Developing Collaborative QSAR Models Without Sharing Structures.
It is widely understood that QSAR models greatly improve if more data are used. However, irrespective of model quality, once chemical structures diverge too far from the initial data set, the predictive performance of a model degrades quickly. To increase the applicability domain we need to increase the diversity of the training set. This can be achieved by combining data from diverse sources. Public data can be easily included; however, proprietary data may be more difficult to add due to intellectual property concerns. In this contribution, we will present a method for the collaborative development of linear regression models that addresses this problem. The method differs from other past approaches, because data are only shared in an aggregated form. This prohibits access to individual data points and therefore avoids the disclosure of confidential structural information. The final models are equivalent to models that were built with combined data sets.


Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl1.
Proneural transcription factors (TFs) such as Ascl1 function as master regulators of neurogenesis in vertebrates, being both necessary and sufficient for the activation of a full program of neuronal differentiation. Novel insights into the dynamics of Ascl1 expression at the cellular level, combined with the progressive characterization of its transcriptional program, have expanded the classical view of Ascl1 as a differentiation factor in neurogenesis. These advances resulted in a new model, whereby Ascl1 promotes sequentially the proliferation and differentiation of neural/stem progenitor cells. The multiple activities of Ascl1 are associated with the activation of distinct direct targets at progressive stages along the neuronal lineage. How this temporal pattern is established is poorly understood. Two modes of Ascl1 expression recently described (oscillatory vs. sustained) are likely to be of importance, together with additional mechanistic determinants such as the chromatin landscape and other transcriptional pathways. Here we revise these latest findings, and discuss their implications to the gene regulatory functions of Ascl1 during neurogenesis.


Expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in Kawasaki disease.
We analyzed the expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in 12 patients with Kawasaki disease (KD) using a fluorescence-activated cell sorter. The absolute counts of CD14+ macrophages/monocytes and CD23+ macrophages/monocytes were high, and were positively correlated during the acute stage of KD. These results indicate that the increased number of macrophages/monocytes during acute KD have the Fc epsilon R2/CD23 antigen present on the surface of the cells, suggesting that peripheral blood macrophages/monocytes have been activated.


In vivo gamma imaging of the secondary tumors of transplanted human fetal striatum neural stem cells-derived primary tumor cells.
This study describes gamma-imaging of the secondary tumors from the transplanted human fetal striatum neural stem cells-derived primary tumor cells in nude mice. The subcutaneous primary tumors were detected to express integrin alphavbeta3, and the corresponding cells were isolated and enriched in vitro, then transplanted to the nude mice. The technetium-99m-labeled Arg-Gly-Asp peptide, with high affinity to integrin alphavbeta3, was prepared for biodistribution and gamma-imaging. The secondary tumors were readily visualized at 1-h postinjection, and the tumor uptake of radiotracer was similar to that of positive control animals transplanted with U87MG human glioma cells. The tumor specificity of radiotracer was demonstrated by blocking experiment. We concluded that gamma-imaging is a promising approach in imaging the tumorigenesis of transplanted stem cells in vivo.


Immunogenicity and safety of early vs delayed BCG vaccination in moderately preterm (31-33 weeks) infants.
Minimum gestation at which infant can be given BCG (Bacillus Calmette-Guerin) vaccine safely at birth is not clearly defined. Our objectives were the following: to compare Mantoux test after 6 months of BCG immunization in moderately preterm babies (31-33 weeks) vaccinated at birth and 34 weeks post conception age and to compare in above groups:(a) Interferon - gamma (IFN-γ) levels in BCG vaccinated infants who did not react to Mantoux test (b) Local BCG reaction at 6, 10, 14 weeks and 6 months (c) Complications of BCG vaccination. Interventional, randomized comparative trial. Moderately preterm infants (31-33 weeks), 90 in each group. At birth, 180 moderately preterm infants were recruited and randomly allocated into 2 groups. Two ml venous blood was drawn for estimation of IFN-γ levels. Infants were given BCG vaccine within 72 hours of birth and followed up after 2, 4, 6, 10, 14 weeks and 6 months (group 1). Infants were recruited at birth and held up till 34 weeks post conception age (group 2) and then given BCG vaccine and followed up similarly as group 1. At each visit, local BCG reaction, any local or unusual complication and anthropometric measurements were noted. At six months, Mantoux test was done and 2 ml venous blood sample was collected for IFN-γ levels post vaccination. Presence or absence of BCG local reaction, PPD conversion rates and complications were analyzed using Chi square or Fisher's exact test. IFN-γ levels were analyzed by ANOVA. In all 117 infants could be followed till 6 months after BCG immunization in 2 groups, and Mantoux test was positive in 38.4% of them. The rate of Mantoux test positivity was similar irrespective of the age of giving BCG immunization (group 1- 39.1% vs group 2- 37.5%; p > 0.05). IFN-γ levels were significantly raised at 6 months in 60% (n = 21/41) and 65% (n = 15/27) Mantoux negative infants in group 1 and group 2 respectively. The sequence and order of local BCG reaction at 2, 4, 6, 10, 14 weeks and 6 months was in the form of papule, pustule, ulcer, scab and scar. Scar was formed in 94.2% and 89.5% infants in group 1 and group 2 respectively. One infant in group 1 showed abortive reaction (0.85%). Only 3.4% of infants developed lymphadenopathy and was similar in both the groups. Moderately preterm infants (31-33 weeks) exhibited 98.3% immunogenicity after BCG immunization at birth and can be safely vaccinated without any risk of severe complications.


Identifying the content and context of pain within paediatric rheumatology healthcare professional curricula in the UK: a summative content analysis.
The curriculum for professionals working in paediatric rheumatology should include pain but it is unclear to what extent this currently occurs. The aim of this study was to identify pain-related curriculum content and the context in which pain is presented in educational and training documentation for healthcare professionals in this clinical speciality. Core curricula documents from UK based professional organisations were identified in partnership with healthcare professionals. Documents were analysed using a summative content analysis approach. Key pain terms were quantified and weighted frequencies were used to explore narrative pain themes. Latent content was interpreted qualitatively to explore the context within which pain terms were positioned. Nine curriculum documents were identified and analysed from doctors, nurses, physiotherapists and occupational therapists specialising in paediatric rheumatology. Pain themes represented a mean percentage of 1.51% of text across all documents. Pain was rarely presented in the context of both inflammatory and non-inflammatory condition types despite being a common feature of each. Musculoskeletal pain was portrayed simply as a 'somatic' symptom, rather than as a complex phenomenon involving biological and psychosocial processes. Content around the assessment and management of pain was vague and inexplicit. Current educational and training documentation in paediatric rheumatology do not include core pain topics. Curricula for these healthcare professionals would benefit from updates in contemporary pain theories and examples of in-context, evidence-based pain practices. This should be a priority starting point for optimising patient pain care in paediatric musculoskeletal healthcare.


[African sleeping sickness in Switzerland (trypanosomiasis rhodesiensis)].
The fatal course of a case of African trypanosomiasis in Switzerland is reported. The feeling of sickness after an African trip is a diagnostic pointer. An infected fly bite and enlargement of lymphatic nodes or even symptoms of involvement of the central nervous system increase the suspicion. The diagnosis may be established simply by microscopic examination of a blood film. Because of the possibility of severe complications due to the sickness itself or due to toxicity of specific drugs, patients should be treated in hospital. Immediate contact with an Institute for tropical diseases seems to be advisable in every case.


lncRNA WT1-AS inhibits the aggressiveness of cervical cancer cell via regulating p53 expression via sponging miR-330-5p.
Emerging evidences have demonstrated that lncRNAs play vital roles in various pathological processes, including cancer. The lncRNA WT1 antisense RNA (WT1-AS) serves as a tumor suppressor in various cancers. Nevertheless, the expression and precise function of WT1-AS in cervical carcinoma still remain not yet investigated. The objective of our study was to explore the expression of WT1-AS and its biological roles in cervical cancer. Differences in the lncRNA expression profiles between cervical cancer and adjacent normal tissues were assessed by lncRNA expression microarray analysis. The expression of p53 in cervical cancer cell was assessed by qRT-PCR and immunofluorescence assay. Loss-of-function studies were used to explore the effect of lncRNA WT1-AS on the growth and metastasis of cervical cancer cell in vitro and in vivo. Our results demonstrated that WT1-AS was remarkably down-regulated in cervical carcinoma. Functional assays proved that up-regulation of WT1-AS significantly suppressed cervical cancer cell proliferation, migration and invasion. In addition, the luciferase reporter assay identified that miR-330-5p was the target of WT1-AS. Moreover, tumor suppressor p53 was identified as the direct target of miR-330-5p and alternation of miR-330-5p/p53 axis reversed the effects of WT1-AS in cervical cancer cell. Altogether, our findings suggested that WT1-AS was down-regulated in cervical carcinoma and WT1-AS suppressed cervical carcinoma cell- proliferation, migration and invasion through regulating the miR-330-5p/p53 axis.


The reliability of the McCarthy Screening Test from the criterion-referenced testing perspective.
The McCarthy Screening Test, used to identify children with learning difficulties, yields a pass-fail decision for each subtest. The reliability of these decisions is studied using several criterion-referenced testing methods (N = 1,323). The several results are evaluated. It is suggested that dependability indices be adopted for clinical instruments such as the MST.


Lymphangioleiomyomatosis: recurrence after lung transplantation.
Pulmonary lymphangioleiomyomatosis is a disease principally affecting women during child-bearing years that eventually leads to respiratory failure. Recently, it has been listed as an indication for lung transplantation. To date, no cases of recurrent lymphangioleiomyomatosis after lung transplantation have been reported, unlike the experience with sarcoidosis and giant cell interstitial pneumonia. At the University of Pittsburgh Medical Center, four patients have undergone single-lung transplantation for lymphangioleiomyomatosis. We now report that one of these cases developed recurrent lymphangioleiomyomatosis in the allograft lung.


[Experimental study of the dental follicle's function in tooth root development].
To study role of dental follicle in tooth root development. Sixteen mandibular first molar dental germs from eight five-day postnatal Balb/c mice were divided into two groups randomly. Dental follicle of germs in one group was undetached and that of another group was removed. Subsequently, each of the germs was separately transplanted to back-muscles of adult nude mice. At seventh and fourteenth day after transplanting, the germs were collected, fixed, demineralized, dehydrated, and embedded in wax in sequence. Serial sections of 5 microm thick were made following the routine methods, stained with haematoxylin-eosin dying solution, and observed under a light microscope. All implantations were located in the back-muscles with abundant capillary vasculature. Under microscope, although all tooth germs could further develop after grafting, tooth germs without dental follicle developed slowly with small size and low calcification compared to those with dental follicle. Although position of Hertwig's epithelial root sheath of all germs seemed no changing, roots of the group with dental follicle could further develop and the roots develop toward the apical direction; this tendency couldn't be seen in the germs of another group. Inflammatory cells could be seen in and out of the pulp cavity of the two groups at 7th day after grafting, while no obvious inflammatory cell was observed at 14th day after grafting. Dental follicle play an important role in tooth root development. It probably can lead tooth root to develop in normal direction.


A micro-fabricated force sensor using an all thin film piezoelectric active sensor.
The ability to measure pressure and force is essential in biomedical applications such as minimally invasive surgery (MIS) and palpation for detecting cancer cysts. Here, we report a force sensor for measuring a shear and normal force by combining an arrayed piezoelectric sensors layer with a precut glass top plate connected by four stress concentrating legs. We designed and fabricated a thin film piezoelectric force sensor and proposed an enhanced sensing tool to be used for analyzing gentle touches without the external voltage source used in FET sensors. Both the linear sensor response from 3 kPa to 30 kPa and the exact signal responses from the moving direction illustrate the strong feasibility of the described thin film miniaturized piezoelectric force sensor.


Skeletal maturity in Austrian children assessed by the GP and the TW-2 methods.
Skeletal maturity was assessed in 637 Austrian children from 7 to 16 years of age. The Greulich - Pyle and the Tanner- Whitehouse -2 ( RUS and TW 20-bone) methods were used. The GP ages showed some major deviations at and after puberty, especially in boys. The RUS and 20-bone ages conformed more closely to the standards although a general advancement in RUS ages was seen in girls after the age of 10 1/2. A similar pattern in RUS ages has been reported for other populations and may indicate a secular trend.


Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease.
Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.


Purification and characterization of ovine angiotensinogen.
The two major forms of ovine angiotensinogen (renin substrate) have been purified to homogeneity from plasma and a third form has been partially purified. The purification procedure involved ammonium sulphate fractionation, gel filtration, ion-exchange chromatography and chromatofocusing. The pure proteins have apparent relative molecular masses of 56 000 as determined by sodium dodecyl sulphate gel electrophoresis. The amino acid compositions of the two major forms appear to be the same; however, they do have different carbohydrate compositions. Antibodies raised against the a form showed complete cross-reactivity with the b and c forms. Both major forms have the same amino-terminal sequence, which includes that of ovine angiotensin I: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu. Thus ovine angiotensin is the Ile5 form and not the Val5 form as had previously been suggested.


Oral doxycycline versus intravenous ceftriaxone for treatment of multiple erythema migrans: an open-label alternate-treatment observational trial.
Several guidelines advocate the same treatment approaches for both early disseminated Lyme borreliosis, manifested as multiple erythema migrans (EM), and early localized Lyme borreliosis, manifested as solitary EM. Oral doxycycline (100 mg q12h) was compared on a non-inferiority premise with intravenous ceftriaxone (2 g q24h) for 14 days in 200 adult European patients with multiple EM in an open-label alternate-treatment observational trial performed in a single-centre university hospital. Treatment outcome was assessed at 14 days and at 2, 6 and 12 months post-enrolment. Non-specific symptoms in patients and 192 control subjects without a history of Lyme borreliosis were evaluated and compared. This trial was registered at http://clinicaltrials.gov (identifier NCT01163994). At the 12 month visit, 4/82 (4.9%) multiple EM patients prescribed doxycycline and 6/88 (6.8%) multiple EM patients prescribed ceftriaxone showed incomplete response manifested predominantly as post-Lyme symptoms (1.9% difference, upper limit of 95% CI 5.1%). The upper limit of 95% CI for the difference in proportion of patients with incomplete response between doxycycline and ceftriaxone groups did not exceed the predetermined non-inferiority margin of 10%. The frequency of non-specific symptoms in patients was similar to that in controls. The 14 day oral doxycycline was not inferior to the 14 day intravenous ceftriaxone in treatment of adult European patients with early disseminated Lyme borreliosis manifested as multiple EM. The frequency of non-specific symptoms in patients was similar to that in controls without a history of Lyme borreliosis.


Changes on depression and suicidal ideation under severe lockdown restrictions during the first wave of the COVID-19 pandemic in Spain: a longitudinal study in the general population.
To assess whether there is a change in the prevalence of depression and suicidal ideation after the strict lockdown measures due to the first wave of the COVID-19 pandemic in Spain, and to assess which are the factors associated with the incidence of a depressive episode or suicidal ideation during the lockdown. Data from a longitudinal adult population-based cohort from Madrid and Barcelona were analysed (n = 1103). Face-to-face home-based (pre-pandemic) and telephone interviews were performed. Depression and suicidal ideation were assessed through an adaptation of the Composite International Diagnostic Interview (CIDI 3.0). Population prevalence estimates and multivariable logistic regressions were computed. Prevalence rates of depression changed significantly from before to after the COVID-19 outbreak (from 3.06% to 12.00%; p = 0.01) and per sex and age groups. Individuals reporting COVID-19 concerns (odds ratio [OR] = 3.11; 95% confidence interval [CI] = 1.45-6.69) and those feeling loneliness (OR = 1.99; 95% CI = 1.52-2.61) during the lockdown were at increased risk of developing depression during the confinement. Resilience showed a protective effect against the risk of depression (OR = 0.57; 95% CI = 0.39-0.83), while individuals perceiving social support during the confinement were at lower risk of developing suicidal thoughts (OR = 0.21; 95% CI = 0.09-0.46). Greater disability during the lockdown was also associated with the risk of suicidal ideation (OR = 2.77; 95% CI = 1.53-5.03). Continuous reinforcement of mental health preventive and intervening measures is of global importance, particularly among vulnerable groups who are experiencing the most distress. Future research should strive to evaluate the long-term effects of the COVID-19 crisis on mental health.


Abnormal esophageal motility in children with congenital central hypoventilation syndrome.
Congenital central hypoventilation syndrome, an unexplained disorder of the central control of breathing that may reflect widespread dysfunction of brainstem structures, is regarded as a form of neuro cristopathy. Because swallowing-induced peristalsis is centrally controlled and depends on neural crest-derived esophageal innervation, we looked for esophageal dysmotility in patients with congenital central hypoventilation syndrome. Seven patients without dysphagia or any other upper gastrointestinal tract symptoms were studied prospectively (5 girls and 2 boys; median age, 14 years; range, 11-18 years). They were compared with 7 age- and sex-matched controls. Esophageal manometry was performed using a low-compliance infusion system and the station pull-through technique. At least 10 wet swallows were analyzed in each subject. Pressure wave propagation was abnormal in all 7 patients (median percentage of swallows propagated, 18%, and range, 0-66; controls, 90% and 80-100; P < 0.001). Lower esophageal sphincter relaxation was abnormal in 5 patients (patients, 73% and 53-100; controls, 95% and 90-100; P = 0.01). In 2 patients, lower esophageal sphincter pressure was above the 95th percentile of control values. These abnormalities are strong evidence of lower esophageal dysfunction in congenital central hypoventilation syndrome. We speculate that the underlying mechanism may be dysfunction of the central structures that control swallowing.


The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma - A targeted literature review.
Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.


Future climate and land uses effects on flow and nutrient loads of a Mediterranean catchment in South Australia.
Mediterranean catchments experience already high seasonal variability alternating between dry and wet periods, and are more vulnerable to future climate and land use changes. Quantification of catchment response under future changes is particularly crucial for better water resources management. This study assessed the combined effects of future climate and land use changes on water yield, total nitrogen (TN) and total phosphorus (TP) loads of the Mediterranean Onkaparinga catchment in South Australia by means of the eco-hydrological model SWAT. Six different global climate models (GCMs) under two representative concentration pathways (RCPs) and a hypothetical land use change were used for future simulations. The climate models suggested a high degree of uncertainty, varying seasonally, in both flow and nutrient loads; however, a decreasing trend was observed. Average monthly TN and TP load decreased up to -55% and -56% respectively and were found to be dependent on flow magnitude. The annual and seasonal water yield and nutrient loads may only slightly be affected by envisaged land uses, but significantly altered by intermediate and high emission scenarios, predominantly during the spring season. The combined scenarios indicated the possibility of declining flow in future but nutrient enrichment in summer months, originating mainly from the land use scenario, that may elevate the risk of algal blooms in downstream drinking water reservoir. Hence, careful planning of future water resources in a Mediterranean catchment requires the assessment of combined effects of multiple climate models and land use scenarios on both water quantity and quality.


Is a positive association between lead exposure and blood pressure supported by animal experiments?
The possible association between low-level lead exposure and blood pressure and the causal nature of any such relationship continue to be debated. A recent meta-analysis of the human model data showed that on average a doubling of blood lead was associated with a rise in blood pressure averaging 1 mm Hg systolic and 0.6 mm Hg diastolic. The older animal studies, however, failed to show a significant pressure increase with massive lead exposure. This review therefore attempts to determine whether the more recent animal studies are supportive of a positive association between lead exposure and blood pressure elevation. Of the 21 animal studies published since 1977, one was carried out in dogs, one in pigeons, and the remainder in various rat strains. In the articles in which all the lead doses had been higher than 1 ppm, the association between blood pressure and exposure was found to be positive in seven, inconsistent in three, absent in four, and negative in one. Of the six animal experiments that employed lead doses not exceeding 1 ppm, five reported a small pressor effect. One of these five positive low-dose studies, however, failed to show a dose-effect relationship when exposure was increased from 0.1 to 1 ppm. In conclusion, most, but not all animal studies published since 1977 found a positive association between blood pressure and lead exposure. However, publication bias may have inflated the number of positive studies appearing in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of path integral molecular dynamics methods for the infrared absorption spectrum of liquid water.
The ring polymer molecular dynamics (RPMD) and partially adiabatic centroid molecular dynamics (PA-CMD) methods are compared and contrasted in an application to the infrared absorption spectrum of a recently parametrized flexible, polarizable, Thole-type potential energy model for liquid water. Both methods predict very similar spectra in the low-frequency librational and intramolecular bending region at wavenumbers below 2500 cm(-1). However, the RPMD spectrum is contaminated in the high-frequency O-H stretching region by contributions from the internal vibrational modes of the ring polymer. This problem is avoided in the PA-CMD method, which adjusts the elements of the Parrinello-Rahman mass matrix so as to shift the frequencies of these vibrational modes beyond the spectral range of interest. PA-CMD does not require any more computational effort than RPMD and it is clearly the better of the two methods for simulating vibrational spectra.


Thalamic infarcts: Effects on cerebral blood flow, metabolism, and neuropsychological function.
In four patients with thalamic infarcts causing severe neuropsychological deficits, regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography using (99m)Tc-d,l,-hexamethylpropyleneamine oxime as tracer. In one of these patients, cerebral glucose metabolism was measured by positron emission tomography using (18)F-fluorodeoxyglucose as tracer. Three patients had left paramedian thalamic infarcts, in one case combined with an infarction of the right cerebellar hemisphere, and one had bilateral paramedian and left anterior thalamic infarcts. Neuropsychological assessment revealed profound impairment of memory, verbal fluency, and abstract reasoning, as well as perseveration and varying degrees of dyscalculia and constructional apraxia in all patients. There were distinct personality changes and deficient judgment and insight. All four patients had reduced cortical rCBF in the left frontoparietal regions. In three cases, flow was also reduced in the left temporal lobe; they all presented with a fluent aphasia, which only partly remitted over time. Prosody and mimics were impaired only in the patient with bilateral thalamic infarction. In one of the patients with unilateral thalamic infarct extending into the mesencephalon, glucose metabolism was reduced in the ipsilateral frontal, temporal, and occipital regions. Thalamic infarcts can alter the activity in widespread functional systems of the brain and thus lead to extensive neuropsychological deficits.


Expression and transient nuclear translocation of proprotein convertase 1 (PC1) during mouse preimplantation embryonic development.
Preimplantation embryos express a number of hormones, neuropeptides, and membrane receptors known to derive from proteolytic activation of their precursors by the seven-member family of subtilisin-like, calcium-dependent serine proteinases known as proprotein convertases (PCs). The goal of this study was to determine the pattern of PC expression in mouse preimplantation embryos. Transcripts for all PCs, except PC2, were detected by reverse transcription-polymerase chain reaction (RT-PCR) in unfertilized and fertilized eggs. Furin, PACE4, PC1, and PC7 transcripts remained present at subsequent stages of preimplantation embryonic development, whereas the levels of transcripts for PC4 and PC5 gradually disappeared after the 2-cell stage. Proprotein convertase 1 (PC1) expression was further examined at the protein level. Immunoblotting revealed the presence of the zymogen and mature forms of this enzyme in eggs and embryos. Immunofluorescence laser confocal microscopy showed PC1-specific staining throughout the cytoplasm of unfertilized eggs. After fertilization, surprisingly, the staining was concentrated in pronuclei. It relocated to the cytoplasm at postzygotic stages and was particularly strong at junctions between blastomeres. The nuclear translocation of PC1 in fertilized eggs is probably mediated by its prodomain. Indeed, when transduced in human colon carcinoma LoVo cells, a mutant proPC1 incapable of cleaving off its prodomain was shown to accumulate in the nucleus. Furthermore, when N-terminally fused to green fluorescent protein, this domain was able to direct the reporter protein to the nucleus of these cells. Collectively, these data establish that eggs and preimplantation embryos express various PCs necessary for proteolytic activation of precursors of hormones and growth factors. They also raise the possibility of a nuclear function for PC1 during zygote formation.


Which temporal resolution to consider when investigating the impact of climatic data on population dynamics? The case of the lesser horseshoe bat (Rhinolophus hipposideros).
Climatic variables are often considered when studying environmental impacts on population dynamics of terrestrial species. However, the temporal resolution considered varies depending on studies, even among studies of the same taxa. Most studies interested in climatic impacts on populations tend to average climatic data across timeframes covering life cycle periods of the organism in question or longer, even though most climatic databases provide at least a monthly resolution. We explored the impact of climatic variables on lesser horseshoe bat (Rhinolophus hipposideros) demography based on count data collected at 94 maternity colonies from 2000 to 2014 in Britanny, France. Meteorological data were considered using different time resolutions (month, life cycle period and year) to investigate their adequacy. Model averaging was used to detect significant predictors for each temporal resolution. Our results show that the finest temporal resolution, e.g. month, was more informative than coarser ones. Precipitation predictors were particularly decisive, with a negative impact on colony sizes when rainfall occurred in October, and a positive impact for June precipitations. Fecundity was influenced by April weather. This highlights the strong impact of climatic conditions during crucial but short time periods on the population dynamics of bats. We demonstrate the importance of choosing an appropriate time resolution and suggest that analogous studies should consider fine-scale temporal resolution (e.g. month) to better grasp the relationship between population dynamics and climatic conditions.


Neurofibromatosis in children.
The clinical diagnosis of neurofibromatosis in childhood will usually be based on the presence of numerous café-au-lait spots. Early diagnosis allows for continuing follow-up and appropriate counselling. Symptomatic therapy can be provided if necessary. The disorder has a tendency via its mesodermal route to affect almost every system in the body; however, few laymen have even heard of the disorder and, except for the "Elephant Man" notoriety, are totally unaware of it, whereas muscular dystrophy, cystic fibrosis, and Down syndrome although occurring less frequently are well known to the general public. The management of neurofibromatosis in children covers an extremely wide spectrum: at times the management appears to be simple, involving little more than clinical evaluation and simple investigations. However, in view of the protean manifestations of the condition, a complete history including family history is obligatory, and investigation must include radiographic studies of the abdomen, chest, spine, and skull, the latter to include special views of the orbits and optic foramina. My investigation of this disorder has been extremely frustrating because of the progressive character of the disease. Nothing seems to alter the natural course of the disease. I cannot say that my investigative efforts have revealed any breakthroughs in treatment. An aggressive surgical approach to the myriad of lesions associated with this disease, especially neuromata or segmental problems, is probably advisable. The early treatment of tibial pseudarthrosis by polyprophylene orthotic and pulsating electromagnetic fields shows encouraging results over the short course, although I am not so sure as to whether or not the patients would do as well with the custom fit orthotic with or without the electronics. Early stabilization of spinal deformity has proven to be more than moderately successful and is strongly recommended following appropriate intraspinal evaluation. The management of tumors of the brain and spinal cord, as well as those associated with limb hypertrophy and congenital tibial pseudarthrosis, is undergoing innovations at this time which may result in a better cure rate. Procedures include the use of CT to evaluate tumors [Coleman et al. have attempted to differentiate neurofibromas from neurofibrosarcoma by contrast enhancement methods], the use of CO2 lasers to remove previously inoperable CNS tumors, microvascular bone transplantation and pulsating electromagnetic field to treat pseudarthrotic bones.4+he National


Magnetoencephalographic analysis of cortical oscillatory activity in patients with brain tumors: Synthetic aperture magnetometry (SAM) functional imaging of delta band activity.
Abnormal focal slow wave activity on electroencephalography and magnetoencephalography (MEG) is often seen in patients with various brain pathologies and MEG is capable of localizing cortical oscillatory activity with enhanced accuracy. In addition, MEG with synthetic aperture magnetometry (SAM) can depict changes in cortical oscillatory activity tomographically. Using SAM, we recorded cortical rhythms in patients with a brain tumor and evaluated the tomographic appearance of focal slow wave activity in relation to clinical signs and symptoms. Spontaneous MEG recordings were obtained in 15 patients with brain tumors. Statistically-determined power distributions in the delta-, theta-, and alpha-frequency bands were displayed tomographically and overlaid on individual magnetic resonance images. The location, strength and volume of enhanced activity were analyzed. Delta and theta band activities were significantly more intense in the cortex adjacent to tumors and in the surrounding edematous cortical areas than in other portions of the cortex. In 13 of the 15 patients, spatial distribution of enhanced focal delta activity coincided with the area responsible for the presenting signs and symptoms. Volumetric analysis revealed that emergence of tumor-related focal delta band activity in the cortex adjacent to a tumor, or with peritumoral edema, was greater for intra-axial tumors involving subcortical fibers than for extra-axial tumors. Patients with an increased volume of enhanced delta activity exhibited poor recovery of function in the early postoperative period. It is concluded that SAM imaging of focal delta activity can reveal functional alterations in cortical activity in patients with brain tumors and is useful for assessing cortical states associated with the existing pathology.


Preparation of highly functionalised benzofurans from ortho-hydroxyphenones and dichloroethylene: applications and mechanistic investigations.
Highly functionalised benzofurans have been prepared from ortho-hydroxyphenones and 1,1-dichloroethylene. The key intermediate, a chloromethylene furan, smoothly rearranged into the corresponding benzofuran carbaldehyde under acidic conditions. Some mechanistic investigations have been performed and several biologically active benzofurans have been synthesised.


Discriminating between Achyranthis Bidentatae Radix and Cyathulae Radix in Chinese medicine preparations by nested PCR and DNA sequencing methods.
The widely used Achyranthis Bidentatae Radix (Niu Xi) in Chinese medicine preparation is easily misused and confused with Cyathulae Radix (Chuan Niu Xi). Taiwan authority has ruled that Achyranthis Bidentatae Radix and Cyathulae Radix should be individually entered in the given preparations. In this study, with the internal transcribed spacer (ITS) as a DNA marker, nested PCR and DNA sequencing were used to distinguish the two herbs in preparations. Authentic Achyranthis Bidentatae Radix and Cyathulae Radix were collected from the original country, mainland China, and twenty two samples of Chinese medicine preparations labeled with Niu Xi as the ingredient were purchased locally. The total DNA of all samples were extracted by organic solution and purified using a kit. For a standard, ITS regions of authentic Achyranthis Bidentatae Radix and Cyathulae Radix were amplified with PCR and analyzed by an auto-sequencer. The ITS regions of preparation samples of DNA were amplified by nested PCR and the data of sequences received from an auto-sequencer. We compared the ITS sequences of preparation samples with the sequences of a standard and Genbank database to check which Achyranthis Bidentatae Radix or Cyathulae Radix is in the preparation samples. The results showed that only one sample contained Achyranthis Bidentatae Radix and the others contained Cyathulae Radix. The Cyathulae Radix components in four preparation samples do not fit into Taiwan authority rules. And our method can be applied for the differentiation of Achyranthis Bidentatae Radix and Cyathulae Radix in Chinese medicine preparations.


Defining the Critical Region for Intellectual Disability and Brain Malformations in 6q27 Microdeletions.
Terminal microdeletions of the long arm of chromosome 6 are associated with a phenotype that includes multiple brain malformations, intellectual disability, and epilepsy. A 1.7-Mb region has been proposed to contain a gene responsible for the brain anomalies. Here, we present the case of a 12-year-old girl with multiple brain alterations and moderate intellectual disability with a 18-kb deletion in chromosome 6q27, which is smaller than the microdeletions previously described by microarray analysis. We refined the smallest region of overlap possibly associated with the phenotype of brain malformations and intellectual disability to a segment of 325 kb, comprising the DLL1, PSMB1, TBP, and PDCD2 genes since these genes were structurally and/or functionally lost in the smaller deletions described to date. We hypothesize that DLL1 is responsible for brain malformations and possibly interacts with other adjacent genes. The TBP gene encodes a transcription factor which is potentially related to cognitive development. TBP is linked to PSMB1 and PDCD2 in a conserved manner among mammals, suggesting a potential interaction between these genes. In conclusion, the 6q27 microdeletion is a complex syndrome with variable expressivity of brain malformations and intellectual disability phenotypes which are possibly triggered by the 4 genes described and adjacent genes susceptible to gene regulation changes.


Contribution of tubular anion and cation secretion to residual renal function in chronic dialysis patients.
The clearance of organic ions by the tubules may contribute to the removal of uremic waste products in dialysis patients. The renal excretion of an exogenous anion p-aminohippurate (PAH) was investigated in 10 peritoneal dialysis patients and 10 hemodialysis patients during one clearance period and compared with the clearance of creatinine (Ccr) and inulin (CIn). The clearance period was 24 hours in the peritoneal dialysis patients and one interdialytic interval of 3 days divided in 4 parts [CPA-D] in hemodialysis patients. In peritoneal dialysis patients the renal clearance of total PAH (median 14.3 ml/min, range 3.8-33.0) exceeded the CIN (median 3.2 ml/min, range 1.6-11.2, p < 0.005) and Ccr (median 4.0 ml/min, range 1.7-15.0, p < 0.005). A positive correlation was found between the tubular clearances of creatinine (cationic pathway) and of total PAH (anionic pathway, r: 0.72, p <0.02). In hemodialysis patients the clearance of total PAH (CPA: median 2.0, range 0.8-9.6; CPD: median 3.8, range 1.7-15.4) also exceeded the clearance of inulin (CPA: median 1.5, range 0.2-3.4; CPD: median 2.7, range 0.9-4.4) in the beginning and the end of the interdialytic interval (p < 0.005). The CIN and the clearance of total PAH increased during the interdialytic interval, but the Ccr (CPA: median 2.2, range 0.4-8.9, CPD: median 2.9, range 1.2-4.6) remained stable. Thus, the change in tubular clearance of creatinine and PAH was opposite during the interdialytic interval: it increased for total PAH and decreased for creatinine. The CTPAH/CIN ratio in hemodialysis patients was lower than in peritoneal dialysis patients. In CPA it was median 1.6 (range 1.1-5.6, p < 0.05) and in CPD it was median 1.7 (range 1.1-5.0, p < 0.02) and in the peritoneal dialysis patients it was median 3.6 (range 1.5-9.1). We conclude that tubular clearances contribute to the residual renal function in dialysis patients, but the tubular handling of anions and cations in relation to the residual GFR is different between peritoneal and hemodialysis patients. A difference in clearance of organic acids caused by the dialysis techniques may be an explanation for the differences in clinical outcome between the two dialysis modalities.


Modeling procrastination: Asymmetric decisions to act between the present and the future.
Although procrastination has troubled people consistently, there is a lack of systematic theories to explain this behavior. The present study aims to propose and validate a temporal decision model to explain procrastination. The temporal decision model predicts that people will procrastinate on a task so long as the aversiveness of a task outweighs the utility of future incentive outcomes that this task can yield. Specifically, people perceive less aversiveness from a task when this task is scheduled in the future than in the present but expect that they can perceive higher utility from the incentive outcome in the future than in the present. Consequently, people are reluctant to do this task in the present but expect that they are willing to do it in the future (i.e., procrastination). We tested these predictions by measuring perceived task aversiveness, outcome utility, and decision for real-life tasks when the same tasks were scheduled with different delays. The results demonstrate that people expect that they would procrastinate a task as long as perceived task aversiveness is stronger than outcome utility and would stop procrastinating when perceived task aversiveness becomes comparable with outcome utility. Furthermore, people perceive less task aversiveness when the task is scheduled further away and expect that outcome utility would be higher when time gets closer to the delivery of outcome in the future. The present study explains procrastination by revealing how perceived aversiveness from a delayed task and expected outcome utility generate asymmetric decisions between the present and the future. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Effect of Fiblaferon-L on the human immune system.
The effect of a new commercial interferon (Fiblaferon L) on the human immune system was studied. Different experiments were performed on human peripheral blood in vitro, in order to observe: (a) the phagocytic capacity of polymorphonuclear leukocytes (PMNL) and monocytes; (b) monocyte adherence index, and (c) percentage of antibody-dependent cellular cytotoxicity (ADCC) against chicken red blood cells (CRBC). Fiblaferon L enhanced all these functions.


[Elastography in the diagnosis of portal hypertension in patients with liver cirrhosis].
To establish the diagnostic accuracy of liver and spleen density (LD and SD) measurements in patients with compensated alcoholic liver cirrhosis (LC) in the diagnosis of portal hypertension. The investigation enrolled 83 patients with compensated alcoholic and viral (hepatitis C virus) LC. All the patients underwent LD and SD determinations, abdominal ultrasonography, and endoscopy to detect esophageal varices (EV), as well as examination of blood indices. In viral LC, there were substantial LD differences in patients with and without EV. The patients with EV were ascertained to have higher LD [27.9 (21-45) kPa] than those without EV [19.5 (16-26.2) kPa]. SD was also significantly higher than that in the EV group than in the non-EV group (p<0.001). There were no statistically significant differences in SD and LD or in spleen size in patients with alcoholic LC in relation to the presence of EV. Comparison of patients with EV of different etiology revealed differences in platelet count and spleen size. Thrombocytopenia was more pronounced in HCV-related LC patients (p=0.04). The spleen size in patients with viral LC was higher than that in those with alcoholic LC. Elastography of the spleen and liver may be used to identify portal hypertension in patients with viral (HCV) LC (83% sensitivity, 75% specificity) with the following threshold values: LD=26 kPa and SD=50 kPa. The threshold LD and SD values obtained for viral LC do not make possible to diagnose clinically significant portal hypertension (EV) in patients with alcoholic LC. There is a need for further investigations to determine the optimal threshold values of LD and SD for the diagnosis of EV.


Light regulation of cadmium-induced cell death in Arabidopsis.
Cadmium is an environmental pollutant with deleterious effects on both prokaryotic and eukaryotic organisms. In plants, the effects of cadmium toxicity are concentration dependent; lower doses destabilize many physiological processes and inhibit cell growth and multiplication, while higher doses evoke a more severe response that triggers activation of cell death. We recently investigated the effects of light on cadmium toxicity in Arabidopsis using a cell suspension culture system. Although not affecting the inhibitory effects on cell multiplication, we found that light is a powerful regulator of Cd-induced cell death. A very specific proteomic response, which was clearly controlled by light, preceded cell death. Here we discuss the implications of these findings and highlight similarities between the regulation of cell death triggered by Cd and fumonisin B1. We consider how both compounds could be useful tools in dissecting plant cell death signaling.


Efficient shapes for microswimming: From three-body swimmers to helical flagella.
We combine a general formulation of microswimmer equations of motion with a numerical bead-shell model to calculate the hydrodynamic interactions with the fluid, from which the swimming speed, power, and efficiency are extracted. From this framework, a generalized Scallop theorem emerges. The applicability to arbitrary shapes allows for the optimization of the efficiency with respect to the swimmer geometry. We apply this scheme to "three-body swimmers" of various shapes and find that the efficiency is characterized by the single-body friction coefficient in the long-arm regime, while in the short-arm regime the minimal approachable distance becomes the determining factor. Next, we apply this scheme to a biologically inspired set of swimmers that propel using a rotating helical flagellum. Interestingly, we find two distinct optimal shapes, one of which is fundamentally different from the shapes observed in nature (e.g., bacteria).


Differential binary encoding method for calibrating image sensors based on IOFBs.
Image transmission using incoherent optical fiber bundles (IOFBs) requires prior calibration to obtain the spatial in-out fiber correspondence necessary to reconstruct the image captured by the pseudo-sensor. This information is recorded in a Look-Up Table called the Reconstruction Table (RT), used later for reordering the fiber positions and reconstructing the original image. This paper presents a very fast method based on image-scanning using spaces encoded by a weighted binary code to obtain the in-out correspondence. The results demonstrate that this technique yields a remarkable reduction in processing time and the image reconstruction quality is very good compared to previous techniques based on spot or line scanning, for example.


Role of Oral Proficiency on Reading Comprehension: Within-Language and Cross-Language Relationships.
This longitudinal study examined the role of oral proficiency, as measured with elicited narratives using a wordless picture book, Frog Where are You? (Meyer, 1969/1994), on English reading comprehension with a total of 102 English Language Learners (ELLs), including both Spanish and Cantonese speakers. Narrative samples were collected in the winter of first grade and reading skills were assessed on the same children one year later in second grade. Children were enrolled in either bilingual programs or mainstream programs. Multiple regression results show it was not the quantity and variety of words used in the narratives that predicted English reading comprehension one year later. Instead, the ability to produce a coherent oral narrative, in either the home language or English, explained a small variance in English reading comprehension for both English learner groups. These findings highlight the importance of examining narrative skills, especially as measured by narrative structure. Implications for parents and educators are discussed.


Failure mode effect and criticality analysis of ultrasound device by classification tracking.
Medical ultrasound device has been more and more widely used in the hospital and Its safety risk is significantly increased when failures occur. However, there is a lack of quantitative risk assessments of different types of failure modes for medical ultrasound device. This study utilizes a failure mode, effect and criticality analysis (FMECA) approach for quantitative risk evaluation of different failure modes for ultrasound devices. The 4216 medical ultrasound device failure records at various hospitals were investigated. A failure mode and effect analysis method was developed for the quantitative evaluation of the risks of different failure modes. Visual correlation analysis was conducted for all categories to identify the causes of various failure modes. Based on the severity, occurrence and detectability of the failure causes determined, the risk priority number (RPN) for each failure mode was back-calculated through the obtained tracking diagram. The failure modes of unclear images, unable to power on and dark shadows on an image had the highest RPNs. One failure mode could be caused by various factors, and the failure location was not necessarily related to the cause of the failure. This quantitative approach more accurately evaluated the risks of different failure modes, and the results of the corresponding analysis of failure modes and causes could support the rapid determination of the causes of failures in clinical practice.


Inflammation induces two types of inflammatory dendritic cells in inflamed lymph nodes.
The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64+CD11c+MHCII+ inflammatory DCs. Through the assessment of chemokine receptor dependency, gene expression profiles, growth factor requirements and DC-specific lineage mapping, we herein unveil a novel inflammatory DC population (we termed 'CD64+ cDCs') that arises from conventional DCs (cDCs), distinguishable from CD64+ monocyte-derived DCs (moDCs) in inflamed LNs. We determined that Listeria-induced type I IFN is a critical inflammatory cue for the development of CD64+ cDCs but not CD64+ moDCs. Importantly, CD64+ cDCs displayed a higher potential to activate T cells than CD64+ moDCs, whereas the latter showed more robust expression of inflammatory genes. Although CD64+ and CD64- cDCs were able to cross-present soluble antigens at a high dose to CD8+ T cells, CD64+ cDCs concentrated and cross-presented a minute amount of soluble antigens delivered via CD64 (FcγRI) as immune complexes. These findings reveal the role of early inflammatory responses in driving the differentiation of two inflammatory DC subsets empowered with distinct competencies.


Involvement of superficial peroneal sensory nerve in common peroneal neuropathy.
Motor involvement in common peroneal neuropathy (CPN) frequently shows a selective pattern with regard to deep and superficial divisions of the peroneal nerve, by clinical examination and needle electromyography. The involvement of the sensory branch of the superficial peroneal nerve (SPN) has not been well established using nerve conduction studies. Among 42 cases of electrophysiologically defined CPN in 35 patients, 37 (88%) had clinical or electrophysiologic evidence for SPN involvement, but only 20 had diminished superficial peroneal sensory response (SPSR) amplitudes. Many of the cases involving normal SPSRs had significant axonal loss involving deep peroneal motor fibers. Sparing of the superficial peroneal sensory fibers provides further evidence for the selective vulnerability of different nerve fascicles to injury. This is an important pattern to recognize; from a practical standpoint, focal segmental conduction abnormalities in the motor nerve and EMG findings can help to differentiate these lesions from L-5 radiculopathy.


Quality of maternal and newborn health care in Ethiopia: a cross-sectional study.
Despite reports of universal access to and modest utilization of maternal and newborn health services in Ethiopia, mothers and newborns continue to die from preventable causes. Studies indicate this could be due to poor quality of care provided in health systems. Evidences show that high quality health care prevents more than half of all maternal deaths. In Ethiopia, there is limited knowledge surrounding the status of the quality of maternal and newborn health care in health facilities. This study aims to assess the quality of maternal and neonatal health care provision at the health facility level in four regions in Ethiopia. This study employed a facility-based cross-sectional study design. It included 32 health facilities which were part of the facilities for prototyping maternal and neonatal health quality improvement interventions. Data was collected using a structured questionnaire, key informant interviews and record reviews. Data was entered in Microsoft Excel and exported to STATA for analysis. Descriptive analysis results are presented in texts, tables and graphs. Quality of maternal and neonatal health care was measured by input, process and outputs components. The components were developed by computing scores using standards used to measure the three components of the quality of maternal and neonatal health care. The study was done in a total of 32 health facilities: 5 hospitals and 27 health centers in four regions. The study revealed that the average value of the quality of the maternal and neonatal health care input component among health facilities was 62%, while the quality of the process component was 43%. The quality of the maternal and neonatal health output component was 48%. According to the standard cut-off point for MNH quality of care, only 5 (15.6%), 3 (9.3%) and 3 (10.7%) of health facilities met the expected input, process and output maternal and neonatal health care quality standards, respectively. This study revealed that the majority of health facilities did not meet the national MNH quality of care standards. Focus should be directed towards improving the input, process and output standards of the maternal and neonatal health care quality, with the strongest focus on process improvement.


Protonated MIL-125-NH2: Remarkable Adsorbent for the Removal of Quinoline and Indole from Liquid Fuel.
The removal of nitrogen-containing compounds (NCCs) from fossil fuels prior to combustion is currently of particular importance, and so we investigated an adsorptive method using metal-organic frameworks (MOFs) for the removal of indole (IND) and quinoline (QUI), which are two of the main NCCs present in fossil fuels. We herein employed an amino (-NH2)-functionalized MIL-125 (MIL-125-NH2) MOF, which was further modified by protonation (P-MIL-125-NH2). These modified MOFs exhibited extraordinary performance in the adsorption of both IND (as representative neutral NCC) and QUI (as representative basic NCC). These MOFs were one of the most efficient adsorbents for the removal of NCCs. For example, P-MIL-125-NH2 showed the highest adsorption capacity for QUI among ever reported adsorbent. The improved adsorption of IND was explained by H-bonding and cation-π interactions for MIL-125-NH2 and P-MIL-125-NH2, respectively, while the mechanisms for QUI were H-bonding and acid-base interactions, respectively. This is a rare phenomenon for a single material (especially not with very high porosity) to exhibit such remarkable performances in the adsorption of both basic QUI and neutral IND. The adsorption results obtained using regenerated MIL-125-NH2 and P-MIL-125-NH2 also showed that these materials can be used several times without any severe degradation.


Leptin as a marker of body fat and hyperinsulinemia in college students.
Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin was strongly correlated with total fat mass (r = .67, p <.001), percentage body fat (r= .81, p < .001), and to a lesser degree Body Mass Index, or BMI, (r = .23, p < .02). Leptin was associated with fasting insulin (beta+/-SE = 0.30+/-0.06, p < .001) and insulin resistance (beta+/-SE = 0.41+/-0.20, p < .001) independent of total fat, gender, and age, suggesting other mechanisms of leptin and insulin regulation besides obesity. Leptin resistance is present even among young and normal-weight college students. Leptin, even more so than BMI, is an important marker of adiposity and hyperinsulinemia in normal-weight college students and may potentially be used to predict type 2 diabetes.


Short-term cardiorespiratory effects of proportional assist and pressure-support ventilation in patients with acute lung injury/acute respiratory distress syndrome.
Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis. Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured. With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes. In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.


Parasitological Indices of Malaria Transmission in Children under Fifteen Years in Two Ecoepidemiological Zones in Southwestern Burkina Faso.
Twenty years after the latest publications performed on the parasitological indices of malaria transmission in northwest of the second city of Burkina Faso, it was important to update the epidemiological profile of malaria in children under the age of 15 years. The objective of this study was to determine and compare the parasitological parameters of malaria transmission by season, area, and age in the two zones (rice and savanna) in the northwest of Bobo-Dioulasso, Burkina Faso. Overall, the results showed that there was no significant difference in the parasitological indices of malaria transmission within children under fifteen years between the rice site and the savannah site and whatever the season (P > 0.05). The profound environmental modifications that occurred in the rice zone would have led to changes in vector behavior and consequently to changes in the epidemiological profile of malaria, contrary to the results obtained since the last publications. An entomological study correlated with this study is therefore necessary for effective decision-making for the malaria control in both areas. Future research must now focus on the impact that these profound environmental modifications of rice area are having on malaria control in Burkina Faso.


Effects of vestibular and support afferentation upon visual pursuit in microgravity.
Evaluation of the accuracy of eye turns (saccades) to fix a jerky pointed stimulus, and smooth pursuit of slow linear and sinusoidal movements of both pointed and optokinetic stimuli was performed in 31 cosmonauts on flight days 2-3, 5-8, 30, and once in one or two months of mission. An additional investigation of the eye pursuit function involved 10 cosmonauts, who, after testing during free floating, fulfilled stimulus tracking following a cycle of active head rotation, and 14 cosmonauts who received support afferentation. It was found that at the beginning of adaptation and periodically in the course of long mission, the systems of slow pursuit tracking adopted the strategy of saccadic approximation whereby gaze fixation was achieved through a sequence of macro- or microsaccadic movements. It was demonstrated that these disturbances, practically in all investigated cosmonauts, were consequent to the vestibular deprivation developing in microgravity. Vestibular afferentation produced by active head rotation improved characteristics of visual pursuit. Support deprivation also affects pursuit tracking by cosmonauts who form the concept of space orientation based on perception of their head and leg position. With support afferentation, these cosmonauts demonstrated improved visual pursuit characteristics.


The Clinical Characteristics of Acute Cerebrovascular Accidents Resulting from Ovarian Hyperstimulation Syndrome.
Ovarian hyperstimulation syndrome (OHSS) is a serious complication that occurs after the ovarian-induction treatment. Acute cerebrovascular accident is one of the most dangerous manifestations of the syndrome. However, the characteristics of stroke resulting from OHSS have so far not been well summarised in any study. We reported 2 cases of acute cerebrovascular accidents secondary to OHSS. And then we performed a literature search for reports on this type of stroke, and summarised their characteristics. Thirty-six published cases of this type of stroke were reviewed. Thirty two out of 36 (88.9%) of the women were 35 years old or younger. Stroke in 28 out of 36 (77.8%) of these cases was caused by arterial thrombosis. In 17 out of 28 cases, the involved cerebral vascular branches were mainly middle cerebral artery (MCA) and internal carotid artery (ICA). The acute cerebrovascular accidents happened 7 and 9.25 days after embryo transplantation or 8 and 8.33 days after last human chorionic gonadotropin treatment respectively. The prognosis of patients was relatively good after anticoagulation and some supportive treatments. The MCA and ICA are easily involved in stroke resulting from OHSS. The young age may be a risk factor for developing stroke secondary to OHSS. Once thromboembolism develops, administering appropriate therapy is crucial.


Development of the South-East Forum on Nursing Science (SEAFONS).
The development of regional cooperation in doctoral programs in Asia is described along with the names of the program in each of the following countries: South Korea, Thailand, Japan, Hong Kong, Philippines, and Taiwan. The need for doctoral education in nursing is also described.


Bird diversity along an urban to rural gradient in large tropical cities peaks in mid-level urbanization.
The gradient from natural to urban areas strongly associates with the structure of avian communities over that gradient. Most research on urban birds is from temperate areas and knowledge from tropical Southeast Asia is lacking. We examined bird species diversity, relative abundance, and species composition along an urban to rural gradient in three Myanmar cities, and assessed potential environmental factors responsible for the changes. We counted birds within 40 point-count sites with 50-m fixed-radius in three large cities of Myanmar, namely Mandalay, Mawlamyine, and Myeik. We distinguished four urban habitat types (Downtown-urban, University Campus-suburban, Paddy Field-agriculture, Hill-forest). We classified all species into migrant or resident and into major feeding groups and related with several environmental parameters such as 'impervious surface'. We counted 5,423 individuals of 103 species with roughly equal species diversity between the three cities. Rock Pigeon (Columba livia) was the most frequent species. The species composition differed significantly between the four major habitat types. Omnivores were more abundant in the city center than all other functional groups. Interestingly, insectivores were also predominant in the city center. In addition, more generalist' species occurred towards the city center compared to the periphery, indicating that the periphery has increased relevance for specialized birds. We found some marked differences in species composition between the three cities of Mandalay, Mawlamyine, and Myeik. Additionally to species composition, species diversity and relative abundance differed significantly between each of the four major habitat types in all three cities.


Directed drug distribution: adding controlled brain activity to a drug.
Environmental factors can alter the state of an organism so as to influence the response to drugs. This fact is widely recognized even though the responsible mechanisms are difficult to understand and control. The capacity of environmental influences to alter local drug pharmacokinetics is rarely considered. Drug localization and resulting action within the brain are influenced by vascular blood flow factors, local concentration differences in competing neurohumours, and receptor density. These are all frequently asymmetrically represented in the brain and drug effects are correspondingly laterality dependent. Attention to regional brain pharmacokinetics and the influence of environment on regional blood flow, local neurohumor concentration, and receptor density represents an untapped opportunity to enhance the desired effect of a centrally active drug at its site of action without enhancing general systemic toxicity. Combined pharmacotherapy and psychotherapy may result in superior therapeutic responses. Psychotherapy is a potential tool deliberately to manipulate environmental factors that influence physiological and physical chemical parameters that determine drug disposition.


The characterization of scintillons. Bioluminescent particles from the marine dinoflagellate, Gonyaulax polyedra.
A new type of biological particle, isolated from the marine dinoflagellate Gonyaulax polyedra, has been partially purified and characterized. When the pH is lowered, the particle emits light in vitro in a fashion closely mimicking the flash of the living cell, and it is referred to as a scintillon (flashing unit). Scintillons are obtained by breaking the cells in buffer at pH 8.2 and purifying by differential and sucrose density gradient centrifugation. The particle has a density of about 1.23 g cc(-1), and activity is quantitatively correlated with the number of crystal-like birhombohedral structures. These have been found to contain guanine, but since the density of authentic guanine is about 1.73 g cc(-1), the scintillon is believed to comprise additional but as yet unidentified components. The properties of the scintillon and the effects of various physical and chemical treatments are described. The reasons for believing that this particle is responsible for the flash of the intact cell are discussed.


Novel Field-Based Protein Detection Method Using Light Transmission Spectroscopy and Antibody Functionalized Gold Nanoparticles.
Protein detection is a universal tool critical to many applications in medicine, agriculture, and biotechnology. We developed a novel protein detection method combining light transmission spectroscopy and particle-size analysis of gold nanospheres monovalently functionalized with polyclonal antibodies and applied it to an emerging challenge for such technologies─the monitoring of environmental proteins (eProteins) present in natural aquatic systems. These are an underreported source of pollution and include the pseudopersistent Cry toxins that enter aquatic ecosystems from surrounding genetically engineered crops. The assay is capable of detecting proteins in complex matrices, such as water samples collected in the field, making it a competitive assay for eProtein detection. It is sensitive, reaching 1.25 ng mL-1, and we demonstrate its application to the detection of Cry1Ab from subsurface tile-drain and streamwater samples from agricultural waterways. The assay can also be quickly adapted for other protein detection applications in the future.


Dilemmas in the Clinical Management of pT1 Colorectal Cancer.
Implementation of population-based colorectal cancer screening programs has led to increases in the incidence of pT1 colorectal cancer. These incipient invasive cancers have a very good prognosis and can be treated locally, but more than half of these cases are treated with surgery due to the presence of histological high-risk criteria. These high-risk criteria are suboptimal, with no consensus among clinical guidelines, heterogeneity in definitions and assessment, and poor concordance in evaluation, and recent evidence suggests that some of these criteria considered high risk might not necessarily affect individual prognosis. Current criteria classify most patients as high risk with an indication for additional surgery, but only 2-10.5% have lymph node metastasis, and the residual tumor is present in less than 20%, leading to overtreatment. Patients with pT1 colorectal cancer have excellent disease-free survival, and recent evidence indicates that the type of treatment, whether endoscopic or surgical, does not significantly impact prognosis. As a result, the protective role of surgery is questionable. Moreover, surgery is a more aggressive treatment option, with the potential for higher morbidity and mortality rates. This article presents a comprehensive review of recent evidence on the clinical management of pT1 colorectal cancer. The review analyzes the limitations of histological evaluation, the prognostic implications of histological risk status and the treatment performed, the adverse effects associated with both endoscopic and surgical treatments, and new advances in endoscopic treatment.


Stress Concentration of Periodic Collinear Square Holes in an Infinite Plate in Tension.
A numerical approach for the stress concentration of periodic collinear holes in an infinite plate in tension is presented. It involves the fictitious stress method and a generalization of Bueckner's principle. Numerical examples are concluded to show that the numerical approach is very efficient and accurate for analyzing the stress concentration of periodic collinear holes in an infinite plate in tension. The stress concentration of periodic collinear square holes in an infinite plate in tension is studied in detail by using the numerical approach. The calculated stress concentration factor is proven to be accurate.


The Main Coronary Artery (LMCA) Thrombus Presented as an ST Elevation Myocardial Infarction in a Hypercoagulable Patient.
Left main coronary artery (LMCA) thrombus is a clinically rare event and is thought to be secondary to plaque rupture with subsequent thrombus formation, persistent hypercoagulable state, cocaine use, or vasospasm. (Klein et al., 2008) here we present a case of LMCA thrombus that presented as an ST elevation myocardial infarction (STEMI) in a hypercoagulable patient.


Biosynthesis of the Klebsiella oxytoca Pathogenicity Factor Tilivalline: Heterologous Expression, in Vitro Biosynthesis, and Inhibitor Development.
Tilvalline is a pyrrolo[4,2]benzodiazepine derivative produced by the pathobiont Klebsiella oxytoca and is the causative toxin in antibiotic associated hemorrhagic colitis (AAHC). Heterologous expression of the tilivalline biosynthetic gene cluster along with in vitro reconstitution of the respective NRPS (NpsA, ThdA, NpsB) was employed to reveal a nonenzymatic indole incorporation via a spontaneous Friedel-Crafts-like alkylation reaction. Furthermore, the heterologous system was used to generate novel tilivalline derivatives by supplementation of respective anthranilate and indole precursors. Finally, it could be shown that salicylic and acetylsalicylic acid inhibit the biosynthesis of tilivalline in K. oxytoca liquid culture, presumably by blocking the peptidyl carrier protein ThdA, pointing toward a potential application in combination therapy to prevent or alleviate the symptoms of AAHC.


Systemic Alanine Glyoxylate Aminotransferase mRNA Improves Glyoxylate Metabolism in a Mouse Model of Primary Hyperoxaluria Type 1.
Primary Hyperoxaluria Type 1 (PH1) is an autosomal recessive disorder of glyoxylate metabolism. Loss of alanine glyoxylate aminotransferase (AGT) function to convert intermediate metabolite glyoxylate to glycine causes the accumulation and reduction of glyoxylate to glycolate, which eventually is oxidized to oxalate. Excess oxalate in PH1 patients leads to the formation and deposition of calcium oxalate crystals in the kidney and urinary tract. Oxalate crystal deposition causes a decline in renal function, systemic oxalosis, and eventually end-stage renal disease and premature death. mRNA-based therapies are a new class of drugs that work by replacing the missing enzyme. mRNA encoding AGT has the potential to restore normal glyoxylate to glycine metabolism, thus preventing the buildup of calcium oxalate in various organs. Panels of codon-optimized AGT mRNA constructs were screened in vitro and in wild-type mice for the production of a functional AGT enzyme. Two human constructs, wild-type and engineered AGT (RHEAM), were tested in Agxt-/- mice. Repeat dosing in Agxt-/- mice resulted in a 40% reduction in urinary oxalate, suggesting therapeutic benefit. These studies suggest that mRNA encoding AGT led to increased expression and activity of the AGT enzyme in liver that translated into decrease in urinary oxalate levels. Taken together, our data indicate that AGT mRNA may have the potential to be developed into a therapeutic for PH1.


Grb7 protein RA domain oligomerization.
The growth factor receptor bound protein 7 (Grb7) is an adaptor protein that is often coamplified with the erythroblastosis oncogene B 2 receptor in 20% to 30% of breast cancer patients. Grb7 overexpression has been linked to increased cell migration and cancer metastasis. The ras associating and pleckstrin homology domain region of Grb7 has been reported to interact with various other downstream signaling proteins such as four and half Lin11, Isl-1, Mec-3 (LIM) domains isoform 2 and filamin α. These interactions are believed to play a role in regulating Grb7-mediated cell migration function. The full-length Grb7 protein has been shown to dimerize, and the oligomeric state of the Grb7SH2 domain has been extensively studied; however, the oligomerization state of the ras associating and pleckstrin homology domains, and the importance of this oligomerization in Grb7 function, is yet to be fully known. In this study, we characterize the oligomeric state of the Grb7RA domain using size exclusion chromatography, nuclear magnetic resonance, nuclear relaxation studies, glutaraldehyde cross linking, and dynamic light scattering. We report the Grb7RA domain can exist in transient multimeric forms and, based upon modeling results, postulate the potential role of Grb7RA domain oligomerization in Grb7 function.


Oral assessment of the edentulous elderly patient.
While the need for regular oral examinations increases in the aged, edentulous elderly persons generally see their dentists rarely, while most see their physicians relatively frequently. If these patients cannot be convinced to see a dentist, the physician should perform regular oral screening examinations. A technique is described for accomplishing this.


Patterned array of nanoparticles on substrates via contact printing method with CNTs/AAO stamp.
Patterned arrays of Fe oxide nanoparticles were transferred via contact printing method on a substrate surface using carbon nanotubes embedded in anodic aluminum oxide (CNTs/AAO) as a stamp, in which vertically aligned CNTs in hexagonally patterned array was first fabricated by chemical vapor deposition into the AAO, followed by a partial chemical etching to expose the CNTs from the AAO. Fe precursor inked CNTs stamp was contact-printed on a Pt-coated Si substrate, and after heat treatment at 200 degrees C, patterned array of Fe oxide nanoparticles with ca. 80 nm of diameter and ca. 120 nm of inter-distance between the nanoparticles was consequently obtained.


Dental Anxiety among Medical and Paramedical Undergraduate Students of Malaysia.
Aim. To assess the dental anxiety level among dental, medical, and pharmacy students of MAHSA University, Malaysia. Materials and Methods. A cross-sectional questionnaire study was conducted among 1500 undergraduate students of MAHSA University. The Modified Dental Anxiety Scale (MDAS) was used to measure dental anxiety among the study population. The responses were assessed by 5-point likert scale ranging from 1 to 5. The level of anxiety was categorized into lowly anxious (5-11), moderately anxious (12-18), and severely anxious ≥19. Out of 1500 students enrolled, 1024 students (342 males and 682 females) completed and returned the questionnaire having response rate of 68.26%. Results. There was a statistically significant difference (P < 0.001) when the mean dental anxiety scores were compared among the three faculties and dental students had lowest mean score (11.95 ± 4.21). The fifth year (senior) dental students scored significantly (P = 0.02) lower mean anxiety score as compared to the first dental students (junior). The students were anxious mostly about tooth drilling and local anesthetic injection. Conclusions. Dental students have a significantly low level of dental anxiety as compared with medical and pharmacy students. Incorporation of dental health education in preuniversity and other nondental university curriculums may reduce dental anxiety among the students.


Asian oral-facial cleft birth prevalence.
To determine the clefting birth prevalence among Asian populations, specifically Chinese and Japanese, using raw counts from nonoverlapping published studies of Asian populations, and to investigate whether Asian clefting rates have been interpreted accurately as being up to twice the Caucasian rate. A literature review of articles giving raw counts of clefting in Asian populations, primarily Japanese and Chinese. Where possible, clefts were identified by the patients' ethnicity, country of origin, cleft type, syndromic status, and birth status. Prevalence rates of cleft lip with or without cleft palate per 1000 live births are reported. Syndromic plus nonsyndromic cleft lip with or without cleft palate: Chinese, 1.30; Japanese, 1.34; Other Asian, 1.47; and total, 1.33. Nonsyndromic cleft lip with or without cleft palate: Chinese, 1.20; Japanese, 1.18; Other Asian, 1.22; and total, 1.19. Overall, Chinese and Japanese live birth prevalence rates for nonsyndromic cleft lip with or without cleft palate, based on the published reports of birth prevalence, are significantly lower than the oft-quoted rate of 2 per 1000 for Asians. The apparent reason for the discrepancy is that many published prevalence rates included all pregnancies (live births plus pregnancy losses) and do not distinguish between syndromic and nonsyndromic clefts or between cleft palate alone and cleft lip with or without cleft palate. These results demonstrate that it is extremely important for current population-based studies of clefts to include careful delineation of population groups, syndromes, cleft type, and birth status.


Effect of interferon-alpha on the expression of tumour necrosis factor-alpha by metastatic malignant melanoma in vivo.
To our knowledge modulation of the expression of tumour necrosis factor-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. The specificity of the staining reaction was demonstrated by absorption of the TNF-alpha antibody with human recombinant TNF-alpha, which inhibited the staining reaction. The TNF-alpha expression was also verified by in situ hybridization for mRNA. Metastases from 37 patients were studied, 21 of whom were treated with IFN-alpha. All 16 metastases from untreated patients were positive for TNF-alpha. Based on the average staining intensity of the melanoma cells for TNF-alpha, the metastases were classified into two groups. The expression of TNF-alpha varied considerably between metastases from different patients and also within the same metastasis. Melanoma cells in areas with low cellularity and large numbers of infiltrating inflammatory cells were generally weakly stained. This is in good agreement with a low staining score for TNF-alpha in metastases showing marked histopathological regression. Seven out of 13 patients with a low staining score for TNF-alpha showed a marked regression of their tumours. In contrast one out of five patients with a high staining score for TNF-alpha showed a marked tumour regression, suggesting that tumour cells sensitive to immune-mediated regression express less TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF-alpha. Significantly more patients treated with IFN-alpha had metastases with a low TNF-alpha staining score compared with untreated patients. Thus, seven out of 21 patients treated with IFN-alpha showed a high expression of TNF-alpha in contrast to 13 out of 16 in the untreated group (P = 0.01).


Fundamentals of Joint Injection.
Using image guidance for joint access is a valuable fundamental skill. The purpose of this article is to review fluoroscopic and ultrasound-guided techniques and the medications used for injection into the glenohumeral, elbow, wrist, hip, knee, and ankle joints. Thorough understanding of basic injection principles, knowledge of the underlying anatomy, and consideration of the advantages and disadvantages of the imaging approaches should facilitate selection of the most appropriate technique for any clinical scenario.


Negation Scope Detection in Clinical Notes and Scientific Abstracts: A Feature-enriched LSTM-based Approach.
Electronic Health Records contain a wealth of clinical information that can potentially be used for a variety of clinical tasks. Clinical narratives contain information about the existence or absence of medical conditions as well as clinical findings. It is essential to be able to distinguish between the two since the negated events and the non-negated events often have very different prognostic value. In this paper, we present a feature-enriched neural network-based model for negation scope detection in biomedical texts. The system achieves a robust high performance on two different types of texts, scientific abstracts, and radiology reports, achieving the new state-of-the-art result without requiring the availability of gold cue information for negation scope detection task on the scientific abstracts part of BioScope1 corpus and competitive result on the radiology report corpus.


CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases.
Mantle cell lymphoma is usually negative for CD10 which is useful in distinguishing MCL from other CD10 + B cell lymphomas. Here we assessed the clinicopathologic features of 30 cases of CD10+ MCL, the largest series to date in the English literature, and compared them with a group of 212 typical MCL cases (CD5+, CD10-negative, CD23-negative, cyclin D1+). The 30 patients with CD10+ MCL included 17 men and 13 women with a median age of 68 years. Compared with CD10-negative MCL, patients with CD10+ MCL showed a lower male predominance (p = 0.01), more often had a diffuse growth pattern (p = 0.04) and blastoid/pleomorphic morphology (p < 0.0001), and more often showed BCL6 expression (p = 0.009). In all MCL patients, CD10 expression was not associated with overall survival (OS) (p = 0.16). However, in more aggressive subsets of MCL patients including those with high Ki67 (> 60%), blastoid/pleomorphic morphology, or high MCL International Prognostic Index (MIPI), CD10 expression was associated with a worse OS (p = 0.003, 0.04, and 0.001, respectively). High Ki67 (> 60%), blastoid/pleomorphic morphology, and high MIPI were also been identified as poor prognostic factors patients with in CD10+ MCL (p = 0.001, 0.0003, and 0.01, respectively). In summary, CD10+ MCL more often has a diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression. In MCL patients with a high Ki-67 (> 60%), blastoid/pleomorphic morphology, or high MIPI, CD10 expression contributes to an even worse prognosis. MCL should be included in the differential diagnosis of CD10 + B cell lymphomas.


Molecular crowding effect on dynamics of DNA-binding proteins search for their targets.
DNA-binding proteins locate and bind their target sequences positioned on DNA in crowded environments, but the molecular crowding effect on this search process is not clear. Using analytical techniques and Langevin dynamics simulations in two dimensions (2D), we find that the essential physics for facilitated diffusion in 2D search and 3D search is the same. We observe that the average search times have minima at the same optimal nonspecific binding energy for the cases with and without the crowding particle. Moreover, the molecular crowding increases the search time by increasing the average search rounds and the one-dimensional (1D) sliding time of a round, but almost not changing the average 2D diffusion time of a round. In addition, the fraction of 1D sliding time out of the total search time increases with increasing the concentration of crowders. For 2D diffusion, the molecular crowding decreases the jumping length and narrows its distribution due to the cage effect from crowders. These results shed light on the role of facilitated diffusion in DNA targeting kinetics in living cells.


Photocorrosion inhibition and enhancement of photocatalytic activity for ZnO via hybridization with C60.
C60 molecules with monomolecular layer state dispersed on the surface of ZnO and formed the hybridized interaction between ZnO and C60. C60-hybridized ZnO photocatalyst showed enhanced photocatalytic activity for the degradation of the organic dye and the photocorrosion of ZnO was successfully inhibited bythe hybridization of C60 molecules. The photocorrosion inhibition of ZnO by C60 molecule could be attributed to the reduced activation of surface oxygen atom. The enhanced photocatalytic activity for C60-hybridized ZnO was originated from the high migration efficiency of photoinduced electrons on the interface of C60 and ZnO, which was produced by the interaction of C60 and ZnO with a conjugative pi-system. The enhancement degree of photocatalytic activity was strongly depended on the coverage of C60 molecules on the surface of ZnO nanoparticles, and the optimum hybridization effect was found at a weight ratio of 1.5% (C60/ZnO). The hybridization of C60 with semiconductors could be used to improve the photocatalytic activity as well as the photostability.


Substituted beta-cyclodextrin and calix[4]arene as encapsulatory vehicles for platinum(II)-based DNA intercalators.
The encapsulation of three platinum(II)-based anticancer complexes, [(5,6-dimethyl-1,10-phenanthroline)(1 S,2 S-diaminocyclohexane)platinum(II)] (2+) ( 56MESS), [(5,6-dimethyl-1,10-phenanthroline)(1 R,2 R-diaminocyclohexane)platinum(II)] (2+) ( 56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)] (2+) ( 56MEEN), with carboxylated-beta-cyclodextrin (c-beta-CD) and p-sulfonatocalix[4]arene (s-CX[4]) has been examined by one- and two-dimensional (1)H nuclear magnetic resonance (NMR) spectroscopy, pulsed gradient spin-echo NMR, ultraviolet spectrophotometry, glutathione degradation experiments, and growth inhibition assays. Titration of any of the three metal complexes with c-beta-CD resulted in 1:1 encapsulation complexes with the cyclodextrin located over the intercalating ligand of the metal complexes, with a binding constant of 10 (4)-10 (5) M (-1). In addition to binding over the phenanthroline ligand of 56MEEN, c-beta-CD was also found to portal bind to the ethylenediamine ligand, with fast exchange kinetics on the NMR timescale between the two binding sites. In contrast, the three metal complexes all formed 2:2 inclusion complexes with s-CX[4] where the two metal complexes stacked in a head-to-tail configuration and were capped by the s-CX[4] molecules. Interestingly, the 56MEEN-s-CX[4] complex appeared to undergo a thermodynamically controlled rearrangement to a less soluble complex over time. Encapsulation of the metal complexes in either c-beta-CD or s-CX[4] significantly decreased the metal complexes' rate of diffusion, consistent with the formation of larger particle volumes. Encapsulation of 56MESS within s-CX[4] or c-beta-CD protected the metal complex from degradation by reduced L-glutathione, with a reaction half-life greater than 9 days. In vitro growth inhibition assays using the LoVo human colorectal cancer cell line showed no significant change in the cytotoxicity of 56MESS when encapsulated by either s-CX[4] or c-beta-CD.


[Effect of medium components on callus induction and contents of polysaccharides in calli from Achyranthes bidentata].
To study the effect of medium components on the callus induction and the contents of polysaccharides in calli from Achyranthes bidentata. Leaves and stems were selected as explants. The effects of six kinds of factors including basal culture medium, carbon source, 2,4-D, 6-BA, TDZ, CH on the callus induction and the contents of ABPS in calli on the high growth point were studied by orthogonal design method. The data were analyzed with range analysis and variance analysis. To leaf, the optimal medium of callus induction was B5 with 2 mg x L(-1) 2,4-D, 0.5 mg x L(-1) 6-BA, 30 g x L(-1) glucose and 1 g x L(-1) CH; to stem, the optimal one was B5 with2 mg x L(-1) 2,4-D, 1 mg x L(-1) 6-BA, 30 g x L(-1) glucose and 0.5 g x L(-1) CH. In order to obtain higher contents ABPS, to leaf calli, the optimal medium was LS with 1 mg x L(-1) 6-BA, 1 mg x L(-1) TDZ and 30 g x L(-1) sucrose; to stem calli, the optimal one was LS with 1 mg L(-1) 2,4-D, 0.5 mg x L(-1) 6-BA, 1 mg x L(-1) TDZ and 30 g x L(-1) glucose. The optimal media of callus induction were established with stems and leaves of A. bidentata as explants and with a view to an industrial production of polysaccharides by tissue and cell culture.


Regulation of microbe-associated molecular pattern-induced hypersensitive cell death, phytoalexin production, and defense gene expression by calcineurin B-like protein-interacting protein kinases, OsCIPK14/15, in rice cultured cells.
Although cytosolic free Ca(2+) mobilization induced by microbe/pathogen-associated molecular patterns is postulated to play a pivotal role in innate immunity in plants, the molecular links between Ca(2+) and downstream defense responses still remain largely unknown. Calcineurin B-like proteins (CBLs) act as Ca(2+) sensors to activate specific protein kinases, CBL-interacting protein kinases (CIPKs). We here identified two CIPKs, OsCIPK14 and OsCIPK15, rapidly induced by microbe-associated molecular patterns, including chitooligosaccharides and xylanase (Trichoderma viride/ethylene-inducing xylanase [TvX/EIX]), in rice (Oryza sativa). Although they are located on different chromosomes, they have over 95% nucleotide sequence identity, including the surrounding genomic region, suggesting that they are duplicated genes. OsCIPK14/15 interacted with several OsCBLs through the FISL/NAF motif in yeast cells and showed the strongest interaction with OsCBL4. The recombinant OsCIPK14/15 proteins showed Mn(2+)-dependent protein kinase activity, which was enhanced both by deletion of their FISL/NAF motifs and by combination with OsCBL4. OsCIPK14/15-RNAi transgenic cell lines showed reduced sensitivity to TvX/EIX for the induction of a wide range of defense responses, including hypersensitive cell death, mitochondrial dysfunction, phytoalexin biosynthesis, and pathogenesis-related gene expression. On the other hand, TvX/EIX-induced cell death was enhanced in OsCIPK15-overexpressing lines. Our results suggest that OsCIPK14/15 play a crucial role in the microbe-associated molecular pattern-induced defense signaling pathway in rice cultured cells.