Percent body fat and chronic disease risk factors in U.S. children and youth.
The dramatic increase in pediatric obesity has renewed interest in accurate methods and screening indexes for identifying at-risk children and youth. Whether age-specific standards are needed is a factor that remains uncertain. This study was designed to describe the age-specific fatness-risk factor relationship in boys and girls across a wide age range. Data were from 12,279 white, black, and Mexican-American children and adolescents from the National Health and Nutritional Examination Surveys (NHANES) III (1998-1994) and IV (1999-2004). Children were grouped based on percent fat, estimated from subscapular and triceps skinfolds, and the age-specific relationships between percent fat and chronic disease risk factors (e.g., blood pressure, lipids and lipoprotein levels, glucose, insulin, and circulating C-reactive protein levels) were described in boys and girls, aged 6-18 years. Percent fat was significantly related to risk factor levels. At higher levels of percent fat, the prevalence of adverse cardiovascular disease risk factors was higher, particularly above 20% fat in boys and above 30% fat in girls. In boys and girls, the interaction term age by percent fat was a significant predictor of risk factors, whereas the percent fat by race interaction term was nonsignificant. The results demonstrate a strong relationship between chronic disease risk factors and percent fat in children and youth that varies by age in boys and girls.


Respiratory system compliance decreases after cardiopulmonary resuscitation and stomach inflation: impact of large and small tidal volumes on calculated peak airway pressure.
The purpose of the present study was to evaluate respiratory system compliance after cardiopulmonary resuscitation (CPR) and subsequent stomach inflation. Further, we calculated peak airway pressure according to the different tidal volume recommendations of the European Resuscitation Council (7.5 ml/kg) and the American Heart Association (15 ml/kg) for ventilation of an unintubated cardiac arrest victim. After 4 min of ventricular fibrillation, and 6 min of CPR, return of spontaneous circulation (ROSC) after defibrillation occurred in seven pigs. Respiratory system compliance was measured at prearrest, after ROSC, and after 2 and 4 l of stomach inflation in the postresuscitation phase; peak airway pressure was subsequently calculated. Before cardiac arrest the mean (+/- S.D.) respiratory system compliance was 30 +/- 3 ml/cm H2O, and decreased significantly (P < 0.05) after ROSC to 24 +/- 5 ml/cm H2O, and further declined significantly to 18 +/- 4 ml/cm H2O after 2 l, and to 13 +/- 3 ml/cm H2O after 4 l of stomach inflation. At prearrest, the mean +/- S.D. calculated peak airway pressure according to European versus American guidelines was 9 +/- 1 versus 18 +/- 3 cm H2O, after ROSC 12 +/- 2 versus 23 +/- 4 cm H2O, and 15 +/- 2 versus 30 +/- 5 cm H2O after 2 l, and 22 +/- 6 versus 44 +/- 12 cm H2O after 4 l of stomach inflation. In conclusion, respiratory system compliance decreased significantly after CPR and subsequent induction of stomach inflation in an animal model with a wide open airway. This may have a significant impact on peak airway pressure and distribution of gas during ventilation of an unintubated patient with cardiac arrest.


Non-nucleoside inhibitors of the hepatitis C virus NS5B RNA-dependant RNA polymerase: 2-aryl-3-heteroaryl-1,3-thiazolidin-4-one derivatives.
Hepatitis C virus (HCV) NS5B RNA polymerase is crucial for replicating the HCV RNA genome and is an attractive target for developing anti-HCV drugs. A novel series of 2,3-diaryl-1,3-thiazolidin-4-one derivatives were evaluated for their ability to inhibit HCV NS5B. Of this series, compounds 4c, 5b, 5c and 6 emerged as more potent, displaying over 95% inhibition of NS5B RNA polymerase activity in vitro. The two most active compounds 4c and 5c exhibited an IC(50) of 31.9 microM and 32.2 microM, respectively, against HCV NS5B.


Protective effect of low doses of an anti-IL-4 monoclonal antibody in a murine model of acute toxoplasmosis.
Treatment with an anti-IL-4 monoclonal antibody protected susceptible C57BL/6 mice against challenge with an avirulent strain of T. gondii. Antibody therapy with 100 micrograms on days 0 and 7 post infection resulted in 100% survival of C57/BL6 mice infected orally. Survival was dose-dependent. Treatment prolonged parasitaemia but did not alter tissue parasite load. Increased serum IgG2a and IFN-gamma levels, together with low levels of IgG1, in mice treated with anti-IL-4 or an isotype control, indicated a trend towards a predominant Th1 response in all survivors. The persistence of an IgE response after treatment suggests that endogenous IL-4 was only partly neutralized or that other factors can induce the production of IgE in murine toxoplasmosis.


Mouse brain deoxyglucose uptake after footshock, ACTH analogs, alpha-MSH, corticosterone or lysine vasopressin.
The cerebral uptake of subcutaneously injected [3H]2-deoxy-D-glucose (2DG) in 16 brain regions was examined following 30 noncontingent random footshocks or the acute injection of saline, ACTH1-24 (0.5 microgram/g), ACTH/MSH4-10 (0.25 microgram/g), [D-Phe7]ACTH4-10 (0.25 microgram/g), [Met4SO2,D-Lys8,Phe9]ACTH4-9 (0.01 microgram/g), ALPHA-MSH (0.5 microgram/g), corticosterone (2.5 microgram/g) or lysine vasopressin (0.05 microgram/g). Footshock selectively decreased 2DG uptake in parietal cortex and brain stem, and increased that in the hypothalamus. Whole brain 2DG uptake was decreased by injection of saline or most of the hormones relative to uninjected animals, but this effect was probably peripheral since plasma glucose content was increased by the injections. The only regionally specific effect of the hormones was an increased 2DG uptake in olfactory bulb by saline, ACTH/MSH4-10 And corticosterone relative to uninjected animals. Since alpha-MSH had been reported previously to decrease blood flow (measured by antipyrene uptake) in all brain regions except occipital cortex [5,6], we directly compared antipyrene uptake with 2DG uptake in the same animals using a double-isotope procedure. The results revealed an increase in 2DG uptake relative to antipyrene in cortical regions relative to subcortical regions, contradicting earlier assumptions [19].


miR-21-5p promotes NASH-related hepatocarcinogenesis.
The mechanisms governing the progression of non-alcoholic fatty liver disease (NAFLD) towards steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain elusive. Here, we evaluated the role of hsa-miRNA-21-5p in NASH-related hepatocarcinogenesis. Hepatic hsa-miR-21-5p expression was evaluated in two cohorts of patients with biopsy-proven NAFLD (n = 199) or HCC (n = 366 HCC and n = 11 NAFLD-HCC). Serum/liver metabolomic profiles were correlated with hsa-miR-21-5p in NAFLD obese patients. Wild-type (WT) and Mir21 KO mice were fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks to induce NASH and NASH-HCC, respectively. In obese individuals, hsa-miR-21-5p expression increased with NAFLD severity and associated with a hepatic lipotoxic profile. CDAA-fed WT mice displayed increased hepatic mmu-miR-21-5p levels and progressively developed NASH and fibrosis, with livers presenting macroscopically discernible pre-neoplastic nodules, hyperplastic foci and deregulated cancer-related pathways. Mir21 KO mice exhibited peroxisome-proliferator-activated receptor α (PPARα) activation, augmented mitochondrial activity, reduced liver injury and NAS below the threshold for NASH diagnosis, with the pro-inflammatory/fibrogenic milieu reversing to baseline levels. In parallel, Mir21 KO mice displayed reduced number of pre-neoplastic nodules, hepatocyte proliferation and activation of oncogenic signalling, being protected from NASH-associated carcinogenesis. The hsa-miRNA-21-5p/PPARα pathway was similarly deregulated in patients with HCC- or NASH-related HCC, correlating with HCC markers and worse prognosis. Hsa-miR-21-5p is a key inducer of whole-spectrum NAFLD progression, from simple steatosis to NASH and NASH-associated carcinogenesis. The inhibition of hsa-miR-21-5p, leading to a pro-metabolic profile, might constitute an appealing therapeutic approach to ameliorate NASH and prevent progression towards HCC.


Organization of microtubules in stabilized meristematic plant cells revealed by a rat monoclonal antibody reacting only with the tyrosinated form of alpha-tubulin.
A rat monoclonal antibody against yeast tubulin (clone YL 1/2; Kilmartin et al., 1982) that reacts specifically with mammalian alpha-tubulin carrying a carboxyterminal tyrosine residue (Wehland et al., 1983) was used to localize microtubules in plant cells derived from onion root apices (Allium cepa L.). YL 1/2 reacted with all types of microtubular arrays known to occur in higher plant meristematic cells such as interphase cortical microtubules, pre-prophase bands, the mitotic spindle and phragmoplast microtubules. The specific labeling of microtubules in isolated cells from onion root tips by YL 1/2 indicates that plant cells like animal cells contain tubulin tyrosine ligase, the enzyme which posttranslationally modifies alpha-tubulin. This enzyme could be involved in the dynamic regulation of microtubular arrays in all eukaryotic cells.


Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection.
To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. Converted effective doses in SCT and ULDCT were 2.81 ± 0.92 and 0.17 ± 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free-response receiver operating characteristic analysis, the mean values of figure-of-merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT.


An interphase pool of KIF11 localizes at the basal bodies of primary cilia and a reduction in KIF11 expression alters cilia dynamics.
KIF11 is a homotetrameric kinesin that peaks in protein expression during mitosis. It is a known mitotic regulator, and it is well-described that KIF11 is necessary for the formation and maintenance of the bipolar spindle. However, there has been a growing appreciation for non-mitotic roles for KIF11. KIF11 has been shown to function in such processes as axon growth and microtubule polymerization. We previously demonstrated that there is an interphase pool of KIF11 present in glioblastoma cancer stem cells that drives tumor cell invasion. Here, we identified a previously unknown association between KIF11 and primary cilia. We confirmed that KIF11 localized to the basal bodies of primary cilia in multiple cell types, including neoplastic and non-neoplastic cells. Further, we determined that KIF11 has a role in regulating cilia dynamics. Upon the reduction of KIF11 expression, the number of ciliated cells in asynchronously growing populations was significantly increased. We rescued this effect by the addition of exogenous KIF11. Lastly, we found that depleting KIF11 resulted in an increase in cilium length and an attenuation in the kinetics of cilia disassembly. These findings establish a previously unknown link between KIF11 and the dynamics of primary cilia and further support non-mitotic functions for this kinesin.


Questioning conflict adaptation: proportion congruent and Gratton effects reconsidered.
Conflict adaptation is one of the most popular ideas in cognitive psychology. It purports to explain a wide range of data, including both brain and behavioral data from the proportion congruent and Gratton paradigms. However, in recent years, many concerns about the viability of this account have been raised. It has been argued that contingency learning, not conflict adaptation, produces the proportion congruent effect. Similarly, the Gratton paradigm has been shown to contain several confounds-most notably, feature repetition biases. Newer work on temporal learning further calls into question the interpretability of the behavioral results of conflict adaptation studies. Brain data linking supposed conflict adaptation to the anterior cingulated cortex has also come into question, since this area seems to be responsive solely to time-on-task, rather than conflict. This review points to the possibility that conflict adaptation may simply be an illusion. However, the extant data remain ambiguous, and there are a lot of open questions that still need to be addressed in future research.


Initial Experience with a Wireless Ultrasound-Guided Vacuum-Assisted Breast Biopsy Device.
To determine the imaging characteristic of frequent target lesions of wireless ultrasound (US)-guided, vacuum-assisted breast biopsy (Wi-UVAB) and to evaluate diagnostic yield, accuracy and complication of the device in indeterminate breast lesions. From March 2013 to October 2014, 114 women (age range, 29-76 years; mean age, 50.0 years) underwent Wi-UVAB using a 13-gauge needle (Mammotome Elite®; Devicor Medical Products, Cincinnati, OH, USA). In 103 lesions of 96 women with surgical (n = 81) or follow-up (n = 22) data, complications, biopsy procedure, imaging findings of biopsy targets and histologic results were reviewed. Mean number of biopsy cores was 10 (range 4-25). Nine patients developed moderate bleeding. All lesions were suspicious on US, and included non-mass lesions (67.0%) and mass lesions (33.0%). Visible calcifications on US were evident in 57.3% of the target lesions. Most of the lesions (93.2%) were nonpalpable. Sixty-six (64.1%) were malignant [ductal carcinoma in situ (DCIS) rate, 61%] and 12 were high-risk lesions (11.7%). Histologic underestimation was identified in 11 of 40 (27.5%). DCIS cases and in 3 of 9 (33.3%) high-risk lesions necessitating surgery. There was no false-negative case. Wi-UVAB is very handy and advantageous for US-unapparent non-mass lesions to diagnose DCIS, especially for calcification cases. Histologic underestimation is unavoidable; still, Wi-UVAB is safe and accurate to diagnose a malignancy.


Genetic polymorphism in association with susceptibility to tuberculosis: a study in a Pakistani population.
Tuberculosis is becoming a global issue with raising occurrences; particularly in developing countries, the situation is alarming. Besides environmental factors, host genetic factors are vital in disease development. A demographical and genotypic analysis in relation to tuberculosis commencement is conducted in a Pakistani population, and genotypic frequency of EBI3 (rs4740) was analyzed. Allelic frequencies of EBI3 (rs4740) were significantly associated with disease susceptibility in the reviewed population. Analysis for EBI3 (rs4740) genotyping showed a significant association of "GG" with reduced risk for disease. Moreover, females and older age found to be more perilous to develop TB while smoking and a family history of TB are additional risk factors for disease development. Further work with a larger population is necessary to identify the true causative variants of tuberculosis.


Protein intake at 9 mo of age is associated with body size but not with body fat in 10-y-old Danish children.
During the complementary feeding period, infants shift from a daily protein intake (PI) of approximately 1 g/kg body wt to an intake 3-4 times as high. A high PI probably has both endocrine and physiologic effects and may increase the risk of obesity. We examined the associations between PI in infancy and body size and composition in late childhood. We conducted an observational cohort study of 142 Danish healthy term infants (63 boys) born during 1987-1988. At 9 mo of age, diet, weight, length, skinfold thicknesses, insulin-like growth factor I, and serum urea nitrogen were determined. At 10 y of age, 105 children (51 boys) participated in a follow-up study. Diet, weight, height, skinfold thicknesses, percentage of body fat (dual-energy X-ray absorptiometry), insulin-like growth factor I, and serum urea nitrogen were determined. At 9 mo of age, PI (in g/d and percentage of energy) was strongly correlated with body size (length and weight) but not with measures of adiposity. PI at 9 mo of age was positively associated with height and weight but not with percentage of body fat at 10 y of age. Inclusion of parental body size in the models did not change the associations, but the significant associations were attenuated when body size at 9 mo of age was included. PI in infancy seems to stimulate early growth. This might explain part of the association between early PI and body size at 10 y of age, but a continuous effect of protein on growth during childhood cannot be excluded. PI in infancy was not associated with any measure of body fat at 10 y of age.


Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix.
Human papillomavirus (HPV) infection is the most common sexually transmitted disease, with more than 80% of the population infected at some time in their life. In rare cases, this infection may lead to cervical cancer. Virtually all squamous cell carcinomas and the overwhelming majority of adenocarcinomas of the cervix are HPV positive. HPV integration in the genome will lead to inactivation of the p53 pathway and the Rb pathway. Integration is essential for the onset of cervical carcinogenesis, but is probably not sufficient for progression to invasive cervical cancers. It is likely that several cofactors, such as environmental, viral and host-related factors, are necessary for the development of cervical cancer. There are several similarities and differences between the two major histological types. This article will address the role of HPV in cervical carcinogenesis as well as the molecular biology involved in the process.


Sharing the Patient Experience: A "Talk Story" Intervention for Heart Failure Management in Native Hawaiians.
Native Hawaiians (NHs) suffer disproportionately from cardiovascular disease morbidity and mortality. To test a narrative intervention of patient stories to support heart disease self-management in NHs. Six NH storyteller videos were developed with community feedback following established methods. The NH participants with heart failure (N = 35) were recruited from a major medical center in Hawai'i. Participants completed demographic questionnaires, watched videos via iPad, and described experiences. Follow-up was 4 weeks later. Mean participant age was 57.0 years (standard deviation [SD]:13.0) and 31% (11) were female. On a scale of 1 (worst) to 4 (best), respondents rated the videos 3.7 (SD: 0.5) in relevance for helping them manage their heart disease and 3.6 (SD: 0.5) in their experience using these videos. When asked what they liked best, the most common response was that they are "like me" (from 14 respondents, ranging from a 43-year-old woman to an 84-year-old man). Of those completing follow-up (n = 15), 87% said videos helped them. Our narrative "talk story" intervention showed promise as a culturally relevant method to share patient experiences and reduce health disparities.


2,3-Di-ethyl-benzo[g]quinoxaline.
The title compound, C16H16N2, was synthesized by dispersing 3,4-hexa-nedione in a methanol-water solution containing the acid catalyst NH4HF2, then adding 1,2-di-aminona-phthalene. The fused-ring system of the title compound is close to planar (r.m.s. deviation = 0.028 Å); one of the pendant methyl C atoms lies close to the ring plane [deviation = 0.071 (2) Å; N-C-C-C = -0.27 (18)°] whereas the other is significantly displaced [-1.7136 (18) Å; 91.64 (16)°]. The mol-ecules pack in space group I in a distinctive criss-cross motif supported by numerous aromatic π-π stacking inter-actions [shortest centroid-centroid separation = 3.5805 (6) Å].


Photoredox-Catalyzed Three-Component Tandem Process: An Assembly of Complex Trifluoromethylated Phthalans and Isoindolines.
A novel photoredox-mediated tandem three-component process afforded a wide variety of CF3-containing phthalans and isoindolines in respectable yields and with moderate to excellent diastereoselectivity.


Association of actin with chromaffin granule membranes and the effect of cytochalasin B on the polarity of actin filament elongation.
Membranes of chromaffin granules isolated from bovine adrenal medulla are shown to bind dihydrocytochalasin B with high affinity. These membranes also bound [3H]actin in a time- and Mg2+-dependent manner and electron microscopy showed the presence of membrane-attached actin filaments following addition of exogenous actin. Binding of [3H]actin was partially inhibited by cytochalasin B. Electron microscopic analysis of heavy meromyosin-decorated, membrane-attached filaments showed terminally (end-on) attached filaments with both possible polarities (i.e., filaments with arrowheads pointing both towards and away from the membranes). Treatment of samples with cytochalasin B preferentially inhibited growth of filaments with their 'barbed' ends pointing away from membranes. These results are discussed with respect to the role of actin in secretory granule function and the mechanism of cytochalasin action.


A method for monitoring the collapse of plastic sections as a function of electron dose.
We present a method for monitoring the collapse of plastic sections when irradiated in the electron microscope. The two surfaces of the section are separately coated with colloidal gold particles. The section is then tilted to an angle of 45 degrees in the microscope and a series of micrographs recorded, corresponding to increasing total electron dose. The collapse of the specimen normal to the plane of the section causes a relative movement in the image of the two sets of particles marking the two surfaces. By measuring the positions of a few gold particles on each side of the section in each exposure of the series, the collapse and also the in-plane shrinkage can be computed. The sections exhibit a rapid initial collapse, followed by a much slower phase of thinning. These effects should be taken into account when producing quantitative three-dimensional maps from tilt series of sectioned material.


Is patient identification of 'comfortable' print size a useful clinical parameter for low vision reading assessment?
The purpose of this study was to determine what a person with vision loss considers a 'comfortable' print size to read, and examine whether this reflects any of three currently used parameters for identifying print size required for sustained reading tasks: minimum size to achieve maximum reading speed (the critical print size (CPS)); minimum size for functional reading at 80 wpm and/or a size that is double the reading acuity (representing an acuity reserve of 2:1). Forty-seven participants entering low vision rehabilitation (mean age 77 years, 24 with macular degeneration) were assessed using MNREAD charts to determine reading acuity, maximum reading speed, CPS and the minimum size allowing functional (80 wpm) reading. Comfortable print size was assessed by asking participants to identify 'the smallest print size that you would find comfortable using' on the MNREAD chart. There was little difference between comfortable print size and CPS (mean difference 0.05 logMAR (SD 0.18); p = 0.08, limits of agreement ±0.35 logMAR), and no trend for the difference between values to differ across the functional range. Size for functional reading could only be assessed for 41 participants, and the difference between this and comfortable print size varied across the functional range. Comfortable print size was consistently smaller than twice the reading acuity size (mean difference 0.11 logMAR (SD 0.17); p < 0.001), with an average acuity reserve of 1.74:1. Asking people with visual impairment to identify a print size that is comfortable to read provides a print size similar to the CPS. This can be used as a guide in selecting magnification for sustained reading without having to undertake further analyses. Identification of perceived comfortable print size may offer a time-efficient clinical method of estimating magnification requirements, and be relevant for undertaking effective remote consultations.


First evidence of octacalcium phosphate@osteocalcin nanocomplex as skeletal bone component directing collagen triple-helix nanofibril mineralization.
Tibia trabeculae and vertebrae of rats as well as human femur were investigated by high-resolution TEM at the atomic scale in order to reveal snapshots of the morphogenetic processes of local bone ultrastructure formation. By taking into account reflections of hydroxyapatite for Fourier filtering the appearance of individual alpha-chains within the triple-helix clearly shows that bone bears the feature of an intergrowth composite structure extending from the atomic to the nanoscale, thus representing a molecular composite of collagen and apatite. Careful Fourier analysis reveals that the non-collagenous protein osteocalcin is present directly combined with octacalcium phosphate. Besides single spherical specimen of about 2 nm in diameter, osteocalcin is spread between and over collagen fibrils and is often observed as pearl necklace strings. In high-resolution TEM, the three binding sites of the γ-carboxylated glutamic acid groups of the mineralized osteocalcin were successfully imaged, which provide the chemical binding to octacalcium phosphate. Osteocalcin is attached to the collagen structure and interacts with the Ca-sites on the (100) dominated hydroxyapatite platelets with Ca-Ca distances of about 9.5 Å. Thus, osteocalcin takes on the functions of Ca-ion transport and suppression of hydroxyapatite expansion.


Nitric oxide and cGMP activate the Ras-MAP kinase pathway-stimulating protein tyrosine phosphorylation in rabbit aortic endothelial cells.
The free radical nitric oxide is a very effective signal transducer, stimulating the enzyme guanylyl cyclase, the oncoprotein p21Ras, and protein tyrosine phosphorylation. In the present study using rabbit aortic endothelial cells (RAEC), it is demonstrated that the nitric-oxide-generating substances sodium nitroprusside and S-nitroso-N-acetylpenicillamine, and a stable analog of cyclic GMP, 8BrcGMP stimulate p21Ras activity. Tyrosine phosphorylation of cytosolic proteins was stimulated and intracellular production of cGMP was increased, indicating that the NO/cGMP-stimulated tyrosine phosphorylation-dependent signaling pathway is most likely associated with the activation of p21Ras. NO and cGMP-dependent activation of p21Ras result in binding of the oncoprotein to the Ras-binding domain of Raf-1 kinase. Incubation of RAEC with FPT II, a potent and selective inhibitor of p21Ras, prevented NO-dependent tyrosine phosphorylation. ODQ, a potent inhibitor of the soluble form of guanylyl cyclase, inhibited the signal as well. Conversely, the use of KT5823, a cGMP-dependent protein kinase (PKG) blocker, showed no effect on protein tyrosine phosphorylation. To further establish a role for p21Ras on the NO-stimulated tyrosine phosphorylation-signaling pathway, RAEC were constitutively transfected with a dominant negative mutant of p21Ras, N17Ras. NO and cGMP-stimulated tyrosine phosphorylation were prevented in N17Ras-expressing RAEC exposed to NO donors and 8BrcGMP. The above findings indicate that NO and cGMP stimulation of protein tyrosine phosphorylation requires the participation of fully functional p21Ras. ERK1/2 MAP kinases and their subsequent targets, the transcription factors, lie downstream to Ras, Raf-1 kinase, and MEK. Treatment of both RAEC and mock-transfected RAEC with NO resulted in phosphorylation and activation of ERK1/2. On the other hand, NO did not stimulate phosphorylation of ERK1/2 in N17Ras-expressing RAEC. In addition, PD98059, a MEK inhibitor, prevented overall tyrosine phosphorylation and phosphorylation of ERK1/2. Upstream to Ras ERK1/2 MAP kinases target the EGF receptor. Incubation of RAEC or mock-transfected RAEC with NO donors resulted in activation of the EGF receptor autophosphorylation. PD98059 effectively blocked this activation. EGF receptor autophosphorylation was insensitive to NO stimulation in N17Ras-expressing RAEC. It is concluded that NO and cGMP stimulate a signaling pathway involving p21Ras-Raf-1 kinase-MEK-ERK1/2. Activation of this signaling pathway is connected to NO-stimulated overall tyrosine phosphorylation that also involves the transactivation of the EGF receptor mediated by ERK1/2.


Effect of differentiation inducers on growth characteristics of human glioma cell lines.
The effect of dimethylsulfoxide (DMSO) and iododeoxyuridine (IUdR) on the growth characteristics of two established human glioblastoma cell lines (FG and HMCN-1) was studied. The FG cell line has been characterized. The HMCN-1 cell line, established in our laboratory, consisted of fibroblastoid and polygonal cells that grew without contact inhibition. Subcutaneous injection of these cells into weanling athymic nude mice induced slowly growing, solid tumors that were histologically spindly with areas that were similar to the original tumor. Chromosomal analyses revealed a human heteroploid pattern with a modal number of 69. The cells of the original human glioma contained S-100 protein and glial fibrillary acidic protein (GFA protein), whereas the established cells failed to express markers. Prolonged treatment of glioma cells with DMSO generated a more adherent, normal human fibroblastoid phenotype that grew with contact inhibition. The new phenotype and proliferative restriction of these cells was evident as late as 50 days after discontinuation of treatment. The chemical induction of cell differentiation resulted in decreased tumorigenic potential in athymic nude mice.


Pulmonary adenocarcinoma metastatic to the adrenal gland mimicking normal adrenal cortical epithelium on fine needle aspiration.
Fine needle aspiration (FNA) of enlarged adrenal glands detected by computed tomography is a valuable method for extrathoracic staging of pulmonary carcinomas. This paper presents the case of a middle-aged man with pulmonary adenocarcinoma metastatic to the adrenal glands, the FNA sample of which closely resembled normal adrenal cortical epithelium. Through review of the case and comparison with cytologic preparations from normal adrenal glands, the aspiration cytologic features suggesting carcinoma are described.


Cuproptosis- and m6A-Related lncRNAs for Prognosis of Hepatocellular Carcinoma.
Cuproptosis and N6-methyladenosine (m6A) have potential as prognostic predictors in cancer patients, but their roles in hepatocellular carcinoma (HCC) are unclear. This study aimed to screen a total of 375 HCC samples were retrieved from the TCGA database, and lncRNAs related to cuproptosis and m6A were obtained through correlation analysis. To construct a risk assessment model, univariate Cox regression analysis and LASSO Cox regression were employed. Analyze the regulatory effect of relevant risk assessment models on tumor mutation load (TMB) and immune microenvironment. A total of five lncRNAs (AC007405.3, AL031985.3, TMCC1-AS1, MIR210HG, TMEM220-AS1) with independent overall survival-related risk models were obtained by LASSO survival regression. TP53 and CTNNB1 were the three genes found to have the most mutations in high-risk group patients. The high-risk group with low TMB had the worst survival, whereas the low-risk group with high TMB had the best survival. KEGG pathway analysis revealed that the high-risk group was enriched with cell cycle, oocyte meiosis, cell senescence, and glycolysis/glucose production pathways. We constructed a reliable cuproptosis- and m6A-related lncRNA model for the prognosis of HCC. The model may provide new insights into managing HCC patients, but further research is needed to validate it.


Maternal hypertension and neonatal outcome among small for gestational age infants.
To determine whether maternal hypertension might improve perinatal outcome among small for gestational age (SGA) infants (< 10th percentile). Our prospective cohort comprised 17 Canadian neonatal intensive care units (NICUs) and 3,244 SGA singletons. Multivariable regression was used to analyze the relation between maternal hypertension and each of the following: SNAP-II (Score of Neonatal Acute Physiology; ordinal regression) and neonatal survival and survival without severe intraventricular hemorrhage (logistic regression), adjusting for potential confounders. There were 698 (21.5%) neonates born to hypertensive mothers. Inversely associated with lower SNAP-II scores (healthier infant) were antenatal steroids (complete course: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.54-0.83; incomplete: OR 0.71, 95% CI 0.56-0.88), lower gestational age (< 27 weeks: OR 0.06, 95% CI 0.05-0.08; 27-28 weeks: OR 0.11, 95% CI 0.07-0.17; 29-32 weeks: OR 0.28, 95% CI 0.23-0.35), 5-minute Apgar < 7 (OR 0.30, 95% CI 0.25-0.36), male gender (OR 0.80, 95% CI 0.70-0.92), and anomalies (OR 0.49, 95% CI 0.41-0.58). Maternal hypertension was associated with lower SNAP-II (healthier infant) (7.54 +/- 11.16 [hypertensive] versus 7.21 +/- 11.85 [normotensive]) on multivariable regression analysis (adjusted OR 1.25, 95% CI 1.05-1.49), as well as higher neonatal survival (93.0% versus 91.2%, and adjusted OR 1.9, 95% CI 1.2-3.0), but not survival without severe intraventricular hemorrhage (91.4% versus 87.0%, and adjusted OR 1.4, 95% CI 1.0-2.0), respectively. Among SGA neonates in NICU, maternal hypertension is associated with improved admission neonatal physiology and survival.


Periprosthetic joint infection: are patients with multiple prosthetic joints at risk?
Patients who present with a periprosthetic joint infection in a single joint may have multiple prosthetic joints. The risk of these patients developing a subsequent infection in another prosthetic joint is unknown. Our purposes were (1) to identify the risk of developing a subsequent infection in another prosthetic joint and (2) to describe the time span and organism profile to the second prosthetic infection. We retrospectively identified 55 patients with periprosthetic joint infection who had another prosthetic joint in place at the time of presentation. Of the 55 patients, 11 (20%) developed a periprosthetic joint infection in a second joint. The type of organism was the same as the first infection in 4 (36%) of 11 patients. The time to developing a second infection averaged 2.0 years (range, 0-6.9 years).


Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia.
Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD.


Development of a control algorithm for the ultrasound scanning robot (NCCUSR) using ultrasound image and force feedback.
Clinicians who frequently perform ultrasound scanning procedures often suffer from musculoskeletal disorders, arthritis, and myalgias. To minimize their occurrence and to assist clinicians, ultrasound scanning robots have been developed worldwide. Although, to date, there is still no commercially available ultrasound scanning robot, many control methods have been suggested and researched. These control algorithms are either image based or force based. If the ultrasound scanning robot control algorithm was a combination of the two algorithms, it could benefit from the advantage of each one. However, there are no existing control methods for ultrasound scanning robots that combine force control and image analysis. Therefore, in this work, a control algorithm is developed for an ultrasound scanning robot using force feedback and ultrasound image analysis. A manipulator-type ultrasound scanning robot named 'NCCUSR' is developed and a control algorithm for this robot is suggested and verified. First, conventional hybrid position-force control is implemented for the robot and the hybrid position-force control algorithm is combined with ultrasound image analysis to fully control the robot. The control method is verified using a thyroid phantom. It was found that the proposed algorithm can be applied to control the ultrasound scanning robot and experimental outcomes suggest that the images acquired using the proposed control method can yield a rating score that is equivalent to images acquired directly by the clinicians. The proposed control method can be applied to control the ultrasound scanning robot. However, more work must be completed to verify the proposed control method in order to become clinically feasible. Copyright © 2016 John Wiley & Sons, Ltd.


Risk Stratification in Pediatric Wolff-Parkinson-White: Practice Variation Among Pediatric Cardiologists and Electrophysiologists.
Published guidelines provide recommendations for risk stratification in pediatric Wolff-Parkinson-White (WPW). There are no data on provider concordance with these guidelines. We hypothesized that significant practice variation exists between pediatric cardiologists (PC) and electrophysiologists (EP). The records of all patients, age 8 to 21 years, with a new ECG diagnosis of WPW between 1/1/2013 and 12/31/2018, from a single center, were retrospectively reviewed. Subjects were categorized on the basis of symptoms and resting ECG findings as one of the following: asymptomatic intermittent WPW, asymptomatic persistent WPW, or symptomatic WPW. The performance and results of diagnostic testing, including Holter monitor, event monitor, exercise stress test (EST), and electrophysiology study (EPS), were recorded. The primary outcome was concordance with published guidelines. A secondary outcome was documentation of a discussion of sudden cardiac death (SCD) risk. 615 patient encounters were analyzed in 231 patients with newly diagnosed WPW pattern on ECG (56% male; mean age at diagnosis 13.9 ± 2.5 years). EP were observed to have a significantly higher rate of guideline concordance than PC (95% vs. 71%, p < 0.001). There was significant practice variation between PC and EP in the documentation of a discussion of SCD risk: 96% in EP vs. 39% in PC (p < 0.001). Significant practice variation exists in the non-invasive and invasive risk stratification of pediatric WPW, with lower concordance to published guidelines amongst PC, when compared to EP. This report highlights the need to promote awareness of current WPW guidelines in the pediatric cardiology community at large.


The g3mclass is a practical software for multiclass classification on biomarkers.
The analytes qualified as biomarkers are potent tools to diagnose various diseases, monitor therapy responses, and design therapeutic interventions. The early assessment of the diverseness of human disease is essential for the speedy and cost-efficient implementation of personalized medicine. We developed g3mclass, the Gaussian mixture modeling software for molecular assay data classification. This software automates the validated multiclass classifier applicable to single analyte tests and multiplexing assays. The g3mclass achieves automation using the original semi-constrained expectation-maximization (EM) algorithm that allows inference from the test, control, and query data that human experts cannot interpret. In this study, we used real-world clinical data and gene expression datasets (ERBB2, ESR1, PGR) to provide examples of how g3mclass may help overcome the problems of over-/underdiagnosis and equivocal results in diagnostic tests for breast cancer. We showed the g3mclass output's accuracy, robustness, scalability, and interpretability. The user-friendly interface and free dissemination of this multi-platform software aim to ease its use by research laboratories, biomedical pharma, companion diagnostic developers, and healthcare regulators. Furthermore, the g3mclass automatic extracting information through probabilistic modeling is adaptable for blending with machine learning and artificial intelligence.


Production of human surfactant protein C in milk of transgenic mice.
Respiratory distress syndrome (RDS), caused by lack of pulmonary surfactant, affects 65 000 infants annually in the USA. Surfactant replacement therapy reduces the morbidity and mortality associated with RDS. Human surfactant protein C (SP-C) is an important component of pulmonary surfactant. To produce human SP-C, a construct using the rat whey acidic protein (WAP) promoter and 3' untranslated regions to target expression of the human SP-C gene to the mammary gland of transgenic mice was created. WAP/SP-C mRNA expression was detected in all transgenic lines analysed. SP-C was expressed in a copy-number-dependent and integration-site-independent fashion, with levels of expression ranging from 0.01% to 36.0% of the endogenous mouse WAP mRNA, and WAP/SP-C mRNA expression levels were greater than those of of the endogenous mouse lung SP-C mRNA. Expression at the RNA level was specific to the mammary gland and paralleled the endogenous WAP expression pattern during mammary gland development. Expression and secretion of the SP-C protein in the lactating mammary gland was demonstrated by western blots performed on whole milk using an anti-SP-C polyclonal antibody. Immunoreactive proteins of MW 22 and 12-14 kDa appeared only in transgenic milk. The 22 kDa protein represents the proprotein, and the 12-14 kDa is a processed form of SP-C.


Influence of nasotrigeminal afferents on medullary respiratory neurones and upper airway patency in the rat.
Noxious stimulation of the nasal mucosa evokes a nasotrigeminal reflex (diving response), consisting of apnoea, bradycardia and vasoconstriction. However, the central mechanisms underlying the respiratory component remain unclear. Here, we describe the influence of nasotrigeminal stimulation (NS) on different types of ventral medullary respiratory neurones and upper airway patency in the rat. In an arterially perfused working heart-brainstem preparation (WHBP), NS was induced by either irrigation of the nasal passage with cold saline (100-200 microl) or electrical stimulation of the trigeminal ethmoidal nerve (EN5, 20 Hz, 10 s, 100 micros, 0.5-2 V). Both stimuli evoked apnoea, bradycardia, a pressor response, persistent discharge in the recurrent laryngeal nerve and marked glottal adduction (P<0.001). NS evoked a distinct pattern of response in respiratory neurones: inspiratory (I) neurones ceased firing and hyperpolarized (n=19), while postinspiratory neurones depolarized (n=10) and discharged persistently. The latency of EN5-evoked synaptic responses (excitatory to postinspiratory neurones 12.3+/-2.8 ms, n=10; inhibitory to inspiratory neurones 11.8+/-1.9 ms; n=19) was comparable. During the NS-evoked apnoea burst discharges were superimposed on a maintained level of tonic activity recorded from both the recurrent laryngeal nerve (n=4) and some postinspiratory neurones (n=7). The physiological significance of these "apnoeic rhythms" is discussed. We conclude that the cardiorespiratory components of the diving response are mediated by activation of distinct sets of postinspiratory respiratory neurones.


The independent synthesis and secretion of cartilage proteoglycan and link protein by embryonic chicken chondrocytes.
The synthesis of cartilage link proteins was studied in organ cultures of sterna from normal and nanomelic chick embryos. Nanomelic chondrocytes synthesize cartilage-specific proteoglycans at 1 to 2% of normal levels, and therefore, nanomelic cartilage contains very little proteoglycan aggregate. The defect in proteoglycan synthesis results from a reduced availability of proteoglycan core protein. Link protein synthesis was monitored by the incorporation of [35S]cysteine into protein. Radiolabeled proteins were extracted from cartilage in 4 M guanidine hydrochloride and separated from proteoglycan monomer by centrifugation in dissociative cesium chloride density equilibrium gradients. The top one-sixth (D6) fraction of these gradients contained link protein and was used to extract one unlabeled normal sternum. These extracts were dialyzed to conditions permitting the formation of proteoglycan aggregates and chromatographed on controlled pore glass (CPG 2500). Proteoglycan aggregates chromatograph in the void volume (V0) of these columns. Radioactivity eluting in the CPG 2500 (V0 from normal and nanomelic D6 fractions was identified as link protein by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and subsequent fluorography. Link proteins were also extracted from unlabeled cartilages and identified by the Western blotting technique using link-specific antiserum. Immunoprecipitation of [35S]cysteine-labeled link protein from normal and nanomelic D6 fractions indicated that nanomelic chondrocytes synthesize link protein at normal levels.


Splanchnic elimination and systemic toxicity of bupivacaine and etidocaine in man.
Fifteen healthy young volunteers were studied in connection with an intravenous infusion of a local anaesthetic agent. Seven received bupivacaine and eight etidocaine in a dose rate of 2 mg.min-1 over a period of 150 min. The hepatic blood flow and arterial-hepatic venous differences of the two drugs were measured. The estimated hepatic blood flow increased during the infusion of both drugs. While the splanchnic extraction ratio decreased during infusion of bupivacaine to 0.41 +/- 0.13, the same variable did not change (0.76 +/- 0.07) when etidocaine was infused. After 150 min infusion, the splanchnic clearance of bupivacaine and etidocaine was 0.76 +/- 0.27 and 1.32 +/- 0.21 1.min-1, respectively. Slight symptoms of central nervous toxicity were noted towards the end of the bupivacaine infusion, while no such symptoms appeared with etidocaine. A comparison between earlier published data on the blocking properties and the disposition pharmacokinetics of the two drugs shows that etidocaine is likely to confer a clinical advantage over bupivacaine as regards toxicity.


Identification and characterization of novel bi-functional cathelicidins from the black-spotted frog (Pelophylax nigromaculata) with both anti-infective and antioxidant activities.
Cathelicidins are an important family of antimicrobial peptides (AMPs), which play pivotal roles in vertebrate immune responses against microbial infections. They are regarded as potential drug leads for the development of novel antimicrobial agents and three related drugs have been developed into clinical trials. Thus, it is meaningful to identify more cathelicidins from vertebrate species. Cathelicidins from ranid frogs possess special structural characteristics and activities, but to date only 12 ranid frog cathelicidins have been identified. In the present study, two novel cathelicidins (PN-CATH1 and 2) were identified from the black-spotted frog, Pelophylax nigromaculata. PN-CATHs possess low sequence similarity with the known cathelicidins. They exhibited moderate, but broad-spectrum and rapid antimicrobial activities against the tested bacteria. They kill bacteria by mainly inducing bacterial membrane disruption and possibly generating intracellular ROS formation. They also possess potent anti-biofilm and persister cell killing activity, indicating their potential in combating infections induced by biofilms-forming bacteria. Besides direct antimicrobial activity, they exhibited potent anti-inflammatory activity by effectively inhibiting the LPS-induced production of pro-inflammatory cytokines in mouse macrophages, which could be partly ascribed to their direct LPS-neutralizing ability. Furthermore, PN-CATHs demonstrated powerful in vitro free radical scavenging activities. Ultraviolet radiation significantly increased their in vivo gene expression in frog skin. Meanwhile, they possess weak cytotoxic activity and extremely low hemolytic activity. PN-CATHs represent the first discovery of cathelicidins family AMPs with both potent anti-infective and antioxidant activities. The discovery of PN-CATHs provides potential peptide leads for the development of novel anti-infective and antioxidant drugs.


Editorial.
In this issue ofNurse Researcher, Hillier and Gibbs cite two articles that assert: 'The performance of clinical trials without proper size calculations is unethical.' This argument can be expanded to encompass the undertaking of any clinical study irrespective of the methodological approach employed.


Claudin-11 expression increased in spermatogenic defect in human testes.
Expression of claudin-11, which builds up blood-testis barrier (BTB), was increased in decreased spermatogenesis, including in hypospermatogenesis, spermatocytic and maturation arrest, and Sertoli cell only (SCO) testes. Increased claudin-11 immunoreactivity was observed at the inter-Sertoli tight junctions in maturation arrest and in the cytoplasm of Sertoli cells in SCO. The late spermatogenic wave may negatively regulate claudin-11 gene activation and the subcellular localization of claudin-11 in Sertoli cells, thus altering the BTB in the human testis.


Optimization of engine parameters using NSGA II for the comprehensive reduction of emissions from VCR engine fuelled with ROME biodiesel.
Diesel engines are most widely used as power plant for many applications, like automotive, agricultural purposes, portable machines and remote location power generation, because of their higher torque, power output, energy content per unit mass and cost of fuel. Because of the higher compression ratios, the diesel engines are able to produce greater cylinder pressures resulting in higher temperatures and thermal efficiency. On other hand, the diesel engines produce COx, NOx, Soot and sulphur emissions which are harmful and these pollute the environment leading to acid rain, global warming and variety of human diseases. Also, the present emission regulations are framed such a way to ensure the environmental sustainability in addition to the economic and social importance. These constraints make the researchers find an alternate fuel for replacing the diesel fuel on the existing diesel engines for the reduction of environmental pollutions. Biodiesel is found to be a very good alternative fuel obtained from natural resources and having good energy with least possible emissions. Rubber seed methyl ester (ROME) is one kind of the biofuel can be used in the existing diesel without any engine modifications. The ROME is produced using trans esterification process and the biodiesel blends are prepared in the sequence of B20, B40, B60 and B80. The ROME is tested on the Variable Compression Ratio (VCR) engine to test the emission characteristic in line with the performance characteristics. To reduce the emissions, the prediction models are developed for CO and NOx using the Response Surface Methodology (RSM). The models are verified through the ANOVA and p-test for their adequacy to create the hypothesis of the experimentation. The NSGA II evolutionary multi-objective optimization is used to optimise the engine parameters to minimise the pollutions from the ROME fuelled engine. The optimized parameters are tested and verified experimentally for the least possible emissions.


Pictures in health information and their pitfalls: Focus group study and systematic review.
Health information often includes different categories of pictures. This study comprises: A) exploration of the perception of photos presented in a brochure on the prevention of osteoporosis and B) a systematic review on the effects of pictures in health information. A) We conducted four focus groups. Participants with heterogeneous cultural and educational background were included. The interviews were subjected to qualitative content analysis. B) We searched PubMed, CENTRAL, PSYNDEX, PsycINFO, CINAHL, Campbell Collaboration and DIMDI. Randomized controlled trials (RCTs) on predefined cognitive and affective outcomes were included. Two reviewers independently extracted data and assessed the quality of evidence. Descriptive data synthesis was conducted. A) Within the focus groups comprising 37 participants, four generic categories were identified: comprehension, perception, congruence between photos and content, and alternatives. Identification with portrait photos and the connection between photos and text were important to participants. B) In total, 13 RCTs were included. Quality of evidence was moderate. Types of pictures and their intention varied between studies. Cartoons enhanced comprehension, satisfaction and readability. Photos did not improve cognitive or affective outcomes. Effects of anatomical pictures, pictographs, and drawings were ambiguous. The overall effect of using pictures in health information remains unclear. The type of pictures and readers' characteristics may influence both perception and interpretation. Type, amount, and intention of the pictures should be considered carefully.


[One-stop outpatient cardiology clinics: 10 years' experience].
A one-stop outpatient cardiology clinic was set up at the Vic General Hospital in Spain in 1996. The aims were to provide patients with a rapid response, and to ensure that, on the same day, they saw a specialist and were referred for any relevant investigations required, primarily echocardiography, exercise testing, and Holter monitoring. We report experience from 10 years of follow-up, involving 19,515 consultations. The mean waiting time for a consultation was 3 days. We analyzed the reasons for the consultations, the investigations carried out, and the reductions in follow-up visits and hospital admissions. Primary care physicians' level of satisfaction was increased by this approach. The one-stop clinic proved feasible in clinical practice and proved robust during the follow-up period. This clinical model was beneficial for patients, was highly acceptable to primary care physicians, reduced the need for patients to contact the hospital, and, possibly, reduced hospital admissions.


In vitro and in silico analysis of the predicted human MOB gene encoding a phylogenetically conserved transmembrane protein.
A novel evolutionary conserved human MOB gene of seven exons is predicted on the chromosome 10. MOB is supposed to express predominately in brain. At least three types of MOB transcripts are proposed. A protein encoded by MOB is five-pass transmembrane molecule.


[A selective review of recent research results in biological psychiatry].
In accordance with the motto of this year's German Society for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) conference, this article surveys very recent developments in biological psychiatry and neurosciences that have the potential to open up new vistas for the psychiatry and psychotherapy of the future. The work reported includes progress in genome-wide association studies, the implications of these findings for psychiatric nosology and gene-environment interactions, new methods to characterize mechanisms of altered brain function in animal models and humans and the translation of these findings into new therapies. As a core methodology for the psychiatry of the future, biological and applied neuroscience approaches should benefit from sustained structural funding to ensure that these advances impact real-world patient care.


Integration of ozone, UV/H2O2 and GAC in a multi-barrier treatment for secondary effluent polishing: Reuse parameters and micropollutants removal.
Current studies tend to combine different advanced treatment technologies to reduce costs and increase efficiency. The objective of this work was to assess the combination of ozonation and UV/H2O2 with activated carbon adsorption for the removal of effluent quality parameters and micropollutants from secondary effluent samples. The experiments were carried out using the following configurations: O3 + GAC + O3 (1); O3 + GAC + UV/H2O2 (2); UV/H2O2 + GAC + O3 (3); UV/H2O2 + GAC + UV/H2O2 (4). Configurations 1, 3 and 4 were the most efficient for organic matter removal, while configuration 1 had the lowest cost on laboratory scale. An additional ultra-filtration membrane unit (UF) was tested at the end of configuration 1, which was optimized in terms of ozone doses for the removal of three organophosphate micropollutants in ultrapure water (TNBP, TCIPP and TPHP at 10 μgL-1). The best cost-effective configuration of this treatment train was the one using 1 mg L-1 of ozone before and after GAC, which achieved around 100% of micropollutants abatement. The role of each treatment to the final micropollutant removal was also discussed, being the first ozone treatment responsible for about 15% removal of the mixture of contaminants, while GAC was responsible for an additional 80% removal. The complete treatment train reached almost 100% of contaminants removal (under detection limit of the method), as well as added security to the system. The achieved results were also compared to international reuse legislations, proving that the combination of O3 and GAC was an interesting option to achieve enough quality for some reuse purposes.


Bending and metallurgical properties of rotary endodontic instruments. IV. Gates Glidden and Peeso drills.
A laboratory study was performed on Gates Glidden and Peeso drills to determine the bending characteristics and related metallurgical properties. Sizes #1 to #6 stainless steel Gates Glidden drills, sizes #1 to #6 stainless steel and carbon steel type P Peeso drills, and sizes #009 to #023 carbon steel-type B-1 Peeso drills were evaluated in cantilever bending with a Tinius Olsen stiffness tester. The bending moments were measured for a 12.5-mm test span at deflection angles of 2 to 90 degrees. The mean maximum bending moments in g cm and the corresponding deflection angles in degrees were plotted graphically to ascertain the bending characteristics of the instruments. The stainless steel Gates Glidden and Peeso drills exhibited considerable permanent bending deformation during testing. Some stainless steel drill samples were able to withstand the full bending deflection of 90 degrees without fracturing. In contrast, the carbon steel Peeso drills were able only to undergo bending deflections of less than 20 degrees and exhibited brittle fracture. If the drill fractured during the in vitro testing, the failure site was always located near the handpiece end.


Functional redundancy in natural pico-phytoplankton communities depends on temperature and biogeography.
Biodiversity affects ecosystem function, and how this relationship will change in a warming world is a major and well-examined question in ecology. Yet, it remains understudied for pico-phytoplankton communities, which contribute to carbon cycles and aquatic food webs year-round. Observational studies show a link between phytoplankton community diversity and ecosystem stability, but there is only scarce causal or empirical evidence. Here, we sampled phytoplankton communities from two geographically related regions with distinct thermal and biological properties in the Southern Baltic Sea and carried out a series of dilution/regrowth experiments across three assay temperatures. This allowed us to investigate the effects of loss of rare taxa and establish causal links in natural communities between species richness and several ecologically relevant traits (e.g. size, biomass production, and oxygen production), depending on sampling location and assay temperature. We found that the samples' biogeographical origin determined whether and how functional redundancy changed as a function of temperature for all traits under investigation. Samples obtained from the slightly warmer and more thermally variable regions showed overall high functional redundancy. Samples from the slightly cooler, less variable, stations showed little functional redundancy, i.e. function decreased when species were lost from the community. The differences between regions were more pronounced at elevated assay temperatures. Our results imply that the importance of rare species and the amount of species required to maintain ecosystem function even under short-term warming may differ drastically even within geographically closely related regions of the same ecosystem.


A review on EMG/EEG based control scheme of upper limb rehabilitation robots for stroke patients.
Stroke is a common worldwide health problem and a crucial contributor to gained disability. The abilities of people, who are subjected to stroke, to live independently are significantly affected since affected upper limbs' functions are essential for our daily life. This review article focuses on emerging trends in BCI-controlled rehabilitation techniques based on EMG, EEG, or EGM + EEG signals in the last few years. Working on developing rehabilitation robotics, is considered a wealthy scientific area for researchers in the last period. There is a significant advantage that the human acquires from the interaction between the machine and his body, rehabilitation for a patient's limb is very important to get the body limb recovery, and this is what is provided mostly by applying robotic devices.


Risk factor analysis of thymoma resection and its value in guiding clinical treatment.
In this study, relationships between clinicopathologic characteristics and progression-free survival (PFS) of patients after thymomectomy were analyzed to provide valuable suggestions regarding the treatment of thymoma. Data from 187 thymoma patients undergoing surgery at Beijing Tongren Hospital between January 1, 2006, and December 31, 2015, were retrospectively reviewed. We explored the risk factors for PFS among sex, age, thymoma-associated MG, completeness of resection, histologic type and TNM stage, and investigated their interrelationship. Among the 187 patients, 18 patients (9.63%) had tumor recurrence/metastasis, and all of whom had in situ recurrence or pleural metastasis, and most of them (10 of 18 patients) had MG symptoms that reappeared or were aggravated. Fifteen patients (8.02%) died, and myasthenic crisis was a leading cause. Based on Cox regression analysis, only age (HR = 3.16; 95% CI: 1.44-6.91; p = 0.004) and the completeness of resection (HR = 9.03; 95% CI: 2.58-31.55; p = 0.001) were independent risk factors for PFS. Furthermore, we found that the completeness of resection was related to the histologic type (p = 0.009) and TNM stage (p < 0.001) by Fisher's exact test. The results of this cohort study remind us that we should pay attention to the reappearance or aggravation of MG after thymoma resection, because it is the leading cause of death and may indicate tumor progression. Furthermore, completeness of resection was related to the histologic type and TNM stage, but it was the independent risk factors of thymoma. Therefore, R0 resection is critical to the prognosis of thymoma.


An inexpensive method of indirect ophthalmoscopy.
Attention is drawn to the possibility of performing monocular indirect ophthalmoscopy with a pen torch and a condensing lens when facilities for binocular indirect ophthalmoscopy are not available.


The glutathione status of the rat liver.
For the determination of cellular total glutathione, a new method is presented based on a fluorometric procedure. The relation between reduced glutathione, mixed glutathione disulfides and disulfide glutathione will be designated the glutathione status.


Type V collagen. Quantitation in normal lungs and in lungs of rats with bleomycin-induced pulmonary fibrosis.
Type V collagen was first isolated in 1976; there is still controversy as to how many molecular species of type V collagen exist. Although its structural and functional roles remain unclear, reports of changes in the relative amount of type V collagen from that present in normal tissue have been reported in such diverse pathologic conditions as atherosclerotic aortas, prolapsed mitral valves, and fibrotic lungs. Methods for quantitating type V collagen relative to other collagens have consisted of solubilizing the collagen with pepsin and then analyzing the ratios of the intact chains by gel electrophoresis or by column chromatography. In tissues in which only a small percentage of the total collagen can be solubilized by pepsin, such analyses may not accurately reflect changes in the total collagen present. In this report, a method for quantitating type V collagen relative to types I and III collagens based on CNBr peptide mapping is presented. CNBr solubilizes virtually all the collagen present in any tissue. The method is applied to a model of bleomycin-induced pulmonary fibrosis in rats. It was found that type I collagen increased relative to types III and V collagens, which seemed to remain at values comparable to those observed in lungs from control (normal) rats, both in terms of newly synthesized collagen (collagen synthesized by lung minces during 4 h in culture) and total unlabeled lung collagen (collagen synthesized during the life of the animal).


Hydrogen sulfide: Recent development of its dual donors and hybrid drugs.
Hydrogen sulfide (H2 S) is an important gaseous signalling molecule known to be critically involved in regulating cellular redox homeostasis. As the beneficial and therapeutic effects of H2 S in pathophysiology, such as in cardiovascular and neurodegenerative diseases, have emerged, so too has the drive for the development of H2 S-releasing compounds (aka donors) and their therapeutic applications. Most reported donor compounds singularly release H2 S through biocompatible triggers. An emerging area in the field is the development of compounds that can co-deliver H2 S with other drugs or biologically relevant species, such as reactive oxygen and nitrogen species (ROS and RNS, respectively). These H2 S-based dual donors and hybrid drugs are expected to offset negative side effects from individual treatments or achieve synergistic effects rendering them more clinically effective. Additionally, considering that molecules exist and interact physiologically, dual donors may more accurately mimic biological systems as compared to single donors and allow for the elucidation of fundamental chemistry and biology. This review focuses on the recent advances in the development of H2 S-based dual donors and hybrid drugs along with their design principles and synergistic effects.


Efficient route to high-bandwidth nanoscale magnetometry using single spins in diamond.
Nitrogen-vacancy (NV) center in diamond is a promising quantum metrology tool finding applications across disciplines. The spin sensor measures magnetic fields, electric fields and temperature with nano-scale precision and is fully operable under ambient conditions. Moreover, it achieves precision scaling inversely with total measurement time σB ∝ 1/T (Heisenberg scaling) rather than as the inverse of the square root of T, with σB = √T the Shot-Noise limit. This scaling can be achieved by means of phase estimation algorithms (PEAs), in combination with single-shot read-out. Despite their accuracy, the range of applicability of PEAs is limited to sensing single frequencies with negligible temporal fluctuations. Nuclear Magnetic Resonance (NMR) signals from molecules often contain multifrequency components and sensing them using PEA is ruled out. Here we propose an alternative method for precision magnetometry in frequency multiplexed signals via compressive sensing (CS) techniques focusing on nanoscale NMR. We show that CS can provide for precision scaling approximately as σB ≈ 1/T, as well as for a 5-fold increase in sensitivity over dynamic-range gain, in addition to reducing the total number of resources required. We illustrate our method by taking model solid-state spectra of Glycine acquired under Magic Angle Spinning conditions.


Theoretical perspectives accounting for adolescent homosexuality.
Few topics in sexology elicit such a diversity of opinions and emotions as the question of etiology of homosexuality. Views frequently carry with them implicit or explicit messages concerning the psychologic health of this sexual orientation. Theories of sexual development usually portray adolescence as a critical time in the life course because of changes in: 1) anatomy and physiology; 2) psychologic functioning: the reawakening, renewal, and reliving of previously established sexual relations and drives; and/or 3) social conditions: an increased exposure and adherence to societal messages concerning appropriate and inappropriate social and sexual behaviors and relationships. This paper provides a brief overview of several major theories--evolutionary biology, psychoanalysis, and social processes--as they relate to the development of sexual orientation. In addition, an ethologic perspective that synthesizes various etiologic theories, as they relate to homosexuality during adolescence, is briefly reviewed. In these discussions, the issue of whether homosexuality is a normal or abnormal developmental state during adolescence is also addressed.


An Update on Inpatient Hypertension Management.
Hypertension is highly prevalent affecting nearly one third of the US adult population. Though generally approached as an outpatient disorder, elevated blood pressure is observed in a majority of hospitalized patients. The spectrum of hypertensive disease ranges from patients with hypertensive emergency including markedly elevated blood pressure and associated end-organ damage to asymptomatic patients with minimally elevated pressures of unclear significance. It is important to note that current evidence-based hypertension guidelines do not specifically address inpatient hypertension. This narrative review focuses primarily on best practices for diagnosing and managing nonemergent hypertension in the inpatient setting. We describe examples of common hypertensive syndromes, provide suggestions for optimal post-acute management, and point to evidence-based or consensus guidelines where available. In addition, we describe a practical approach to managing asymptomatic elevated blood pressure observed in the inpatient setting. Finally, arranging effective care transitions to ensure optimal ongoing hypertension management is appropriate in all cases.


Biomechanical study of the programming of anticipatory postural adjustments associated with voluntary movement.
The present research concerns anticipatory postural adjustments (APA), with the purpose of determining whether they are preprogrammed and of specifying their biomechanical finality. The experimental situation allowed us to distinguish between the voluntary movement itself (an upper limb elevation) and the postural adjustments associated with it. To this aim, the upper limb kinematics, evaluated from an accelerometer fixed at wrist level, were compared to the whole body dynamics, recorded by means of a force platform. Movements, executed in series of five, were studied according to three conditions: bilateral flexions (BF) and unilateral flexions (UF), with (IUF) and without (OUF) an additional inertia, of the stretched upper limb(s). Six right handed adults were tested twice. Results showed that the ground reaction resultant forces as well as the ground reaction resultant moment about the vertical axis presented reproducible variations before and after the onset of upper limb acceleration. The biomechanical organization of APA corresponded, for the three experimental conditions, to an upward and forward acceleration of the body center of gravity, and also, for UF, to a resultant moment directed towards the contralateral side. The duration of APA varied with the characteristics of the forthcoming voluntary movement, increasing significantly from BF to OUF and from OUF to IUF. It is concluded that APA correspond to dynamic phenomena which are centrally preprogrammed. The inertia forces associated with APA may, when the time comes, balance the inertia forces due to the movement of the mobile limb therefore counteracting the disturbance to postural equilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)


Forensic discrimination of blue ballpoint pens on documents by laser ablation inductively coupled plasma mass spectrometry and multivariate analysis.
The differentiation of blue ballpoint pen inks written on documents through an LA-ICP-MS methodology is proposed. Small common office paper portions containing ink strokes from 21 blue pens of known origin were cut and measured without any sample preparation. In a first step, Mg, Ca and Sr were proposed as internal standards (ISs) and used in order to normalize elemental intensities and subtract background signals from the paper. Then, specific criteria were designed and employed to identify target elements (Li, V, Mn, Co, Ni, Cu, Zn, Zr, Sn, W and Pb) which resulted independent of the IS chosen in a 98% of the cases and allowed a qualitative clustering of the samples. In a second step, an elemental-related ratio (ink ratio) based on the targets previously identified was used to obtain mass independent intensities and perform pairwise comparisons by means of multivariate statistical analyses (MANOVA, Tukey's HSD and T2 Hotelling). This treatment improved the discrimination power (DP) and provided objective results, achieving a complete differentiation among different brands and a partial differentiation within pen inks from the same brands. The designed data treatment, together with the use of multivariate statistical tools, represents an easy and useful tool for differentiating among blue ballpoint pen inks, with hardly sample destruction and without the need for methodological calibrations, being its use potentially advantageous from a forensic-practice standpoint. To test the procedure, it was applied to analyze real handwritten questioned contracts, previously studied by the Department of Forensic Document Exams of the Criminalistics Service of Civil Guard (Spain). The results showed that all questioned ink entries were clustered in the same group, being those different from the remaining ink on the document.


Synthesis of Chalcones Derivatives and Their Biological Activities: A Review.
Chalcone derivatives are considered valuable species because they possess a ketoethylenic moiety, CO-CH=CH-. Due to the presence of a reactive α,β-unsaturated carbonyl group, chalcones and their derivatives possess a wide spectrum of antiproliferative, antifungal, antibacterial, antiviral, antileishmanial, and antimalarial pharmacological properties. Recent developments in heterocyclic chemistry have led to the synthesis of chalcone derivatives, which had been biologically investigated toward certain disease targets. The major aspect of this review is to present the most recent synthesis of chalcones bearing N, O, and/or S heterocycles, revealing their biological potential during the past decade (2010-2021). Based on a review of the literature, many chalcone-heterocycle hybrids appear to exhibit promise as future drug candidates owing to their similar or superior activities compared to those of the standards. Thus, this review may prove to be beneficial for the development and design of new potent therapeutic drugs based on previously developed strategies.


Acute pro-inflammatory actions of endothelin-1 in the guinea-pig lung: involvement of ETA and ETB receptors.
1. Although recent observations suggest that endothelin-1 (ET-1) may play a role in the pathogenesis of asthma, to date little is known about the effects of ET-1 on parameters other than bronchoconstriction. The objectives of the present experiments were to study whether intravenously administered ET-1 could exert pro-inflammatory actions in the guinea-pig lung and to assess the involvement of endothelin ETA and ETB receptors in these events by using the ETA receptor-selective antagonist, FR 139317, the novel ETA/ETB receptor antagonist, bosentan and the ETB receptor-selective agonist, IRL 1620. 2. Bolus i.v. injection of ET-1 (0.1-1 nmol kg-1) to anaesthetized guinea-pigs evoked dose-dependent increases in mean arterial blood pressure which lasted for 6-12 min. This was accompanied by a dose-dependent haemoconcentration (8-15% plasma volume losses) and increases (up to 546%) in albumin extravasation in the trachea, upper and lower bronchi, but not in the pulmonary parenchyma. Qualitatively similar changes were observed following i.v. injection of the ETB receptor agonist, IRL 1620 (0.3 and 1 nmol kg-1), although IRL 1620 appeared to be about 3 times less potent than ET-1. The ETA receptor-selective antagonist, FR 139317 (2.5 mg kg-1) inhibited the ET-1 (1 nmol kg-1)-induced pressor response, haemoconcentration and albumin extravasation by 75, 77 and 60-70%, respectively, whereas it did not attenuate IRL 1620 (1 nmol kg-1)-induced changes. The ETA/ETB receptor antagonist, bosentan (10 mg kg-1) almost completely inhibited the pressor, haemoconcentration and permeability effects of both ET-1 and IRL 1620. 3. ET-1, but not IRL 1620 (0.1-1 nmol kg-1), produced a dose-dependent neutropenia with relative lymphocytosis and monocytosis, but did not induce influx of neutrophil granulocytes into pulmonary tissues or the bronchoalveolar space. ET-1 (1 nmol kg-1)-induced neutropenia was prevented by pretreatment of the animals with FR 139317 (2.5 mg kg-1), bosentan (10 mg kg-1) or adrenaline (90 nmol kg-1), indicating that ET-1 caused intravascular sequestration of neutrophil granulocytes. 4. ET-1 or IRL 1620 (10(-10)-10(-6) M) alone did not activate alveolar macrophages in vitro, whereas at a concentration of 10(-8) M, ET-1, but not IRL 1620, markedly potentiated superoxide production in response to f-Met-Leu-Phe (10(-9)-10(-7) M) and platelet-activating factor (PAF, 10(-9)-10(-7) M), but not to phorbol 12-myristate 13-acetate (10(-9) M). ET-1 did not affect f-Met-Leu-Phe- or PAF-induced increases in intracellular free calcium concentration. This potentiating effect of ET-1 was abolished by FR 139317(1.5 X 10-7 M).5. We conclude that, in addition to evoking airway contractions, ET-1 exerts pro-inflammatory actions via activation of the ETA and to a lesser extent the ETB receptors, and therefore, might contribute to the airway inflammation present in asthma. These findings also suggest the therapeutic potential of ETA/ETB receptor and perhaps ETA receptor-selective antagonists in this disease.


Properties of an E. coli O26 mutant with modified cell wall and improved efficiency as recipient in conjugation for an FII plasmid.
Among populations of an E. coli O26 strain two types of mutants have been found to be present which act as better recipients in conjugation for an FII plasmid. Some properties of one of these mutants, O26SMB9, are here described. They indicate that a defect in the cell-wall structure has occurred which corresponds to a smooth----semirough transition.


Technology-Enhanced Preclinical Medical Education (Anatomy, Histology and Occasionally, Biochemistry): A Practical Guide.
The recent explosion of technological innovations in mobile technology, virtual reality (VR), digital dissection, online learning platform, 3D printing, and augmented reality (AR) has provided new avenues for improving preclinical education, particularly in anatomy and histology education. Anatomy and histology are fundamental components of medical education that teach students the essential knowledge of human body structure and organization. However, these subjects are widely considered to be some of the most difficult disciplines for healthcare students. Students often face challenges in areas such as the complexity and overwhelming volume of knowledge, difficulties in visualizing body structures, navigating and identifying tissue specimens, limited exposure to learning materials, and lack of clinical relevance. The COVID-19 pandemic has further exacerbated the situation by reducing face-to-face teaching opportunities and affecting the availability of body donations for medical education.To overcome these challenges, educators have integrated various educational technologies, such as virtual reality, digital 3D anatomy apps, 3D printing, and AI chatbots, into preclinical education. These technologies have effectively improved students' learning experiences and knowledge retention. However, the integration of technologies into preclinical education requires appropriate pedagogical approaches and logistics to align with educational theories and achieve the intended learning outcomes.The chapter provides practical guidance and examples for integrating technologies into anatomy, histology, and biochemistry preclinical education. The author emphasizes that every technology has its own benefits and limitations and is best suited to specific learning scenarios. Therefore, it is recommended that educators and students should utilize multiple modalities for teaching and learning to achieve the best outcomes. The chapter also acknowledges that cadaver-based anatomy education is essential and proposes that educational technologies can serve as a crucial complement for promoting active learning, problem solving, knowledge application, and enhancing conventional cadaver-based education.


Somatic Embryogenesis in Broad-Leaf Woody Plants: What We Can Learn from Proteomics.
Proteomic approaches have been used to understand several regulatory aspects of plant development. Somatic embryogenesis is one of those developmental pathways that have beneficiated from the integration of proteomics data to the understanding of the molecular mechanisms that control embryogenic competence acquisition, somatic embryo development and conversion into viable plants. Nevertheless, most of the results obtained are based on the traditional model systems, very often not easily compared with the somatic embryogenesis systems of economical relevant woody species. The aim of this work is to summarize some of the applications of proteomics in the understanding of particular aspects of the somatic embryogenesis process in broad-leaf woody plants (model and non-model systems).


Applying a Strengths-Based Psychoeducational Model of Rehabilitation to the Treatment of Intimate Partner Violence: Program Theory and Logic Model.
In the United Kingdom, there is an increasing need to develop prevention programs for intimate partner violence and abuse (IPVA). However, this need has increased within a context of increasing financial pressure. Consequently, commissioners are expressing interest in models of prevention that are brief. This article first reviews the effectiveness of domestic violence (DV) prevention programs, including those from England and Wales. This article then describes the theoretical development of an emerging IPVA prevention program that combines solution-focused brief therapy (SFBT) and cognitive behavioral therapy (CBT) methods. The article addresses how CBT content is integrated within the SFBT approach and provides details of the intervention logic model.


Indocyanine green angiography in isolated primary retinal arterial macroaneurysms.
The study was carried out to describe the indocyanine green angiographic findings in isolated primary retinal arterial macroaneurysms and their contribution to the diagnosis of this condition. Fluorescein and indocyanine green angiography examination techniques were used to study isolated primary retinal arterial macroaneurysms in 8 consecutive patients with retinal or preretinal haemorrhage over a period of 12 months. The fluorescein angiography examination showed the macroaneurysm in four cases; pulsatility was not observed in any case. Indocyanine green angiography disclosed the macroaneurysm in six cases; pulsatility was observed in two cases. Indocyanine green angiography allows better visualization of arterial macroaneurisms in the first examination and therefore facilitates the diagnosis, follow-up and laser treatment of this vascular abnormality.


A stimulator for studies of mechanical nociception based upon a commercially available translation table.
We have developed a mechanical stimulator that can be used for studies of sensory physiology, psychophysics and tissue mechanics. The stimulator operates in either displacement or force-servo modes. It surpasses other available stimulators in respect to displacement range, measurement sensitivity and cost, and it can be easily assembled from parts that are commercially available.


[Validated diagnostics for dysgrammatism].
Non-standardized procedures are used to evaluate, in particular, grammatical performance in most German institutions performing diagnostic procedures on children with impaired speech and language development. This makes a comparison of results difficult. We studied 181 boys and 72 girls aged between 5 and 6 years using four subtests of IDIS additionally to the routine procedure. Results were compared to the "degree of dysgrammatism" determined from the traditional evaluation based on expert rating. The new procedure is able to divide the children into groups with normal speech and language ability, with deficits accessible to a traditional logopedic treatment, and with severe speech and language impairment that necessitates intensive treatment. The proposed tests allow an accurate evaluation of grammatical performance instead of subjective estimates.


Age-Specific Functional Response of Aphidius matricariae and Praon volucre (Hymenoptera: Braconidae) on Myzus persicae (Hemiptera: Aphididae).
The green peach aphid, Myzus persicae (Sulzer), is one of the most important aphid pests on pepper. Aphidius matricariae Haliday and Praon volucre (Haliday) are known as biological control agents for aphids in vegetable crops. In this research, age-specific functional responses of these two parasitoids were evaluated on different densities of 2, 4, 8, 16, 32, and 64 green peach aphids. Type of functional response varied from type II to type III for different ages of A. matricariae, but type of functional response was not affected by female age for P. volucre. The functional response of P. volucre was determined as type II in the whole parasitoid lifetime. The searching efficiency (a), b, and handling time (T h ) were estimated using the Rogers equations. The highest searching efficiency (a) and lowest handling time were observed during the first half of lifetime of A. matricariae and P. volucre. Aphidius matricariae and P. volucre caused reasonable mortality of the green peach aphid by parasitism of 52.17 and 47.05 host aphids, respectively, in 24 h. Therefore, they are suggested as suitable candidates for control of M. persicae in pepper greenhouses.


Short O-O separation in layered oxide Na0.67CoO2 enables an ultrafast oxygen evolution reaction.
The layered oxide Na0.67CoO2 with Na+ occupying trigonal prismatic sites between CoO2 layers exhibits a remarkably high room temperature oxygen evolution reaction (OER) activity in alkaline solution. The high activity is attributed to an unusually short O-O separation that favors formation of peroxide ions by O--O- interactions followed by O2 evolution in preference to the conventional route through surface O-OH- species. The dependence of the onset potential on the pH of the alkaline solution was found to be consistent with the loss of H+ ions from the surface oxygen to provide surface O- that may either be attacked by solution OH- or react with another O-; a short O-O separation favors the latter route. The role of a strong hybridization of the O-2p and low-spin CoIII/CoIV π-bonding d states is also important; the OER on other CoIII/CoIV oxides is compared with that on Na0.67CoO2 as well as that on IrO2.


CpG motifs as adjuvant in DNA vaccination against Chlamydophila psittaci in turkeys.
Plasmid DNA (pcDNA1::MOMP) expressing the major outer membrane protein (MOMP) of an avian Chlamydophila psittaci serovar D strain and recombinant MOMP (rMOMP) with or without the immunomodulating CpG oligonucleotides (CpG ON) were tested for their ability to elicit an immune response and to induce protection in turkeys against homologous challenge. Two CpG ON were chosen for in vivo application based on their in vitro capacity to stimulate the production of nitric oxide (NO) in chicken macrophages and their in vitro capacity to induce turkey lymphocyte proliferation. Priming and boosting of turkeys with pcDNA1::MOMP was able to prevent severe clinical signs and bacterial replication in a turkey model of C. psittaci infection. rMOMP boosting induced high antibody titers, but these did not correlate with the level of protection. Although the CpG ON induced a significant in vitro response, the presence of the CpG ON as an adjuvant generated no significant effect on the immune response or on the protective capacity of the tested vaccination methods.


Novel antimalarial chloroquine- and primaquine-quinoxaline 1,4-di-N-oxide hybrids: Design, synthesis, Plasmodium life cycle stage profile, and preliminary toxicity studies.
Emergence of drug resistance and targeting all stages of the parasite life cycle are currently the major challenges in antimalarial chemotherapy. Molecular hybridization combining two scaffolds in a single molecule is an innovative strategy for achieving these goals. In this work, a series of novel quinoxaline 1,4-di-N-oxide hybrids containing either chloroquine or primaquine pharmacophores was designed, synthesized and tested against both chloroquine sensitive and multidrug resistant strains of Plasmodium falciparum. Only chloroquine-based compounds exhibited potent blood stage activity with compounds 4b and 4e being the most active and selective hybrids at this parasite stage. Based on their intraerythrocytic activity and selectivity or their chemical nature, seven hybrids were then evaluated against the liver stage of Plasmodium yoelii, Plasmodium berghei and Plasmodium falciparum infections. Compound 4b was the only chloroquine-quinoxaline 1,4-di-N-oxide hybrid with a moderate liver activity, whereas compound 6a and 6b were identified as the most active primaquine-based hybrids against exoerythrocytic stages, displaying enhanced liver activity against P. yoelii and P. berghei, respectively, and better SI values than primaquine. Although both primaquine-quinoxaline 1,4-di-N-oxide hybrids slightly reduced the infection of mosquitoes, they inhibited sporogony of P. berghei and compound 6a showed 92% blocking of transmission. In vivo liver efficacy assays revealed that compound 6a showed causal prophylactic activity affording parasitaemia reduction of up to 95% on day 4. Absence of genotoxicity and in vivo acute toxicity were also determined. These results suggest the approach of primaquine-quinoxaline 1,4-di-N-oxide hybrids as new potential dual-acting antimalarials for further investigation.


Combined scalp reduction and autologous fat implant treatment of localized soft tissue defects.
Autologous fat grafts have recently gained popularity in the treatment of soft tissue defects of the face. We report on two patients with circumscribed scalp alopecia and linear forehead depressions treated with a combination of scalp reduction and autologous fat implants. The patients had significant cosmetic improvement without complications.


Variation of carbon and isotope natural abundances (δ15N and δ13C) of whole-plant sweet potato (Ipomoea batatas L.) subjected to prolonged water stress.
Sweet potato (Ipomoea batatas L.) is an important crop in the world, cultivated in temperate climates under low inputs. Drought changes the plant biomass allocation, together with the carbon and nitrogen isotopic composition (δ13C and δ15N), whose changes are faintly known in sweet potato crops. Here, we show the biomass allocation of eight sweet potato accessions submitted to drought during 3 months, using the δ13C, δ15N, carbon isotope discrimination (Δ13C), total carbon (TC) and water use efficiency (WUE) traits. The tolerant accessions had improved WUE, with higher TPB and TC. Storage roots and shoots had a heavier δ13C content under drought stress, with greater 13C fixation in roots. The Δ13C did not show a significant association with WUE. The δ15N values indicated a generalised N reallocation between whole-plant organs under drought, as a physiological integrator of response to environmental stress. This information can aid the selection of traits to be used in sweet potato breeding programs, to adapt this crop to climate change.


Porphyrinosilica and metalloporphyrinosilica: hybrid organic-inorganic materials prepared by sol-gel processing
New materials porphyrinosilica and metalloporphyrinosilica template have been obtained by a sol-gel processing where functionalyzed porphyrins and metalloporphyrins "building blocks" were assembled into a three-dimensional silicate network. The optimized conditions for preparation of these materials are revised. The monomer precursors porphyrinopropylsilyl and metalloporphyrinopropylsilyl preparation reactions and subsequent one pot sol-gel processing with tetraethoxysilane are discussed. In the case of metalloporphyrins the nitrogen base coordinates to the central metal and acts as a template in the molecular imprinting technique. UV-visible absorption spectroscopy, thermogravimetric analysis, electron paramagnetic resonance, nuclear magnetic spectra, infrared spectra, luminescence spectra, surface area and electron spectroscopy imaging of the materials are used to characterize the prepared materials. The catalytic activities of these metalloporphyrinosilica-template are compared.


Community acquired multi-drug resistant clinical isolates of Escherichia coli in a tertiary care center of Nepal.
Multi-drug resistance (MDR) in Gram-negative organisms is an alarming problem in the world. MDR and extensively-drug resistance (XDR) is in increasing trend due to the production of different types of beta (β)-lactamases. Thus the aim of this study was to document the incidence of MDR and XDR in clinical isolates of Escherichia coli and also to find out the enzymatic mechanisms of β-lactam antibiotics resistance. Two hundred clinical isolates of Escherichia coli (E. coli) identified by standard laboratory methods were studied. Antibiotic susceptibility profile was performed for all the isolates and the suspected isolates were phenotypically tested for the production of extended spectrum β-lactamase (ESBL), metallo β-lactamase (MBL) and AmpC β-lactamase (AmpC) by recommended methods. Around three-fourth (78%) of the total isolates were multi-drug resistant. ESBL, MBL and AmpC production was found in 24%, 15% and 9% of isolates respectively. Amikacin, chloramphenicol and colistin were found to be the most effective antibiotics. High percentage of MDR was observed. β-lactamase mediated resistance was also high. Thus, regular surveillance of drug resistance due to β-lactamases production and infection control policy are of utmost importance to minimize the spread of resistant strains.


Scheduling in the Random-Order Model.
Makespan minimization on identical machines is a fundamental problem in online scheduling. The goal is to assign a sequence of jobs to m identical parallel machines so as to minimize the maximum completion time of any job. Already in the 1960s, Graham showed that Greedy is ( 2 - 1 / m ) -competitive. The best deterministic online algorithm currently known achieves a competitive ratio of 1.9201. No deterministic online strategy can obtain a competitiveness smaller than 1.88. In this paper, we study online makespan minimization in the popular random-order model, where the jobs of a given input arrive as a random permutation. It is known that Greedy does not attain a competitive factor asymptotically smaller than 2 in this setting. We present the first improved performance guarantees. Specifically, we develop a deterministic online algorithm that achieves a competitive ratio of 1.8478. The result relies on a new analysis approach. We identify a set of properties that a random permutation of the input jobs satisfies with high probability. Then we conduct a worst-case analysis of our algorithm, for the respective class of permutations. The analysis implies that the stated competitiveness holds not only in expectation but with high probability. Moreover, it provides mathematical evidence that job sequences leading to higher performance ratios are extremely rare, pathological inputs. We complement the results by lower bounds, for the random-order model. We show that no deterministic online algorithm can achieve a competitive ratio smaller than 4/3. Moreover, no deterministic online algorithm can attain a competitiveness smaller than 3/2 with high probability.