Preparation and evaluation of novel chitosan: gelrite ocular system containing besifloxacin for topical treatment of bacterial conjunctivitis: scintigraphy, ocular irritation and retention assessment.
This study was aimed to prepare, characterize and evaluate in situ gel formulations based on a blend of chitosan (CS), polyvinyl alcohol (PVA) and gellan gum (Gelrite™) for a sustained ocular delivery of besifloxacin (BSF). The developed formulations were evaluated for physicochemical properties, gelation time (Tsol-gel), rheological behaviour, antimicrobial efficacy, pharmacokinetic assessment, gamma scintigraphy study and ocular irritation. The results showed BSF sol-gel system were found to be sensitive enough which underwent instantaneous phase transition upon getting physiological stimulation. The ex vivo permeation experiments indicated that the developed formulation was able to enhance the retention of BSF at corneal surface. The HET-CAM confirmed the non-irritancy of developed formulation and also demonstrated the ability of ocular protection against strongly irritant substances. The results of gamma scintigraphy study revealed the higher concentration of drug retains at the corneal surface. In addition, optimized BSF sol-gel system showed enhanced anti-bacterial activity compared to BSF suspension.


TCR-MHC/peptide interaction: prospects for new anti-tumoral agents.
Tumor-related antigens can be presented as peptides forming complexes with major histocompatibility complex (MHC) molecules that interact with T-cell receptors, thus generating an immunologic anti-tumor response. Unfortunately, however, this response can be decreased by many effectors and pathways. On the other hand, such peptide-MHC complexes are unique starting points for therapeutic intervention. We present strategies for eliciting an anti-tumoral response by T-cell receptor-based fusion proteins with interleukin (IL)2 and antibody constant region domains, superantigens, and T-cell recruiting antibodies, as well as using genetically modified autologous T-cells as effectors. Another strategy is to direct peptide-MHC complexes to tumors as fusion proteins with an antibody-derived targeting moiety. Finally, we describe T-cell receptor-mimicking antibodies and antibody conjugates as anti tumoral agents.


Gender differences in upper airway compliance during NREM sleep: role of neck circumference.
It has been proposed that the gender difference in sleep apnea prevalence is related to gender differences in upper airway structure and function. We hypothesized that men would have smaller retropalatal cross-sectional area and higher compliance during sleep compared with women. Using upper airway imaging, we measured upper airway cross-sectional area and retropalatal compliance in wakefulness and non-rapid eye movement (NREM) sleep in 15 men and 15 women without sleep-disordered breathing. Cross-sectional area at the beginning of inspiration tended to be larger in men compared with women in both wakefulness [194.5 +/- 21.3 vs. 138.8 +/- 12.0 (SE) mm(2)] and NREM sleep (111.1 +/- 17.6 vs. 83.3 +/- 11.9 mm(2); P = 0.058). There was no significant difference, however, after correction for body surface area. Retropalatal compliance also tended to be higher in men during both wakefulness (5.9 +/- 1.4 vs. 3.1 +/- 1.4 mm(2)/cmH(2)O; P = 0.006) and NREM sleep (12.6 +/- 2.7 vs. 4.7 +/- 2.6 mm(2)/cmH(2)O; P = 0.055). However, compliance was similar in men relative to women after correction for neck circumference. We conclude that the gender difference in retropalatal compliance is more accurately attributed to differences in neck circumference between the genders.


Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.
One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution-a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota-the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome-nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering.


Endogenous flow-induced nitric oxide reduces superoxide-stimulated Na/H exchange activity via PKG in thick ascending limbs.
Luminal flow stimulates endogenous nitric oxide (NO) and superoxide (O2 (-)) production by renal thick ascending limbs (TALs). The delicate balance between these two factors regulates Na transport in TALs; NO enhances natriuresis, whereas O2 (-) augments Na absorption. Endogenous, flow-stimulated O2 (-) enhances Na/H exchange (NHE). Flow-stimulated NO reduces flow-induced O2 (-), a process mediated by cGMP-dependent protein kinase (PKG). However, whether flow-stimulated, endogenously-produced NO diminishes O2 (-)-stimulated NHE activity and the signaling pathway involved are unknown. We hypothesized that flow-induced NO reduces the stimulation of NHE activity caused by flow-induced O2 (-) via PKG in TALs. Intracellular pH recovery after an acid load was measured as an indicator of NHE activity in isolated, perfused rat TALs. l-Arginine, the NO synthase substrate, decreased NHE activity by 34 ± 5% (n = 5; P < 0.04). The O2 (-) scavenger tempol decreased NHE activity by 46 ± 8% (n = 6; P < 0.004) in the absence of NO. In the presence of l-arginine, the inhibitory effect of tempol on NHE activity was reduced to -19 ± 6% (n = 6; P < 0.03). The soluble guanylate cyclase inhibitor LY-83583 blocked the effect of l-arginine thus restoring tempol's effect on NHE activity to -42 ± 4% (n = 6; P < 0.0005). The PKG inhibitor KT-5823 also inhibited l-arginine's effect on tempol-reduced NHE activity (-43 ± 5%; n = 5; P < 0.03). We conclude that flow-induced NO reduces the stimulatory effect of endogenous, flow-induced O2 (-) on NHE activity in TALs via an increase in cGMP and PKG activation.


Prenatal and childhood exposure to chlordecone and sex-typed toy preference of 7-year-old Guadeloupean children.
Chlordecone was used intensively as an insecticide in the French West Indies. Because of its high persistence, the resulting contamination of food and water has led to chronic exposure of the general population as evidenced by its presence in the blood of people of Guadeloupe, in particular in pregnant women and newborns, and in maternal breast milk. Chlordecone is recognized as a reproductive and developmental toxicant, is neurotoxic and carcinogenic in rodents, and is considered as an endocrine-disrupting compound with well-established estrogenic and progestogenic properties both in vitro and in vivo. The question arises of its potential consequences on child neurodevelopment following prenatal and childhood exposure, in particular on behavioral sexual dimorphism in childhood. We followed 116 children from the TIMOUN mother-child cohort study in Guadeloupe, who were examined at age 7. These children were invited to participate in a 7-min structured play session in which they could choose between different toys considered as feminine, masculine, or neutral. The play session was video recorded, and the percentage of the time spent playing with feminine or masculine toys was calculated. We estimated associations between playtime and prenatal exposure to chlordecone (assessed by concentration in cord blood) or childhood exposure (determined from concentrations in child blood obtained at the 7-year follow-up), taking into account confounders and co-exposures to other environmental chemicals. We used a two-group regression model to take into account sex differences in play behavior. Our results do not indicate any modification in sex-typed toy preference among 7-year-old children in relation with either prenatal or childhood exposure to chlordecone.


The genome sequence of the Round-winged Muslin, Thumatha senex (Hübner, 1804).
We present a genome assembly from an individual female Thumatha senex (the Round-winged Muslin; Arthropoda; Insecta; Lepidoptera; Erebidae). The genome sequence is 810.3 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 15.5 kilobases in length.


Self-catalytic polymerization of a water-soluble selenium/polypyrrole nanocomposite and its nonlinear optical properties.
A facile one-step method for the synthesis of a water-soluble selenium/polypyrrole (Se/PPy) nanocomposite was developed. In the aqueous synthesis process, the pyrrole acted as a reductant for the reduction of H2SeO3, and then the elemental Se formed in situ acted as a catalyst for the polymerization of pyrrole. The characterization results show that the as-obtained composite (Se/PPy) is a spherical (Φ80 nm) product that is made up of amorphous Se particles coated by PPy layers. The formation mechanism and influence factors of the products were discussed, based on a series of experiments. It is proposed that remainder H2SeO3 adsorbed on the PPy chains increased the water-solubility and conductivity of the Se/PPy nanocomposite. Significantly, relying on the synergistic effect of photo-conductive Se nanoparticles and electric-conductive PPy molecules, the Se/PPy nanocomposite possesses a large two-photon absorption (2PA) cross-section and good optical limiting properties, which were demonstrated by the Z-scan technique using a femtosecond laser. We believe that this work should be an interesting strategy for developing polymer composites with excellent optoelectrical properties.


Membrane orientation of Gα(i)β(1)γ(2) and Gβ(1)γ(2) determined via combined vibrational spectroscopic studies.
The manner in which the heterotrimeric G protein complexes Gβ1γ2 and Gαiβ1γ2 interact with membranes is likely related to their biological function. We combined complementary measurements from sum frequency generation (SFG) vibrational and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy to determine the possible membrane orientations of Gβ1γ2 and the Gαiβ1γ2 heterotrimer more precisely than could be achieved using SFG alone. The most likely orientations of Gβ1γ2 and the Gαiβ1γ2 heterotrimer were both determined to fall within a similar narrow range of twist and tilt angles, suggesting that Gβ1γ2 may bind to Gαi without a significant change in orientation. This "basal" orientation seems to depend primarily on the geranylgeranylated C-terminus of Gγ2 along with basic residues at the N-terminus of Gαi, and suggests that activated G protein-coupled receptors (GPCRs) must reorient G protein heterotrimers at lipid bilayers to catalyze nucleotide exchange. The innovative methodologies developed in this paper can be widely applied to study the membrane orientation of other proteins in situ.


Treatment effects of mandibular total arch distalization using a ramal plate.
The purpose of this study was to evaluate treatment effects after distalization of the mandibular dentition using ramal plates through lateral cephalograms. Pre- and post-treatment lateral cephalograms and dental casts of 22 adult patients (11 males and 11 females; mean age, 23.9 ± 5.52 years) who received ramal plates for mandibular molar distalization were analyzed. The treatment effects and amount of distalization of the mandibular molars were calculated and tested for statistical significance. The significance level was set at p < 0.001. The mandibular first molar distalization at the crown and root were 2.10 mm (p < 0.001) and 0.81 mm (p = 0.011), respectively. In the evaluation of skeletal variables, there was a significant increase in the Wits appraisal (p < 0.001). In the evaluation of the soft tissue, there was no significant effect on upper lip position, but the lower lips showed a significant retraction of 2.2 mm (p < 0.001). The mandibular molars showed a significant amount of distalization accompanied by limited extrusion and mesiobuccal rotation of the crowns. A ramal plate may be a viable device for mandibular total arch distalization in Class III patients who are reluctant to undergo orthognathic surgery.


Users' information-seeking behavior on a medical library Website.
The Central Medical Library (CMK) at the Faculty of Medicine, University of Ljubljana, Slovenia, started to build a library Website that included a guide to library services and resources in 1997. The evaluation of Website usage plays an important role in its maintenance and development. Analyzing and exploring regularities in the visitors' behavior can be used to enhance the quality and facilitate delivery of information services, identify visitors' interests, and improve the server's performance. The analysis of the CMK Website users' navigational behavior was carried out by analyzing the Web server log files. These files contained information on all user accesses to the Website and provided a great opportunity to learn more about the behavior of visitors to the Website. The majority of the available tools for Web log file analysis provide a predefined set of reports showing the access count and the transferred bytes grouped along several dimensions. In addition to the reports mentioned above, the authors wanted to be able to perform interactive exploration and ad hoc analysis and discover trends in a user-friendly way. Because of that, we developed our own solution for exploring and analyzing the Web logs based on data warehousing and online analytical processing technologies. The analytical solution we developed proved successful, so it may find further application in the field of Web log file analysis. We will apply the findings of the analysis to restructuring the CMK Website.


Electrografted diazonium salt layers for antifouling on the surface of surface plasmon resonance biosensors.
Electrografted diazonium salt layers on the surface of surface plasmon resonance (SPR) sensors present potential for a significant improvement in antifouling coatings. A pulsed potential deposition profile was used in order to circumvent mass-transport limitations for layer deposition rate. The influence of number of pulses with respect to antifouling efficacy was evaluated by nonspecific adsorption surface coverage of crude bovine serum proteins. Instead of using empirical and rough estimated values, the penetration depth and sensitivity of the SPR instrument were experimentally determined for the calculation of nonspecific adsorption surface coverage. This provides a method to better examine antifouling surface coatings and compare crossing different coatings and experimental systems. Direct comparison of antifouling performance of different diazonium salts was facilitated by a tripad SPR sensor design. The electrografted 4-phenylalanine diazonium chloride (4-APhe) layers with zwitterionic characteristic demonstrate ultralow fouling.


Food consumption and food exchange of caged honey bees using a radioactive labelled sugar solution.
We measured the distribution of sugar solution within groups of caged honey bees (Apis mellifera) under standard in vitro laboratory conditions using 14C polyethylene glycol as a radioactive marker to analyze ingestion by individual bees after group feeding. We studied the impact of different experimental setups by varying the number of bees, age of bees, origin of bees, duration of experiment, the amount of available diet, and the influence of the neurotoxic pesticide imidacloprid in the diet on the feeding and food sharing behavior (trophallaxis). Sugar solution was non-uniformly distributed in bees in 36 out of 135 cages. As a measure of the extent to which the sugar diet was equally distributed between caged bees, we calculated the (inner 80%) intake ratio by dividing the intake of the 90th percentile bee by the intake of the 10th percentile bee. This intake ratio ranged from 1.3 to 94.8 in 133 individual cages, further supporting a non-uniform distribution of food among caged bees. We can expect a cage with 10 or 30 bees containing one bee that ingests, on average, the 8.8-fold of the bee in the same cage ingesting the smallest quantity of food. Inner 80% intake ratios were lower in experiments with a permanent or chronic offering of labelled sugar solution compared to temporary or acute feedings. After pooling the data of replicates to achieve a higher statistical power we compared different experimental setups. We found that uniform food distribution is best approached with 10 newly emerged bees per cage, which originate from a brood comb from a single colony. We also investigated the trophallaxis between caged honey bees which originally consumed the diet and newly added bees. Color marked bees were starved and added to the cages in a ratio of 10:5 or 20:20 after the initial set of bees consumed all the labelled sugar solution. The distribution of the labelled sugar solution by trophallaxis within 48 hours to added bees was 25% (10:5) or 45% (20:20) of the initial sugar solution. Imidacloprid at its median lethal dose (LD50) in the sugar solution reduced this post-feeding food transmission to 27% (20:20). Our results show that differences in food intake exist within caged bees that may lead to differential exposure that can influence the interpretation of toxicity tests.


Effect of extracellular alkalosis upon calcium distribution within the B cells.
Insulin secretion and the pattern of calcium distribution in B cells, assessed with the pyroantimonate precipitation technique, were simultaneously studied in rat pancreases perfused with 3.3 and 16.6 mM glucose solutions of pH 7.4 and 7.8. We have previously demonstrated the blocking effect of the latter pH upon glucose-induced insulin secretion. Glucose (16.6 mM) caused an increase in the total number of calcium pyroantimonate precipitates (CPP), as well as their number bound to different B cell structures, at every sampling period studied, with respect to the 3.3 mM glucose experiments. Extracellular alkalosis strongly inhibited both phases of the B cell response to the glucose stimulus, and greatly affected the distribution of CPP in the cells with respect to the pH 7.4 ones. During the first phase of glucose induced-insulin secretion, most of the CPP appeared within B granules at pH 7.4, while on the development of the second phase of secretion, they appeared mainly attached to the cell plasma membranes. Conversely, in pH 7.8 experiments, at the first minutes of the glucose challenge, CPP appeared principally located in the cytoplasm, being almost absent from the plasma membrane during the second phase of insulin secretion. These observations suggest that during the glucose stimulus, the cell calcium distribution within the B cells followed a clear chronological sequence. Such sequence might be determined, at least in part, according to the different Ca2(+)-set points of the different B cell structures. In our case, the extracellular alkalosis might interfere with the normal intracellular calcium fluxes, which in consequence might impair release of insulin by affecting several B cell functions.


[Type 4 renal tubular acidosis caused by spironolactone. A case report].
The authors describe a case of type 4 renal tubular acidosis, observed in a subject with liver cirrhosis, the pathogenetic cause of which was probably the assumption of spironolactone. It is thought that, even if such an eventuality is not very frequent, it must be considered in clinical practice, in view of the negative consequences that the reduction in urinary ammonium excretion and hyponatriemia, together with this particular form of acidosis, may have on the neurological state of the patients.


Effects of bufalin on up-regulating methylation of Wilm's tumor 1 gene in human erythroid leukemic cells.
To explore the effects of bufalin on inhibiting proliferation, up-regulating methylation of Wilm' tumor 1 gene (WT1) as well as its possible mechanisms in human erythroid leukemic (HEL) cells. The HEL cells were treated with bufalin at various concentrations to observe cellular morphology, proliferation assay and cell cycle. The mRNA and protein expression levels of WT1 were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry, DNA methylation of WT1 and protein expression levels of DNA methyltransferase 3a (DNMT3a) and DNMT3b were analyzed by methylation-specific PCR, and Western blot respectively. The bufalin was effective to inhibit proliferation of HEL cells in a dose-dependent manner, their suppression rates were from 23.4%±2.1% to 87.2%±5.4% with an half maximal inhibit concentration (IC50) of 0.046 μmol/L. Typical apoptosis morphology was observed in bufalin-treated HEL cells. The proliferation index of cell cycle decreased from 76.4%±1.9% to 49.7%±1.3%. The expression levels of WT1 mRNA and its protein reduced gradually with increasing doses of bufalin, meanwhile, the methylation status of WT1 gene changed from unmethylated into partially or totally methylated. While, the expression levels of DNMT3a and DNMT3b protein gradually increased by bufalin treatment in a dose-dependent manner. Bufalin can not only significantly inhibit the proliferation of HEL cells and arrest cell cycle at G0/G1 phase, but also induce cellular apoptosis and down-regulate the expression level of WT1. Our results provide the evidence of bufalin for anti-leukemia, its mechanism may involve in increasing WT1 methylation status which is related to the up-regulation of DNMT3a and DNMT3b proteins in erythroid leukemic HEL cells.


Pseudomonas formosensis sp. nov., a gamma-proteobacteria isolated from food-waste compost in Taiwan.
A taxonomic study was carried out on a novel aerobic bacterial strain, designated CC-CY503(T), isolated from food-waste compost in Taiwan. Cells were Gram-stain-negative short rods, motile by means of a monopolar flagellum. Strain CC-CY503(T) was able to grow at 20-50 °C and pH 6.0-10.0 and to tolerate <6% NaCl (w/v). Phylogenetic analysis of 16S rRNA gene sequences showed that this bacterium belonged to the genus Pseudomonas, with Pseudomonas pertucinogena ATCC 190(T) as the closest neighbour, sharing a sequence similarity of 97.9%. The DNA-DNA relatedness value of strain CC-CY503(T) with P. pertucinogena ATCC 190(T) was 37.8 ± 2.3%. The phylogenetic trees reconstructed based on gyrB and rpoB gene sequences supported the classification of strain CC-CY503(T) as a novel member of the genus Pseudomonas. The predominant quinone system was ubiquinone (Q-9) and the DNA G+C content was 63.1 ± 0.4 mol%. The major fatty acids were C(12:0), C(16:0), C(17:0) cyclo, C(19:0) cyclo ω8c and summed features 3 and 8 consisting of C(16:1)ω7c/C(16:1)ω6c and C(18:1)ω7c/C(18:1)ω6c, respectively. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylcholine. On the basis of its distinct phylogenetic, phenotypic and chemotaxonomic features, strain CC-CY503(T) ( =BCRC 80437(T) =JCM 18415(T)) is proposed to represent a novel species within the genus Pseudomonas, for which the name Pseudomonas formosensis sp. nov. is proposed.


Childhood lung function following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study.
Despite the introduction of antiretroviral therapy (ART), HIV-associated pulmonary complications remain prevalent in children following perinatal HIV infection. In the post-ART era the incidence of opportunistic infections has decreased; however, non-infectious complications including diminished lung function are common. It is unclear whether early initiation of ART influences lung function later in life. We performed a cross-sectional study examining pulmonary function tests (PFT) (spirometry, plethysmography, carbon monoxide diffusing capacity) in HIV-unexposed (HU), HIV-exposed-uninfected (HEU) and perinatally HIV-infected children on early ART (HIV+) recruited from the Cape Town arms of the CHER and IMPAACT 1060 trials. PFT was performed once children could participate (October 2013 to January 2020). Global Lung Initiative reference software was used for Z-standardisation of lung function by sex, age and height. In total 394 children (HU n=90, HEU n=162, HIV+ n=142) underwent PFT, median age 8.7 (IQR 7.7-9.8) years. HIV+ had ART initiated at a median age of 17.6 (8.0-36.7) weeks. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC Z-scores were similar in all groups. Plethysmography demonstrated air-trapping with increased total lung capacity (TLC), functional residual capacity, residual volume (RV) and RV/TLC Z-scores in HIV+. There were no differences in alveolar volume; however, diffusing capacity was increased in HIV+. Our findings indicate that following perinatal HIV infection, early ART may attenuate HIV-associated lung disease and is associated with normal childhood spirometry. However plethysmography demonstrates that small airway dysfunction is more pronounced in HIV+. Longitudinal follow-up is required to assess if these children are at risk of obstructive airway disease later in life.


Cardiac tamponade as a complication of pseudocyst in chronic pancreatitis.
Authors report a case of relapsing chronic calcifying pancreatitis with pleural and pericardial effusions during an episode of acute exacerbation. A large multilocular pancreatic pseudocyst expanded into the mediastinal space resulting in pericardial effusion that caused cardiac tamponade with severe circulatory deterioration. After resuscitation and pericardiocentesis a successful surgical procedure was performed, which produced rapid clinical improvement. Authors discuss this uncommon complication and review the proposed pathogenic mechanisms and possible therapeutic interventions.


Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX--a pilot study.
The first study of photodynamic therapy in the human gastrointestinal tract using 5 aminolaevulinic acid (ALA) induced protoporphyrin IX as the photosensitising agent is described. Eighteen patients with colorectal, duodenal, and oesophageal tumours were studied. After 30-60 mg/kg of ALA given orally, biopsy specimens of tumour and adjacent normal mucosa were taken 1-72 hours later. These specimens were examined by quantitative fluorescence microscopy for assessment of sensitisation with protoporphyrin IX. Ten patients were given a second dose of ALA a few weeks later and their tumours were treated with red laser light (628 nm). With 30 mg/kg ALA, the highest fluorescence values were detected in the duodenum and oesophagus, and the lowest in the large bowel. Doubling the ALA dose in patients with colorectal tumours gave protoporphyrin IX fluorescence intensities similar to those in patients with upper gastrointestinal lesions and improved the tumour:normal mucosa protoporphyrin IX sensitisation ratio. The treated patients showed superficial mucosal necrosis in the areas exposed to laser light. Six patients had transient rises in serum aspartate aminotransferases, two mild skin photosensitivity reactions, and five mild nausea and vomiting. In conclusion, photodynamic therapy with systemically administered ALA may be a promising technique for the treatment of small tumours and areas of dysplasia such as in Barrett's oesophagus.


[Evaluation of a program for reducing the surgical waiting list on the basis of on the spot payment].
The aim of this study was to evaluate a program to shorten the surgical waiting list on the basis of on the spot payment for each intervention performed outside the ordinary time schedule. The evaluation was based on preestablished hypothesis concerning the possible beneficial and adverse effects of on the spot payment. Eighty-four units corresponding to 6 surgical specialties in 14 hospitals of the Valencian Public Health Care Department were included in the study. The effects of this program were compared between the units which carried out the program from March to June 1992 (experimental group: EG) and the units which did not undertake the program (control group: CG). The interventions performed in the program constituted 31% of the initial waiting list of the EG units. Bed profitability increased in the EG with surgeon productivity decreasing within the ordinary time schedule in the units of general surgery in the EG (16%) and the selection of diagnoses did not coincide with clinical priorities (positive selection of fimosis, fallopian tube tieing and negative selection of goiter and prostatic hyperplasia). The design of programs based on the spot payment should take the possible adverse effects into account establishing mechanisms to avoid the decrease in ordinary activity and the selection of patients on the basis of criteria different to clinical priorities.


Better pulmonary function is associated with greater handgrip strength in a healthy Chinese Han population.
Handgrip strength (HGS) has been widely studied in clinical and epidemiological settings, but the relationship between HGS and pulmonary function is still controversial. This study analysed pulmonary function and HGS stratified by sex and age in a healthy Chinese Han population, as well as the associations between HGS and pulmonary function parameters. HGS was measured by a Jamar dynamometer and pulmonary function was tested using a portable spirometer. Frequencies and variables are presented as percentages and means ± standard deviations, respectively. Chi-square tests were used for comparisons of categorical variables, and Student's t-tests or Mann-Whitney U-tests were used for continuous variables. Pearson's correlation coefficients were used to analyse the normally distributed variables, and Spearman correlation coefficients were used to analyse the non-normally distributed variables. Multivariate linear regression models were employed to explore the relationships between HGS and parameters of pulmonary function. The statistical significance was set at p < 0.01. Cross-sectional data were available for 1519 subjects (59.0% females, 57.9 ± 13.3 years old). Males had higher average HGS than females (40.2 vs. 25.0 kg, p < 0.01), as well as better pulmonary function. Both HGS and pulmonary function parameters were significantly inversely correlated with age (r ≤ - 0.30, p < 0.01). The maximum value of vital capacity (VC max), forced expiratory volume in 3 s (FEV 3) and forced vital capacity (FVC) were strongly correlated with HGS among the pulmonary function indices (r = 0.72, 0.70 and 0.69, respectively, p < 0.001). In the multivariate linear regression analysis, HGS and height were positively correlated, while age and pulse pressure were negatively correlated with HGS. In males, the FVC, VC max and FEV3 increased by 0.02 L, 0.023 L and 0.03 L in per 1 kg increase in HGS, respectively. The HGS coefficients for females were smaller than those for males. Both pulmonary function and HGS were inversely correlated with age, and better pulmonary function was associated with greater handgrip strength.


Netrin-1 signaling regulates de novo protein synthesis of kappa opioid receptor by facilitating polysomal partition of its mRNA.
The expression of kappa opioid receptor (KOR) is subjected to both transcriptional and posttranscriptional controls. We report that KOR translation is regulated by netrin-1 in primary neurons of dorsal root ganglion (DRG) and in P19 embryonal carcinoma cells. Without stimulation, a significant portion of KOR mRNA is maintained in a dormant state and partitions in the translationally inactive, post-polysomal fraction. During netrin-1 stimulation, which activates its downstream target focal adhesion kinase (FAK), KOR mRNA rapidly partitions to the translationally active polysomal fraction. Functionally, the newly synthesized KOR proteins in DRG neurons are able to bind to specific ligands. This report describes the first example of netrin-1 signaling in the translational control of a drug receptor KOR, which involves the mediator of netrin-1, FAK, and a novel mechanism that enhances the association of target mRNA with polysomes for translational activation.


Determination of plasmatic copper and zinc in uncomplicated pregnancies.
The copper and zinc plasmatic concentrations were determined in a group of 50 pregnant women and in a control group. We found higher copper and lower zinc plasmatic levels in pregnancy than in control group. No correlation was found between the copper and zinc plasmatic levels and the weeks of pregnancy.


Measuring fat and fat-free mass: clinical significance and limitations.
Measuring body composition is part of clinical nutritional assessment. Simultaneous measurements of fat mass, and fat-free mass, or, preferably, the components of fat-free mass, will yield the most clinical information, but may be limited by laboratory availability. In obese subjects, measurements of fat mass and fat distribution is complemented by a simultaneous assessment of cell mass or total body protein, since management will involve following changes in all of these parameters. Similarly, in osteoporosis, assessment of fat mass and distribution at the same time as bone mass and density, where hormonal replacement therapy has been instituted is a necessary pan of the total management of the patient. Since fat distribution has been recognised as an important indicator of health risk, it has become increasingly important to know how to quantify risk and risk change in individuals with abdominal fat distribution. Little information is available about this, or the risks peculiar to peripheral fat distribution. As compartmental models of body composition become more complex, changes in these compartments in various illnesses are becoming clearer. The use of IVNAA for measuring total body protein changes in haemodialysis, and alcoholic cirrhosis, and the recent development of multifrequency BIA to assess extracellular water provide good examples. Although many hospitals clinics now have DEXA and BIA available, body composition laboratories per se are still a rarity, limiting clinical measurements to anthropometry. The errors involved in measurement using the various techniques mentioned still do not allow assessment of short-term changes in fat mass, or the components of fat-free mass.


Defects in CTP:PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE affect embryonic and postembryonic development in Arabidopsis.
A TILLING strategy (for targeting-induced local-scale lesions in genomes) was used in Arabidopsis thaliana to isolate mutants of a gene encoding CTP:PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE (PECT; EC 220.127.116.11), a rate-limiting enzyme in phosphatidylethanolamine biosynthesis. A null mutation, pect1-6, caused embryo abortion before the octant stage. However, reciprocal crosses revealed that pect1-6 caused no significant gametophytic defect. In pect1-4, PECT activity was decreased by 74%. Growth was generally normal in these mutants, despite delays in embryo maturation and reduced fertility. At low temperatures, however, homozygotic pect1-4 plants displayed dwarfism. PECT activity was decreased by 47% in heterozygotic pect1-6 plants and by 80% in pect1-4/pect1-6 F1 plants, which also displayed a small but significant decrease of phosphatidylethanolamine and a reciprocal increase in phosphatidylcholine. These lipid changes were fully reversed by wild-type PECT1 expression. pect1-4/pect1-6 F1 plants displayed severe dwarfism, tissue abnormalities, and low fertility, which was attributable in part to inhibition of anther, embryo, and ovule development, as was the reduced fertility of pect1-4 seedlings. PECT1 cDNA expression under the control of an inducible promoter partially rectified the mutant phenotypes observed in pect1-4/pect1-6 F1 seedlings, indicating that malfunctions in different tissues have a synergistic effect on the mutant phenotypes.


Hydrogen peroxide stimulates mitogen-activated protein kinase in bovine tracheal myocytes: implications for human airway disease.
We have shown that hyperoxic exposure of immature rats induces airway smooth muscle layer thickening and cell turnover parallel to that found in the airways of patients with bronchopulmonary dysplasia and chronic, severe asthma. We hypothesized that reactive oxygen species could promote the observed airway remodeling by directly stimulating signal transduction pathways that regulate cell growth. To test this hypothesis in cultured cells, we assessed the effects of hydrogen peroxide (H2O2) on mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes. The MAP kinases are a family of 40 to 46 kD cytosolic serine/threonine kinases that participate in the transduction of mitogenic signals to the cell nucleus. Quiescent cells were exposed to H2O2 (25 to 200 microns; 2 to 60 min), after which SDS-PAGE of cell extracts was performed. Western analysis using an anti-MAP kinase antiserum revealed a decrease in the mobility of the 42 and 44 kD MAP kinase bands after H2O2 exposures of 5 to 30 min, reflecting the phosphorylation at threonine and tyrosine residues required for enzymatic activity. MAP kinase activation was demonstrated by kinase renaturation assays, which showed an almost 4-fold increase in 42 and 44 kD MAP kinase activity. Down-regulation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) partially reduced H2O2-stimulated MAP kinase activity, suggesting that H2O2 induces MAP kinase activation via both PKC-dependent and PKC-independent pathways. Western analysis using a phosphotyrosine monoclonal antibody revealed increased tyrosine phosphorylation of proteins with approximate molecular weights of 72 and 125 kD after H2O2 exposure, demonstrating that H2O2 can stimulate the tyrosine phosphorylation of multiple cytosolic proteins, including MAP kinase.(ABSTRACT TRUNCATED AT 250 WORDS)


Design and development of a smart blind walking stick using machine learning.
Visually impaired people are often subjugated under extreme circumstances even in their day-to-day life. The daily requirements of a common man appear to be an impediment in their routine life. Simplest of tasks like walking, eating, bathing, conversing and even eating is of utmost difficulty to them. Moreover, with such difficulties their only way-out seems to be dependency on the privileged lot, which further diminishes their confidence in themselves and gradually makes them even more dependent. The conventional devices that are used by visually impaired people include basic walking sticks which fail at the job in hand by not providing adequate stabilisation on rough surfaces and misguiding the users into unfavourable conditions. There is no way for the person to know what the object in front of them is without hitting it with the stick, which could also lead to accidents. To solve these problems, a smart walking stick is developed which not only recognises the object in front of it using Machine Learning (ML) models, but also gives a voice output to alert its user about the particular object thereby limiting the chance of any and all accidents. The concept is realised in hardware and integrated to the walking stick. This helps in stabilisation of phone and to produce better results in object identification. Further an application is developed to alert the user by converting the obtained image into a voice messages.


Cord Blood Alkaline Phosphatase as an Indicator of Neonatal Jaundice.
Management of hyperbilirubinemia remains a challenge for neonatal medicine because of the risk of neurological complications related to the toxicity of severe hyperbilirubinemia. The purpose of this study was to examine the validity of cord blood alkaline phosphatase level for predicting neonatal hyperbilirubinemia. Between October and December 2013 a total of 102 healthy term infants born to healthy mothers were studied. Cord blood samples were collected for measurement of alkaline Phosphatase levels immediately after birth. Neonates were followed-up for the emergence of jaundice. Newborns with clinical jaundice were recalled and serum bilirubin levels measured. Appropriate treatment based on serum bilirubin level was performed. Alkaline phosphatase levels between the non-jaundiced and jaundiced treated neonates were compared. The incidence of severe jaundice that required treatment among followed-up neonates was 9.8%. The mean alkaline phosphatase level was 309.09 ± 82.51 IU/L in the non-jaundiced group and 367.80 ± 73.82 IU/L in the severely jaundiced group (P = 0.040). The cutoff value of 314 IU/L was associated with sensitivity 80% and specificity 63% for predicting neonatal hyperbilirubinemia requiring treatment. The cord blood alkaline phosphatase level can be used as a predictor of severe neonatal jaundice.


Timing of feather molt related to date of spring migration in male white-throated sparrows, Zonotrichia albicollis.
In migratory birds, the ability to depart wintering grounds at the appropriate time is an important determinant of fitness. Understanding the regulation of this timing will be essential for predicting whether timing of bird migration keeps up with global climate change. We examined whether the timing of the late-winter molt, in which white-throated sparrows (Zonotrichia albicollis) replace head and body feathers in advance of mating, may constrain the timing of northward migratory departure. In an observational study, we found a significant correlation between timing of molt and the date on which free-living male white-throated sparrows disappeared from our study site during migration. The following year, we tested whether experimentally manipulating molt date by advancing photoperiod during temporary captivity would subsequently advance disappearance date once the birds were released. Sparrows that were experimentally induced to molt early disappeared from the wintering site before controls. However, the captive control birds also molted and disappeared from the site earlier than free-living controls, suggesting that the diet during captivity had played a role. In the third winter we completed the study by advancing or delaying molt using only dietary manipulation. Together, these results show that the ability to molt early in spring is related to early disappearance from the wintering site. Early molt likely has carry-over effects on reproduction and the requirements of molt may prevent populations from adjusting migration timing in response to global climate change.


Altered levels of endogenous retrovirus-like sequence (VL30) RNA during mouse epidermal cell carcinogenesis.
Gene expression during mouse keratinocyte carcinogenesis was examined in a clonal cell model. Tumor cells from three separate initiated cell lineages were compared with their nontumorigenic precursors and with the progenitor cell strain prior to treatment with 7,12-dimethylbenz[a]anthracene (DMBA). The steady-state levels of VL30 RNA in normal and papilloma cells were regulated by extracellular Ca2+ (which controls proliferation and differentiation in normal epidermal keratinocytes) and culture density. In contrast, steady-state levels of VL30 RNA were not regulated by these factors in the squamous cell carcinoma or the anaplastic carcinoma cells. VL30 expression was Ca2+ dependent in the initiated cell precursors within each tumor cell lineage, suggesting that the loss of response to extracellular Ca2+ was associated with the malignant conversion stage of carcinogenesis. No differences between normal and tumor cells were found in the cellular RNA levels of five additional proto-oncogenes. The mouse epidermal cell model should provide a means for direct assessment of a potential functional role of VL30 sequences in cancer development.


Photo Epilation with Intense Pulsed Light for Thinning of Anterior Hairline after Hairline Correction Surgery in East Asians.
Thin hairs are critical to achieve natural result in female hairline correction surgery. However, there are few studies on the usefulness of hair thinning by intense pulsed light (IPL) after hairline correction surgery in East Asian females. Hair thinning using IPL was performed in 54 women who had complained about thick hairs along the frontal hairline after hairline correction surgery. Patient mean age was 31.2 years old and patients were an average of 2.1 years post-hairline correction surgery. Initial treatment used 10 J, while second and third sessions were conducted with 10 to 15 J according to responsiveness to treatment. Mean thickness of individual hairs assessed before the procedure was 78.86 µm. The mean number of procedures was 1.6 per patient. Forty of 54 subjects (74%) achieved satisfactory hair thinning with only one procedure from 78.01 to 66.14 µm after treatment. The measured thickness was 66.43 µm at the end of the first year in patients who were satisfied after one procedure. Thirteen cases achieved satisfactory hair thinning after two sessions. Mean thickness was 74.44 µm and 67.51 µm, before and after the second session. One case required a third session with 15J, thinning from 89.00 to 66.50 µm. Hair thinning by IPL is a very useful method to provide a natural look after hairline correction surgery in East Asians, who have naturally thick hair.


Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis.
Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNP-specific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs). Here we show that depletion of coilin in zebrafish embryos leads to CB dispersal, deficits in snRNP biogenesis and expression of spliced mRNA, as well as reduced cell proliferation followed by developmental arrest. Notably, injection of purified mature human snRNPs restored mRNA expression and viability. snRNAs were necessary but not sufficient for rescue, showing that only assembled snRNPs can bypass the requirement for coilin. Thus, coilin's essential function in embryos is to promote macromolecular assembly of snRNPs, likely by concentrating snRNP components in CBs to overcome rate-limiting assembly steps.


Energetics of adsorbed CH3 on Pt(111) by calorimetry.
The enthalpy and sticking probability for the dissociative adsorption of methyl iodide were measured on Pt(111) at 320 K and at low coverages (up to 0.04 ML, where 1 ML is equal to one adsorbate molecule for every surface Pt atom) using single crystal adsorption calorimetry (SCAC). At this temperature and in this coverage range, methyl iodide produces adsorbed methyl (CH(3,ad)) plus an iodine adatom (I(ad)). Combining the heat of this reaction with reported energetics for Iad gives the standard heat of formation of adsorbed methyl, ΔH(f)(0)(CH3,ad), to be −53 kJ/mol and a Pt(111)–CH3 bond energy of 197 kJ/mol. (The error bar of ±20 kJ/mol for both values is limited by the reported heat of formation of I(ad).) This is the first direct measurement of these values for any alkyl fragment on any surface.


Myopic discounting of future rewards after medial orbitofrontal damage in humans.
Choices are often intertemporal, requiring tradeoff of short-term and long-term outcomes. In such contexts, humans may prefer small rewards delivered immediately to larger rewards delivered after a delay, reflecting temporal discounting (TD) of delayed outcomes. The medial orbitofrontal cortex (mOFC) is consistently activated during intertemporal choice, yet its role remains unclear. Here, patients with lesions in the mOFC (mOFC patients), control patients with lesions outside the frontal lobe, and healthy individuals chose hypothetically between small-immediate and larger-delayed rewards. The type of reward varied across three TD tasks, including both primary (food) and secondary (money and discount vouchers) rewards. We found that damage to mOFC increased significantly the preference for small-immediate over larger-delayed rewards, resulting in steeper TD of future rewards in mOFC patients compared with the control groups. This held for both primary and secondary rewards. All participants, including mOFC patients, were more willing to wait for delayed money and discount vouchers than for delayed food, suggesting that mOFC patients' (impatient) choices were not due merely to poor motor impulse control or consideration of the goods at stake. These findings provide the first evidence in humans that mOFC is necessary for valuation and preference of delayed rewards for intertemporal choice.


[Herpesviruses in patients after renal transplantation].
To estimate graft function after kidney transplantation during active herpesviruses or superinfection Materials and methods. The study included 32 patients (men 21, women 11) with end-stage chronic kidney disease. The median age was 43 years. Cytomegalovirus (CMV), EpsteinBarr virus (EBV) and human herpes virus 6 (HHV-6) DNAs were screened by RT-PCR in the donor's transplant biopsy, and recipients peripheral blood and urine after kidney transplantation (KT) on 0, 1, 2, 4, 6, 12 months. Antiviral antibodies (IgM and IgG) were also screened by Enzyme-linked immunoassay analysis (ELISA) along with PCR. The 500 or less copies of viral DNA per 105 nuclear cells or 1 ml of urine was considered as low, more than 1000 copies high. On the first month after KT CMV DNA was detected in 50% of pts., EBV DNA in 40% and HHV-6 DNA in 33%. During first year after KT two or three viruses simultaneously were found in 12 recipients: CMV, EBV, and HHV-6 were detected in 5 recipients; CMV and EBV in 4 patients; CMV and HHV-6 in 2 pts; EBV and HHV-6 in 1 pt. Graft dysfunction was observed in 9 patients with a high concentration of viral DNA of one, two or three viruses simultaneously. An upraise of the concentration of virus DNA (CMV, EBV and HHV 6) was detected primarily in the urine, while in the blood its concentration was less than 500 cop or undetectable. Renal dysfunction was not observed on the background of low concentrations of viral DNA in urine and blood. However, with an increase of DNA concentration, an impaired graft function in 8 of 12 patients appeared. Low viral DNA level proved to be a background for another virus activation or bacterial/fungal superinfection. Graft dysfunction occurs at high viral DNA levels detection during mono-or superinfection. Low viral load can serve as a background for another virus activation and/or bacterial/fungal superinfection.


Histopathological and blood-brain barrier changes in rats induced by an intracerebral injection of human recombinant interleukin 2.
Adoptive immunotherapy utilizing human recombinant interleukin 2 (rIL-2) in conjunction with lymphokine-activated killer cells has shown some efficacy in the treatment of various types of cancers, particularly renal carcinoma and melanoma. Intravenous administration of rIL-2, with or without lymphokine-activated killer cells, produces a variety of serious side effects and approximately one-third of the patients experience a decrease in neurological status. Our previous investigations in animals have indicated that a single intravenous injection of rIL-2 can compromise the integrity of the blood-brain barrier (BBB). The present study examined the histopathological effect and BBB changes in rats which occur after a single intracerebral injection of rIL-2, its excipient, or saline into the parietal lobe. Animals were killed at various intervals up to 8 days (1 hour after intravenous injection of horseradish peroxidase), and the brain tissue was sectioned and processed for light microscopy. All animals showed increased cerebrovascular permeability for horseradish peroxidase due to traumatic BBB disruption at 4, 12, and 24 hours after injection. Extravasation of horseradish peroxidase persisted at 3 and 8 days only in animals injected with rIL-2. Injections of rIL-2 led to an increased leukocytic infiltration into the injection site, perivascular cuffing, and localized edema by 24 hours, which continued to increase over the 8-day study period. These results suggest that a single injection of human rIL-2 into the brain of rats induces an influx of leukocytes into the brain and may contribute to the cellular events that perpetuate a trauma-induced compromise in the integrity of the BBB.


Willingness to Pay and Preferences Among Patients Undergoing Cystoscopies: Results from a Large Survey-Based Study in Spain.
Cystoscopy procedures can cause distress among patients. Patient perspectives on health services are essential inputs in decision-making. This study investigated the patient preferences in Spain regarding single-use cystoscopes (SUC) compared to reusable cystoscopes and their willingness to pay (WTP) for cystoscopy procedures. Between May and June 2021, an anonymous survey was distributed to Spanish patients who had previously undergone a cystoscopy. The survey included patient preference measures on reusable cystoscopes compared to SUCs and a discrete choice experiment. The survey was distributed through a human data science company (IQVIA), collected using an online survey tool (QuestionPro®), and analyzed using Stata/MP, StataCorp. Of 300 respondents, 148 (49.33%) were female and 150 (50%) were male, and mainly between 18-49 years (247, 82.33%). Most (265, 88%) preferred to have their procedure performed with a SUC rather than a reusable cystoscope. Among these patients, 215 (80%) could imagine asking their doctor to use a SUC. A total of 231 (77%) respondents indicated an increased level of concern about the risk of exposure to contamination related to their cystoscopy following the COVID-19 pandemic. Patients would pay 62 EUR to have their initial consultation and cystoscopy procedure on the same day (p < 0.001), 59 EUR to reduce the environmental impact, and 57 EUR to reduce the risk of contamination (p < 0.001). Patients prefer to undergo cystoscopy using an SUC on the same day as their initial consultation. The increased contamination concerns due to the COVID-19 pandemic and WTP to reduce the risk of cystoscope contamination may explain patients' preferences for SUCs. The most important attributes related to their cystoscopy procedure are the ability to have their procedure performed on the same day as their initial consultation, the reduction of the environmental impact, and the reduction of the contamination risk.


Cancer registration of leukaemias and lymphomas: results of a comparison with a specialist registry.
Registrations of leukaemias and lymphomas for 1986 available during October 1987 from three Regional Cancer registries have been cross-checked against a specialist registry of haematopoietic malignancies. The process has increased the specialist registries numbers by 7 per cent. At that time the cancer registries had not registered 50 per cent of identified cases.


Photophobia as a Presenting Feature in Adie's Tonic Pupil.
A 34 years old female presented with complains of photophobia since 6-7 months. On examination, she had anisocoria of 4 mm in room light which increased in bright light. The left pupil was dilated and unresponsive to direct and indirect light stimuli. It did however, constrict slowly on near fixation followed by slow redilatation on distance fixation. A diagnosis of Adie's tonic pupil was made since left pupil constricted with instillation of dilute pilocarpine 0.1%. Her symptoms of photophobia and blurred vision immediately resolved. Photochromatic glasses and dilute pilocarpine 0.1% three times a day were prescribed. Prompt symptomatic relief of photophobia and blurred vision was observed.


Doppler sonography of maternal cerebral arteries in pregnancy: side-to-side differences.
To study side-to-side differences in blood flow of the common and internal carotid arteries, and the vertebral arteries (VAs) in women with uncomplicated pregnancies as a first step to build a reference values chart. A total of 155 healthy pregnant women between 20 and 40 weeks' gestation were included. Doppler sonography of the common and internal carotid arteries and VAs was performed on both sides. Parameters measured included diameter, peak systolic velocity, systolic-diastolic ratio, end-diastolic velocity, pulsatility index and resistance index. Statistical analysis was performed using the S-Plus 8.0 program. Normality was determined using the Kolmogorov-Smirnov test. Differences between sides were tested using Student's paired t test, association using linear correlation, and agreement using the Bland-Altman method. Mean values were equal between sides for all parameters with the exception of the end-diastolic velocity in the VAs. The association and agreement between the measurements taken from the right and left sides were poor. Bland-Altman plots also indicated low agreement between sides. All parameters showed significant right-to-left differences. Despite the equality between means, right and left flows through the vessels studied differed as there was poor association and agreement.


Genome-wide selection signatures reveal widespread synergistic effects of two different stressors in Drosophila melanogaster.
Experimental evolution combined with whole-genome sequencing (evolve and resequence (E&R)) is a powerful approach to study the adaptive architecture of selected traits. Nevertheless, so far the focus has been on the selective response triggered by a single stressor. Building on the highly parallel selection response of founder populations with reduced variation, we evaluated how the presence of a second stressor affects the genomic selection response. After 20 generations of adaptation to laboratory conditions at either 18°C or 29°C, strong genome-wide selection signatures were observed. Only 38% of the selection signatures can be attributed to laboratory adaptation (no difference between temperature regimes). The remaining selection responses are either caused by temperature-specific effects, or reflect the joint effects of temperature and laboratory adaptation (same direction, but the magnitude differs between temperatures). The allele frequency changes resulting from the combined effects of temperature and laboratory adaptation were more extreme in the hot environment for 83% of the affected genomic regions-indicating widespread synergistic effects of the two stressors. We conclude that E&R with reduced genetic variation is a powerful approach to study genome-wide fitness consequences driven by the combined effects of multiple environmental factors.


Fat meets the cholinergic antiinflammatory pathway.
The cholinergic antiinflammatory pathway is a neural mechanism that is controlled by the vagus nerve and inhibits local cytokine release, thereby preventing the damaging effects of cytokine overproduction. A new study now shows that dietary fat can activate this pathway, a finding that may help explain the immune system's failure to react to food antigens and commensal bacteria. Here we discuss this new data and its potential implications for dietary intervention in the treatment of inflammatory diseases.


Gut ischemia induces bone marrow failure and increases risk of infection.
Hemorrhagic shock leads to bone marrow (BM) failure and renders the host susceptible to infection. We hypothesized that splanchnic hypoperfusion may play a mechanistic role in this process. BM was harvested from normal rats and, on Postprocedure Days 1 and 3, from rats that had undergone laparotomy (LAP) or gut ischemia/reperfusion (I/R; 45 min superior mesentery artery occlusion). Granulocyte-macrophage colony-forming unit (CFU-GM) proliferation, a measure of BM myeloid progenitors, was quantitated using a standard soft agar culture technique. On Postprocedure Days 1 and 3, BM proliferation of CFU-GM was depressed in gut I/R rats, compared to control and LAP animals (P < 0.05). Next, six rats were subjected to I/R, LAP, ANEST (anesthesia control), or no treatment (NL, normal control); 1 day later, 3.5 x 10(7) Staphylococcus aureus, suspended in 0.25 ml of saline, were injected subcutaneously in four sites on the back of each animal. Five days later, the NL rats had developed 23 abscesses, ANEST 23, and LAP 22, while the gut I/R rats had 24. The abscesses were excised, weighed, and measured. The weight and size of abscesses were greater in the gut I/R animals (P < 0.05). In summary, gut I/R depressed BM proliferation and rendered animals susceptible to infection in a manner similar to that observed following hemorrhagic shock. These data suggest that splanchnic hypoperfusion, a common sequela of hemorrhagic shock, may play a mechanistic role in BM failure and infection after hemorrhage.


[Relationship between mitotic phases at different stages of embryonic development of axolotl].
Indices and durations of mitotic phases and interphase have been determined in the axolotl embryos at the late blastula, early gastrula and mid-neurula stages. The data obtained suggest that the ratio of mitotic phases changes during embryogenesis and differs in different rudiments of the embryo at the same developmental stage.


Malignant rhabdoid tumor of the central nervous system.
Originally described and most frequently reported in association with the kidney, the malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm with distinctive morphologic features. Extrarenal sites reported for this neoplasm include the liver, thymus, and various soft tissue sites. Young infants are affected with rare exceptions. We report the case of a 3-month-old boy who presented with hyperirritability and increasing head size over several weeks. The patient died following a two-week hospital stay marked by development of seizures, paralysis, and apnea. At autopsy, significant findings were limited to the central nervous system. The subarachnoid space contained neoplasm throughout, with multiple areas of parenchymal invasion. A predominating intraparenchymal mass was present in the inferior cerebellum contiguous with the neoplasm in the subarachnoid space and probably represented the site of origin. Microscopically, the neoplasm was composed of a highly cellular monomorphic population of polygonal cells with roughly ovoid vesicular nuclei and conspicuous nucleoli. Variable amounts of cytoplasm were present, and many cells contained a single, well-demarcated eosinophilic hyaline globule adjacent to the nucleus. Ultrastructurally, the cytoplasmic globules were composed of whorled aggregates of intermediate filaments. Immunoperoxidase studies confirmed that the filaments were composed, at least in part, of vimentin. The morphologic and immunohistochemical features are diagnostic of MRT, an entity of unknown histogenesis that has not been reported previously as a primary neoplasm of the CNS.


PreBötzinger complex and pacemaker neurons: hypothesized site and kernel for respiratory rhythm generation.
Identification of the sites and mechanisms underlying the generation of respiratory rhythm is of longstanding interest to physiologists and neurobiologists. Recently, with the development of novel experimental preparations, especially in vitro en bloc and slice preparations of rodent brainstem, progress has been made In particular, a site in the ventrolateral medulla, the preBötzinger Complex, is hypothesized to contain neuronal circuits generating respiratory rhythm. Lesions or disruption of synaptic transmission within the preBötzinger Complex, either in vivo or in vitro, can abolish respiratory activity. Furthermore, the persistence of respiratory rhythm following interference with postsynaptic inhibition and the subsequent discovery of neurons with endogenous bursting properties within the preBötzinger Complex have led to the hypothesis that rhythmogenesis results from synchronized activity of pacemaker or group-pacemaker neurons.


Morphology of the femoral intercondylar notch.
During anterior cruciate ligament reconstruction, proper femoral tunnel placement is important. The purpose of the present study was to characterize the osseous anatomy of the femoral intercondylar notch. We studied the morphology of the femoral intercondylar notch in 200 human femora from skeletally mature donors, with specific attention being paid to the morphology of the ridge on the lateral wall of the intercondylar notch and the posterolateral rim of the intercondylar notch. The distances from the posterolateral rim of the intercondylar notch to the lateral intercondylar ridge and from the posterolateral rim of the intercondylar notch to the inlet of the intercondylar notch (notch depth) were measured at the nine, ten, and eleven o'clock positions for right knees and at the one, two and three o'clock positions for left knees. The lateral intercondylar ridge was present in 194 femora and absent in six. The mean distance from the posterolateral rim of the intercondylar notch to the lateral intercondylar ridge was 9.0, 11.0, and 12.7 mm at the nine, ten, and eleven o'clock positions in right knees and the one, two, and three o'clock positions in left knees, respectively. We observed three different types of morphology of the posterolateral rim of the intercondylar notch. The morphology of the posterolateral rim of the intercondylar notch was distinct in 183 of 200 specimens. A distinct, straight border (type 1) was seen in 175 femora (87.5%); a distinct, V-shaped border (type 2) was seen in eight (4%); and an indistinct border (type 3) was seen in seventeen (8.5%). The morphology of the femoral intercondylar notch varies little. Occasionally, the posterolateral rim of the intercondylar notch is not well-defined. In these knees, accurate placement of commercial femoral tunnel aiming guides may be difficult.


Protein disulfide isomerase acts as a molecular chaperone during the assembly of procollagen.
Protein-disulfide isomerase (PDI) has been shown to be a multifunctional enzyme catalyzing the formation of disulfide bonds, as well as being a component of the enzymes prolyl 4-hydroxylase (P4-H) and microsomal triglyceride transfer protein. It has also been proposed to function as a molecular chaperone during the refolding of denatured proteins in vitro. To investigate the role of this multifunctional protein within a cellular context, we have established a semi-permeabilized cell system that reconstitutes the synthesis, folding, modification, and assembly of procollagen as they would occur in the cell. We demonstrate here that P4-H associates transiently with the triple helical domain during the assembly of procollagen. The release of P4-H from the triple helical domain coincides with assembly into a thermally stable triple helix. However, if triple helix formation is prevented, P4-H remains associated, suggesting a role for this enzyme in preventing aggregation of this domain. We also show that PDI associates independently with the C-propeptide of monomeric procollagen chains prior to trimer formation, indicating a role for this protein in coordinating the assembly of heterotrimeric molecules. This demonstrates that PDI has multiple functions in the folding of the same protein, that is, as a catalyst for disulfide bond formation, as a subunit of P4-H during proline hydroxylation, and independently as a molecular chaperone during chain assembly.


Physiological conditions can be reflected in human urine proteome and metabolome.
Biomarkers are the measurable changes associated with physiological or pathophysiological processes. Urine, unlike blood, lacks mechanisms for maintaining homeostasis: it is therefore an ideal source of biomarkers that can reflect systemic changes. Urinary proteome and metabolome have been studied for their diagnostic capabilities, ability to monitor disease and prognostic utility. In this review, the effects of common physiological conditions such as gender, age, diet, daily rhythms, exercise, hormone status, lifestyle and extreme environments on human urine are discussed. These effects should be considered when biomarker studies of diseases are conducted. More importantly, if physiological changes can be reflected in urine, we have reason to expect that urine will become widely used to detect small and early changes in pathological and/or pharmacological conditions.


Fractalkine: an important candidate for directing periglomerular leukocyte accumulation in irradiated mouse kidneys.
Radiation-induced impairment of renal function is preceded by capillary endothelial cell damage, which initiates a cascade of inflammatory and thrombotic events. Accumulation of leukocytes in the irradiated kidney, especially in areas surrounding the glomeruli, has been clearly demonstrated. The chemokine fractalkine has recently been identified as a key mediator of leukocyte adhesion that functions without the requirement of integrins or selectin-mediated rolling. In this study we investigate the possible involvement of fractalkine in the inflammatory response of the irradiated kidney. Mouse kidneys were irradiated with single doses of 16 or 0 Gy, and protein and mRNA levels of fractalkine and PECAM-1 were examined after 10 to 40 weeks. These changes were correlated with the progressive increase and distribution of leukocytes in the irradiated kidneys. Increased fractalkine immunoreactivity was seen at glomerular sites 30 to 40 weeks after irradiation. This fractalkine expression was strongly associated with the presence of leukocytes surrounding the Bowman's capsule of the same glomeruli. No significant changes in mRNA levels of fractalkine were seen in whole kidney extracts after irradiation, but expression levels were not determined for isolated glomeruli. PECAM-1 protein levels did not change with time after irradiation, although a significant decrease in mRNA expression was seen at 10 weeks. This study is the first demonstration of increased fractalkine after irradiation and the results suggest that fractalkine may be an important mechanism of leukocyte trafficking in the development of a radiation induced inflammatory response.


Clinical presentation and management of gastro-intestinal and pancreatic secondary metastatic tumors.
As progress regarding the treatment has occurred over recent years in oncology, more patients with metastatic disease are presented for diagnosis and further management. The purpose of this study was to reveal the incidence, location and to describe the clinical characteristics and outcome in a series of patients diagnosed with pancreatic, small and large bowel metastatic tumors that underwent metastasectomy. A total of 12 patients (7 male and 5 female) diagnosed with extrahepatic gastrointestinal (GI) and pancreatic metastases from 2001 to 2013 were operated for resection of secondary metastatic tumors to the small and large bowel and the pancreas. Four out of 12 patients were asymptomatic and a secondary tumor was detected during follow up. The median interval revealing the metastatic tumor since the management of the primary tumor was 6.5 years (range 1-27). Primary tumors were malignant melanoma (4 patients), renal cell carcinoma (RCC; 2 patients), leiomyosarcoma of the uterus (2 patients), lobular breast cancer, mesenchymal chondrosarcoma of the skull, endometrial adenocarcinoma and a non-Hodgkin lymphoma (one case each). The median follow-up was 15 months (range 4-120). Metastatic secondary tumors have to be considered especially when the patient's medical history includes a previous malignancy. They may also occasionally present as the initial manifestation of an occult primary lesion leading to diagnostic difficulty. Although radical surgery is the most effective approach, treatment and survival grossly depend on histological type and the stage of the primary disease. Hence, management of these patients should be individualized by a multidisciplinary team.


Natural polyphenolic inhibitors against the antiapoptotic BCL-2.
The apoptotic mechanism is regulated by the BCL-2 family of proteins, such as BCL-2 or Bcl-xL, which block apoptosis while Bad, Bak, Bax, Bid, Bim or Hrk induce apoptosis. The overexpression of BCL-2 was found to be related to the progression of cancer and also providing resistance towards chemotherapeutic treatments. In the present study, we found that all polyphenols (apigenin, fisetin, galangin and luteolin) bind to the hydrophobic groove of BCL-2 and the interaction is stable throughout MD simulation run. Luteolin was found to bind with highest negative binding energy and thus, claimed highest potency towards BCL-2 inhibition followed by fisetin. The hydrophobic interactions were found to be critical for stable complex formation as revealed by the vdW energy and ligplot analysis. Finally, on the basis of data obtained during the study, it can be concluded that these polyphenols have the potential to be used as lead molecules for BCL-2 inhibition.


Synchronous RCC and TCC of the Kidney in a Patient With Multiple Recurrent Bladder Tumors.
Development of concomitant renal TCC and RCC is an uncommon occurrence, yet many interesting issues can be addressed with this model. The possibility of misdiagnosing a renal TCC for an RCC, the options and importance of treating a retained ureteral stump after performing a radical nephrectomy for a renal TCC, and the risk of developing lower tract TCC in patients with upper tract TCC are some of the issues raised in this case review.


Influence of granulation liquid flow rate on particle-size distribution in spray-granulate products.
Granulations were made at various air speeds and various rates of addition of granulating liquid in a spray-granulatin assembly. The ensuring particle sizes were log-normal, and the data substantiate that the process is of the nature previously described. The mean diameter obtained was approximately proportional to the liquid flow rate squared but was independent of air rate. The standard deviation was independent of both parameters.


[Prevention of alcohol-related problems. From therapy to primary health care: experience at the Udine "Healthy City"].
This paper is about a community action for the implementation of a WHO Collaborative Project on the reduction of hazardous drinking in Primary Health Care Settings called "Drink-less". The article stresses the need to shift the attention from alcoholic treatment towards the reduction of alcohol consumption. After the development of a valid screening instrument and counselling material ("Drink-less" Package), the strategies to involve General Practitioners in early intervention are studied. A Pilot Project was implemented in the City of Udine by the Municipality through its Healthy City Project Office. "Healthy City" is a WHO project that stimulates Local Administrations to implement health promotion and Community actions through an intersector work. Besides the undoubted validity of the overall "Drink-less Project", the study emphasizes the importance of GPs in secondary prevention of hazardous drinking and the necessity to re-orient programmed action in Public Health and health promotion. "Healthy City WHO Project" can be an important tool for the implementation of Community actions in Public Health.


Sleep and Delirium in Pediatric Critical Illness: What Is the Relationship?
With growing recognition of pediatric delirium in pediatric critical illness there has also been increased investigation into improving recognition and determining potential risk factors. Disturbed sleep has been assumed to be one of the key risk factors leading to delirium and is commonplace in the pediatric critical care setting as the nature of intensive care requires frequent and invasive monitoring and interventions. However, this relationship between sleep and delirium in pediatric critical illness has not been definitively established and may, instead, reflect significant overlap in risk factors and consequences of underlying neurologic dysfunction. We aim to review the existing tools for evaluation of sleep and delirium in the pediatric critical care setting and review findings from recent investigations with application of these measures in the pediatric intensive care unit.


Quantitative structure-activity relationship study of bitter peptides.
A database consisting of 224 di- to tetradecapeptides and five amino acids was compiled to study quantitative structure-activity relationships of bitter peptides. Partial least-squares regression-1 analysis was conducted using the amino acid three z-scores and/or three parameters (total hydrophobicity, residue number, and log mass values) as X-variables and bitterness values (log 1/T where T is the bitterness threshold) as Y-variables. Using the three parameters only, significant models (p < 0.001) were obtained describing the entire data set as well as data subsets, except that comprised only of octa- to tetradecapeptides. For data sets comprising different peptide lengths, the models were improved by including the three z-scores at the N-terminal and C-terminal positions. Correlation coefficients for bitterness prediction of 48 dipeptides and 12 pentapeptides were 0.75 (RMSEP = 0.53) and 0.90 (RMSEP = 0.48), respectively. Bulky hydrophobic amino acids at the C terminus and bulky basic amino acids at the N terminus were highly correlated to bitterness.


Lung Transplant Recipients and COVID-19: Report of Two Cases.
Although the WHO has declared the end of the pandemic emergency, COVID-19 still poses a threat to immunocompromised patients. The COVID-19 pandemic has spread throughout the world over the last two years, causing a significant number of deaths. After three years, SARS-CoV-2 has lost its initial lethality but has shown a significantly worse prognosis for immunocompromised patients, especially those who have undergone lung transplantation, compared with the general population. This paper presents two compelling case studies that highlight the complex challenges of COVID-19 infection in lung transplant recipients. The first case involves a patient who received a bilateral lung transplant for pulmonary artery hypertension in 2009, followed by a kidney transplant in 2022. Surprisingly, despite an initially favorable clinical course after contracting COVID-19, the patient deteriorated rapidly and died within a few days due to extensive lung involvement. This case highlights the unpredictable nature of COVID-19 and its potentially devastating impact on lung transplant recipients. The second case involves a patient who underwent bilateral lung transplantation five years earlier for chronic obstructive pulmonary disease (COPD). This individual also contracted COVID-19 and had pre-existing complications, including chronic lung allograft rejection (CLAD) and diffuse bronchial stenosis. Following viral infection, the patient's clinical condition deteriorated rapidly, with worsening bronchial stenosis. This case highlights the ability of COVID-19 to exacerbate pre-existing pulmonary complications in transplant recipients. These cases highlight the urgent need for increased vigilance and tailored management strategies when dealing with COVID-19 in lung transplant recipients. The unpredictable and detrimental course of the disease observed in these patients highlights the importance of implementing stringent preventive measures, such as vaccination and strict adherence to infection control protocols, in this vulnerable population. Further research is essential to gain a full understanding of the unique dynamics of COVID-19 in lung transplant recipients and to develop targeted interventions to improve their outcomes.


Biomaterial optimization in total disc arthroplasty.
Knowledge gained through the clinical history of total joint replacement materials combined with the current promise of new biomaterials provides improved guidelines for biomaterial selection in total disc arthroplasty. The following will detail: 1) current biomaterials technology; 2) how current designs of total disc arthroplasty seek to optimize implant performance through judicious biomaterial selection; and 3) what technical obstacles and clinical concerns remain. Metals and polymers remain the central material components of state-of-the-art total joint arthroplasties. Polymers provide low friction surfaces for articulating bearings and some degree of shock absorption. Metals provide appropriate material properties such as high strength, ductility, fracture toughness, hardness, corrosion resistance, formability, and biocompatibility necessary for use in load-bearing roles required total disc replacement. There are three principal metal alloys used in orthopaedics and particularly in total joint replacement: 1) titanium based alloys; 2) cobalt based alloys; and 3) stainless steel alloys. Alloy specific differences in strength, ductility, and hardness generally determine which of these three alloys is used for a particular application or implant component. Current designs. Two examples of current lumbar (Charitè and Prodisc) and cervical (Bryan and Prestige) disc replacements are compared. The similarities and differences in the biomaterials used for each demonstrate prevailing consensus and some idea of how to best optimize implant performance through biomaterial selection. The primary factors governing total disc arthroplasty biomaterials are similar to those of all total joint arthroplasties: generation of wear debris is the primary source of implant degradation, and the subsequent tissue reaction to such debris is the primary factor limiting the longevity of joint replacement prostheses. Particulate debris generated by wear, fretting, or fragmentation induces the formation of an inflammatory reaction, which at a certain point promotes a foreign-body granulation tissue response that has the ability to invade the bone-implant interface. This commonly results in progressive, local bone loss that threatens the fixation of both cemented and cementless devices alike. All metal alloy implants corrode in vivo. When severe, the degradative process may reduce structural integrity of the implant, and the release of corrosion products is potentially toxic to the host. The corrosion resistance of implant alloys is primarily due to the formation of passive oxide films to prevent significant electrochemical dissolution from taking place. The result of this knowledge is a consensus of opinion as to which materials are best suited for use in current total disc arthroplasty designs, where most total disc replacement designs incorporate cobalt-chromium-molybdenum alloy endplates articulating internally on a relatively soft polymeric core and externally coated with titanium or titanium alloy for enhanced bone fixation.


Ultrasound guided block of the saphenous neuroma following use of an AFO in a patient with paraplegia. A case report.
The saphenous nerve is the terminal branch of the femoral nerve and a pure sensory nerve that provide sensation to medial leg. Injury to saphanous nerve following trauma or surgery of the knee can result in formation of a painful neuroma along its distribution. We present a case of saphenous neuroma following use of an ankle-foot orthosis (AFO) in a patient with paraplegia. A 36-year-old patient with paraplegia who was capable of walking independently with his AFO presented to our department with a 3-month history of pain in his left calf. Examination revealed tenderness, paresthesias and positive Tinel sign over the anteromedial aspect of the calf. Ultrasonographic examination of the painful area showed a mass with heterogenous echogenity which was consistent with a saphenous neuroma at the site where fastener band of AFO compressed to skin. We performed a nerve block with steroid and local anesthetic injection under ultrasound guidance to the neuroma. The patient reported pain relief following injection. The use of the AFO may cause a painful saphenous neuroma which is an unusual cause of extremity pain in patients with paraplegia. Ultrasound may be a beneficial diagnostic tool and a guidance for the therapeutic interventions in this condition.


Understanding how physician perceptions of job demand and process benefits evolve during CPOE implementation.
We examine how physicians' perceptions of two computerized provider order entry (CPOE) capabilities, standardisation of care protocols and documentation quality, are associated with their perceptions of turnaround time, medical error, and job demand at three phases of CPOE implementation: pre-go-live, initial use, and continued use. Through a longitudinal study at a large urban hospital, we find standardisation of care protocols is positively associated with turnaround time reduction in all phases but positively associated with job demand increase only in the initial use phase. Standardisation also has a positive association with medical error reduction in the initial use phase, but later this effect becomes fully mediated through turnaround time reduction in the continued use phase. Documentation quality has a positive association with medical error reduction in the initial use phase and this association strengthens in the continued use phase. Our findings provide insights to effectively manage physicians' response to CPOE implementation.


Dynorphin A-(1-13)-Tyr14-Leu15-Phe16-Asn17-Gly18-Pro19 : a potent and selective kappa opioid peptide.
Dynorphin A-(1-13)-Tyr14-Leu15-Phe16-Asn17-Gly18-Pro19+ ++ (dynorphin Ia: a peptide derived from the structure of adrenal dynorphin I) was synthesized by the solid-phase procedure. The product was purified and compared with dynorphin A-(1-13) and [D-Pro10]dynorphin A-(1-11) for its ability to inhibit the electrically evoked contractions of the guinea pig ileum (GPI) and mouse vas deferens (MVD) and to compete with the binding of [3H]ethylketocyclazocine (kappa ligand), [3H][D-Ala2,MePhe4,Glyol5]enkephalin (mu ligand) and [3H][D-Ser2,Thr6]Leu-enkephalin (delta ligand) to membrane preparations of the guinea pig cerebellum or rat brain. Additionally, the antinociceptive effects of the synthetic peptide were assessed in rat paw-pressure and tail-flick tests. In the GPI, dynorphin Ia possessed a relative potency (IC50 0.5 nM) that was comparable to that of [D-Pro10]dynorphin A-(1-11) (IC50 0.5 nM) or dynorphin A-(1-13) (IC50 0.7 nM). In the delta specific MVD assay, dynorphin Ia displayed a reduced potency (IC50 235 nM) as compared with that of dynorphin A-(1-13) (IC50 20 nM) or [D-Pro10]dynorphin A-(1-11) (IC50 46 nM). The affinity of dynorphin Ia for the kappa site in the guinea pig cerebellum (Ki 0.25 nM) was comparable to those of dynorphin A-(1-13) (Ki 0.11 nM) and [D-Pro10]dynorphin A-(1-11) (Ki 0.10 nM). However, the peptide possessed reduced affinities for the mu (Ki 6.7 nM) and delta (Ki 71 nM) opioid receptors as compared with [D-Pro10]dynorphin A-(1-11) (Ki 1.7 and 1.5 nM) an dynorphin A-(1-13) (Ki 0.5 and 4.4 nM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of NlHox3, an essential gene for embryonic development in Nilaparvata lugens.
Hox genes encode transcriptional regulatory proteins that control axial patterning in all bilaterians. The brown planthopper (BPH), Nilaparvata lugens (Hemiptera: Delphacidae), is a destructive insect pest of rice plants in Asian countries. During analysis of the N. lugens transcriptome, we identified a Hox3-like gene (NlHox3) that was highly and specifically expressed in the embryonic stage. We performed functional analysis on the gene to identify its roles in embryonic development and its potential use as a target in RNA interference (RNAi) based pest control. The sequence analysis showed that NlHox3 was homologous to the Hox3 gene and was most closely related with zen of Drosophila. There were no significant differences in oviposition between the treated and control females after injecting double-stranded RNA of NlHox3 (dsNlHox3) into newly emerged female adult BPHs; however, there was a significant difference in the hatchability of those eggs laid, which no egg from the treated group hatched normally. Injecting female adult BPHs with dsNlHox3 led to necrosis of these offspring embryos, with eye reversal and undeveloped organs, suggesting that NlHox3 was an essential gene for embryonic development and might be a potential target for RNAi-based control of this insect pest.


Ten years of "civilization": fitness of Canadian Inuit.
Data on the cardiorespiratory fitness of the Canadian Inuit has been obtained before and after 10 yr exposure to "white civilization." The population tested comprises 201 males (aged 9-76 yr) and 143 females (aged 10-69 yr), about 70% of the eligible population of Igloolik (69 degrees 40'N). During direct maximum tests to exhaustion, a higher maximum heart rate was attained in 1980-81 (194.4 beats X min-1) than in 1970-71 (184.5 beats X min-1); this probably reflects a closer approach to a centrally limited maximum as the Inuit have become familiar with white investigators. The Astrand nomogram currently underestimates the directly measured maximum O2 intake (VO2max) by some 3% in subjects making a good maximum effort. Comparing the 1980-81 data with results for 1970-71, there has been a 15% decrease of predicted VO2max, accompanied by a 2- to 4-kg increase of body mass, accumulation of subcutaneous fat, and a decrease of leg extension strength, these changes affecting all subjects except boys aged 9-15 yr. It is suggested that the loss of personal fitness is related to adoption of a more sedentary lifestyle, particularly the use of tracked vehicles in place of walking through deep snow.


Site-selective post-translational modification of proteins using an unnatural amino acid, 3-azidotyrosine.
An efficient method for site-selective modification of proteins using an unnatural amino acid, 3-azidotyrosine has been developed. This method utilizes the yeast amber suppressor tRNA(Tyr)/mutated tyrosyl-tRNA synthetase pair as a carrier of 3-azidotyrosine in an Escherichia coli cell-free translation system, and triarylphosphine derivatives for specific modification of the azido group. Using rat calmodulin (CaM) as a model protein, we prepared several unnatural CaM molecules, each carrying an azidotyrosine at predetermined positions 72, 78, 80 or 100, respectively. Post-translational modification of these proteins with a conjugate compound of triarylphosphine and biotin produced site-selectively biotinylated CaM molecules. Reaction efficiency was similar among these proteins irrespective of the position of introduction, and site-specificity of biotinylation was confirmed using mass spectrometry. In addition, CBP-binding activity of the biotinylated CaMs was confirmed to be similar to that of wild-type CaM. This method is intrinsically versatile in that it should be easily applicable to introducing any other desirable compounds (e.g., probes and cross-linkers) into selected sites of proteins as far as appropriate derivative compounds of triarylphosphine could be chemically synthesized. Elucidation of molecular mechanisms of protein functions and protein-to-protein networks will be greatly facilitated by making use of these site-selectively modified proteins.


Age, period, and cohort effects in heavy episodic drinking in the US from 1985 to 2009.
Evaluating population-level patterns of heavy episodic drinking by age, period, and cohort is critical to understanding population-level influences on rates over time and to forecasting future trends for public health planning efforts. The present study examined trends in heavy episodic drinking in the US from 1985 through 2009 in a nationally representative sample that included adolescents and adults. Data are drawn from repeated cross-sectional surveys of US households as part of the National Household Survey on Drug Use and Health conducted in 1985, 1988, and annually from 1990 though 2009, inclusive (N=809,281). Heavy episodic drinking was defined as any instance of consuming five or more drinks in one sitting in the past month. Age-period-cohort models were identified using the Intrinsic Estimator algorithm. Heavy episodic drinking is decreasing in the US among adolescents and young adults, with the most recently born cohorts (born in the 1990s) at lower odds of heavy episodic drinking compared with cohorts born in the 1960s, 1970s, and 1980s. Results were consistent across sex and race/ethnicity, with the exception that the decrease is not apparent among Hispanics. These data are promising in that young cohorts appear to be reducing heavy episodic drinking, however the lack of decrease among Hispanics suggests targeted intervention and prevention as well as increased surveillance are necessary.


Understanding salinity responses and adopting 'omics-based' approaches to generate salinity tolerant cultivars of rice.
Soil salinity is one of the main constraints affecting production of rice worldwide, by reducing growth, pollen viability as well as yield of the plant. Therefore, detailed understanding of the response of rice towards soil salinity at the physiological and molecular level is a prerequisite for its effective management. Various approaches have been adopted by molecular biologists or breeders to understand the mechanism for salinity tolerance in plants and to develop salt tolerant rice cultivars. Genome wide analysis using 'omics-based' tools followed by identification and functional validation of individual genes is becoming one of the popular approaches to tackle this task. On the other hand, mutation breeding and insertional mutagenesis has also been exploited to obtain salinity tolerant crop plants. This review looks into various responses at cellular and whole plant level generated in rice plants toward salinity stress thus, evaluating the suitability of intervention of functional genomics to raise stress tolerant plants. We have tried to highlight the usefulness of the contemporary 'omics-based' approaches such as genomics, proteomics, transcriptomics and phenomics towards dissecting out the salinity tolerance trait in rice. In addition, we have highlighted the importance of integration of various 'omics' approaches to develop an understanding of the machinery involved in salinity response in rice and to move forward to develop salt tolerant cultivars of rice.


Predictive value of serum human epididymis protein 4 for heart failure in patients with chronic kidney disease.
To investigate the predictive value of human epididymis protein 4 (HE4) for heart failure in patients with chronic kidney disease (CKD). This study retrospectively analyzed the data of 241 patients with CKD admitted to Zhangjiakou First Hospital from January 2019 to January 2021. The subjects were divided into a heart failure (HF) group (n=117) and a non-HF group (n=124) according to whether heart failure occurred. The baseline data and laboratory hematologic indicators (complete set of HE4, blood routine and biochemistry) were collected and analyzed by univariate analysis. Subsequently, the variables that were significant in the correlation analysis were included in a multi-factor logistic regression analysis. The HF group exhibited higher serum creatinine, HE4, hemoglobin, total cholesterol, triglycerides (TG), high-density lipoprotein (P<0.05), as well as higher B-type natriuretic peptide (BNP), creatine kinase, and creatine kinase-MB than the non-HF group, with significant differences (P<0.05). Spearman's rank correlation analysis revealed that age, HE4, calcium, TG, BNP and left ventricle ejection fraction were associated with the occurrence of heart failure (P<0.05). Multivariate analysis demonstrated that HE4 was a significant factor that could predict the development of heart failure in CKD patients (P<0.01), and the risk of heart failure was higher when HE4>27.2368 pmol/L. HE4 is an important factor for predicting the occurrence of heart failure in CKD patients. A higher HE4 level predicts greater possibility of heart failure.


Exercise electrocardiograms: Code for their clinical evaluation.
This report suggests the use of a simple clinical method of codification of the most significant electrocardiographic changes as a result of the exercise stress test. It uses common abbreviations in the evaluation of the electrocardiographic findings before, during and after exercise. The five major categories to be codified include: (1) the basic electrocardiographic pattern, (2) the heart rate, (3) the pattern of ventricular conduction, (4) the pattern of rhythm and (5) the ST segment deviation. The initial sequence of five symbols indicates the findings in the preexercise electrocardiogram. This is followed by the word "to" with a subscript number. The number in subscript indicates the peak heart rate achieved during the exercise. The sequence of symbols following "to[]" serves to indicate the electrocardiographic changes observed in the postexercise period. The data codified using this system have been found to be concise and easily comparable. The familiarity of the symbols used facilitates its learning and application.