Cytotoxic effects of one-step self-etching adhesives on an odontoblast cell line.
The aim of this study was to evaluate the cytotoxic effects of one-step self-etching adhesives. Cells from an immortalized mouse odontoblast cell line (MDPC-23) were cultured with six different dental adhesive systems (diluted to concentrations of 0.5% for 4 h): Adper Easy Bond (EB), Xeno V (XV), iBond (IB), AdheSE One (AO), Clearfil SE primer (CS), and Adper Single Bond 2 (SB). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometric apoptosis assays were used to evaluate cell viability and the rate of apoptosis. The odontoblasts were also examined under a scanning electron microscope. While all of the cultures with adhesives showed reduced viability, the viabilities in the IB and SB groups were not significantly different from the control group. Although increased apoptosis rates were observed in all of the cultures with adhesives, the rate in the SB group was not significantly different from the rate in the control. The control group showed the lowest apoptosis rate followed by the SB, AO, IB, EB, XV, and CS groups. When examined under a scanning electron microscope, control odontoblasts and the SB group exhibited relatively large cytoplasmic extensions. In contrast, in the EB and CS groups, fewer fibroblasts remained adhered to the plate surface. Cytoplasmic membrane shrinkage and cell-free areas with residual membrane fragments from dead cells were observed. In conclusion, all cultures with one-step self-etching adhesives showed increased apoptotic activity. SB, an etch-and-rinse adhesive, was comparable to the control group, and CS and EB showed the lowest odontoblast viabilities according to the MTT assay.


Abscisic acid in salt stress predisposition to phytophthora root and crown rot in tomato and chrysanthemum.
Plants respond to changes in the environment with complex signaling networks, often under control of phytohormones that generate positive and negative crosstalk among downstream effectors of the response. Accordingly, brief dehydration stresses such as salinity and water deficit, which induce a rapid and transient systemic increase in levels of abscisic acid (ABA), can influence disease response pathways. ABA has been associated with susceptibility of plants to bacteria, fungi, and oomycetes but relatively little attention has been directed at its role in abiotic stress predisposition to root pathogens. This study examines the impact of brief salinity stress on infection of tomato and chrysanthemum roots by Phytophthora spp. Roots of plants in hydroponic culture exposed to a brief episode of salt (sodium chloride) stress prior to or after inoculation were severely diseased relative to nonstressed plants. Tomato roots remained in a predisposed state up to 24 h following removal from the stress. An increase in root ABA levels in tomato preceded or temporally paralleled the onset of stress-induced susceptibility, with levels declining in roots prior to recovery from the predisposed state. Exogenous ABA could substitute for salt stress and significantly enhanced pathogen colonization and disease development. ABA-deficient tomato mutants lacked the predisposition response, which could be restored by complementation of the mutant with exogenous ABA. In contrast, ethylene, which exacerbates disease symptoms in some host-parasite interactions, did not appear to contribute to the predisposition response. Thus, several lines of evidence support ABA as a critical and dominant factor in the salinity-induced predisposition to Phytophthora spp. infection.


Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review of its use in the management of asthma.
Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone propionate alone. The combination product also appears to improve HR-QOL relative to placebo or salmeterol alone.


Following vegetative to embryonic cellular changes in leaves of Arabidopsis overexpressing LEAFY COTYLEDON2.
Embryogenesis in flowering plants is controlled by a complex interplay of genetic, biochemical, and physiological regulators. LEAFY COTYLEDON2 (LEC2) is among a small number of key transcriptional regulators that are known to play important roles in controlling major events during the maturation stage of embryogenesis, notably, the synthesis and accumulation of storage reserves. LEC2 overexpression causes vegetative tissues to change their developmental fate to an embryonic state; however, little information exists about the cellular changes that take place. We show that LEC2 alters leaf morphology and anatomy and causes embryogenic structures to form subcellularly in leaves of Arabidopsis (Arabidopsis thaliana). Chloroplasts accumulate more starch, the cytoplasm fills with oil bodies, and lytic vacuoles (LVs) appear smaller in size and accumulate protein deposits. Because LEC2 is responsible for activating the synthesis of seed storage proteins (SSPs) during seed development, SSP accumulation was investigated in leaves. The major Arabidopsis SSP families were shown to accumulate within small leaf vacuoles. By exploiting the developmental and tissue-specific localization of two tonoplast intrinsic protein isoforms, the small leaf vacuoles were identified as protein storage vacuoles (PSVs). Confocal analyses of leaf vacuoles expressing fluorescently labeled tonoplast intrinsic protein isoforms reveal an altered tonoplast morphology resembling an amalgamation of a LV and PSV. Results suggest that as the LV transitions to a PSV, the tonoplast remodels before the large vacuole lumen is replaced by smaller PSVs. Finally, using vegetative and seed markers to monitor the transition, we show that LEC2 induces a reprogramming of leaf development.


Interferon-beta1A-induced polyarthritis in a patient with the HLA-DRB1*0404 allele.
Human interferon-alpha (IFNalpha) and IFNbeta are administered for treatment of several diseases, including viral infections, malignancies, and multiple sclerosis (MS). IFNalpha therapy has been associated with the production of autoantibodies and the development of a variety of autoimmune disorders, including polyarthritis. This report describes the development of seronegative, symmetric polyarthritis in a patient with relapsing-remitting MS, after 8 weeks of therapy with IFNbeta1a. HLA phenotyping analysis of the patient revealed the presence of HLA-DRB1*0404, an allele known to be associated with the development of rheumatoid arthritis. Therefore, IFNbeta1a may have induced arthritis in a patient who was genetically predisposed to develop arthritis on the basis of HLA determinants. The English-language literature regarding IFNalpha- and IFNbeta-induced polyarthritis is reviewed, and possible mechanisms for IFNalpha- and IFNbeta-induced autoimmunity, including the contribution of HLA determinants and nitric oxide overproduction, are discussed.


[Automated micro-determination by transfer analyzer of circulating alpha-amino nitrogen].
An automated method for the determination of plasma free amino groups is described. The analysis is performed on a discrete computerized analyzer after plasma deproteinization using trichloracetic acid. The method is based on the formation of a complex between terminal NH2 radicals and 2,4,6-trinitrobenzene sulfonate (TNBS). The method is accurate (coefficient of variation = 2%), linear over a range of 0.2-7 mM/l and requires small analytic volumes; it also correlates well in the bovine with results from standard liquid chromatography (r = 0.953). With this method a single operator can determine free amino group contents of 50 samples per h.


Nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones: probing the hard/soft nature of fluorinated carbanions.
We have successfully accomplished the nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones. It was found that for acylic alpha,beta-enones, although the reaction medium and the structure of the enones can all influence the regioselectivity of the nucleophilic alkylation reactions, the hard/soft nature of the carbanions played a major role. By using the 1,4- and 1,2-addition product ratio as a probe to determine the hard/soft nature of the above-mentioned four halogenated carbanions, the order of the softness of these carbanions can be given as follows: [(PhSO2)2CF(-)] (20) approximately = PhSO2CCl2(-) (32) > PhSO2CHF(-) (31) > PhSO2CF2(-) (30). In the case of fluoroalkylation of aryne (35 as the precursor) and alpha,beta-acetylenic ketones 46 with fluorobis(phenylsulfonyl)methane (21), fluorobis(phenylsulfonyl)methylated arenes 36 and beta-fluorobis(phenylsulfonyl)methylated alpha,beta-enones 47 were obtained as the corresponding products in good yields. During the reaction between 2-fluoro-2-(phenylsulfonyl)acetophenone (34) and arynes or activated alkynes 46, an intramolecular tandem reaction process leads to the formation of acyl-fluoroalkylated arenes 43 or alpha-acyl-beta-fluoroalkylated alpha,beta-enones 48. It turned out that the softness of a fluorine-bearing carbanion (such as 20 or 33 derived from 21 or 34) plays a crucial role for the success of the nucleophilic fluoroalkylation reactions with arynes and some activated alkynes (alpha,beta-acetylenic ketones).


Autoimmunity as a result of escape from RNA surveillance.
In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in approximately 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity.


Immersive virtual reality as a teaching tool for neuroanatomy.
Three-dimensional (3D) computer modeling and interactive virtual reality (VR) simulation are validated teaching techniques used throughout medical disciplines. Little objective data exists supporting its use in teaching clinical anatomy. Learner motivation is thought to limit the rate of utilization of such novel technologies. The purpose of this study is to evaluate the effectiveness, satisfaction, and motivation associated with immersive VR simulation in teaching medical students neuroanatomy. Images of normal cerebral anatomy were reconstructed from human Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) imaging and magnetic resonance imaging (MRI) into 3D VR formats compatible with the Oculus Rift VR System, a head-mounted display with tracking capabilities allowing for an immersive VR experience. The ventricular system and cerebral vasculature were highlighted and labeled to create a focused interactive model. We conducted a randomized controlled study with 66 medical students (33 in both the control and experimental groups). Pertinent neuroanatomical structures were studied using either online textbooks or the VR interactive model, respectively. We then evaluated the students' anatomy knowledge, educational experience, and motivation (using the Instructional Materials Motivation Survey [IMMS], a previously validated assessment). There was no significant difference in anatomy knowledge between the 2 groups on preintervention, postintervention, or retention quizzes. The VR group found the learning experience to be significantly more engaging, enjoyable, and useful (all p < 0.01) and scored significantly higher on the motivation assessment (p < 0.01). Immersive VR educational tools awarded a more positive learner experience and enhanced student motivation. However, the technology was equally as effective as the traditional text books in teaching neuroanatomy.


Spinal reflexes and seizure patterns in the two-toed sloth.
In striking contrast to the seizure patterns of other animals, the electroshock seizure of the sloth consists of weak extension followed by tonic flexion and terminal clonus. A similar pattern is seen with direct spinal cord stimulation. Strychnine produces a pure flexor convulsion. In the spinal sloth, painful stimulation of one foot causes extension at some joints of that limb and strong flexion at all joints of the contralateral limb.


Understanding the effects of establishing various cutoff criteria in the definition of men with premature ejaculation.
Over the past decade, professional organizations and consensus groups have offered a variety of definitions for premature ejaculation (PE), all generally including a set of common concepts but all varying in specific language and operationalization. Clearly articulated definitions of such conditions are important because they not only affect prevalence rates but also diagnostic inclusion-who is deemed to have the condition and therefore who might be eligible for treatment. The current study had two goals: (i) to examine the effects on prevalence rates of moving the cutoff points from more stringent to less stringent for each of three PE criteria-ejaculatory latency, distress, and ejaculating before desired; and (ii) to explore in detail the relationships among the three criteria. Using an Internet-based sample of 1,183 men, we examined the responses of 374 with PE-type symptoms based on consensus definitions, and determined the effect of decreasing restrictions on the cutoff criteria. In addition, we calculated both correlations and concordance rates among criteria. Numeric and graphic depiction of the effects of moving the cutoff point for each of the three criteria is provided in the URL "PE Prevalence," a dynamic tool developed specifically for this study (https://sites.google.com/a/valpo.edu/PEprevalence/). In addition, statistical relationships among the PE criteria suggest sufficient independence to warrant inclusion of all three in a diagnostic procedure as well as to consider a 2-minute ejaculatory latency as the threshold for a PE diagnosis. Based on our data, clinicians should approach the 1-minute ejaculatory latency time (ELT) criterion with flexibility, considering ELTs up to 2 minutes for a PE diagnosis. At the same time, frequency of occurrence of either ejaculating before desired or of distress about the condition, as long as they reach at least 50% of the time, had only minor impact on PE diagnostic inclusion.


eIF4A3-mediated circEHMT1 regulation in retinal microvascular endothelial dysfunction in diabetic retinopathy.
Literature has reported that circular RNAs (circRNAs) are crucially associated with diabetic retinopathy (DR). Furthermore, circEHMT1 has been identified to maintain endothelial cell barrier function. This study aimed to investigate the mechanisms that regulate aberrant circEHMT1 expression and its role in the pathogenesis of DR. In this study, retinal microvascular endothelial cells were exposed to a high glucose (HG) environment, and subsequently, tube formation and intercellular junction proteins were evaluated. Furthermore, the biological functions of circEHMT1 and its potential regulatory factor, eIF4A3, in microvascular endothelial cells under HG conditions were also assessed. In addition, the regulatory role of eIF4A3 on circEHMT1 expression was confirmed. Moreover, to elucidate the in vivo functions of eIF4A3 and circEHMT1, streptozotocin (STZ) was used to establish a DR model in rats. It was revealed that HG condition decreased circEHMT1 and eIF4A3 expressions and reduced ZO-1, Claudin-5, and Occludin levels in retinal microvascular endothelial cells. Furthermore, it was observed that eIF4A3 could regulate the expression of circEHMT1. Overexpression of eIF4A3 or circEHMT1 under HG conditions improved endothelial cell injury and decreased tube-formation ability. Additionally, in the DR rat model, eIF4A3 overexpression restored circEHMT1 levels and ameliorated retinal vasculature changes. Altogether, eIF4A3 regulates circEHMT1 expression, thereby affecting microvascular endothelial cell injury and tube formation. Further understanding the regulatory effect of eIF4A3 on circEHMT1 may provide novel therapeutic targets for DR.


Prevalence of and Risk Factors for Sexually Transmitted Infections among Korean Adolescents under Probation.
There is limited research on sexually transmitted infections (STIs) among adolescents in Korea. The objective of this study was to explore the prevalence of and risk factors for STIs among Korean adolescents under probation. A cross-sectional analysis was conducted in one juvenile-delinquent center and five probation offices in Korea to determine the prevalence of STIs caused by the following pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, herpes simplex virus (HSV), human immunodeficiency virus (HIV), Treponema pallidum, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum. Of the 237 (208 male and 29 female) participating adolescents, 152 (64.1%) had a history of coitus. Overall, 133 (56.1%) subjects tested positive for at least one microorganism in their genitourinary tract. The most prevalent pathogen was U. urealyticum (24.7%, n = 65), followed by U. parvum (24.1%, n = 57), M. hominis (17.3%, n = 41), C. trachomatis (13.9%, n = 33), N. gonorrhoeae (1.7%, n = 4), T. vaginalis (0.8%, n = 2), and HSV (0.8%, n = 2). The prevalence of syphilis was 0.8% (n = 2). There were no reported cases of HIV infection. Fifty-four participants (35.5%) were positive with more than two pathogens. We did not find any significant difference between STIs and socioeconomic factors, behavioral factors or sexual practices. In conclusion, the prevalence of STIs among adolescents under probation was high. Systematic screening programs, more practical sexual education, and adequate provision of treatment are essential for the prevention and management of STIs among adolescents, especially those under probation.


Pain-like behavior in the collagen antibody-induced arthritis model is regulated by lysophosphatidic acid and activation of satellite glia cells.
Inflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain, and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA1/3 receptor inhibitor, but joint inflammation was not affected. Autotaxin, an LPA synthesizing enzyme was upregulated in dorsal root ganglia (DRG) neurons during both CAIA phases, but not in joints or spinal cord. Late-phase pronociceptive neurochemical changes in the DRG were blocked in Lpar1 receptor deficient mice and reversed by LPA neutralization. In vitro and in vivo studies indicated that LPA regulates pain-like behavior via the LPA1 receptor on satellite glia cells (SGCs), which is expressed by both human and mouse SGCs in the DRG. Furthermore, CAIA-induced SGC activity is reversed by phospholipid neutralization and blocked in Lpar1 deficient mice. Our findings suggest that the regulation of CAIA-induced pain-like behavior by LPA signalling is a peripheral event, associated with the DRGs and involving increased pronociceptive activity of SGCs, which in turn act on sensory neurons.


Distinctive messages in infant-directed lullabies and play songs.
Mothers were recorded singing a song of their choice in both a lullaby style and a play-song style to their 6-month-olds. Adult raters identified the play-song-style and lullaby-style versions with 100% accuracy. Play-song-style renditions were rated as being more brilliant, clipped, and rhythmic and as having more smiling and more prominent consonants. Lullaby-style renditions were characterized as being more airy, smooth, and soothing. Adults observed videotapes (without sound) of 6-month-olds listening to alternating lullaby-style and play-song-style trials and performed at above chance levels when determining which music the infants were hearing. Coding analyses revealed that infants focused their attention more toward themselves during lullaby-style trials and more toward the external world during play-song-style trials. These results suggest that singing may be used to regulate infants' states and to communicate emotional information.


Reduction of lens size in PAX6-related aniridia.
Heterozygous mutation of PAX6 in humans leads to congenital aniridia (OMIM 106210) which is typified by congenital iris and foveal defects, and later onset glaucoma, aniridic keratopathy, and cataract. Mice heterozygous for Pax6 mutations phenocopy many aspects of aniridia including the iris defects, keratopathy and cataract, although Pax6 mutant mice have small lenses, a phenotype which is not typically reported in human aniridia, perhaps due to difficulties in measuring lens diameter during typical ophthalmic examinations as the lens periphery is shielded by the iris. In order to overcome this, records of patients diagnosed with congenital aniridia between April 2015 and May 2021 at the Necker-Enfants Malades Hospital, and genetically confirmed with a disease-causing PAX6 variant, were retrospectively reviewed for those with normal axial length whose iris defects allowed visualization of the lens margins and corneal diameter to allow calculation of a lens/corneal diameter ratio. This value was compared with values obtained from a cohort of patients with Sjödell grade IV oculocutaneous albinism type 1 (OCA1; OMIM 203100) which allowed visualization of the lens periphery via iris transillumination. This analysis revealed that patients with congenital aniridia had a significantly lower lens/corneal ratio when compared to those with albinism, suggesting that humans haploinsufficient for PAX6, like mice, rats, frogs, and zebrafish, exhibit reductions in lens size.


Relevance of dietary exposure to acrylamide formed in heat-processed agri-food products.
Acrylamide (AA) is considered one of the contaminants that occur in heat-processed agri-food products, which through diet can increase the risk of developing cancer for consumers of all age groups. This review analysed the level of acrylamide of the most important heat-processed agri-food products that contribute to the dietary exposure of the population of different European countries and the assessment of health risks related to the presence of AA in food. The results of monitoring AA concentrations in agri-food products, reported individually by researchers or projects such as CONTAM in 2015 and the UK Food Standard Agency in 2017, show that some products exceeding the recently set European reference level are reported as such for specific values - mean UB/RLs in µg.kg-1: French fries (550/500), coffee dry (523/400), coffee substitutes (1,499/500, 400), processed cereal-based baby foods (76/40), potato crisps and snacks (2,214/750), breakfast cereals (744/300), biscuits and crackers (637/350, 400), and coffee substitutes (1,897/500). Average values (µg/kg body weight per day) of exposure to AA from food for different age groups (EFSA) are estimated at 0.4-1.9, but in different European countries, as reported by several studies (including Romania), are between 1.4 and 3.4. Starting from the genotoxic and carcinogenic potential of acrylamide, it is important to regularly monitor the presence of acrylamide and its levels in food and to investigate the food pattern of the population to detect the share of foods at risk of exposure.


Ventricular wall granulations and draining of cerebrospinal fluid in chronic giant hydrocephalus.
In rare cases, adults with normal or almost normal cognition may have giant brain ventricles surrounded by a sliver of brain. Because the usual flow of cerebrospinal fluid (CSF) is interrupted in these individuals, they may develop alternative CSF pathways to preserve brain function. To describe novel morphologic autopsy findings in a patient with chronic giant hydrocephalus that suggest the existence of alternative CSF draining pathways. Case report. Autopsy study. A 48-year-old man with chronic compensated hydrocephalus associated with a Dandy-Walker malformation. Autopsy findings. We observed microscopic structures on the ventricular wall that may facilitate CSF resorption. Their histologic appearance, reminiscent of pacchionian granulations, showed the opposite relation in regard to CSF/blood compartments: whereas the core of a pacchionian granulation contains CSF and the granulation is bathed in blood of the venous sinus, the core of the ventricular granulation in our patient contained venules, with the granulation bathed in ventricular CSF. These previously unreported (to our knowledge) ventricular wall granulations may facilitate draining of CSF into the venous system when CSF outflow from the ventricular system is occluded. The presence of these ventricular structures illustrates biologic adaptation to anomalous conditions and successful compensation.


Seismic amplitude measurements suggest foreshocks have different focal mechanisms than aftershocks.
The ratio of the amplitudes of P and S waves from the foreshocks and aftershocks to three recent California earthquakes show a characteristic change at the time of the main events. As this ratio is extremely sensitive to small changes in the orientation of the fault plane, a small systematic change in stress or fault configuration in the source region may be inferred. These results suggest an approach to the recognition of foreshocks based on simple measurements of the amplitudes of seismic waves.


Fishing cat Prionailurus viverrinus distribution and habitat suitability in Nepal.
The fishing cat Prionailurus viverrinus is a wetland specialist species endemic to South and Southeast Asia. Nepal represents the northern limit of its biogeographic range, but comprehensive information on fishing cat distribution in Nepal is lacking. To assess their distribution, we compiled fishing cat occurrence records (n = 154) from Nepal, available in published literature and unpublished data (2009-2020). Bioclimatic and environmental variables associated with their occurrence were used to predict the fishing cat habitat suitability using MaxEnt modeling. Fishing cat habitat suitability was associated with elevation (152-302 m), precipitation of the warmest quarter, i.e., April-June (668-1014 mm), precipitation of the driest month (4-7 mm), and land cover (forest/grassland and wetland). The model predicted an area of 4.4% (6679 km2) of Nepal as potential habitat for the fishing cat. About two-thirds of the predicted potentially suitable habitat lies outside protected areas; however, a large part of the highly suitable habitat (67%) falls within protected areas. The predicted habitat suitability map serves as a reference for future investigation into fishing cat distribution as well as formulating and implementing effective conservation programs in Nepal. Fishing cat conservation initiatives should include habitats inside and outside the protected areas to ensure long-term survival. We recommend conservation of wetland sites, surveys of fishing cats in the identified potential habitats, and studying their genetic connectivity and population status.


Predictive factors for recurrence progression and cancer specific survival in high-risk bladder cancer.
Despite standard treatment with transurethral resection (TUR) and adjuvant Bacillus Calmette-Guérin (BCG), a large percentage of high-risk bladder cancer (HRBC) recur, and some progress. On the basis of review of the current guidelines and literature, we have developed actualized clinical and molecular prognostic factors of recurrence, progression and cancer specific survival (CSS) in patients with HRBC. A Medline search was conducted to identify the current literature updating the most important clinic and pathological predictive factors published in the last years. Also, there have been reviewed the new molecular markers that can assess prognosis and BCG response. Despite different methodological bias, as short follow-up, a small number of patients and a different definition of prognostic factors, increased evidence supports sex, age, grade, stage, multifocality, history of previous recurrences, carcinoma in situ in the prostatic urethra and early recurrence as prognostic factors for recurrence, progression and CSS in nonmuscle invasive bladder cancer. Also lymphovascular invasion in TUR and new molecular markers (galectin-3, profilin-1, and combination of markers) are increasingly useful in predicting prognosis and BCG response. Moreover, there is enough evidence to consider the implementation of new specific risk tables for patients treated with BCG. In cases with poor prognostic factors after TUR in HRBC early cystectomy should be considered.


Unspoken inequality: how COVID-19 has exacerbated existing vulnerabilities of asylum-seekers, refugees, and undocumented migrants in South Africa.
An estimated 2 million foreign-born migrants of working age (15-64) were living in South Africa (SA) in 2017. Structural and practical xenophobia has driven asylum-seekers, refugees, and undocumented migrants in SA to abject poverty and misery. The Coronavirus Disease 2019 (COVID-19) containment measures adopted by the SA government through the lockdown of the nation have tremendously deepened the unequal treatment of asylum-seekers and refugees in SA. This can be seen through the South African government's lack of consideration of this marginalized population in economic, poverty, and hunger alleviation schemes. Leaving this category of our society out of the national response safety nets may lead to negative coping strategies causing mental health issues and secondary health concerns. An effective response to the socioeconomic challenges imposed by the COVID-19 pandemic should consider the economic and health impact of the pandemic on asylum-seekers, refugees, and undocumented migrants.


Current Status of Malnutrition and Stunting in Pakistani Children: What Needs to Be Done?
Malnutrition is one of the greatest health challenges that affects about 2 billion people globally. Multiple factors including poverty, food insecurity, maternal health and nutritional status, mother's age at marriage and educational status, low birthweight or small for gestational age (SGA), premature births, suboptimal breastfeeding practices, unhealthy dietary and lifestyle patterns, health and immunization status of children, socioeconomic status of family, environmental and household conditions, together with cultural practices and myths, play vital role in affecting the growth of children at early age. Although child stunting has declined in Pakistan, the reduction rate is only 0.5%, which is very low. This may be due to ineffective or inappropriate intervention programs as they are mostly addressing only one issue at a time and don't use the multi-sector approach to address numerous determinants of stunting. It is therefore important to initiate cost-effective multi-tiered intervention approaches to be implemented at pre-conception, pregnancy and early postpartum stages to prevent the problems of malnutrition and stunting in Pakistani children. This review discusses the etiology of child malnutrition and stunting in Pakistan, role of various determinants of stunting and what type of intervention strategies and approaches should be developed and implemented to deal with these problems. Key teaching pointsMalnutrition is one of the greatest global health challenges.Poverty, food insecurity, socioeconomic status, unhealthy dietary patterns, maternal health and nutritional status, low birthweight, suboptimal breast feeding, environmental conditions, cultural practices and myths, are the main factors for child malnutrition and stunting in Pakistan.The slow reduction rate in child stunting may be due to inappropriate intervention programs.Cost-effective multi-tiered intervention approaches must be implemented at pre-conception, pregnancy and early postpartum stages to prevent child malnutrition and stunting in Pakistan.A holistic approach comprising nutrition and WASH interventions, together with strategies to improve the socioeconomic status be developed and implemented to resolve this dilemma.


Inventory and perspectives of chronic disease management programs in Switzerland: an exploratory survey.
To describe chronic disease management programs active in Switzerland in 2007, using an exploratory survey. We searched the internet (Swiss official websites and Swiss web-pages, using Google), a medical electronic database (Medline), reference lists of pertinent articles, and contacted key informants. Programs met our operational definition of chronic disease management if their interventions targeted a chronic disease, included a multidisciplinary team (>/=2 healthcare professionals), lasted at least six months, and had already been implemented and were active in December 2007. We developed an extraction grid and collected data pertaining to eight domains (patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment, clinical outcomes). We identified seven programs fulfilling our operational definition of chronic disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, psychosis and breast cancer. Interventions were multifaceted; all included education and half considered planned follow-ups. The recipients of the interventions were patients, and healthcare professionals involved were physicians, nurses, social workers, psychologists and case managers of various backgrounds. In Switzerland, a country with universal healthcare insurance coverage and little incentive to develop new healthcare strategies, chronic disease management programs are scarce. For future developments, appropriate evaluations of existing programs, involvement of all healthcare stakeholders, strong leadership and political will are, at least, desirable.


Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices.
Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.


Unveiling Local Optical Properties Using Nanoimaging Phase Mapping in High-Index Topological Insulator Bi2Se3 Resonant Nanostructures.
Topological insulators are materials characterized by an insulating bulk and high mobility topologically protected surface states, making them promising candidates for future optoelectronic and quantum devices. Although their electronic properties have been extensively studied, their mid-infrared (MIR) properties and prospective photonic capabilities have not been fully uncovered. Here, we use a combination of far-field and near-field nanoscale imaging and spectroscopy to study chemical vapor deposition-grown Bi2Se3 nanobeams (NBs). We extract the MIR optical constants of Bi2Se3, revealing refractive index values as high as n ∼ 6.4, and demonstrate that the NBs support Mie resonances across the MIR. Local near-field reflection phase mapping reveals domains of various phase shifts, providing information on the local optical properties of the NBs. We experimentally measure up to 2π phase-shift across the resonance, in excellent agreement with finite-difference time-domain simulations. This work highlights the potential of Bi2Se3 for quantum circuitry, nonlinear generation, high-Q metaphotonics, and photodetection.


Bacteriophage resistance in Escherichia coli K-12: general pattern of resistance.
Resistant mutants were isolated to 42 virulent bacteriophages in one strain of Escherichia coli K-12 and tested for resistance or sensitivity to a set of 56 bacteriophages. Most of the mutants fell into 11 groups with respect to their resistance patterns. It was possible to classify the bacteriophages broadly, according to the variety of mutants that were resistant to them.


Task-evoked pupil response for accurately recognized accented speech.
Unfamiliar second-language (L2) accents present a common challenge to speech understanding. However, the extent to which accurately recognized unfamiliar L2-accented speech imposes a greater cognitive load than native speech remains unclear. The current study used pupillometry to assess cognitive load for native English listeners during the perception of intelligible Mandarin Chinese-accented English and American-accented English. Results showed greater pupil response (indicating greater cognitive load) for the unfamiliar L2-accented speech. These findings indicate that the mismatches between unfamiliar L2-accented speech and native listeners' linguistic representations impose greater cognitive load even when recognition accuracy is at ceiling.


Cholesterol oxidase: ultrahigh-resolution crystal structure and multipolar atom model-based analysis.
Examination of protein structure at the subatomic level is required to improve the understanding of enzymatic function. For this purpose, X-ray diffraction data have been collected at 100 K from cholesterol oxidase crystals using synchrotron radiation to an optical resolution of 0.94 Å. After refinement using the spherical atom model, nonmodelled bonding peaks were detected in the Fourier residual electron density on some of the individual bonds. Well defined bond density was observed in the peptide plane after averaging maps on the residues with the lowest thermal motion. The multipolar electron density of the protein-cofactor complex was modelled by transfer of the ELMAM2 charge-density database, and the topology of the intermolecular interactions between the protein and the flavin adenine dinucleotide (FAD) cofactor was subsequently investigated. Taking advantage of the high resolution of the structure, the stereochemistry of main-chain bond lengths and of C=O···H-N hydrogen bonds was analyzed with respect to the different secondary-structure elements.


Physiological involvement of presynaptic L-type voltage-dependent calcium channels in GABA release of cerebellar molecular layer interneurons.
While high threshold voltage-dependent Ca2+ channels (VDCCs) of the N and P/Q families are crucial for evoked neurotransmitter release in the mammalian CNS, it remains unclear to what extent L-type Ca2+ channels (LTCCs), which have been mainly considered as acting at postsynaptic sites, participate in the control of transmitter release. Here, we investigate the possible role of LTCCs in regulating GABA release by cerebellar molecular layer interneurons (MLIs) from rats. We found that BayK8644 (BayK) markedly increases mIPSC frequency in MLIs and Purkinje cells (PCs), suggesting that LTCCs are expressed presynaptically. Furthermore, we observed (1) a potentiation of evoked IPSCs in the presence of BayK, (2) an inhibition of evoked IPSCs in the presence of the LTCC-specific inhibitor Compound 8 (Cp8), and (3) a strong reduction of mIPSC frequency by Cp8. BayK effects are reduced by dantrolene, suggesting that ryanodine receptors act in synergy with LTCCs. Finally, BayK enhances presynaptic AP-evoked Ca2+ transients and increases the frequency of spontaneous axonal Ca2+ transients observed in TTX. Taken together, our data demonstrate that LTCCs are of primary importance in regulating GABA release by MLIs.


Upregulation of renal and vascular nitric oxide synthase in young spontaneously hypertensive rats.
The available data on the role of the L-arginine/nitric oxide (NO) pathway in the genesis of hypertension in spontaneously hypertensive rats (SHR) are limited and contradictory. In an attempt to address this issue, male SHR were studied during the early phase of evolution of hypertension (age 8 to 12 weeks) to distinguish the primary changes of NO metabolism from those caused by advanced hypertension, vasculopathy, and aging late in the course of the disease. A group of age-matched male Wistar-Kyoto rats (WKY) served as controls. The SHR exhibited a marked rise in arterial blood pressure and a significant increase in urinary excretion and plasma concentration of NO metabolites (nitrite/nitrate [NOx]). Likewise, the SHR showed a significant elevation of thoracic aorta NO synthase (NOS) activity coupled with significant increases of kidney, aorta, inducible NOS (iNOS), and endothelial NOS (eNOS) proteins. In an attempt to determine whether the enhanced L-arginine/NO pathway is a consequence of hypertension, studies were repeated using 3-week-old animals before the onset of hypertension. The study revealed significant increases in urinary NOx excretion as well as vascular eNOS and renal iNOS proteins. In conclusion, the L-arginine/NO pathway is upregulated in young SHR both before and after the onset of hypertension. Thus, development of hypertension is not due to a primary impairment of NO production in SHR. On the contrary, NO production is increased in young SHR both before and after the onset of hypertension.


The biochemistry and biology of the myeloid haemopoietic cell growth factors.
In the adult, blood cell production or haemopoiesis takes place mainly in the bone marrow. The blood cell types produced are a reflection of the needs of the organism at any moment, for example bacterial infection leads to a large increase in neutrophil production. The rate and scale of blood cell production in vivo are regulated, at least in part, by the synthesis and release of specific cytokines both within the bone marrow and also from other tissues. Here we detail the range of cytokines which act directly on haemopoietic stem cells and myeloid progenitor cells. Also cellular systems which will permit the elucidation of the specific interactions between these various cytokines which regulate stem cell self-renewal, differentiation and proliferation are described.


Neuroanatomical dissociation for taxonomic and thematic knowledge in the human brain.
It is thought that semantic memory represents taxonomic information differently from thematic information. This study investigated the neural basis for the taxonomic-thematic distinction in a unique way. We gathered picture-naming errors from 86 individuals with poststroke language impairment (aphasia). Error rates were determined separately for taxonomic errors ("pear" in response to apple) and thematic errors ("worm" in response to apple), and their shared variance was regressed out of each measure. With the segmented lesions normalized to a common template, we carried out voxel-based lesion-symptom mapping on each error type separately. We found that taxonomic errors localized to the left anterior temporal lobe and thematic errors localized to the left temporoparietal junction. This is an indication that the contribution of these regions to semantic memory cleaves along taxonomic-thematic lines. Our findings show that a distinction long recognized in the psychological sciences is grounded in the structure and function of the human brain.


Differential effect of imidazole antibiotics on untransformed and virus-transformed rat cell lines.
The imidazole antimycotics clotrimazole and miconazole were tested on untransformed rat cell line 3Y1-B clone 1-6 (3Y1) and six transformed cell lines, which were independently isolated from 3Y1 or 3Y1-B clone 1 after infection with adenovirus 12 (AD-12) or with SV40, to determine their sensitivities to these drugs. The relative plating efficiency of three cell lines (T3, W4, and W5) transformed with AD-12 was reduced to 10(-1( of the initial value by clotrimazole (2 to 4 microgram/ml), whereas that of the parental cell line 3Y1 was reduced to 10(-1) of the initial value by clotrimazole (20 to 25 microgram/ml). By contrast, the differential effect of miconazole on 3Y1 and AD-12-transformed cell lines was found to be a factor of 2. The sensitivity of the SV40-transformed 3Y1 and the AD-12-transformed cell lines. The cellular sensitivity of untransformed 3Y1 cells to clotrimazole was significantly enhanced when exposed to various doses of the unsaturated fatty acid, linoleic acid. The untransformed and transformed cell lines showed sensitivities similar to the cytocidal activity of sterol-binding antimycotics, amphotericin B and filipin.


Parallel language activation and cognitive control during spoken word recognition in bilinguals.
Accounts of bilingual cognitive advantages suggest an associative link between cross-linguistic competition and inhibitory control. We investigate this link by examining English-Spanish bilinguals' parallel language activation during auditory word recognition and nonlinguistic Stroop performance. Thirty-one English-Spanish bilinguals and 30 English monolinguals participated in an eye-tracking study. Participants heard words in English (e.g., comb) and identified corresponding pictures from a display that included pictures of a Spanish competitor (e.g., conejo, English rabbit). Bilinguals with higher Spanish proficiency showed more parallel language activation and smaller Stroop effects than bilinguals with lower Spanish proficiency. Across all bilinguals, stronger parallel language activation between 300-500ms after word onset was associated with smaller Stroop effects; between 633-767ms, reduced parallel language activation was associated with smaller Stroop effects. Results suggest that bilinguals who perform well on the Stroop task show increased cross-linguistic competitor activation during early stages of word recognition and decreased competitor activation during later stages of word recognition. Findings support the hypothesis that cross-linguistic competition impacts domain-general inhibition.


Gut microbiome structure and metabolic activity in inflammatory bowel disease.
The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.


The regulation of p27Kip1 expression following the polyclonal activation of murine G0 T cells.
Polyclonal activation of murine G0 T cells with immobilized anti-CD3 induces entry into the cell cycle as well as the subsequent cytokine-dependent proliferative response. G0 T cells express high levels of p27Kip1 protein and specific mRNA, which decline rapidly following activation. The decline in the expression of p27Kip1 and sequestering of the inhibitory protein by cdk4 and cdk6 correlated with the increase in cdk2 kinase activity during the G1 phase. Anti-CD3 activation of G0 T cells in the presence of cyclosporin A or rapamycin inhibited the down-regulation of p27Kip1, the cellular levels of the inhibitor remained high, and the cells remained in the G1 phase. PBu2 activation of G0 T cells also did not result in the down-regulation of p27Kip1 and the cells remained in G1. In each instance IL-2 restored the down-regulation of p27Kip1, resulting in a significant reduction in the level of the inhibitor, and stimulated the cells to progress through the cell cycle. Jurkat cells transfected with the p27GL-988 plasmid containing +1 to -988 nt of the p27Kip1 promoter region and subsequently exposed to rIL-2 resulted in a significant reduction in the activity of the p27Kip1 promoter. These findings suggest that in addition to providing the signals required for activated T cells to traverse G1/S, IL-2 also influences the promoter function of p27Kip1, which effectively induces transcriptional down-regulation of the gene.


[Cryofractographic study of intercellular junctions in the populations of agar-cultivated Bordetella pertussis].
The characteristic feature of replicas obtained from the freeze-fractures of B. pertussis unfixed cultures developing on casein charcoal agar for 1-7 days is the associative growth of highly polymorphic cells, ensured by the ramified system of intercellular connections (IC) formed by the derivatives of the outer layers of the cell wall. This proves that the associative location of bacterial cells, linked by numerous IC, in the preparation is not the artefact appearing in the process of their chemical fixation. In replicas obtained from the freeze-fractures of B. pertussis cultures, previously fixed with glutaraldehyde, osmic acid and uranyl acetate, oval cells with the cytoplasm having a relatively homogeneous structure and with the smoothed-out three-layer cell wall prevail. As a rule, IC are limited to the sites of direct contacts between individual cells.


Comparison of Pollutant Effects on Cutaneous Inflammasomes Activation.
The skin is the outermost layer of the body and, therefore, is exposed to a variety of stressors, such as environmental pollutants, known to cause oxinflammatory reactions involved in the exacerbation of several skin conditions. Today, inflammasomes are recognized as important modulators of the cutaneous inflammatory status in response to air pollutants and ultraviolet (UV) light exposure. In this study, human skin explants were exposed to the best-recognized air pollutants, such as microplastics (MP), cigarette smoke (CS), diesel engine exhaust (DEE), ozone (O3), and UV, for 1 or 4 days, to explore how each pollutant can differently modulate markers of cutaneous oxinflammation. Exposure to environmental pollutants caused an altered oxidative stress response, accompanied by increased DNA damage and signs of premature skin aging. The effect of specific pollutants being able to exert different inflammasomes pathways (NLRP1, NLRP3, NLRP6, and NLRC4) was also investigated in terms of scaffold formation and cell pyroptosis. Among all environmental pollutants, O3, MP, and UV represented the main pollutants affecting cutaneous redox homeostasis; of note, the NLRP1 and NLRP6 inflammasomes were the main ones modulated by these outdoor stressors, suggesting their role as possible molecular targets in preventing skin disorders and the inflammaging events associated with environmental pollutant exposure.


Breast carcinoma in elderly women: features of disease presentation, choice of local and systemic treatments compared with younger postmenopasual patients.
Aging remains one of the single greatest risk factors for the development of new breast carcinoma. The aim of the study was to evaluate the relation between biologic features at first diagnosis of breast carcinoma and treatment choice for postmenopausal women > or = 50 years to optimize treatment in the elderly. The sample included 2999 consecutive postmenopausal patients referred for surgery at the European Institute of Oncology (Milan, Italy) from April 1997 to February 2002. The patients were grouped according to age: young postmenopausal (YPM; 50-64 years, n = 2052), older postmenopausal (OPM; 65-74, n = 801), and elderly postmenopausal (EPM; > or = 75, n = 146). EPM patients referred to surgery had larger tumors compared with YPM patients (pT4: 6.7% vs. 2.4%) as well as greater lymph node involvement (lymph node positive: 62.5% vs. 51.3%). EPM patients showed a higher degree of estrogen and progesterone receptor expression (P < 0.01), less peritumoral vascular invasion (P < 0.01), and less HER-2/neu expression (P < 0.01) than YPM patients. Comorbidities were more often recorded for elderly patients (72% EPM vs. 45% YPM; P < 0.001), did not influence surgical choices, and were similar across groups (breast conservation: 73.9%, 76.9%, and 72.9%, respectively). No systemic therapy (either chemotherapy or endocrine therapy) was recommended for 19.1% of the EPM compared with 5.4% and 4.7% of the two other groups. In spite of larger tumor size at presentation, older patients had tumors with more favorable biologic characteristics, when compared with younger postmenopausal patients. Reluctance to prescribe systemic treatments was due to the complexity of evaluation for these patients. Taking into account the data from the current study and given the climate of uncertainty regarding optimal treatment, the authors decided to individualize care on the basis of biologic characteristics, comorbidity, social support, functional status, and patient preferences. Trials of tailored adjuvant therapy should be a health care priority.


A spatiotemporal model for predicting grain aphid population dynamics and optimizing insecticide sprays at the scale of continental France.
We expose here a detailed spatially explicit model of aphid population dynamics at the scale of a whole country (Metropolitan France). It is based on convection-diffusion-reaction equations, driven by abiotic and biotic factors. The target species is the grain aphid, Sitobion avenae F., considering both its winged and apterous morphs. In this preliminary work, simulations for year 2004 (an outbreak case) produced realistic aphid densities, and showed that both spatial and temporal S. avenae population dynamics can be represented as an irregular wave of population peak densities from southwest to northeast of the country, driven by gradients or differences in temperature, wheat phenology, and wheat surfaces. This wave pattern fits well to our knowledge of S. avenae phenology. The effects of three insecticide spray regimes were simulated in five different sites and showed that insecticide sprays were ineffective in terms of yield increase after wheat flowering. After suitable validation, which will require some further years of observations, the model will be used to forecast aphid densities in real time at any date or growth stage of the crop anywhere in the country. It will be the backbone of a decision support system, forecasting yield losses at the level of a field. The model intends then to complete the punctual forecasting provided by older models by a comprehensive spatial view on a large area and leads to the diminution of insecticide sprayings in wheat crops.


Sex Does Not Sell: Effects of Sexual Advertising Parameters on Women Viewers' Implicit and Explicit Recall of Ads and Brands.
This study investigated implicit and explicit memory effects of sexual and non-sexual advertisements embedded in either a sexual or non-sexual program among women viewers. We predicted that sexual appeals would facilitate implicit memory for the brand, and we explored whether program-type (sexual or non-sexual) and its associated congruity would impact or moderate recall of the surrounding advertisement among a small sample (n = 52) of exclusively women advertisement viewers. Sexual (versus non-sexual) advertising led to significantly worse implicit memory for the brand logo but better explicit recall for the advertisement scene itself. There was no effect of sexual appeals on explicit brand name recall, and no significant effect on advertisement recall of the program type. There was a significant interaction effect for program type and advertisement type for explicit recall of the advertisement scene, in which program-type moderated sexual advertisement recall. These results suggest that sexual advertising may increase memory for the advertisement at the expense of recalling the brand advertised. Limitations and implications of this study are discussed.


Levels of dioxins and polybrominated diphenyl ethers in human milk from three regions of northern China and potential dietary risk factors.
Human milk samples were collected from 50 breast-feeding mothers in Shijiazhuang, 60 in Tianjin and 48 in Yantai from November 2006 to April 2007. The three areas are located in northern China. We selected randomly 20 samples from each area for detection of polychlorinated dibenzodioxins/frans (PCDD/Fs), polycholorinated biphenyls (dl-PCBs) and polybrominated diphenyl ethers (PBDEs) by high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Our results show the average concentrations of PCDD/Fs plus dl-PCBs were 6.24 TEQ pg g(-1)fat, 7.54 TEQ pg g(-1)fat and 6.69 TEQ pg g(-1) fat in human milk from Shijiazhuang, Tianjin and Yantai, respectively. The average concentrations of PBDEs were 3.71 ng g(-1) fat, 3.42 ng g(-1) fat and 4.16 ng g(-1) fat in human milk from Shijiazhuang, Tianjin and Yantai, respectively. Among congeners of PBDEs, the high and low brominated congeners BDE209, BDE207, BDE197, BDE153, BDE15, BDE28 and BDE47 were the predominant PBDE congeners, accounting for 91%, 90% and 84% of total PBDEs in samples from Shijiazhuang, Tianjin and Yantai, respectively. Based on the results of an in-person interview of mothers using a questionnaire, freshwater fish consumption was found to correlate with total mono-ortho dl-PCBs (mo-PCBs) and sea fish consumption was found to correlate with total non-ortho dl-PCBs (no-PCBs) of human milk in these areas. However, no correlation was found between concentrations of total PBDEs and total TEQ of PCDD/Fs plus dl-PCBs and food consumption. Continuous surveillance on dioxins and dl-PCBs levels in human milk is needed to correctly evaluate both the environmental impact and human health risk in China.


The dependence of thiol-inducible radiation resistance in Escherichia coli K12 on the medium and catalytic metal.
Radiation protection by thiols in procaryotes and lower eucaryotes has been demonstrated repeatedly to require a competent DNA repair phenotype, suggesting that simple chemical radical scavenging and hydrogen donation are only a portion of the mechanism of radiation protection by thiols. In the present report, thiol-induced radiation resistance--a model in which cells are pretreated with dithiothreitol and then irradiated in the absence of thiol--is shown to be a medium-dependent process. Wild-type log-phase cells treated with dithiothreitol in minimal-glucose medium are induced to radioresistance that persists after the thiol has been removed. Although the thiol pretreatment affected the antioxidants (catalase, superoxide dismutase, and glutathione) in cells at the time of irradiation, various antioxidant levels did not predict radiation resistance. Thiol-induced radioresistance is not expressed in rich medium-treated cells or in DNA repair (recA)-deficient cells. Addition of the efficient chelator, DETAPAC, to the thiol treatment medium leads to additional radioresistance in the case of minimal medium and a moderate expression of resistance in rich medium. Experiments using the intracellular chelator, 1,10-phenanthroline, in the presence of thiol led to inhibition of thiol-induced resistance in minimal medium and radiosensitization in rich medium. These results can be explained by a "site-specific" mechanism of thiol oxidation in which the chelators control the site(s) and rate of thiol oxidation, subsequently determining the type of cellular response.


The aPKC-PAR-6-PAR-3 cell polarity complex localizes to the centrosome attracting body, a macroscopic cortical structure responsible for asymmetric divisions in the early ascidian embryo.
Posterior blastomeres of 8-cell stage ascidian embryos undergo a series of asymmetric divisions that generate cells of unequal sizes and segregate muscle from germ cell fates. These divisions are orchestrated by a macroscopic cortical structure, the ;centrosome attracting body' (CAB) which controls spindle positioning and distribution of mRNA determinants. The CAB is composed of a mass of cortical endoplasmic reticulum containing mRNAs (the cER-mRNA domain) and an electron dense matrix, but little is known about its precise structure and functions. We have examined the ascidian homologues of PAR proteins, known to regulate polarity in many cell types. We found that aPKC, PAR-6 and PAR-3 proteins, but not their mRNAs, localize to the CAB during the series of asymmetric divisions. Surface particles rich in aPKC concentrate in the CAB at the level of cortical actin microfilaments and form a localized patch sandwiched between the plasma membrane and the cER-mRNA domain. Localization of aPKC to the CAB is dependent on actin but not microtubules. Both the aPKC layer and cER-mRNA domain adhere to cortical fragments prepared from 8-cell stage embryos. Astral microtubules emanating from the proximal centrosome contact the aPKC-rich cortical domain. Our observations indicate that asymmetric division involves the accumulation of the aPKC-PAR-6-PAR-3 complex at the cortical position beneath the pre-existing cER-mRNA domain.


Work-related asthma: diagnosis and prognosis of immunological occupational asthma and work-exacerbated asthma.
The incidence and prevalence of asthma are increasing. One reason for this trend is the rise in adult-onset asthma, especially occupational asthma, which is 1 of the 2 forms of work-related asthma. Occupational asthma is defined as asthma caused by agents that are present exclusively in the workplace. The presence of pre-existing asthma does not rule out the possibility of developing occupational asthma. A distinction has traditionally been made between immunological occupational asthma (whether IgE-mediated or not) and nonimmunological occupational asthma caused by irritants, the most characteristic example of which is reactive airway dysfunction syndrome. The other form of work-related asthma is known as work-exacerbated asthma, which affects persons with pre-existing or concurrent asthma that is worsened by work-related factors. It is important to differentiate between the 2 entities because their treatment, prognosis, and medical and social repercussions can differ widely. In this review, we discuss diagnostic methods, treatment, and avoidance/nonavoidance of the antigen in immunological occupational asthma and work-exacerbated asthma. Key words: Specific inhalation challenge. Peak expiratory flow. Workplace. Irritants.


Effect of nandrolone decanoate on skeletal muscle repair.
This study analyzed the effect of nandrolone decanoate (ND) on muscle repair and the expression of myogenic regulatory factors following cryoinjury in rat skeletal muscle. Adult male Wistar rats were randomly divided into 4 groups: control group, sham group, cryoinjured group treated with ND and non-injured group treated with ND. Treatment consisted of subcutaneous injections of ND (5 mg/kg) twice a week. After sacrifice, the tibialis anterior muscle was removed for the isolation of total RNA and analysis of myogenic regulatory factors using real-time PCR as well as morphological analysis using the hematoxylin-eosin assay. There was a significant increase in MyoD mRNA after 7 days and in myogenin mRNA after 21 days in the cryoinjured ND group in comparison to other groups in the same period. The morphological analysis revealed no edema or myonecrosis after 7 days as well as no edema or inflammatory infiltrate after 14 days in the cryoinjured ND group. In conclusion the anabolic steroid nandrolone decanoate can modulate the muscle repair process in rats following cryoinjury by influencing the expression of regulatory myogenic factors and phases of muscle repair.


The mouse L-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region.
To investigate the regulation of mouse L-histidine decarboxylase (HDC) gene expression, we isolated genomic DNA clones encoding HDC. Structural analysis revealed that the mouse HDC gene was composed of 12 exons, spanning approximately 24 kb. Northern blotting analysis indicated that, among the cell lines examined, a high level of HDC gene expression was restricted to mature mast cell lines and an erythroblastic cell line. The gene was induced strongly in the mouse immature mast cell line P815 after incubation in the peritoneal cavity of BDF1 mice. We observed that the promoter region was demethylated in the HDC-expressing cell lines and in induced P815 cells. Interestingly, forced demethylation by 5-azacytidine (5-azaC) treatment induced high expression of HDC mRNA in P815 cells. The activity of a mouse HDC promoter-reporter construct stably transfected in P815 cells was repressed by in vitro patch-methylation. This low promoter activity of the patch-methylated reporter construct was restored after 5-azaC treatment, which demethylated the patch-methylated promoter. These results indicate that DNA methylation state of the promoter region controls HDC gene expression.


Body-Weight Fluctuations and Outcomes in Coronary Disease.
Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .).


Circuit topology for synchronizing neurons in spontaneously active networks.
Spike synchronization underlies information processing and storage in the brain. But how can neurons synchronize in a noisy network? By exploiting a high-speed (500-2,000 fps) multineuron imaging technique and a large-scale synapse mapping method, we directly compared spontaneous activity patterns and anatomical connectivity in hippocampal CA3 networks ex vivo. As compared to unconnected pairs, synaptically coupled neurons shared more common presynaptic neurons, received more correlated excitatory synaptic inputs, and emitted synchronized spikes with approximately 10(7) times higher probability. Importantly, common presynaptic parents per se synchronized more than unshared upstream neurons. Consistent with this, dynamic-clamp stimulation revealed that common inputs alone could not account for the realistic degree of synchronization unless presynaptic spikes synchronized among common parents. On a macroscopic scale, network activity was coordinated by a power-law scaling of synchronization, which engaged varying sets of densely interwired (thus highly synchronized) neuron groups. Thus, locally coherent activity converges on specific cell assemblies, thereby yielding complex ensemble dynamics. These segmentally synchronized pulse packets may serve as information modules that flow in associatively parallel network channels.


Probing DNA-lipid membrane interactions with a lipopeptide nanopore.
Association of DNA molecules with lipid bilayer membranes is of considerable interest for a large variety of applications in biotechnology. Here we introduce syringomycin E (SRE), a small pore-forming lipopeptide produced by the bacterium Pseudomonas syringae, as a facile sensor for the detection of DNA interactions with lipid membranes. SRE forms highly reproducible pores in cellular and artificial membranes. The pore structure involves bilayer lipids, which have a pronounced influence on open channel conductance and gating. SRE channels act as ionic diodes that serve as current rectifiers sensitive to the charge of the bilayer. We employ this intrinsic property to electronically monitor the association of DNA molecules with the membrane in a variety of different settings. We show that SRE can be used for quantitatively probing electrostatic interactions of DNA and DNA-cholesterol conjugates with a lipid membrane. Furthermore, we demonstrate that SRE channels allow monitoring of hybridization reactions between lipid-anchored probe strands and complementary strands in solution. In the presence of double-stranded DNA, SRE channels display a particularly high degree of rectification. Finally, the formation of multilayered structures assembled from poly-(L)-lysine and DNA oligonucleotides on the membrane was precisely monitored with SRE.


Costs of providing care for HIV-infected adults in an urban HIV clinic in Soweto, South Africa.
As access to antiretroviral therapy (ART) in sub-Saharan Africa expands, estimates of the costs of initiating and maintaining patients on ART are important to program planning, budgeting, and cost-effectiveness analyses. Total costs of providing HIV care, including ART, in an urban, nongovernmental, adult clinic in Soweto, South Africa, were estimated from October 2004 through March 2005. Personnel costs were estimated using individuals' work time and salary, and for across-organization services (eg, information technology), a proportion of entire annual costs was applied. Utilization of medications, laboratories, and radiographic tests were estimated by a random sample of patient charts (10%) and applied to the entire cohort. Nine hundred sixty-six adult patients received care during the study period (75% female, median age 34 years, median CD4 count at ART initiation: 109 cells/mm). Seventeen percent were stable on ART at entry, 61% initiated ART, and 22% did not receive ART over the course of the study. Mean cost of the entire program (in US $) was $92,388 per month, and mean per patient cost of care-regardless of ART treatment status-was $98.1 per month. Among adults on ART, costs were lowest for those already on ART ($119.0/month) and highest for those initiating ART ($209.7/month) in the first month and $130.0 the following month. Human resources and antiretrovirals each accounted for one third of overall costs. The monthly cost of treating HIV-infected patients in an urban South African clinic was highest in the month of initiation and lower for stable patients, with costs driven predominantly by antiretrovirals and personnel.


Transcatheter aortic valve implantation using a direct aortic approach: a single-centre Heart Team experience.
The transaortic (TAo) approach has been introduced as an alternative to transapical and transaxillary aortic valve implantation for patients with symptomatic severe aortic stenosis in whom a transfemoral approach is not feasible. However, only very limited data from a minimal number of specialized centres are available on this approach. Therefore, the aim of this study was to evaluate the early postoperative 30-day outcomes of the direct aortic approach performed by a single-centre multidisciplinary Heart Team. Between May 2011 and July 2013, 159 patients underwent transcatheter aortic valve implantation (TAVI) at our institution; of which, 44 were believed to benefit most from the TAo as assessed by a multidisciplinary Heart Team. All patients underwent an upper 'J' median hemi-sternotomy through a 6-cm incision. The evaluation of early operative results was made according to the Valve Academic Research Consortium (VARC) consensus criteria. These include device success endpoints and combined safety endpoints at 30 days. The mean age of the patients was 78 years, the mean logistic EuroSCORE was 25.9 ± 14.4% and the mean Society of the Thoracic Surgeons score 5.8 ± 4.5%. Seventeen patients (39%) underwent redo operations; 4 (9%) received a transcatheter valve in a degenerated bioprosthesis. The procedure was performed using the Medtronic CoreValve Revalving system in 36 patients, with the Edwards SAPIEN XT in 7 cases and the St Jude Medical Portico valve in 1. Device success was achieved in 90.8% of the cases. Complications included; major stroke (n = 1), re-exploration for cardiac tamponade (n = 3), transient renal failure requiring temporary haemodialysis (n = 1) and permanent pacemaker implantation (n = 5). There were no myocardial infarctions. The total 30-day mortality rate was 6.8% (3 patients). Postoperative intensive care unit stay was 2.6 ± 3.6 days, and the mean hospitalization was 12 ± 9.6 days. The TAo TAVI approach is feasible and offers a safe alternative for patients in whom a transfemoral approach is not feasible or desirable.


A Prediction Model for Types of Treatment Indicated for Patients with Temporomandibular Disorders.
To identify potential predictors of types of treatment indicated for patients with temporomandibular disorders (TMD) and to develop, validate, and calibrate a prediction model for type of treatment. The derivation cohort at baseline was comprised of 356 adult patients with TMD. Patient and disease characteristics were recorded at baseline as potential predictors. Types of treatment indicated for TMD patients were the end points of the model, classified into no treatment, physical treatment only (including splint and/or physiotherapy), and combined physical and psychological treatment. Multinomial logistic regression analysis was used to develop the prediction model. The internal validation, calibration, discrimination, and external validation of the model were determined. For practical use, the prediction model was converted into score charts and line charts. The score of each included predictor was produced based on the shrunken regression coefficients. Patient age, gender, anxiety, sleep bruxism, pain-related TMD, function-related TMD, stress, passive stretch of maximum mouth opening, and depression were significantly associated with the type of treatment indicated for TMD patients. The multinomial model showed reasonable calibration and good discrimination, with area under the curve values of 0.76 to 0.86. The internal validity of the model was good, with a shrinkage factor of 0.89. The external validity of the model was acceptable. Potential predictors in patient profiles for prediction of type of treatment indicated for TMD patients were identified. The internal validity, calibration, discrimination, and external validity of the model were acceptable.


Childhood asthma, air quality, and social suffering among Mexican Americans in California's San Joaquin Valley: "Nobody talks to us here".
Nearly one in five Mexican American children residing in California's San Joaquin Valley (the Valley) in 2007 had an asthma attack at some point in their life. Numerous epidemiological studies have suggested that compared with other ethnic groups and Latino subgroups residing in the United States, Mexican origin children have the lowest rates of pediatric asthma. Ethnographic research conducted in central California, however, suggests otherwise. Known for its agricultural produce, extreme poverty, and poor air quality, the Valley is a magnet for the Mexican immigrant farm worker population. We conducted an exploratory ethnographic study to examine health disparities, social suffering, and childhood asthma in the Valley. Many Valley residents believe that their children's health concerns are being ignored. Open-ended interviews uncovered a largely rural community suffering not only from the effects of childhood asthma but the inability to have their experiences taken seriously.


Effects of thyroidectomy on the metabolic clearance rate of prolactin and prolactin release in the rat.
The effects of thyroidectomy on both the secretion of rat prolactin (PRL) in vivo and the release of PRL from rat anterior pituitary glands (Aps) in vitro in the absence of ovarian steroids were studied. Rats were ovariectomized (Ovx) 42 days after thyroidectomy or sham-thyroidectomy. On day 15 following ovariectomy the rats were either decapitated for examining the in vitro release of PRL from AP or anesthetized for measuring the metabolic clearance rate (MCR) of rat PRL. After decapitation, blood samples were collected and APs were incubated with or without the extract of rat medial basal hypothalamus (rHE) at 37 degrees C for 4 h. The MCR of iodinated rat PRL was determined by a single injection method. Blood samples were collected by heart puncture at frequent intervals. Serum PRL concentrations of decapitated thyroidectomized-ovariectomized (TX-Ovx) rats were 56% lower than those found in Ovx rats. Thyroidectomy in Ovx rats resulted in a significant reduction of the spontaneous release of PRL from AP. The rHE decreased PRL levels in the medium after incubation with APs from sham Tx rats, but not those from Tx rats. MCR of PRL was reduced in Ovx rats by thyroidectomy. These results indicate that thyroidectomy reduces the spontaneous release of rat PRL by AP and secretion rate of rat PRL in the absence of ovarian steroids.


Immunolocalization of Leishmania (Viannia) braziliensis membrane antigens recognized by mAbs SST-2, SST-3, and SST-4.
The immunolocalization of Leishmania (Viannia) braziliensis stage-specific antigens recognized by mAbs was analysed by transmission electron microscopy. The antigen recognized by mAb SST-2 was present at the surface of promastigotes, including the flagellum and flagellar pocket. The reactivity of SST-2 with isolates of different serodemes showed a pronounced microheterogeneity in terms of the number of reactive bands within the low molecular weight range from 24 to 33 kDa. The 180 kDa glycoprotein recognized by mAb SST-3 was present only in the flagellar membrane. SST-3 also recognized multiple discrete bands from 160 to 200 kDa, as observed in several serodemes. In contrast, mAb SST-4, which recognizes a 98 kDa antigen, showed weak labelling on the promastigote surface by transmission electron microscopy and indirect immunofluorescence. Based on Western blotting, indirect immunofluorescence, and solid-phase radioimmunoassay, the antigens recognized by mAbs SST-2, SST-3 and SST-4 were present in all L. (V.) braziliensis analysed, from 7 different serodemes.


Emerging Multimodality Approaches to Treat Localized Esophageal Cancer.
Esophageal cancer has a poor prognosis, with 5-year survival rates ranging from 20% to 35% in the nonmetastatic setting. Despite advances in surgical techniques and optimization of chemoradiotherapy regimens, overall survival benefits have been incremental at best. Esophageal cancer requires a concerted multidisciplinary approach, perhaps more so than any other tumor type given the integral role played by the esophagus in maintaining calorific intake and the propensity for early spread through the lymphatics. This review describes the latest in surgical techniques to minimize postoperative complications and examines previous and ongoing systemic therapy approaches. Strategies that harness a patient's own immune system hold great promise, and shifting checkpoint inhibitors from the metastatic setting to the neoadjuvant/adjuvant setting is currently being evaluated in phase II and III clinical trials. In addition, a much better understanding of the interplay between tumors and their immune microenvironment is clearly needed to better judge how best to engage each patient's immune system, and there will be likely demonstrable differences between early-stage tumors and metastatic disease. This review highlights emerging data, which demonstrate that, in addition to The Cancer Genome Atlas classification of esophageal squamous cell carcinoma having a distinct molecular makeup compared with esophageal adenocarcinoma, there are also differing responses to PD-1 inhibitors. Histology and the underlying immune milieu may have important ramifications for the management of localized disease in the future, above and beyond PD-L1 expression, microsatellite instability status, and tumor mutational burden.


Intake of dietary fats and colorectal cancer risk: prospective findings from the UK Dietary Cohort Consortium.
Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ. We conducted a case-control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements. We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ. Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC.


Molecular biology of prions causing infectious and genetic encephalopathies of humans as well as scrapie of sheep and BSE of cattle.
Considerable progress has been made in deciphering the role of an abnormal isoform of the prion protein (PrP) in scrapie of animals and Gerstmann-Sträussler syndrome (GSS) of humans. Transgenic (Tg) mice expressing both Syrian hamster (Ha) and mouse (Mo) PrP genes, which encode proteins differing at 16 residues out of 254, were used to probe the mechanism of scrapie prion replication. Four Tg lines expressing HaPrP exhibited distinct incubation times ranging from 48 to 277 days after Ha prion inoculation, which were inversely correlated with the steady-state levels of HaPrP mRNA and HaPrPc. Bioassays of brain extracts from two scrapie-infected Tg lines showed that the prion inoculum dictates which prions are synthesized de novo, even though the cells express both PrP genes. Tg mice inoculated with Ha prions had approximately 10(9) ID50 units of Ha prions per gram of brain while less than 10 units of Mo prions were found. Conversely, Tg mice inoculated with Mo prions had approximately 10(6) ID50 units of Mo prions and less than 10 units of Ha prions. Consistent with the analysis of prion synthesis, Tg mice inoculated with Ha prions exhibited neuropathologic changes characteristic of hamsters with scrapie while Mo prions produced changes similar to those in non-Tg mice with scrapie. Our results argue that species specificity of scrapie prions resides in the primary structure of PrP and formation of infectious prions is initiated by a species-specific interaction between PrPSc in the inoculum and homologous, cellular PrP. Studies on Syrian, Armenian and Chinese hamsters suggest that the domain of the PrP molecule between codons 100 and 120 controls both the length of the incubation time and the deposition of PrP in amyloid plaques. Ataxic GSS in families shows genetic linkage to a mutation in the PrP gene leading to the substitution of Leu for Pro at codon 102. Discovery of a point mutation in the PrP gene from humans with GSS established that GSS is unique among human diseases--it is both genetic and infectious. These results have revised thinking about sporadic Creutzfeldt-Jakob disease (CJD) suggesting it may arise from a somatic mutation. Pulse-chase radiolabeling experiments of scrapie-infected cultures of mouse neuroblastoma cells indicate that protease-resistant PrPSc is synthesized during the chase period with t1/2 approximately 15 h from a protease-sensitive precursor, consistent with the conclusion that PrPc and PrPSc differ due to a post-translational event.(ABSTRACT TRUNCATED AT 400 WORDS)


Postoperative infection rates in foot and ankle surgery: a clinical audit of Australian podiatric surgeons, January to December 2007.
Surgical site infections are one of the most common post-operative complications encountered by foot and ankle surgeons. The incidence reported in the literature varies between 0.5 and 6.5%. The results of a 12-month Australia-wide clinical audit analysing the rates of postoperative infections in association with podiatric surgery are presented. De-identified patient data was collected from nine podiatric surgeons Australia-wide. Infections were identified according to Australian Council on Health Care Standards (ACHS) definitions and data was entered no earlier than thirty days post procedure. A total of 1339 patient admissions and 2387 surgical procedures were reported using the International Classification of Diseases (ICD-10) and Medicare Benefit Schedule (MBS) coding systems. The overall infection rate was 3.1% and the rate of infection resulting in hospital re-admission was 0.25%. The benchmark results presented in this paper suggest that infection rates associated with podiatric surgery are well within accepted industry standards as stated in recent literature.


The effect of fatigue and training status on firefighter performance.
Firefighting is a strenuous occupation that requires optimal levels of physical fitness. The National Fire Protection Association suggests that firefighters should be allowed to exercise on duty to maintain adequate fitness levels. However, no research has addressed the effect of exercise-induced fatigue on subsequent fire ground performance. Therefore, the primary purpose of this study was to determine the effect that a single exercise session had on the performance of a simulated fire ground test (SFGT). Secondarily, this study sought to compare the effect of physical training status (i.e., trained vs. untrained firefighters) on the performance of an SFGT. Twelve trained (age: 31.8 ± 6.9 years; body mass index [BMI]: 27.7 ± 3.3 kg·m(-2); VO2peak: 45.6 ± 3.3 ml·kg(-1)·min(-1)) and 37 untrained (age: 31.0 ± 9.0 years; BMI: 31.3 ± 5.2 kg·m(-2); VO2peak: 40.2 ± 5.2 ml·kg(-1)·min(-1)) male career firefighters performed a baseline SFGT. The trained firefighters performed a second SFGT after an exercise session. Time to complete the SFGT, heart rate, and blood lactate were compared between baseline and exercise SFGT (EX-SFGT) conditions. In the trained firefighters, time to complete the SFGT (9.6% increase; p = 0.002) and heart rate (4.1% increase; p = 0.032) were greater during the EX-SFGT compared with baseline, with no difference in post-SFGT blood lactate (p = 0.841). The EX-SFGT time of the trained firefighters was faster than approximately 70% of the untrained firefighters' baseline SFGT time. In addition, the baseline SFGT time of the trained firefighters was faster than 81% of the untrained firefighters. This study demonstrated that on-duty exercise training reduced the work efficiency in firefighters. However, adaptations obtained through regular on-duty exercise training may limit decrements in work efficiency because of acute exercise fatigue and allow for superior work efficiency compared with not participating in a training program.


Pharmacological Activation of Thermo-Transient Receptor Potential Vanilloid 3 Channels Inhibits Hair Growth by Inducing Cell Death of Hair Follicle Outer Root Sheath.
Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature-activated Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome, characterized by skin diseases and alopecia, indicating an important role for TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference, and pharmacological approaches. We found that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining, and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B and short-hairpin RNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle-related skin diseases.


Reassessing how society prioritizes the health of young people.
A number of important health policy issues, such as the allocation of flu vaccines during a pandemic, require society to determine priorities across different age groups. Cost-effectiveness analysis (CEA) and related methods of economic evaluation are often useful for determining optimal resource allocations. Using the examples of recently evaluated vaccine interventions, we show that current methods of CEA are likely to under-value health interventions for young people, relative to societal preferences inferred from research on age preferences and the value of health over time. These findings demonstrate important considerations regarding how society distributes health resources across age groups.


Autoantibody against N(epsilon)-(carboxymethyl)lysine: an advanced glycation end product of the Maillard reaction.
Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure.