Basic cardiovascular risk assessment in naïve patients with colon cancer.
Cardiovascular assessment of oncological patients suggests that cancer can lead to subclinical damage of the heart. The aim of the present study was to analyze the value of baseline cardiovascular biomarkers in patients with newly diagnosed colon cancer prior to treatment. Additionally, another aim was to establish baseline cut-off alert values for this low-intensity neoplastic damage. A total of 51 patients with newly diagnosed colon cancer, without history of cardiac disease, were enrolled in a prospective, cross-sectional study. All patients underwent clinical, biochemical and basic echocardiographic evaluation before starting treatment. Patients were assessed for myocardial damage using high-sensitivity troponin T (hs-TnT), creatine kinase-MB (CK-MB) and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A group of 28 healthy controls was included for comparison. Cardiac ultrasound revealed similar left ventricular (LV) ejection fraction but enlarged LV chambers compared with the control group (LV at end systole, 29.50 vs. 26.00 mm; LV at end diastole, 44.50 vs. 38.00 mm; P<0.001 in both cases). The levels of cardiovascular biomarkers of myocardial damage were higher in the patients than in the control group (CK-MB, 17.00 vs. 11.00 IU/l, P<0.001; hs-TnT, 8.20 vs. 3.00 ng/l, P<0.001; NT-proBNP, 155.40 vs. 48.50 pg/ml, P=0.001). In multivariate analysis, CK-MB and hs-TnT retained statistical significance (P=0.004 and P=0.045, respectively). Moreover, it was demonstrated that new cut-offs for hs-TnT (8.00 ng/l) and NT-proBNP (220.00 pg/ml) can identify cardiac damage in patients ≥65 years old. Thus, the present study confirmed the hypothesis that a basic cardiovascular assessment of treatment-naïve patients with colon cancer can identify important pre-treatment myocardial impact. Adapted cut-off values should be set for cardiovascular biomarkers in the cancer population, different from those currently accepted for acute coronary syndromes or heart failure.


An investigation of the impact of Melbourne Zoo's "Seal-the-Loop" donate call-to-action on visitor satisfaction and behavior.
Modern zoos are uniquely positioned to educate the public about environmental issues and promote conservation action. This report investigates the introduction of a donation request during an interactive fur seal presentation (as part of Melbourne Zoo's "Seal-the-Loop" initiative) on visitor satisfaction, perceptions of donation as a way to help wild fur seals, and donation behaviors. Comparisons are made between three groups surveyed upon exit: (1) viewed the interactive fur seal presentation prior to the donation request implementation (pledge-presentation: N = 86; see Mellish, Pearson, Sanders, and Litchfield []; International Zoo Yearbook 129:129-154); (2) viewed the interactive fur seal presentation including the donation request (donate-presentation: N = 82); and (3) viewed the fur seal exhibit and donation point but not the presentation and were not directly asked to make a donation (donate-exhibit: N = 82). Findings demonstrate visitor satisfaction with the interactive fur seal presentation was not negatively impacted following the implementation of the donate request (with >92% of pledge-presentation and donate-presentation visitors providing a "satisfied" or "very satisfied" rating). Only the donate-presentation visitors reported donation as a conservation action to help wild fur seals (19.18%; 0% for pledge-presentation visitors). While both donate-exhibit (39.51%) and donate-presentation visitors (60.75%) self-reported making donations or intending to do so, donation behavior was significantly increased for visitors who had viewed the fur seal presentation. Findings provide preliminary support that zoos may utilize interactive educational presentations to effectively ask visitors for donations to support specific conservation projects, without negatively impacting on satisfaction and with a relatively high level of visitor engagement.


Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione.
Dandruff/seborrhoeic dermatitis is a common scalp condition that is characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect tissue level events that are poorly understood at the molecular level. The purpose of this work was: (i) to compare gene expression profiles in subjects with dandruff vs. those of subjects without dandruff to determine the key physiological disruptions manifest in the condition; and (ii) to determine the effect on this profile of treatment with a shampoo containing potentiated zinc pyrithione (ZPT). In study 1, scalp biopsies were taken from 16 normal subjects and from involved and uninvolved sites in 15 subjects with dandruff. In study 2, 30 subjects with dandruff were treated for 3 weeks with a commercial ZPT shampoo (n = 15) or a vehicle (n = 15), and scalp lesional biopsies were collected at baseline and end of study for transcriptomic analysis. RNA was extracted from all biopsies and Affymetrix gene chips were used to analyse transcriptomic profiles, followed by bioinformatic analysis. Analysis of study 1 biopsies revealed more than 7000 individual probes differentially regulated in dandruff lesional skin relative to normal. Enriched Gene Ontology categories included: lipid metabolism, immune response, response to stimulus, apoptosis, cell proliferation, and epidermal development. The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. Induced inflammatory genes were also enriched in dandruff uninvolved skin, suggesting the existence of predisposing factors associated with inflammation. Many genes increased in lesional skin were increased at the level of protein in stratum corneum samples (e.g. IL-1RA, S100A8, S100A9, S100A11, IL-8). Under conditions known to improve overall scalp condition, the ZPT shampoo treatment in study 2 produced a transcriptomic profile resembling that of normal scalp skin. These data provide novel insights into the nature of dandruff and the therapeutic action of potentiated ZPT-containing shampoo, and provide a basis to explore many new mechanistic questions related to these topics.


Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan.
The pastoral lifestyle of Indigenous communities of Bajaur Agency is bringing them close to natural remedies for treating their domestic animals. Several studies have been conducted across the globe describing the importance of traditional knowledge in veterinary care. Therefore, this study was planned with the aim to record knowledge on ethnoveterinary practices from the remote areas and share sit with other communities through published literature. Data was gathered from community members through semi-structured interviews and analyzed through informant consensus factor (Fic) to evaluate the consent of current ethnoveterinary practices among the local people. In total, 73 medicinal plants were recorded under the ethnoveterinary practices. Most widely used medicinal plants with maximum use reports (URs) were Visnaga daucoides Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. New medicinal values were found with confidential level of citations for species including Heracleum candicans and Glycerhiza glabra. Family Apiaceae was the utmost family with high number (7 species) of medicinal plants. Maximum number of medicinal plants (32) was used for gastric problems. High Fic was recorded for dermatological (0.97) followed by reproductive (0.93) and gastrointestinal disorders (0.92). The main route of remedies administration was oral. Current study revealed that the study area has sufficient knowledge on ethnoveterinary medicinal plants. This knowledge is in the custody of nomadic grazers, herders, and aged community members. Plants with new medicinal uses need to be validated phytochemically and pharmacologically for the development of new alternative drugs for veterinary purposes.


[An experimental model of the lymphatic vessels transplantation].
The aim of this work is to describe a procedure of primary reconstruction of the lymphatic vessels on a model of heterotopic intestine transplantation in a rat. Both the donor and the recipient part of the procedure are described in a detail, as well as diagnostic methods of postoperative patency of the lympahatic anastomosis. In the end, the authors' own trial group is presented. However, no statistically significant differences were detected in histological findings of the intestinal graft rejection in rats with lymphatic anastomosis, compared with the control group.


Specific IgG glycosylation differences precede relapse in PR3-ANCA associated vasculitis patients with and without ANCA rise.
Immunoglobulin G (IgG) contains a conserved N-glycan in the fragment crystallizable (Fc), modulating its structure and effector functions. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) alterations of IgG Fc-glycosylation have been observed to correlate with the disease course. Here, we examined longitudinal changes in N-linked Fc glycans of IgG in an AAV patient cohort and their relationship with disease flares. Using liquid chromatography coupled with mass spectrometry, we analysed IgG Fc-glycosylation in 410 longitudinal samples from 96 individuals with AAV. Analysis of the cross-sectional differences as well as longitudinal changes demonstrated that IgGs of relapsing PR3-ANCA patients have higher ΔFc-bisection at diagnosis (P = 0.004) and exhibit a decrease in Fc-sialylation prior to the relapse (P = 0.0004), discriminating them from non-relapsing patients. Most importantly, PR3-ANCA patients who experienced an ANCA rise and relapsed shortly thereafter, exhibit lower IgG Fc-fucosylation levels compared to non-relapsing patients already 9 months before relapse (P = 0.02). Our data indicate that IgG Fc-bisection correlates with long-term treatment outcome, while lower IgG Fc-fucosylation and sialylation associate with impending relapse. Overall, our study replicated the previously published reduction in total IgG Fc-sialylation at the time of relapse, but showed additionally that its onset precedes relapse. Furthermore, our findings on IgG fucosylation and bisection are entirely new. All these IgG Fc-glycosylation features may have the potential to predict a relapse either independently or in combination with known risk factors, such as a rise in ANCA titre.


Biodegradable poly(L-lactic acid)-lavender nanocapsules: synthesis, controlled release, and application in remedy of sleep disorder.
In this study, nanocapsules of poly(L-lactic acid) (PLLA) containing lavender oil were synthesized by solvent evaporation emulsion. Poly(L-lactic acid) is a biodegradable aliphatic polyester derived from lactic acid formed by bacterial fermentation of glucose-rich substances. Lavender oil is a plant extract that finds uses in phytotherapy. It is reputed as anti-septic, anti-depressant and sleep promoter. Encapsulation is a technique used to encase tiny oil droplets with a thin and permeable coating that allows for a controlled release of the volatile oil. The size and morphology of the nanocapsules were characterized by scanning electron microscope. The particle size and distribution were measured by photon correlation spectroscopy. The time-controlled release of the lavender oil was studied and the use of the lavender capsules in the remedy of sleep disorder was investigated.


Comparison of normalization methods for differential gene expression analysis in RNA-Seq experiments: A matter of relative size of studied transcriptomes.
In recent years, RNA-Seq technologies became a powerful tool for transcriptome studies. However, computational methods dedicated to the analysis of high-throughput sequencing data are yet to be standardized. In particular, it is known that the choice of a normalization procedure leads to a great variability in results of differential gene expression analysis. The present study compares the most widespread normalization procedures and proposes a novel one aiming at removing an inherent bias of studied transcriptomes related to their relative size. Comparisons of the normalization procedures are performed on real and simulated data sets. Real RNA-Seq data sets analyses, performed with all the different normalization methods, show that only 50% of significantly differentially expressed genes are common. This result highlights the influence of the normalization step on the differential expression analysis. Real and simulated data sets analyses give similar results showing 3 different groups of procedures having the same behavior. The group including the novel method named "Median Ratio Normalization" (MRN) gives the lower number of false discoveries. Within this group the MRN method is less sensitive to the modification of parameters related to the relative size of transcriptomes such as the number of down- and upregulated genes and the gene expression levels. The newly proposed MRN method efficiently deals with intrinsic bias resulting from relative size of studied transcriptomes. Validation with real and simulated data sets confirmed that MRN is more consistent and robust than existing methods.


Scattering phase function of a charged spherical particle.
We deduced the scattering phase function (SPF) of a charged spherical particle, which is significantly different from the SPF of an uncharged spherical sphere. The difference between the SPF of a charged spherical particle and the SPF of an uncharged spherical sphere is related to the surface conductivity, particle size parameter, frequency of the electromagnetic (EM) waves, and refractive index of the particle. The surface charges carried by the particle make the backward scattering of EM waves increase. Given the EM wave frequency and the refractive index, there is a threshold of surface conductivity for each particle size number, beyond which the SPF mainly depends on the surface conductivity.


Nanostructured Silica/Gold-Cellulose-Bonded Amino-POSS Hybrid Composite via Sol-Gel Process and Its Properties.
It is demonstrated in this paper that silica nanoparticles coated with core/shell gold provide efficient thermal, optical, and morphological properties with respect to the cellulose-polyhedral oligomeric silsesquioxanes (POSS) hybrid system. The one-step synthesis of a silica/gold nanocomposite is achieved with a simultaneous hydrolysis and reduction of gold chloride in the presence of formic acid, and the trimethoxysilane group acts as a silica precursor. The focus here comprises the synthesis of cellulose-POSS and silica/gold hybrid nanocomposites using the following two methods: (1) an in situ sol-gel process and (2) a polyvinyl alcohol/tetrakis (hydroxymethyl)phosphonium chloride process. Accordingly, the silica/gold core/shell nanoparticles are synthesized. The growth and attachment of the gold nanoparticles onto the functionalized surface of the silica at the nanometer scale is achieved via both the sol-gel and the tetrakis (hydroxymethyl) phosphonium chloride processes. The cellulose-POSS-silica/gold nanocomposites are characterized according to Fourier transformed infrared spectroscopy, Raman, X-ray diffraction, UV, photoluminescence, SEM, energy-dispersive X-ray spectroscopy, TEM, thermogravimetric, and Brunauer-Emmett-Teller analyses.


Medial Patellofemoral Ligament Tear Associated with an Intra-articular Axial Spilt Osteochondral Fracture of the Lateral Femoral Condyle: a "Knee Trap-door" Fracture.
Medial patellofemoral ligament (MPFL) prevents lateral dislocation of the patella and acts as a major stabilizer. The tear could be associated with osteochondral avulsion fractures; however, intra-articular split fractures are not seen. Here, we present one unusual case of such a presentation. A 16-year-old male presented with a history of recurrent patellar dislocation and inability to bear weight following the last episode. The patient was diagnosed with an MPFL tear with an unusual intra-articular femoral condyle split fracture. The case had significant improvement in functional scores post-surgery. In physically active populations, twisting of the knee could result in an MPFL tear, leading to recurrent patellar dislocation. The treatment remains ligament reconstruction, open, or arthroscopic. Associated intra-articular fractures are very rare with such injuries and need to be addressed due to the high rate of non-union.


PROTOCOL: Effectiveness of economic development interventions in humanitarian settings in low- and middle-income countries: A mixed-method systematic review.
This is the protocol for a Campbell systematic review. The review will address the following research questions: (1) What are the effects of economic development interventions on the economic outcomes of people in humanitarian settings? What factors explain any observed variations in effect such as setting, programme design features or duration? (2) What are the effects of economic development interventions on the food security, nutrition, the psychosocial and mental health, and the physical health outcomes of populations in humanitarian settings? (3) What are the success factors and barriers that affect the implementation and effectiveness of economic development interventions on populations affected by humanitarian crisis?


Alanine polypeptide structural fingerprints at room temperature: what can be gained from non-harmonic Car-Parrinello molecular dynamics simulations.
Structural infrared fingerprints of neutral gas phase alanine peptides of increasing size and complexity (dipeptide, octapeptide, and beta-strand peptide) are characterized through DFT-based Car-Parrinello molecular dynamics simulations. Harmonic and nonharmonic vibrational signatures are calculated from the time correlation of the dipole moment of the gas phase peptide in a direct way (without any approximation) respectively from low temperature (20 K) and room temperature (300 K) molecular dynamics. Our main purpose is to answer the two following questions: (i) Is the direct inclusion of temperature for the calculation of infrared spectra mandatory for the comprehension of the vibrational signatures experimentally recorded at room temperature? (ii) To what extent is the amide I, II, and III domain sensitive enough to the local structure of the peptides, to provide vibrational signatures that can be definitely used to assess the peptide conformation at 300 K?


24-hour BP in children with congenital central hypoventilation syndrome.
To study circadian BP patterns in patients with congenital central hypoventilation syndrome (CCHS). Case-control study. Teaching hospital in Paris, France. Eleven patients with CCHS (median age, 13 years; range, 6 to 18 years) and 11 sex- and height-matched control subjects. None. Each subject underwent 24-h ambulatory BP monitoring. Oxygen saturation and end-tidal PCO(2) were monitored noninvasively. Polysomnography was performed to determine sleep times. All patients with CCHS received mechanical ventilation during sleep. Mean values for systolic BP (SBP) and diastolic BP (DBP) during wakefulness and sleep were analyzed. Nocturnal BP "dipping" was defined as the difference in mean SBP (and/or DBP) between wakefulness and sleep, divided by individual waking mean values. BP "dippers" were defined as subjects showing at least 10% nocturnal dipping. Patients with CCHS had BPs in the low normal range of normative data. As compared to control subjects, patients with CCHS had lower BP during wakefulness (p = 0.003 and p = 0.016 for SBP and DBP, respectively), and higher BP during sleep (p = 0.016 and p = 0.002). Nocturnal BP dipping was abnormally reduced in patients with CCHS (p = 0.000). Ten of the 11 patients with CCHS were BP nondippers, compared to none of the control subjects. The abnormal circadian BP pattern observed in children and adolescents with CCHS may be related to autonomic nervous dysfunction. Lifelong cardiovascular follow-up is recommended for patients with CCHS.


Perspective Taking and Avatar-Self Merging.
Today, avatars often represent users in digital worlds such as in video games or workplace applications. Avatars embody the user and perform their actions in these artificial environments. As a result, users sometimes develop the feeling that their self merges with their avatar. The user realizes that they are the avatar, but the avatar is also the user-meaning that avatar's appearance, character, and actions also affect their self. In the present paper, we first introduce the event-coding approach of the self and then argue based on the reviewed literature on human-avatar interaction that a self-controlled avatar can lead to avatar-self merging: the user sets their own goals in the virtual environment, plans and executes the avatar's actions, and compares the predicted with the actual motion outcomes of the avatar. This makes the user feel body ownership and agency over the avatar's action. Following the event-coding account, avatar-self merging should not be seen as an all-or-nothing process, but rather as a continuous process to which various factors contribute, including successfully taking the perspective of the avatar. Against this background, we discuss affective, cognitive, and visuo-spatial perspective taking of the avatar. As evidence for avatar-self merging, we present findings showing that when users take the avatar's perspective, they can show spontaneous behavioral tendencies that run counter to their own.


Ethnobotanical inventory and medicinal perspectives of herbal flora of Shiwalik mountainous range of District Bhimber, Azad Jammu and Kashmir, Pakistan.
The present study was carried out to document traditional ethnobotanical knowledge (TEK) of herbal flora of District Bhimber, Azad Jammu and Kashmir (AJK), Pakistan to explore medicinal potential of wild indigenous plants (WIPs) for drug discovery. The research data was conducted during years 2015-2017 using questionnaire proforma employing structured and semi-structured interview models. The informants belonged from indigenous communities comprising of both genders with age ranging from 35-105 years. The interviews were conducted using local translator or guide who knew the dialects of all local languages. The study produced ethnobotanical inventory of 173 herbal species belonging to 45 families and out of these Poaceae was dominant family with 27 species. It was explored that maximum herbal species depicted multi-usage especially food, fodder and fuel. Among 173 herbal plant species, 69% species were used as fodder, 72% species as fuel source, 9.8% as ethnoveterinary medicines, 16% for home construction, 12% for cosmetics, 5.2% as honeybee plants and 2.7% were used as fiber source by the local people. Many local plants have been in promulgation for cure of different diseases in traditional cultures such as for cure of stomach problems, cough, cancer, jaundice, kidney diseases, diabetes, snake biting and tooth problems. Different parts of plants such as leaf, root, stem bark, flower, seed and gums are used for the treatment of different diseases by the local people. The major aliments being cured are classified into 12 disease categories by using informant consensus factor (ICF) protocol. According to ICF, the highest numbers of plant species were used against wound healing, snake bite, skin diseases, eye diseases and asthma. Fidelity level (FL) was assessed to check the reliability and use consistency of herbal drugs by the indigenous communities of the study area. The use value index (UVI) of different herb species ranged from 0.29 to 0.57 while the highest value was calculated for Alternanthera pungens L. (UVI: 0.57). Relative frequency of citation (RFC) value was calculated on the bases of the response of the interviewees recorded during survey in correlation with authenticating of traditional data. The RFC values represented the relative popularity of individual species in study area according to their use values. The highest value was calculated for Alternanthera pungens L. (0.90) and followed by Achyranthes aspera L. (0.80. The study reveals that many species are known for commonly used in traditional ethnomedicines (TEMs). Due to different biotic and abiotic factors in conjunction with climatic changes many herbal flora of Shiwalik mountain range (SMR) of District Bhimber of AJK is under threat. The factors like habitat loss, overgrazing, construction of communication infrastructure, silviculture practices, shelter construction (houses) and other more domestic use of wild land by clearing wild lands are boosting towards plant biodiversity loss. There is dare need to work on comprehensive exploration of TEMs to discover neo drugs from wild indigenous plants and do work for conservation of wild flora of the area for future generations.


Theory of plasmon-assisted transmission of entangled photons.
The recent surface plasmon entanglement experiment [Nature (London) 418, 304 (2002)]] is theoretically analyzed. The entanglement preservation upon transmission in the nonfocused case is found to provide information about the interaction of the biphoton and the metallic film. The entanglement degradation in the focused case is explained in the framework of a fully multimode model. This phenomenon is a consequence of the polarization-selective filtering behavior of the metallic nanostructured film. It is shown that the "which-way" labels that degrade entanglement are not located in the degrees of freedom of the metallic film but rather in the spatial degrees of freedom of the photon field.


Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.
Species A rotavirus non-structural protein 3 (NSP3) is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A) binding protein (PABP) from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD). We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E), whereas one mutation had the opposite effects (Y192A). Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.


Heterobasidiomycetes form symbiotic associations with hepatics: Jungermanniales have sebacinoid mycobionts while Aneura pinguis (Metzgeriales) is associated with a Tulasnella species.
In order to evaluate substrate dependence of the symbiotic fungal associations in leafy liverworts (Jungermanniopsida), 28 species out of 12 families were investigated by transmission electron microscopy and molecular methods. Samples were obtained from the diverse substrates: from naked soil, from the forest floor on needle litter, from between peat moss, from rotten bark of standing trees, and from stumps and rotten wood. Associations with ascomycetes were found in most of the specimens independent from the substrate. Seven species sampled from soil were found to contain basidiomycete hyphae. Ultrastructure consistently showed dolipores with imperforate parenthesomes. Molecular phylogenetic studies revealed that three specimens belonging to the Jungermanniales were associated with members of Sebacinaceae, while Aneura pinguis (Metzgeriales) was associated with a Tulasnella species. These taxa are so far the only basidiomycetes known to be symbiotically associated with leafy liverworts. The probability that the associations with Sebacinaceae are evolutionary old, but the Tulasnella associations more derived is discussed. The sebacinoid mycobionts form a similar interaction type with the jungermannialian leafy liverworts as do the associated ascomycetes. The term 'jungermannioid mycorrhiza' is proposed for this distinctive symbiotic interaction type.


Long-term weight loss: the effect of pharmacologic agents.
We reviewed 20 English-language weight-reduction studies, reported between 1967 and March 1993, of the effect of > or = 6 mo of pharmacologic therapy on weight loss and its maintenance to determine the clinical benefits of extended treatment, propose treatment guidelines, and identify future research needs. Pharmacologic agents included phentermine, mazindol, fenfluramine, dexfenfluramine, and fluoxetine. Study designs varied with respect to blinding, use of a single agent vs a combination, dosing, length of therapy, patient selection, adjunctive therapy, and visit frequency. At endpoint, weight loss varied from study to study but a plateauing of weight loss or weight regain was observed after approximately 6 mo. The benefits of extended treatment appear to outweigh the risks for those patients who are unable to lose sufficient weight without pharmacologic therapy but who maintain adequate weight loss with long-term pharmacologic therapy. Future studies should define and evaluate pharmacologically responsive and unresponsive subgroups.


Comparative evaluation of antioxidant reactivity within obstructed and control rabbit urinary bladder tissue using FRAP and CUPRAC assays.
Partial urinary bladder outlet obstruction mediates cyclic ischemia and reperfusion resulting in the generation of both reactive oxygen species and reactive nitrogen species. It is theorized that with an increase in the level of free radicals, the level of protective antioxidants should decrease. To test this hypothesis, two electron transfer assays, the FRAP method and the CUPRAC method, were used to determine the level of antioxidant reactivity of obstructed and control bladder tissue. The results showed that the CUPRAC assay detected a significant decrease in the reactivity of antioxidants found within the obstructed bladder tissue as compared to the control bladder tissue in both the muscle and mucosa. The FRAP assay did not detect any difference between the muscle and mucosa of the obstructed and control bladder tissue.


Comparing the prevalence of chronic pain after sternotomy in patients undergoing coronary artery bypass grafting using the internal mammary artery and other open heart surgeries.
The prevalence of chronic postoperative pain after cardiac surgery has been reported from 17% to 56%. We aimed to compare the prevalence of postoperative pain between patients who had undergone CABG using the internal mammary artery (IMA) and those who had undergone other cardiac surgeries including CABG using the saphenous vein or cardiac valvular surgeries. In this cohort study, medical records of 188 patients were evaluated and divided into two equal groups (94 in each group); patients who had undergone CABG using the IMA (IMA group) and those who had undergone other cardiac surgeries using the saphenous vein or other cardiac valvular surgeries (non-IMA group). The patients' data were recorded in a self-structured questionnaire and then phone interviews were performed 3 months after the operations regarding the rate of postoperative pain. The severity of chronic pain was rated based on the numerical rating pain scale. The two groups differed significantly regarding the prevalence of pain (P = 0.023). In the IMA group, 83 (88.3%) patients experienced pain lasting for more than three months compared to 71 (75.5%) patients in non-IMA group. The two groups differed significantly with respect to the severity of chronic pain after cardiac surgery via sternotomy (P = 0.001). The groups did not differ significantly regarding the effects of chronic pain on their sleep, referral to a physician, and drug consumption to alleviate their pain. The IMA group experienced more complications at work and during their occupational activity. The rate and severity of chronic pain after cardiac surgery via sternotomy was higher in patients undergoing CABG with separation of IMA for revascularization.


Levels of vascular endothelial growth factor and matrix metalloproteinase-9 proteins in patients with glioma.
To investigate the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) proteins in patients with glioma, in order to determine if either protein has prognostic value. The presence of VEGF and MMP-9 proteins in paraffin-embedded tumour specimens from patients with glioma was detected using immunohistochemistry. The correlation between the levels of VEGF and MMP-9 proteins and tumour grade was analysed. A total of 32 patients with low-grade gliomas (World Health Organization [WHO] grade II) and 48 patients with high-grade gliomas (WHO grades III-IV) participated in the study. Positive immunohistochemical staining of VEGF and MMP-9 proteins was detected in 58/80 (72.5%) and 60/80 (75.0%) of patients, respectively. The level of VEGF immunostaining was significantly positively correlated with the level of MMP-9 immunostaining (r = 0.78). Significantly more high-grade gliomas (grades III-IV) demonstrated positive VEGF and MMP-9 immunostaining compared with the low grade gliomas (grades I-II). These data suggest that VEGF and MMP-9 play an important role in the malignant behaviour of gliomas.


Inhibition of heterosensory thalamocortical evoked potentials by delta-9-tetrahydrocannabinol.
The effects of delta-9-tetrahydrocannabinol on sensory activity in the thalamic intralaminar nuclei, centralis lateralis and the mesencephalic reticular formation were compared with the effects on cortical association or heterosensory systems in alpha-chloralose-anesthetized cats. The drug depressed the anterior marginal responses to multiple-modality sensory stimulation 30 min after administration of 2 mg/kg. Posterior suprasylvian responses were not significantly depressed except during 15 min postadministration. The drug did not depress sensory responses at the centralis lateralis or the mesencephalic reticular formation. Cortical responses evoked by stimulation of the latter were globally depressed by the drug. In contrast, delta-9-tetrahydrocannabinol depressed the anterior marginal response to centralis lateralis stimulation and not the posterior suprasylvian response similarly to the responses to sensory stimulation. The drug was without effect on caudate nucleus responses to stimulation of the mesencephalic reticular formation or centralis lateralis. These data demonstrate that, unlike pentobarbital, delta-9-tetrahydrocannabinol maintains heterosensory afferent activity to mesencephalic and thalamic sites and that its unique properties appear to be due, in part, to the selective disruption of heterosensory thalamocortical function.


Phylogenetic analyses of Ixodes rugicollis with notes on its morphology in comparison with Ixodes cornutus.
The subgenus Pholeoixodes contains Ixodes species typically associated with birds that nest in cavities or with carnivorous mammals that are burrow-dwelling. Among ticks infesting the latter, Ixodes rugicollis is regarded as the rarest species in the western Palearctic. Despite the unique morphology of this species, its identification (especially of subadult stages) is difficult, and molecular-phylogenetic data to offer other diagnostic methods and a better understanding of its taxonomy are not available. In this study, a female and a male of I. rugicollis were collected in Romania. The female was compared morphologically to another female of this species collected in France and to the lectotype of Ixodes cornutus (from Tajikistan), which has similar morphology and host association. Following DNA extraction, two mitochondrial (cytochrome c oxidase subunit I: cox1 and the 16S rRNA gene) and two nuclear genetic markers (18S and 28S rRNA genes) of I. rugicollis were amplified and analyzed in a phylogenetic context. Females of I. rugicollis and I. cornutus differed in the shape of their palps, scutum and areae porosae and the size of peritremes, but they were similar in palpal setal length, dental formula and arrangement of anal setae. Measurements of two I. rugicollis females examined were not less different from each other than from I. cornutus. Phylogenetically, I. rugicollis clustered with other members of its subgenus. The topology of all trees showed the position of bat-associated tick species of the subgenus Eschatocephalus among Pholeoixodes species. For the first time to our knowledge, this study provides high-resolution digital pictures of male and female I. rugicollis as well as corresponding molecular data. Morphological comparison of this species with I. cornutus could not resolve uncertainties in the validity of the latter species, which can only be accomplished after collecting new specimens of I. cornutus and consequent molecular comparisons. This study includes the first comprehensive molecular-phylogenetic analysis of western Palearctic Pholeoixodes species based on both nuclear and mitochondrial genetic markers and including I. rugicollis. The results of these confirm the phylogenetic position of subgenus Eschatocephalus within Pholeoixodes, justifying the need to merge them to comply with the taxonomic criterion of monophyly.


Cell cycle control in the early embryonic development of aquatic animal species.
The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease.


Landfill leachate-induced toxicity in mice.
Microbial, plant and studies in aquatic animals have shown that landfill leachate is toxic. However, more information about its effects in terrestrial animals is required. As a part of ongoing research into the toxic effects of landfill leachate in Nigeria, we evaluated the acute effects of raw and simulated leachates from Abadina, Orita-Aperin and Oworonsoki dump sites, all in Southwest Nigeria, in mice. Raw leachates were obtained directly from the dumps while the simulated leachates were obtained from the solid wastes in the laboratory by using the ASTM method. The samples were designated Abadina raw leachate (ARL), Orita-Aperin raw leachate (OARL) and Oworonsoki raw leachate (OWRL); and Abadina simulated leachate (ASL), Orita-Aperin simulated leachate (OASL) and Oworonsoki simulated leachate (OWSL). Their physico-chemical properties were determined in accordance with standard analytical methods. Young male mice (12-15 wk) weighing 24-31 g were exposed to 1%, 5%, 10%, 25%, 50% and 100% concentrations of each test samples for 5 consecutive days and were observed for a period of 96 h for toxic response. Mortality recorded at different times for each sample at the various concentrations was mostly within the last 48 h of the exposure period. The LC50 obtained are 100% for both ARL and OARL, and 50% for OWRL; and 83.50% and 50% for ASL and OWSL, respectively. It was indeterminate for OASL. Apart from this, other toxic effects like weight loss, sluggishness, loss of hair and reduced food intake were observed. The investigated samples were ranked as OWRL > OWSL > ASL > OARL > ARL > OASL. The observed effects were due to the toxic constituents present in the leachate samples. This suggests that the mixtures have the potential to cause harmful effect to public health and our environment through seepage into ground or surface water.


Insulinotropic effect of cinnamaldehyde on transcriptional regulation of pyruvate kinase, phosphoenolpyruvate carboxykinase, and GLUT4 translocation in experimental diabetic rats.
Diabetes mellitus is a chronic metabolic disorder affecting about 6% of population worldwide with its complications and is rapidly reaching epidemic scale. Cinnamomum zeylanicum is widely used in alternative system of medicine for treatment of diabetes. In the present study, we have performed bioassay guided fractionation of chloroform extract of C. zeylaniucm and identified cinnamaldehyde (CND) as an active principle against diabetes. In continuation to it, a detailed study was undertaken to elucidate its mode of antidiabetic action in STZ induced diabetic rats. Oral administration of CND (20 mg/kg bw) to diabetic rats for 2 months showed significant improvement (p<0.001) in muscle and hepatic glycogen content. In vitro incubation of pancreatic islets with CND enhanced the insulin release compared to glibenclamide. The insulinotropic effect of CND was found to increase the glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues. The treatment also showed a significant improvement in altered enzyme activities of pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) and their mRNA expression levels. Furthermore, the median lethal dose (LD(50)) of CND could not be obtained even at 20 times (0.4 g/kg bw) of its effective dose. With the high margin of safety of CND, it can be developed as a potential therapeutic candidate for the treatment of diabetes.


Systematic review of the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion for the treatment of refractory chronic cluster headache.
This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache. Various medical databases were used to perform a systematic review of the scientific literature. The search for articles continued until 31 October 2016, and included clinical trials, systematic reviews and/or meta-analyses, health technology assessment reports, and clinical practice guidelines that included measurements of efficiency/effectiveness or adverse effects associated with the treatment. The review excluded cohort studies, case-control studies, case series, literature reviews, letters to the editor, opinion pieces, editorials, and studies that had been duplicated or outdated by later publications from the same institution. Regarding effectiveness, we found that SPG stimulation had positive results for pain relief, attack frequency, medication use, and patients' quality of life. In the results regarding safety, we found a significant number of adverse events in the first 30 days following the intervention. Removal of the device was necessary in some patients. Little follow-up data, and no long-term data, is available. These results are promising, despite the limited evidence available. We consider it essential for research to continue into the safety and efficacy of SPG stimulation for patients with refractory chronic cluster headache. In cases where this intervention may be indicated, treatment should be closely monitored.


Review of pediatric functional outcomes measures used to evaluate surgical management in pediatric patients with an upper extremity fracture.
For two decades, many scores, questionnaires, and rating systems have been used to evaluate the functional outcome of children with an upper extremity fracture (UEF). However, only a few of these were created specifically for children, and many assess only elbow function. In the absence of any published review on this topic, we set out to identify and categorize different scores used to evaluate the clinical and functional outcomes of surgically treated pediatric UEFs. A literature search was performed, and 38 studies were identified. The scores used more often were the shortened version of the Disability of the Arm, Shoulder and Hand questionnaire and the Mayo Elbow Performance Score/Index. In a lower number of studies, authors used other scoring systems, including the Mayo Wrist Score, the Patient-Rated Wrist Evaluation, the Patient-Rated Elbow Evaluation, the Métaizeau functional scoring system, the Oxford Elbow Score, the Price and Flynn criteria, the Hardacre Functional Score, the Neer Shoulder Score, the Constant-Murley Shoulder Score, the Modified Orthopedic Trauma Association Score, the Medical Outcomes Study Short Form-36, and the Pediatric Outcomes Data Collection Instrument. Some specific pediatric scoring systems to evaluate the functional outcome of children with a UEF have been suggested, but a single tool that is valid and reliable for skeletally immature patients of all ages is not yet available. Further studies are needed to identify specific pediatric measurements to increase validity, responsiveness, sensitivity, and interpretability of upper limb functional outcome scores in common clinical practice.


Cocaine: A Rare Cause of Left-Sided Renal Infarction.
Cocaine abuse is commonly associated with myocardial ischemia, mesenteric ischemia, and cerebrovascular accidents. Renal infarction is an uncommon complication of cocaine abuse. Various mechanisms have been postulated for this cocaine-related injury. There are only 15 cases reported on cocaine-induced renal infarction. Among the cases with available data, very few cases had left kidney involvement. We report a case of a 65-year-old African American man with history of cocaine abuse who presented with left flank pain and had left renal infarction.


Protease-activated receptors: novel central role in modulation of gastric functions.
Protease-activated receptors (PARs) are members of a subfamily of G-protein-coupled receptors that regulate diverse cell functions in response to proteolytic cleavage of an anchored peptide domain that acts as a 'tethered' receptor-activating ligand. PAR-1 and PAR-2 in particular are present throughout the gastrointestinal (GI) tract and play prominent roles in the regulation of GI epithelial function, motility, inflammation and nociception. In a recent article in Neurogastroenterology and Motility, Wang et al. demonstrate, for the first time, that PAR-1 and PAR-2 are present on preganglionic parasympathetic neurons within the rat brainstem. As in other cellular systems, proteases such as thrombin and trypsin activate PAR-1 and PAR-2 on neurons of the dorsal motor nucleus of the vagus (DMV), leading to an increase in intracellular calcium levels via signal transduction mechanisms involving activation of phospholipase C and inositol triphosphate (IP3). The authors also report that the level of PAR-1 and PAR-2 transcripts in DMV tissue is increased following experimental colitis, suggesting that inflammatory conditions may modulate neuronal behavior or induce plasticity within central vagal neurocircuits. It seems reasonable to hypothesize, therefore, that the activity and behavior of vagal efferent motoneurons may be modulated directly by local and/or systemic proteases released during inflammation. This, in turn, may contribute to the increased incidence of functional GI disorders, including gastric dysmotility, delayed emptying and gastritis observed in patients with inflammatory bowel diseases.


Retrotransposition and cell-to-cell transfer of foamy viruses.
A remarkable feature of the prototype foamy virus (PFV) replication pathway has been reported to consist of the ability to retrotranspose intracellularly with high efficiency (M. Heinkelein, T. Pietschmann, G. Jármy, M. Dressler, H. Imrich, J. Thurow, D. Lindemann, M. Bock, A. Moebes, J. Roy, O. Herchenröder, and A. Rethwilm, EMBO J. 19:3436-3345, 2000). PFV intracellular retrotransposition (IRT) was reported to be enhanced by coexpression of fusion-defective envelope protein. To investigate the possibility of cell-to-cell transfer of PFV genomes, which could mimic IRT, we performed cocultivation experiments with cells transfected with an IRT-competent and marker gene-expressing PFV vector together with cells expressing a different marker and measured cells positive for both markers. The findings corroborated the initial report on IRT of Env-deficient PFV. Furthermore, they indicated that viral cores that have incorporated fusion-deficient Env can be transferred from cell to cell in a cell type-specific manor. One possible explanation consists of a minor alternative cleavage site in Env that can be used to expose the fusion peptide of the Env transmembrane protein, which appears to be required for virus uptake.


Treatment of arsenical keratosis and Bowen's disease with acitretin.
Long-term exposure to arsenic is associated with the development of arsenical keratosis, Bowen's disease, squamous cell carcinoma, and basal cell carcinoma. The efficacy of acitretin therapy was examined in two patients with cutaneous arsenical neoplasms. Lipid profile, hematological and liver function tests were performed regularly during the therapy at monthly intervals. After the third month of treatment, improvement of lesions of arsenical keratosis and Bowen's disease were observed in both patients. For the first patient who received 1 mg/kg daily acitretin for 10 months nearly total clearing was obtained at the end of therapy. The second patient discontinued the treatment after a period of 5 months because of symptomatic side-effects. During therapy no new lesions and no laboratory side-effects were observed in either patient. Although these results need to be confirmed by larger, long-term trials, it appears that acitretin is effective in the treatment of Bowen's disease related with arsenic, as well as arsenical keratosis.


PPARα Targeting GDF11 Inhibits Vascular Endothelial Cell Senescence in an Atherosclerosis Model.
Atherosclerosis (AS) is a complex vascular disease that seriously harms the health of the elderly. It is closely related to endothelial cell aging, but the role of senescent cells in atherogenesis remains unclear. Studies have shown that peroxisome proliferator-activated receptor alpha (PPARα) inhibits the development of AS by regulating lipid metabolism. Our previous research showed that PPARα was involved in regulating the repair of damaged vascular endothelial cells. Using molecular biology and cell biology approaches to detect senescent cells in atherosclerosis-prone apolipoprotein E-deficient (Apoe -/-) mice, we found that PPARα delayed atherosclerotic plaque formation by inhibiting vascular endothelial cell senescence, which was achieved by regulating the expression of growth differentiation factor 11 (GDF11). GDF11 levels declined with age in several organs including the myocardium, bone, central nervous system, liver, and spleen in mice and participated in the regulation of aging. Our results showed that PPARα inhibited vascular endothelial cell senescence and apoptosis and promoted vascular endothelial cell proliferation and angiogenesis by increasing GDF11 production. Taken together, these results demonstrated that PPARα inhibited vascular endothelial cell aging by promoting the expression of the aging-related protein GDF11, thereby delaying the occurrence of AS.


Assessment of the Peradeniya Organophosphorus Poisoning Scale as a Severity and Prognostic Marker in Patients With Acute Organophosphorus Poisoning Presenting to an Emergency Medicine Department.
Background Organophosphorus (OP) compound poisoning is the most common toxicological medical emergency in India, where the majority of the population lives on agriculture. The Peradeniya Organophosphorus Poisoning (POP) scale can be a simple and effective system to determine the need for ventilatory support early in the course of admission. The objective of this study was to evaluate the prognostic value of the clinical parameters of the POP scale in predicting the severity of organophosphorus compound poisoning, by comparing early predicted patient prognosis evaluated by the POP scale on admission with the patient outcome. Methods This was a prospective observational study of acute organophosphorus compound poisoning presenting to the emergency department of Sir Sayajirao General (SSG) Hospital and Medical College, Baroda. We included patients over 12 years of age with a history of, or symptoms suggestive of, acute OP poisoning. The patients received initial resuscitation according to airway, breathing, circulation, disability, and exposure simultaneously with decontamination and gastric lavage by Ryle's tube. They also received the standard antidotes of atropine and pralidoxime immediately. We applied the POP scale to each patient upon admission and graded the poisoning severity as mild (a POP scale score of 0-3), moderate (4-7), or severe (8-11). This scale assessed the patients' need for mechanical ventilation and ICU management and their final clinical outcome. Results We enrolled 60 patients in the study. Most of them were under 20 years of age, and 65% of them were male. Social laborers were the major population, and most of them had suicidal intention. Monocrotophos was the most commonly consumed OP compound. Most of the patients were brought to the hospital within two to six hours of consumption. Vomiting and profuse secretions were the primary presenting symptoms. A majority of the patients (47) fell into the mild POP scale range. None of the patients had severe poisoning. Out of 60 patients, 49 patients improved and 11 patients died. Seven patients (15%) with mild POP scale scores and four patients (31%) with moderate scores died. Overall, 61.7% of patients with mild POP scale scores and 100% of patients with moderate scores needed mechanical ventilation. Conclusion The POP scale is an effective tool to measure severity and make a prognosis in patients with acute OP compound exposure. It may be a simple, inexpensive tool that may help predict the need for ventilatory support at admission. Early identification of danger signs may help in the reduction of mortality and morbidity when resources are limited. However, we found incorporating other clinical parameters and biochemical markers provides better prognostication than using the POP scale alone.


Application of curve resolution algorithms in the study of drug photodegradation kinetics -- the example of moclobemide.
The photodegradation of moclobemide was studied in methanolic media. Ultra-HPLC (UHPLC)/MS/MS analysis proved decomposition to 4-chlorobenzamide as a major degradation product and small amounts of Ro 16-3177 (4-chloro-N-[2-[(2-hydroxyethyl)amino] ethyl]benzamide) and 2-[(4-chlorobenzylidene)amino]-N-[2-ethoxyethenyl]ethenamine. The methanolic solution was investigated spectrophotometrically in the UV region, registering the spectra during 30 min of degradation. Using reference spectra and a multivariate chemometric method (multivariate curve resolution-alternating least squares), the spectra were resolved and concentration profiles were obtained. The obtained results were in good agreement with a quantitative approach, with UHPLC-diode array detection as the reference method.


Prediction of lithium dose: a mathematical alternative to the test-dose method.
A method of estimating the optimal dose of lithium is presented. The charts of 548 patients were reviewed to obtain data regarding the factors thought to affect the lithium dose, and an equation to estimate the dose was derived by stepwise multiple linear regression. The equation was also applied to 390 patients to determine the difference between the estimated and the actual dose; the mean difference was only 19 mg/day and the standard deviation was 325 mg/day. Lithium level, presence of a cyclic antidepressant, age, sex, and weight were found to be important variables for estimation of lithium dose.


Isolation and characterization of the sarcoplasmic reticulum of skeletal muscle.
The sarcoplasmic reticulum (SR) of rabbit skeletal muscle was studied after isolation of a vesicle fraction and of vesicular subfractions by means of differential and density gradient centrifugations. The different fractions were examined electron microscopically by negative and positive staining; their content in protein and phospholipid and their ability to bind Ca(++) were determined. After homogenization, differential centrifugation yielded a "sarcovesicular fraction" (SVF) which was mainly composed of numerous vesicles of different types mixed with fibrous proteins and mitochondrial fragments. This SVF contained 2% of the protein and 25% of the phospholipid of the initial tissue extract. It had a high Ca(++) binding activity that was preserved for several days by storage in the presence of oxalate. After centrifugations of the SVF on sucrose density gradients, two vesicular subfractions were obtained which were characterized by different sedimentation rates, isopycnic banding, morphology, and composition in protein and phospholipid. (a) The low-density subfraction (rho 1.10-1.12) contained a heterogeneous population of membranous structures: thick- and thin-walled vesicles, tubular formations, triads, and plasma membranes. Its content in protein and phospholipid was very low. (b) The high-density subfraction (rho 1.13-1.17) was a very pure subfraction composed only of thin-walled vesicles. Its content in phospholipid was high and the ratio of phospholipid-phosphorus to protein was about 20. The calcium-binding activity found in the total SVF was recovered only in this latter homogeneous subfraction. The origin of these two subfractions from the SR is discussed.


Epigenetics, depression and antidepressant treatment.
The heritability of major depression has been documented in a number of epidemiologic studies. Twin studies have estimated the heritability at about 37% and these estimation can rise up to 70% if severity, relapse rate and age of onset are considered. Despite the relative importance of genetic risk factors in the pathogenesis of this disease, molecular genetic studies, including large genome-wide association studies, only a very small number of candidate genes, explaining little of the variance have been identified. This fact has been termed "missing heritability" and could be accounted by a number of factors including that the presumed causal variants are not tagged by the current genetic approaches, that major depression is truly polygenic, with each polymorphism only contributing very small increases in risk, unaccounted environmental influences and complex epigenetic factors. Epigenetics refers to the regulation of DNA transcription without alteration of the original sequence and is controlled by DNA methylation, histone modifications and non-coding RNAs and can be transmitted through generations. A number of clinical and preclinical studies suggest that epigenetic mechanisms could play an important role in the pathogenesis and treatment of major depression. So far, most studies investigated genes within the hypothalamicpituitary- adrenal (HPA) axis or the neurotrophin system. It is also of interest that current psychopharmacologic drugs including antidepressants, antipsychotics and mood stabilizers may exert some of their effects by inducing epigenetic changes. Most notably, epigenetic alterations are potentially reversible and accessibe for drug treatment, which lead to the development of novel classes of antidepressant drugs.


Reliability of police-reported information for determining crash and injury severity.
Posted speed limit and police-reported injury codes are commonly used by researchers to approximate vehicle impact and occupant injury severity. In-depth crash investigations, however, produce more precise measures of crash and injury severity: change in velocity (delta-V) for crash severity and Abbreviated Injury Scale (AIS) scores for injury severity. A comparison of data from police crash reports with that gathered by National Automotive Sampling System (NASS) investigators highlighted the inadequacy of speed limit and police injury codes as proxies for delta-V and AIS injury severity. In general, delta-V increased with speed limit and higher values of AIS were associated with higher police-coded injury severity, but there were a number of anomalies. In particular, 49% of the drivers coded by police as having incapacitating injuries actually had sustained no more than minor injuries. This overstatement of injury severity was less frequent among male (44%) and elderly (37%) drivers than among female (53%) and nonelderly (50%) drivers. Also, 79% of the investigated vehicles that crashed on roads posted at 60 mph (96 km/h) or higher experienced a delta-V less than 25 mph (40 km/h). Safety studies depending on data from only police reports to establish injury or crash severity therefore could produce erroneous results.


Progesterone--promoter or inhibitor of breast cancer.
Based on the results of a French cohort of postmenopausal women, it has been claimed that micronized progesterone does not enhance breast cancer risk. The impact of reproductive factors on breast cancer risk and a high prevalence of occult breast carcinomas at the time of menopause suggest an involvement of endogenous progesterone in the development of breast cancer. High mammographic density in the luteal phase and during treatment with estrogen/progestogen combinations reflect a change in the composition of mammary stroma and an increased water accumulation in the extracellular matrix which is caused by hygroscopic hyaluronan-proteoglycan aggregates. Proteoglycans are also involved in the regulation of proliferation, migration, and differentiation of epithelial cells and angiogenesis, and may influence malignant transformation of breast cells and progression of tumors. Reports on a lack of effect of estrogen/progesterone therapy on breast cancer risk may be rooted in a selective prescription to overweight women and/or to the very low progesterone serum levels after oral administration owing to a strong inactivation rate. The contradictory results concerning the proliferative effect of progesterone may be associated with a different local metabolism in normal compared to malignant breast tissue. Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection.


Influences on patient participation and decision-making in care.
Encouragement for patients to participate in their own care and to share decision-making with nurses and doctors is a common theme in the literature and government directives. But how do patients feel about it? An observation-and-interview-based study found five main factors that influenced patients' willingness and ability to actively participate in their care.


Head banging persisting during adolescence: A case with polysomnographic findings.
Head banging is a sleep-related rhythmic movement disorder of unknown etiology. It is common during infancy; however, available literature suggests that prevalence decreases dramatically after childhood. We report the case of a 16-year-old male who presented with head banging. The symptoms were interfering with his functioning and he had been injured because of the same in the past. We are presenting the video-polysomnographic data of the case. Possible differential diagnoses, etiology, and treatment modalities are discussed. The boy was prescribed clonazepam and followed up for 3 months. Parents did not report any episode afterward.


Trafficking and subcellular localization of multiwalled carbon nanotubes in plant cells.
Major barriers to delivery of biomolecules are crossing the cellular membranes and achieving a high cytoplasmic concentration by circumventing entrapment into endosomes and other lytic organelles. Motivated by such aim, we have investigated the capability of multiwalled carbon nanotubes (MWCNTs) to penetrate the cell membrane of plant protoplasts (plant cells made devoid of their cell walls via enzymatic treatment) and studied their internalization mechanism via confocal imaging and TEM techniques. Our results indentified an endosome-escaping uptake mode of MWCNTs by plant protoplasts. Moreover, short MWCNTs (<100 nm) were observed to target specific cellular substructures including the nucleus, plastids, and vacuoles. These findings are expected to have a significant impact on plant cell biology and transformation technologies.


[Protective effect of Yiqi Mingmu solution on rat's retina with ischemia reperfusion injury].
To investigate the protective effect of the Yiqi Mingmu solution irrigated into rat on retinal injury of rat induced by ischemia reperfusion. SD rats were divided into four groups randomly: negative control group, model control group, low and high dose group. Increasing the intraocular pressure with anterior chambers infused liquid induced the models of retinal ischemia reperfusion of rats. Different doses of Yiqi Mingmu solution were respectively irrigated into rats 7 days before ischemia in low and high dose group. Normal salire instead was used in normal and model control group. At 1, 3, 7, 15 days after the ischemia reperfusion injury, the content of MDA and activity of SOD in rat's retina were measured. The histopathologic changes were observed with transmission electron microscopy and light microscopy. At 3, 7, 15 days after the ischemia reperfusion injury, the activity of SOD in Yiqi Mingmu solution low and high dose group were higher than in the model control group, the content of MDA in Yiqi Mingmu solution high dose group were lower than in the model control group. The histopathologic injury of retina in the Yiqi Mingmu solution low and high dose group were less than in the model control group. Yiqi Mingmu solution has protective effect on rat's retina ischemia reperfusion injury, and it is an effective traditional Chinese recipe to treat the diseases of retina ischemia.


Cardiovascular disease in diabetes and operative risk.
Among the complications of diabetes, cardiovascular disease is one of the most frequent, severe and invalidating. In the era before the introduction of insulin treatment, the most frequent cause of death in diabetes were acute metabolic and infectious complications; at present, after the introduction of insulin therapy and the consequent major change in the clinical evolution of the disease, the most frequent cause of death is due to cardiovascular complications. From the Framingham study it is possible to observe that in the adult diabetic population, the annual incidence of death from cardiovascular causes is about 17%, both in men and women, as against 8.5% in non diabetic males and 3.6% in non diabetic females. Major clinical forms of cardiovascular disease in diabetics are myocardial ischemia, autonomic neuropathy and cardiomyopathy.


Transcatheter embolization of an isolated lumbar arterial bleeding complicating radical nephrectomy for renal infarction with infected perirenal haematoma.
Lumbar arterial bleedings are rare but potentially life threatening. We report a case of an isolated right lumbar arterial bleeding after radical nephrectomy for renal infarction with infected perirenal haematoma. The diagnosis was suggested by computed tomography and confirmed with angiography. Definitive treatment of this vascular injury was obtained after percutaneous transcatheter embolization of the fourth right lumbar artery. General anaesthesia, further blood loss due to difficult surgical dissection, or even failure to find and ligate the injured artery, especially in redo-operations, can be avoided by this minimal invasive procedure. Endovascular embolization of a lumbar artery injured after radical nephrectomy might be a valuable treatment alternative in patients with postoperative retroperitoneal bleeding.


micro-Oxo-bis{{2,2'-[2,2-dimethylpropane-1,3-diylbis(nitrilomethylidyne)]diphenolato}oxorhenium(V)}
The title compound, [Re(2)O(3)(C(19)H(20)N(2)O(2))(2)], is a hexacoordinate complex containing an [Re(2)O(3)](4+) core with a linear O=Re-O-Re=O bridge. The distorted octahedral coordination of the Re(V) atom is achieved by an N(2)O(2) donor set from the tetradentate imine-phenol ligand. The overall charge of the compound is neutral due to deprotonation of the phenol groups, and the terminating and bridging O atoms. The Re=O and Re-O bond distances of the [Re(2)O(3)](4+) core are 1.699 (4) and 1.911 (1) A, respectively. The Re-O and Re-N bond distances of the equatorial plane are in the ranges 2.024 (4)-2.013 (4) and 2.128 (5)-2.120 (5) A, respectively.


Barriers for integrating personalized medicine into clinical practice: a qualitative analysis.
Personalized medicine-tailoring interventions based on individual's genetic information-will likely change routine clinical practice in the future. Yet, how practitioners plan to apply genetic information to inform medical decision making remains unclear. We aimed to investigate physician's perception about the future role of personalized medicine, and to identify the factors that influence their decision in using genetic testing in their practice. We conducted three semi-structured focus groups in three health regions (Fraser, Vancouver coastal, and Interior) in British Columbia, Canada. In the focus groups, participants discussed four topics on personalized medicine: (i) physicians' general understanding, (ii) advantages and disadvantages, (iii) potential impact and role in future clinical practice, and (iv) perceived barriers to integrating personalized medicine into clinical practice. Approximately 36% (n = 9) of physicians self-reported that they were not familiar with the concept of personalized medicine. After introducing the concept, the majority of physicians (68%, n = 19 of 28) were interested in incorporating personalized medicine in their practice, provided they have access to the necessary knowledge and tools. Participants mostly believed that genetic developments will directly affect their practice in the future. The key concerns highlighted were physician's access to clinical guidelines and training opportunities for the use of genetic testing and data interpretation. Despite the challenges that personalized medicine can create, in general, physicians in the focus groups expressed strong interest in using genetic information in their practice if they have access to the necessary knowledge and tools.


Associations between co-detected respiratory viruses in children with acute respiratory infections.
Viruses are the major etiological agents of acute respiratory infections (ARIs) in young children. Although respiratory virus co-detections are common, analysis of combinations of co-detected viruses has never been conducted in Japan. Nineteen respiratory viruses or subtypes were surveyed using multiplex real-time PCR on 1,044 pediatric (patient age < 6 years) ARI specimens collected in Osaka City, Japan between January 2010 and December 2011. In total, 891 specimens (85.3%) were virus positive (1,414 viruses were detected), and 388 of the virus-positive specimens (43.5%, 388/891) were positive for multiple viruses. The ratio of multiple/total respiratory virus-positive specimens was high in children aged 0-35 months. Statistical analyses revealed that human bocavirus 1 and human adenovirus were synchronously co-detected. On the other hand, co-detections of human parainfluenza virus type 1 (HPIV-1) with HPIV-3, HPIV-3 with human metapneumovirus (hMPV), hMPV with respiratory syncytial virus A (RSV A), hMPV with influenza virus A (H1N1) 2009 (FLUA (H1N1) 2009), RSV A with RSV B, and human rhinovirus and FLUA (H1N1) 2009 were exclusive. These results suggest that young children (<3 years) are highly susceptible to respiratory viruses, and some combinations of viruses are synchronously or exclusively co-detected.


L-carnitine administration reduces number of episodes in cyclic vomiting syndrome.
Patients with cyclic vomiting syndrome suffer from recurring episodes of severe nausea and vomiting. This paper presents 6 patients who responded to 1-carnitine administration. Average time between episodes was 1.7 months before carnitine administration and increased to 1.1 years after carnitine administration. Average dose of carnitine administered was 50 mg/kg. Oral carnitine may be useful to control the symptoms in patients with cyclic vomiting syndrome.


Pharmacological properties of blood pressure and heart rate control in suncus.
Blood pressure and heart rate and responses to various physiological substances in suncus were characterized and compared with those in mice. The blood pressures of the two species were similar, but the heart rate of suncus (about 400 beat/min) was significantly lower than that of mice. Norepinephrine increased the blood pressure but decreased the heart rate in suncus. The latter was blocked by cervical vagotomy. Sensitivities to acetylcholine and isoproterenol were lower in suncus. These results suggest that regulation of blood pressure and heart rate in suncus is very unique and different from the well-defined system of the rodents.


Component interactions and electron transfer in toluene/o-xylene monooxygenase.
The multicomponent protein toluene/o-xylene monooxygenase (ToMO) activates molecular oxygen to oxidize aromatic hydrocarbons. Prior to dioxygen activation, two electrons are injected into each of two diiron(III) units of the hydroxylase, a process that involves three redox active proteins: the ToMO hydroxylase (ToMOH), Rieske protein (ToMOC), and an NADH oxidoreductase (ToMOF). In addition to these three proteins, a small regulatory protein is essential for catalysis (ToMOD). Through steady state and pre-steady state kinetics studies, we show that ToMOD attenuates electron transfer from ToMOC to ToMOH in a concentration-dependent manner. At substoichiometric concentrations, ToMOD increases the rate of turnover, which we interpret to be a consequence of opening a pathway for oxygen transport to the catalytic diiron center in ToMOH. Excess ToMOD inhibits steady state catalysis in a manner that depends on ToMOC concentration. Through rapid kinetic assays, we demonstrate that ToMOD attenuates formation of the ToMOC-ToMOH complex. These data, coupled with protein docking studies, support a competitive model in which ToMOD and ToMOC compete for the same binding site on the hydroxylase. These results are discussed in the context of other studies of additional proteins in the superfamily of bacterial multicomponent monooxygenases.


Exploring the declines in older driver fatal crash involvement.
The number of drivers 70 and older is growing at a fast pace, and older drivers are keeping their licenses longer and driving more. Despite these trends, older driver crash deaths and fatal crash involvements declined steadily during the decade 1997-2006 following an upward trend for many years. The present study explored various facets of the decline in older driver fatal crash involvement during 1997-2006. Declines in the rates of older driver fatal crashes were found per licensed driver and per population during 1997-2006; crash involvement per mile traveled also declined during 1995-2001. Relative to drivers aged 35-54, driver fatal crash involvement rates declined at significantly faster rates for drivers 70 and older, and an even more substantial decline was experienced by drivers 80 and older. Especially notable were greater declines in fatal crash involvement rates for intersection crashes and two-vehicle crashes among older drivers relative to drivers aged 35-54; such crash types have accounted for disproportionate numbers of crashes among older drivers in the past.


Comparison of propofol-alfentanil and propofol-remifentanil anaesthesia in percutaneous nephrolithotripsy.
Percutaneous nephrolithotripsy (PCNL) is used for the fragmentation and removal of stones from the renal pelvis and renal calyceal systems. We compared the effects of propofol-alfentanil or propofol-remifentanil anaesthesia on haemodynamics, recovery characteristics and postoperative analgesic requirements during percutaneous nephrolithotripsy. Thirty non-premedicated patients were randomly allocated to receive either propofol-alfentanil (Group A) or propofol-remifentanil (Group R). The loading dose of the study drug was administered over 60 s (alfentanil 10 microg kg(-1) or remifentanil 1 microg kg(-1)) followed by a continuous infusion (alfentanil 15 microg kg(-1) h(-1) or remifentanil 0.15 microg kg(-1) min(-1)). Propofol was administered until loss of consciousness and maintained with a continuous infusion of 75 microg kg(-1) min(-1) in both groups. Atracurium was given for endotracheal intubation at a dose of 0.5 mg kg(-1) and maintained with a continuous infusion of 0.4 mg kg(-1) h(-1). Mean arterial pressure heart rate, the total amount of propofol, time of recovery of spontaneous ventilation, extubation and eye opening in response to verbal stimulus and analgesic requirement were recorded. In Group A, mean arterial pressure was higher at the first minute in the prone position, and during skin incision and lithotripsy, and heart rate was higher during skin incision and lithotripsy when compared with Group R (P < 0.05). The total amount of propofol did not differ between groups. Time of recovery of spontaneous ventilation, extubation and eye opening were significantly shorter in Group R than Group A (P < 0.05). Both propofol-remifentanil and propofol-alfentanil anaesthesia provided stable haemodynamics during percutaneous nephrolithotripsy, whereas propofol-remifentanil allowed earlier extubation.


Dose calculation along the nonwedged direction for externally wedged beams: improvement of dosimetric accuracy with comparatively moderate effort.
Wedge filters ideally modify photon intensities only in one direction. However, in the other, the "nonwedged" direction, the intensity is affected too; it usually decreases with increasing off-axis distance. For external wedges on a particular treatment machine (Varian Clinac 2100C) and 6 MV photons, for example, this decrease is as big as 8%, depending on wedge angle and material, off-axis distance, and phantom depth. We present a way to account for this effect in prescriptions to points off-center in the nonwedged direction. The goal was to minimize the amount of additional data required for this purpose, without unduly compromising the final prescription accuracy. We measure the effective attenuation coefficients in narrow beam geometry for the wedge materials (lead and steel) as a function of thickness and off-axis angle, and the corresponding attenuation in water, again as a function of wedge material thickness and off-axis angle. The data allow us to extract a correction factor for off-axis distances in the nonwedged direction. Neglecting the contribution of scattered radiation and using primary beam data only, shortens data acquisition and simplifies calculations, but still yields surprisingly accurate results. Application of the derived correction reduces the off-axis distance related dose calculation error in wedged fields to < or =1%.


AGREEMENT BETWEEN PHYSICAL BEST AND FITNESSGRAM CRITERION-REFERENCED STANDARDS FOR MUSCULAR STRENGTH AND ENDURANCE.
To verify the agreement between PHYSICAL BEST and FITNESSGRAM health-related criteria for muscle strength and endurance. This agreement study had a sample of 81 children and adolescents. Participants were submitted to the PHYSICAL BEST (Sit-up and Pull-up) and FITNESSGRAM (Curl-up and Modified Pull-up) test batteries. Additionally, FITNESSGRAM also proposed criteria for Pull-up test. Results of tests were classified in accordance with their respective criteria. Each group had an interval of seven days between the first and second battery of tests. Statistical analysis used the Kappa index (p<0.05). Sit-up and Curl-up tests among the boys agreed in 72.2% (Kappa=0.368; p=0.004) of cases, and for the girls, in 64.4% (Kappa=0.130; p=0.076). Pull-up (PHYSICAL BEST versus FITNESSGRAM) agreed in 83.3% (Kappa=0.599; p<0.001) for boys. The agreement between Pull-up and Modified Pull-up (PHYSICAL BEST versus FITNESSGRAM) for boys was 47.2% (Kappa=0.071; p=0.533), and for girls, 44.5% (Kappa=0.102; p=0.120). The agreement between the Pull-up and Modified Pull-up tests (FITNESSGRAM) for boys was 58.4% (Kappa=0.215; p=0.143), and for girls, 44.5% (Kappa=0.102; p=0.120). For individual analysis over time, as well as for the comparison of passing rates between different populations, caution is advised when using different criterion-referenced standards for strength and endurance, particularly if using different tests.


Fate of grainhandlers with bronchial hyperreactivity.
Bronchial reactivity to methacholine and to grain dust were determined in a group of grainhandlers whose spirometry was being studied prospectively. Six workers showed specific bronchial responses to grain dust (indicative of occupational asthma), 21 did not show reactivity to grain dust but had bronchial hyperreactivity to methacholine and 40 had neither. Those with hyperreactivity were older, had lower FEV1 at initial examination and were more likely to experience a significant decline in FEV1 over a single working shift. Over 6 years of follow-up, those with hyperreactivity were not more likely to leave work and although they showed a more rapid decline in lung function over the period, because of the small number of individuals studied the difference between those with and without bronchial hyperreactivity was not significant. Among those with hyperreactivity to methacholine, there was a significant positive association between change in FEV1 over a single workshift and change in FEV1 over six years of followup, not seen in those without hyperreactivity to methacholine. Moreover, reactivity to methacholine was a stable observation over 6 years in the majority of studied individuals. We conclude that in the presence of bronchial hyperreactivity to methacholine, change in FEV1 over a single workshift more precisely predicts the trend in FEV1 over time in grainhandlers.


The Aging Care 5Ms Competencies: A Modified Delphi Study to Revise Medical Student Competencies for the Care of Older Adults.
To revise the 2009 Canadian Geriatrics Society (CGS) Core Competencies in the Care of Older Persons for Canadian Medical Students by applying current frameworks and using a modified Delphi process. The working group chose the Geriatric 5Ms model and CanMEDS framework to develop and structure the competencies. National (i.e., Canadian) Delphi participants were recruited, and 3 Delphi survey rounds were conducted from 2019-2021. Each survey round collected quantitative data using a 7-point Likert scale (LS) and qualitative data using free-text comments. The purpose of the first round was to establish the importance of the components of the proposed competencies (categorized into 13 subsections) and identify additional themes. The second round assessed agreement with 31 proposed competencies organized into 7 themes: aging, caring for older adults, mind, mobility, medications, multi-complexity, and matters the most. The third survey rated agreement levels after further revisions to the competencies were applied. The final 33 competencies were shared with survey participants for feedback and other stakeholders for external validation. Mean LSs for the importance of the 13 competency component subsections on the first survey varied from 5.11-6.54, with an agreement level of 73-93%. New themes emerged from the qualitative comments. Mean LSs for the 31 competencies on the second survey ranged from 5.57-6.81, with an agreement level of 80-97%. Mean LSs for the revised competencies on the third survey ranged from 5.83-6.65, with an agreement level of 83-95%. The authors developed the 33 Aging Care 5Ms Competencies for Canadian medical students using a consensus process. The competencies fulfill an important need in medical education, and ultimately, society. The authors strongly believe that the competencies can be woven into existing undergraduate medical curricula through purposeful integration and collaboration, including with other specialties.


[Estimating the net cost of clinical hematologic studies].
The authors describe the method for estimating the net cost of hematologic clinical laboratory studies, which is based on the development of a standard basis. Reference value of the productive time of physicians and laboratory assistants was estimated from consumption elements using auto-recording of a work day. It has made up 71 percent of physicians' work time and 75 percent of laboratory assistants' work time. Development of cost account in public health system, introduction of standard mechanisms for the formation and distribution of resources will augment the regulating role of such planned and calculated differentiated parameters as net cost, cost, labour intensity of medical workers. Development of a standard basis and estimation of net cost of investigations will help a clinical diagnostic laboratory to convert to new forms of economy and to render paid medical service to institutions and citizens.


Influencing factors of loneliness among older adults in China: a systematic review and meta-analysis.
China has a large and rapidly growing older population. Loneliness is associated with a range of negative health outcomes in older adults. However, to date, there is still a lack of comprehensive and systematic evidence on the factors influencing loneliness among older adults in China. Nine Chinese and English databases were searched by computer from inception to March 2022: China Knowledge Network, WanFang Data, Chinese Scientific Journal Database, SinoMed, PubMed, Embase, Web of Science, PsycINFO, and Cochrane Library. Studies on factors influencing loneliness among older adults in China were included. Two reviewers independently completed the literature screening, quality evaluation, and data extraction, and statistical analyses were performed using Review Manager 5.4 software. A total of 15 studies were included in the review, with 47 066 participants in total. Fifty-nine influencing factors of loneliness in older Chinese were involved. Twenty factors with a total of 30 subfactors that were involved in two or more studies and with extractable data were included in the data synthesis. Eleven subfactors were not statistically significantly associated with loneliness, namely, male, female, lower age, higher education level, health status-fair, health status-poor, social support-none/low, no health insurance, smoking, alcohol consumption, and body mass index-overweight and above (all P > 0.05), while the remaining 19 subfactors (concerning 15 factors) were significantly associated with loneliness in older adults in China (all P < 0.05). This study suggested that age, education level, marital status, living arrangement, having (no) children, receiving family support, relationship with family members, being with or without chronic diseases, health status, activities of daily living, social support, social activities, financial status, satisfaction with housing conditions, and the decision-making right for major household expenditures were the main influencing factors of loneliness among older adults in China.


Photochemotherapy (PUVA) in the pretumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.
Fifty-one patients with mycosis fungoides of pretumour stage were treated with oral 8-MOP and UVA photochemotherapy (PUVA). Complete remission was induced within 2--3 months in 58% of the cases. Twenty-seven patients are still in remission on maintenance therapy 9--53 months after starting treatment. In 9 cases PUVA treatment was stopped due to therapeutic failure and in another 15 cases due to various side effects. Maintenance therapy was given weekly, monthly, or at even longer intervals. Maintenance at long intervals seems preferable.


Comparing Practice Intentions and Patterns of Family Physicians in Canada.
In Canada, competency-based medical education prepares family medicine (FM) graduates to provide a broad scope of practice (SoP). We compared the practice intentions of FM residents at the end of training with actual practice patterns of early career family physicians (FPs) for SoP activities reflective of comprehensive family medicine. We collected self-reported data from cross-sectional family medicine longitudinal surveys for exiting FM residents in 2015 and 2016 and from a separate cohort of FPs who were 3 years into practice in 2018 and 2019 from 15 programs. We measured outcomes from exiting FM residents intending to participate in SoP activities and FPs participating in 15 SoP domains of family medicine. A total of 1,409 exiting FM residents (58.2% response rate) and 523 early career FPs (21% response rate) responded to the surveys. A high correlation existed between the percentage of exiting residents who intended to participate in each SoP activity and the percentage of FPs who participated in those activities (r2=0.95). However, we found statistically significant declines in the percentage of FPs reporting involvement in the SoP activities compared to their reported practice intentions for 14 of the 15 domains. We saw the greatest declines in providing care in long-term care facilities, rural communities, emergency departments, intrapartum care, and care for Indigenous populations (P<.001). While SoP patterns are highly correlated with practice intentions, early-career FPs are less likely to provide care as intended for all SoP activities. Further research is needed on the factors influencing practice patterns in specific areas to determine how FP graduates can be supported to provide comprehensive care.


Targeted therapies in metastatic renal cell carcinoma: the light at the end of the tunnel.
The year 2006 will mark a turning point in the daily management of patients with metastatic renal cell carcinoma. The impact of immunotherapy with interferon-alpha or interleukin-2 has been shown to be restricted to a minority of patients. The growing understanding of molecular mechanisms involved in the pathogenesis of the disease, especially clear-cell carcinoma, has led to the development of multiple targeted therapies with significant clinical benefits. Two compounds that predominantly inhibit the tyrosine kinase activity of the vascular endothelial growth factor receptor have been shown to improve the progression-free survival of patients in first- (sunitinib versus interferon-alpha) or second-line (sorafenib versus placebo) treatment. Temsirolimus, an agent that inhibits the serine-threonine kinase activity of the mammalian target of rapamycin, offers better overall survival than interferon in patients with poor-risk characteristics. Further studies are needed to determine the optimal combinations of these agents in metastatic disease and to assess their impact in the adjuvant setting.


Plasminogen activator inhibitor type 1 gene polymorphism and sepsis.
Plasminogen activator inhibitor type 1 (PAI-1) is a 50-kilodalton glycoprotein of the serine protease inhibitor family. The primary role of PAI-1 in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators. In addition to this function, PAI-1 acts as an acute-phase protein during acute inflammation. PAI-1 is a pivotal player in the pathogenesis of sepsis, a complex clinical syndrome that results from a systemic inflammatory response. In patients with sepsis, the levels of PAI-1 are positively related to poor outcome, increased severity of disease, and increased levels of various cytokines, acute-phase proteins, and coagulation parameters. The 4G/5G insertion/deletion promoter polymorphism, which leads to differences in PAI-1 production, has been demonstrated to affect the risk of developing severe complications and dying from sepsis during meningococcal infection and multiple trauma.


Blind source separation based x-ray image denoising from an image sequence.
Blind source separation (BSS) based x-ray image denoising from an image sequence is proposed. Without priori knowledge, the useful image signal can be separated from an x-ray image sequence, for original images are supposed as different combinations of stable image signal and random image noise. The BSS algorithms such as fixed-point independent component analysis and second-order statistics singular value decomposition are used and compared with multi-frame averaging which is a common algorithm for improving image's signal-to-noise ratio (SNR). Denoising performance is evaluated in SNR, standard deviation, entropy, and runtime. Analysis indicates that BSS is applicable to image denoising; the denoised image's quality will get better when more frames are included in an x-ray image sequence, but it will cost more time; there should be trade-off between denoising performance and runtime, which means that the number of frames included in an image sequence is enough.


Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.
Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor. Mechanical damage to nerve tissue is a feature of complex surgical procedures. To explore this aspect of VS treatment, the authors compressed rat auditory nerves with 2 different degrees of injury while monitoring the compound action potentials of the auditory nerve and the auditory brainstem responses. In this experimental model, the axons of the auditory nerve were quantitatively and highly selectively damaged in the cerebellopontine angle without permanent compromise of the blood supply to the cochlea. The temporal bones were processed for immunohistochemical analysis at 1 week and at 8 weeks after compression. Reactive gliosis was induced not only in the auditory nerve but also in the cochlear nucleus following mechanical trauma in which the general shape of the auditory brainstem response was maintained. There was a substantial outgrowth of astrocytic processes from the transitional zone into the peripheral portion of the auditory nerve, leading to an invasion of dense gliotic tissue in the auditory nerve. The elongated astrocytic processes ran in parallel with the residual auditory neurons and entered much further into the cochlea. Confocal images disclosed fragments of neurons scattered in the gliotic tissue. In the cochlear nucleus, hypertrophic astrocytic processes were abundant around the soma of the neurons. The transverse diameter of the auditory nerve at and proximal to the compression site was considerably reduced, indicating atrophy, especially in rats in which the auditory nerve was profoundly compressed. The authors found for the first time that mechanical stress to the auditory nerve causes substantial reactive gliosis in both the peripheral and central auditory pathways within 1-8 weeks. Progressive reactive gliosis following surgical stress may cause dysfunction in the auditory pathways and may be a primary cause of progressive hearing loss following microsurgical treatment for VS.


Changes in lamina structure are followed by spatial reorganization of heterochromatic regions in caspase-8-activated human mesenchymal stem cells.
Apoptosis is fundamental to the regulation of homeostasis of stem cells in vivo. Whereas the pathways underlying the molecular and biochemical details of nuclear breakdown that accompanies apoptosis have been elucidated, the precise nature of nuclear reorganization that precedes the demolition phase is not fully understood. Here, we expressed an inducible caspase-8 in human mesenchymal stem cells, and quantitatively followed the early changes in nuclear organization during apoptosis. We found that caspase-8 induces alteration of the nuclear lamina and a subsequent spatial reorganization of both centromeres, which are shifted towards a peripheral localization, and telomeres, which form aggregates. This nuclear reorganization correlates with caspase-3 sensitivity of lamina proteins, because the expression of lamin mutant constructs with caspase-3 hypersensitivity resulted in a caspase-8-independent appearance of lamina intranuclear structures and telomere aggregates, whereas application of a caspase inhibitor restrains these changes in nuclear reorganization. Notably, upon activation of apoptosis, we observed no initial changes in the spatial organization of the promyelocytic leukemia nuclear bodies (PML-NBs). We suggest that during activation of the caspase-8 pathway changes in the lamina structure precede changes in heterochromatin spatial organization, and the subsequent breakdown of lamina and PML-NB.


[Fractional and component composition of dust in the air of workplace at machinery enterprise].
The authors present results of assessment of fractional and component composition of dust entering workplace of machinery enterprises. The results prove topicality of data accumulation on actual contents of dusts for more reliable and precise evaluation of the dusts mixture influence on the workers' health.