Growth of yeasts on D-xylulose 1.
Nine of eleven yeasts of different species or genera grew in the presence of air on the intermediate of D-xylose catabolism, D-xylulose (D-threo-pentulose). Growth on this substrate was efficient as judged by the optical density in stationary phase being generally similar to that after growth on glucose. Yeasts which grew on D-xylose also did so on D-xylulose, but among those which grew are included several which utilise neither D-xylose nor xylitol: Saccharomyces cerevisiae, Saccharomyces carlsbergensis, and Schizosaccharomyces pombe. Since catabolism of a sugar generally requires an initial phosphorylation step, growth of these strains suggests that they contain an enzyme which can function as a D-xylulose kinase. The D-xylulose-5-phosphate formed thereby is considered to enter the pentose-phosphate pathway. Glucose-grown inocula of S. carlsbergensis and Schizosaccharomyces pombe, and of several other yeasts, began to grow logarithmically when placed on D-xylulose with no apparent delay, or one which was minimal, suggesting that the D-xylulose kinase was already present in such cells, or was rapidly induced. Petites of S. cerevisiae did not grow on D-xylulose indicating that, in this species, mitochondria are involved in its utilisation.


Supporting academic health centers with knowledge management: learning from the Web.
In a 2003 publication, the Association of Academic Health Sciences Libraries (AAHSL) made explicit the many ways in which a library might contribute to an academic health center's success through knowledge management (KM). Building on Success: Charting the Future of Knowledge Management within the Academic Health Center elucidated the ways in which a library can serve as the center of an organization's KM initiatives. The study and application of knowledge management tools is formidable; unlike information management (IM), the field of knowledge management has roots in a seemingly infinite and wide-ranging number of professional and academic disciplines. The planning of institutional KM initiatives is not commonly discussed, and history shows knowledge management projects often fail to thrive. This column introduces the topic of knowledge management and includes suggested Web-based resources for further understanding and project planning.


Impact of genotypic and phenotypic differences in sarcoma models on the outcome of photochemical internalization (PCI) of bleomycin.
The low curative response to current treatment regimens for most soft tissue sarcomas indicates a strong need for alternative treatment strategies and predictive markers for treatment outcome. PCI (photochemical internalization) is a novel treatment strategy to translocate drugs into cytosol that otherwise would have been degraded in lysosomes. Two highly geno-and phenotypically different uterine and vulvar leiomyosarcoma cell lines, MES-SA and SK-LMS-1, were treated with bleomycin (BLM) activated by PCI (PCIBLM). The MES-SA cells were much more sensitive to PCIBLM than the SK-LMS-1 cells and the treatment induced a 7-8 fold higher increase in DNA double-strand breaks at the same dose of light as measure by γH2AX staining. A 3-fold higher induction of apoptosis and stronger activation of Bax and p21 was also measured in the P53WT MES-SA cells, compared to the P53mut SK-LMS-1 cells. The basal formation of reactive oxygen species (ROS) was 3-fold higher in SK-LMS-1 cells than in the MES-SA cells and SK-LMS-1 cells expressed glutathione peroxidase 1 (GPx1) and more superoxide dismutase 2 (SOD2) than the MES-SA cells. Glutathione depletion with the glutathione synthetase inhibitor buthionine sulfoximine increased the cytotoxic effect of the photochemical treatment (PDT) most strongly in the SK-LMS-1 cells, and reduced PCIBLM-induced H2AX activation in the MES-SA cells, but not in the SK-LMS-1 cells. The results indicate PCIBLM as a potential novel treatment strategy for soft tissue sarcomas, with antioxidant enzymes, in particular GPx1, and the P53 status as potential predictive markers for response to PCIBLM.


Fine mapping of de novo CMT1A and HNPP rearrangements within CMT1A-REPs evidences two distinct sex-dependent mechanisms and candidate sequences involved in recombination.
The molecular mechanism resulting in the duplication or deletion of a 1.5 Mb region of 17p11.2-p12, associated, respectively, with Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), has been proposed to be an unequal crossing-over during meiosis between the two chromosome 17 homologues generated by misalignment of the proximal and distal CMT1A-REP repeats, two homologous sequences flanking the 1.5 Mb CMT1A/HNPP monomer unit. In a recent study of a large series of de novo cases of CMT1A and HNPP, two distinct sex-dependent mechanisms were identified. Rearrangements of paternal origin, essentially duplications, were indeed generated by unequal meiotic crossing-over between the two chromosome 17 homologues, but duplications and deletions of maternal origin resulted from an intrachromosomal process, either unequal sister chromatid exchange or, in the case of deletion, excision of an intrachromatidal loop. In order to determine how these recombinations occur, 24 de novo crossover breakpoints were localized within the 1.7 kb rearrangement hot spot by comparing the sequences of the parental CMT1A-REPs with the chimeric copy in affected offspring. Nineteen out of 21 paternal crossovers were found in a 741 bp hot spot. All the breakpoints of maternal origin (n = 3), however, were located outside this interval, but in closely flanking sequences, supporting the hypothesis that two distinct sex-dependent mechanisms are involved. Several putative recombination promoting sequences in the hot spot, which are rare or absent in the surrounding 7.8 kb, were identified.


Specific neuroprotective effects of manual stimulation of real acupoints versus non-acupoints in rats after middle cerebral artery occlusion.
The objective of this study was to investigate the effectiveness and specific effects of acupuncture on ischemic-induced damage in rats after permanent middle cerebral artery occlusion. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. The rats were divided into the following 4 groups: normal controls, ischemic, real acupuncture-treated (Shuigou, DU26), and non-acupoint-treated groups. On the third postoperative day, neurological deficit scores, cerebral blood flow, infarction volume, and neuronal cell death counts were measured. In the real acupuncture-treated group, the neurological deficit scores and cerebral blood flow were improved (p < 0.05) and the infarction volume and neuronal cell death counts were reduced (p < 0.01) compared to the ischemic and non-acupoint-treated groups. The present study demonstrated that real acupuncture was effective against focal ischemia-induced damage in rats after middle cerebral artery occlusion, and the effects were specifically related to the right needling location.


Biology of Inherited Cataracts and Opportunities for Treatment.
Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.


[Treatment of hepatocellular carcinoma--partial hepatic resection under hand-assisted laparoscopic surgery and local ablation therapy with ethanol and radio frequency].
A 76-year old female patient with chronic B type hepatitis had HCC expanding into the extra-hepatic space. In July 2001, we safely performed partial hepatic resection under hand-assisted laparoscopic surgery (HALS). Three months after the treatment, computed tomography of the liver revealed HCC close to the first branch of right portal vein and bile duct. Although we performed transcatheter arterial chemoembolization (TACE) for the tumor, this treatment was not effective. So we treated percutaneous ethanol injection therapy (PEIT) for the tumor area neighboring Glisson's capsule and radiofrequency ablation therapy (RFA) for the tumor. After this treatment the tumor showed no viability on dynamic CT, and there was no liver infarction or damage to the bile duct. Four months after the final treatment, enhanced CT revealed no viable lesion, and serum alpha-fetoprotein level was declining toward the normal range. We conclude that selection of an applicable treatment and approach is of importance for safe and effective therapy.


Immunologic Parameters for Disease Activity in Rheumatoid Arthritis.
This study aimed to determine the correlation of disease activity of rheumatoid arthritis (RA) with Th17/regulatory T cell (Treg) and Forkhead box protein 3 (Foxp3) cells ratio in patients under therapy with anti-tumor necrosis factor (TNF)-α. Totally, 84 patients with RA and 13 healthy controls were included in this case-control study. The patients were divided into four groups to receive only methotrexate (MTX) (n=25), monotherapy (anti-TNF) (n=18), and combined therapy (MTX+anti-TNF) (n=26); however, one group received no medications (n=15) and was regarded as a positive control. Other 13 healthy controls that were considered negative controls were also enrolled in this study. Patients with RA were attending Basrah General Hospital, Rheumatology Unit, Biological Therapy Center for receiving anti-TNF therapy. Flow cytometry was used for measuring Treg/Foxp3 and Th17 markers, and the DAS-28 score was utilized to measure RA disease activity. Anti-TNF inhibitors (e.g., infliximab and etanercept), as well as other inflammatory and hematological parameters (e.g., erythrocyte sedimentation rate, total white blood cells, lymphocytes, monocytes, and neutrophil counts), were also measured in this study. DAS-28 as a disease activity score was significantly correlated with Th17/Treg/Foxp3 ratio and the Th17 cells count. Statistically, Th17/Treg/Foxp3 ratio was not correlated with body mass index, morning stiffness, and duration of the disease. Th17/Treg/Foxp3 ratio correlated significantly with DAS-28 as an RA disease activity. The lower Treg/Foxp3 frequency led to the higher DAS score reflecting higher disease activity. In the combined therapy group, disease activity was found lower than that in other patient groups indicating the effect of this combination on the relationship between MTX and anti-TNF. This study demonstrated that the main advantage of this combined therapy in RA patients was the reversion of Th17 cell expansion.


Sunlight induced biosynthesis of silver nanoparticle from the bark extract of Amentotaxus assamica D.K. Ferguson and its antibacterial activity against Escherichia coli and Staphylococcus aureus.
Green synthesis of nanoparticles has gained importance due to its eco-friendly, low toxicity and cost effective nature. This study deals with the biosynthesis of silver nanoparticles (AgNPs) from the bark extract of Amentotaxus assamica. The AgNPs have been synthesised by reducing the silver ions into stable AgNPs using the bark extract of Amentotaxus assamica under the influence of sunlight irradiation. The characterisation of the biosynthesised AgNPs was carried out by UV-vis spectroscopy, X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray analysis. The UV-vis spectrum showed a broad peak at 472 nm. Also, the XRD confirmed the crystalline structure of the AgNPs. Moreover, the SEM analysis revealed that the biosynthesised AgNPs were spherical in shape. Also, dynamic light scattering techniques were used to evaluate the size distribution profile of the biosynthesised AgNPs. Furthermore, the biosynthesised AgNPs showed a prominent inhibitory effect against both Escherichia coli (MTCC 111) and Staphylococcus aureus (MTCC 97). Thus the biosynthesis of AgNPs from the bark extract of Amentotaxus assamica is found to eco-friendly way of producing AgNPs compared to chemical method.


[Clinical investigation on AC/A ratio in intermittent exotropia coexisting with ametropia].
To investigate AC/A ratio and coexisting ametropia in intermittent exotropia. To discuss the relation between AC/A ratio and the development of intermittent exotropia. The medical records of 135 patients who had an exotropia were retrospectively reviewed. Patients were divided into 3 groups based on the type of ametropia: exotropia without ametropia (-0.50-+3.00 D between the age of 3-6 years old, -0.50-+2.00 D between the age of 7-40 years old) , exotropia coexisting with myopia (-0.50-7.75 D) and exotropia coexisting with hypermetropia ( ≥ + 3.00 D of 3-6 years old , ≥ + 2.00 D of 7 ∼ 40 years old). AC/A ratios of all patients were assessed using synoptophore method. Distance and near deviations were assessed using prism cover test. AC/A ratios and deviation angles of 3 groups were compared. The relationship between AC/A ratios and ametropia/age were investigated. There were obvious differences in AC/A ratios(2.686 ± 1.372, 1.773 ± 1.110, 4.581 ± 1.552, F = 36.323, P < 0.001) and in near deviation angles (44.473(Δ) ± 19.008(Δ), 53.621(Δ) ± 20.749(Δ), 34.455(Δ) ± 13.292(Δ), F = 8.762, P = < 0.001) between 3 groups of patients, no obvious differences were seen in distance deviation angles (40.333(Δ) ± 19.474(Δ), 44.052(Δ) ± 23.722(Δ), 35.590(Δ) ± 11.143(Δ), F = 1.444, P = 0.24). AC/A ratios were negative linear correlated with refractive powers for patients of intermittent extropia coexisting with myopia or with hypermetropia (r = 0.320, P = -0.469 and r = -0.046, P = 0.036, respectively) . A trend of decline with age was found for AC/A ratios only in patients of intermittent extropia without ametropia (r = -0.320, P = 0.019; r = -0.023, P = 0.865; r = 0.246, P = 0.296 for the other 2 groups, respectively). Myopia and hypermetropia, when coexisting with abnormally low or high AC/A ratio, can destroy the balance between extraocular muscles and induce exophoria to be manifest.


Selective induction of high levels of IgA synthesis in Peyer's patch B cells by protein kinase C-activating phorbol esters.
To understand mechanisms of signal transduction involved in the regulation of isotype differentiation of B lymphocytes, we investigated effects of activation of protein kinase C (PKC) by phorbol esters and elevation of intracellular free calcium (Ca2+) by the calcium ionophore ionomycin (Ion) on Ig secretion by mouse Peyer's patch (PP) and spleen B cells. Results show that Ion suppressed production of IgM, IgG, and IgA by LPS-stimulated B cells whereas PKC-activating phorbol esters also inhibited LPS-induced IgM and IgG secretion, but induced a substantial IgA synthesis, as well as alpha-chain mRNA transcription, in B cells whether stimulated or not by LPS. Phorbol esters enhanced IgA response by directly activating PKC, inasmuch as the other phorbol ester, 4 alpha-phorbol 12,13-didecanoate, which is inactive with respect to PKC, had no effect on B cell differentiation. The increase in IgA secretion occurred in whole PP B cells, but not in the membrane IgA- B cell subset, suggesting that PKC activation does not promote the switching rate of IgM+ cells to IgA+ cells. Results from double staining studies of mIgA using FITC-labeled anti-IgA antibodies and DNA content using the DNA-binding propidium iodide showed that enhanced IgA response was not caused by IgA B cell clonal expansion. PMA induced low level of IL-6 production by highly purified PP B cells. However, addition of anti-mouse IL-6 antibody did not prevent PMA-enhanced IgA secretion, suggesting that IL-6 was not responsible for IgA induction by PMA. Collectively, the present data demonstrate that PKC activation and Ca2+ mobilization, which synergistically trigger cell proliferation, have differential effects on B cell isotype differentiation. Elevation of intracellular Ca2+ suppresses Ig production, but activation of PKC selectively enhances IgA secretion by directly promoting terminal differentiation of IgA-committed PP B cells into IgA-secreting plasma cells.


Reduced density matrices of Richardson-Gaudin states in the Gaudin algebra basis.
Eigenvectors of the reduced Bardeen-Cooper-Schrieffer Hamiltonian have recently been employed as a variational wavefunction ansatz in quantum chemistry. This wavefunction is a mean-field of pairs of electrons (geminals). In this contribution, we report optimal expressions for their reduced density matrices in both the original physical basis and the basis of the Richardson-Gaudin pairs. Physical basis expressions were originally reported by Gorohovsky and Bettelheim [Phys. Rev. B 84, 224503 (2011)]. In each case, the expressions scale like O(N4), with the most expensive step being the solution of linear equations. Analytic gradients are also reported in the physical basis. These expressions are an important step toward practical mean-field methods to treat strongly correlated electrons.


The Impact of Late Onset Arterial Hypotension on Respiratory Outcome in Extremely Premature Infants.
In extremely premature infants, arterial hypotension in the first days after birth has been associated with an increased risk for bronchopulmonary dysplasia (BPD). Some infants present with hypotension at a later postnatal age, but the relationship between late onset hypotension (LOH) and BPD has not been evaluated. To evaluate the association between LOH and BPD and to identify pre- and postnatal factors associated with LOH. Prospectively collected data from a cohort of 23-28 weeks gestational age (GA) infants born during years 2005-2015 and alive at day 28 were analyzed. LOH was defined as the receipt of vasopressor treatment during days 8-28. BPD was defined as need for oxygen at 36 weeks postmenstrual age. Late mortality was defined as death after day 28. Of 1,058 infants in the cohort, 90 (9%) had LOH during days 8-28. Infants with LOH had a higher incidence of BPD than normotensive infants (55 vs. 21%, p < 0.001). Multivariate logistic regression analysis (LRA) showed that LOH was associated with an increased risk for BPD (OR 1.87, 95% CI 1.10-3.17). LOH was also associated with an increased risk for late mortality. LRA showed the risk for LOH increased with lower GA, sepsis and patent ductus arteriosus during days 8-28. In this cohort of extremely premature infants, LOH was associated with an increased the risk for BPD. This association could be secondary to underlying factors that predispose to LOH and BPD or to the deleterious effects of LOH or its treatments on the lung. Further investigation is needed to assess causality.


Predictors of Over-Reporting HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Young Men Who Have Sex With Men (YMSM) in Self-Reported Versus Biomarker Data.
Young men who have sex with men (YMSM) face a disproportionately high burden of HIV. Oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV acquisition, but adherence to PrEP among YMSM may be inadequate. Medication adherence may be assessed via biomarkers, which are expensive and invasive, or via self-report through Audio Computer Assisted Self-Interview (ACASI), which may result in over-reporting of adherence. In this paper we assess the potential of a new method of self-report, the Interactive Questionnaire System (iQS), in validly estimating true adherence rates. PrEP adherence among 167 YMSM aged 15-23 was measured via dried blood spot (DBS), ACASI, and iQS twice over a 24-week study period. Both ACASI- and iQS-reported data revealed that over 40% of individuals self-reporting adequate PrEP adherence had DBS-estimated drug levels indicating inadequate adherence. Adjusted logistic repeated measures random intercept regression analyses indicated that younger YMSM had higher odds of over-reporting adherence than older YMSM-each 1 year increase in age was associated with 0.79 times the odds of over-reporting adherence (95% CI 0.63, 0.98; p value = 0.031), and being African American was associated with 3.22 times greater odds of over-reporting than non-African Americans (95% CI 1.51, 6.90; p-value = 0.0003). These results suggest that ACASI and iQS methods of self-report significantly overestimate true PrEP adherence rates among YMSM, and that the odds of over-reporting adherence may be affected by both age and race.


Neurogenic factors and hypertension in chronic renal failure.
The association between hypertension and chronic renal disease is well recognized. Various factors may play a role in the pathogenesis of hypertension in chronic renal failure. Those include sodium retention and volume expansion, and increased activity of vasoconstrictors, such as the renin-angiotensin system. More recently, increased activity of the sympathetic nervous system has emerged as a leading factor in the pathogenesis of hypertension in these patients. We have used the model of 5/6 nephrectomized rats to study the role of the sympathetic nervous system in the pathogenesis of this form of hypertension. We have shown greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. An acute injury to the kidney produced by intrarenal injection of phenol, causes an immediate rise in blood pressure and in NE secretion from the posterior hypothalamus, that can be prevented by renal denervation. Dorsal rhizotomy prevented the development of hypertension in rats with chronic renal failure. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for the rise in blood pressure in chronic renal failure.


Pseudomesotheliomatous carcinoma of the lung. An immunohistochemical and ultrastructural study of three cases.
The authors report immunohistochemical and electron microscopic studies on three new cases of pseudomesotheliomatous carcinoma of the lung. Although the distinct clinical and histopathologic features of this peripheral lung cancer were described many years ago, its recognition as a distinct variety of lung carcinoma has not gained wide acceptance. Little is known of its incidence and only few cases have been reported until now. In the current study the authors demonstrate the epithelial nature of this tumor by its positive immunohistochemical reactions for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu-M1, B 72.3, and surfactant apoprotein. The ultrastructural features and staining of nuclear inclusions with surfactant apoprotein indicate differentiation into type II cells as found in other forms of peripheral lung adenocarcinoma. Despite these morphologic similarities, pseudomesotheliomatous carcinoma is characterized by extensive invasion of the pleura and rapidly fatal course. Because of this biologic behavior it deserves recognition as a distinct variant of peripheral lung carcinoma.


Sexual selection: an evolutionary force in plants?
Sexual selection has traditionally been used to explain exaggerated sexual traits in male animals. Today the concept has been developed and various other sexually related traits have been suggested to evolve in the same manner. In nearly all new areas where the theory of sexual selection has been applied, there has been an intense debate as to whether the application is justified. Is it the case that some scientists are all too ready to employ fashionable ideas? Or are there too many dogmatic researchers refusing to accept that science develops and old ideas are transformed? Maybe the controversies are simply a reflection of the difficulty of defining a theory under constant re-evaluation. Thus, we begin by summarizing the theory of sexual selection in order to assess the influence of sexual selection on the evolution of plant morphology. We discuss empirical findings concerning potentially affected traits. Although we have tried to address criticisms fairly, we still conclude that sexual selection can be a useful tool when studying the evolution of reproductive traits in plants. Furthermore, by including the evidence from an additional kingdom, a fuller understanding of the processes involved in sexual selection can be gained.


Nucleomodulin BspJ as an effector promotes the colonization of Brucella abortus in the host.
Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. BspJ gene deletion reduced the survival and intracellular proliferation of Brucella at the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.


The Role of the Neonatologist in Fetuses Diagnosed with Congenital Heart Disease.
Prenatal diagnosis of congenital heart disease (CHD) can decrease preoperative morbidity and mortality. Delivery room planning can improve cardiac hemodynamics and time to critical catheter and surgical interventions. Care algorithms have defined lesion-specific level-of-care assignments and delivery room action plans that can facilitate team-based approaches to safe deliveries. Neonatologists play critical roles in the care of fetuses diagnosed with CHD, from the time of diagnosis through the postnatal intensive care unit (ICU) stays. Prenatally, neonatologists are members of the multidisciplinary counseling teams, with expertise to counsel expectant parents about what to expect during the ICU stay, which is especially valuable in CHD associated with extracardiac or genetic anomalies. Neonatologists' role in delivery planning includes identification of the optimal delivery location and allocation of appropriate personnel and resources. After delivery, postnatal care considerations include hemodynamic stability, optimization of end-organ function, genetics consultation, developmentally appropriate care practices to encourage caregiver bonding, and optimization of care to improve neurodevelopmental outcomes of neonates with CHD.


Homodimericin A: A Complex Hexacyclic Fungal Metabolite.
Microbes sense and respond to their environment with small molecules, and discovering these molecules and identifying their functions informs chemistry, biology, and medicine. As part of a study of molecular exchanges between termite-associated actinobacteria and pathogenic fungi, we uncovered a remarkable fungal metabolite, homodimericin A, which is strongly upregulated by the bacterial metabolite bafilomycin C1. Homodimericin A is a hexacyclic polyketide with a carbon backbone containing eight contiguous stereogenic carbons in a C20 hexacyclic core. Only half of its carbon atoms have an attached hydrogen, which presented a significant challenge for NMR-based structural analysis. In spite of its microbial production and rich stereochemistry, homodimericin A occurs naturally as a racemic mixture. A plausible nonenzymatic reaction cascade leading from two identical achiral monomers to homodimericin A is presented, and homodimericin A's formation by this path, a six-electron oxidation, could be a response to oxidative stress triggered by bafilomycin C1.


Is the frequency content of the calls in north american treefrogs limited by their larynges?
A high diversity of mating calls is found among frogs. The calls of most species, however, are simple, in comparison to those of mammals and birds. In order to determine if the mechanics of the larynx could explain the simplicity of treefrog calls, the larynges of euthanized males were activated with airflow. Laryngeal airflow, sound frequency, and sound intensity showed a positive direct relationship with the driving air pressure. While the natural calls of the studied species exhibit minimal frequency modulation, their larynges produced about an octave of frequency modulation in response to varying pulmonary pressure. Natural advertisement calls are produced near the higher extreme of frequency obtained in the laboratory and at a slightly higher intensity (6 dB). Natural calls also exhibit fewer harmonics than artificial ones, because the larynges were activated with the mouth of the animal open. The results revealed that treefrog larynges allow them to produce calls spanning a much greater range of frequencies than observed in nature; therefore, the simplicity of the calls is not due to a limited frequency range of laryngeal output. Low frequencies are produced at low intensities, however, and this could explain why treefrogs concentrate their calling at the high frequencies.


Study of the in vitro modulation exerted by the antidepressant drug escitalopram on the expression of candidate microRNAs and their target genes.
Recent studies indicated a role of microRNAs (miRNAs, small non-coding RNAs which regulate the expression of target genes by acting on mRNAs) in several neural processes, in the pathogenetic mechanisms of neuropsychiatric diseases and in the action of psychotropic drugs. A modulation induced by the antidepressant drug escitalopram on the expression levels of 30 miRNAs was highlighted in the blood of patients suffering from major depressive disorder. With the aim to investigate the effects of escitalopram in an in vitro model, we performed an analysis of the effects produced by escitalopram on the profiles of the 6 miRNAs found to be more significantly modulated in the above-mentioned study (miR-130b, miR-26a and -26b, let-7f, miR-770-5p, miR-34c-5p) in human U87 glioblastoma cells. Cells were treated with the drug for 24, 48 and 72h. The obtained results confirmed a significant increase of let-7f, both after 48 (p=0.031) and 72h (p=0.022), and of miR-26a after 48h (p=0.032). On the same experimental model, a transcriptome analysis was conducted after 72h, highlighting a drug-induced modulation of 1184 protein-coding genes, 207 of which represent let-7f targets. Particularly interesting was the downregulation of BCOR, CCND1 and ATR, validated let-7f targets, which play a key role in the mechanisms of neurogenesis, neuroplasticity and protection from oxidative stress in the brain, indicating that escitalopram could exert downstream effects on gene expression through the regulation of specific miRNAs.


Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer.
Estrogen receptor-positive (ER+) breast cancer is the most common form of breast cancer. Antiestrogens were the first therapy aimed at treating this subtype, but resistance to these warranted the development of a new treatment option. CDK4/6 inhibitors address this problem by halting cell cycle progression in ER+ cells, and have proven to be successful in the clinic. Unfortunately, both intrinsic and acquired resistance to CDK4/6 inhibitors are common. Numerous mechanisms of how resistance occurs have been identified to date, including the activation of prominent growth signaling pathways, the loss of tumor-suppressive genes, and noncanonical cell cycle function. Many of these have been successfully targeted and demonstrate the ability to overcome resistance to CDK4/6 inhibitors in preclinical and clinical trials. Future studies should focus on the development of biomarkers so that patients likely to be resistant to CDK4/6 inhibition can initially be given alternative methods of treatment.


Epidemiology of actinic keratoses and squamous cell carcinoma.
The purpose of this article was to review the frequency, distribution, and determinants of actinic keratoses (AKs) and squamous cell carcinoma (SCC). A review of the literature was done. AKs are extremely common lesions on the sun-exposed skin of Caucasian persons. The most important risk factors are a combination of genetic propensity ("fair skin phenotype") and cumulative sun exposure. Their prevalence increases with advancing age. The epidemiology of SCC is virtually the same, but the lesions occur most often on the head rather than on the upper extremities where most AKs are located. AKs are the most important risk factor identifying those most predisposed to the development of an SCC. AKs are a reliable marker for those people most predisposed to development of an invasive SCC. In addition, AKs are probably an early stage in a biologic continuum that culminates in SCC. However, there are many more AKs than SCCs, and it is difficult to predict exactly which lesions will progress to invasive cancer.


Insulin secretion and growth failure in uremia.
Glucose and insulin metabolism was studied in 16 adolescents with uremia on hemodialysis. Glucose tolerance was measured by i.v. glucose tolerance tests (IVGTT). Insulin sensitivity was measured by the euglycemic clamp technique. Insulin secretion during constant hyperglycemia was measured by the hyperglycemic clamp technique. Controls consisted of eight healthy young adults. These patients could be further subdivided into two groups with respect to their growth velocity SD score (GVSDS). Group one consisted of eight patients with GVSDS more than -2. This group had normal 1,25(OH)2D3 and demonstrated insulin resistance, hyperinsulinemia, and normal glucose tolerance when compared with adult controls. Group two consisted of eight patients with GVSDS less than -2. This latter group had low 1,25(OH)2D3, insulin resistance, but normoinsulinemia and glucose intolerance compared with adult controls. Published data in the literature showed that normal pubertal adolescents demonstrated insulin resistance and hyperinsulinemia compared with normal adults. Compared with normal values of insulin sensitivity in adolescents, both groups of patients on hemodialysis were still insulin resistant. The insulin secretion values in group one was similar to reported values for normal adolescents, whereas the values in group two were lower. GVSDS correlated significantly only with insulin secretion and not with glucose tolerance, insulin sensitivity, 1,25(OH)2D3, or PTH. Normal adolescents demonstrate an increase in insulin secretion as they go into puberty. It seems that the puberty growth spurt in adolescents both with normal health and renal failure may require increased insulin secretion as one of its hormonal requirements.


In vivo three-dimensional evaluation of leukocyte behavior in retinal microcirculation of mice.
To evaluate new physiologic and three-dimensional methods for monitoring leukocyte behavior in mouse retina. Endotoxin-induced uveitis (EIU) was produced in mice by footpad injection of lipopolysaccharide (LPS). Leukocytes were labeled with acridine orange (AO). Leukocyte rolling in the retinal microcirculation was evaluated in vivo with AO digital fluorography. The number of migrated leukocytes was counted in flatmounted retina. The behavior of leukocyte migration was observed three-dimensionally at the time of peak migration. After leukocytes were labeled with AO, the mice were perfused with rhodamine-labeled concanavalin A lectin to stain the vascular endothelium. Leukocyte migration into the retina was then monitored three-dimensionally with confocal microscopy, and the velocity of the migration was measured. Both leukocyte rolling and migration peaked at 48 hours after LPS injection. Leukocytes were seen to extravasate from the deeper capillary layers and to migrate toward the outer layer of the retina. The traveling velocity of extravasated leukocytes in retinal tissue was 2.0 +/- 0.1 microm/h. New methods have been demonstrated for the three-dimensional and quantitative evaluation of leukocyte behavior in mouse retina.


Temperature-programmed precise control over the sizes of carbon nanospheres based on benzoxazine chemistry.
On the basis of benzoxazine chemistry, we have established a new way to synthesize highly uniform carbon nanospheres with precisely tailored sizes and high monodispersity. Using monomers including resorcinol, formaldehyde, and 1,6-diaminohexane, and in the presence of Pluronic F127 surfactant, polymer nanospheres are first synthesized under precisely programmed reaction temperatures. Subsequently, they are pseudomorphically and uniformly converted to carbon nanospheres in high yield, due to the excellent thermal stability of such polybenzoxazine-based polymers. The correlation between the initial reaction temperature (IRT) and the nanosphere size fits well with the quadratic function model, which can in turn predict the nanosphere size at a set IRT. The nanosphere sizes can easily go down to 200 nm while retaining excellent monodispersity, i.e., polydispersity <5%. The particle size uniformity is evidenced by the formation of large areas of periodic assembly structure. NMR, FT-IR, and elemental analyses prove the formation of a polybenzoxazine framework. As a demonstration of their versatility, nanocatalysts composed of highly dispersed Pd nanoparticles in the carbon nanospheres are fabricated, which show high conversion and selectivity, great reusability, and regeneration ability, as evidenced in a selective oxidation of benzyl alcohol to benzaldehyde under moderate conditions.


Probing the magnetic and magnetothermal properties of M(II)-Ln(III) complexes (where M(II) = Ni or Zn; Ln(III) = La or Pr or Gd).
We establish the coordination potential of the Schiff base ligand (2-methoxy-6-[(E)-2'-hydroxymethyl-phenyliminomethyl]-phenolate (H2L)) via the isolation of various M(II)-Ln(III) complexes (where M(II) = Ni or Zn and Ln(III) = La or Pr or Gd). Single crystals of these five complexes were isolated and their solid state structures were determined by single crystal X-ray diffraction. Structural determination revealed molecular formulae of [NiGd(HL)2(NO3)3] (1), [NiPr(HL)2(NO3)3] (2) and [Ni2La(HL)4(NO3)](NO3)2 (3), [Zn2Gd(HL)4(NO3)](NO3)2 (4), and [Zn2Pr(HL)4(NO3)](NO3)2 (5). Complexes and were found to be neutral heterometallic dinuclear compounds, whereas 3-5 were found to be linear heterometallic trinuclear cationic complexes. Direct current (dc) magnetic susceptibility and magnetization measurements conclusively revealed that complexes 1 and 4 possess a spin ground state of S = 9/2 and 7/2 respectively. Empirically calculated ΔχMT derived from the variable temperature susceptibility data for all complexes undoubtedly indicates that the Ni(II) ion is coupled ferromagnetically with the Gd(III) ion, and antiferromagnetically with the Pr(III) ion in 1 and 2 respectively. The extent of the exchange interaction for was estimated by fitting the magnetic susceptibility data using the parameters (g = 2.028, S = 9/2, J = 1.31 cm(-1) and zJ = +0.007), supporting the phenomenon observed in an empirical approach. Similarly using a HDVV Hamiltonian, the magnetic data of 3 and 4 were fitted, yielding parameters g = 2.177, D = 3.133 cm(-1), J = -0.978 cm(-1), (for 3) and g = 1.985, D = 0.508 cm(-1) (for 4). The maximum change in magnetic entropy (-ΔSm) estimated from the isothermal magnetization data for was found to be 5.7 J kg(-1) K(-1) (ΔB = 7 Tesla) at 7.0 K, which is larger than the -ΔSm value extracted from 4 of 3.5 J kg(-1) K(-1) (ΔB = 7 Tesla) at 15.8 K, revealing the importance of the exchange interaction in increasing the overall ground state of a molecule for better MCE efficiency.


[Amino acid transporter molecule as a drug target].
Amino acids, especially essential amino acids are required for protein synthesis and as energy sources in all living cells. Since most amino acids are hydrophilic, special membrane proteins are necessary for their transmembrane transport particularly in transformed cells. We cloned a cDNA encoding L-type amino acid transporter, and named it LAT1. LAT1 is highly expressed in most tumor cells and in a few normal tissues such as the bone marrow, spleen, placenta and brain. As a homolog of LAT1, we also cloned LAT2 which is expressed in various normal tissues. In order to clarify the role of LAT1 in tumor cells, we tested a relatively specific inhibitor to LAT1, BCH (2-aminobicyclo-2(2,2,1)-heptane-2-caboxylic acid), and found that BCH inhibited mortality of mice treated with sarcoma cells. In addition, BCH also suppressed strongly T24 carcinoma cell growth. Moreover, LAT1 transports amino acid mimetic drugs. Thus, these results indicate that amino acid transporter molecule such as LAT1 can be a drug target.


Anesthetic depression of myocardial contractility: a review of possible mechanisms.
The bulk of experimental evidence indicates that anesthetics do not produce their negative inotropic effect via an inhibitory action on mitochondrial electron transport. Anesthetics decrease energy need, rather than energy production. Anesthetics also decrease the rate of sequestration of Ca2+ by mitochondria, but, again, this appears not to be an important cause of reduced myocardial contractility. The role played by direct anesthetic depression of the myofibrils in reducing contractility is uncertain. Most experimental evidence now available suggests that significant myofibrillar depression, measured in terms of inhibition of actomyosin ATPase activity or inhibition of force production, occurs only at anesthetic concentrations which are high compared to concentrations employed clinically. This would seem to indicate that the myofibrils are not an important target for anesthetics in regard to the production of depressed myocardial contractility. However, the experimental act of removing myofibrils from their intracellular environment, or of removing the sarcolemma or making it hyperpermeable, appears to prevent some regulatory myofibrillar phosphorylation reactions from taking place. As stated by Winegrad, "certain forms of regulation of the cardiac myofibril are fragile and can be seen only when cellular constituents and structure are maintained." It is possible that this type of regulation is susceptible to inhibition by anesthetics. Methods for preserving this regulation are available, and will need to be employed before a depressant action of anesthetics on the myofibril can be definitely dismissed as a significant cause of the inhibition of cardiac contractility. A single study, of intracellular Ca2+ levels in the intact cell (where myofibrillar regulation was presumably preserved), has indicated that halothane may decrease myofilament Ca2+ sensitivity. However, for reasons stated above, this study cannot be taken as unequivocal proof of such an action. Despite the fact that the normal action potential is little affected by anesthetics, the sarcolemma appears to play a pivotal role in the production of anesthetic-induced contractile depression. Significant depression of the rate of upstroke of the slow (Ca2+-mediated) action potential by clinical concentrations of both inhalation and intravenous anesthetics has been demonstrated by several workers. This has been interpreted to mean that anesthetics inhibit the influx of Ca2+ through the slow channel, and such has been confirmed (to date, for halothane and thiamylal) by direct measurement of the slow inward Ca2+ current using a voltage clamp technique.(ABSTRACT TRUNCATED AT 400 WORDS)


Human induced pluripotent stem cell region recognition in microscopy images using Convolutional Neural Networks.
We present a deep learning architecture Convolutional Neural Networks (CNNs) for automatic classification and recognition of reprogramming and reprogrammed human Induced Pluripotent Stem (iPS) cell regions in microscopy images. The differentiated cells that possibly undergo reprogramming to iPS cells can be detected by this method for screening reagents or culture conditions in iPS induction. The learning results demonstrate that our CNNs can achieve the Top-1 and Top-2 error rates of 9.2% and 0.84%, respectively, to produce probability maps for the automatic analysis. The implementation results show that this automatic method can successfully detect and localize the human iPS cell formation, thereby yield a potential tool for helping iPS cell culture.


Amyloid-β plaques disrupt axon initial segments.
Amyloid-β (Aβ) plaques are one of the central pathologies of Alzheimer's disease (AD). Plaque formation in animal models of AD coincides with the appearance of synaptic abnormalities, aberrant neuronal excitability, and cognitive decline. Aβ plaques may disrupt neuronal excitability since they have been proposed to be synaptotoxic, to induce axonal varicosities and neurite breakage, and to significantly decrease spine density. Axon initial segments (AIS) also regulate neuronal excitability and help maintain neuronal polarity. Despite these essential functions, the effects of plaques on AIS structure have not been fully determined. Using a mouse AD model, we measured a significant decrease in the density of AIS up to 75μm away from the center of fibrillar, thioflavin-labeled plaques. The reduction was observed in animals with both moderate and severe plaque loads, and was associated with increased densities of microglia near the plaques. Furthermore, animals with severe plaque loads had significantly reduced AIS lengths adjacent to Aβ plaques. These results suggest the local environment surrounding Aβ plaques may be harmful to the AIS. We propose that AIS loss is a previously unappreciated consequence of AD that could significantly impact brain function. This paper demonstrates that neurons near Aβ plaques have disrupted axon initial segments. Loss or disruption of AIS is predicted to have detrimental consequences for brain function.


A single tyrosine residue in the amyloid precursor protein intracellular domain is essential for developmental function.
The Aβ-precursor protein (APP) intracellular domain is highly conserved and contains many potentially important residues, in particular the (682)YENPTY(687) motif. To dissect the functions of this sequence in vivo, we created an APP knock-in allele mutating Tyr(682) to Gly (Y682G). Crossing this allele to APP-like protein 2 (APLP2) knock-out background showed that mutation of Tyr(682) results in postnatal lethality and neuromuscular synapse defects similar to doubly deficient APP/APLP2 mice. Our results demonstrate that a single residue in the APP intracellular region, Tyr(682), is indispensable for the essential function of APP in developmental regulation.


Characterization, Antioxidant and Antibacterial Activity of Essential Oils and Their Encapsulation into Biodegradable Material Followed by Freeze Drying.
The study assessed the antimicrobial and antioxidant activities of commonly used and commercially available essential oils as an alternative to synthetic preservatives. The plant sources were as follows: lavender (Lavandula angustifolia), tea tree (Melaleuca alternifolia), bergamot (Citrus bergamia) and peppermint (Mentha piperita). The antioxidant activity of essential oils was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2´-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods. The microdilution broth susceptibility assay revealed that lavender and bergamot essential oils were more efficient in inhibiting the bacterial growth than other tested oils, with the minimum inhibitory concentration of 5 μg/mL. This study also reports the successful implementation of an electrostatic extrusion technique for encapsulating essential oils into alginate beads, which enables the essential oils to maintain their free radical scavenging ability over time.


Specific deletion of CMF1 nuclear localization domain causes incomplete cell cycle withdrawal and impaired differentiation in avian skeletal myoblasts.
CMF1 is a protein expressed in embryonic striated muscle with onset of expression preceding that of contractile proteins. Disruption of CMF1 in myoblasts disrupts muscle-specific protein expression. Preliminary studies indicate both nuclear and cytoplasmic distribution of CMF1 protein, suggesting functional roles in both cellular compartments. Here we examine the nuclear function of CMF1, using a newly characterized antibody generated against the CMF1 nuclear localization domain and a CMF1 nuclear localization domain-deleted stable myocyte line. The antibody demonstrates nuclear distribution of the CMF1 protein both in vivo and in cell lines, with clustering of CMF1 protein around chromatin during mitosis. In more differentiated myocytes, the protein shifts to the cytoplasm. The CMF1 NLS-deleted cell lines have markedly impaired capacity to differentiate. Specifically, these cells express less contractile protein than wild-type or full-length CMF1 stably transfected cells, and do not fuse properly into multinucleate syncytia with linear nuclear alignment. In response to low serum medium, a signal to differentiate, CMF1 NLS-deleted cells enter G0, but continue to express proliferation markers and will reenter the cell cycle when stimulated by restoring growth medium. These data suggest that CMF1 is involved in regulation the transition from proliferation to differentiation in embryonic muscle.


Recommendations for investigation of hyperandrogenism.
1. Total testosterone assay is recommended as the first-line approach. 2. Radioimmunological assay following prior treatment of the sample (extraction or extraction + chromatography) is the recommended method pending wider experience with mass spectrometry. 3. Where testosterone is twice the upper limit of normal, it is recommended that DHEAS assay be performed. DHEAS is primarily of cortico-adrenal origin in women. Thus, a DHEAS level over 600 mg/dl indicates a diagnosis of androgen-secreting adrenal cortical adenoma.. If DHEAS is normal, the diagnosis could be either ovarian hyperthecosis, normally associated with insulin resistance, or androgen-secreting ovarian tumour. 4. More rarely, elevated testosterone is associated with a marked elevation of SHBG possibly as the result of use of medication having an estrogenic effect (tamoxifen, raloxifene, Op'DDD), or of hyperthyroidism or liver disease. 5. Normal testosterone levels in patients with clear clinical symptoms of hyperandrogenism (hirsutism, seborrhoeic acne) must be interpreted with care. SHBG is normally reduced in the event of overweight, metabolic syndrome or familial history of diabetes.


Analgesic effect of electroacupuncture on chronic neuropathic pain mediated by P2X3 receptors in rat dorsal root ganglion neurons.
Adenosine 5'-triphosphate disodium (ATP) gated P2X receptors, especially the subtype P2X(3), play a key role in transmission of pain signals in neuropathic pain, ATP has been documented to play a significant role in the progression of pain signals, suggesting that control of these pathways through electroacupuncture (EA) is potentially an effective treatment for chronic neuropathic pain. EA has been accepted to effectively manage chronic pain by applying the stimulating current to acupoints through acupuncture needles. To determine the significance of EA on neuropathic pain mediated by P2X(3) receptors in the dorsal root ganglion (DRG) neurons, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded, and the expression of P2X(3) receptors in the DRG neurons was assessed by immunohistochemistry (IHC) and in situ hybridization (ISH). In addition, the currents which were evoked in DRG neurons isolated from rats following chronic constriction injury (CCI) by the P2X(3) receptors agonists i.e. ATP and α,β-methylen-ATP (α,β-meATP) were examined through the experimental use of whole cell patch clamp recording. The present study demonstrates that EA treatment can increase the MWT and TWL values and decrease the expression of P2X(3) receptors in DRG neurons in CCI rats. Simultaneously, EA treatment attenuates the ATP and α,β-meATP evoked currents. EA may be expected to induce an apparent induce analgesic effect by decreasing expression and inhibiting P2X(3) receptors in DRG neurons of CCI rats. There is a similar effect on analgesic effect between rats with contralateral EA and those with ipsilateral EA.


The Effect of Direct-to-Plant Styrene-Butadiene-Styrene Block Copolymer Components on Bitumen Modification.
Five types of material, styrene-butadiene-styrene block copolymer (SBS), ethyl-vinyl-acetate (EVA), naphthenic oil, maleic anhydride grafted ethylene-vinyl acetate copolymer (EVA-g-MAH) and butylated hydroxytoluene (BHT) were used as the raw ingredients for manufacturing direct-to-plant SBS in this paper. Thirteen kinds of direct-to-plant SBS with different EVA/SBS and naphthenic oil/SBS were prepared as well as the processes diagrammatic sketch of dispersion and swelling of direct-to-plant SBS modifier in bitumen were discussed. Microscopic images of direct-to-plant SBS modified bitumen with different components were obtained using fluorescence microscopy. The micro-images were analysed and quantified with MATLAB software. The influence of key components on the micro-morphology of direct-to-plant SBS-modified bitumen is discussed, followed with the tests on melting points and the melting indexes of direct-to-plant SBS with different EVA/SBS and naphthenic oil/SBS. The performances test of bitumen and bituminous mixture modified by these direct-to-plant SBS were also conducted. Results show that, with the ratio improvement of EVA/SBS or naphthenic oil/SBS, the number of the pixel dot number of area (SBS) in microscopic images increased. Enlargement of the pixel dot number of centre line elongate and the structure fineness was observed, indicating that the dispersion and swelling effect of the SBS modifier in bitumen had been improved. Meanwhile, the macro index, such as the melting point and melting index of direct-to-plant SBS, was also improved corresponding to the increase of EVA/SBS ratio or naphthenic oil/SBS ratio. With the addition of EVA or naphthene oil content, penetration and ductility of direct-to-plant SBS modified bitumen received gradual enhancement, but the softening point and viscosity were found out to be decreased. The high-temperature and low-temperature performances of direct-to-plant SBS modified bituminous mixture can be effectively improved by adding EVA or naphthenic oil. By meeting the required performances of direct-to-plant SBS, modified bitumen and bituminous mixture, the component of direct-to-plant SBS is recommended as, SBS:EVA:naphthenic oil:EVA-g-MAH:BHT is 1:0.1⁻0.5:0.05⁻0.2:0.03:0.05. For the compatibleness of SBS with different bitumen are different, necessary tests verification is recommended to be carried out prior to usage.


Plain language summary: Does the amount of time it takes for prostate-specific antigen to double affect how long men with nonmetastatic castration-resistant prostate cancer live and their healthcare costs?
This is a plain language summary of a research article originally published in Clinical Genitourinary Cancer. The original article described the effect of rapidly rising prostate-specific antigen (PSA) levels on how long men with a type of advanced prostate cancer live and their healthcare costs. The prostate is a part of the male body that helps make semen. PSA is a protein produced by the prostate that can show how advanced prostate cancer has become. One measure of prostate cancer growth is assessing how quickly a patient's PSA level doubles. This is known as the PSA doubling time (PSADT). People with a shorter PSADT usually have faster-growing prostate cancer compared with people who have a longer PSADT of more than 12 months (long PSADT). Researchers wanted to know if PSADT can predict cancer spread (known as metastasis) or death for people with a type of advanced prostate cancer called non-metastatic castration-resistant prostate cancer (nmCRPC). Researchers also wanted to know if PSADT can predict healthcare costs. This could help doctors choose the right treatment for their patients with nmCRPC. This was a real-world study, not a clinical trial. This means that researchers looked at what happened when men received the treatments prescribed by their own doctor as part of their usual healthcare treatment. In this study, researchers used insurance claim information. Researchers looked at information for 2800 men with nmCRPC. Six out of every 10 men (60%) had a long PSADT of more than 12 months. Researchers found that it took longer for the cancer to spread to other parts of the body in men with a longer PSADT than men with PSADT of 12 months or less. Researchers also found that men with a longer PSADT lived longer than men with PSADT of 12 months or less. The long PSADT group had fewer healthcare visits overall than men with PSADT of 10 months or less. Over time, it cost less to treat men with a long PSADT than men with PSADT of 10 months or less. Generally, if PSADT was shorter, patients tended to do worse. In this real-world study, researchers found that men with nmCRPC lived longer and had lower healthcare costs if they had a long PSADT of more than 12 months compared with men who had a shorter PSADT. Men with nmCRPC and a shorter PSADT may benefit from approved treatments that slow cancer spread and help them live longer. However, these treatments may have side effects and cost more than standard treatment. Doctors take all these things into account when choosing treatments for their patients. Most men in this study had a long PSADT of more than 12 months. Standard treatment may be the right choice for them because they are more likely to have better outcomes than men with a shorter PSADT.


Do Program Implementation Factors or Fidelity Affect Chronic Disease Self-Management Education Programs' Outcomes?
To evaluate whether implementation factors or fidelity moderate chronic disease self-management education program outcomes. Meta-analysis of 34 Arthritis Self-Management Program and Chronic Disease Self-Management Program studies. Community. N = 10 792. Twelve implementation factors: program delivery fidelity and setting and leader and participant characteristics. Eighteen program outcomes: self-reported health behaviors, physical health status, psychological health status, and health-care utilization. Meta-analysis using pooled effect sizes. Modest to moderate statistically significant differences for 4 of 6 implementation factors; these findings were counterintuitive with better outcomes when leaders and participants were unpaid, leaders had less than minimum training, and implementation did not meet fidelity requirements. Exploratory study findings suggest that these interventions tolerate some variability in implementation factors. Further work is needed to identify key elements where fidelity is essential for intervention effectiveness.


Lewis Base Plays a Double-Edged-Sword Role in Trap State Engineering of Perovskite Polycrystals.
We report the double-edged-sword effect of the thiourea (a typical Lewis base) additive for tailoring the trap state distribution of perovskite polycrystalline films. Through the thiourea treatment, the polycrystal grain size is greatly increased because of the reduced crystallization activation energy, which, together with the surface defect passivation, alters the density of the energetically "deep" and "shallow" trap states in a trade-off manner. Based on this finding and further photoelectric and spectral studies, the nonmonotonic dependence of the photoluminescence intensity on the thiourea concentration and the complicated time-resolved photoluminescence behavior are excellently clarified. As a proof of concept, the photophysical performance of perovskite polycrystals is optimized via a modified Lewis base treatment by taking the proposed double-edged-sword effect into account.


SSTR2a is constantly expressed in lymphoepithelioma-like carcinoma with squamous differentiation other than that with glandular differentiation.
Somatostatin receptor 2a (SSTR2a) is an important diagnostic marker of meningioma and neuroendocrine tumours and is frequently expressed in primary and metastatic non-keratinising nasopharyngeal carcinoma (NK-NPC). Since NK-NPC cases are considered a kind of lymphoepithelioma-like carcinoma (LELCs) which originate from the nasopharynx, information on the expression profile of SSTR2a in LELC in other sites with squamous and glandular differentiations is still lacking. This study aimed to assess the expression of SSTR2a in LELC of various organs and clarify its expression profile. Expression of SSTR2a in 164 cases of LELC was retrospectively analysed by immunohistochemistry in paraffin-embedded tissues, including 146 cases of LELC with squamous differentiation (120 cases of the nasopharynx, 21 cases of the lung and 5 cases of the parotid gland) and 18 cases of LELC with glandular differentiation (15 cases of the stomach and 3 cases of the liver). We found that all (100%) cases of LELC of the lung (21/21) and parotid gland (5/5), and 93.3% (112/120) cases of LELC of the nasopharynx showed a diffused and strong expression of SSTR2a, while cases of gastric (0/15) and biliary (0/3) showed no SSTR2a expression. SSTR2a is constantly expressed in LELC with squamous differentiation, but not expressed in LELC with glandular differentiation. However, the selective expression mechanism of SSTR2a remains unknown, which needs further investigation. Our novel findings might provide potential therapeutic approaches for the treatment of LELC with squamous cell differentiation.


Nickel contact allergy and a nickel-restricted diet.
More than half of nickel-allergic patients develop secondary eruptions, that is, dermatitis in areas of the skin that are not in obvious contact with nickel-plated items. Similar eruptions occur after placebo-controlled oral challenge with inorganic nickel salts. The possible relationship between ingestion of nickel in food and secondary eruptions in nickel-sensitive patients is discussed, making reference to the available literature. Recommendations are given for the management of patients suspected to have nickel dermatitis aggravated by nickel in food.


EGM Toolbox-Interface for Controlling ABB Robots in Simulink.
The development of industrial robotics requires the use of increasingly sophisticated control algorithms. In modern tasks posed by industry, it is not sufficient for the manipulator to move along a programmed path, reaching individual points with the greatest accuracy. There is a need for solutions that can allow detection and avoidance of obstacles appearing on the robot's path and that can compensate the path for low-repetitive workpieces, adjust the strength of the impact of manipulator tools on the workpiece or enable safe cooperation of manipulators with people. To support this development, this work proposes an interface for controlling industrial robots in the Simulink environment. With its use, we can easily test our control algorithms using an external controller without the need to write an extensive program in the RAPID language. The robot controller's task is to control the drives to achieve the set trajectory.


Observations on the sonographic measurement of cervical length and the risk of premature birth.
There is increasing evidence that sonographic measurement of cervical length may be a useful predictor of the risk of spontaneous premature birth. The purpose of this study is to determine whether the measurement of cervical length in a high-risk population at 24 weeks gestation, or the relative change over 24-28 weeks gestation, is more accurate in predicting the risk of spontaneous preterm birth before 35 weeks gestation. Over a 4-year period from 1993-1996, 443 patients with a singleton pregnancy who were at increased risk of preterm birth were studied by serial endovaginal sonography performed at 24 and 28 weeks gestation. There was a positive association between a short cervix and increased risk of preterm birth (F = 13.3, P < .0001). The variable with the highest predictive value for preterm birth was the cervical length at 24 weeks gestation. Changes over time did not substantially improve the predictive accuracy for spontaneous preterm birth. We conclude that a short cervix as determined by endovaginal sonography has a significant association with preterm birth in a high-risk obstetric population. Measurements taken at 24 weeks gestation are most accurate in assessing this risk, and serial observations of the cervix over time have less accuracy for predicting preterm birth.


Changes in radial artery volume assessed using intravascular ultrasound: a comparison of two vasodilator regimens in transradial coronary interventions.
This study used intravascular ultrasound (IVUS) to evaluate radial artery volume changes after intraarterial administration of nitroglycerin and/or verapamil. Radial artery spasm, which is associated with radial artery size, is the main limitation of the transradial approach in percutaneous coronary interventions (PCI). This prospective, randomized study compared the effect of two intra-arterial vasodilator regimens on radial artery volume: 0.2 mg of nitroglycerin plus 2.5 mg of verapamil (Group 1; n = 15) versus 2.5 mg of verapamil alone (Group 2; n = 15). Radial artery lumen volume was assessed using IVUS at two time points: at baseline (5 minutes after sheath insertion) and post-vasodilator (1 minute after drug administration). The luminal volume of the radial artery was computed using ECOC Random Fields (ECOC-RF), a technique used for automatic segmentation of luminal borders in longitudinal cut images from IVUS sequences. There was a significant increase in arterial lumen volume in both groups, with an increase from 451 ± 177 mm³ to 508 ± 192 mm³ (p = 0.001) in Group 1 and from 456 ± 188 mm³ to 509 ± 170 mm³ (p = 0.001) in Group 2. There were no significant differences between the groups in terms of absolute volume increase (58 mm³ versus 53 mm³, respectively; p = 0.65) or in relative volume increase (14% versus 20%, respectively; p = 0.69). Administration of nitroglycerin plus verapamil or verapamil alone to the radial artery resulted in similar increases in arterial lumen volume according to ECOC-RF IVUS measurements.


An investigation of environmental impact on health of workers at retail petrol pumps.
Ninety-four male pump workers, employed in 41 petrol filling stations in Kanpur (formerly Cawnpore) and Lucknow--both in the Ganges plain of north India--were clinically examined. Headache, redness in eyes, lacrimation and signs like coated and/or furred tongue, throat and/or conjunctival congestion and carious teeth were significantly higher (P less than 0.05) in workers exposed to petrol fumes than in controls, as also was the level of phenol in urine (P less than 0.01). Environmental measurements revealed higher concentrations of benzene, sulphur dioxide and photoionizable dust in the air at petrol stations, and most of the symptoms and signs could be attributed to petrol fumes and other environmental pollution.


Cost-effectiveness of pneumococcal conjugate vaccines of 7, 10, and 13 valences in Colombian children.
Currently there are three pneumococcal conjugate vaccines with different coverage of serotypes for use in children under one year. We evaluate the cost-effectiveness of the introduction of pneumococcal conjugate vaccines of 7, 10, and 13 valences in the Colombian EPI. A Markov model, which followed a cohort of children under one year to life expectancy, was developed. Parameters of occurrence and care costs were based on data from National Health System and literature review. PCV-7 is a dominated strategy. PCV-10 and PCV-13 were each compared to no vaccination or PCV-10 vaccination, respectively. A 2+1 schedule and a vaccination price of US$ 14.00, US$ 14.85 and US$ 16.34 per dose were assumed in the base case for PCV-7, -10, and PCV-13 vaccines. Introduction of PCV-13 rather than PCV-10 increases the number of life years gained (LYG). From the societal perspective, in the 'competing choice' framework cost per LYG was US$ 1837 with PCV-10 and US$ 9514 with PCV-13, while PCV-7 is a dominated strategy. The ICER of PCV-13 is above the per capita Gross Domestic Product. Incremental cost-effectiveness ratios (ICERs) were influenced mainly by effectiveness against radiologically-confirmed pneumonia and AOM, vaccine price, and discount rate. Routine vaccination against Streptococcus pneumoniae in Colombia would be cost-effective with PCV-10, with ICER below the per-capita GDP, but its inclusion requires evaluating the budget impact. PCV-13 would prevent more disease and deaths with a higher LYG, but PCV-10 would save more cost to the healthcare system due its higher impact in the prevention of AOM. There is limitation in the clinical evidence of both strategies.


Using time- and size-resolved particulate data to quantify indoor penetration and deposition behavior.
Because people spend approximately 85-90% of their time indoors, it is widely recognized that a significant portion of total personal exposures to ambient particles occurs in indoor environments. Although penetration efficiencies and deposition rates regulate indoor exposures to ambient particles, few data exist on the levels or variability of these infiltration parameters, in particular for time- and size-resolved data. To investigate ambient particle infiltration, a comprehensive particle characterization study was conducted in nine nonsmoking homes in the metropolitan Boston area. Continuous indoor and outdoor PM2.5 and size distribution measurements were made in each of the study homes over weeklong periods. Data for nighttime, nonsource periods were used to quantify infiltration factors for PM2.5 as well as for 17 discrete particle size intervals between 0.02 and 10 microns. Infiltration factors for PM2.5 exhibited large intra- and interhome variability, which was attributed to seasonal effects and home dynamics. As expected, minimum infiltration factors were observed for ultrafine and coarse particles. A physical-statistical model was used to estimate size-specific penetration efficiencies and deposition rates for these study homes. Our data show that the penetration efficiency depends on particle size as well as home characteristics. These results provide new insight on the protective role of the building shell in reducing indoor exposures to ambient particles, especially for tighter (e.g., winterized) homes and for particles with diameters greater than 1 micron.


Effects of low-dose doxycycline and bisphosphonate clodronate on alveolar bone loss and gingival levels of matrix metalloproteinase-9 and interleukin-1β in rats with diabetes: a histomorphometric and immunohistochemical study.
Bisphosphonates (BPs) and low-dose doxycycline (LDD) have been shown to inhibit bone resorption and to improve the levels of proinflammatory mediators and destructive enzymes in gingival tissues, respectively. The purpose of this study is to evaluate the effect of mono and combined BP clodronate and LDD therapies in reducing gingival levels of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and alveolar bone loss in rats with diabetes. Fifty adult Wistar rats were divided into five study groups as follows: 1) group 1 = diabetes control; 2) group 2 = diabetes + periodontitis; 3) group 3 = diabetes + periodontitis + LDD; 4) group 4 = diabetes + periodontitis + clodronate; and 5) group 5 = diabetes + periodontitis + LDD + clodronate. LDD and clodronate were given as a single agent or as combination therapy during the 7 days of the post-experimental periodontitis period. On day 7, the rats were sacrificed, the mobility of the tooth was recorded, and block biopsies were removed. The gingival tissues were analyzed histologically and immunohistochemically for expression of MMP-9 and IL-1β. Alveolar bone loss was evaluated morphometrically under a light microscope. Data analysis was performed statistically by Kruskal-Wallis and post hoc Tukey and Spearman correlation tests. Alveolar bone loss was significantly greater in groups 2 through 5 than group 1 (P <0.05) but was not significantly different among groups 2 through 5 (P >0.05). Animals with periodontitis (group 2) expressed significantly higher levels of MMP-9 and IL-1β compared with those without periodontitis (group 1) (P <0.05). MMP-9 expression was significantly lower in group 3 than groups 1, 2, and 5 (P <0.05). IL-1β expression was significantly lower in the groups 1, 3, 4, and 5 than 2 (P <0.01) but was not significantly different among groups 1, 3, 4, and 5. Positive correlations were found between alveolar bone loss and density of inflammation (ρ = 0.319, P = 0.021) and between MMP-9 and IL-1β (ρ = 0.418, P = 0.002), respectively. Our findings suggest that ligature-induced periodontitis in animals with diabetes results in significantly higher levels of MMP-9 and IL-1β expression in gingiva. The use of mono and combined clodronate and LDD administrations may significantly reduce levels of MMP-9 and IL-1β expression. However, drug administration did not affect alveolar bone levels during the study period.


Interactions in developmental toxicology: combined action of restraint stress, caffeine, and aspirin in pregnant mice.
Stress can result in an increased use of substances such as caffeine and aspirin. The effect of maternal stress on concurrent exposure to caffeine and aspirin on prenatal development was assessed in mice. On gestational day 9, mice were assigned to three treatment groups orally exposed to caffeine (30 mg/kg), aspirin (250 mg/kg), or a combination of caffeine (30 mg/kg) and aspirin (250 mg/kg). Three additional groups of pregnant animals received similar caffeine and aspirin doses and were immediately subjected to restraint for 14 hr. Control groups included unrestrained and restrained pregnant mice not exposed to caffeine or aspirin. All dams were euthanized on gestational day 18. Live fetuses were evaluated for sex, body weight, and external, internal, and skeletal malformations and variations. A single oral dose of caffeine or aspirin did not cause significant maternal toxicity. However, coadministration of these drugs with restraint produced some adverse maternal effects (i.e., reduction in maternal weight gain and food consumption on gestational days 9-11). In relation to embryo/fetal toxicity, the incidence of some skeletal defects was significantly increased after exposure to caffeine, aspirin, or maternal restraint, and their binary and ternary combinations. Although caffeine and aspirin were given in a single dose in this study, the results suggest that prenatal stress could slightly exacerbate the maternal and developmental toxicity of the combination of these drugs in mice.


[Laboratory procedures following thrombocytopenia diagnosis].
Thrombocytopenia--decrease in the blood platelets count below 100 x 10(9)/L--may represent a significant clinical complication--bleeding. A risk of haemorrhagic complications increases with the severity of thrombocytopenia. Even severe thrombocytopenia, however, may be a sign of a condition with predominant symptoms of thrombosis where bleeding is on the background (thrombotic microangiopathy, for example) or where bleeding occurs concurrently with symptoms of thrombosis (so called thrombohaemorrhagic syndromes). It is necessary to exclude pseudothrombocytopenia when thrombocytopenia is first diagnosed. It is then recommended to follow a standardized differential diagnosis algorithm that should be available at each clinical site. We summarize the general rules of thrombocytopenia differential diagnosis with a specific focus on laboratory processes.


A Lipophilic Pt(IV) Oxaliplatin Derivative Enhances Antitumor Activity.
Side effects and acquired resistance by cancer cells limit the use of platinum anticancer drugs. Modification of oxaliplatin (OXA) into a lipophilic Pt(IV) complex [Pt(DACH)(OAc)(OPal)(ox)] (1), containing both lipophilic and hydrophilic axial ligands, was applied to improve performance and facilitate incorporation into polymeric nanoparticles. Complex 1 exhibited unique potency against a panel of cancer cells, including cisplatin-resistant tumor cells. [Pt(DACH)(OAc)(OPal)(ox)] incorporated nanoparticles (2) presented a mean diameter of 146 nm with encapsulation yields above 95% as determined by HPLC. Complexes 1 and 2 showed enhanced in vitro cellular Pt accumulation, DNA platination, and antiproliferative effect compared to OXA. Results of an orthotopic intraperitoneal model of metastatic ovarian cancer (SKOV-3) and a xenograft subcutaneous model of colon (HCT-116) tumor in SCID-bg mice showed that the activity of 1 and 2 significantly decreased tumor growth rates compared to control and OXA treatment groups. Consequently, these findings warrant further development toward clinical translation.


The status of oral hygiene in cleft lip, palate patients after surgical correction.
The cleft lip and palate patients usually present a number of problems viz. altered oral anatomy leading to changes in oral physiology diminishing the self-cleansing ability of individual. The handicapped children are unable to maintain their oral hygiene properly. The present study was formulated with the aim that does normalization of oral anatomy have its effect on improvement of oral hygiene? An assessment of oral hygiene index-simplified was performed between preoperative and postoperative values in the same patient at KGMU and KGDU. A total of 50 cases were recorded in two groups of 25 each: (i) 6 years. The observations are statistically analyzed by paired 't' test to get the significance of results. The data analyzed showed the significant decrease in oral hygiene indices observed in both groups. A relative significance in oral hygiene status following surgery was observed. Both groups expressed greater significance when compared pre and postoperatively which is indicative of considerable improvement of oral hygiene after surgical correction. The study concludes that oral hygiene improves more in older cleft lip-palate cases following reconstruction of palatal vault, premaxilla and anterior lip seal by secondary bone grafting method when compared with oral hygiene indices results in primary periosteoplasty cases. The surgical correction of cleft lip palate enhances self-cleaning ability and better compliance to maintain oral hygiene in children as the age advances.


Optimal experimental conditions for Welan gum production by support vector regression and adaptive genetic algorithm.
Welan gum is a kind of novel microbial polysaccharide, which is widely produced during the process of microbial growth and metabolism in different external conditions. Welan gum can be used as the thickener, suspending agent, emulsifier, stabilizer, lubricant, film-forming agent and adhesive usage in agriculture. In recent years, finding optimal experimental conditions to maximize the production is paid growing attentions. In this work, a hybrid computational method is proposed to optimize experimental conditions for producing Welan gum with data collected from experiments records. Support Vector Regression (SVR) is used to model the relationship between Welan gum production and experimental conditions, and then adaptive Genetic Algorithm (AGA, for short) is applied to search optimized experimental conditions. As results, a mathematic model of predicting production of Welan gum from experimental conditions is obtained, which achieves accuracy rate 88.36%. As well, a class of optimized experimental conditions is predicted for producing Welan gum 31.65g/L. Comparing the best result in chemical experiment 30.63g/L, the predicted production improves it by 3.3%. The results provide potential optimal experimental conditions to improve the production of Welan gum.


Using whole genome sequencing to investigate transmission in a multi-host system: bovine tuberculosis in New Zealand.
Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is an important livestock disease raising public health and economic concerns around the world. In New Zealand, a number of wildlife species are implicated in the spread and persistence of bTB in cattle populations, most notably the brushtail possum (Trichosurus vulpecula). Whole Genome Sequenced (WGS) M. bovis isolates sourced from infected cattle and wildlife across New Zealand were analysed. Bayesian phylogenetic analyses were conducted to estimate the substitution rate of the sampled population and investigate the role of wildlife. In addition, the utility of WGS was examined with a view to these methods being incorporated into routine bTB surveillance. A high rate of exchange was evident between the sampled wildlife and cattle populations but directional estimates of inter-species transmission were sensitive to the sampling strategy employed. A relatively high substitution rate was estimated, this, in combination with a strong spatial signature and a good agreement to previous typing methods, acts to endorse WGS as a typing tool. In agreement with the current knowledge of bTB in New Zealand, transmission of M. bovis between cattle and wildlife was evident. Without direction, these estimates are less informative but taken in conjunction with the low prevalence of bTB in New Zealand's cattle population it is likely that, currently, wildlife populations are acting as the main bTB reservoir. Wildlife should therefore continue to be targeted if bTB is to be eradicated from New Zealand. WGS will be a considerable aid to bTB eradication by greatly improving the discriminatory power of molecular typing data. The substitution rates estimated here will be an important part of epidemiological investigations using WGS data.


Removal of Nickel Ions from Aqueous Solutions by 2-Hydroxyethyl Acrylate/Itaconic Acid Hydrogels Optimized with Response Surface Methodology.
The adsorption of Ni2+ ions from water solutions by using hydrogels based on 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA) was studied. Hydrogel synthesis was optimized with response surface methodology (RSM). The hydrogel with the best adsorption capacity towards Ni2+ ions was chosen for further experiments. The hydrogel was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis before and after the adsorption of Ni2+ ions. Batch equilibrium experiments were conducted to investigate the influence of solution pH, hydrogel weight, ionic strength, adsorption time, temperature and initial concentration of nickel ions on the adsorption. Time-dependent adsorption fitted the best to the pseudo-second-order kinetic model. A thermodynamic study revealed that the adsorption was an exothermic and non-spontaneous process. Five isotherm models were studied, and the best fit was obtained with the Redlich-Peterson model. Consecutive adsorption/desorption studies indicated that the HEA/IA hydrogel can be efficiently used as a sorbent for the removal of Ni2+ ions from the water solution. This study develops a potential adsorbent for the effective removal of trace nickel ions.


[Autotransplantation of a part of the spleen. Experimental studies].
Experimental studies on 38 dogs were carried out. As a result the proper site of transplantation was pointed out: the bigger omentum or any site along the mesentrium. The factors of a greater importance for the success were found to be: a) the thickness of the transplantat (2-3 mm) and b) the quantity of it (> 5% of the original spleen weight). Hematological and immunological tests proved the lack of asplenic syndrome and confirmed the normal functioning of the transplants. Morphological studies revealed normal macroscopic and microscopic picture of the latter one.


Fumonisin B1 production by Fusarium moniliforme and Fusarium proliferatum as affected by cycling temperatures.
The effects of temperatures cycling between 5 and 20 degrees C, 10 and 25 degrees C, and 15 and 30 degrees C on the production of fumonisin B1 (FB1) and ergosterol by Fusarium moniliforme and Fusarium proliferatum on rice was studied. Temperatures were cycled at 12-h intervals by manually moving cultures from one temperature to another. Constant temperature incubation at 25 degrees C and a low temperature stress were compared with the cycling temperature incubations. Low temperature stress was achieved by incubating rice cultures at 25 degrees C for 2 weeks followed by 15 degrees C for 4 weeks. The maximum yields of FB1 were found to be 247 microg/g by F. moniliforme at temperatures that cycled between 10 and 25 degrees C after 2 weeks and 284 microg/g by F. proliferatum when the temperatures cycled between 5 and 20 degrees C after 6 weeks. Ergosterol content of the rice cultures was also monitored. Overall, the two Fusarium species showed differences in production of FB1 and ergosterol under the various temperature treatments. The most notable differences were that the temperature treatments that stimulated greatest FB1 production were different for each species: cycling temperatures between 10 and 25 degrees C for F. moniliforme and cycling temperatures between 5 and 25 degrees C for F. proliferatum. At most temperatures, F. proliferatum produced more ergosterol than F. moniliforme. Maximum production of ergosterol by F. proliferatum occurred at 6 weeks, with temperatures that cycled between 10 and 25 degrees C, whereas F. moniliforme produced maximum amounts of ergosterol at 6 weeks, with temperatures that cycled between 15 and 30 degrees C.


High-nuclearity sulfide-rich molybdenum[bond]iron[bond]sulfur clusters: reevaluation and extension.
High-nuclearity Mo[bond]Fe[bond]S clusters are of interest as potential synthetic precursors to the MoFe(7)S(9) cofactor cluster of nitrogenase. In this context, the synthesis and properties of previously reported but sparsely described trinuclear [(edt)(2)M(2)FeS(6)](3-) (M = Mo (2), W (3)) and hexanuclear [(edt)(2)Mo(2)Fe(4)S(9)](4-) (4, edt = ethane-1,2-dithiolate; Zhang, Z.; et al. Kexue Tongbao 1987, 32, 1405) have been reexamined and extended. More accurate structures of 2-4 that confirm earlier findings have been determined. Detailed preparations (not previously available) are given for 2 and 3, whose structures exhibit the C(2) arrangement [[(edt)M(S)(mu(2)-S)(2)](2)Fe(III)](3-) with square pyramidal Mo(V) and tetrahedral Fe(III). Oxidation states follow from (57)Fe Mössbauer parameters and an S = (3)/(2) ground state from the EPR spectrum. The assembly system 2/3FeCl(3)/3Li(2)S/nNaSEt in methanol/acetonitrile (n = 4) affords (R(4)N)(4)[4] (R = Et, Bu; 70-80%). The structure of 4 contains the [Mo(2)Fe(4)(mu(2)-S)(6)(mu(3)-S)(2)(mu(4)-S)](0) core, with the same bridging pattern as the [Fe(6)S(9)](2-) core of [Fe(6)S(9)(SR)(2)](4-) (1), in overall C(2v) symmetry. Cluster 4 supports a reversible three-member electron transfer series 4-/3-/2- with E(1/2) = -0.76 and -0.30 V in Me(2)SO. Oxidation of (Et(4)N)(4)[4] in DMF with 1 equiv of tropylium ion gives [(edt)(2)Mo(2)Fe(4)S(9)](3-) (5) isolated as (Et(4)N)(3)[5].2DMF (75%). Alternatively, the assembly system (n = 3) gives the oxidized cluster directly as (Bu(4)N)(3)[5] (53%). Treatment of 5 with 1 equiv of [Cp(2)Fe](1+) in DMF did not result in one-electron oxidation but instead produced heptanuclear [(edt)(2)Mo(2)Fe(5)S(11)](3-) (6), isolated as the Bu(4)N(+)salt (38%). Cluster 6 features the previously unknown core Mo(2)Fe(5)(mu(2)-S)(7)(mu(3)-S)(4) in molecular C(2) symmetry. In 4-6, the (edt)MoS(3) sites are distorted trigonal bipramidal and the FeS(4) sites are distorted tetrahedral with all sulfide ligands bridging. Mössbauer spectroscopic data for 2 and 4-6 are reported; (mean) iron oxidation states increase in the order 4 < 5 approximately 1 < 6 approximately 2. Redox and spectroscopic data attributed earlier to clusters 2 and 4 are largely in disagreement with those determined in this work. The only iron and molybdenum[bond]iron clusters with the same sulfide content as the iron[bond]molybdenum cofactor of nitrogenase are [Fe(6)S(9)(SR)(2)](4-) and [(edt)(2)Mo(2)Fe(4)S(9)](3-)(,4-).


Sleep habits of students attending elementary schools, and junior and senior high schools in Akita prefecture.
It is widely accepted that students in Japan sleep fewer hours than what they actually need. However, epidemiological data on sleep habits among students are scarce. The sleep habits and related problems among 1650 students in Akita prefecture were studied. The results revealed that schoolchildren attending elementary schools seemed to sleep for a sufficient number of hours, whereas students attending junior or senior high schools were not sleeping enough. In particular, approximately half of the students attending senior high schools answered that they slept 6 h or less on weekdays and nodded off during classes more than twice a week.


An active site phenylalanine of 3-oxo-delta 5-steroid isomerase is catalytically important for proton transfer.
3-oxo-delta 5-steroid isomerase (KSI) from Pseudomonas testosteroni catalyzes the isomerization of a variety of 3-oxo-delta 5-steroids to their conjugated delta 4-isomers through the intermediate formation of a dienolate ion. This dienolate is formed by proton transfer from C-4 of the substrate to Asp-38, which then protonates the dienolate at C-6. Catalysis is enhanced by electrophilic assistance (hydrogen bonding) to the 3-oxygen by Tyr-14. We have investigated the effect of modifying phenylalanine-101 (F101), a hydrophobic residue that is located in the binding pocket of KSI. Two mutant enzymes (F101L and F101A) of KSI were prepared, and their kinetic properties were examined with 5-androstene-3, 17-dione (1) as the substrate. Both of the mutants show reduced values of kcat compared to the wild type (WT), by about 30-fold (F101L) and by 270-fold (F101A), with only a small difference in Km values. There is little change in the Ki's ( < or = 4-fold) for the product 4-androstene-3,17-dione (3), although both enzymes bind the intermediate analog d-equilenin (4) about 25-fold less tightly than does the WT. Fluorescence spectra of 4 bound to each of these enzymes suggest that 4 is ionized at the active site of WT, un-ionized at the active site of F101A and a mixture of these ionization states at the active site of F101L. Free energy profiles are constructed for each of the mutant enzymes, and these are compared to the free energy profile for the WT.(ABSTRACT TRUNCATED AT 250 WORDS)


Pediatric atopic dermatitis: should we treat it differently?
Atopic dermatitis is an extremely common childhood skin disease that can have far-reaching impact on patients and families. Pediatric patients, particularly infants, pose special concerns for parents and providers, and equal emphasis must be placed on both nonpharmacologic and prescription interventions. Concerns for adverse effects of prescription therapies and a universal parental fear of an undetected allergy are hallmarks of pediatric atopic dermatitis care. The purpose of the present study is to highlight important educational and therapeutic strategies designed to optimally care for this patient population.


[Cooperation study of health eating index and china diet balance index].
The evaluation methods of Both health eating index (HEI) and China diet balance index (DBI) were established based on dietary guidelines of diet quality. The characteristics of HEI and DBI were reviewed from several aspects of establishment foundation and development, scoring system and methods, application, advantages and disadvantages.


Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy.
Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.


Allelochemicals of the phenoxazinone class act at physiologically relevant concentrations.
Plants compete with their neighbors via the release of chemical compounds into the rhizosphere. These phytotoxins originate from a series of secondary metabolites and can be processed further by soil-living microorganisms before exerting their activity on the target plant. To determine the molecular mode of action and the physiological relevance of potential phytotoxins, it is important to simulate true-to-life conditions in laboratory experiments, for example by applying physiologically relevant concentrations. Here, we report on an improved experimental setting to study the function of allelochemicals of the benzoxazolinone class. By adjusting the solvent and the application of the chemicals, we reduced by more than 2fold the concentration that is necessary to induce growth defects in the model plant Arabidopsis thaliana.


Protection of intestinal occludin tight junction protein by dietary gangliosides in lipopolysaccharide-induced acute inflammation.
Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation. Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined. Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS. Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.


Predicting peritumoral Glisson's sheath invasion of intrahepatic cholangiocarcinoma with preoperative CT imaging.
To investigate the differences of clinicopathological characteristics and computed tomography (CT) features between intrahepatic cholangiocarcinomas (ICC) with and without peritumoral Glisson's sheath invasion (PGSI), and to construct a nomogram to predict PGSI of ICCs preoperatively. The clinicopathological characteristics and CT features of 84 ICCs were retrospectively analyzed and compared between ICCs with (30/84, 35.7%) and without PGSI (54/84, 64.3%). Multivariate logistic regression analysis was used to identify preoperative independent predictors of PGSI in ICCs. A nomogram was constructed to predict PGSI preoperatively. ICCs with and without PGSI differed significantly in the presence of abdominal pain, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels, TNM and T stages, tumor location, intratumoral calcifications, intrahepatic bile duct dilatation, intrahepatic bile duct calculus, morphologic type and dynamic enhancement pattern on CT images (all P<0.05). Abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type were independent predictors of PGSI in ICCs. A nomogram based on those predictors was constructed to predict PGSI preoperatively with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.908 (P<0.001). Clinicopathological characteristics and CT features differed significantly between ICCs with and without PGSI. A nomogram including abdominal pain, serum CEA level, intrahepatic bile duct dilatation, and morphologic type could predict PGSI accurately.