Association between blood pressure and cognitive function in a biracial community population of older persons.
We examined whether or not blood pressure is related to cognitive function in a cross-sectional study of a biracial community of 5,816 persons aged 65 years and older. Blood pressure had a curvilinear association with cognitive performance in linear regression models adjusted for age, sex, race and education. Scores were lower by 2-5 percentiles at 100 mm Hg systolic pressure compared to scores at the mean of 140 mm Hg and lower by <1 percentile at 180 mm Hg. For diastolic pressure, scores were lower by 2-3 percentiles at 60 mm Hg and by 1-2 percentiles at 100 mm Hg compared to scores at the mean (77 mm Hg). The differences in the scores with low blood pressure were reduced with further adjustment for body mass index, self-perceived health status, depressive symptoms, alcohol use and smoking. The curvilinear associations were stronger among persons with histories of stroke, myocardial infarction and hypertension. The cross-sectional association between blood pressure and cognitive functions is small and curvilinear and more apparent in persons with cardiovascular conditions.


Rosuvastatin and Atorvastatin Are Ligands of the Human Constitutive Androstane Receptor/Retinoid X Receptor α Complex.
Statins are well known lipid lowering agents that inhibit the enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. They also activate drug metabolism but their exact receptor-mediated action has not been proven so far. We tested whether atorvastatin and rosuvastatin are direct ligands of human constitutive androstane receptor (CAR). We measured binding activities of atorvastatin and rosuvastatin to the human constitutive androstane receptor/retinoid X receptor α ligand-binding domain (CAR/RXRα-LBD) heterodimer with surface plasmon resonance (SPR). Additionally, three-dimensional models of CAR/RXRα-LBD were constructed by ligand-based and structure-based in silico modeling. Experiments and computational modeling show that atorvastatin and rosuvastatin bind to the human CAR/RXRα-LBD heterodimer, suggesting both can modulate the activity of CAR through direct interaction with the LBD of this receptor. We confirm that atorvastatin and rosuvastatin are direct ligands of CAR. The clinical consequences of CAR activation by statins are in their potential drug-drug interactions, and changes in glucose and energy metabolism.


The presence of zinc in the mouse ovary vitrification medium: histological evaluation and follicle growth.
Cryopreservation of ovary is a relevant option for preserving fertility of cancer patients undergoing chemotherapy. To evaluate the effect of zinc in the vitrification medium on histology and follicle growth. Mouse ovaries were vitrified in vitrification medium supplemented with 0, 100, 150 or 200 μg/dl zinc, identified as V0, V1, V2 and V3 groups, respectively. Histological evaluation of ovaries was carried out. The isolated pre-antral follicles were cultured. The size and growth of follicles were assessed. The percentage of morphologically normal follicles increased with increasing zinc concentration in the vitrification medium (P < 0.05). Follicle viability was higher in the V3 than V0 group at the beginning and end of culture (P < 0.05). The highest follicle diameter was obtained in the V3 group after 6 days of culture (P < 0.05). Supplementation of the vitrification medium with zinc can improve follicle viability and growth.


Taro Mucilage: Extraction, Characterization, and Application in Cosmetic Formulations.
Taro mucilage, a hydrocolloid present in the rhizome of Colocasia esculenta (L.) Schott, was extracted and characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermal analysis, and proximal composition. In addition, cosmetic formulations based on extracted mucilage were developed and studied. The mucilage presented a semicrystalline structure with high thermal stability, the presence of granules along its surface area, and good emulsifying activity. High physical-chemical stability was also found in the mucilage and the cosmetic formulations during storage. All cream samples presented pseudoplastic behavior, with a flow behavior index lower than 1, which is a desirable characteristic for cosmetics, as it improves its applicability. The mucilage demonstrates potential for application in cosmetic products, and its commercial use as an ingredient in cosmetics could be a strategic tool for the creation of a new product chain and adding value to the culture of Colocasia0 esculenta.


Design and Development of a Novel Chalcone Derivative as an Anticholinesterase Inhibitor for Possible Treatment of Dementia.
BACKGROUND Cognitive decline (e.g., memory loss), which mainly occurs in the elderly, is termed dementia. In the present study, we intended to explore the cholinesterase inhibitory activity of some novel synthesized chalcones, together with their effect on β-amyloid anti-aggregation. MATERIAL AND METHODS A novel class of chalcone derivatives have been synthesized and characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and mass and elemental analysis. These derivatives were later used for the determination of acetylcholinesterase (AChE) inhibitory and b-amyloid anti-aggregation activity. RESULTS The results of the study showed that among the developed compounds, 8g inhibits AChE more prominently than BuChE, as suggested by a selectivity index (SI) of 2.88. Furthermore, the most potent compound, 8g, showed considerable action in inhibition of β-secretase and Aβ aggregation, but not as prominent as that of curcumin as a standard. CONCLUSIONS In conclusion, our study revealed a novel class of chalcone derivatives as a selective inhibitor of AChE with considerably action against β-secretase and Aβ aggregation. Our results may be useful in developing AD drug therapy and warrant further investigation to generate more advanced analogues.


Capacity of human serum to depolymerize actin filaments.
Human blood depolymerizes filamentous (F-)actin. The interaction of actin filaments and monomers with human serum was studied by following the kinetics and extent of the depolymerization of pyrene-labeled F-actin and by analysis of serum proteins adhering to immobilized actin monomers. In physiologic Ca2+ concentrations, the depolymerization of F-actin proceeds in two stages: a rapid phase, attributed to direct severing of filaments by plasma gelsolin, and a slow phase attributed to the binding of actin monomers to vitamin D-binding protein (DBP). Without Ca2+, only the slow phase is observed. Human serum can completely depolymerize 10 to 18 mumol/L of actin, of which approximately 5 mumol/L occurs rapidly. Depolymerization can be accounted for by the normal serum concentrations of gelsolin and DBP. Fibrin(ogen) and fibronectin, which bind actin in vitro, do not contribute to the kinetics or extent of its depolymerization. Affinity chromatography and functional assays for the presence of gelsolin-actin complexes show that addition of G-actin to serum results in preferential formation of actin-DBP complexes, but that addition of F-actin to serum produces both gelsolin-actin complexes and DBP-actin complexes. The distinctive binding of actin monomers and polymers to these two serum proteins suggests a means by which their coordinated actions are maximized in vivo, from the standpoint of depolymerizing filaments and clearing monomers from the circulation.


Hydrogen bond-Driven Self-Assembly between Amidinium Cations and Carboxylate Anions: A Combined Molecular Dynamics, NMR Spectroscopy, and Single Crystal X-ray Diffraction Study.
A combination of molecular dynamics (MD), NMR spectroscopy, and single crystal X-ray diffraction (SCXRD) techniques was used to probe the self-assembly of para- and meta-bis(amidinium) compounds with para-, meta-, and ortho-dicarboxylates. Good concordance was observed between the MD and experimental results. In DMSO solution, the systems form several rapidly exchanging assemblies, in part because a range of hydrogen bonding interactions is possible between the amidinium and carboxylate moieties. Upon crystallization, the majority of the systems form 1D supramolecular polymers, which are held together by short N-H⋅⋅⋅O hydrogen bonds.


Utilizing metagenomic next-generation sequencing for diagnosis and lung microbiome probing of pediatric pneumonia through bronchoalveolar lavage fluid in pediatric intensive care unit: results from a large real-world cohort.
Metagenomic next-generation sequencing (mNGS) is a powerful method for pathogen detection in various infections. In this study, we assessed the value of mNGS in the pathogen diagnosis and microbiome analysis of pneumonia in pediatric intensive care units (PICU) using bronchoalveolar lavage fluid (BALF) samples. A total of 104 pediatric patients with pneumonia who were admitted into PICU between June 2018 and February 2020 were retrospectively enrolled. Among them, 101 subjects who had intact clinical information were subject to parallel comparison of mNGS and conventional microbiological tests (CMTs) for pathogen detection. The performance was also evaluated and compared between BALF-mNGS and BALF-culture methods. Moreover, the diversity and structure of all 104 patients' lung BALF microbiomes were explored using the mNGS data. Combining the findings of mNGS and CMTs, 94.06% (95/101) pneumonia cases showed evidence of causative pathogenic infections, including 79.21% (80/101) mixed and 14.85% (15/101) single infections. Regarding the pathogenesis of pneumonia in the PICU, the fungal detection rates were significantly higher in patients with immunodeficiency (55.56% vs. 25.30%, P =0.025) and comorbidities (40.30% vs. 11.76%, P=0.007). There were no significant differences in the α-diversity either between patients with CAP and HAP or between patients with and without immunodeficiency. Regarding the diagnostic performance, the detection rate of DNA-based BALF-mNGS was slightly higher than that of the BALF-culture although statistically insignificant (81.82% vs.77.92%, P=0.677) and was comparable to CMTs (81.82% vs. 89.61%, P=0.211). The overall sensitivity of DNA-based mNGS was 85.14% (95% confidence interval [CI]: 74.96%-92.34%). The detection rate of RNA-based BALF-mNGS was the same with CMTs (80.00% vs 80.00%, P>0.999) and higher than BALF-culture (80.00% vs 52.00%, P=0.045), with a sensitivity of 90.91% (95%CI: 70.84%-98.88%). mNGS is valuable in the etiological diagnosis of pneumonia, especially in fungal infections, and can reveal pulmonary microecological characteristics. For pneumonia patients in PICU, the mNGS should be implemented early and complementary to CMTs.


5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis.
Serotonin (5-hydroxytryptamine or 5-HT) is a neuroendocrine peptide endowed with immunomodulatory functions. Regulatory B cells (Bregs) play an important role in maintaining intestinal immune homeostasis. We analyzed the differences of 5-HT and Bregs between peripheral blood of ulcerative colitis (UC) and healthy controls (HC). Besides, 5-HT-treated B cells were adoptively transferred into colitis mice to elucidate the role of 5-HT in regulating Bregs. The level of serum 5-HT and IL-10 in UC patients was lower and both were negatively correlated with disease activity. 5-HT7 receptor (5-HT7R) was higher expressed on Bregs in UC. 5-HT promoted IL-10 production in Bregs through the activation of STAT3. And adoptive transfer of 5-HT-treated B cells alleviated intestinal inflammation via inducing IL-10-producing B cells in mice. Our results suggest that 5-HT/5-HT7R signaling pathway facilitate functional Bregs in constraining inflammation in UC, which may be a new potential prospect in the treatment of UC.


II. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: co-milling.
Nateglinide is an oral antidiabetic agent that should be administered 10-30 min before the meal, but it shows low and pH-dependent solubility that may reduce its oral bioavailability. To improve nateglinide dissolution rate, the active was co-milled with three different super-disintegrants or with some hydrophilic excipients, in 1:1, 1:2, and 1:4 drug to carrier ratio (w:w). The three super-disintegrants were crosslinked polyvinylpyrrolidone (PVPC), sodium starch glycolate (SSG) and crosslinked carboxymethyl cellulose (CMCC). The three hydrophilic excipient were amorphous silica (AS), mannitol (M) and Poloxamer (PO). A strong enhancement of drug dissolution rate was obtained from the nateglinide:super-disintegrant co-milled systems in 1:4 ratio, which can be explained by a combination of several factors: an increase in wettability, due to the hydrophilic nature of the carriers, a possible reduction of particle size and a more intimate dispersion of the drug onto the carrier, as a result of the mechanical treatment.


An imputation-based genome-wide association study on traits related to male reproduction in a White Duroc × Erhualian F2 population.
Boar reproductive traits are economically important for the pig industry. Here we conducted a genome-wide association study (GWAS) for 13 reproductive traits measured on 205 F2 boars at day 300 using 60 K single nucleotide polymorphism (SNP) data imputed from a reference panel of 1200 pigs in a White Duroc × Erhualian F2 intercross population. We identified 10 significant loci for seven traits on eight pig chromosomes (SSC). Two loci surpassed the genome-wide significance level, including one for epididymal weight around 60.25 Mb on SSC7 and one for semen temperature around 43.69 Mb on SSC4. Four of the 10 significant loci that we identified were consistent with previously reported quantitative trait loci for boar reproduction traits. We highlighted several interesting candidate genes at these loci, including APN, TEP1, PARP2, SPINK1 and PDE1C. To evaluate the imputation accuracy, we further genotyped nine GWAS top SNPs using PCR restriction fragment length polymorphism or Sanger sequencing. We found an average of 91.44% of genotype concordance, 95.36% of allelic concordance and 0.85 of r(2) correlation between imputed and real genotype data. This indicates that our GWAS mapping results based on imputed SNP data are reliable, providing insights into the genetic basis of boar reproductive traits.


Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods.
Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.


Epidemiology of Salmonella sofia in Australia.
In recent years, the incidence of isolation of Salmonella sofia in Australia has risen from 33% of all poultry isolates in 1982 to a peak of 49% of isolates in 1988. A parallel rise has not been seen in S. sofia isolated from humans. In Israel, however, S. sofia has been commonly isolated from both humans and poultry. We investigated the possibility that the Israeli strains may belong to a different clonal group and express virulence determinants not seen in the Australian isolates, accounting for the apparent differences in the virulence seen within this species. A number of S. sofia isolates from Australian chickens and humans, as well as from Israeli humans and chickens, were compared by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of outer membrane proteins, plasmid profiles, and restriction fragment length polymorphism analysis. No reproducible differences could be detected by analysis of outer membrane proteins. A small 6.4-kb plasmid, pIMVS2, was detected in all Australian isolates from chickens but not in the Israeli isolates. Restriction fragment length polymorphism studies with cosmid clones as probes provided the most discrimination among isolates, allowing us to divide them into seven groups. This technique revealed that significant differences exist between Australian and Israeli isolates and provided additional insights into the epidemiology of these Salmonella isolates.


Genetic analysis of nuclear DNA restriction fragment patterns.
Restriction fragment length polymorphism (RFLP) analysis in the broad sense is the analysis of differences in restriction fragment pattern produced by defined target segments within or between cell compartments, cell types, etc., in a single individual or in different individuals. Thus both molecular hybridization and DNA amplification by two-primer extension using the polymerase chain reaction can define target segments for RFLP analysis. The two techniques are outlined with special consideration of characteristics important for genetic analysis. The mode of inheritance of restriction fragment patterns as a prerequisite for their use as genetic markers in inheritance studies is explained, leading to criticism of common usage. The importance of internal restriction sites for the determination of allelic variation is stressed. It is shown that, if target segments are under the control of a single nuclear diploid restriction fragment locus, then complete reconstruction of all parental target segments requires controlled crosses between individuals of like restriction fragment pattern.


Environmental change and the option value of genetic diversity.
Rapid anthropogenic environmental change is altering selection pressures on natural plant populations. However, it is difficult to predict easily the novel selection pressures to which populations will be exposed. There is heavy reliance on plant genetic diversity for future crop security in agriculture and industry, but the implications of genetic diversity for natural populations receives less attention. Here, we examine the links between the genetic diversity of natural populations and aspects of plant performance and fitness. We argue that accumulating evidence demonstrates the future benefit or 'option value' of genetic diversity within natural populations when subject to anthropogenic environmental changes. Consequently, the loss of that diversity will hinder their ability to adapt to changing environments and is, therefore, of serious concern.


Photobehavior of stony corals: responses to light spectra and intensity.
Tentacle expansion and contraction were investigated in four zooxanthellate coral species and one azooxanthellate coral (Cladopsammia gracilis). Favia favus, Plerogyra sinuosa and Cladopsammia gracilis expand their tentacles at night, while tentacles in Goniopora lobata and Stylophora pistillata are expanded continuously. Light at wavelengths in the range 400-520 nm was most effective in eliciting full tentacle contraction in F. favus and in P. sinuosa. Higher light intensities in the range 660-700 nm also caused tentacle contractions in F. favus. Tentacles in C. gracilis did not respond to light. Zooxanthellar densities in tentacles were significantly higher in G. lobata, which has continuously expanded tentacles, than in F. favus and P. sinousa, where tentacles are expanded at night. Photosynthetic efficiency in F. favus and P. sinuosa was lower in specimens with contracted tentacles. However, in the dark, no differences were found in the maximum quantum yield of photochemistry in PSII (Fv/Fm) of the expanded versus the contracted tentacles of any of the four species. This work suggests that species whose tentacles remain continuously expanded have either dense algal populations in their tentacles, as in G. lobata, or minute tentacles, like S. pistillata. Dense algal populations in tentacles allow harvesting of light while small tentacles do not scatter light or shade zooxanthellae in the underlying body of the polyp.


Expression and epigenetic regulation of DACT1 and DACT2 in oral squamous cell carcinoma.
DACT genes regulates Wnt as well TGF-β pathway, and were already associated with hepatocellular and lung cancer. Alterations on Wnt/β-catenin were associated with head and neck cancer through β-catenin cytoplasmatic accumulation. The aim of the study was to evaluate DACT1 and DACT2 expression and methylation on oral squamous cell cancer (OSCC). 47 samples of salivary rinse and tissue were collected from 29 OSCC and 18 control patients. qMSP and RT-PCR reactions were performed in order to detect hypermethylation and expression of DACT1 and DACT2 genes. Statistical analysis was conducted to evaluate these genes as possible biomarkers for OSCC. As expected man over 60 years old with tobacco and alcohol consumption history were associated with OSCC. There was no statistical difference between groups concerning DACT1 and DACT2 either in promoter hypermethylation or transcript levels. Age was associated with DACT2 promoter hypermethylation, especially over 56 years old. Patients older than 56 years old were about 5 times more likely to have DACT2 promoter hypermethylation. These findings could partially explain why older subjects are more prone to carcinogenesis. Wnt/β-catenin pathway plays an important role in carcinogenesis, and the study of their regulators may help understand malignant transformation.


General prescribing principles. Supplementary prescribing: an overview.
The independent prescriber (doctor) is responsible for the diagnosis and setting the parameters of the clinical management plan. The supplementary prescriber decides on the product, dosage, frequency, and other variables within the confines of the management plan. The patient's progress must be regularly reviewed by the independent prescriber. The independent prescriber may at any time review the patient's treatment and/or resume full responsibility for the patient's care. The independent and supplementary prescriber must share a common patient record. There must be a good working relationship between the prescribers. Nurse prescribers need to be clear at all times which prescribing regime they are working under--district nurse/health visitor prescriber, extended formulary nurse prescriber or supplementary prescriber.


Exercise-induced hypoxia secondary to an atrial septal defect and cor triatriatum dexter.
A 14-year-old boy presented to us with a diagnosis of severe asthma and oxygen desaturation of 76% on a 6-minute-walk test. A contrast echocardiogram revealed echocontrast in the left and right atria simultaneously. A secundum atrial septal defect and partial cor triatriatum dexter were diagnosed, and the atrial defect was closed by cardiac catheterisation.


Birth Admission Length-of-Stay and Hospital Readmission in Children With Congenital Diaphragmatic Hernia.
The objective of this study was to identify factors associated with prolonged birth admission length of stay (LOS) and to evaluate the association between these characteristics and readmission in the year following discharge for children with congenital diaphragmatic hernia (CDH). This was a single-center retrospective cohort study of children with isolated CDH born in the Special Delivery Unit and admitted to the Newborn/Infant Intensive Care Unit at Children's Hospital of Philadelphia from April 2008 to August 2019. Birth admission hospitalization was categorized into 3 groups (≤35, 36-75, and >76 days) based on the data distribution. Participant factors included gestational age (days), side of CDH (right/left), liver position (up/down), CDH repair technique (open/minimally invasive), exposure to extracorporeal membrane oxygenation, lung-to-head circumference ratio, and feeding tube at discharge. Chi-squared, t-tests and analysis of variance were used to examine bivariable associations between participant characteristics, birth admission LOS and readmission in the year following initial hospital discharge. Multivariable logistic regression was used to evaluate factors associated with readmission. Children hospitalized ≥76 days at birth had 4.33 (95% CI: 1.2, 15.2) higher odds of readmission than those admitted for ≤35 days. Children with a non-operative feeding tube at discharge had 4.12 (895% CI: 1.6, 10.5) higher odds of readmission when compared to those with no feeding tube at discharge. Longer birth hospitalization and non-operative feeding tube are associated with increased readmissions in the year after discharge. Level III.


Evaluation of clinical guidelines for the management of Staphylococcus aureus bacteraemia.
While treatment guidelines have been developed to guide the management of Staphylococcus aureus bacteraemia, there is a need to validate these guidelines in different clinical settings and to relate the effect of compliance to clinical outcome. To assess the impact of adherence to treatment guidelines on clinical outcome and to explore the role of transoesophageal echocardiography (TOE) in risk stratification. We undertook a 2-year mixed retrospective and prospective study of all cases of S. aureus bacteraemia at Fremantle Hospital, documenting the clinical and microbiological features of each case, the results of echocardiography, adherence with published clinical guidelines and clinical outcome. Failure to comply with guidelines was observed in 41% (38 of 93) of cases, the majority receiving abbreviated treatment. An increased rate of relapse was observed among patients who received inadequate therapy (5/38 vs 1/55; P= 0.04). Ten of 28 eligible patients underwent TOE and the test led to significant changes in management in two of those cases. While non-adherence with clinical guidelines was associated with an increased risk of relapse, the role of TOE in risk stratification was limited by factors including cost, limited acceptance of the test and the need for prolonged therapy for other indications.


Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity outcomes in a Brazilian cohort.
Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for muscle invasive bladder cancer and the oncologic outcomes following it are directly related to disease pathology and surgical technique. Therefore, we sought to analyze these features in a cohort from a Brazilian tertiary oncologic center and try to identify those who could negatively impact on the disease control. We identified 128 patients submitted to radical cystectomy, for bladder cancer treatment, from January 2009 to July 2012 in one oncology tertiary referral public center (Mario Penna Institute, Belo Horizonte, Brazil). We retrospectively analyzed the findings obtained from their pathologic report and assessed the complications within 30 days of surgery. We showed similar pathologic and surgical findings compared to other large series from the literature, however our patients presented with a slightly higher rate of pT4 disease. Positive surgical margins were found in 2/128 patients (1.5%). The médium number of lymph nodes dissected were 15. Major complications (Clavien 3 to 5) within 30 days of cystectomy occurred in 33/128 (25.7%) patients. In the management of invasive bladder cancer, efforts should focus on proper disease diagnosis and staging, and, thereafter, correct treatment based on pathologic findings. Furthermore, extended LND should be performed in all patients with RC indication. A critical analysis of our complications in a future study will help us to identify and modify some of the factors associated with surgical morbidity.


The tissue-specific processing of pro-opiomelanocortin.
It is just over 30 years since the definitive identification of the adrenocorticotrophin (ACTH) precursor, pro-opiomelanocotin (POMC). Although first characterised in the anterior and intermediate lobes of the pituitary, POMC is also expressed in a number of both central and peripheral tissues including the skin, central nervous tissue and placenta. Following synthesis, POMC undergoes extensive post-translational processing producing not only ACTH, but also a number of other biologically active peptides. The extent and pattern of this processing is tissue-specific, the end result being the tissue dependent production of different combinations of peptides from the same precursor. These peptides have a diverse range of biological roles ranging from pigmentation to adrenal function to the regulation of feeding. This level of complexity has resulted in POMC becoming the archetypal model for prohormone processing, illustrating how a single protein combined with post-translational modification can have a diverse number of roles.


Lipid-induced conformational switch in the membrane binding domain of CTP:phosphocholine cytidylyltransferase: a circular dichroism study.
CTP:phosphocholine cytidylyltranferase (CCT) regulates phosphatidylcholine (PC) biosynthesis. Its activity is controlled by reversible interactions with membrane lipids, mediated by an internal segment referred to as domain M. Although domain M peptides adopt an amphipathic alpha-helical structure when membrane bound, the structure of this domain in the context of the whole enzyme in the lipid-free and lipid-bound state is unknown. Here we derive lipid-induced secondary structural changes in CCTalpha using circular dichroism and three deconvolution programs. The analysis of two fragments, CCT236 (CCT1-236, housing the catalytic domain) and a synthetic domain M peptide (CCT237-293) aided the assignment of structural change to specific domains. To carry out this study, we developed a micellar lipid activating system that would avoid generation of CCT-induced lipid vesicle aggregates that interfere with the CD analysis. Lysophosphatidylcholine/phosphatidylglycerol (LPC/PG) mixed micelles supported full activation of CCT and caused an increase in the alpha-helix content of full-length CCT from 25 to 41%, at the expense of all other conformations. LPC/PG also induced an increase in alpha-helix content of the domain M peptide from 7 to 85% at the expense of all other conformers. This lipid system did not significantly affect the secondary structure of CCT236, nor did it affect the proteolytic fragmentation pattern of this region within full-length CCT, suggesting that the region containing the catalytic domain changes very little upon membrane activation of CCT. Our data suggest that lipids trigger a conformational switch in domain M from a mixed structure to an alpha-helix, thus creating a hydrophobic face for membrane insertion. Our results negate the idea that domain M is entirely helical in both the soluble and membrane-bound forms of CCT.


Analysis of the impact of optical aberrations in en-face full-field OCT microscopy.
Optical coherence tomography (OCT) is a powerful technique for cross-sectioning imaging. However, the lateral resolution may be degraded by optical aberrations originating from the sample or the setup. We present an extensive quantitative study of the impact of aberrations in time-domain en-face full-field OCT (FFOCT). Using an adaptive optics loop integrated in an FFOCT setup, a deformable mirror is used to introduce low-order calibrated aberrations. The experimental analysis of both the line spread functions (SF) and the complex object images has allowed us to measure the loss in contrast and the impact on lateral spatial resolution. We demonstrate that the frequency content of FFOCT image spectra in terms of signal-to-noise ratio and cutoff frequency is degraded by aberrations but remains much higher than in conventional incoherent images. Line SF profiles in conventional imaging display widening, whereas in FFOCT they display oscillations, leading to the possible perception of preserved resolution. Nevertheless, for complex objects, the aberration image blurring is strong due to the convolution process by the point SF, resulting in a significant filtering of the image spatial spectrum.


Antibiotic resistance in the staphylococci.
There has been much interest in the media, international as well as national, on the potential for the development of "superbugs' by which is usually meant pathogenic bacteria resistant to all available antibiotics. Two of the genera most often thought to fall into this category are the staphylococci (MRSA or Methicillin Resistant Staphylococcus aureus) and the enterococci (VRE or Vancomycin Resistant Enterococci) and although this article concentrates on the staphylococci the two share much in the way of transmissible genes.


The characterization of snake venoms using capillary electrophoresis in conjunction with electrospray mass spectrometry: Black Mambas.
Capillary electrophoresis has been used in conjunction with electrospray mass spectrometry using both full-scan and selected ion monitoring modes to supply as much information as possible about the venom of Dendroaspis polylepis polylepis (Black Mamba). As an example of the application of capillary electrophoresis/electrospray mass spectrometry (CE/ESI/MS) to the analysis of a complex mixture of small proteins, we have analyzed the venom of Dendroaspis polylepis polylepis using the combined techniques. Both full-scan and selected ion monitoring modes were employed. CE/ESI/MS provides a rapid and extremely sensitive method for molecular weight determination, particularly when selected ion monitoring is employed. It has been utilized to provide sequence confirmation for those toxins which have already been described in the literature. Our methodology indicates the presence of at least 70 peptides in the molecular weight range 6000-9000.


What factors are associated with high-frequency drug treatment use among a racially and ethnically diverse population of injection drug users?
This study explored the frequency of drug treatment utilization by 36,081 injection drug users (IDUs) in Massachusetts, 1996-2002. A number of multiple and logistic regression analyses examined the relationship between demographic characteristics, parental status, level of and type of drug use, history of mental health treatment use, types of drug treatment entered, and the number of times an IDU had entered drug treatment for the seven-year time period. Homelessness, using heroin as the primary drug of choice, and health insurance status were all associated with number of treatments entered. Logistic regression analysis identified that health insurance was a key factor associated with more frequent treatment: those with private health insurance were ten times more likely to be in the 90th percentile (12-107 entries) with respect to number of treatment entries.


Comparison of neuronal selectivity for stimulus speed, length, and contrast in the prestriate visual cortical areas V4 and MT of the macaque monkey.
1. Prestriate area V4 and the middle temporal area (MT) compose the first stage in which the ventral and dorsal visual cortical pathways are segregated. To better known the functional dichotomy between the two pathways at this level, we recorded cell responses from V4 and MT using anesthetized, immobilized macaque monkeys and compared the selectivity for speed of stimulus motion and stimulus length and the sensitivity to luminance contrast between the two areas. 2. V4 cells were as selective as MT cells for speed. The sharpness of tuning was not different between the two populations. The optimal speed varied widely in both areas, but both of the two distributions showed peaks at 32 degrees/s. 3. V4 and MT cells were similar in that about one-half of the cells (45% in V4 and 48% in MT) showed inhibition by long (16 degrees) bars. However, V4 cells preferred stimuli whose lengths were distributed around the lengths of the receptive field, whereas an overwhelming majority of MT cells preferred stimuli whose lengths were much shorter than the lengths of the receptive field. 4. The cutoff contrast at which one-half the maximum response was elicited was distributed widely in both areas, and the two distributions considerably overlapped. MT cells as a whole, however, were slightly more sensitive to the luminance contrast than V4 cells. 5. There was a tendency toward local clustering for cells with similar speed preferences in MT but not in V4. Pairs of MT cells recorded within 400 microns had smaller difference in the optimal speed than that of cell pairs taken randomly from the whole sample of MT cells.


[Validation of the PCR-based universal heteroduplex generator assay for identification of rifampicin-resistant and multiresistant Mycobacterium tuberculosis in Lima, Peru].
To validate the polymerase chain reaction-based universal heteroduplex generator (PCR UHG-Rif) assay for identifying rifampin-resistant and multidrug-resistant (MDR, resistant to isoniazid and rifampin) Mycobacterium tuberculosis in patients with pulmonary tuberculosis from communities in Lima (Peru) with a high incidence of resistant tuberculosis. To compare the results of antituberculosis drug susceptibility testing in clinical samples performed by the proportion method with those obtained by the PCR UHG-Rif assay, with the aim of analyzing the diagnostic capability of PCR UHG-Rif. Concordance for the identification of antituberculosis drug susceptibility was 0.95 (kappa = 0.899; P < .05), with a sensitivity and specificity of 0.973 and 0.922 (P < .05), respectively. The positive predictive value was 0.939 (95% CI: 0.879-0.970) and the negative predictive value was 0.965 (95% CI: 0.902-0.988). Nevertheless, the probability for MDR prediction was 0.981 (P < .05). PCR UHG-Rif allows the detection of mixed populations; discordant results can be explained by the presence of point mutations, missense mutations and mutations outside the rpoB "hot" region associated with rifampin-resistance. The PCR UHG-Rif assay detects mutations in the rpoB gene with excellent sensitivity and specificity, and suitable predictive values when compared with the standard method for determining susceptibility to antituberculosis drugs. This test can be considered an excellent tool that can contribute to tuberculosis control by correctly identifying patients infected with resistant and MDR bacilli, leading to a reduction in the cases of tuberculosis and resistant tuberculosis.


Metabolic changes of human dental pulp after rapid palatal expansion.
To investigate rapid palatal expansion (RPE)-induced metabolic changes in human dental pulp by measuring the expression and activity of aspartate aminotransferase (AST). mRNA and protein levels of AST in human dental pulp were measured by quantitative real-time polymerase chain reaction and Western blot, respectively. Furthermore, the activity of AST was measured by a full automatic biochemical analyzer. AST mRNA and protein levels were found to be expressed in normal dental pulp. Moreover, the expression of AST was increased significantly after 14 days of RPE and then decreased at 1 month in retention. Three and 6 months after RPE, the AST expression level was gradually decreased to its baseline level. Similarly, AST activity was significantly elevated after 14 days of RPE, which was then down-regulated at 1 month in retention but was still kept at a higher level as compared with the control group. The enzymatic activity of AST was slowly decreased to its baseline level at 3 and 6 months in retention. These results showed that significant reversible metabolic changes occurred in dental pulp during RPE, which revealed the high capacity of the pulp tissue for adaptation to this orthopedic method.


Stimulation of glutathione absorption in rat small intestine by alpha-adrenergic agonists.
The alpha-adrenergic agonist, phenylephrine (1.6 microM), caused a threefold stimulation of glutathione (GSH) transport from the lumen into the vasculature in isolated, vascularly perfused rat small intestine. Stimulation of GSH transport by phenylephrine was blocked by the alpha-adrenergic antagonists, prazosin or phentolamine. Norepinephrine and epinephrine (both alpha and beta agonists) also stimulated GSH absorption but not to the same extent as phenylephrine. Isoproterenol, a strict beta-adrenergic agonist, had no effect on the rate of GSH absorption. Under physiological luminal GSH concentrations, phenylephrine stimulated GSH efflux from the lumen, accumulation in the intestinal mucosa, and transport into the mesenteric vasculature. Phenylephrine did not stimulate the transport of polyethylene glycol, a high molecular weight molecule, and stimulated uptake of cysteine and glycine by 30%. This suggests that the effect of phenylephrine on GSH transport is not due to enhanced bulk flow through paracellular pathways. Studies with isolated small intestinal epithelial cells showed that phenylephrine also stimulated the release of GSH from the cells. Oral administration of phenylephrine with GSH caused a two- to fivefold transient increase in plasma GSH concentrations in rats. Phenylephrine alone or with the amino acid constituents of GSH caused no increase in plasma GSH concentration. Thus, absorption of dietary GSH is under hormonal regulation. The physiological importance of this regulation is not known, although such regulation may function to control utilization of dietary GSH for detoxication and may have therapeutic benefits for individuals with deficient GSH or increased risk of oxidative or chemically induced injury.


Investigation of the effect of phlomisoside F on complete Freund's adjuvant-induced arthritis.
Phlomis younghusbandii Mukerjee (Labiatae) has been reported to be effective in the treatment of rheumatoid arthritis (RA). In the present study, the anti-inflammatory and anti-arthritic effects of phlomisoside F (PF), isolated from P. younghusbandii Mukerjee (Labiatae), were investigated in male Wistar rats subjected to carrageen-induced paw edema and complete Freund's adjuvant (CFA)-induced arthritis. Arthritis scores were evaluated by a 5-point ordinal scale (scores 0-4). Expression levels of TNF-α, IL-1β, IL-6, IL-10, COX-2 and 5-LOX were determined via ELISA and western blot assays. Subsequent to establishing the edema and arthritis models, oral administration of PF (5, 10 and 20 mg/kg) significantly inhibited mean edema rate, compared with the control group in carrageenan-induced paw edema assay. In addition, administration of PF (5, 10 and 20 mg/kg/day) for 28 days markedly exhibited an anti-arthritic activity by offsetting the body weight loss, inhibiting the paw edema, reducing the arthritis scores and the indices of thymus and spleen, inhibiting the expression levels of TNF-α, IL-1β, IL-6, COX-2 and 5-LOX, and increasing the expression of IL-10, when compared with the respective control group in CFA-induced arthritis assay. In conclusion, PF is a valuable anti-arthritic constituent of P. younghusbandii, and the present study results suggest that this herb may be used in the treatment of RA.


Effect of Surface Properties on the Photo-Induced Crawling Motion of Azobenzene Crystals on Glass Surfaces.
Photo-induced crawling motion of a crystal of 3,3'-dimethylazobenzene (DMAB) on a glass substrate having different surface properties was studied. When exposed to UV and visible lights simultaneously from different directions, crystals crawl continuously on a glass surface. On a hydrophilic surface, the crystals crawled faster than those on other surfaces but crystals showed spreading while they moved. On hydrophobic surfaces, on the other hand, the crystals showed little shape change and slower crawling motion. The contact angles of the liquid phase of DMAB on surface-modified glass substrates showed positive correlation with the water contact angles. The interaction of melted azobenzene with glass surfaces plays an important role for the crawling motion. We proposed models to explain the asymmetric condition that leads to the directional motion. Specifically by considering the penetration length of UV and visible light sources, it was successfully shown that the depth of light penetration is different at the position of a crystal. This creates a nonequilibrium condition where melting and crystallization are predominant in the same crystal.


Integration of molecular imaging in the personalized approach of patients with adrenal masses.
Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [18F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [18F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.


MYOPIC CHOROIDAL NEOVASCULARIZATION: Diagnosis and Treatment.
To review and summarize the latest developments in the diagnosis and management of myopic choroidal neovascularization (mCNV). A review of the literature was performed, focusing on tests and investigations for diagnosing mCNV, as well as the key treatment options available for mCNV. Standard essential tests and investigations for diagnosing mCNV include spectral-domain optical coherence tomography for screening, fluorescein angiography for confirmation, and indocyanine green angiography and fundus autofluorescence for providing supplementary information. The current first line treatment of mCNV is the use of anti-vascular endothelial growth factor therapy. Various investigations can assist the differentiation of mCNV from other coexisting retinal pathologies associated with myopia or choroidal neovascularization resulting from other causes. Prompt use of anti-vascular endothelial growth factor therapy has good efficacy and safety in the treatment of mCNV.


Theoretical investigation of the reaction mechanism for the phosphate diester hydrolysis using an asymmetric dinuclear metal complex as a biomimetic model of the purple acid phosphatase enzyme.
In this work we have applied quantum mechanical calculations, at the density functional theory level, to investigate the phosphate diester hydrolysis promoted by a cationic heterodinuclear Fe(III)...Zn(II) complex that mimics the structural and functional properties of the purple acid phosphatase (PAP) enzymes. The hydrolysis of the dimethyl phosphate diester was investigated in the gas phase and in solution by means of the continuum PCM model, using the B3LYP hybrid exchange-correlation functional. Our computed results showed that the hydrolysis of the dimethyl phosphate ester takes place in two steps. The first step corresponds to a slow P-O bond formation through nucleophilic attack of the coordinated (Fe(III))-OH group. The second step consists of a proton transfer process followed by the release of a methanol molecule. The first step is rate determining with activation free energy of 12.3 kcal mol(-1), which is about 3 times lower than the activation free energy for the uncatalyzed reaction. We also show that the heterodinuclear site plays an important role favoring an associative mechanism for the phosphate diester hydrolysis, favoring the formation of a high energy intermediate phosphorane, and orienting the phosphate group to the nucleophilic attack.


Recent Advances on Nutrition in Treatment of Acute Pancreatitis.
Acute pancreatitis (AP) is a common abdominal acute inflammatory disorder and the leading cause of hospital admission for gastrointestinal disorders in many countries. Clinical manifestations of AP vary from self-limiting local inflammation to devastating systemic pathological conditions causing significant morbidity and mortality. To date, despite extensive efforts in translating promising experimental therapeutic targets in clinical trials, disease-specific effective remedy remains obscure, and supportive care has still been the primary treatment for this disease. Emerging evidence, in light of the current state of pathophysiology of AP, has highlighted that strategic initiation of nutrition with appropriate nutrient supplementation are key to limit local inflammation and to prevent or manage AP-associated complications. The current review focuses on recent advances on nutritional interventions including enteral versus parenteral nutrition strategies, and nutritional supplements such as probiotics, glutamine, omega-3 fatty acids, and vitamins in clinical AP, hoping to advance current knowledge and practice related to nutrition and nutritional supplements in clinical management of AP.


Anti-Corrosion Property of Glass Flake Reinforced Chemically Bonded Phosphate Ceramic Coatings.
Glass flake (GF) was used as the reinforcement in chemically bonded phosphate ceramic (CBPC) coatings to promote anti-corrosion property. The crystalline phase, curing behavior, micromorphology and electrochemical performance of the coatings were studied. The results indicate that with the addition of magnesia (MgO), a new bonding phase (Mg3(PO4)2) can be formed, which can help the CBPCs achieve a more compact and denser structure. The effect of the magnesia and the GF additives on curing behavior is obvious: the heat of reaction of the phosphate ceramic materials increases with the addition of the magnesia and the GF, which emphasizes the higher crosslinking density in the phosphate ceramic materials. The phosphate ceramic coatings with the magnesia have a higher impedance value compared with the neat phosphate ceramic coating, while the highest impedance value is obtained with increased content of GF. The corrosion mechanism is mainly contributed by the new bonding phase and GF particles, which can hinder the permeation pathway and make the permeation more circuitous.


Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia). Prospective, multi-centre, observational study. pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness. A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 μm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness. The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 μm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.


[Research progress on attention level evaluation based on electroencephalogram signals].
Attention level evaluation refers to the evaluation of people's attention level through observation or experimental testing, and its research results have great application value in education and teaching, intelligent driving, medical health and other fields. With its objective reliability and security, electroencephalogram signals have become one of the most important technical means to analyze and express attention level. At present, there is little review literature that comprehensively summarize the application of electroencephalogram signals in the field of attention evaluation. To this end, this paper first summarizes the research progress on attention evaluation; then the important methods for electroencephalogram attention evaluation are analyzed, including data preprocessing, feature extraction and selection, attention evaluation methods, etc.; finally, the shortcomings of the current development in the field of electroencephalogram attention evaluation are discussed, and the future development trend is prospected, to provide research references for researchers in related fields.


Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase.
Compartment-specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol-4-phosphate [PI(4)P] in response to nutrient levels and cell growth stages. During exponential growth, Sac1p interacts with Dpm1p at the ER but shuttles to the Golgi during starvation. Here, we report that a C-terminal region in Sac1p is required for retention in the perinuclear ER, whereas the N-terminal domain is responsible for Golgi localization. We also show that starvation-induced shuttling of Sac1p to the Golgi depends on the coat protein complex II and the Rer1 adaptor protein. Starvation-induced shuttling of Sac1p to the Golgi specifically eliminates a pool of PI(4)P generated by the lipid kinase Pik1p. In addition, absence of nutrients leads to a rapid dissociation of Pik1p, together with its non-catalytical subunit Frq1p, from Golgi membranes. Reciprocal rounds of association/dissociation of the Sac1p lipid phosphatase and the Pik1p/Frq1p lipid kinase complex are responsible for growth-dependent control of Golgi phosphoinositides. Sac1p and Pik1p/Frq1p are therefore elements of a unique machinery that synchronizes ER and Golgi function in response to different growth conditions.


Design, synthesis and evaluation of fluorocarbons and surfactants for in vivo applications. New perfluoroalkylated polyhydroxylated surfactants.
The progress achieved since the advent of Fluosol-DA is summarized in this paper, with special focus on the synthesis and evaluation of more adequate, reliable, industrially feasible fluorocarbons, structure/property relationships--molecular weight being recognized as the pre-eminent determining factor of both the fluorocarbon's excretion rate and the emulsion's stability-, the preparation of significantly more concentrated, more efficacious emulsions, etc. The key to further progress and better mastery of the emulsions' characteristics, especially in relation to increased shelf-life, prolonged i.v. persistence, and versatility, now lies in the development of new surfactants, better adapted to this objective. New families of well defined, monodisperse perfluoroalkylated polyhydroxylated surfactants derived from sugars and related compounds have been synthesized and fully characterized. Preliminary evaluation of their surface-active properties, emulsion stabilizing capacity and biocompatibility are reported.


Synthesis and curing of hyperbranched poly(triazole)s with click polymerization for improved adhesion strength.
We successfully synthesized hyperbranched poly(triazole)s by in situ click polymerization of diazides 1 and triyne 2 monomers on different metal surfaces (copper, iron, and aluminum) and characterized their adhesive properties. Optimizations were performed to obtain high adhesive strength at different temperatures by analyzing the effects of curing kinetics, annealing temperature and time, catalyst, monomer ratio, surface conditions, alkyl chain length of diazides 1, etc. The adhesive bonding strength with metal substrate is 2 orders of magnitude higher than similar hyperbranched poly(triazole)s made by click polymerization and clearly higher than some commercial adhesives at elevated temperatures. With the same conditions, adhesives prepared on aluminum and iron substrates have higher adhesive strength than those prepared on copper substrate, and an excess of triyne 2 monomer in synthesis has greater adhesive strength than an excess of diazide 1 monomer. Tof-SIMS experiment was employed to understand these phenomena, and the existence of an interphase between the polymer and metal surface was found to be critical for adhesive bonding with thicker interphase (excess of triyne 2 monomer) and the higher binding energy between polymer atoms and substrate atoms (e.g., aluminum substrate) generating the higher bonding strength. In addition, the light-emitting property of synthesized polymers under UV irradiation can be used to check the failure mode of adhesive bonding.


Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients.
OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM = IGT +/- hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%)--without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7-18.0) vs. 7.0 (2.3-18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3-7.0) vs. 2.5 (0.7-7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.


The value of 18F-FDG-PET/CT in the diagnosis of solitary pulmonary nodules: A meta-analysis.
Solitary pulmonary nodules (SPNs) are common imaging findings. Many studies have indicated that F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) is an accurate test for distinguishing benign and malignant SPNs. The aim of this study was to investigate the value of F-FDG-PET/CT in the diagnosis of malignant SPNs. We systematically searched the PubMed and Embase databases up to March 2017, and published data on sensitivity, specificity, and other measures of diagnostic accuracy of F-FDG-PET/CT in the diagnosis of malignant SPNs were meta-analyzed. Statistical analyses were undertaken using Meta-DiSc 1.4 software and Stata version 12.0. The measures of accuracy of F-FDG-PET/CT in the diagnosis of malignant SPNs were pooled using random-effects models. A total of 20 publications reporting 21 studies were identified. Pooled results indicated that F-FDG-PET/CT showed a diagnostic sensitivity of 0.89 (95% confidence interval [CI], 0.87-0.91) and a specificity of 0.70 (95% CI, 0.66-0.73). The positive likelihood ratio was 3.33 (95% CI, 2.35-4.71) and the negative likelihood ratio was 0.18 (95% CI, 0.13-0.25). The diagnostic odds ratio was 22.43 (95% CI, 12.55-40.07). F-FDG-PET/CT showed insufficient sensitivity and specificity for diagnosing malignant SPNs; it cannot replace the "gold standard" pathology by resection or percutaneous biopsy. Larger studies are required for further evaluation.


Ligand induced ferromagnetism in ZnO nanostructures.
Complementary to the experimental finding that ZnO nanoparticles become ferromagnetic when coated with N and S containing ligands such as dodecylamine and dodecanethiol [Garcia et al., Nano Lett. 7, 1489 (2007)], we provide the first theoretical understanding of the origin of magnetism in ligated ZnO nanoparticles as well as the structural properties of the ligated systems by using density functional theory and generalized gradient approximation for exchange and correlation, and a cluster model for the nanoparticles. We show that N or S atoms of the ligand bind to the Zn sites. The accompanying changes in the Zn-O bond length, hybridization between Zn 4s orbitals with N 2p or S 3p orbitals, and consequently the redistribution of charges between Zn and O atoms result in a magnetic system where the 2p electrons in O and N, and 3p electrons in S sites are spin polarized. Furthermore, the sites nearest to the Zn atom attached to the ligand carry bulk of the magnetic moment. Studies, as a function of cluster size, also illustrate that magnetism resides only on the surface. Our results confirm that the use of ligands can pave a new way for introducing magnetism in ZnO nanostructures, which can be used to develop magnetic sensors to detect N and S containing molecules.


Impact of cannibalism on predator-prey dynamics: size-structured interactions and apparent mutualism.
Direct and indirect interactions between two prey species can strongly alter the dynamics of predator-prey systems. Most predators are cannibalistic, and as a consequence, even systems with only one predator and one prey include two prey types: conspecifics and heterospecifics. The effects of the complex direct and indirect interactions that emerge in such cannibalistic systems are still poorly understood. This study examined how the indirect interaction between conspecific and heterospecific prey affects cannibalism and predation rates and how the direct interactions between both species indirectly alter the effect of the cannibalistic predator. I tested for these effects using larvae of the stream salamanders Eurycea cirrigera (prey) and Pseudotriton ruber (cannibalistic predator) by manipulating the relative densities of the conspecific and heterospecific prey in the presence and absence of the predator in experimental streams. The rates of cannibalism and heterospecific predation were proportional to the respective densities and negatively correlated, indicating a positive indirect interaction between conspecific and heterospecific prey, similar to "apparent mutualism." Direct interactions between prey species did not alter the effect of the predator. Although both types of prey showed a similar 30% reduction in night activity and switch in microhabitat use in response to the presence of the predator, cannibalism rates were three times higher than heterospecific predation rates irrespective of the relative densities of the two types of prey. Cumulative predation risks differed even more due to the 48% lower growth rate of conspecific prey. Detailed laboratory experiments suggest that the 3:1 difference in cannibalism and predation rate was due to the higher efficiency of heterospecific prey in escaping immediate attacks. However, no difference was observed when the predator was a closely related salamander species, Gyrinophilus porphyriticus, indicating that this difference is species specific. This demonstrates that cannibalism can result in the coupling of predator and prey mortality rates that strongly determines the dynamics of predator-prey systems.


Calculations of n→π* Transition Energies: Comparisons Between TD-DFT, ADC, CC, CASPT2, and BSE/GW Descriptions.
Using a large panel of theoretical approaches, namely, CC2, CCSD, CCSDR(3), CC3, ADC(2), ADC(3), CASPT2, time-dependent density functional theory (TD-DFT), and BSE/evGW, the two latter combined with different exchange-correlation functionals, we investigate the lowest singlet transition in 23 n→π* compounds based on the nitroso, thiocarbonyl, carbonyl, and diazo chromophores. First, for 16 small derivatives we compare the transition energies provided by the different wave function approaches to define theoretical best estimates. For this set, it surprisingly turned out that ADC(2) offers a better match with CC3 than ADC(3). Next, we use 10 functionals belonging to the "LYP" and "M06" families and compare the TD-DFT and the BSE/evGW descriptions. The BSE/evGW results are less sensitive than their TD-DFT counterparts to the selected functional, especially in the M06 series. Nevertheless, BSE/evGW delivers larger errors than TD-CAM-B3LYP, which provides extremely accurate results in the present case, especially when the Tamm-Dancoff approximation is applied. In addition, we show that, among the different starting points for BSE/evGW calculations, M06-2X eigenstates stand as the most appropriate. Finally, we confirm that the trends observed on the small compounds pertain in larger molecules.


Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.
Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.


Determinants of stunting among children under age five in Burundi: Evidence from the 2016-2017 Burundi Demographic and Health Survey (BDHS 2016-17).
Burundi has one of the highest prevalence of stunting in the world. This study aimed to identify determinants of stunting among children under age five in Burundi. A total of 4993 children with anthropometric measurements from the 2016-2017 Burundi Demographic and Health Survey were included in the study. Stunting was assessed from the height-for-age Z-scores (HAZ). Logistic regression models were analyzed to identify demographic, maternal, child-related, and structural variables that influence stunting. In total, 56.9% of children under age five were stunted, of those 31.0% moderately and 25.9% severely. Multivariable logistic regression indicated that older children, male children (adjusted OR (aOR) = 1.41, 95% CI 1.24-1.61), and children who were perceived as small (aOR = 2.00, 95% CI 1.55-2.59) or very small at birth (aOR = 2.37, 95% CI 1.57-3.59) were significantly more likely to be stunted. Moreover, children of single mothers, with lower levels of education, who were underweight at the time of the survey (aOR = 1.95, 95% CI 1.42-2.68), who had short stature (aOR = 3.76, 95% CI 2.50-5.66) or who conceived more than four children (aOR = 1.22, 95% CI 1.05-1.42) were more commonly stunted. Stunting was more prevalent in rural areas (aOR = 2.53, 95% CI 1.72-3.73) and in households with no access to improved types of toilet facilities (aOR = 1.27, 95% CI 1.10-1.45). The results of this study show that the prevalence of stunting in children under age five in Burundi is alarmingly high and underscores the urgent need for decisive and determined action.


Multimodal treatment in children and adolescents with attention-deficit/hyperactivity disorder: a 6-month follow-up.
Different treatment approaches aimed at reducing attention-deficit/hyperactivity disorder (ADHD) core symptoms are available. However, factors such as intolerance, side-effects, lack of efficacy, high new technology costs, and placebo effect have spurred on an increasing interest in alternative or complementary treatment. The aim of this study is to explore efficacy of multimodal treatment consisting of standard stimulant medication (methylphenidate) and neurofeedback (NF) in combination, and to compare it with the single treatment in 6-month follow-up in ADHD children and adolescents. This randomized controlled trial with 6-month follow-up comprised three treatment arms: multimodal treatment (NF + MED), MED alone, and NF alone. A total of 130 ADHD children/adolescents participated, and 62% completed the study. ADHD core symptoms were recorded pre-/post-treatment, using parents' and teachers' forms taken from Barkley's Defiant Children: A Clinician's Manual for Assessment and Parent Training, and a self-report questionnaire. Significant ADHD core symptom improvements were reported 6 months after treatment completion by parents, teachers, and participants in all three groups, with marked improvement in inattention in all groups. However, no significant improvements in hyperactivity or academic performance were reported by teachers or self-reported by children/adolescents, respectively, in the three groups. Changes obtained with multimodal treatment at 6-month follow-up were comparable to those with single medication treatment, as reported by all participants. Multimodal treatment using combined stimulant medication and NF showed 6-month efficacy in ADHD treatment. More research is needed to explore whether multimodal treatment is suitable for ADHD children and adolescents who showed a poor response to single medication treatment, and for those who want to reduce the use of stimulant medication.


25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis.
The role of Vitamin D in the development of type 1 diabetes (T1D) is controversial. The Canary Islands have the highest incidence of childhood-onset T1D in Spain and one of the highest in Europe. We aimed to evaluate 25OHVitamin D concentrations in a Canarian pediatric population, to assess the existence of seasonal variation, to study their association with T1D, and to evaluate the role of acidosis in its levels. In a retrospective, case-control study, we obtained data from 146 T1D patients (<15 years of age) and 346 control children; 25OHVitamin D concentrations were assessed in serum by automatic ChemiLuminescence ImmunoAssay technology. We found significantly higher 25OHVitamin D levels in the summer and autumn months and an inverse correlation between T1D and age; 25OHVitamin D sufficiency was similar in both groups (44.5% vs. 45.1%), with significant differences in the percentage of patients presenting vitamin D deficiency (11.6% (T1D) vs. 16.4% (controls)). When stratified according to the presence of ketoacidosis at sampling, only patients with acidosis showed lower 25OHVitamin D concentrations than controls. Despite its subtropical geographic location, Vitamin D deficiency is frequent in children in Gran Canaria, and 25OHVitamin D concentrations show seasonal variation. After adjusting for acidosis, no differences were found between children with and without T1D.


Frontiers in planning optimization for lung SBRT.
Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation therapy (SBRT) in lung cancer management. In this context, the very high doses delivered to the Planning Target Volume, make the planning phase essential for achieving high dose levels conformed to the shape of the target in order to have a good prognosis for tumor control and to avoid an overdose in relevant healthy adjacent tissue. In this non-systematic review we analyzed the technological and the physics aspects of SBRT planning for lung cancer. In particular, the aims of the study were: (i) to evaluate prescription strategies (homogeneous or inhomogeneous), (ii) to outline possible geometrical solutions by comparing the dosimetric results (iii) to describe the technological possibilities for a safe and effective treatment, (iv) to present the issues concerning radiobiological planning and the automation of the planning process.


Examining the Frequency and Contribution of Foods Eaten Away From Home in the Diets of 18- to 30-Year-Old Australians Using Smartphone Dietary Assessment (MYMeals): Protocol for a Cross-Sectional Study.
Young Australians aged between 18 and 30 years have experienced the largest increase in the body mass index and spend the largest proportion of their food budget on fast food and eating out. Frequent consumption of foods purchased and eaten away from home has been linked to poorer diet quality and weight gain. There has been no Australian research regarding quantities, type, or the frequency of consumption of food prepared outside the home by young adults and its impact on their energy and nutrient intakes. The objective of this study was to determine the relative contributions of different food outlets (eg, fast food chain, independent takeaway food store, coffee shop, etc) to the overall food and beverage intake of young adults; to assess the extent to which food and beverages consumed away from home contribute to young adults' total energy and deleterious nutrient intakes; and to study social and physical environmental interactions with consumption patterns of young adults. A cross-sectional study of 1008 young adults will be conducted. Individuals are eligible to participate if they: (1) are aged between 18 and 30 years; (2) reside in New South Wales, Australia; (3) own or have access to a smartphone; (4) are English-literate; and (5) consume at least one meal, snack, or drink purchased outside the home per week. An even spread of gender, age groups (18 to 24 years and 25 to 30 years), metropolitan or regional geographical areas, and high and low socioeconomic status areas will be included. Participants will record all food and drink consumed over 3 consecutive days, together with location purchased and consumed in our customized smartphone app named Eat and Track (EaT). Participants will then complete an extensive demographics questionnaire. Mean intakes of energy, nutrients, and food groups will be calculated along with the relative contribution of foods purchased and eaten away from home. A subsample of 19.84% (200/1008) of the participants will complete three 24-hour recall interviews to compare with the data collected using EaT. Data mining techniques such as clustering, decision trees, neural networks, and support vector machines will be used to build predictive models and identify important patterns. Recruitment is underway, and results will be available in 2018. The contribution of foods prepared away from home, in terms of energy, nutrients, deleterious nutrients, and food groups to young people's diets will be determined, as will the impact on meeting national recommendations. Foods and consumption behaviors that should be targeted in future health promotion efforts for young adults will be identified.


[Vascular endothelial growth factor inhibits dendritic cells from patients with non-small cell lung carcinoma].
To detect the effect of vascular endothelial growth factor (VEGF) on dendritic cells (DC) in patients with non-small cell lung cancer (NSCLC). The measurement of DC in the peripheral blood was performed by a novel flow cytometric assay in 85 patients with NSCLC and 14 healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of VEGF(165) in the plasma. CD(14)(+) peripheral blood mononuclear cells (PBMC) were cultured to obtain DC in vitro with cytokines. VEGF(165) was added to evaluate its effect on DC differentiation and survival. The phenotypes and apoptosis of cultured cells were detected by flow cytometry. In comparison with healthy volunteers, the level of VEGF(165) was significantly increased (P < 0.05), while that of DC was significantly decreased (P < 0.01) in patients with NSCLC. No significant correlation was noted between the concentration of VEGF(165) and age, gender, differentiation and histological types in patients with NSCLC, neither was found in the level of DC (P > 0.05). The concentration of VEGF(165) was closely associated with TNM stage and distal metastasis (P < 0.05), while no correlation was found between the concentration of VEGF(165) and lymph node metastasis (P > 0.05). Significant correlations were noted between the level of DC in patients with NSCLC and TNM stage, lymph node metastasis and distal metastasis (P < 0.05). There was a negative correlation between the concentration of VEGF(165) and the level of DC (P < 0.05). Patients with abnormally elevated VEGF(165) showed significantly fewer DC. Cells cultured in vitro in the presence of VEGF(165) exhibited higher expression of CD(+)(14)(P = 0.000) and increased ratio of apoptic cells (P < 0.01), but decreased expression of CD(40), CD(86) and HLA-DR (P < 0.01), as compared to cells cultured without VEGF(165). The level of DC and the concentration of VEGF in the peripheral blood can reflect the malignancy of NSCLC. NSCLC can over-express VEGF to inhibit DC differentiation and maturation to evade host immune surveillance.


[Human and Social Sciences in the training of the first nurses 'cariocas' and 'paulistanas'].
This historical and documental study aimed to describe and analyze the place that the Human and Social Sciences occupied in the first curriculum of the Anna Nery Nursing School (EEAN) and of the São Paulo Hospital Nursing School (EEHSP), identifying the similarities and differences between them. As a methodology, the curricula of these schools were analyzed by comparing them and seeking, between primary and secondary sources, information of the contribution of Human and Social Sciences in the training of pioneer nurses in modern nursing in Brazil. It was concluded that the humanities subjects occupied a secondary place in the studied curricula in comparison with the technical disciplines and the utilitarian aspect required by this profession at that time.


Distribution and activity of glutathione-S-transferase in normal human lenses and in cataractous human epithelia.
The distribution of glutathione-S-transferase (GST) activity was determined in frozen normal human lenses. The highest activity of GST was found in the peripheral and equatorial regions, whereas the lowest activity was found in the nucleus. Western blot showed that both mu and pi isoenzymes of GST were present in human lenses. This result is similar to that found in rat lenses. In addition, GST activity was analyzed in 50 lens epithelia which were obtained during cataract surgery. Twenty-seven lens epithelia showed no activity. Statistically significant association was found between cortical and mixed cortical--nuclear cataract and loss of GST activity. No association was found between pure nuclear cataract and loss of epithelial GST activity.


Pharmacological treatment for uterine leiomyosarcomas.
Pharmacological treatment plays a major role in the management of advanced, persistent or recurrent uterine leiomyosarcoma (LMS), whereas its usefulness in the adjuvant setting is still debated. A thorough literature search was undertaken using the Pubmed databases. Systematic reviews and controlled trials on medical treatment of uterine LMS were collected and critically analyzed. Other study types were secondarily considered when pertinent. Doxorubicin (DOX), ifosfamide and dacarbazine have been long used in the treatment of this malignancy. Novel active agents are represented by gemcitabine, docetaxel, trabectedin, pazopanib and aromatase inhibitors, whereas the role of eribulin, bevacizumab, aflibercept and mammalian target of rapamycin inhibitors is still investigational. DOX alone, gemcitabine alone, DOX + dacarbazine and gemcitabine + docetaxel may be treatment options for first-line and second-line therapies. However, the clinical benefit of the combination chemotherapy versus single-agent chemotherapy is still debated. Trabectedin is a promising agent for recurrent uterine LMS, able to obtain a prolonged disease control, with 3-month and 6-month progression-free survival rates exceeding 50 and 30%, respectively, and with sometimes unexpectedly durable responses. Pazopanib is the only approved targeted therapy. Hormone therapy with aromatase inhibitors may be a therapeutic option in heavily treated patients with slowly progressive, steroid receptor-positive tumors. Whenever possible, women with recurrent uterine LMS should be encouraged to enter well-designed clinical trials aimed to detect novel active agents.


Acute hemorrhagic complications are associated with lower coated-platelet levels in non-lacunar brain infarction.
Coated platelets are procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. To investigate whether acute hemorrhagic complications occurring during the initial hospital admission for non-lacunar ischemic stroke are associated with lower coated-platelet levels. Coated-platelet levels were determined in 385 consecutive patients with non-lacunar stroke. Hemorrhagic complications were defined as either intracranial hemorrhage or significant extracranial bleeding (drop in hemoglobin of ≥ 2 g dL(-1) ). The rate of acute hemorrhagic complication was compared among subjects categorized into tertiles of coated-platelet levels using an exact Cochrane-Armitage trend test. Logistic regression was used to estimate the adjusted odds of hemorrhagic complication associated with coated-platelet levels. Hemorrhagic complications were present in 15 (3.9%) cases. Of these, four had intracranial hemorrhage and 11 had extracranial hemorrhage. The occurrence of hemorrhagic complications differed among the coated-platelet tertiles: 10.2% for the first tertile (coated-platelet levels < 35.5%), 1.5% for the second tertile and 0% for the third tertile (coated-platelet levels ≥ 47.5%, trend test). Logistic regression showed that the odds of hemorrhagic complication in those with levels < 35.5% were 14.59 times the odds for patients with levels ≥ 35.5% (95% CI: 3.24-65.7). Lower levels of procoagulant platelets are associated with acute hemorrhagic complications following non-lacunar ischemic stroke. These results suggest a role for coated-platelets in risk/benefit assessment in the early stages of stroke.


Evaluating total lymphocyte count as a surrogate marker for CD4 cell count in the management of HIV-infected patients in resource-limited settings: a study from China.
To evaluate the correlation of total lymphocyte count (TLC) and CD4 cell count and the suitability of TLC as a surrogate marker for CD4 cell count of HIV-infected patients in China. Usefulness of TLC as a surrogate marker for a CD4 cell count <350 cells/mm(3) for HIV-positive patients in China was evaluated by 977 pairs of TLC and CD4 cell count from 977 outpatients. The result was then validated by a literature review which was conducted on 9 relevant articles. Further investigation using the 977 pairs of TLC and CD4 cell count data was done to determine a TLC threshold for predicting a CD4 cell count <500 cells/mm(3). Correlation and receiver operating characteristic (ROC) analysis were performed for both CD4 cell counts, and the sensitivity and specificity were computed. Good correlation was noted between TLC and CD4 count (r = 0.60, 95% CI, 0.56-0.64). TLC obtained a relatively high diagnostic performance (area under ROC curve, 0.80) for predicting a CD4 cell count <350 cells/mm(3), with a sensitivity of 0.65 (95% CI, 0.61-0.68) and a specificity of 0.80 (95% CI, 0.75-0.85) at the TLC threshold of 1570 cells/mm(3). The literature review suggested that for a CD4 cell count <350 cells/mm(3), the optimal TLC threshold was 1500 cells/mm(3), which was similar to the figure presented in this observational study. As for predicting a CD4 cell count <500 cells/mm(3), TLC obtained a high diagnostic performance (area under ROC curve, 0.82) as well with a sensitivity of 0.70 (95% CI, 0.67-0.73) and a specificity of 0.80 (95% CI, 0.73-0.87). When considering the antiretroviral therapy for HIV-infected Chinese individuals, total lymphocyte count can be considered as an inexpensive and easily available surrogate marker for predicting two clinically important thresholds of CD4 count of 350 cells/mm(3) and 500 cells/mm(3).


Parotid gland follicular lymphoma lacking both cytoplasmic and surface light chains: a rare case.
Immunoglobulin light chain (LC) restriction is detected in the majority of B-cell non-Hodgkin lymphoma (B-NHL) by flow cytometric immunophenotyping (FCI) and serves as a surrogate marker of monoclonality. Even though it is known a small percentage of mature B-NHLs lacking surface LC, deficiency of both cytoplasmic and surface LCs has been reported in only three B-NHL cases. We report a primary parotid gland follicular lymphoma in a 63-year-old man and the lymphoma cells were deficient of cytoplasmic/surface LCs. Compared to previous reports, we used a more sensitive FCI method by combining both monoclonal and polyclonal anti-LC antibodies. Lacking LCs poses as a pitfall for the initial diagnosis of B-NHL, as well as for detecting minimal residual disease. It is important to be aware of this rare immunophenotypic aberrancy.


Reproductive biology and the process of domestication of the columnar cactus Stenocereus Stellatus in Central Mexico.
Pollination biology, breeding system, and floral phenology of the columnar cactus Stenocereus stellatus were studied in wild, wild managed in situ and cultivated populations of central Mexico, in order to examine whether these aspects have been modified under domestication and whether they determine reproductive barriers between wild and manipulated individuals. Individuals of both wild and manipulated populations are self-incompatible, indicating that artificial selection has not modified the breeding system. Their pollination biology is also similar. Anthesis is mainly nocturnal, with a peak of nectar production between 0200 and 0400 when the stigma presents maximum turgidity. Nocturnal visitors are the effective pollinators. Nearly 75% of flowers exposed for nocturnal pollination set fruit, while none of the flowers exposed for diurnal pollination produced fruits. The bats Leptonycteris curasoae, L. nivalis, and Choeronycteris mexicana (Glossophaginae) are the most likely pollinators, and their time of foraging is synchronized with the time of nectar production and stigma receptivity in S. stellatus. Bats potentially move pollen over a considerable distance, so there is apparently no spatial isolation to prevent pollen exchange between wild and cultivated populations. Phenological studies showed that there are also no apparent temporal barriers. However, manual cross pollination failed between some domesticated and wild phenotypes, suggesting that gene flow between wild and cultivated populations might be limited by pollen incompatibility.


David Ferrier and Luigi Luciani on the localization of brain functions.
Cerebral localizations discovered by Luciani will be compared with those observed by Ferrier, the 'father' of cerebral cartography. The two neurophysiologists' different experimental results will be analyzed from an epistemological point of view, in the light of their respective methodologies, models and theoretical assumptions. Luciani was always profoundly aware of the importance of theoretical assumptions and their impact both on methodological approaches and on how to interpret the results of experiments (results which were often the same as those obtained by Goltz, even though they were interpreted in quite dissimilar ways because they were based on different models). Agreement or disagreement with Ferrier's interpretation of cerebral functioning, and the two men's conception on the functional differentiation of well-identified cortical areas will be interpreted on epistemological ground. Reference will be made, on the one hand, to the theoretical model behind Luciani's experiments, on the other hand, to methods and procedures which allowed him to observe his experimental subjects for a longer period of time after the operation because of their longer survival rates. He was, consequently, able to carry out a more detailed analysis of the effects of experimentation on animal behavior. In this sense the time factor acquired a fundamental importance in the development of notions such as compensation and functional recovery. From Luciani's vast amount of activity in the field of physiology at the turn of the century, we shall take a look at the results of his investigations into cerebral localization in order to highlight the state of Italian neurophysiology in relation to the situation in contemporary Europe and, in particular, to the situation in Great Britain.


Continuing education and the professional orientation of nurses.
The relationships among continuing education (CE) of nurses, their professional orientation, and selected background characteristics were examined. It was hypothesized that attitudes toward, and participation in, CE were related to professional orientation and not to background. Data were obtained from 82% of a random sample of 395 currently registered nurses living in a midwestern state. The results of a multiple regression analysis were consistent with the study hypotheses. Attitudes toward CE were predicted best by attitudes toward the professionalization of nursing and by future career intentions. Participation in CE was predicted best by current employment status, formal education beyond the initial nursing program, and independent learning activities. None of the four background variables (age, initial nursing program, parental status, and marital status) was a significant predictor. CE was seen, therefore, as an activity of professionally oriented nurses.


Obesity and insulin resistance induce early development of diastolic dysfunction in young female mice fed a Western diet.
Cardiovascular disease (CVD), including heart failure, constitutes the main source of morbidity and mortality in men and women with diabetes. Although healthy young women are protected against CVD, postmenopausal and diabetic women lose this CVD protection. Obesity, insulin resistance, and diabetes promote heart failure in females, and diastolic dysfunction is the earliest manifestation of this heart failure. To examine the mechanisms promoting diastolic dysfunction in insulin-resistant females, this investigation evaluated the impact of 8 weeks of a high-fructose/high-fat Western diet (WD) on insulin sensitivity and cardiac structure and function in young C57BL6/J female versus male mice. Insulin sensitivity was determined by hyperinsulinemic-euglycemic clamps and two-dimensional echocardiograms were used to evaluate cardiac function. Both males and females developed systemic insulin resistance after 8 weeks of a WD. However, only the females developed diastolic dysfunction. The diastolic dysfunction promoted by the WD was accompanied by increases in collagen 1, a marker of stiffness, increased oxidative stress, reduced insulin metabolic signaling, and increased mitochondria and cardiac microvascular alterations as determined by electron microscopy. Aldosterone (a promoter of cardiac stiffness) levels were higher in females compared with males but were not affected by the WD in either gender. These data suggest a predisposition toward developing early diastolic heart failure in females exposed to a WD. These data are consistent with the notion that higher aldosterone levels, in concert with insulin resistance, may promote myocardial stiffness and diastolic dysfunction in response to overnutrition in females.


Cross-talk between iron and nitrogen regulatory networks in anabaena (Nostoc) sp. PCC 7120: identification of overlapping genes in FurA and NtcA regulons.
Nitrogen signalling in cyanobacteria involves a complex network in which the availability of iron plays an important role. In the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120, iron uptake is controlled by FurA, while NtcA is the master regulator of nitrogen metabolism and shows a mutual dependence with HetR in the first steps of heterocyst development. Expression of FurA is modulated by NtcA and it is enhanced in a hetR(-) background. Iron starvation in cells grown in the presence of combined nitrogen causes a moderate increase in the transcription of glnA that is more evident in a ntcA(-) background. Those results evidence a tight link between the reserves of iron and nitrogen metabolism that leads us to search for target genes potentially co-regulated by FurA and NtcA. Using a bioinformatic approach we have found a significant number of NtcA-regulated genes exhibiting iron boxes in their upstream regions. Our computational predictions have been validated using electrophoretic mobility shift assay (EMSA) analysis. These candidates for dual regulation are involved in different functions such as photosynthesis (i.e. psaL, petH, rbcL, isiA), heterocyst differentiation (i.e. xisA, hanA, prpJ, nifH), transcriptional regulation (several alternative sigma factors) or redox balance (i.e. trxA, ftrC, gor). The identification of common elements overlapping the NtcA and FurA regulons allows us to establish a previously unrecognized transcriptional regulatory connection between iron homeostasis, redox control and nitrogen metabolism.


Enamelin/ameloblastin gene polymorphisms in autosomal amelogenesis imperfecta among Syrian families.
This study was undertaken to investigate whether a single G deletion within a series of seven G residues (codon 196) at the exon 9-intron 9 boundary of the enamelin gene ENAM and a tri-nucleotide deletion at codon 180 in exon 7 (GGA vs deletion) of ameloblastin gene AMBN could have a role in autosomal amelogenesis imperfecta among affected Syrian families. A new technique - size-dependent, deletion screening - was developed to detect nucleotide deletion in ENAM and AMBN genes. Twelve Syrian families with autosomal-dominant or -recessive amelogenesis imperfecta were included. A homozygous/heterozygous mutation in the ENAM gene (152/152, 152/153) was identified in affected members of three families with autosomal-dominant amelogenesis imperfecta and one family with autosomal-recessive amelogenesis imperfecta. A heterozygous mutation (222/225) in the AMBN gene was identified. However, no disease causing mutations was found. The present findings provide useful information for the implication of ENAM gene polymorphism in autosomal-dominant/-recessive amelogenesis imperfecta. Further investigations are required to identify other genes responsible for the various clinical phenotypes.


Two Capacitive Micro-Machined Ultrasonic Transducers for Wind Speed Measurement.
This paper presents a new wind speed measurement method using a single capacitive micro-machined ultrasonic transducer (CMUT). The CMUT was arranged perpendicular to the direction of the wind flow, and a reflector was set up a short distance away, facing the CMUT. To reduce the size, weight, cost, and power consumption of conventional ultrasonic anemometers this study proposes two CMUT designs for the measurement of wind speed using either the amplitude of the signal or the time of flight (TOF). Each CMUT with a double array element design can transmit and receive signals in five different operation modes. Experiments showed that the two CMUT designs utilizing the TOF were better than those utilizing the amplitude of the signal for wind speed measurements ranging from 1 m/s to 10 m/s, providing a measurement error of less than 0.2 m/s. These results indicate that the sensitivity of the TOF is independent of the five operation modes.