Selective Binding of Folic Acid and Derivatives by Imprinted Nanoparticle Receptors in Water.
Folate receptors are overexpressed on cancer cells and frequently used for targeted delivery. Creation of synthetic receptors to bind folic acid and its analogues in water, however, is challenging because of its complex hydrogen-bonding patterns and competition for hydrogen bonds from the solvent. Micellar imprinting within cross-linkable surfactants circumvented these problems because the nonpolar micellar environment strengthened the hydrogen bonds between the amide group in the surfactant and the template molecule. Incorporation of polymerizable thiouronium functional monomers further enhanced the binding through hydrogen-bond-reinforced ion pairs with the glutamate moiety of the template. The resulting imprinted micelles were able to bind folate and their analogues with submicromolar affinity and distinguish small changes in the hydrogen-bonding patterns as well as the number/position of carboxylic acids. The binding constant obtained was 2-3 orders of magnitude higher than those reported for small-molecule synthetic receptors. Our binding study also revealed interesting details in the binding. For example, the relative contributions of different segments of the molecule to the binding followed the order of carboxylates > pyrimidine ring > pyrazine ring.


[Endothelin 3 (ET3) stimulates the hypothalamic-pituitary-adrenal axis mainly by corticotropin-releasing-hormone (CRH)].
Endothelin 3 (ET3) is a member of the novel vasoconstrictive peptide family, identified in the porcine central nervous system. The effect of ET3 on the hypothalamic-pituitary-adrenal axis in male rats was examined in vivo and in vitro. Intravenous bolus injection of 1000pmol/kg of ET3 in free moving rats caused significant increases in plasma ACTH and corticosterone levels, almost equivalent to those of 100pmol/kg of rat corticotropin-releasing hormone (rCRH). Since an iv bolus injection of ET3 1000pmol/kg did not cause significant changes in the blood pressure of anesthetized rats or the locomotor activity of free moving rats, it seems unlikely that ET3 1000pmol/kg acted as a nonspecific stressor. When ET3 (10(-11) greater than 10(-7)M) was added to cultured anterior pituitary cells, neither direct stimulation of ACTH release nor potentiation of rCRH action was noted. Although it has been shown that ET3 administered systemically probably does not cross the brain-blood-barrier, circulating ET3 may reach the brain tissues through regions lacking the tight barrier, circumventricular structures. The next studies included pretreatment of antagonists or blockers of ACTH stimulating hormones to elucidate the mechanisms of ET3 induced ACTH release. The action of ET3 was virtually abolished by pretreatment of CRH-antagonist alpha helical CRH (150 micrograms/rat icv). But pretreatment of catecholamine-blocker alpha methyl-tyrosine (100mg/kg iv), arginine vasopressin-antagonist dP-thy(Me)AVP (50 micrograms/rat iv) and prostaglandin-blocker indomethacin (3mg/rat iv) did not inhibit the action of ET3. The results indicate that ET3 may play the role of a neuropeptide and that the stimulation of the CRH-neurons is mainly responsible for activation of ACTH and corticosterone release.


Isolation of Bordetella pertussis from swabs.
Four varieties of swabs held in plastic containers and three swab transport media kits, all obtainable in the United Kingdom, were tested to assess their effectiveness in the isolation of Bordetella pertussis. The highest isolation rates up to 48 hours were obtained with Dacron swabs held in plastic containers. Swab-transport media kits proved unsatisfactory. B pertussis may have a stronger affinity to Dacron than to cotton-wool, and pernasal swabs should be made of Dacron to improve the recovery of B pertussis.


Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study.
To examine the relation between blood pressure and the development of early retinopathy in adolescents with childhood onset type 1 diabetes. Prospective cohort study. Diabetes Complications Assessment Service at the Children's Hospital at Westmead, Sydney, Australia. 1869 patients with type 1 diabetes (54% female) screened for retinopathy with baseline median age 13.4 (interquartile range 12.0-15.2) years, duration 4.9 (3.1-7.0) years, and albumin excretion rate of 4.4 (3.1-6.8) microg/min plus a subgroup of 1093 patients retinopathy-free at baseline and followed for a median 4.1 (2.4-6.6) years. Early background retinopathy; blood pressure. Overall, retinopathy developed in 673 (36%) participants at any time point. In the retinopathy-free group, higher systolic blood pressure (odds ratio 1.01, 95% confidence interval 1.003 to 1.02) and diastolic blood pressure (1.01, 1.002 to 1.03) were predictors of retinopathy, after adjustment for albumin excretion rate (1.27, 1.13 to 1.42), haemoglobin A(1c) (1.08, 1.02 to 1.15), duration of diabetes (1.16, 1.13 to 1.19), age (1.13, 1.08 to 1.17), and height (0.98, 0.97 to 0.99). In a subgroup of 1025 patients with albumin excretion rate below 7.5 microg/min, the cumulative risk of retinopathy at 10 years' duration of diabetes was higher for those with systolic blood pressure on or above the 90th centile compared with those below the 90th centile (58% v 35%, P=0.03). The risk was also higher for patients with diastolic blood pressure on or above the 90th centile compared with those below the 90th centile (57% v 35%, P=0.005). Both systolic and diastolic blood pressure are predictors of retinopathy and increase the probability of early retinopathy independently of incipient nephropathy in young patients with type 1 diabetes.


Correlates of HIV-infection among men who have sex with men: results from a community-based, cross-sectional study in Tianjin, China.
China has 747,000 confirmed HIV/AIDS cases and sexual transmission between men who have sex with men (MSM) is the most prevalent mode of transmission. Our study aims to (a) examine HIV prevalence and behavioral risk factors for HIV infection among 1900 MSM recruited from a community-based organization in Tianjin, China, and (b) describe HIV treatment outcomes for those diagnosed with HIV. We used multivariable logistic regression to identify which socio-demographics and behaviors were associated with HIV infection. The overall HIV prevalence was 3.95%. Key behavioral risk factors included: receptive sex role, older age at first sex with man, condomless anal sex, and having used 2+ drugs. Of those living with HIV, 83% were successfully enrolled in antiretroviral therapy and those enrolled were all virally suppressed after one year. These findings highlight key behavioral risk factors for HIV infection in Tianjin, China and can inform interventions to preventing further HIV transmission.


Enhanced Ras activity preserves dendritic size and extension as well as synaptic contacts of neurons after functional deprivation in synRas mice.
The monomeric GTP-binding protein p21Ras has been repeatedly implicated in neuronal stability and plastic changes of the adult nervous system. Recently, we have shown that expression of constitutively active Ras protein in transgenic synRas mice results in a significant increase in the dendritic size and complexity of differentiated pyramidal neurons as well as in increased synaptic connectivity. In the present study, we examined the organization of the vibrissae-barrel cortex in synRas mice and the effects of enhanced Ras activity on deprivation-induced dendritic reorganization after vibrissectomy. The results demonstrate a significant increase in vibrissae-barrel sizes and proportional spacing between barrels in synRas mice, suggesting that the neuronal target specificity of thalamocortical terminals is preserved. Accordingly, the arrangement of double bouquet cells at the borders of barrel columns ensuring functional distinctness is unchanged. Partial vibrissectomy is followed by significant dendritic regression of corresponding pyramidal neurons in the barrel cortex of wild-type mice, which, however, could not be observed in synRas mice. The results provide the first evidence for a role of Ras in preserving neuronal structure after functional deprivation in vivo.


Investigating the Role of Myeloperoxidase and Angiopoietin-like Protein 6 in Obesity and Diabetes.
Myeloperoxidase (MPO) is positively associated with obesity and diet-induced insulin resistance. Angiopoietin-like protein 6 (ANGPTL6) regulates metabolic processes and counteract obesity through increased energy expenditure. This study aims to evaluate the plasma MPO and ANGPTL6 levels in obese and diabetic individuals as well as MPO association with biochemical markers of obesity. A total of 238 participants were enrolled, including 137 control and 101 type 2 diabetes (T2D) patients. ANGPTL6 and MPO levels and other biomarkers were measured via ELISA. ANGPTL6 levels were significantly higher in the diabetic population and obese individuals. When the group was stratified based on T2D, ANGPTL6 levels were significantly higher in obese-diabetic participants compared with non-obese-diabetics, but obese-non-diabetic individuals had similar ANGPTL6 levels to their controls. MPO levels were higher in obese compared with non-obese participants but did not differ between T2D and control participants. MPO levels were upregulated in obese compared with non-obese in both diabetics and non-diabetics. MPO was positively associated with ANGPTL6, triglyceride, BMI, TNF-alpha, high-sensitivity C-reactive protein, interleukin-6, and plasminogen activator inhibitor-1. Taken together, our findings suggest that both MPO and ANGPTL6 may regulate obesity, although MPO exerts this effect independent of diabetes while ANGPTL6 may have a modulatory role in diabetes.


Aerosol microdroplets exhibit a stable pH gradient.
Suspended aqueous aerosol droplets (<50 µm) are microreactors for many important atmospheric reactions. In droplets and other aquatic environments, pH is arguably the key parameter dictating chemical and biological processes. The nature of the droplet air/water interface has the potential to significantly alter droplet pH relative to bulk water. Historically, it has been challenging to measure the pH of individual droplets because of their inaccessibility to conventional pH probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid-functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman microscopy. Using surface-enhanced Raman scattering, we acquired the pH distribution inside approximately 20-µm-diameter phosphate-buffered aerosol droplets and found that the pH in the core of a droplet is higher than that of bulk solution by up to 3.6 pH units. This finding suggests the accumulation of protons at the air/water interface and is consistent with recent thermodynamic model results. The existence of this pH shift was corroborated by the observation that a catalytic reaction that occurs only under basic conditions (i.e., dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe enables pH quantification through the cross-section of an aerosol droplet, revealing a spatial gradient that has implications for acid-base-catalyzed atmospheric chemistry.


The habenula encodes negative motivational value associated with primary punishment in humans.
Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.


Evaluation of microscopic examination for bacteriuria.
In order to find an easily available, simple, reliable and inexpensive method for demonstrating significant bacteriuria in routine urine examination, microscopic observation and bacteriological cultures have been made in parallel on total of 206 urine samples. Microscopic examinations of centrifuged deposit for both pus cells and bacteria were found to be more satisfactory in urine specimens with significant bacteriuria than the examinations for either of these elements alone. The criteria of more than five pus cells per high power field and organisms visible in methylene blue stain had sensitivity of 79% and a false positive rate of 13%.


Iranian student nurses' experiences of clinical placement.
Nursing as a practice-based profession requires that student nurses learn how to become professional in the clinical environment. Many studies have addressed student nurses' clinical learning and related problems, but few have explored the whole clinical experience of being a student nurse. To understand and gain deeper insight into Iranian student nurses' lived experience of clinical placement. Five student nurses were interviewed about their clinical experience during clinical placement. The researchers analysed the verbatim transcripts using van Manen's phenomenological methodology, keeping in mind the recommended six research activities. Five themes emerged by which the phenomenon of clinical experience could be illustrated. These themes were: caring-orientated relationships, attractive aspects of clinical experience, finding oneself in the clinical milieu, being supportive to classmates, and actualizing potential. Fourteen subthemes expanded and clarified the meaning of these themes. The attention paid and acknowledgement given to 'caring' and 'knowledge' by the student nurses showed that they are progressing toward their ultimate goal of being professional nurses. The student nurses' awareness of 'what is going on there?' and also support from other significant people facilitates the students' adaptation process and guarantees this progress.


Vitamin E and cardiovascular disease: observational studies.
Basic research suggests that oxidative stress may play an important role in many chronic diseases and provides plausible mechanisms by which natural antioxidants such as vitamin E may delay or prevent steps in atherogenesis. Dietary research has shown that those who consume higher amounts of fruits and vegetables have lower rates of heart disease and stroke, raising the possibility that antioxidants are protective. Results from large-scale human observational studies suggest that antioxidant consumption reduces the risk of developing cardiovascular disease (CVD). Both case-control and prospective cohort studies have carefully explored the relationship between vitamin E intake and plasma and tissue vitamin E levels and the risk of CVD. In many, but not all, of these studies vitamin E intake over an extended period was associated with decreased risk of cardiovascular events. Results from studies of blood levels are more limited and less consistent. This presentation summarizes data from the major observational studies. Overall, they support the possibility that vitamin E intake either from food or supplements may reduce risk of CVD; however, these studies have important limitations. For example, uncontrolled confounding can be similar in magnitude to the observed health effects, and antioxidant consumption may be merely a marker for a different cardioprotective factor (such as exercise or diet) that is responsible for these effects. In the search for small to moderate effects, randomized trials may be helpful, although to date, data from large-scale trials have been inconsistent. Several large-scale trials currently under way will help identify the potential benefits of vitamin E in the primary prevention of CVD and other chronic illness. Some are designed to test vitamin E alone as well as in combination with other antioxidant supplements because it is possible that antioxidants may be most effective if taken in particular combinations. Currently, the American Heart Association maintains that there are insufficient efficacy data from completed randomized trials to justify population-wide recommendations for use of vitamin E supplements in disease prevention.


Randomized double-blind study of prophylactic treatment with an antihistamine for seasonal allergic rhinitis.
The efficacy of prophylactic treatment before the start of pollen dispersal for prevention of aggravation of symptoms is unclear. The aim of the present study was to examine the efficacy of prophylactic treatment with an antihistamine for seasonal allergic rhinitis (SAR) using an environmental challenge chamber (ECC). The study was performed in a randomized double-blind manner with a 3-way crossover design. The subjects were 50 patients with SAR caused by Japanese cedar pollen who were randomized for treatment with levocetirizine hydrochloride 5 mg (Xyzal®) or placebo as follows: administration of placebo for 8 days (treatment A), single administration of levocetirizine on day 8 after placebo for 7 days (treatment B) or administration of levocetirizine for 8 days (treatment C). Efficacy in each treatment arm was evaluated based on cedar pollen exposure for 3 h on day 9 in an ECC, following 1-hour exposure on day 8. The primary endpoint was the total nasal symptom score for 12 h on day 9. Other nasal and ocular symptoms were secondary endpoints. The evaluation was performed in 45 subjects. The total nasal symptom score on day 9 was significantly lower with treatment B compared with treatment A. Treatment C did not show superior efficacy compared with treatment B. Our results suggest that early intervention with levocetirizine soon after onset of symptoms may attenuate these symptoms as effectively as prophylactic treatment before pollen dispersal. These results are important from the perspective of patient convenience and reduction of medical costs.


Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma.
This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.


Genetic linkage of prostate cancer risk to the chromosome 3 region bearing FHIT.
We conducted linkage analysis of 80 candidate genes in 201 brother pairs affected with prostatic adenocarcinoma. Markers representing two adjacent candidate genes on chromosome 3p, CDC25A and FHIT, showed suggestive evidence for linkage with single-point identity-by-descent allele-sharing statistics. Fine-structure multipoint linkage analysis yielded a maximum LOD score of 3.17 (P = 0.00007) at D3S1234 within FHIT intron 5. For a subgroup of 38 families in which three or more affected brothers were reported, the LOD score was 3.83 (P = 0.00001). Further analysis reported herein suggested a recessive mode of inheritance. Association testing of 16 single nucleotide polymorphisms (SNP) spanning a 381-kb interval surrounding D3S1234 in 202 cases of European descent with 143 matched, unrelated controls revealed significant evidence for association between case status and the A allele of single nucleotide polymorphism rs760317, located within intron 5 of FHIT (Pearson's chi(2) = 8.54, df = 1, P = 0.0035). Our results strongly suggest involvement of germline variations of FHIT in prostate cancer risk.


Au disk nanoelectrode by electrochemical deposition in a nanopore.
In this technical note, we report a process in scaling down the fabrication of Au disk nanoelectrodes as small as approximately 4 nm in radii. We have developed a bottom-up approach toward the fabrication of individual disk-shape Au nanoelectrodes. This new approach is based upon electrochemical deposition of Au in a silica nanopore electrode and involves the following four steps. First, a laser-assisted pulling process is employed to fabricate a disk-shape Pt nanoelectrode. Second, a Pt nanopore electrode is obtained by electrochemically etching the Pt from the disk nanoelectrode. Third, a Au metal nanowire is electrochemically deposited using the Pt nanopore electrode as a template. In the last step, the Au electrode is slightly polished to expose a disk-shape Au nanoelectrode, whose size is determined by the size of the initial Pt nanoelectrode. Steady-state voltammetry in the presence of ferrocene has been used to characterize these Au nanoelectrodes. The Au nanoelectrodes are also characterized using cyclic voltammetry in a H2SO4 solution. The results show characteristic peaks corresponding to the formation of Au surface oxides and their subsequent reduction. The Au nanoelectrodes are modified with 6-(ferrocenyl)hexanethiol molecules, and cyclic voltammetry is used to characterize the ferrocene molecules attached at the Au. As an application, we have constructed Au single-nanoparticle electrodes (SNPEs) using the Au disk nanoelectrodes fabricated by electrochemical deposition. Our initial results of such SNPEs show excellent electrochemical response from single Au nanoparticles.


N-doped ZnO thin film for development of magnetic field sensor based on surface plasmon resonance.
Magnetic-field-dependent optical properties of nitrogen-doped ZnO (ZnO:N) thin films were investigated using surface plasmon resonance (SPR) and a highly sensitive (4.65/Tesla) magnetic field sensor has been realized. The refractive index (RI) of ZnO:N film increases from 1.949 to 2.025 with increase in N doping from 0% to 10% demonstrating tunable RI. In contrast to pure ZnO, SPR curves for ZnO:N films exhibit a shift toward lower angles with increasing applied magnetic field from 0 to 35 mT due to change in reflectance of light upon reflection from ferromagnetic surface. Results indicate promising application of ferromagnetic ZnO:N film as a magnetic field sensor.


Recent advances in the structure, synthesis, and applications of natural polymeric hydrogels.
Hydrogels, polymeric network materials, are capable of swelling and holding the bulk of water in their three-dimensional structures upon swelling. In recent years, hydrogels have witnessed increased attention in food and biomedical applications. In this paper, the available literature related to the design concepts, types, functionalities, and applications of hydrogels with special emphasis on food applications was reviewed. Hydrogels from natural polymers are preferred over synthetic hydrogels. They are predominantly used in diverse food applications for example in encapsulation, drug delivery, packaging, and more recently for the fabrication of structured foods. Natural polymeric hydrogels offer immense benefits due to their extraordinary biocompatible nature. Hydrogels based on natural/edible polymers, for example, those from polysaccharides and proteins, can serve as prospective alternatives to synthetic polymer-based hydrogels. The utilization of hydrogels has so far been limited, despite their prospects to address various issues in the food industries. More research is needed to develop biomimetic hydrogels, which can imitate the biological characteristics in addition to the physicochemical properties of natural materials for different food applications.


Mutations to antibiotic resistance occur during the stationary phase in Lactobacillus plantarum ATCC 8014.
When Lactobacillus plantarum ATCC 8014 was maintained in LCM broth (which consists of buffered tryptone and is sufficient to support the growth of some species of Lactobacillus ) for long periods (120 d), viable bacteria persisted. Rifampicin-, streptomycin- and sodium-fusidate-resistant mutants were recovered from parallel LCM broth cultures following a stochastic pattern. Individual cultures appeared to yield mutants intermittently. One culture in particular yielded rifampicin-resistant colonies at a frequency of 1 in 100 viable bacteria after 20 d incubation and these persisted until the experiment was terminated at 115 d. In a separate experiment two parallel cultures yielded mutants resistant to low concentrations of streptomycin at a similar frequency. Using a chemostat it was shown that in continuous culture in LCM at slow growth rates the highest frequency of recovery of antibiotic-resistant mutants was achieved when the bacteria exhibited doubling times of 90 h or greater. The frequency of recovery of mutants was as high as 1 in 1000 viable bacteria. Thus, mutations to antibiotic resistance in L. plantarum ATCC 8014 can take place in the absence of measurable cell division. The data are consistent with the notion that populations of starved bacteria in stationary phase can be genetically dynamic.


Cattle vocalizations are associated with handling and equipment problems at beef slaughter plants.
Vocalization of cattle in commercial slaughter plants is associated with observable aversive events such as prodding with electric prods, slipping in the stunning box, missed stuns, sharp edges on equipment or excessive pressure form a restraint device. A total of 5806 cattle were observed during handling and stunning in 48 commercial slaughter plants in the United States, Canada and Australia during the calendar year of 1999. Each animal was scored as either a vocalizer or a non-vocalizer. In 20 plants (42%), 0-1% of the cattle vocalized, in 12 plants (25%) 2-3% vocalized, in 12 plants (25%) 4-10% vocalized and in four plants (8%) more than 10% vocalized. In three plants repeated use of an electric prod on 95% or more of the cattle that balked and refused to move was associated with vocalization percentages of 17, 16 and 12%. In five plants, the percentage of cattle that vocalized was reduced by making modifications to plant equipment. Reducing the voltage on a rheostat controlled electric prod reduced the vocalization percentage from 7 to 2% in the first plant. In three other plants, the incidence of cattle backing up and balking was reduced by illuminating a dark entrance or adding a false floor to a conveyor restrainer. A false floor eliminates the visual cliff effect. The percentage of cattle that vocalized was reduced from 8 to 0%, 9 to 0% and 17 to 2%. Since balking was reduced, electric prod use was also reduced. In the fifth plant, reduction of the pressure exerted by a neck restraint reduced the percentage of cattle that vocalized from 23 to 0%. In the five plants where modifications were made, a total of 379 cattle were observed prior to equipment modifications and 342 after modification. The mean percentage of cattle that vocalized was 12.8% before the modifications and 0.8% after the modifications (P<0.001). Vocalization scoring can be used to identify handling and equipment problems that may compromise animal welfare.


Expression dynamics and genome distribution of osmoprotectants in soybean: identifying important components to face abiotic stress.
Despite the importance of osmoprotectants, no previous in silico evaluation of high throughput data is available for higher plants. The present approach aimed at the identification and annotation of osmoprotectant-related sequences applied to short transcripts from a soybean HT-SuperSAGE (High Throughput Super Serial Analysis of Gene Expression; 26-bp tags) database, and also its comparison with other transcriptomic and genomic data available from different sources. A curated set of osmoprotectants related sequences was generated using text mining and selected seed sequences for identification of the respective transcripts and proteins in higher plants. To test the efficiency of the seed sequences, these were aligned against four HT-SuperSAGE contrasting libraries generated by our group using soybean tolerant and sensible plants against water deficit, considering only differentially expressed transcripts (p ≤ 0.05). Identified transcripts from soybean and their respective tags were aligned and anchored against the soybean virtual genome. The workflow applied resulted in a set including 1,996 seed sequences that allowed the identification of 36 differentially expressed genes related to the biosynthesis of osmoprotectants [Proline (P5CS: 4, P5CR: 2), Trehalose (TPS1: 9, TPPB: 1), Glycine betaine (BADH: 4) and Myo-inositol (MIPS: 7, INPS1: 8)], also mapped in silico in the soybean genome (25 loci). Another approach considered matches using Arabidopsis full length sequences as seed sequences, and allowed the identification of 124 osmoprotectant-related sequences, matching ~10.500 tags anchored in the soybean virtual chromosomes. Osmoprotectant-related genes appeared clustered in all soybean chromosomes, with higher density in some subterminal regions and synteny among some chromosome pairs. Soybean presents all searched osmoprotectant categories with some important members differentially expressed among the comparisons considered (drought tolerant or sensible vs. control; tolerant vs. sensible), allowing the identification of interesting candidates for biotechnological inferences. The identified tags aligned to corresponding genes that matched 19 soybean chromosomes. Osmoprotectant-related genes are not regularly distributed in the soybean genome, but clustered in some regions near the chromosome terminals, with some redundant clusters in different chromosomes indicating their involvement in previous duplication and rearrangements events. The seed sequences, transcripts and map represent the first transversal evaluation for osmoprotectant-related genes and may be easily applied to other plants of interest.


Enterococcal burn sepsis. A highly lethal complication in severely burned patients.
A retrospective study was undertaken to examine the incidence and clinical significance of enterococcal bacteremia in burned patients with enterococcal burn-wound infections. During a 26-month period from 1983 to 1985, 38 patients were found to have enterococcal burn-wound infections. Twenty of these patients developed positive blood cultures for enterococcus with no other identifiable source for the bacteremia. Cases occurred sporadically during the study period without evidence of a specific epidemic. Ten patients died within ten days of the bacteremia, while nine others eventually died from other complications. Only one patient survived to discharge. Prior antibiotic therapy did not appear to increase the risk for enterococcal infection, and specific therapy against the enterococcus after the bacteremia was identified appeared to have no effect on mortality. Mortality was significantly greater for bacteremic patients than for patients with enterococcal wound infection alone or for burned patients without enterococcal infections. Although previously not considered pathogenic, enterococcal burn-wound infections should prompt aggressive therapy to prevent the development of enterococcal sepsis with its associated high mortality.


G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry.
The nervous system can modulate neurotransmitter release by neurotransmitter activation of heterotrimeric GTP-binding protein (G protein)-coupled receptors. We found that microinjection of G protein betagamma subunits (Gbetagamma) mimics serotonin's inhibitory effect on neurotransmission. Release of free Gbetagamma was critical for this effect because a Gbetagamma scavenger blocked serotonin's effect. Gbetagamma had no effect on fast, action potential-evoked intracellular Ca2+ release that triggered neurotransmission. Inhibition of neurotransmitter release by serotonin was still seen after blockade of all classical Gbetagamma effector pathways. Thus, Gbetagamma blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal.


Valproic acid is a novel activator of AMP-activated protein kinase and decreases liver mass, hepatic fat accumulation, and serum glucose in obese mice.
Valproic acid (VPA) is a widely prescribed anticonvulsant for the treatment of epilepsy. Here we demonstrate that VPA is a novel activator of AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism, using primary mouse and human hepatocytes. Incubation of primary mouse hepatocytes with VPA resulted in increased levels of phosphorylated AMPK and acetyl-CoA carboxylase (ACC). This finding was recapitulated using primary human hepatocytes. Pretreatment of mouse hepatocytes with a small-molecule inhibitor of AMPK, Compound C (6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine), abrogated the phosphorylation of ACC following treatment with VPA. The cytochrome P450 inhibitor 1-aminobenzotriazole blocked the VPA-stimulated phosphorylation of AMPK, suggesting a requirement for biotransformation of VPA. In line with this, treatment of hepatocytes with metabolites of VPA resulted in increased phosphorylation of AMPK/ACC as compared with VPA. Treatment of ob/ob mice with VPA for 14 days resulted in decreased liver masses, hepatic fat accumulation, and serum glucose. These results paralleled those observed in mice treated with metformin. In addition, a targeted mass spectrometry-based metabolomics assay revealed several small molecules that were differentially abundant in the serum of ob/ob mice treated with VPA as compared with vehicle-treated mice. These studies are the first to establish VPA and its metabolites as in vitro activators of AMPK.


Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches.
Great efforts are being made worldwide to identify the specific clinical characteristics of infected critically ill patients that mediate the associated pathogenesis, including vascular dysfunction, thrombosis, dysregulated inflammation, and respiratory complications. Recently, coronavirus disease 2019 has been closely related to sepsis, which suggests that most deaths in ICUs in infected patients are produced by viral sepsis. Understanding the physiopathology of the disease that lead to sepsis after severe acute respiratory syndrome coronavirus 2 infection is a current clinical need to improve intensive care-applied therapies applied to critically ill patients. Although the whole representative data characterizing the immune and inflammatory status in coronavirus disease 2019 patients are not completely known, it is clear that hyperinflammation and coagulopathy contribute to disease severity. Here, we present some common features shared by severe coronavirus disease 2019 patients and sepsis and describe proposed anti-inflammatory therapies for coronavirus disease 2019 which have been previously evaluated in sepsis.


Isolation and mutational assessment of pancreatic cancer extracellular vesicles using a microfluidic platform.
Cancer cells release extracellular vesicles known as extracellular vesicles (EVs), containing tumor-derived DNA, RNA and proteins within their cargo, into the circulation. Circulating tumor-derived extracellular vesicles (TEV) can be used in the context of serial "liquid biopsies" for early detection of cancer, for monitoring disease burden in patients, and for assessing recurrence in the post-resection setting. Nonetheless, isolating sufficient TEV by ultracentrifugation-based approaches, in order to enable molecular assessment of EVs cargo, can be an arduous, time-consuming process and is inconsistent in the context of yield and purity among institutions. Herein, we describe a microfluidic platform, which we have named MITEV (Microfluidic Isolation of Tumor-derived Extracellular Vesicles) for the rapid isolation of TEV from the plasma of pancreatic cancer patients. The device, which has ~100,000 pillars placed in a zigzag pattern and is coated with antibodies against generic EV surface proteins (anti-CD63, -CD9, and -CD81 antibodies) or the TEV specific anti-Epithelial Cell Adhesion Molecule (EpCAM) antibody, is capable of high-throughput EVs isolation and yields sufficient DNA (total of ~2-14 ng from 2-ml plasma) for downstream genomic analysis. Using two independent quantitative platforms, droplet digital polymerase chain reaction (ddPCR) and molecular barcoding using nanoString nCounter® technology, we can reliably identify KRAS mutations within isolated TEV of treatment-naïve metastatic pancreatic cancer patients. Our study suggests that the MITEV device can be used for point-of-care applications, such as in the context of monitoring residual or recurrent tumor presence in pancreatic cancer patients undergoing therapy.


[Changes in blood composition and properties in children with external fistulae].
The investigation of the composition and properties of blood in 20 children with small intestine fistulas has revealed hypovolemia, disorders in the electrolyte composition, increased hematocrit and viscosity, changes of tests of coagulogram and thromboelastogram pointing to disseminated intravascular coagulation. Similar changes were noted in experimental studies in 20 dogs with duodenal fistulas. Drugs improving rheological properties of blood and anticoagulants gave better results of the treatment.


Targeted laser photocoagulation of larger capillary aneurysms with rim in diabetic macular edema.
This is a retrospective series of five eyes of four cases with diabetic macular edema (DME) secondary to large capillary aneurysms. Larger capillary aneurysms were identified noninvasively based on the presence of white rim in color photograph. On optical coherence tomography (OCT), the larger capillary aneurysms were seen as vertically oval structures with heterogeneous lumen and hyperreflective margin. Two of the four eyes were treated with intravitreal therapy with poor response before considering laser photocoagulation. In one eye, laser photocoagulation was considered as primary therapy in view of the poor response to intravitreal therapy in the fellow eye. In one eye, intravitreal steroid with prompt laser was considered. In one eye, laser was considered as primary therapy. Complete obliteration of the capillary lumen was noted on OCT in all the five eyes after laser photocoagulation. Complete resolution of macular edema was noted in all the five eyes with no recurrence over a follow-up period of 4-18 months. DME secondary to larger capillary aneurysms responds well to targeted laser photocoagulation. These larger capillary aneurysms can be identified on clinical examination and color photograph by the presence of white rim and can be confirmed on OCT.


Prevalence of Chronic Mountain Sickness in high altitude districts of Himachal Pradesh.
Chronic Mountain Sickness (CMS) is a maladaptation condition that can affect people who reside permanently at high altitude (HA). It is characterized by polycythemia, hypoxemia and dyspnea and can be fatal. Over 140 million people live permanently at HA around the world. Unfortunately, research into CMS is lacking and accurate data on the prevalence of this condition do not exist for many regions around the world. In this study, we sought to examine prevalence rates of CMS in the Indian Himalayas, focusing on the Northern State of Himachal Pradesh. We surveyed 83 individuals (69 males) in eight towns across the HA districts of Sirmaur, Kinnaur and Lahaul and Spiti in Himachal Pradesh, India. Altitudes ranged from 2350 to 4150 m. We used an adapted Qinghai CMS scoring system to diagnose CMS. Information related to subject demographics, medical history, socioeconomic status, and geography were collected to identify risk factors for CMS. Physiologic recordings of oxygen saturation (SpO2) and pulse rate were made through pulse oximetry. Overall CMS prevalence was 6.17% and mean altitude was 3281 m. At altitudes above 3000 m CMS prevalence rose to 13.73%. All cases of CMS were mild and there was a significant positive correlation between CMS scores and altitude (R = 0.784, P = 0.0213). Mean SpO2 was 90.7 ± 0.4% and mean pulse rate was 80.3 ± 1.3 bpm. SpO2 significantly correlated with altitude (R = -0.929, P < 0.001). In our study, age, gender, and tobacco use were not independent risk factors for CMS. Individuals with CMS lived at higher altitudes than their non-CMS counterparts (3736.00 ± 113.30 m vs. 3279.80 ± 69.50 m, respectively; P = 0.017). CMS prevalence in HA towns of the Indian Himalayas of Himachal Pradesh is 6.17% and 13.73% for towns above 3000 m. Further research is required to determine the prevalence of CMS in other regions of the world and to determine risk factors associated with CMS.


Patch clamp studies of lymphocyte activation.
In both T- and B-lymphocyte activation, antigen receptor or mitogen stimulation results in phosphoinositide turnover, generation of InsP3 and diacylglycerol, and a sustained rise in intracellular Ca2+, from both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. There is also an associated K+ efflux and membrane hyperpolarization. Patch clamp studies in T and B cells have revealed the presence of several types of ion channels that apparently contribute to the ion fluxes and to the membrane potential changes associated with lymphocyte activation. Three types of T-cell channels are described in this review. First, patch clamp studies have revealed the presence of a nonvoltage-gated, Ca2+ permeable channel, the probability of whose opening increases upon exposure of the T cell to activating ligands. Enhanced opening probability appears to be mediated by the second messenger InsP3, implying that InsP3 is responsible for both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. The Ca2+ permeable channel also undergoes a Ca2(+)-dependent inactivation process in an autoregulatory fashion. In addition, voltage-gated K+ channels, which closely resemble the delayed rectifier K+ channel of nerve and muscle, can be classified into three subtypes, according to their voltage dependence of activation, inactivation kinetics, and pharmacological sensitivity. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. The voltage-activated K+ channel is postulated to have a role in mitogenesis, based on studies that demonstrate an increase in K+ channel amplitude in the 24-48 hr following mitogen stimulation, and on studies that demonstrate that K+ channel blockers inhibit mitogenesis in a dose-dependent manner with the same potency sequence for ion channel block. The precise functional role of the voltage-activated K+ channel remains to be determined. Finally, a Ca2(+)-activated K+ channel in T cells has recently been described. This channel presumably underlies the K+ efflux and membrane hyperpolarization that accompany the mitogen-induced increase in [Ca2+]i. Three channel types that may contribute to activation have also been described in B lymphocytes. In murine myeloma and hybridoma cells, a voltage-gated Ca2+ channel similar to Ca2+ channels in nerve, heart, and muscle is present. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines.(ABSTRACT TRUNCATED AT 400 WORDS)


Differential requirement for autoantibody-producing B cells for induction of lymphocytic versus granulomatous experimental autoimmune thyroiditis.
Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTG transfer experimental autoimmune thyroiditis (EAT) in which the thyroid cellular infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of anti-IL2R antibody to cultures with MTg leads to activation of cells that induce granulomatous EAT, accompanied by high serum anti-MTg autoantibody responses, in recipient mice. CD4+ T cells are required to induce both forms of EAT; whether B cells and/or autoantibodies produced by MTg-sensitized B cells also contribute to disease severity or the type of thyroid histopathology is unknown. In our study, B cells and autoantibody responses produced in recipient mice were reduced either by column removal of B cells from donor spleen cells or by treatment of recipient mice with anti-I-AK mAb at the time of cell transfer. These maneuvers only slightly reduced the severity of lymphocytic EAT but markedly reduced the severity and incidence of granulomatous EAT developing in recipient mice. Delaying the initiation of anti-I-AK treatment until 6 days after cell transfer was less effective in reducing anti-MTg autoantibody responses or granulomatous EAT. These studies all suggested that anti-MTg autoantibodies were required for development of granulomatous but not lymphocytic EAT. However anti-I-AK-treated recipients receiving injections of anti-MTg antibody or having serum antibody induced by prior immunization with MTg and LPS also developed less severe granulomatous EAT than controls. These results suggest that sensitized CD4+ T cells and circulating anti-MTg autoantibody are not sufficient for development of granulomatous thyroid lesions. It is possible that antibodies having a unique function or specificity are produced in mice developing granulomatous EAT or thyroid-infiltrating B cells may directly contribute to the granulomatous inflammatory response.


Cancer-associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin-L and tumor cell invasion.
EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors. The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of cancer associated EpCAM mutations. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. In vitro and in vivo models were used to determine the effect of wild type (WT) and mutant EpCAM on CTSL activity and invasion. Immunoprecipitation and localization studies tested EpCAM and CTSL protein binding and determined compartmental expression patterns of EpCAM mutants. We demonstrate that WT EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastases in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. These studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.


PST 2238: a new antihypertensive compound that modulates the Na-K pump 'in vivo' and 'in vitro'.
A primary renal alteration due to a genetic polymorphism of the cytoskeletal protein adducin associated with an up-regulation of the renal Na-K pump and increased levels of ouabainlike factor (OLF) has been identified as a possible causes of hypertension in Milan rats (MHS). This adducin polymorphism has also been found to be associated with hypertension and the blood pressure changes related to renal Na handling in humans and increased OLF levels have been found in a relevant portion of hypertensive patients. Increased activity and expression of the Na-K pump has also been observed under the following 'in vitro' and 'in vivo' conditions: rat renal cells transfected with the 'hypertensive' variant of adducin, as compared with normal cells; normal rat renal cells incubated for 5 days with 10(-9) M ouabain and normal rats made hypertensive by a chronic infusion of low doses of ouabain (OS rats). An up-regulation of the Na-K pump seems therefore to be a common biochemical alteration induced both by an adducin polymorphism and/or chronic exposure to low concentrations of ouabain (or OLF). A new antihypertensive compound, PST 2238, that selectively antagonizes the pressor effect and the alteration of the renal Na-K pump induced both by an adducin polymorphism and OLF, is described. The ability of PST 2238 to lower blood pressure and normalize the Na-K pump both in MHS and OS rats suggests that this compound could be useful in the treatment of those forms of essential hypertension in which renal Na-handling alterations are associated with either adducin polymorphisms and/or increased OLF levels.


Polymerase chain reaction detection of aspergillus DNA in experimental models of invasive aspergillosis.
To determine the sensitivity of polymerase chain reaction (PCR) assays for the diagnosis of invasive aspergillosis, results of quantitative culture, PCR-ELISA, and a quantitative LightCycler assay (Roche Diagnostics) of blood and organ specimens of experimentally infected mice and rabbits were compared. By PCR-ELISA, 297 of 379 murine lung specimens were positive, but only 235 of 379 were culture positive. Whereas 64 culture-negative lungs were positive by PCR, Aspergillus was grown from only 2 PCR-negative samples. The PCR assay was 19.4 times more sensitive than culture. None of the 68 blood cultures from mice and rabbits were positive for Aspergillus fumigatus, whereas PCR detected Aspergillus DNA in 17 of 68 blood samples. Quantitative PCR analysis of blood samples showed a fungus load of 10(1)-10(2) cfu/mL of blood. The data confirm the superior sensitivity of PCR for the diagnosis of experimental Aspergillus infections.


Phylogenetics of Camelina Crantz. (Brassicaceae) and insights on the origin of gold-of-pleasure (Camelina sativa).
Camelina sativa (false flax or gold-of-pleasure) is an Old World oilseed crop that fell out of use in the mid 20th Century but has recently gained renewed interest as a biofuel source. The crop is hexaploid, and its relationship to its diploid and polyploid congeners has remained unresolved. Using 54 accessions representing five species sampled across Camelina's center of diversity in Turkey and the Caucasus, we performed phylogenetic and genetic diversity analyses using RADseq genotyping and ITS sequencing. Flow cytometry was performed to assess relationships between genome size and phylogenetic groupings. Accessions fell into distinct, highly-supported clades that accord with named species, indicating that morphological characters can reliably distinguish members of the genus. A phylogenetically distinct lineage from Turkey may represent a currently unrecognized diploid species. In most analyses, C. sativa accessions nest within those of C. microcarpa, suggesting that the crop is descended from this wild hexaploid species. This inference is further supported by their similar genome size, and by lower genetic diversity in C. sativa, which is consistent with a domestication bottleneck. These analyses provide the first definitive phylogeny of C. sativa and its wild relatives, and they point to C. microcarpa as the crop's wild ancestor.


Cytogenetic analysis of a primary salivary gland myoepithelioma.
Myoepithelioma, a rare benign salivary gland neoplasm, is a tumor composed entirely of myoepithelial cells. Unlike pleomorphic adenoma, these tumors lack any ductal epithelial differentiation, and manifest a minor stromal element. Previous cytogenetic and molecular genetic studies have mainly investigated pleomorphic adenomas and reported recurring specific chromosomal alterations at 8q12 and 12q13-q15 regions. The cell origin of these alterations, however, remains speculative. We report the cytogenetic analysis of a parotid myoepithelioma and discuss the putative origin for the cells with cytogenetic alterations. Our analysis shows 12q12 involved in a translocation with a previously unreported partner (1q), and nonrandom del(9)(q22.1q22.3) and del(13)(q12q22). Our results indicate that the myoepithelial cell is the source of those cells with chromosomal alterations, and that myoepithelioma shares 12q alterations reported in a subset of pleomorphic adenomas.


Decreased production of insulin-like growth factor-binding protein (IGFBP)-6 by transfection of colon cancer cells with an antisense IGFBP-6 cDNA construct leads to stimulation of cell proliferation.
: Previously, we have observed that highly unsaturated dietary (n-3) fatty acids inhibit cell proliferation in conjunction with stimulation of insulin-like growth factor-binding protein (IGFBP)-6 secretion in Caco-2 cells, a human colon carcinoma cell line. : To test the converse hypothesis that inhibition of endogenous IGFBP-6 secretion stimulates Caco-2 cell proliferation, cells were transfected with the antisense IGFBP-6 expression construct or pcDNA3 vector only, and single colonies resistant to G418 sulfate were isolated. : Our initial studies indicated that three antisense clones grew faster and produced less IGFBP-6 than two pcDNA3 clones, so antisense IGFBP-6 #5 and pcDNA3 #8 were selected for further detailed analysis. Both the control and antisense clones grew in serum-free medium reaching a plateau density at day eight. However, the antisense clone grew at a rate faster than that of the control and reached a final density that was 31 +/- 3% higher than the control. Northern blot, ligand blot and immunoblot analyses revealed that accumulation of IGFBP-6 mRNA and concentrations of IGFBP-6 peptide produced by the antisense clone were decreased by 80-90% compared to the control. The doubling times of the antisense and control clones were 21.9 +/- 0.4 and 24.8 +/- 0.3 h (P < 0.05), respectively. Exogenous IGF-I and IGF-II (0.2-200 nmol/L) stimulated proliferation of both the control and antisense clones in a dose-dependent manner, but the relative potency and efficacy of IGF-II was higher in the antisense clone compared to the control. These results indicate that suppression of IGFBP-6 secretion correlates with an increase in the basal rate of Caco-2 cell growth. : Our findings are consistent with the hypothesis that IGFBP-6 inhibits cell growth by binding to endogenously produced IGF-II, thereby preventing IGF-II from interacting with the IGF-I receptor to stimulate cellular proliferation by an autocrine mechanism.


Parallel Fock matrix construction program for molecular orbital calculation--specific computer with a hierarchical network.
A parallel Fock matrix construction program for a hierarchical network has been developed on the molecular orbital calculation-specific EHPC system. To obtain high parallelization efficiency on the hierarchical network system, a multilevel dynamic load-balancing scheme was adopted, which provides equal load balance and localization of communications on a tree-structured hierarchical network. The parallelized Fock matrix construction routine was implemented into a GAMESS program on the EHPC system, which has a tree-structured hierarchical network. Benchmark results on a 63-processor system showed high parallelization efficiency even on the tree-structured hierarchical network.


Inequalities in self-rated health in Japan 1986-2007 according to household income and a novel occupational classification: national sampling survey series.
Japan, for the past two decades, has seen economic stagnation and substantial social change. We examined whether health inequalities increased over this period. Using eight triennial waves of a series of large nationally representative surveys between 1986 and 2007 (n=398 303), temporal trends in relative and slope indices of inequality (RII, SII, respectively) were tested based on self-rated health in relation to theory-based social class and household income. Age-standardised prevalence of self-rated fair or poor health showed V-shaped time trends in both sexes with the lowest prevalence in early/mid-1990s. In 1986, RII and SII in household social class and income were significant for both sexes. In men, RII and SII according to income showed significant narrowing of temporal trends in poor health (-1.4% and -0.1% annually, respectively), but these were stable in women. After multilevel multiple imputation for missing income data, the findings in men were not altered but narrowing trends became evident and significant in women (-1% and -0.1% annually, respectively). Inequality indices for social class remained constant over the study period in both sexes. Relative and absolute health inequalities for social class and income based on self-rated fair or poor health narrowed or remained stable between 1986 and 2007, despite the economic stagnation and adverse social changes. Overall population health across socioeconomic groups initially improved but then worsened. The positive finding regarding the health inequality trend seen in the Japanese context is informative for the wider international community during this period of economic uncertainty.


Agathisflavone as a Single Therapy or in Association With Mesenchymal Stem Cells Improves Tissue Repair in a Spinal Cord Injury Model in Rats.
Agathisflavone is a flavonoid with anti-neuroinflammatory and myelinogenic properties, being also capable to induce neurogenesis. This study evaluated the therapeutic effects of agathisflavone-both as a pharmacological therapy administered in vivo and as an in vitro pre-treatment aiming to enhance rat mesenchymal stem cells (r)MSCs properties-in a rat model of acute spinal cord injury (SCI). Adult male Wistar rats (n = 6/group) underwent acute SCI with an F-2 Fogarty catheter and after 4 h were treated daily with agathisflavone (10 mg/kg ip, for 7 days), or administered with a single i.v. dose of 1 × 106 rMSCs either unstimulated cells (control) or pretreated with agathisflavone (1 µM, every 2 days, for 21 days in vitro). Control rats (n = 6/group) were treated with a single dose methylprednisolone (MP, 60 mg/kg ip). BBB scale was used to evaluate the motor functions of the animals; after 7 days of treatment, the SCI area was analyzed after H&E staining, and RT-qPCR was performed to analyze the expression of neurotrophins and arginase. Treatment with agathisflavone alone or with of 21-day agathisflavone-treated rMSCs was able to protect the injured spinal cord tissue, being associated with increased expression of NGF, GDNF and arginase, and reduced macrophage infiltrate. In addition, treatment of animals with agathisflavone alone was able to protect injured spinal cord tissue and to increase expression of neurotrophins, modulating the inflammatory response. These results support a pro-regenerative effect of agathisflavone that holds developmental potential for clinical applications in the future.


Reconstructive hip surgery in children with cerebral palsy: factors influencing risk of femoral head avascular necrosis.
Femoral head avascular necrosis (AVN) is a complication of hip reconstruction in children with cerebral palsy (CP) with uncertain incidence. The purpose of this study was to establish the rate of AVN in children undergoing hip reconstruction and to identify the factors associated with AVN. Medical records and radiographs of patients aged 1-18 with a diagnosis of CP who have undergone hip reconstruction over a 9-year period (2010-2018) with at least 1-year follow-up were reviewed. Age at time of surgery, sex, Gross Motor Function Classification System (GMFCS), procedure(s), preoperative migration percentage (MP), and signs of AVN on anterioposterior pelvis radiographs at routine follow-up visits (3 months, 6 months, and years 1-9, annually) according to the Bucholz-Ogden (BO) and Kalamchi-MacEwen (KM) classification systems were recorded. Univariate analysis was used to test for significance. Three hundred forty-nine hips in 209 patients met our inclusion criteria. Eleven hips (rate; 3%), in 11 patients, developed AVN. Classification of AVN was found to consist of: class I-4 (36%), class II-1 (9%), class III-[BO: 4 (36%)] [KM: 3 (27%)], and Class IV-[BO: 2 (18%)] [KM: 3 (27%)]. Average follow-up was of 3.5 years. The AVN cohort displayed older age (11.0 ± 2.8 vs. 8.1 ± 3.4; P = 0.005). Open reduction was associated with increased AVN, occurring in 9% of the hips (P = 0.004). No significant association was found between preoperative MP, GMFCS, or acetabular osteotomy. The method of open reduction (anterior vs. medial) was not significantly associated with AVN (P = 0.4471). In this large series, the observed rate of AVN was 3%, associated with open reductions at time of hip reconstruction. If possible, closed reduction would be preferred at time of hip reconstruction in children with CP to lower the risk of AVN. Level of evidence: III.


Assessment of adiponectin level in obese and lean Nepalese population and its possible correlation with lipid profile: A cross-sectional study.
Adiponectin- one of the most important adipokines plays a pivotal role in carbohydrate and lipid metabolism and vascular biology. Changing food trend and lifestyle has tremendously affected the health status of Nepalese population. Studies have shown that between 1996 and 2006 obesity in Nepal has increased from 1.6% to 10%. Studies have been conducted in Nepal on the prevalence of obesity and its correlation with lipid profile. But based on our knowledge, this is the first study correlating adiponectin with obesity and lipid profile in Nepal. This piece of work will certainly help to assess the impact of obesity in Nepalese population. Fifty four obese and Thirty six normal/lean participants were included from different locations of Kathmandu Valley. Anthropometric measurements like age, BMI, Waist circumference, hip circumference, waist to hip ratio, mid thigh circumference and chest circumferences were taken from each participant. Blood glucose, lipid profile and serum adiponectin levels were measured from overnight fasting samples. Significant differences were observed in BMI, Waist Circumference, Hip Circumference, Waist to Hip Ratio (WHR) and Chest circumference between obese and normal groups. Fasting Blood Glucose, Serum Triglyceride, HDL Cholesterol, LDL Cholesterol, Total Cholesterol/HDL ratio, Non-HDL Cholesterol and Adiponectin Levels were significant between the groups. Inverse correlations were observed between adiponectin level and BMI, Waist Circumference, Hip Circumference, Waist to Hip ratio, Chest Circumference, Fasting Blood Glucose, Triglyceride, Total Cholesterol/HDL ratio, LDL/HDL Cholesterol ratio and Non-HDL Cholesterol levels. Positive correlation was found between adiponectin and HDL Cholesterol levels. Our study showed significant inverse association of serum adiponectin with obesity and lipid profile parameters except for Serum HDL Cholesterol level in Nepalese population.


Two-dimensional optical control of electron spin orientation by linearly polarized light in InGaAs.
Optical absorption of circularly polarized light is well known to yield an electron spin polarization in direct band gap semiconductors. We demonstrate that electron spins can even be generated with high efficiency by absorption of linearly polarized light in InxGa(1-x)As. By changing the incident linear polarization direction we can selectively excite spins in both polar and transverse directions. These directions can be identified by the phase during spin precession using time-resolved Faraday rotation. We show that the spin orientations do not depend on the crystal axes suggesting an extrinsic excitation mechanism.


Behavioural variation and learning across the lifespan in wild white-faced capuchin monkeys.
Natural selection has evidently mediated many species characteristics relevant to the evolution of learning, including longevity, length of the juvenile period, social organization, timing of cognitive and motor development, and age-related shifts in behavioural propensities such as activity level, flexibility in problem-solving and motivation to seek new information. Longitudinal studies of wild populations can document such changes in behavioural propensities, providing critical information about the contexts in which learning strategies develop, in environments similar to those in which learning strategies evolved. The Lomas Barbudal Monkey Project provides developmental data for the white-faced capuchin, Cebus capucinus, a species that has converged with humans regarding many life-history and behavioural characteristics. In this dataset, focused primarily on learned aspects of foraging behaviour, younger capuchins are more active overall, more curious and opportunistic, and more prone to inventing new investigative and foraging-related behaviours. Younger individuals more often seek social information by watching other foragers (especially older foragers). Younger individuals are more creative, playful and inventive, and less neophobic, exhibiting a wider range of behaviours when engaged in extractive foraging. Whereas adults more often stick with old solutions, younger individuals often incorporate recently acquired experience (both social and asocial) when foraging. This article is part of the theme issue 'Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.


Serious bacterial infections and antibiotic prescribing in primary care: cohort study using electronic health records in the UK.
This study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates. Cohort study. 706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017. 10.1 million registered patients with 69.3 million patient-years' follow-up. All antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications. First episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates. The age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430-1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074). We did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.


Factors Associated with Cervical Cancer Screening Uptake: Implications for the Health of Women in Jordan.
The existing factors that influence cervical cancer screening uptake worldwide do not necessarily reflect the situation in Jordan. Therefore, the aim of this study was to determine the factors associated with cervical cancer screening uptake among Jordanian women. In this cross-sectional study, 500 married Jordanian women aged 21 to 65 years were recruited from eight nongovernmental organisations and community settings in Amman. Data were collected with a self-administered questionnaire regarding sociodemographic and reproductive data, a health utilisation data form, and scales on the perceived benefits of screening, perceived barriers to screening, perceived susceptibility to cervical cancer, and perceptions regarding the severity of cervical cancer. Descriptive statistics, multivariate logistic regressions, and independent t-tests were used in the data analysis. Among the 500 age-eligible women, only 156 (31.2%) had been screened for cervical cancer. Healthcare provider encouragement, years of marriage (odds ratio (OR) = 5.24, confidence interval (CI) = 95%, p = 0.00), and use of the private healthcare sector (OR = 2.20, CI = 95%, p = 0.012) were significant predictors of cervical cancer screening. Cervical cancer screening uptake among Jordanian women is significantly low; determining factors for the decision to undergo screening include encouragement from the healthcare provider, the number of years of marriage, and use of the private healthcare sector. To improve uptake, structured screening programmes need to be implemented in collaboration with national partners and institutions to decrease the incidence of cervical cancer in Jordan.


The Application of Skin Care Product in Melasma Treatment.
Melasma is an acquired and chronic hyperpigmentation disorder which is recognized as one of the most psychologically distressing and difficult to cure forms of skin hyperpigmentation. It is associated with substantial quality of life impairments. Treatments of melasma include local application, oral medication, physical laser therapy and program combination therapy. However, routine treatment usually leads to the damage of skin barrier function, resulting in adverse reactions such as erythema, pruritus, post-inflammatory pigmentation and even scar. Skin care products contain a variety of active ingredients, which are widely concerned by cosmetic dermatologists because of high safety, good tolerance and the effect of improving the damaged skin barrier. Using skin care products alone or in combination with routine treatment not only can improve the curative effect for melasma, reduce side effects and recurrence rate, but also improve patient satisfaction. This article mainly describes the application of skin care products in the treatment of melasma.


Leucocyte migration inhibitory activity (LMIA) on concanavalin A (Con-A) stimulated human lymphocytes. Comparison of leucocyte migration capillary technique (LMCT), leucocyte migration agarose technique (LMAT), and leucocyte migration fibrinolysis technique (LMFT).
Leucocyte migration and migration inhibition in fibrin medium may reveal new aspects of lymphokine activity associated with immunological inflammation. Leucocyte migration fibrinolysis technique is compared with the leucocyte migration capillary technique and the leucocyte migration agarose technique. In the present model experiment the three methods gave comparable results. The leucocyte migration fibrinolysis technique involves a new principle for detection of lymphokines and can probably be developed to give more exact information about the interrelationship between thrombosis, fibrinolysis and lymphokines.


Electrophysiological correlates of object location and object identity processing in spatial scenes.
The ability to quickly detect changes in our surroundings has been crucial to human adaption and survival. In everyday life we often need to identify whether an object is new and if an object has changed its location. In the current event-related potential (ERP) study we investigated the electrophysiological correlates and the time course in detecting different types of changes of an objecṫs location and identity. In a delayed match-to-sample task participants had to indicate whether two consecutive scenes containing a road, a house, and two objects, were either the same or different. In six randomly intermixed conditions the second scene was identical, one of the objects had changed its identity, one of the objects had changed its location, or the objects had switched locations. The results reveal different time courses for the processing of identity and location changes in spatial scenes. Whereas location changes elicited a posterior N2 effect, indicating early mismatch detection, followed by a P3 effect reflecting post-perceptual processing, identity changes elicited an anterior N3 effect, which was delayed and functionally distinct from the N2 effect found for the location changes. The condition in which two objects switched position elicited a late ERP effect, reflected by a P3 effect similar to that obtained for the location changes. In sum, this study is the first to cohesively show different time courses for the processing of location changes, identity changes, and object switches in spatial scenes, which manifest themselves in different electrophysiological correlates.


[Efficacy and Organoprotection of Triple Combinations in the Treatment of Arterial Hypertension].
The 2022 draft Russian guidelines on arterial hypertension recommend initiation of antihypertensive therapy with a combination of drugs in most patients with blood pressure above 150 / 90 mm Hg and / or in the presence of high-risk criteria. In 2021, the results of a 12-year analysis of the Brisighella Heart Study (BHS) were published. The aim of this study was to compare the use of different triple antihypertensive drug combinations in an Italian cohort of patients in real-life clinical practice. Combination antihypertensive therapy with a renin-angiotensin-aldosterone system inhibitor, amlodipine, and thiazide/thiazide-like diuretics provides a better blood pressure control compared to other antihypertensive drug combinations. The use of the triple combination of amlodipine/indapamide/perindopril is associated with a better metabolic profile than any other considered combination of antihypertensive drugs and a more pronounced organ-protective effect.


Comparison of Two ESI MS Based H/D Exchange Methods for Extracting Protein Folding Energies.
In this report, the model proteins staphylococcal nuclease and ubiquitin were used to test the applicability of two new hydrogen/deuterium exchange (HX) electrospray ionization mass spectrometry (ESI-MS) methods for estimating protein folding energies. Both methods use the H/D exchange of globally protected amide protons (amide protons which are buried in the hydrophobic core) to elucidate protein folding energies. One method is a kinetic-based method and the other is equilibrium-based. The first method, the HX ESI-MS kinetic-based approach is conceptually identical to SUPREX (stability of unpurified proteins from rates of H/D exchange) method but is based on ESI-MS rather than MALDI-MS (matrix assisted laser desorption mass spectrometry). This method employs the time-dependence of H/D exchange using various denaturant concentrations to extract folding energies. Like SUPREX, this approach requires the assumption of EX2 exchange kinetics. The second method, which we call a protein equilibrium population snapshot (PEPS) by HX ESI-MS uses data collected only for a single time point (usually the shortest possible) to obtain a snapshot of the open and closed populations of the protein. The PEPS approach requires few assumptions in the derivation of the equations used for calculation of the folding energies. The extraction of folding energies from mass spectral data is simple and straightforward. The PEPS method is applicable for proteins that follow either EX1 or EX2 HX mechanisms. In our experiments the kinetic-based method produced less accurate ΔG(H(2)O) and m(GdHCl) values for wild-type staphylococcal nuclease and mutants undergoing H/D exchange by EX1, as would be expected. Better results were obtained for ubiquitin which undergoes HX by an EX2 mechanism. Using the PEPS method we obtained ΔG(H(2)O) and m(GdHCl) values that were in good agreement with literature values for both staphylococcal nuclease (EX1) and ubiquitin (EX2). We also show that the observation of straight lines in linear extrapolation method (LEM) plots is not a reliable indicator of the validity of the data obtained using the LEM approach.


Comparative Transcriptome Profiling Reveals Defense-Related Genes against Meloidogyne incognita Invasion in Tobacco.
Root-knot nematodes Meloidogyne incognita are one of the most destructive pathogens, causing severe losses to tobacco productivity and quality. However, the underlying resistance mechanism of tobacco to M. incognita is not clear. In this study, two tobacco genotypes, K326 and Changbohuang, which are resistant and susceptible to M. incognita, respectively, were used for RNA-sequencing analysis. An average of 35 million clean reads were obtained. Compared with their expression levels in non-infected plants of the same genotype, 4354 and 545 differentially expressed genes (DEGs) were detected in the resistant and susceptible genotype, respectively, after M. incognita invasion. Overall, 291 DEGs, involved in diverse biological processes, were common between the two genotypes. Genes encoding toxic compound synthesis, cell wall modification, reactive oxygen species and the oxidative burst, salicylic acid signal transduction, and production of some other metabolites were putatively associated with tobacco resistance to M. incognita. In particular, the complex resistance response needed to overcome M. incognita invasion may be regulated by several transcription factors, such as the ethylene response factor, MYB, basic helix⁻loop⁻helix transcription factor, and indole acetic acid⁻leucine-resistant transcription factor. These results may aid in the identification of potential genes of resistance to M. incognita for tobacco cultivar improvement.


N-terminal tyrosine residues within the potassium channel Kir3 modulate GTPase activity of Galphai.
trkB activation results in tyrosine phosphorylation of N-terminal Kir3 residues, decreasing channel activation. To determine the mechanism of this effect, we reconstituted Kir3, trkB, and the mu opioid receptor in Xenopus oocytes. Activation of trkB by BDNF (brain-derived neurotrophic factor) accelerated Kir3 deactivation following termination of mu opioid receptor signaling. Similarly, overexpression of RGS4, a GTPase-activating protein (GAP), accelerated Kir3 deactivation. Blocking GTPase activity with GTPgammaS also prevented Kir3 deactivation, and the GTPgammaS effect was not reversed by BDNF treatment. These results suggest that BDNF treatment did not reduce Kir3 affinity for Gbetagamma but rather acted to accelerate GTPase activity, like RGS4. Tyrosine phosphatase inhibition by peroxyvanadate pretreatment reversibly mimicked the BDNF/trkB effect, indicating that tyrosine phosphorylation of Kir3 may have caused the GTPase acceleration. Tyrosine to phenylalanine substitution in the N-terminal domain of Kir3.4 blocked the BDNF effect, supporting the hypothesis that phosphorylation of these tyrosines was responsible. Like other GAPs, Kir3.4 contains a tyrosine-arginine-glutamine motif that is thought to function by interacting with G protein catalytic domains to facilitate GTP hydrolysis. These data suggest that the N-terminal tyrosine hydroxyls in Kir3 normally mask the GAP activity and that modification by phosphorylation or phenylalanine substitution reveals the GAP domain. Thus, BDNF activation of trkB could inhibit Kir3 by facilitating channel deactivation.


Progressive sensorineural hearing loss in childhood.
A progressive sensorineural hearing loss in childhood, with an extremely variable prevalence (from 4% to 30%), has been reported in the literature. This wide range of reported figures could depend on the different criteria used for identifying the deterioration, the groups, and the examined age ranges. The most frequent etiology of progressive sensorineural hearing loss in childhood includes hereditary causes, both syndromic and nonsyndromic, and developmental and infectious causes, whereas metabolic, toxic, autoimmune, traumatic, and vascular etiologies are less common; however, the origin of the hearing impairment often remains unknown. The population for this study consisted of 178 children with bilateral sensorineural hearing loss who were examined between 1971 and 1993 using audiologic tests. Syndromal genetic hearing loss was excluded from the study. A progressive loss of acuity was found in 11 subjects, with a prevalence of 6.2%. The etiology was hereditary deafness in five patients, congenital infection in one, and congenital inner ear anomaly in another patient; in the last four children the etiology was unknown. Onset of deterioration was after 4 years of age in 73% of the patients. The progressive evolution was binaural in almost all patients (10 of 11) and asymmetric in most, with a tendency to a greater deterioration at the frequencies initially least affected.


[Mathematics, milieu, text].
Greek theoretical mathematics emerges among sixth-century Ionians from a background of professional practitioners, concerned chiefly with arithmetical operations. Its characteristical features (impersonalization, standardization, diagrams) develop as part of an elitist play of distinction at fifth- and fourth-century Athens, mainly to ascertain the tradition of that knowledge without adequate institutions. Sophists challenge the mathematicians' practices, philosophers adopt the mathematicians' knowledge as a model of truth, but the mathematicians themselves remain autonomous. Even hellenistic mathematics, semi-institutionalized at royal courts, is little more than a private affair of a narrow circle of intellectuals. All this time the practitioners' traditions persist basically unaltered and constantly present the theoreticians with a social and epistemic background to differentiate "their" mathematics from. Finally, these two branches of Greek mathematics, a practical and a theoretical one, are describable as reciprocally systematized forms of knowledge.


Palladium mediated intramolecular multiple C-X/C-H cross coupling and C-H activation: synthesis of carbazole alkaloids calothrixin B and murrayaquinone A.
Straightforward palladium mediated syntheses of calothrixin B and murrayaquinone A are described. Regioselective palladium mediated intramolecular multiple C-X/C-H cross coupling reaction on N-(4-((2-bromophenyl)amino)-2,5-dimethoxybenzyl)-N-(2-iodophenyl)acetamide followed by CAN oxidation afforded calothrixin B in excellent yield in two steps. A linear synthesis has also been developed for calothrixin B. Utilizing C-H functionalization as well as palladium mediated intramolecular C-X/C-H cross coupling reaction, murrayaquinone A synthesis was achieved. Overall, these synthetic methodologies provide an expedient entry to these biologically active alkaloids in a short reaction sequence.


Differences in reactions to paintings by male and female college students.
38 male and 55 female college students rated digitized color facsimiles of 40 paintings that varied in artistic period (Renaissance, Rococo, Impressionist, Post-Impressionist, 20th Century) and subject matter (portrait, landscape, still life, behavior depiction) on 12 7-point semantic differential scales, e.g., simple-complex. Women judged the content of Rococo and Impressionist paintings as more pleasing than did men and Impressionist paintings evoked greater feelings of pleasure and relaxation among women than among men. In addition, paintings that depicted behaviors evoked more pleasure and alertness among women than among men. The results were interpreted in terms of underlying differences between men and women in perceptual style and emotional sensitivity.


Improving Access to Care Through the Establishment of a Local, Teledermatology Network.
Introduction: Access to dermatologic care is a major issue in the United States, especially within the un- and underinsured populations; technology, including teledermatology, will pay a role in improving access to care. Methods: We performed a prospective study between November 2016 and September 2017. We leveraged a partnership between Mayo Clinic and Mountain Park Health Clinic, a community clinic that primarily serves un- and underinsured populations. We implemented a mobile phone-based store and forward (SAF) teledermatology service, which integrated an external community health clinic to an existing electronic health record (EHR) using standardized data capture forms, real-time support, and simple workflows. Results: Thirty-seven patients were enrolled in the study, 65% female and 35% male with an average age of 47.9 (SD = 15.9). The ethnic breakdown was: 81.1% Hispanic, 13.5% Caucasian, and 5.4% African American. The majority, 62.2%, did not have a high school education, 45.9% were unemployed, and 51.4% were uninsured. 64.9% earned less than $25,000 for annual household income. Teledermatology consultation increased the absolute diagnostic and management concordance by 36.6% (p = 0.01, 95% CI 12.2%-61.0%) and 34.2% (p < 0.01, 95% CI 11%-57%), respectively. Primary care providers had a significant increase in mean confidence in the diagnosis and management of dermatology conditions pre and poststudy (3.60 vs. 3.70 and 3.21 vs. 3.60, respectively; p < 0.01). Ninety-six percent of the primary care providers agreed (52.0%) and strongly agreed (44.0%) that they would send another patient for teleconsultation.Conclusion: We successfully implemented a SAF teledermatology consultative service in a community health clinic outside our EHR. A similar approach can be used by other large health care organizations to provide integrated, high-quality consultation to clinics with rural, un- and underinsured populations.


Multiple malignant meningiomas in a young cat.
A 2-year-old cat was presented with generalised muscle tremors and progressive fore- and hindlimb ataxia, 5 months after the initiation of chemotherapy for thymic lymphoma. The lymphoma was treated with combination chemotherapy (cyclophosphamide, vincristine and prednisolone), which resulted in remission. The neurological signs progressed to paralysis and the cat subsequently died. On autopsy, multiple meningiomas were diagnosed, which is an unusual finding. It is possible that the lymphoma chemotherapy resulted in the development of the multiple meningiomas as secondary malignancies.


SARS-CoV-2 infection in cystic fibrosis: A multicentre prospective study with a control group, Italy, February-July 2020.
To describe the symptoms and clinical course of SARS-CoV-2 infection in patients with cystic fibrosis (CF). We carried out a prospective multicentre cohort study based on 32 CF centres and 6597 patients. Centres were contacted to collect baseline and follow-up data of patients who reported symptoms suggestive of COVID-19 or who had contact with a positive/suspected case between the end of February and July 2020. Symptoms and clinical course of the infection were compared between patients who tested positive by molecular testing (cases) and those who tested negative (controls). Thirty patients were reported from the centres, 16 of them tested positive and 14 tested negative. No differences in symptoms and outcome of the disease were observed between groups. Fever, cough, asthenia and dyspnea were the most frequently reported symptoms. Eight cases (50%) were hospitalized but none required ICU admission. Two adults with a history of lung transplant required non-invasive ventilation, none required ICU admission and all patients fully recovered without short-term sequelae. The course of SARS-CoV-2 in our patients was relatively favorable. However, COVID-19 should not be considered a mild disease in CF patients, particularly for those with severely impaired respiratory function and organ transplant.


Binding Capabilities of Different Genetically Engineered pVIII Proteins of the Filamentous M13/Fd Virus and Single-Walled Carbon Nanotubes.
Binding functional biomolecules to non-biological materials, such as single-walled carbon nanotubes (SWNTs), is a challenging task with relevance for different applications. However, no one has yet undertaken a comparison of the binding of SWNTs to different recombinant filamentous viruses (phages) bioengineered to contain different binding peptides fused to the virus coat proteins. This is important due to the range of possible binding efficiencies and scenarios that may arise when the protein's amino acid sequence is modified, since the peptides may alter the virus's biological properties or they may behave differently when they are in the context of being displayed on the virus coat protein; in addition, non-engineered viruses may non-specifically adsorb to SWNTs. To test these possibilities, we used four recombinant phage templates and the wild type. In the first circumstance, we observed different binding capabilities and biological functional alterations; e.g., some peptides, in the context of viral templates, did not bind to SWNTs, although it was proven that the bare peptide did. The second circumstance was excluded, as the wild-type virus was found to hardly bind to the SWNTs. These results may be relevant to the possible use of the virus as a "SWNT shuttle" in nano-scale self-assembly, particularly since the pIII proteins are free to act as binding-directing agents. Therefore, knowledge of the differences between and efficiencies of SWNT binding templates may help in choosing better binding phages or peptides for possible future applications and industrial mass production.


ERG rearrangement is present in a subset of transition zone prostatic tumors.
A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and ≥8 in 7 cases. Median tumor volume was 200 mm(2). TMPRSS2-ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2-ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.


Sexual function after sacrocolpopexy.
Pelvic organ prolapse affects approximately 50% of parous women over 50 years of age and has a lifetime risk of 30-50%. Vault descent or prolapse occurs in about 20% after hysterectomy and can have a negative effect on sexual function. Sacrocolpopexy is the gold standard of surgical treatment for apical prolapse in fit, sexually active patients. Few data exist which determine sexual function after sacrocolpopexy. The aim of this study was to determine sexual function in sexually active patients before and after sacrocolpopexy for the treatment of vault prolapse or descent. Main outcome measures were the International Continence Society (ICS) Pelvic Organ Prolapse (ICS POP) Staging and the Female Sexual Function Index, which were filled in before the intervention and at follow-up. Between December 2000 and December 2009, we asked sexually active female patients who were to undergo sacrocolpopexy for vault descent or prolapse to participate in this study. The patients were gynecologically examined before and after surgery and prolapse staging was performed using the ICS POP Staging. Sixty-two patients were included in the study and follow-up was 24 months. The domains sexual desire, arousal, lubrication, satisfaction, and pain improved significantly postoperatively but orgasm remained unchanged. There was no vaginal shortening postoperatively, and no serious intra- or postoperative complications occurred. Sacrocolpopexy is a valuable option for sexually active patients with vault descent or prolapse with an amelioration of most aspects of sexual function but not all. Other factors as hormonal treatment, concomitant surgery, physiological, and psychological factors have to be taken into consideration.


High Input of Nitrogen Fertilization and Short Irrigation Frequencies Forcefully Promote the Development of Verticillium Wilt of Olive.
It is known that high N doses, N/K imbalances, and frequent irrigation favor Verticillium wilt. The influence of fertilization and its interaction with the frequency of irrigation on the development of Verticillium wilt of olive (VWO) has been evaluated. A split-split-plot design in microplots with two naturally infested soils of different texture was established for studying three fertilization treatments (NO3Ca, NPK and without fertilization), plus two irrigation frequencies (daily and deficit). The treatments were applied by means of fertigation, evaluating the susceptible cultivar Picual. Final disease incidence in plants subjected to NO3Ca daily treatment was 100% regardless of soil texture. However, final mortality in these plants was 37% and 85.2% in clay and sandy loam soils, respectively. In addition, the area under the disease progress curve values were significantly higher (49.1%) in plants subjected to NO3Ca fertilization compared to those not fertilized or fertilized with N-P-K when plants were grown in clay soil. This value in the sandy loam soil was significantly higher in the NO3Ca daily irrigation treatment (94.3%), followed by the N-P-K-daily treatment (61.1%) which also was significantly higher than the unfertilized daily, N-deficit and NPK-deficit treatments (37.8, 42.6 and 44.9%, respectively). The plants submitted to unfertilized-deficit treatment reached the lowest value (9.6%). In this work it can be concluded that the application of fertilizer or the application of fertilizer with daily irrigation in naturally infested soils increases the development of VWO in Picual.


From battlefront to homefront: creation of a civilian walking blood bank.
Hemorrhagic shock remains the leading cause of preventable death on the battlefield, despite major advances in trauma care. Early initiation of balanced resuscitation has been shown to decrease mortality in the hemorrhaging patient. To address transfusion limitations in austere environments or in the event of multiple casualties, walking blood banks have been used in the combat setting with great success. Leveraging the success of the region-wide whole blood program in San Antonio, Texas, we report a novel plan that represents a model response to mass casualty incidents.


The relationship of paranoid states to schizophrenia.
The author interviewed relatives of 32 paranoid patients, 32 matched depressed patients, and 15 schizophrenic patients regarding family history. Two (1.3%) of the relatives of paranoid patients and one (0.6%) of the relatives of depressed patients had possible paranoid states. Significantly more relatives of schizophrenic patients than relatives of paranoid or depressed patients had schizophrenia, but the rates were similar among relatives of paranoid and depressed patients. The author concludes that there is little evidence of familial occurrence of paranoid states and no evidence that paranoid states are familially related to schizophrenia.