical and surgical history data. Mean questionnaire scores were compared to population based norms. Median age of the 55 patients was 14 years, 69% were male and 84% were white. Diagnoses included bladder exstrophy in 48 cases and epispadias in 7. Of the participants 29 (53%) reported urinary incontinence. The median number of lifetime surgeries was 9. Although physical and psychosocial summary measure scores were comparable to norms, the mean general health perception score was significantly worse than that of a population based sample (65.8 points, 95% CI 61.4-70.2 vs 73, 95% CI 71.3-74.7, p = 0.004). Mean family activity and parent emotional impact scores were also significantly worse than in a population based sample (83.6 points, 95% CI 79.3-88.0 vs 89.7, 95% CI 87.9-91.5, p = 0.02 and 67.7, 95% CI 61.9-73.6 vs 80.3, 95% CI 78.4-82.2, p <0.0001, respectively). Comparison of incontinent to continent children revealed a lower mean score on the parent emotional impact scale (62.6 points, 95% CI 55.5-69.8 vs 73.4, 95% CI 63.9-82.9), which approached significance (p = 0.06). Although overall adolescent quality of life was comparable to norms, parents reported significantly impaired adolescent general health and family activity as well as a negative parental emotional impact. Further research is needed to identify interventions that can decrease the adverse impact of bladder exstrophy-epispadias on family activity and parent emotional distress.


Emigration and wages in an open economy: some evidence from Pakistan.
"This paper examines the impact of labour emigration on the wages of both the skilled and unskilled workers....Using... Pakistani data, it is found that unskilled labour is used extremely intensively in the agriculture sector (exportable), skilled labour is used extremely intensively in the manufacturing sector (importable), and capital is used as the middle factor in both the traded goods sectors. Moreover, capital is used significantly less intensively in the construction (non-traded) sector relative to both the traded sectors.... The results suggest that the higher wages to both the skilled and unskilled workers must be compensated by a reduction in the rate of returns to capital if export-oriented and import-competing sectors in Pakistan are to remain internationally competitive."


Screening of pure synthetic coating substrates for induced pluripotent stem cells and iPSC-derived neuroepithelial progenitors with short peptide based integrin array.
Simple and pure synthetic coating substrates are needed to overcome the disadvantages of traditional coating products like animal derived Matrigel in stem cell research. Since integrins are of great importance in cell adhesion and cell-ECM communication, in this study, a commercially available integrin array established by synthetic integrin binding peptides is used to screen coating substrates for iPSCs and NEPs. The results showed that binding peptides of integrin α5β1, αVβ1, αMβ2 and αIIbβ3 supported cell adhesion of iPSCs, while α5β1, αVβ1 and αIIbβ3 binding peptides supported NEPs adhesion. Additionally, integrin α5β1 binding peptide was revealed to support rapid expansion of iPSCs and iPSC-derived NEPs, as well as the process of NEPs generation, with equal efficiency as Matrigel. In this work, we demonstrated that by supporting stem cell growth in an integrin dependent manner, the integrin array and coating system has the potential to develop more precise and efficient systems in neurological disease modeling.


Knowledge and use of contraception in rural and urban Iraq.
"This paper investigates variation in birth control knowledge and practices in Iraq as reported in the 1974 National Fertility Sample Survey. The descriptive and inferential statistical analysis indicated the existence of significant rural-urban differentials in knowledge and use of contraceptive methods by ever-married women. With the continuation of the war with Iran, the Iraqi government has adopted pro-natal policy to spur population growth. Whether such a policy achieves its goals is a matter deserving further investigation."


[Volume kinetics--a new method to control intravenous fluid infusion].
The body's handling of fluid given by intravenous infusion can be analysed and simulated by means of volume kinetics, in which pharmacokinetic principles are applied to dilution-time profiles obtained during fluid therapy. In volume kinetics, the emphasis is on the distribution of fluid to body fluid spaces which accordingly become expanded. These spaces do not always correspond to known anatomical or physiological fluid compartments. The time course of the effect of volume fluid distribution to these spaces may be investigated by means of computer-assisted simulation, or a nomogram based on values for volume kinetic variables obtained from infusion experiments.


Therapeutic options following second-line platinum-based chemotherapy in patients with recurrent ovarian cancer: Comparison of active surveillance and maintenance treatment.
Most women with advanced ovarian cancer respond to initial treatment, consisting of surgical resection and ≈6 cycles of platinum-based chemotherapy. However, disease recurrence occurs in most patients, and subsequent therapies become necessary. Historically, close monitoring following treatment (active surveillance) was the only available option, as continued maintenance chemotherapy treatment led to increased toxicity without providing any meaningful clinical benefit. Recently, targeted therapy with the angiogenesis inhibitor bevacizumab and the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib, niraparib, and rucaparib have demonstrated significant clinical benefits as maintenance treatment for recurrent disease. Despite consensus guidelines recommending their use, maintenance treatments are currently underutilized. Here, we review evidence from pivotal clinical trials of approved second-line maintenance treatments demonstrating efficacy in terms of progression-free survival and postprogression efficacy outcomes for patients with recurrent ovarian cancer. Adverse events frequently associated with bevacizumab include hypertension, proteinuria, and non-central nervous system bleeding, whereas PARP inhibitors are associated with nausea, vomiting, fatigue, and anemia. Patient-centered outcomes analyses show that PARP inhibitors provide significant benefits to patient health status, even when accounting for the toxicities associated with treatment. Many factors influence the selection of second-line maintenance treatment for patients with recurrent ovarian cancer, including the maintenance treatment received in the first-line setting. Overall, targeted maintenance treatment represents a new standard of care for patients with ovarian cancer, and we recommend that maintenance treatment should be offered to all eligible patients with recurrent ovarian cancer.


Estimating the reproductive number in the presence of spatial heterogeneity of transmission patterns.
Estimates of parameters for disease transmission in large-scale infectious disease outbreaks are often obtained to represent large groups of people, providing an average over a potentially very diverse area. For control measures to be more effective, a measure of the heterogeneity of the parameters is desirable. We propose a novel extension of a network-based approach to estimating the reproductive number. With this we can incorporate spatial and/or demographic information through a similarity matrix. We apply this to the 2009 Influenza pandemic in South Africa to understand the spatial variability across provinces. We explore the use of five similarity matrices to illustrate their impact on the subsequent epidemic parameter estimates. When treating South Africa as a single entity with homogeneous transmission characteristics across the country, the basic reproductive number, R0, (and imputation range) is 1.33 (1.31, 1.36). When fitting a new model for each province with no inter-province connections this estimate varies little (1.23-1.37). Using the proposed method with any of the four similarity measures yields an overall R0 that varies little across the four new models (1.33 to 1.34). However, when allowed to vary across provinces, the estimated R0 is greater than one consistently in only two of the nine provinces, the most densely populated provinces of Gauteng and Western Cape. Our results suggest that the spatial heterogeneity of influenza transmission was compelling in South Africa during the 2009 pandemic. This variability makes a qualitative difference in our understanding of the epidemic. While the cause of this fluctuation might be partially due to reporting differences, there is substantial evidence to warrant further investigation.


Optical spectroscopic investigation of the alkaline transition in umecyanin from horseradish root.
Umecyanin (UMC) from horseradish root belongs to the stellacyanin subclass of the phytocyanins, a family of plant cupredoxins. The protein possesses the typical type-1 His(2)Cys equatorial ligand set at its mononuclear copper site but has an axial Gln ligand in place of the usual weakly coordinated Met of the plantacyanins, uclacyanins, and most other cupredoxins. UMC exhibits, like other phytocyanins, altered visible, EPR, and paramagnetic (1)H NMR spectra at elevated pH values and also a modified reduction potential. This alkaline transition occurs with a pK(a) of approximately 10 [Dennison, C., Lawler, A. T. (2001) Biochemistry 40, 3158-3166]. In this study, we investigate the alkaline transition by complementary optical spectroscopic techniques. The contemporary use of absorption, fluorescence, dynamic light scattering, and resonance Raman spectroscopy allows us to demonstrate that the alkaline transition induces a reorganization of the protein and that the overall size of UMC increases, but protein aggregation does not occur. The transition does not have a dramatic influence on the active-site environment of UMC, but there are subtle alterations in the Cu site geometry. Direct evidence for the strengthening of a Cu-N(His) bond is presented, which is in agreement with the hypothesis that the deprotonation of the N(epsilon2)H moiety of one of the His ligands is the cause of the alkaline transition. A weakening of the Cu-S(Cys) bond is also observed which, along with a weakened axial interaction, must be due to the enhanced Cu-N(His) interaction.


Beyond the patch-clamp resolution: functional activity of nonelectrogenic vacuolar NHX proton/potassium antiporters and inhibition by phosphoinositides.
We combined the patch-clamp technique with ratiometric fluorescence imaging using the proton-responsive dye BCECF as a luminal probe. Upon application of a steep cytosol-directed potassium ion (K+ ) gradient in Arabidopsis mesophyll vacuoles, a strong and reversible acidification of the vacuolar lumen was detected, whereas no associated electrical currents were observed, in agreement with electroneutral cation/H+ exchange. Our data show that this acidification was generated by NHX antiport activity, because: it did not distinguish between K+ and sodium (Na+ ) ions; it was sensitive to the NHX inhibitor benzamil; and it was completely absent in vacuoles from nhx1 nhx2 double knockout plants. Our data further show that NHX activity could be reversed, was voltage-independent and specifically impaired by the low-abundance signaling lipid PI(3,5)P2 , which may regulate salt accumulation in plants by acting as a common messenger to coordinately shut down secondary active carriers responsible for cation and anion uptake inside the vacuole. Finally, we developed a theory based on thermodynamics, which supports the data obtained by our novel experimental approach. This work, therefore, represents a proof-of-principle that can be applied to the study of proton-dependent exchangers from plants and animals, which are barely detectable using conventional techniques.


Construction of a human hTERT RPE-1 cell line with inducible Cre for editing of endogenous genes.
The human retinal pigment epithelial RPE-1 cell line immortalized with hTERT retains a stable karyotype with a modal chromosome number of 46 and has been widely used to study physiological events in human cell culture systems. To facilitate inducible knock-out or knock-in experiments in this cell line, we have modified the AAVS1 locus to harbour a DNA fragment encoding ERT2-Cre-ERT2 fusion protein under regulation of a Tet-On expression system. In the generated cell line, active Cre recombinase was induced by simple addition of doxycycline and tamoxifen to the culture medium. As proof of concept, we successfully introduced an oncogenic point mutation to the endogenous KRAS gene locus of this cell line. The cell line will serve as a powerful tool to conduct functional analyses of human genes.


Current limitations in native mass spectrometry based structural biology.
Nowadays, mass spectrometry plays an important role in structural biology. At one end it can be used to investigate intact protein complexes, providing details about the complex composition, topology, stability, and dynamics, whereas at the other end the protein's identity and possible modifications can be visualized using proteomics approaches. Combining all this information allows the generation of detailed models for functional biological assemblies. Here, a perspective on the application of native mass spectrometry in structural biology is presented. The potential of this technique and some important current limitations are discussed. This includes issues regarding the quality/homogeneity of the sample, the dissociation efficiency of protein complexes during tandem mass spectrometric analysis, and some boundaries of ion mobility mass spectrometry.


Self-assembled boronic ester cavitand capsule as a photosensitizer and a guard nanocontainer against photochemical reactions of 2,6-diacetoxyanthracene.
The optical properties of 2,6-diacetoxyanthracene 4 encapsulated in the self-assembled boronic ester cavitand capsule 3 in C(6)H(6) are described. Upon excitation at 285 nm, the encapsulated 4 showed strong fluorescence emission as a result of the energy transfer from the excited 3 to the encapsulated 4, while 4 alone in C(6)H(6) exhibited very weak emission. Upon photoirradiation at 365 nm, the encapsulated 4 also showed strong fluorescence emission and remained almost intact, whereas 4 alone in C(6)H(6) gradually underwent photodimerization and photooxygenation to afford photodimers 5 and 5' and 9,10-anthraquinone 6 via 9,10-endoperoxide 7, respectively. Thus, the capsule 3 serves as a photosensitizer for the encapsulated 4 as well as a guard nanocontainer to protect against the photochemical reactions of 4.


The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro.
The effect of various inhibitors on insulin release from pieces of rabbit pancreas incubated in vitro was studied. Insulin release was stimulated by glucose (3mg./ml.), leucine (5mm), tolbutamide (200mug./ml.), ouabain (10mum), a raised extracellular K(+) concentration (60mm) and substitution of the Ca(2+) content of the incubation medium by Ba(2+) (2.5mm). (a) Mannoheptulose (6mg./ml.) inhibited glucose-stimulated insulin release only. (b) Anoxia abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide and K(+), but had little or no effect on release stimulated by ouabain or Ba(2+). (c) 2,4-Dinitrophenol (0.25mm) abolished or inhibited insulin release stimulated by glucose, ouabain or Ba(2+). (d) Diazoxide (250mug./ml.) abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba(2+) (0.25 or 1mm). Diazoxide had no effect on insulin release stimulated by Ba(2+) (2.5mm) and potentiated release stimulated by K(+). (e) Adrenaline (1mum) abolished insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba(2+). K(+)-stimulated release was inhibited by adrenaline. (f) Tetrodotoxin (1mum) had no effect on insulin release stimulated by glucose, leucine, tolbutamide, ouabain, K(+) or Ba(2+). (g) Nupercaine (1mm) abolished insulin release stimulated by glucose or Ba(2+).


Channel regulation by extracellular redox protein.
The most widely studied stimuli for ion channel activation are changes in membrane voltage and binding of a chemical ligand in a pocket of the channel protein. While modulation by redox potential has also been appreciated our study shows previously unrecognised channel activation via electron donation from the extracellular redox protein thioredoxin (TRX).(1) The ion channel type involved is a member of the Transient Receptor Potential (TRP) family. Activation by TRX led us to consider the relevance of TRP channels to the inflammatory condition of rheumatoid arthritis, where functions of ion channels are relatively unknown and TRX concentrations are high. TRP channel activation was found to be inhibitory for secretion of matrix metalloproteinases, suggesting activation by TRX may have a protective role against disease. Here we expand on our original article and discuss the potential wider implications of the findings in terms of concepts for channel activation and relevance to other ion channel types and systems.


Synergistic Intra- and Intermolecular Noncovalent Interactions for Ultralong Organic Phosphorescence.
Metal-free ultralong organic phosphorescence (UOP) materials have attracted significant attention owing to their anomalous photophysical properties and potential applications in various fields. Here, three pyrimidine-based organic luminogens, 9-(pyrimidin-2-yl)-9H-carbazole, 9-(4,6-dimethylpyrimidin-2-yl)-9H-carbazole, and 9-(5-bromopyrimidin-2-yl)-9H-carbazole are designed and synthesized, which show efficient yellow UOP with the longest lifetimes up to 1.37 s and the highest absolute phosphorescence quantum yields up to 23.6% under ambient conditions. Theoretical calculations, crystal structures, and photophysical properties of these compounds reveal that intramolecular hydrogen bonding, intermolecular π-π interactions, and intermolecular electronic coupling are responsible for forming dimers and generating highly efficient UOP. Their efficacy as solid materials for data encryption is demonstrated.


Quality improvement in local health departments: results of the NACCHO 2008 survey.
To assess the current status of quality improvement (QI) within local health departments (LHDs) and examine the characteristics associated with such QI efforts. A QI module was administered to a representative sample of 545 LHDs along with the core instrument in the 2008 NACCHO Profile survey of all LHDs nationally. Using the Profile survey data set, a quantitative approach was employed to determine the current status of QI within LHDs. Statistical analysis was performed to identify characteristics of LHDs associated with QI. The response rate to the QI module was 82 percent. Of the 448 LHDs that responded to the QI Module, 55 percent reported conducting formal QI efforts during the previous 2 years. Forty-four percent of these LHDs used a specific framework for QI, 56 percent used at least one of four commonly employed QI tools or techniques, and customer focus and satisfaction was the most frequently reported area (76%) of QI efforts. LHDs with large size of jurisdiction population and those with centralized governance were more likely to have engaged in quality or performance improvement, have managers who received formal QI training, and have provided QI training to staff. The 2008 NACCHO Profile QI module furnishes an excellent baseline for measuring progress of health department QI activities as accreditation and other related activities intensify. A clear definition of QI in public health that is understood by practitioners will greatly increase our ability to measure the adoption of QI by LHDs. Further research is necessary to identify and explore some of the predictors and possible barriers to increasing the application of QI by LHDs.


[Endoscopic dacryocystorhinostomy: a modified technique].
Dacryocystorhinostomy (DCR) is a surgical technique which has been adopted by otolaryngologists in the last years, because of the improvement in the endonasal approach by means of endoscopes. Although the results with the different techniques regarding permeability of the lacrimal duct are similar, we present some modifications in the surgical technique which contribute to a better postoperatory mucosal recovery, due to its more functional and less aggressive nature, improving the cost-benefit ratio. Two groups are compared, the first one (96 DCR) performing osteotomies with a chisel, without doing lacrimal duct and mucosa flaps, the second one (40 DCR) applying the modified technique using Smith-Kerrison forceps to perform osteotomies and creating lacrimal duct and mucosa flaps. Final results referred to permeability are similar (92.7% vs 87.5%). No major complications were found, and the most common minor complication was postoperative eyelid hematoma in cases of orbital fat exposure (5 cases vs 7 cases).


Role of the WT1 tumor suppressor in murine hematopoiesis.
The WT1 tumor-suppressor gene is expressed by many forms of acute myeloid leukemia. Inhibition of this expression can lead to the differentiation and reduced growth of leukemia cells and cell lines, suggesting that WT1 participates in regulating the proliferation of leukemic cells. However, the role of WT1 in normal hematopoiesis is not well understood. To investigate this question, we have used murine cells in which the WT1 gene has been inactivated by homologous recombination. We have found that cells lacking WT1 show deficits in hematopoietic stem cell function. Embryonic stem cells lacking WT1, although contributing efficiently to other organ systems, make only a minimal contribution to the hematopoietic system in chimeras, indicating that hematopoietic stem cells lacking WT1 compete poorly with healthy stem cells. In addition, fetal liver cells lacking WT1 have an approximately 75% reduction in erythroid blast-forming unit (BFU-E), erythroid colony-forming unit (CFU-E), and colony-forming unit-granulocyte macrophage-erythroid-megakaryocyte (CFU-GEMM). However, transplantation of fetal liver hematopoietic cells lacking WT1 will repopulate the hematopoietic system of an irradiated adult recipient in the absence of competition. We conclude that the absence of WT1 in hematopoietic cells leads to functional defects in growth potential that may be of consequence to leukemic cells that have alterations in the expression of WT1.


Kinesthetic memory in distance reproduction task: importance of initial hand position information.
The role of the initial hand position in planning and implementation of a goal-directed movement is a matter of debate. We designed a non-visually guided repetitive reaching movement task to investigate the role of proprioceptive information of the initial or end hand position in implementation of kinesthetic memory. The experimental design consisted four experiments. Each experiment consisted two phases: the training phase and the test phase. In the training phase the subjects were asked to learn and memorize the distance between start and end points by moving their hands ten times between them. In the test phase, the end point was removed, and starting from the same initial position, the subjects were asked to reproduce the memorized distance. In all experiments, varied conditions called "mask phase" preceded the test phase: a 5-s delay in experiment 1, shifting both initial and end points while keeping the distance constant in experiment 2, shifting only the end point, while keeping the initial point constant in experiment 3 and shifting only the initial point and keeping the end point constant in experiment 4. In comparison to experiment 1 (which was considered as the control group), no significant error in distance reproduction occurred in experiment 3, while experiments 2 and 4 showed significant error. These findings mean that although the distance information was available during the mask phase of experiment 2, subjects could not efficiently use this information to reproduce the distance. The other two experiments suggest that this error was caused by changing the initial hand position and not the end point. We conclude that in a kinesthetic-guided distance reproduction task, the initial hand position is more important for implementation of distance memory rather than the end point.


[The updating of the hospital pharmacist. Orient yourself in a sea of information and knowledge.]
The output of medical and scientific literature is on the rise and the health emergency caused by the covid-19 pandemic has led to a further growth in the number of articles published each year in International medical journals. Finding your way around this ocean of information is very difficult: the critical evaluation of scientific documentation requires time and specific skills, which are not easy to acquire. In addition to doctors and nurses, hospital and clinical pharmacists also struggle to keep up to date. Also for this reason, many institutions and various players in the publishing arena are developing tools that enable health personnel to access the best scientific knowledge, minimizing the risk inherent in the individually performed evaluation of evidence. In any case, it is essential to reconsider and update the methods of continuous education of the hospital pharmacist, also considering the changes that have taken place in his role, now integrated into the clinical teams together with the other professionals who guarantee health care.


Adansonia digitata L. leaf extract attenuates lead-induced cortical histoarchitectural changes and oxidative stress in the prefrontal cortex of adult male Wistar rats.
Objectives Adansonia digitata L. is popularly known for the management of various neurological diseases in ethno-medicine. Studies have shown that lead toxicity is a possible risk factor for early onset of neurodegenerative disease. Hence, this study was designed to evaluate the effect of A. digitata aqueous leaf extract (ADALE) against lead-induced oxidative stress and histo-architectural changes in the prefrontal cortex of adult Wistar rats. Methods Saline (10 mL/kg), ADALE (500 and 1000 mg/kg) and EDTA (55 mg/kg) were pretreated orally 30 min prior to lead acetate (LA) (120 mg/kg) administration to male Wistar rats (n=7) for 21 days. Thereafter, standard biochemical (superoxide dismutate, catalase, glutathionxe and malondialdehyde), histological (H&E) and histochemical assessment (crystyl fast violet stain for nissil substance) were carried out in the prefrontal cortex. Results ADALE significantly (p<0.05) reversed LA-induced oxidative stress, as evidenced by increased catalase, superoxide dismutase and oxidized glutathione levels, and decreased malondialdehyde concentration in the prefrontal cortex. Also, the increase chromatolysis and neuronal pyknosis of the pyramidal neurons of the prefrontal cortex were significantly attenuated by ADALE. Conclusions The result of this study showed that A. digitata aqueous leaf extract attenuated lead acetate-induced cortical neurodegeneration via inhibition of oxidative stress.


Association Between Perforating Scleral Vessel and Myopic Maculopathy: A Cross-Sectional Study of a Chinese Cohort.
Purpose: To investigate the association between perforating scleral vessel (PSV) and different types of myopic maculopathy (MM) in a highly myopic population. Methods: In total, 188 highly myopic eyes (117 participants) were enrolled. Each participant underwent detailed history taking and ocular examinations. Based on fundus photographs and optical coherence tomography, patients were subdivided into the non-MM group and MM group. Based on a new classification system (ATN), MM cases were classified as myopic atrophy maculopathy (MAM), myopic tractional maculopathy (MTM), and myopic neovascular maculopathy (MNM). The number of PSV and the macular choroidal thickness (mChT) were measured. Results: Compared with non-MM group, MM group was characterized by relatively larger age (48.40 vs. 32.34; p < 0.001), longer axial length (AL, 29.72 vs. 27.75, p < 0.001), thinner mChT (52.90 vs. 122.52; p < 0.001), and lower PSV counts (6.73 vs. 9.47, p ≤ 0.001). The non-MM group had higher PSV counts in total area (0-9 mm, 9.47 vs. 6.73, p < 0.001) and perifovea area (3-9 mm, 7.25 vs. 4.71, p < 0.001) compared to the MM group. Univariate and multivariate analyses showed that PSV count had no association with MAM (p = 0.2419) and MTM (p = 0.5678). Total PSV count [odds ratio (OR) 0.78, 95% CI 0.64-0.95, p = 0.0149] and perifovea PSV count (OR 0.80, 95% CI 0.65-0.98, p = 0.0299) were both protective factors for MNM. The stratified analysis revealed that in groups with AL <28 mm, or mChT <50 μm, or mChT ≥100 μm, or eyes with cilioretinal artery, PSV count had no significant association with MNM. Conclusion: Higher PSV counts in perifovea area (3-9 mm centered fovea) and total area (0-9 mm centered fovea) were protective factors for MNM, whereas PSV count had no association with MAM and MTM. These findings may provide novel insights into the mechanisms of pathologic myopia.


Suitability of gingival indices for use in therapeutic trials. Is bleeding a sine qua non?
A number of gingival indices have been described which include visual and invasive components, either separately or in combination. In selecting indices for use in gingivitis therapeutic trials, some investigators maintain that only invasive indices should be used, since indices that include a bleeding-on-provocation component are deemed to be the most objective. Other investigators, however, maintain that non-invasive indices are the more appropriate insofar as invasive procedures will not only disrupt the plaque at the gingival margin, but could also mildly traumatize the tissue and present an impediment to assessing examiner standardization and reproducibility. This paper discusses these aspects of gingivitis evaluation. The data indicate that all validated indices, whether invasive or non-invasive, have some degree of both objectivity and subjectivity. Therefore, the selection of an appropriate index will depend upon the ability of a given index to achieve the objectives of the clinical trial in which it is to be utilized.


[An old looped lead removal, complicated by its knotting over the active right ventricular lead - a case report].
We present a 59 year old patient with advanced heart failure who underwent lead extraction. The lead was implanted 11 years ago, and 2 years later looped spontaneously following its fracture. The transvenous extraction process through inferior vena cava was complicated by knotting of the inactive lead over the active ventricular lead. The patient was pacemaker-dependent. Finally, the old lead was successfuly explanted. The active intact lead was used to create resynchronisation system.


Endocutter no-knife and extraparenchymal control of the main hepatic veins for major hepatectomy.
Extraparenchymal control of the main hepatic veins (ECHV) and use of vascular staplers are now considered as effective methods to prevent intraoperative hemorrhage and duration of hepatic transection. The aim of the present preliminary study was to investigate whether extraparenchymal control of the hepatic veins combined with inflow occlusion and a new articulating linear stapler without a knife (Endocutter no-knife) were effective for major hepatectomy. Twenty patients with hepatic malignant disease underwent major hepatectomies in which 4 or more Couinaud's segments were removed. Extraparenchymal control of the hepatic veins and Endocutter no-knife were used in 7 (Recent group) of the 20 patients after June 2003. Hemihepatic devascularization before hepatic transection, and intermittent hepatic inflow occlusion were also performed in these 7 patients. In the other 13 (Previous group) patients before June 2003, major hepatectomy was performed under only intermittent hepatic inflow occlusion. Intraoperative blood loss volume, transfusion of packed red blood cells, and duration of hepatic transection were compared between the Recent group and Previous group. Estimated blood loss and number of intraoperative blood transfusion were significantly smaller in the Recent group than in the Previous group. Duration of hepatic transection was also significantly shorter in the Recent group than in the Previous group. The present preliminary study showed that extraparenchymal control of the hepatic veins and Endocutter no-knife are useful for major hepatectomy.


Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T.
Previous studies have shown that the diagnostic accuracy for prostate cancer improved with diffusion tensor imaging (DTI) or quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) only. However, the efficacy of combined DTI and quantitative DCE-MRI in detecting prostate cancer at 3.0 T is still indeterminate. To investigate the utility of diffusion tensor imaging (DTI), quantitative DCE-MRI, and the two techniques combined at 3.0 T in detecting prostate cancer of the peripheral zone (PZ). DTI and DCE-MRI of 33 patients was acquired prior to prostate biopsy. Regions of interest (ROIs) were drawn according to biopsy zones which were apex, mid-gland, and base on each side of the PZ. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume transfer constant (K(trans)), and rate constant (kep) values of cancerous sextants and non-cancerous sextants in PZ were calculated. Logistic regression models were generated for DTI, DCE-MRI, and DTI + DCE-MRI. Receiver-operating characteristic (ROC) curves were used to compare the ability of these models to differentiate cancerous sextants from non-cancerous sextants of PZ. There were significant differences in the ADC, FA, K(trans), and kep values between cancerous sextants and non-cancerous sextants in PZ (P < 0.0001, P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under curve (AUC) for DTI + DCE-MRI was significantly greater than that for either DTI (0.93 vs. 0.86, P = 0.0017) or DCE-MRI (0.93 vs. 0.84, P = 0.0034) alone. The combination of DTI and quantitative DCE-MRI has better diagnostic performance in detecting prostate cancer of the PZ than either technique alone.


Detection of DNA methylation adducts in Hodgkin's disease patients treated with procarbazine.
Abstract The aim of the present study was to assess the relationship between dose of the methylating agent procarbazine (PCZ), DNA methylation adduct formation andresponse to chemotherapy treatment in 23 Hodgkin's disease patients receiving MOPP/ABV combination therapy. The DNA adducts, 7-methyldeoxyguanosine (7-medG) and0(6)-methyldeoxyguanosine (0(6)-medG), were measured in leucocytes at the end of the first cycle of PCZ treatment (77-100 mg m(Z) per day). 7-medG was detected in only two patients prior to treatment and0(6)-medG was below the detection limit (0.08 pole per mole dG) in all subjects prior to treatment. The mean levels after PCZ treatment were 12.55 pmole 7-medG per mole dG and0.254 μmole 0(6)-medG per mole dG with a 2-3 fold variation between individuals. No correlation was observed between the levels of the two adducts suggesting inter-individual differences in formation andremoval of the two adducts. Failure of treatment was observed in five patients andthis was not correlated with higher or lower levels of 7-medG or 0(6)-medG. Other adducts formed as a consequence of treatment with PCZ or other MOPP/ABV components could have more relevance in this respect. The ability to measure DNA methylation adducts at the individual level following exposure to PCZ or other methylating chemotherapeutic drugs (e.g. dacarbazine) could be useful in prospective studies of secondary cancer in Hodgkin's disease patients.


Improvement in depression scores after 1 hour of light therapy treatment in patients with seasonal affective disorder.
The purpose of this study was to investigate possible rapid effects of light therapy on depressed mood in patients with seasonal affective disorder. Participants received 1 hour of bright light therapy and 1 hour of placebo dim red light in a randomized order crossover design. Depressed mood was measured at baseline and after each hour of light treatment using two self-report depression scales (Profile of Mood States-Depression-Dejection [POMS-D] subscale and the Beck Depression Inventory II [BDI-II]). When light effects were grouped for the two sessions, there was significantly greater reduction in self-report depression scores by -1.3 (p = 0.02) on the BDI-II and -1.2 (p = 0.02) on the POMS-D. A significant but modest improvement was detected after a single active light session. This is the first study, to our knowledge, to document an immediate improvement with light treatment using a placebo-controlled design with a clinical sample of depressed individuals.


Dependence of enzyme reaction mechanism on protonation state of titratable residues and QM level description: lactate dehydrogenase.
We have studied the dependence of the chemical reaction mechanism of L-lactate dehydrogenase (LDH) on the protonation state of titratable residues and on the level of the quantum mechanical (QM) description by means of hybrid quantum-mechanical/molecular-mechanical (QM/MM) methods; this methodology has allowed clarification of the timing of the hydride transfer and proton transfer components that hitherto had not been possible to state definitively.


Menin Inhibitors in Acute Myeloid Leukemia-What Does the Future Hold?
Menin inhibitors constitute a novel class of agents targeting the underlying biology of nucleophosmin (NPM1) mutant and KMT2A (formerly known as MLL1) rearranged (KMT2Ar) acute leukemias. KMT2Ar acute leukemias constitute 5% to 10% of acute leukemias, and NPM1 mutations are identified in 30% of newly diagnosed acute myeloid leukemias (AMLs). In preclinical AML models, small molecule inhibitors of the menin-KMT2A protein-protein interaction induce differentiation, downregulate critical gene expression programs, and confer a survival advantage in patient-derived xenograft models of NPM1 mutant and KMT2Ar AML. Multiple clinical trials evaluating oral menin inhibitors in acute leukemias are ongoing. Preliminary results in relapsed/refractory NPM1 mutant and KMT2Ar AML have shown on-target effects, tolerable toxicity, and promising clinical activity. This review details the current clinical experience of menin inhibitors in AML and discusses how these agents can be successfully integrated into future therapeutic approaches.


Expression of type IV pili by Moraxella catarrhalis is essential for natural competence and is affected by iron limitation.
Type IV pili, filamentous surface appendages primarily composed of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Although previous electron microscopic studies suggested that pili might be present on the surface of Moraxella catarrhalis isolates, detailed molecular and phenotypic analyses of these structures have not been reported to date. We identified and cloned the M. catarrhalis genes encoding PilA, the major pilin subunit, PilQ, the outer membrane secretin through which the pilus filament is extruded, and PilT, the NTPase that mediates pilin disassembly and retraction. To initiate investigation of the role of this surface organelle in pathogenesis, isogenic pilA, pilT, and pilQ mutants were constructed in M. catarrhalis strain 7169. Comparative analyses of the wild-type 7169 strain and three isogenic pil mutants demonstrated that M. catarrhalis expresses type IV pili that are essential for natural genetic transformation. Our studies suggest type IV pilus production by M. catarrhalis is constitutive and ubiquitous, although pilin expression was demonstrated to be iron responsive and Fur regulated. These data indicate that additional studies aimed at elucidating the prevalence and role of type IV pili in the pathogenesis and host response to M. catarrhalis infections are warranted.


Isozymes of the glycolytic enzymes in endosperm from developing castor oil seeds.
Ion filtration chromatography on diethylaminoethyl-Sephadex A-25 has been used to separate two isozymes each of triose phosphate isomerase, glyceraldehyde 3-phosphate dehydrogenase, glycerate 3-phosphate kinase, enolase, and phosphoglycerate mutase from homogenates of developing castor oil (Ricinus communis L. cv. Baker 296) seeds. Crude plastid fractions, prepared by differential centrifugation, were enriched in one of the isozymes, whereas the cytosolic fractions were enriched in the other. These data (and data published previously) indicate that plastids from developing castor oil seeds have a complete glycolytic pathway and are capable of conversion of hexose phosphate to pyruvate for fatty acid synthesis. The enzymes of this pathway in the plastids are isozymes of the corresponding enzymes located in the cytosol.


Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients: A cross-sectional PET-MRI study.
Although chemotherapy-induced leukoencephalopathy has been described in case and cohort studies, literature remains inconclusive about its prevalence and mechanisms. Therefore, we investigated the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes. In this exploratory study, 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA translocator protein (TSPO) radioligand [18F]DPA-714. Total and regional (juxtacortical, periventricular, deep white matter and infratentorial) lesion burden were compared between the groups with one-way ANOVA. With paired t-tests, [18F]DPA-714 volume of distribution [VT, including partial volume correction (PVC)] in lesioned and normal appearing white matter (NAWM) were compared within subjects, to investigate inflammation. Finally, two general linear models were used to examine the predictive values of neurofilament light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [18F]DPA-714 VT of lesions showing elevated inflammation. No significant differences were found in total or localized lesion burden. However, significantly higher (20-45%) TSPO uptake was observed in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90) compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated patients after PVC (p = 0.005, t = 4.30). NfL serum levels were not associated with total lesion volume or tracer uptake in juxtacortical lesions. This multimodal neuroimaging study suggests that neuroinflammatory processes could be involved in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly after chemotherapy for early-stage breast cancer.


The differentiation of beige adipocyte in pericardial and epicardial adipose tissues induces atrial fibrillation development.
Growing evidence has identified that excessive accumulation of pericardial adipose tissues (PAT) and epicardial adipose tissues (EAT) is associated with atrial fibrillation (AF) development. Moreover, beige adipocytes, present in PAT and EAT, have been proved beneficial in consumption of fatty acid and promotion of weight lose by nonshivering thermogenesis. The objective of this prospective, observational study was to reveal the potential association between beige adipocytes and AF development. Fat tissues from subcutaneous adipose tissue (SAT), PAT and EAT were obtained from 70 AF and 30 sinus rhythm patients. Hematoxylin and eosin (H&E) staining were performed to analyze morphological changes in fat tissues. Real-time PCR was performed to identify mRNA expression of unique uncoupling protein-1 (UCP-1). Western blotting and immunohistochemistry (IHC) were performed to determine protein expression of UCP-1. Our results indicated that pericardial and epicardial adipocytes in AF patients demonstrated white-like change tendency and had lower expression of UCP-1 when compared to sinus rhythm patients. Additionally, the decrease of UCP-1 mRNA expression in PAT and EAT, together with LA enlargement, were independent risk factors of AF. Further, UCP-1 mRNA expression in EAT, but not in PAT, have a significant correlation with LA diameter. The function of nonshivering thermogenesis in PAT and EAT was impaired in AF patients, and this dysfunction in EAT had a great correlation with LA dilation. Our data provide a new therapeutic target for LA remodeling and AF treatment.


Acute neurobehavioral effects of co-inhalation of toluene and n-hexane on schedule-controlled behavior in rats.
Whether coexposure to toluene and n-hexane had any combined effects on the shock avoidance performance in rats was studied. Eighteen Wistar male rats with an avoidance rate of over 80% were selected and divided to three groups based on performance and body weight: (1) toluene, (2) n-hexane, and (3) toluene + n-hexane. Each group was exposed alternately first to air and then to a particular organic solvent for 4 hr at various concentrations (50, 100, 200, 400, or 800 ppm, in ascending order). The effects of each organic solvent were evaluated by comparing the performance of rats during and after exposure with their own performance under the sham exposure to air by three-way ANOVA. The main results were that (1) 200, 400, or 800 ppm toluene exposures increased lever press rates, (2) 50 ppm n-hexane exposure decreased lever press and avoidance rates in a transitory manner and 800 ppm n-hexane exposure increased the lever press rate, (3) the 50 ppm mixture (25 ppm toluene + 25 ppm n-hexane) decreased lever press and avoidance rates persistently during and after the 4-hr exposure and the 800 ppm mixture (400 ppm toluene + 400 ppm n-hexane) decreased lever press and avoidance rates unpredictably when compared to the results of 400 or 800 ppm of toluene or n-hexane alone. In conclusion, n-hexane showed narcotic effects at 800 ppm and modified the acute neurobehavioral effects of toluene in rats at 400 ppm toward unpredictable results.


Congenital malaria with chloroquine resistance.
A preterm infant with possible congenital clinical malaria is described. The infant developed persistent pyrexia, hyperbilirubinaemia, anaemia, increasing gastric residuals and hepatosplenomegaly from the 7th day of life. Thick and thin smears of the infant's blood were heavily loaded with various asexual stages of Plasmodium falciparum. The parasite exhibited R1 resistance. There was no satisfactory response to chloroquine, but response to intravenous quinine therapy was achieved on day 15. The initial 6-month follow-up period was uneventful. The mother had apparently had chloroquine-resistant malaria which responded to sulfadoxine-pyrimethamine (Fansidar).


Vitamin K deficiency bleeding (VKDB) in early infancy.
Vitamin K deficiency bleeding (VKDB) is a rare and potentially life-threatening bleeding disorder of early infancy. Vitamin K stores are low at birth; thereafter breast-fed infants are at risk because of low concentrations in human milk. Classical VKDB occurs in the first week of life, is related to delayed or inadequate feeding and is readily prevented by small doses of vitamin K at birth. Late VKDB peaks at 3-8 weeks, typically presents with intracranial haemorrhage often due to undiagnosed cholestasis with resultant malabsorption of vitamin K. Diagnosis can be difficult but PIVKA-II measurements can provide confirmation even several days post-treatment. Without vitamin K prophylaxis, the incidence of late VKDB in Europe is 4-7 cases per 10(5) births; it is higher in SE Asia where in rural, low-income areas some 0.1% of affected infants may suffer intracranial bleeding. Late VKDB is largely preventable with parenteral vitamin K providing the best protection. The efficacy of oral prophylaxis is related to the dose and frequency of administration. Most multi-dose oral regimens provide protection for all except a small reservoir of infants with undetected hepatobiliary disease. Targeted surveillance of high-risk groups (e.g. biliary atresia) offers a novel approach to assess efficacy of prophylaxis.


Idiopathic Normal Pressure Hydrocephalus - What We Know.
Idiopathic normal pressure hydrocephalus is a neurological disorder with clinical diagnosis and imaging confirmation that benefits from a neurosurgical therapeutic solution in the vast majority of cases. Prevalence among the general population is not well defined at this time, but prevalence and incidence in developed countries is certainly steadily increasing due to increased life expectancy and evolution of diagnostic methods. Early diagnosis and appropriate treatment contribute to improving living conditions and can significantly reduce the cost of medical care for the elderly.


The risk of CNS involvement in aggressive lymphomas in the rituximab era.
The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.


Sleep problems: a group approach.
Reports on a successful approach to sleep disturbance jointly facilitated by clinical psychologists and health visitors. Where the clinical psychologist and health visitor were able to work closely together, it was shown that this increased knowledge of behaviour therapy techniques and enabled the health visitors to run future groups independently. Health visitors also reported feeling able to apply such techniques to other management problems in young children.


Initially Nondiagnosed Fabry's Disease when Electron Microscopy Is Lacking: The Continuing Story of Focal and Segmental Glomerulosclerosis.
Focal and segmental glomerulosclerosis is classified as either primary or secondary. We present a patient with a past history of biopsy-proven focal and segmental glomerulosclerosis. Despite initial response to dual blockade and steroids, proteinuria raised when steroids were decreased. After the patient was restarted on steroids, proteinuria did not improve. Another biopsy confirmed the previous diagnosis but suggested Fabry's disease, later confirmed by electron microscopy, α-galactosidase A serum and leukocyte deficiency as well as genetic studies. Proteinuria decreased when agalsidase β was prescribed in parallel with steroid tapering, increased with steroid discontinuation and improved with meprednisone administration. This report highlights the relevance of electron microscopy in kidney biopsy. In glomerulosclerosis, despite specific treatment, secondary hemodynamic and immunologic pathways may contribute to the development of proteinuria and accelerate the renal disease progression due to the primary disease. We discuss possible pathophysiologic pathways involved in proteinuria in Fabry's disease according to the biopsy and the therapeutic response.


Plasmon-assisted nanophase engineering of titanium dioxide for improved performances in single-particle based sensing and photocatalysis.
Titanium dioxide (TiO2) due to its large bandgap, has a very limited efficiency in utilizing sunlight for photocatalysis and photoanode applications. Sensitizing with metallic nanoparticles is one of the promising routes for resolving this issue but it requires thermal annealing and proper bandgap engineering to optimize the Schottky junctions. Here we use plasmonic nanoheating to locally anneal the TiO2 medium with a sub-nanometer (sub-nm) feature, which results in a nanophase transition from amorphous TiO2 to anatase and rutile with a gradient configuration. Such gradient nanocoatings of rutile/anatase establish a cascade hot electron transfer via a conduction band and defect states, which improves the surface enhanced Raman scattering (SERS) performance and photocatalytic efficiency over an order of magnitude. Unlike conventional global annealing, this nanoannealing strategy with plasmonic heating enables sub-nm control at the interface between the metal and semiconductors, and this strategy not only provides new opportunities for single particle SERS, but also shows significant implications for photocatalysis and hot-electron chemistry.


Synchronous primary lung cancers: a multidisciplinary approach in diagnosis.
BACKGROUND. For patients with two or more primary cancers a correct diagnosis is critically important because prognosis and treatment vary considerably between multiple primary cancers and metastatic disease. Two bilateral synchronous primary lung malignancies of different histological types were diagnosed and immunohistochemically confirmed in a 60-year-old woman. In biopsy specimens of the right lung pure squamous cell carcinoma was detected (stage IIIa). The tumor expressed AE1/AE3, cytokeratin 5 and 34βE12. In biopsy specimens of the left lung small cell carcinoma was detected (stage IIIa). The small cells expressed synaptophysin, chromogranin A and CD56. DNA was extracted from paraffin-embedded tissue of both tumors. Exons 5-9 of the TP53 gene were examined for genetic mutations by polymerase chain reaction and DNA sequencing analysis. Direct sequencing of DNA isolated from the small cell carcinoma revealed a TGC to TTC mutation at codon 404 of TP53 exon 5. In DNA isolated from the squamous cell carcinoma no TP53 mutation was found. The tumors' different response to chemotherapy also suggested that they belonged to different histological types. The patient lived 24 months after the diagnosis, which is more typical for stage III than for stage IV lung carcinoma. Discrimination of synchronous primary lung cancers from intrapulmonary metastases based only on clinical findings can be very difficult. Multidisciplinary diagnostic evaluation is therefore very helpful in cases like this, because a correct diagnosis will determine the best treatment for the patient and consequently a better prognosis.


[Study on the preparation and spectral characteristics of CeO2 nanocrystallines].
Ceria (CeO2) nanoparticles were prepared by precipitation method using cerium nitrate (Ce(NO3)3 x 6H2O) and ammonia (25 Wt%) as raw materials under the reaction for 3 h and ageing for 9 h at 80 degrees C without any surfactants and further calcination. The powder X-ray diffraction (XRD) pattern shows the as-prepared CeO2 crystals belong to the cubic phase and are well crystallized. Transmission electron microscopic (TEM) studies reveal that the appearance of as-prepared CeO2 is hexagonal, which is proposed to be the projection of polyhedral shape. The regular fringes spacing of 0.31 nm is in agreement with the d value of (111) lattice planes of cubic phase CeO2 from high-magnification TEM image. Reaction conditions such as the concentration of precipitant, reaction temperature and ageing duration exert important influence on the purity and morphology of the product. Ce(OH)3 was detected when the reaction was processed at lower pH (< 9) or with ageing duration less than 8 h at 80 degrees C. The size of polyhedral ceria nanoparticles increased with longer ageing time (> 15 h). If the reaction went on at a temperature lower than 40 degrees C, a large quantity of rodlike Ce(OH)3 was produced according to TEM observation. Raman spectra of CeO2 nanocrystallines exhibit a Raman shift at 465 cm(-1), corresponding to a F2g Raman band from the space group Fm3m of a cubic fluorite structure, while the Raman shift at about 600 cm(-1) may be attributed to the second Raman vibration mode of O2- vacancy due to Ce3+ impurity. Photoluminescence spectrum of CeO2 shows an emission at 465 nm at room temperature, which may be explained by charge transition from the 4f band to the valence band of CeO2.


Polysomatic apatites.
Certain complex structures are logically regarded as intergrowths of chemically or topologically discrete modules. When the proportions of these components vary systematically a polysomatic series is created, whose construction provides a basis for understanding defects, symmetry alternation and trends in physical properties. Here, we describe the polysomatic family A(5N)B(3N)O(9N + 6)X(Ndelta) (2 < or = N < or = infinity) that is built by condensing N apatite modules (A(5)B(3)O(18)X(delta)) in configurations to create B(n)O(3n + 1) (1 < or = n < or = infinity) tetrahedral chains. Hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2)] typifies a widely studied polysome where N = 2 and the tetrahedra are isolated in A(10)(BO(4))(6)X(2) compounds, but N = 3 A(15)(B(2)O(7))(3)(BO(4))(3)X(3) (ganomalite) and N = 4 A(20)(B(2)O(7))(6)X(4) (nasonite) are also known, with the X site untenanted or partially occupied as required for charge balance. The apatite modules, while topologically identical, are often compositionally or symmetrically distinct, and an infinite number of polysomes is feasible, generally with the restriction being that an A:B = 5:3 cation ratio be maintained. The end-members are the N = 2 polysome with all tetrahedra separated, and N = infinity, in which the hypothetical compound A(5)B(3)O(9)X contains infinite, corner-connected tetrahedral strings. The principal characteristics of a polysome are summarized using the nomenclature apatite-(A B X)-NS, where A/B/X are the most abundant species in these sites, N is the number of modules in the crystallographic repeat, and S is the symmetry symbol (usually H, T, M or A). This article examines the state-of-the-art in polysomatic apatite synthesis and crystallochemical design. It also presents X-ray and neutron powder diffraction investigations for several polysome chemical series and examines the prevalence of stacking disorder by electron microscopy. These insights into the structure-building principles of apatite polysomes will guide their development as functional materials.


Histamine H₃ receptors, the complex interaction with dopamine and its implications for addiction.
Histamine H₃ receptors are best known as presynaptic receptors inhibiting the release of histamine, as well as other neurotransmitters including acetylcholine and dopamine. However, in the dorsal and ventral striatum, the vast majority of H₃ receptors are actually located postsynaptically on medium sized spiny output neurons. These cells also contain large numbers of dopamine (D₁ and D₂) receptors and it has been shown that H₃ receptors form heterodimers with both D₁ and D₂ receptors. Thus, the anatomical localization of H₃ receptors suggests a complex interaction that could both enhance and inhibit dopaminergic neurotransmission. Dopamine, especially within the striatal complex, plays a crucial role in the development of addiction, both in the initial reinforcing effects of drugs of abuse, as well as in maintenance, relapse and reinstatement of drug taking behaviour. It is, therefore, conceivable that H₃ receptors can moderate the development and maintenance of drug addiction. In the present review, we appraise the current literature on the involvement of H₃ receptors in drug addiction and try to explain these data within a theoretical framework, as well as provide suggestions for further research.


Long-chain dietary fatty acids affect the capacity of Drosophila melanogaster to tolerate ethanol.
Four-day post-hatch larvae (mid-third instar) of Drosophila melanogaster were fed an intermediate diet with or without supplement of an individual fatty acid for 2 d and then transferred to a diet with a growth-limiting level of 0.94 mol/L ethanol (5.5%, v/v) or an ethanol-free diet. The ethanol stress decreased survival and larval development rate but increased the weight of surviving adult males. Dietary long-chain fatty acids altered the fatty acid composition of tissue lipids of larvae. When an unsaturated fatty acid was fed, except for 18:2(n-6), the tissue level of total unsaturated fatty acids was markedly increased. Both saturated and unsaturated 18-carbon fatty acids shortened larval development time. Linoleic acid [18:2(n-6)] and linolenic acid [18:3(n-3)] enhanced survival overall and, together with stearic acid (18:0), gave marked protection from ethanol stress in terms of survival. Correlation analysis across the different fatty acid diets indicated a strong positive association between tissue 18-carbon fatty acid levels and ethanol tolerance and between 18-carbon fatty acid levels and development rate. No major differences were observed in the effects of the fatty acids on the Canton-S and OD4 (Tahbilk) wild-type strains. Thus, the fatty acid content of D. melanogaster larvae is important for growth and survival in ethanol-rich habitats.


Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.
Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 cells is a key element of the adaptive immune system driving appropriate immune responses. Besides those canonical Th-cell lineages, hybrid phenotypes such as Th1/2 cells arise in vivo, and their generation could be reproduced in vitro. While master-regulator transcription factors like T-bet for Th1 and GATA-3 for Th2 cells drive and maintain differentiation into the canonical lineages, the transcriptional architecture of hybrid phenotypes is less well understood. In particular, it has remained unclear whether a hybrid phenotype implies a mixture of the effects of several canonical lineages for each gene, or rather a bimodal behavior across genes. Th-cell differentiation is a dynamic process in which the regulatory factors are modulated over time, but longitudinal studies of Th-cell differentiation are sparse. Here, we present a dynamic transcriptome analysis following Th-cell differentiation into Th1, Th2, and Th1/2 hybrid cells at 3-h time intervals in the first hours after stimulation. We identified an early bifurcation point in gene expression programs, and we found that only a minority of ~20% of Th cell-specific genes showed mixed effects from both Th1 and Th2 cells on Th1/2 hybrid cells. While most genes followed either Th1- or Th2-cell gene expression, another fraction of ~20% of genes followed a Th1 and Th2 cell-independent transcriptional program associated with the transcription factors STAT1 and STAT4. Overall, our results emphasize the key role of high-resolution longitudinal data for the characterization of cellular phenotypes.


Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms.
Dental caries (i.e., tooth decay), which is caused by biofilm formation on tooth surfaces, is the most prevalent oral disease worldwide. Unfortunately, many anti-biofilm drugs lack efficacy within the oral cavity due to poor solubility, retention, and penetration into biofilms. While drug delivery systems (DDS) have been developed to overcome these hurdles and improve traditional antimicrobial treatments, including farnesol, efficacy is still modest due to myriad resistance mechanisms employed by biofilms, suggesting that synergistic drug treatments may be more efficacious. Streptococcus mutans (S. mutans), a cariogenic pathogen and biofilm forming model organism, has several key virulence factors including acidogenicity and exopolysaccharide (EPS) matrix synthesis. Flavonoids, such as myricetin, can reduce both biofilm acidogenicity and EPS synthesis. Therefore, a nanoparticle carrier (NPC) DDS with flexibility to co-load farnesol in the hydrophobic core and myricetin within the cationic corona, was tested in vitro using established and developing S. mutans biofilms. Co-loaded NPC treatments effectively disrupted biofilm biomass (i.e., dry weight) and reduced biofilm viability by ~3 log CFU/mL versus single drug-only controls in developing biofilms, suggesting dual-drug delivery exhibits synergistic anti-biofilm effects. Mechanistic studies revealed that co-loaded NPCs synergistically inhibited planktonic bacterial growth compared to controls and reduced S. mutans acidogenicity due to decreased atpD expression, a gene associated with acid tolerance. Moreover, the myricetin-loaded NPC corona enhanced NPC binding to tooth-mimetic surfaces, which can increase drug efficacy through improved retention at the biofilm-apatite interface. Altogether, these findings suggest promise for co-delivery of myricetin and farnesol DDS as an alternative anti-biofilm treatment to prevent dental caries.