Novel navigation surgery using image fusion of PET/CT and sonography for axillary neoplasm: First experience.
Ultrasound sonography (US)-guided navigation systems are widely used in various organs, including the breast and liver, to locate precisely lesions that are difficult to palpate or isolate after being identified by other imaging techniques. A recent new method, "volume navigation" (Vnav), delivers real-time image fusion of US with other modalities such as MRI, CT, and PET/CT to facilitate identification and excision of suspected pathology. The present report describes a novel navigation technique using Vnav-PET/CT, which delivers image fusion of US with PET/CT. To identify the axillary targets using Vnav-PET/CT, we set at least two landmarks then injected 0.2ml viscous blue dye in and around the capsule, which resulted in precise resection. Case 1: A 53-year-old woman with 2 PET/CT-positive lymph nodes in the right axilla underwent easy identification of the targets using the navigation technique followed by lymph node dissection. Among 32 lymph nodes dissected, only the two lymph nodes stained by blue dye were shown histologically to be malignant. Case 2: A 68-year-old woman had a PET/CT-positive lymph node in the left axilla. Vnav-PET/CT easily identified the target, which was successfully dissected under local anaesthesia. This navigation and marking using Vnav-PET/CT helped us easily approach the target, resulted in less surgical time, and avoided unsatisfactory axillary complications. These advances of the navigation system enable us to perform precise minimally invasive surgery. This is the first report of navigation surgery using Vnav-PET/CT, which may assist minimally invasive procedures, especially in the axilla.


Segmental atresia of the transverse colon in a foal with concurrent equine herpes virus-1 infection.
Segmental atresia of the transverse colon was observed at necropsy in a neonatal foal. The dorsal and ventral components of the large colon were fused, and ended blindly. The small colon was collapsed and completely closed at its cranial end. The right and left dorsal and ventral colons were fused into one blind-ended tube. Histologically, eosinophilic intranuclear inclusion bodies demonstrative of Equine Rhinopneumonitis were present in the thymus.


Ethnicity and cardiovascular disease prevention in the United Kingdom: a practical approach to management.
The United Kingdom is a diverse society with 7.9% of the population from black and minority ethnic groups (BMEGs). The causes of the excess cardiovascular disease (CVD) and stroke morbidity and mortality in BMEGs are incompletely understood though socio-economic factors are important. However, the role of classical cardiovascular (CV) risk factors is clearly important despite the patterns of these risk factors varying significantly by ethnic group. Despite the major burden of CVD and stroke among BMEGs in the UK, the majority of the evidence on the management of such conditions has been based on predominantly white European populations. Moreover, the CV epidemiology of African Americans does not represent well the morbidity and mortality experience seen in black Africans and black Caribbeans, both in Britain and in their native African countries. In particular, atherosclerotic disease and coronary heart disease are still relatively rare in the latter groups. This is unlike the South Asian diaspora, who have prevalence rates of CVD in epidemic proportions both in the diaspora and on the subcontinent. As the BMEGs have been under-represented in research, a multitude of guidelines exists for the 'general population.' However, specific reference and recommendation on primary and secondary prevention guidelines in relation to ethnic groups is extremely limited. This document provides an overview of ethnicity and CVD in the United Kingdom, with management recommendations based on a roundtable discussion of a multidisciplinary ethnicity and CVD consensus group, all of whom have an academic interest and clinical practice in a multiethnic community.


The Tribulations of Trials: Lessons Learnt Recruiting 777 Older Adults Into REtirement in ACTion (REACT), a Trial of a Community, Group-Based Active Aging Intervention Targeting Mobility Disability.
Challenges of recruitment to randomized controlled trials (RCTs) and successful strategies to overcome them should be clearly reported to improve recruitment into future trials. REtirement in ACTion (REACT) is a United Kingdom-based multicenter RCT recruiting older adults at high risk of mobility disability to a 12-month group-based exercise and behavior maintenance program or to a minimal Healthy Aging control intervention. The recruitment target was 768 adults, aged 65 years and older scoring 4-9 on the Short Physical Performance Battery (SPPB). Recruitment methods include the following: (a) invitations mailed by general practitioners (GPs); (b) invitations distributed via third-sector organizations; and (c) public relations (PR) campaign. Yields, efficiency, and costs were calculated. The study recruited 777 (33.9% men) community-dwelling, older adults (mean age 77.55 years (SD 6.79), mean SPPB score 7.37 (SD 1.56)), 95.11% white (n = 739) and broadly representative of UK quintiles of deprivation. Over a 20-month recruitment period, 25,559 invitations were issued. Eighty-eight percent of the participants were recruited via GP invitations, 5.4% via the PR campaign, 3% via word-of-mouth, and 2.5% via third-sector organizations. Mean recruitment cost per participant was £78.47, with an extra £26.54 per recruit paid to GPs to cover research costs. REACT successfully recruited to target. Response rates were lower than initially predicted and recruitment timescales required adjustment. Written invitations from GPs were the most efficient method for recruiting older adults at risk of mobility disability. Targeted efforts could achieve more ethnically diverse cohorts. All trials should be required to provide recruitment data to enable evidence-based planning of future trials.


Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.
Amyotrophic lateral sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with amyotrophic lateral sclerosis also have frontotemporal degeneration, and gene mutations account for ∼10%. Amyotrophic lateral sclerosis is a variable heterogeneous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons. There is a profound need to clearly articulate and measure pathological process that occurs. Such information is needed to tailor treatments to individuals with amyotrophic lateral sclerosis according to an individual's pathological fingerprint. For new candidate therapies, there is also a need for methods to select patients according to expected treatment outcomes and measure the success, or not, of treatments. Biomarkers are essential tools to fulfil these needs, and urine is a rich source for candidate biofluid biomarkers. This review will describe promising candidate urinary biomarkers of amyotrophic lateral sclerosis and other possible urinary candidates in future areas of investigation as well as the limitations of urinary biomarkers.


Acute phase proteins and biomarkers of oxidative status in feline spontaneous malignant mammary tumours.
Acute phase proteins (APP) and biomarkers of oxidative status change in human and canine mammary tumours, however, they have not been studied in feline mammary tumours. The aims of this study were to investigate the APP and antioxidant responses in feline malignant mammary tumours, to evaluate their relation with tumour features, and to assess their prognostic value. Serum amyloid A (SAA), haptoglobin (Hp), albumin, butyrylcholinesterase (BChE), insulin-like growth factor1 (IGF1), paraoxonase1 (PON1), total serum thiols (Thiol), glutathione peroxidase (GPox) and total antioxidant capacity determined by different assays, including trolox equivalent antioxidant capacity assessed by two different methodologies (TEAC1/2), ferric reducing ability of plasma (FRAP), and cupric reducing antioxidant capacity (CUPRAC), were determined in serum of 50 queens with spontaneous mammary carcinomas and of 12 healthy female cats. At diagnosis, diseased queens presented significantly higher SAA and Hp, and lower albumin, BChE, GPox, TEAC1, TEAC2 and CUPRAC than controls. Different tumour features influenced concentrations of APP and antioxidants. Increases in serum Hp, and decreases in albumin, Thiol and FRAP were significantly associated with neoplastic vascular emboli, metastasis in regional lymph nodes and/or in distant organs. Distant metastasis development during the course of the disease was associated with increases in SAA and TEAC1. At diagnosis, decreased albumin was associated with a longer survival, and BChE <1.15 μmoL/mL.minute was associated with a shorter survival time on multivariate analysis. Feline malignant mammary tumours are associated with an APP response and oxidative stress, and different tumour features influence the inflammatory response and the oxidative damage. Furthermore, some of these analytes proved to have prognostic value.


Detection of E. coli using a microfluidics-based antibody biochip detection system.
This work demonstrates the detection of E. coli using a 2-dimensional photosensor array biochip which is efficiently equipped with a microfluidics sample/reagent delivery system for on-chip monitoring of bioassays. The biochip features a 4 x 4 array of independently operating photodiodes that are integrated along with amplifiers, discriminators and logic circuitry on a single platform. The microfluidics system includes a single 0.4 mL reaction chamber which houses a sampling platform that selectively captures detection probes from a sample through the use of immobilized bioreceptors. The independently operating photodiodes allow simultaneous monitoring of multiple samples. In this study the sampling platform is a cellulosic membrane that is exposed to E. coli organisms and subsequently analyzed using a sandwich immunoassay involving a Cy5-labeled antibody probe. The combined effectiveness of the integrated circuit (IC) biochip and the immunoassay is evaluated for assays performed both by conventional laboratory means followed by detection with the IC biochip, and through the use of the microfluidics system for on-chip detection. Highlights of the studies show that the biochip has a linear dynamic range of three orders of magnitude observed for conventional assays, and can detect 20 E. coli organisms. Selective detection of E. coli in a complex medium, milk diluent, is also reported for both off-chip and on-chip assays.


Description of Thermogemmatispora carboxidivorans sp. nov., a carbon-monoxide-oxidizing member of the class Ktedonobacteria isolated from a geothermally heated biofilm, and analysis of carbon monoxide oxidation by members of the class Ktedonobacteria.
A thermophilic, aerobic, Gram-stain-positive bacterium (strain PM5(T)), which formed mycelia of irregularly branched filaments and produced multiple exospores per cell, was isolated from a geothermally heated biofilm. Strain PM5(T) grew at 40-65 °C and pH 4.1-8.0, with optimal growth at 55 °C and pH 6.0. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain PM5(T) belonged to the class Ktedonobacteria, and was related most closely to Thermogemmatispora onikobensis ONI-1(T) (97.7 % similarity) and Thermogemmatispora foliorum ONI-5(T) (96.1 %). Morphological features and fatty acid profiles (major fatty acids: iso-C17 : 0, iso-C19 : 0 and 12,17-dimethyl C18 : 0) supported the affiliation of strain PM5(T) to the genus Thermogemmatispora. Strain PM5(T) oxidized carbon monoxide [CO; 10±1 nmol h(-1) (mg protein)(-1)], but did not grow with CO as a sole carbon and energy source. Results from analyses of related strains indicated that the capacity for CO uptake occurred commonly among the members of the class Ktedonobacteria; 13 of 14 strains tested consumed CO or harboured coxL genes that potentially enabled CO oxidation. The results of DNA-DNA hybridization and physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain PM5(T) from the two recognized species of the genus Thermogemmatispora. Strain PM5(T) differed from Thermogemmatispora onikobensis ONI-1(T) in its production of orange pigment, lower temperature optimum, hydrolysis of casein and starch, inability to grow with mannitol, xylose or rhamnose as sole carbon sources, and utilization of organic acids and amino acids. Strain PM5(T) is therefore considered to represent a novel species, for which the name Thermogemmatispora carboxidivorans sp. nov. is proposed. The type strain is PM5(T) ( = DSM 45816(T) = ATCC BAA-2534(T)).


[Clinical characteristics of disorders of sexual functions in patients with rheumatoid arthritis].
The method of structural analysis was used to study the presence of sexual disorders in 26 male patients with rheumatoid arthritis (RA). The incidence of sexual disorders was 42.3 per cent (11 patients). In this case the ejaculatory and neurohumoral components of the copulative cycle were mostly disturbed. Sexual dysfunction developed during the disease and was often associated with exacerbation of RA. Disorders in pubertal development were revealed in none of the patients. But patients with a disturbed sexual function exhibited a significant decrease in the total cumulative index in the male sexual formula, in the level of total and free testosterone, a rise in the content of prolactin. Possible causes and mechanisms of sexual disorders in male patients with RA are discussed.


A mixed ecologic-cohort comparison of physical activity & weight among young adults from five populations of African origin.
Examination of patterns and intensity of physical activity (PA) across cultures where obesity prevalence varies widely provides insight into one aspect of the ongoing epidemiologic transition. The primary hypothesis being addressed is whether low levels of PA are associated with excess weight and adiposity. We recruited young adults from five countries (500 per country, 2500 total, ages 25-45 years), spanning the range of obesity prevalence. Men and women were recruited from a suburb of Chicago, Illinois, USA; urban Jamaica; rural Ghana; peri-urban South Africa; and the Seychelles. PA was measured using accelerometry and expressed as minutes per day of moderate-to-vigorous activity or sedentary behavior. Obesity (BMI ≥ 30) prevalence ranged from 1.4% (Ghanaian men) to 63.8% (US women). South African men were the most active, followed by Ghanaian men. Relatively small differences were observed across sites among women; however, women in Ghana accumulated the most activity. Within site-gender sub-groups, the correlation of activity with BMI and other measures of adiposity was inconsistent; the combined correlation across sites was -0.17 for men and -0.11 for women. In the ecological analysis time spent in moderate-to-vigorous activity was inversely associated with BMI (r = -0.71). These analyses suggest that persons with greater adiposity tend to engage in less PA, although the associations are weak and the direction of causality cannot be inferred because measurements are cross-sectional. Longitudinal data will be required to elucidate direction of association.


[Rare foreign body fistulas of the female bladder].
Fistulae between kidney and vagina caused by foreign bodies are very rare nowadays. Two casuistics illustrate the curious anamnesis of such patients: in an 18-year-old girl a foreign body inserted during masturbation led to a perforation, in the case of a 66-year-old woman a pessary which had been forgotten since 35 years penetrated into the urinary bladder.


[Histogenesis and classification of primary liver tumors in children].
Combined morphological examinations of 55 primary tumors of the liver in children as well as livers of 7 human embryos and fetuses were carried out. The finding in hepatoblastoma tissue of the elements of hepatic diverticulum of endoderm persisting in the tumor tissue and comparison of the study results with the data on the embryogenesis and organogenesis of human liver suggest that primary hepatic tumors originate from the pluripotent endodermal germination layer. Islets of tissues not found in the normal liver as well as "osteoid" and squamous epithelium most likely result from cataplasia of "polygonal" myoepithelial-like cells of biliary epithelium in the period of synthesis of basal membrane substance. A classification of primary liver tumors in children taking into account the level of tumor anlage in the ontogenesis and based on the histogenetic principle is proposed.


Tremella fuciformis Polysaccharides Attenuate Oxidative Stress and Inflammation in Macrophages through miR-155.
To investigate the function of Tremella fuciformis polysaccharides (TFPS) in LPS-induced inflammation and oxidative stress of macrophages. RAW264.7 cells were pretreated with TFPS and then stimulated with 0.1 μg/ml LPS. NFκB, Akt, p38MAPK, MCP-1, and SOD-1 were analyzed by Western blotting. Cell viability was measured using MTT assays. Reactive oxygen species (ROS) production, real-time PCR, ELISA, and immunofluorescence staining were performed on RAW264.7 cells that were treated with LPS and/or TFPS to investigate the anti-inflammatory effect of TFPS. LPS induced inflammation and ROS production and promoted the secretion of cytokines such as TNF-α and IL-6. LPS also enhanced the nuclear translocation of NFκB, which promoted inflammation by oxidative stress. However, pretreatment with TFPS profoundly inhibited the activation of Akt, p38MAPK, and NFκB and attenuated the expression of MCP-1 in macrophages. Meanwhile, TFPS also decreased cytokine and ROS levels and attenuated cell inflammation after treatment with LPS. Moreover, miR-155, one of the key small RNAs which regulate NFκB and inflammation in macrophages, was significantly downregulated. TFPS inhibits LPS-induced oxidative stress and inflammation by inhibiting miR-155 expression and NFκB activation in macrophages, which suggests that TFPS may be a potential reagent for inhibiting the development of inflammation.


Dog owner mental health is associated with dog behavioural problems, dog care and dog-facilitated social interaction: a prospective cohort study.
Despite numerous qualitative and cross-sectional studies investigating how dog-related factors may impact owners' well-being, empirical studies to test these causal effects are lacking. This prospective cohort study examined the correlation and potential causal effect of 17 dog-related factors with six well-being outcomes (depression, anxiety, loneliness, suicidal ideation, hedonic well-being and eudaimonic well-being) in dog owners. Over a four-week period, 709 adult dog owners reported their weekly well-being and occurrence of each dog-related factor (e.g. how many times they ran with their dogs). A random intercept cross-lagged panel model (RI-CLPM) with significance threshold set at 0.001 was used. Six factors correlated with poorer owner well-being (i.e. aggressive dog behaviour, fearful dog behaviour, poor dog health, failure to provide for the dog, lack of control over the dog, and dog presence). Only 'friendly conversation with others due to the dog' correlated with better well-being. Purposeful reductions in the frequency of dog behavioural and health-related issues are likely to improve owner well-being, as well as greater consistency in dog care (i.e. provide for the dog) and more engagement in friendly dog-facilitated social interactions. No potential causal effects were significant. Further studies investigating causal relationships are essential to improve people's well-being through dog ownership.


Immediate start of hormonal contraceptives for contraception.
Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. At the time of the initial review, how immediate start compared to conventional menses-dependent start was unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception. This review examined randomized controlled trials (RCTs) of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability. In August 2012, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. Earlier searches also included EMBASE. We included RCTs that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other. Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated. Five studies were included. No new eligible studies have been found since the review was initially conducted. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77). A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. Also, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22). We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, i.e., immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.


Distribution of peripheral blood flow in primary tissue hypoxia induced by inhalation of carbon monoxide.
1. The effects of primary tissue hypoxia induced by the inhalation of small concentrations of carbon monoxide in air on the distribution of blood flow in the portal, renal, muscle and skin beds have been studied in normal unanaesthetized rabbits, in animals without functioning autonomic effectors (;de-efferented' rabbits) and in animals with section of the carotid sinus and aortic nerves (;de-afferented' rabbits).2. The pattern of blood flow distribution during CO hypoxia was similar in ;de-efferented' and ;de-afferented' animals, suggesting that the effects in the latter were determined by local mechanisms. The susceptibility of the various beds to the local dilator effects of CO hypoxia was markedly different, the greatest dilator effects being observed in the portal bed, followed by skin, kidney, and muscle. The pattern is somewhat different from that observed in arterial hypoxia.3. In this type of hypoxia the arterial baroreceptors are probably the main afferent source of reflex activity. In normal animals reflex constrictor effects affect the portal and renal beds most, ;moderating' the local dilator effects of hypoxia in these beds. In muscle there is vasodilatation, probably the result of adrenaline secretion, but the response in skin is largely determined by the local effects of hypoxia. The total orthosympathetic activity evoked in this type of hypoxia appears to be less than in severe arterial hypoxia.


YY1's DNA-binding motifs in mammalian olfactory receptor genes.
YY1 is an epigenetic regulator for a large number of mammalian genes. While performing genome-wide YY1 binding motif searches, we discovered that the olfactory receptor (OLFR) genes have an unusual cluster of YY1 binding sites within their coding regions. The statistical significance of this observation was further analyzed. About 45% of the olfactory genes in the mouse have a range of 4-8 YY1 binding sites within their respective 1 kb coding regions. Statistical analyses indicate that this enrichment of YY1 motifs has likely been driven by unknown selection pressures at the DNA level, but not serendipitously by some peptides enriched within the OLFR genes. Similar patterns are also detected in the OLFR genes of all mammals analyzed, but not in the OLFR genes of the fish lineage, suggesting a mammal-specific phenomenon. YY1, or YY1-related transcription factors, may help regulate olfactory receptor genes. Furthermore, the protein-coding regions of vertebrate genes can contain cis-regulatory elements for transcription factor binding as well as codons.


Determinant and outcome of early diagnosis of HIV infection among HIV-exposed infants in southwest Ethiopia.
Preventing mother-to-child transmission (PMTCT) of human immunodeficiency virus infection (HIV) has been a fundamental advancement in the acquired immunodeficiency syndrome (AIDS) response for the past decade. Several countries have made great strides in the efforts to prevent HIV through mother-to-child transmission. The objective of this study is to assess the determinant and outcome of early diagnosis of HIV infection among HIV-exposed infants in southwest Ethiopia. An institutional based retrospective cohort study was conducted in a hospital. Medical records of HIV-exposed infants and their mothers enrolled into the program were reviewed. Data entry and analysis was carried out using SPSS version 20 for Windows. A total of 426 HIV exposed infant-mother pairs where both mother and infants received a minimum ARV intervention for PMTCT were included in the study. Two hundred fifty-four (59.6%) of mothers had attended antenatal care (ANC). Of all participants, 234(54.9%) mothers did not receive any PMTCT prophylaxis during ANC, while only 104(24.4) received antiretroviral (ART) as PMTCT prophylaxis and 163(38.3%) claimed that did not observe any infant PMTCT interventions while 135(31.7%) of the infants received single-dose NVP + AZT. About 385(90.4%) infants were not infected at their final infection status. Those mothers who did not attended ANC follow-up, infants on mixed and complementary feeding and infants weaned off and mothers who were in WHO clinical stage III and IV were more likely to have HIV sero positive infant. This study showed that 385(90.4%) of the infants were not infected at their final infection status. Therefore, encouraging pregnant women to visit health facilities during their course of pregnancy, focusing on exclusive breast feeding counseling and promotion, and early initiation of antiretroviral treatment to HIV infected pregnant women are recommend.


Medication counselling and dispensing practices at community pharmacies: a comparative cross sectional study from Pakistan.
The study aimed to assess and compare medication counselling and dispensing practices at community pharmacies in three major cities of Pakistan. A total of 1113 patient dispenser interactions were observed from a randomly selected sample of 371 pharmacies by using convenient sampling technique in the three respective cities namely Islamabad (118), Peshawar (120) and Lahore (133). The data collection tool was adapted from WHO structure observation form and was modified according to the objectives of the study. The process of prescription handling at community pharmacies in terms of patient dispenser interaction, prescription validation and medication counseling was assessed. The data was coded, entered and analyzed by using SPSS Version 16. A total of 1113 patient dispenser interactions were observed at the community pharmacies in the three respective cities namely Islamabad (n = 354), Peshawar (n = 360) and Lahore (n = 399). Out of 1113 patient/dispenser interactions the providers present at the community pharmacies were; pharmacist (degree of B-pharm/pharm D) 1.6% (n = 18), pharmacy assistant (diploma in pharmacy) 7% (n = 78), diploma holder (certified course of drug dispensing) 5.6% (n = 62) and salesmen (no medicine related education) 85.8% (n = 955).There was no significant difference in the practice between pharmacists, pharmacy assistants, diploma holders and salesmen. Prescription validation was carried out in 18% (n = 206) of the cases, drugs verification in 32% (n = 360) of the cases while labelling of drugs was performed in only 6% (n = 76) of the cases. Completely counselling about medication was provided in 3.1% (n = 35) of the cases while no counselling at all was given in 52.7% (n = 582) of the cases. The process of medication counselling and dispensing practices at community pharmacies in Pakistan is not satisfactory. The patients are largely handled by unqualified salesmen. Thus there is a strong need to improve medication counselling and dispensing practices at community pharmacies by improving the skills of the dispensers through a mix of interventions, and law should be implemented to ensure presence of qualified person which in turn will result in the provision of better patient oriented services at community pharmacies.


Casein-phosphatidylcholine emulsifier remodels LPS-induced intestinal barrier disfunction via regulating ferroptosis and lipid metabolism.
Recently, the biosafety of synthetic emulsifier in intestinal barrier has raised significant concerns. Casein- phosphatidylcholine (CP), which is a natural emulsifier, has better emulsification and stability. However, the effect of CP on intestinal barrier remains unknow. Intestinal permeability and lipomics analysis showed that carboxymethyl cellulose (CMC) and CP have no significant effect on intestinal barrier in normal intestinal barrier model, whereas CP increased transmembrane resistance value and remodeled lipid homeostasis in LPS induced intestinal barrier dysfunction model, indicating its superior biosafety. To explore the underlying molecular mechanism of emulsifier on intestinal barrier dysfunction, the bioinformatics analysis of six original microarray datasets including 168 cases in NCBI-Gene Expression Omnibus database showed ferroptosis-related genes showed a significant differential expression. The quantitative polymerase chain reaction analysis demonstrated that CP can repair the imbalance of lipid homeostasis induced by LPS and restore normal intestinal permeability by regulating the expression of ferroptosis-related genes, while CMC could can enhance intestinal permeability by inducing ferroptosis of intestinal epithelial cells through lipid peroxidation. In conclusion, this study highlighted CP could remodel LPS-induced intestinal barrier disfunction via regulating ferroptosis and lipid metabolism. These findings can be used as a new insight for the design of new healthy emulsifier.


Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light.
Green fluorescent protein (GFP) and GFP-like proteins represent invaluable genetically encoded fluorescent probes. In the last few years a new class of photoactivatable fluorescent proteins (PAFPs) capable of pronounced light-induced spectral changes have been developed. Except for tetrameric KFP1 (ref. 4), all known PAFPs, including PA-GFP, Kaede, EosFP, PS-CFP, Dronpa, PA-mRFP1 and KikGR require light in the UV-violet spectral region for activation through one-photon excitation--such light can be phototoxic to some biological systems. Here, we report a monomeric PAFP, Dendra, derived from octocoral Dendronephthya sp. and capable of 1,000- to 4,500-fold photoconversion from green to red fluorescent states in response to either visible blue or UV-violet light. Dendra represents the first PAFP, which is simultaneously monomeric, efficiently matures at 37 degrees C, demonstrates high photostability of the activated state, and can be photoactivated by a common, marginally phototoxic, 488-nm laser line. We demonstrate the suitability of Dendra for protein labeling and tracking to quantitatively study dynamics of fibrillarin and vimentin in mammalian cells.


The role of cilia during organogenesis in zebrafish.
Cilia are hair-like organelles that protrude from the surface of eukaryotic cells and are present on the surface of nearly all human cells. Cilia play a crucial role in signal transduction, organ development and tissue homeostasis. Abnormalities in the structure and function of cilia can lead to a group of human diseases known as ciliopathies. Currently, zebrafish serves as an ideal model for studying ciliary function and ciliopathies due to its relatively conserved structure and function of cilia compared to humans. In this review, we will summarize the different types of cilia that present in embryonic and adult zebrafish, and provide an overview of the advantages of using zebrafish as a vertebrate model for cilia research. We will specifically focus on the roles of cilia during zebrafish organogenesis based on recent studies. Additionally, we will highlight future prospects for ciliary research in zebrafish.


A Bayesian nonparametric approach to dynamic item-response modeling: An application to the GUSTO cohort study.
Statistical analysis of questionnaire data is often performed employing techniques from item-response theory. In this framework, it is possible to differentiate respondent profiles and characterize the questions (items) included in the questionnaire via interpretable parameters. These models are often crosssectional and aim at evaluating the performance of the respondents. The motivating application of this work is the analysis of psychometric questionnaires taken by a group of mothers at different time points and by their children at one later time point. The data are available through the GUSTO cohort study. To this end, we propose a Bayesian semiparametric model and extend the current literature by: (i) introducing temporal dependence among questionnaires taken at different time points; (ii) jointly modeling the responses to questionnaires taken from different, but related, groups of subjects (in our case mothers and children), introducing a further dependency structure and therefore sharing of information; (iii) allowing clustering of subjects based on their latent response profile. The proposed model is able to identify three main groups of mother/child pairs characterized by their response profiles. Furthermore, we report an interesting maternal reporting bias effect strongly affecting the clustering structure of the mother/child dyads.


Establishment and maintenance of human embryonic stem cell lines on human feeder cells derived from uterine endometrium under serum-free condition.
Human embryonic stem (hES) cells are usually established and maintained on mouse embryonic fibroblast (MEFs) feeder layers. However, it is desirable to develop human feeder cells because animal feeder cells are associated with risks such as viral infection and/or pathogen transmission. In this study, we attempted to establish new hES cell lines using human uterine endometrial cells (hUECs) to prevent the risks associated with animal feeder cells and for their eventual application in cell-replacement therapy. Inner cell masses (ICMs) of cultured blastocysts were isolated by immunosurgery and then cultured on mitotically inactivated hUEC feeder layers. Cultured ICMs formed colonies by continuous proliferation and were allowed to proliferate continuously for 40, 50, and 55 passages. The established hES cell lines (Miz-hES-14, -15, and -9, respectively) exhibited typical hES cells characteristics, including continuous growth, expression of specific markers, normal karyotypes, and differentiation capacity. The hUEC feeders have the advantage that they can be used for many passages, whereas MEF feeder cells can only be used as feeder cells for a limited number of passages. The hUECs are available to establish and maintain hES cells, and the high expression of embryotrophic factors and extracellular matrices by hUECs may be important to the efficient growth of hES cells. Clinical applications require the establishment and expansion of hES cells under stable xeno-free culture systems.


Clostridium perfringens toxin types from freshwater fishes in one water reservoir of Shandong Province of China, determined by PCR.
Four hundred and twenty intestinal content samples (not including intestinal tissues) of freshwater fishes (60 silver carps, 100 carps, 100 crucian carps, 60 catfishes and 100 zaieuws) caught from one water reservoir were examined bacteriologically for the occurrence of C. perfringens. Isolates were examined by polymerase chain reaction (PCR) for genes encoding the four lethal toxins (alpha, beta, epsilon and iota) for classification into toxin types and for genes encoding enterotoxin and the novel beta2 toxin for further subclassification. C. perfringens could be isolated in 75 intestinal contents samples (17.9%) from freshwater fish including: 13 silver carps, 2 carps, 12 crucian carps, 40 zaieuws, and 8 catfishes. In 75 isolates, 58 strains (77.3%) were C. perfringens toxin type C (alpha and beta toxin positive), 13 strains (17.3%) were toxin type A (alpha toxin positive) and 4 strains (5.3%) were toxin type B (alpha, beta and epsilon toxin positive). In addition, the gene encoding for beta2 toxin was found in 47 strains (62.7%) of all the isolates, seven from type A, two from type B, and 38 from type C. The gene encoding for enterotoxin was not found in any isolate. These amplified toxin gene fragment were cloned and sequenced and compared with reference strains, the identity varied from 98.15% to 99.29%. This is the first report of C. perfringens alpha, beta, epsilon, beta2 toxins in freshwater fish and of beta, epsilon toxins in fish in general, and is the first discovery that the beta2 toxin could be detected in strains of type B. The origin of this bacterium and its importance to human food poisoning in freshwater fish is discussed.


Evolution of sex-determination in dioecious plants: From active Y to X/A balance?
Sex chromosomes in plants have been known for a century, but only recently have we begun to understand the mechanisms behind sex determination in dioecious plants. Here, we discuss evolution of sex determination, focusing on Silene latifolia, where evolution of separate sexes is consistent with the classic "two mutations" model-a loss of function male sterility mutation and a gain of function gynoecium suppression mutation, which turned an ancestral hermaphroditic population into separate males and females. Interestingly, the gynoecium suppression function in S. latifolia evolved via loss of function in at least two sex-linked genes and works via gene dosage balance between sex-linked, and autosomal genes. This system resembles X/A-ratio-based sex determination systems in Drosophila and Rumex, and could represent a steppingstone in the evolution of X/A-ratio-based sex determination from an active Y system.


A comparison of population air pollution exposure estimation techniques with personal exposure estimates in a pregnant cohort.
There is increasing evidence of the harmful effects for mother and fetus of maternal exposure to air pollutants. Most studies use large retrospective birth outcome datasets and make a best estimate of personal exposure (PE) during pregnancy periods. We compared estimates of personal NOx and NO2 exposure of pregnant women in the North West of England with exposure estimates derived using different modelling techniques. A cohort of 85 pregnant women was recruited from Manchester and Blackpool. Participants completed a time-activity log and questionnaire at 13-22 weeks gestation and were provided with personal Ogawa samplers to measure their NOx/NO2 exposure. PE was compared to monthly averages, the nearest stationary monitor to the participants' home, weighted average of the closest monitor to home and work location, proximity to major roads, as well as to background modelled concentrations (DEFRA), inverse distance weighting (IDW), ordinary kriging (OK), and a land use regression model with and without temporal adjustment. PE was most strongly correlated with monthly adjusted DEFRA (NO2r = 0.61, NOxr = 0.60), OK and IDW (NO2r = 0.60; NOxr = 0.62) concentrations. Correlations were stronger in Blackpool than in Manchester. Where there is evidence for high temporal variability in exposure, methods of exposure estimation which focus solely on spatial methods should be adjusted temporally, with an improvement in estimation expected to be better with increased temporal variability.


Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS.
To examine sex differences in baseline characteristics and outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Cox models were used to analyse the association between sex and outcomes in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, placebo-controlled trial assessing the impact of sitagliptin on cardiovascular (CV) outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. A total of 4297 women and 10 374 men were followed for a median of 3.0 years. Women were slightly older and more often had cerebrovascular disease and peripheral arterial disease but less often coronary heart disease than men. At baseline, women were less likely to use aspirin or statins. The primary composite outcome of CV death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 418 women (9.7%) and 1272 men (12.3%; 3.48 vs 4.38 events/100 participant-years, crude hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.89, adjusted HR 0.64, 95% CI 0.55-0.74; P < .0001). Women also had a significantly lower risk of secondary CV outcomes and all-cause death. In this large prospective study of people with type 2 diabetes and CV disease, women had different CV disease burden, worse CV risk factor profiles, and less use of indicated medications than men. Despite this, women had significantly lower risk of CV events, suggesting that the cardioprotective effects of female sex extend to populations with type 2 diabetes.


Mind-mindedness and preschool children's behavioral difficulties: The moderating role of maternal parenting distress.
Mind-mindedness (MM) is a caregiver's tendency to appreciate their infant's internal mental states. This longitudinal study investigated whether maternal MM (10 months) was linked with children's later behavioral problems (51 months) and the moderating role of maternal parenting distress (PD; 36 months) in a sample of 91 mother-infant dyads. Appropriate MM comments were coded from video-recorded, semi-structured play interactions between mothers and their infants; PD was obtained from maternal completion of the PD subscale of the Parenting Stress Index - Short Form (PSI-SF); and child internalizing and externalizing behavior problems were gathered from maternal report on the Strengths and Difficulties Questionnaire (SDQ). Moderated regression analyses revealed higher early appropriate MM was associated with significantly fewer internalizing emotional problems at 51 months among mothers with lower PD at 36 months, and higher early appropriate MM was associated with lower conduct problems at 51 months in mothers with higher PD at 36 months. Findings demonstrated the importance of considering nuanced contexts such as at-risk mothers and differential presentations of child difficulties in the analysis of the relationship between MM and child behavioral difficulties and the development of MM interventions.


Geriatric falls: injury severity is high and disproportionate to mechanism.
Falls are a well-known source of morbidity and mortality in the elderly. Fall-related injury severity in this group, however, is less clear, particularly as it relates to type of fall. Our purpose is to explore the relationship between mechanism of fall and both pattern and severity of injury in geriatric patients as compared with a younger cohort. Our trauma registry was queried for all patients evaluated by the trauma service over a 412-year period (1994-1998). Two cohorts were formed on the basis of age greater than 65 or less than or equal to 65 years and compared as to mechanism, Injury Severity Score (ISS), Abbreviated Injury Scale score, and mortality. Over the study period, 1,512 patients were evaluated, 333 greater than 65 years and 1,179 less than or equal to 65 years of age. Falls were the injury mechanism in 48% of the older group and 7% of the younger group (p < 0.05). Falls in the older group constituted 65% of patients with ISS >15, with 32% of all falls resulting in serious injury (ISS >15). In contrast, falls in the younger group constituted only 11% of ISS >15 patients, with falls causing serious injury only 15% of the time (both p < 0.05). Notably, same-level falls resulted in serious injury 30% of the time in the older group versus 4% in the younger group (p < 0.05), and were responsible for an ISS >15 30-fold more in the older group (31% vs. <1%; p < 0.05). Abbreviated Injury Scale evaluation revealed more frequent head/neck (47% vs. 22%), chest (23% vs. 9%), and pelvic/extremity (27% vs. 15%) injuries in the older group for all falls (all p < 0.05). The mean ISS for same-level falls in the older group was twice that for the younger group (9.28 vs. 4.64, p < 0.05), whereas there was no difference in mean ISS between multilevel and same-level falls within the older group itself (10.12 vs. 9.28, p > 0.05). The fall-related death rate was higher in the older group (7% vs. 4%), with falls seven times more likely to be the cause of death compared with the younger group (55% vs. 7.5%) (both p < 0.05). Same-level falls as a cause of death was 10 times more common in the elderly (25% vs. 2.5%, p < 0.05). Falls among the elderly, including same-level falls, are a common source of both high injury severity and mortality, much more so than in younger patients. A different pattern of injury between older and younger fall patients also exists.


Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis.
To gain insight into the molecular mechanisms underlying the control of morphogenetic signals by H+ flux during embryogenesis, we tested Fusicoccin-A (FC), a compound produced by the fungus Fusicoccum amygdali Del. In plant cells, FC complexes with 14-3-3 proteins to activate H+ pumping across the plasma membrane. It has long been thought that FC acts on higher plants only; here, we show that exposing frog embryos to FC during early development specifically results in randomization of the asymmetry of the left-right (LR) axis (heterotaxia). Biochemical and molecular-genetic evidence is presented that 14-3-3-family proteins are an obligate component of Xenopus FC receptors and that perturbation of 14-3-3 protein function results in heterotaxia. The subcellular localization of 14-3-3 mRNAs and proteins reveals novel cytoplasmic destinations, and a left-right asymmetry at the first cell division. Using gain-of-function and loss-of-function experiments, we show that 14-3-3E protein is likely to be an endogenous and extremely early aspect of LR patterning. These data highlight a striking conservation of signaling pathways across kingdoms, suggest common mechanisms of polarity establishment between C. elegans and vertebrate embryos, and uncover a novel entry point into the pathway of left-right asymmetry determination.


Resuscitation of carbon-contaminated mirrors and gratings by oxygen-discharge cleaning. in the 4-40-eV range.
The dc oxygen-discharge cleaning of optical elements contaminated by synchrotron radiation has been studied for a variety of contamination levels, optical materials, electrode and reflecting-surface configurations, discharge powers, and exposure times. Cleaning with a proper electrode-surface configuration resulted in the removal of contaminant layers within 1 h even for highly contaminated elements. The reflectance of mirrors and the diffraction efficiency of gratings were almost completely restored after cleaning over the 4-40- eV energy range; the enhancement even amounted to 1 order of magnitude in some cases. This cleaning procedure did not cause any increased roughness; rather, it resulted in a reduced scattering level of contaminated elements. The removal of contaminants also led to a restoration of the grating blaze; essentially, this contributed to an improvement in the inside first-order efficiency around the blazed energy. From the results with controlled power and exposure time, it was shown that an optimum exposure is achieved within several minutes after the disappearance of visible contamination.


In vitro detection of endothelial cell damage using 2-deoxy-D-3H-glucose: comparison with chromium 51, 3H-leucine, 3H-adenine, and lactate dehydrogenase.
To develop a sensitive in vitro assay for detecting endothelial cell damage, we radiolabeled endothelial cell monolayers with tracer amounts of 2-deoxy-D-[1-3H]-glucose (3HDOG). We damaged identical cohorts of endothelial cells radiolabeled with 3HDOG or chromium 51 by exposing monolayers to toxic oxygen radicals generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), a surface active agent (Triton X-100), and anti-HLA antibodies and complement. With each mechanism of injury, the 3HDOG assay detected significant (P less than 0.01) endothelial cell damage at lower concentrations of the injurious agent than the 51Cr assay. When endothelial monolayers were damaged by xanthine-xanthine oxidase or PMA-activated PMNs, efflux of 3HDOG was reduced (range 71% to 94% reduction) by superoxide dismutase and catalase, indicating that efflux of 3HDOG was mediated by toxic oxygen radicals. When monolayers were damaged with xanthine oxidase in the absence of glucose, a much lower concentration of xanthine oxidase was required to initiate efflux of 3HDOG as compared with xanthine oxidase injury in the presence of glucose. Additional studies compared the 3HDOG assay with 3H-adenine, 3H-leucine, and lactate dehydrogenase (LDH) release when endothelial cells were exposed to toxic oxygen radicals generated by PMA-activated PMNs and xanthine-xanthine oxidase. Again, the 3HDOG assay was more sensitive in detecting in vitro endothelial cell damage. We conclude that the 3HDOG assay is more sensitive than the 51Cr, 3H-adenine, 3H-leucine, or LDH release assays in detecting endothelial cell damage in vitro.


The biology of Dactylopius tomentosus (Hemiptera: Dactylopiidae).
Dactylopius tomentosus (Lamarck) (Hemiptera: Dactylopiidae) is a cochineal insect whose host range is restricted to Cylindropuntia species (Caryophyllales: Cactaceae). This insect has been utilized successfully for biological control of Cylindropuntia imbricata (Haw.) F.M. Knuth in Australia and South Africa. Despite this, its biology has not been studied previously, probably due to the widely held belief that the biology of all Dactylopius species is similar. This study investigated the life cycle and the morphological and reproductive characteristics of D. tomentosus. Results revealed some unique characteristics of D. tomentosus: (i) eggs undergo a much longer incubation period, an average of 17 days compared to <1 day in its congeners; (ii) eggs are laid singly but are retained as an egg mass secured in a mesh of waxy threads attached to the female; (iii) the developmental times of males and females are longer compared to other Dactylopius spp. due to a longer egg incubation period; (iv) D. tomentosus does not undergo parthenogenesis; (v) D. tomentosus is smaller in size than its congeners; and (vi) male mating capacity and reproductive potential were both high and variable between males. There was a significant, strong, positive relationship (r = 0.93) between female mass and fecundity, whereas the relationship between the number of females mated per male that became gravid and their fecundity was negative (r = -0.68). Besides contributing to our knowledge of this economically important species, the finding of unique characteristics of D. tomentosus biology underlines the need to study each species in this genus.


Optimizing metapopulation sustainability through a checkerboard strategy.
The persistence of a spatially structured population is determined by the rate of dispersal among habitat patches. If the local dynamic at the subpopulation level is extinction-prone, the system viability is maximal at intermediate connectivity where recolonization is allowed, but full synchronization that enables correlated extinction is forbidden. Here we developed and used an algorithm for agent-based simulations in order to study the persistence of a stochastic metapopulation. The effect of noise is shown to be dramatic, and the dynamics of the spatial population differs substantially from the predictions of deterministic models. This has been validated for the stochastic versions of the logistic map, the Ricker map and the Nicholson-Bailey host-parasitoid system. To analyze the possibility of extinction, previous studies were focused on the attractiveness (Lyapunov exponent) of stable solutions and the structure of their basin of attraction (dependence on initial population size). Our results suggest that these features are of secondary importance in the presence of stochasticity. Instead, optimal sustainability is achieved when decoherence is maximal. Individual-based simulations of metapopulations of different sizes, dimensions and noise types, show that the system's lifetime peaks when it displays checkerboard spatial patterns. This conclusion is supported by the results of a recently published Drosophila experiment. The checkerboard strategy provides a technique for the manipulation of migration rates (e.g., by constructing corridors) in order to affect the persistence of a metapopulation. It may be used in order to minimize the risk of extinction of an endangered species, or to maximize the efficiency of an eradication campaign.


Importance of the C-1 substituent in classical cannabinoids to CB2 receptor selectivity: synthesis and characterization of a series of O,2-propano-delta 8-tetrahydrocannabinol analogs.
The separation of the mood-altering effects of cannabinoids from their therapeutic effects has been long sought. Results reported here for a series of C-9 analogs of the cyclic ether O,2-propano-delta 8-tetrahydrocannabinol (O,2-propano-delta 8-THC) point to the C-1 position in classical cannabinoids as a position for which CB2 subtype selectivity occurs within the cannabinoid receptors. O,2-Propano-11-delta 8-THC, O,2-propano delta 9,11-THC, O,2-propano-9-oxo-11-nor-hexahydrocannabinol (O,2-propano-9-oxo-11-nor-HHC), and O,2-propano-9 alpha- and O,2-propano-9 beta-OH-11-nor-HHC were synthesized and evaluated in radioligand displacement assays for affinity at the CB1 and CB2 receptors and in the mouse vas deferens in vitro assay and the mouse tetrad in vivo assay for cannabinoid activity. Evaluation of binding affinity at the CB1 and CB2 receptors revealed that each compound possesses a modest increased affinity for the CB2 receptor. Analogs which contained an oxygen attached to C-9 (i.e., oxo and hydroxy derivatives) showed the highest affinity and selectivity for CB2 (for O,2-propano-9-oxo-11-nor-HHC, Ki(CB1) = 90 nM, Ki(CB2) = 23 nM, selectivity ratio 3.9; for O,2-propano-9 beta-OH-11-nor-HHC, Ki(CB1) = 26 nM, Ki(CB2) = 5.8 nM, selectivity ratio 4.5). Each compound was found to produce a dose-dependent inhibition of electrically-evoked contractions of the mouse isolated vas deferens when administered at submicromolar concentrations. This inhibition could readily be prevented by the selective CB1 cannabinoid receptor antagonist SR-141716A. The analogs exhibited unique in vivo profiles with O,2-propano-delta 9,11-THC exhibiting antinociception with reduced activity in three other in vivo measures and O,2-propano-9 beta-OH-HHC exhibiting lack of dose responsiveness in all measures. The CB2 selectivities in the O,2-propano analogs may be due to differences in solvation/desolvation that occur when the ligands enter the CB1 vs CB2 binding site. Alternatively, the CB2 selectivities may be a results of an amino acid change from a hydrogen bond-accepting residue in CB1 to a hydrogen bond-donating residue in CB2.


Can we predict radiation-induced changes in pulmonary function based on the sum of predicted regional dysfunction?
To determine whether changes in whole-lung pulmonary function test (PFT) values are related to the sum of predicted radiation therapy (RT)-induced changes in regional lung perfusion. Between 1991 and 1998, 96 patients (61% with lung cancer) who were receiving incidental partial lung irradiation were studied prospectively. The patients were assessed with pre- and post-RT PFTs (forced expiratory volume in one second [FEV1] and diffusion capacity for carbon monoxide [DLCO]) for at least a 6-month follow-up period, and patients were excluded if it was determined that intrathoracic recurrence had an impact on lung function. The maximal declines in PFT values were noted. A dose-response model based on RT-induced reduction in regional perfusion (function) was used to predict regional dysfunction. The predicted decline in pulmonary function was calculated as the weighted sum of the predicted regional injuries: equation [see text] where Vd is the volume of lung irradiated to dose d, and Rd is the reduction in regional perfusion anticipated at dose d. The relationship between the predicted and measured reduction in PFT values was significant for uncorrected DLCO (P = .005) and borderline significant for DLCO (P = .06) and FEV1 (P = .08). However, the correlation coefficients were small (range,.18 to.30). In patients with lung cancer, the correlation coefficients improved as the number of follow-up evaluations increased (range,.43 to.60), especially when patients with hypoperfusion in the lung adjacent to a central mediastinal/hilar thoracic mass were excluded (range,.59 to.91). The sum of predicted RT-induced changes in regional perfusion is related to RT-induced changes in pulmonary function. In many patients, however, the percentage of variation explained is small, which renders accurate predictions difficult.


The association of winds with the spread of EHDV in dairy cattle in Israel during an outbreak in 2006.
Winds may play a major role in spread of arthropod-borne viruses (arboviruses). Arboviruses like epizootic hemorrhagic disease virus (EHDV), bluetongue virus and bovine ephemeral fever virus (BEFV) frequently cause major outbreaks in Israel with a unique pattern of spread. Most of these outbreaks begin in the Jordan valley, near the Sea of Galilee and then spread to the north, south and west through the major valleys of Israel. The aim of this study was to describe the spread pattern in such an outbreak and to find if this pattern can be explained by winds. Herein, we compared the spread rate to each direction and used Cox proportional hazards model to test factors associated with the spread of EHDV, which emerged in diary cattle in Israel during the summer of 2006. Documented, clinical and serological data on spread of the outbreak were then compared with wind data collected by meteorological stations along the trail of virus spread and with modeled winds at high altitude (>500 m). The analysis revealed that both the hazard and the rate of outbreak spread to the south and to the north were significantly higher than to the west. Average rate of outbreak spread during periods in which at least 3 h of winds to spread direction were recorded was 20,880 m/week (SD=13,230) vs. 7486 m/week (SD=4936) in periods during which no such winds were recorded. Serological evidence demonstrated exposure to the virus up to 166 km away from the location of the initial outbreak center. Modeled wind data showed that this spread may be explained by winds at high altitudes. Animal movements due to shipments of feedlot calves and slaughters could not explain the spread pattern observed during the outbreak. This study therefore shows that winds are probably a major contributory factor for long and medium distance spread of Culicoides borne viruses in this region.


The effects of melatonin in glutamate-induced neurotoxicity of rat cerebellar granular cell culture.
In the present study, melatonin was tested in subsequent doses in glutamate induced neurotoxicity in cerebellar granular cell culture of rat pups. Glutamate at 10(-7) M was found to induce neuronal cell death. The dead cell score was 2.75+/-0.7 in the control, while it was found to be 35.12+/-1.8 in the glutamate-administered group (P<0.0001). Melatonin very potently blocked glutamate neurotoxicity at all doses tested, with 10(-3) M, the highest dose tested, being the most effective. Glutamate may exert a neuroprotective effect by blocking one or more steps of the oxidation cascade in neurons and this effect may be blocked by melatonin.


Double blind evaluation of long acting diethylpropion hydrochloride in obese patients from a general practice.
Obese patients encountered in general practice were studied in order to determine whether a long-acting form of diethylpropion hydrochloride (Tenuate Dospan) was more effective than placebo for weight loss. One hundred and two patients completed this double blind, 16-week crossover study. During the first eight weeks, the patients treated with diethylpropion hydrochloride lost significantly (P smaller than 0.001) more weight than the patients treated with placebo (an average of 11-1 lb or 6-4% of their initial weight as compared with 6-2 lb or 3-6% of their initial weight). When the group taking diethylpropion hydrochloride crossed over to placebo for a second eight weeks, they lost an average of 1-5 lb (0-9% of their weight at the start of the second period), while the group who crossed from placebo over to diethylpropion hydrochloride lost an average of 6-7 lb (3-8%). The advantages of diethylpropion hydrochloride over placebo are statistically significant.


Thrombocytosis after trauma: incidence, aetiology, and clinical significance.
Our aim was to assess the occurrence, aetiology, and clinical significance of a platelet count greater than 600 x 10(3)/mm(3) in trauma patients. All trauma patients admitted to the intensive care unit (ICU) during a 13-month period were prospectively studied. Platelet counts were performed daily. We recorded the patient's age, sex, nature of trauma, severity of illness scores, episodes of infections in the ICU, acute lung injury, bleeding, and thromboembolic events. Patients with thrombocytosis were also followed during their hospital stay and 1 month after hospital discharge. A total of 176 patients were included. Thrombocytosis developed in 36 patients (20.4%) at a mean (sd) time of 14.0 (4.0) days and the platelet count normalized 35.0 (13.0) days after admission to the ICU. All patients with thrombocytosis had one or more possible predisposing conditions before the occurrence of thrombocytosis: nosocomial infection occurred in 30 patients (83%), acute lung injury in 17 (47%), bleeding in 27 (75%), and administration of cathecholamines in 24 (67%). Three venous thromboembolic complications occurred in the ICU (1.7%) and one during follow-up. Only one patient presented thrombocytosis at the time of diagnosis. Despite the fact that patients with thrombocytosis had a greater severity of illness, the ICU mortality was comparable among patients with and without thrombocytosis (8 vs 14%, P=0.34). Reactive thrombocytosis is a common finding after severe trauma and was found to be associated with a better survival than predicted by severity of illness score. Unless additional risk factors are present, reactive thrombocytosis is not associated with an increased risk of thromboembolic events.


Summer-winter difference in 24-h melatonin rhythms in subjects on a 5-workdays schedule in Siberia without daylight saving time transitions.
The study aimed to quantify a seasonal change in circadian rhythms and its relationship to the social/sleep regimen in humans living in Novosibirsk (55°N), using the naturalistic situation that daylight saving time transitions have been abolished in Russia. Sixty-three volunteers entered the study, and 46 completed it. One group got up at ~6 a.m. and another at ~7 a.m. during their regular 5-workdays schedule. They collected 19 saliva samples at home over 24 h (including 2 samples during the night) on July 3-4, and December 18-19, 2015. Salivary melatonin was measured using radioimmunoassay; the times of evening onset and morning offset were objectively determined using the hockey-stick algorithm and served as circadian phase markers. Nearly all melatonin profiles were normal in summer (high nighttime and low daytime levels), whereas in winter, significantly more - 8 profiles - were abnormal (additional daytime peak, out-of-phase daytime secretion, or absence of secretion), of which 3 (plus 1 for other reasons) could not be included in the further analysis. The duration of melatonin secretion (somewhat less than 12 h) and amount of melatonin secreted did not differ between seasons. In winter compared to summer the melatonin rhythm, on average, significantly phase delayed by half-an-hour, with a tendency for greater inter-individual phase variability. The phase delay was attributable to those subjects who got up at ~7 a.m. (and who were longer sleepers). The melatonin rhythm reflected well the sleep timing difference between the two groups in summer, whereas in winter this coherence was lost. In summary, timing of the circadian system is strictly synchronised in summer by the long light: short dark photoperiod (with sleep as a constituent of the 7 h 10 min dark phase of the cycle), whereas in winter, with the long dark nights (17 h 12 min), an inter-individual phase desynchrony and even abnormal melatonin patterns emerge, despite a constant sleep/social regimen, suggesting that the winter season is unfavourable for circadian status.


Acute myocarditis associated with cardiac amyloidosis manifesting as transient complete atrioventricular block and slow ventricular tachycardia.
This is the first report of conduction system disturbances and slow ventricular tachycardia (VT), related to acute myocarditis associated with cardiac amyloidosis. A 57-year-old female was presented with chest pain and pre-syncope after flu-like symptoms, and was promptly diagnosed with acute myocarditis. The initial electrocardiogram (ECG) revealed complete atrioventricular (AV) block, and transient slow VT was observed after an atropine injection (0.5 mg). This AV conduction disturbance persisted for 12 days, and spontaneously resolved. Left ventricular function was relatively well preserved, and an endomyocardial biopsy revealed acute myocardial inflammation and underlying amyloid deposits. A His-bundle recording, taken 6 weeks after the initial manifestation, indicated normal AV nodal conduction. Endomyocardial biopsies have proven helpful with regard to the diagnosis of acute myocarditis superimposed on amyloidosis, in patients who present with conduction disorder and relatively preserved ventricular function, as was seen in this case.


Downregulation of DUOX1 function contributes to aging-related impairment of innate airway injury responses and accelerated senile emphysema.
Aging is associated with a gradual loss of lung function due to increased cellular senescence, decreased regenerative capacity, and impaired innate host defense. One important aspect of innate airway epithelial host defense to nonmicrobial triggers is the secretion of alarmins such as IL-33 and activation of type 2 inflammation, which were previously found to depend on activation of the NADPH oxidase (NOX) homolog DUOX1, and redox-dependent signaling pathways that promote alarmin secretion. Here, we demonstrate that normal aging of C57BL/6J mice resulted in markedly decreased lung innate epithelial type 2 responses to exogenous triggers such as the airborne allergen Dermatophagoides pteronyssinus, which was associated with marked downregulation of DUOX1, as well as DUOX1-mediated redox-dependent signaling. DUOX1 deficiency was also found to accelerate age-related airspace enlargement and decline in lung function but did not consistently affect other features of lung aging such as senescence-associated inflammation. Intriguingly, observations of age-related DUOX1 downregulation and enhanced airspace enlargement due to DUOX1 deficiency in C57BL/6J mice, which lack a functional mitochondrial nicotinamide nucleotide transhydrogenase (NNT), were much less dramatic in C57BL/6NJ mice with normal NNT function, although the latter mice also displayed impaired innate epithelial injury responses with advancing age. Overall, our findings indicate a marked aging-dependent decline in (DUOX1-dependent) innate airway injury responses to external nonmicrobial triggers, but the impact of aging on DUOX1 downregulation and its significance for age-related senile emphysema development was variable between different C57BL6 substrains, possibly related to metabolic alterations due to differences in NNT function.


Micelle-forming HPMA copolymer conjugates of ritonavir bound via a pH-sensitive spacer with improved cellular uptake designed for enhanced tumor accumulation.
We describe design, synthesis, physico-chemical characterization and preliminary biological evaluation of micelle-forming polymer drug conjugates with controlled drug release intended for tumor treatment. The structure of the conjugates was designed to enable tumor tissue- and cell-specific drug release and micelle disassembly to avoid side effects accompanying classic chemotherapy and guarantee safe elimination of the drug-free carrier from the organisms. The amphiphilic polymer conjugates consisted of a hydrophobic hexaleucine block and a hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer with an antiviral and cytostatic drug, ritonavir, bound through a pH-sensitive spacer. Diblock copolymers with low dispersity (Đ∼ 1.1) were prepared via reversible addition-fragmentation chain transfer (RAFT) copolymerization using a hexaleucine derivative as a chain transfer agent. The associative properties of the copolymers depend on the hydrophilic polymer block length and the hydrophobic ritonavir content. The micelles dissociated under mild acidic conditions mimicking the environment inside tumor tissue/cells, because of the decrease in polymer hydrophobicity after the rapid release of the hydrophobic drug from the polymer carrier. Unexpectedly, the polymer-ritonavir conjugates internalized into HeLa cells significantly more than the polymers without ritonavir. The enhanced cell penetration and pH-triggered micelle disassembly predetermine the polymer-ritonavir conjugates to become promising tumor-targeted drug carriers.


Functional magnetic resonance imaging in pediatrics.
Functional magnetic resonance imaging (fMRI) allows non-invasive assessment of human brain function in vivo by detecting blood flow differences. In this review, we want to illustrate the background and different aspects of performing functional magnetic resonance imaging (fMRI) in the pediatric age group. An overview over current and future applications of fMRI will be given, and typical problems, pitfalls, and benefits of doing fMRI in the pediatric age group are discussed. We conclude that fMRI can successfully be applied in children and holds great promise for both research and clinical purposes.


Large Cell Neuroendocrine Carcinoma of the Extrahepatic Bile Duct.
Primary neuroendocrine tumors originating from the extrahepatic bile duct are rare. Among these tumors, large cell neuroendocrine carcinomas (NECs) are extremely rare. A 59-year-old man was admitted to Sanggye Paik Hospital with jaundice that started 10 days previously. He had a history of laparoscopic cholecystectomy, which he had undergone 12 years previously due to chronic calculous cholecystitis. Laboratory data showed abnormally elevated levels of total bilirubin 15.3 mg/dL (normal 0.2-1.2 mg/dL), AST 200 IU (normal 0-40 IU), ALT 390 IU (normal 0-40 IU), and gamma-glutamyl transferase 1,288 U/L (normal 0-60 U/L). Serum CEA was normal, but CA 19-9 was elevated 5,863 U/mL (normal 0-37 U/mL). Abdominal CT revealed a 4.5 cm sized mass involving the common bile duct and liver hilum and dilatation of both intrahepatic ducts. Percutaneous transhepatic drainage in the left hepatic duct was performed for preoperative biliary drainage. The patient underwent radical common bile duct and Roux-en-Y hepaticojejunostomy for histopathological diagnosis and surgical excision. On histopathological examination, the tumor exhibited large cell NEC (mitotic index >20/10 high-power field, Ki-67 index >20%, CD56 [+], synaptophysin [+], chromogranin [+]). Adjuvant concurrent chemotherapy and radiotherapy were started because the tumor had invaded the proximal resection margin. No recurrence was detected at 10 months by follow-up CT.


What terminally ill patients care about: toward a validated construct of patients' perspectives.
Citizens have conveyed to professionals that care at the end of life is less than optimal. Efforts to improve matters have tended to work in piecemeal fashion, on tangible more than personal aspects of care, and without the benefit of documented perspectives of those who face dying. Policy initiatives and clinical interventions need guidance from a broad framework that is validated by patients' perspectives. Our goals were to: (1) assess the construct validity and stability over time of the portions of a conceptual framework that concern patients' subjective experiences; (2) develop a foundation for measurement of these personally meaningful factors; and (3) examine these factors' associations for potential clinical or policy significance. Patients were from six diverse geographical areas whose physicians judged their survival prognosis to be 6 months or less. Physicians who referred the patients were randomly selected from state and specialty association lists. We used in-person survey methodology and multivariate analysis of patient responses. The analysis fell into two parts. Using exploratory factor analysis, we looked for evidence of discrete dimensions of experiences. Using regression analysis, we examined associations among them. Of 1,131 eligible patients, 988 were interviewed (87.4% response rate). Of 682 patients who survived to follow-up interview 4-6 months later, 650 were interviewed (95.3% response rate). Exploratory factor analysis identified 12 discrete factors (accounting for 55% of variance; maximum Spearman's p = 0.24), 8 of which met criteria for representing measurable dimensions (accounting for 46% of variance). These 8 were: patient-clinician relationship; social connectedness; caregiving needs; psychological distress; spirituality/religiousness; personal acceptance; sense of purpose; and clinician communication. Eigenvalues ranged from 1.45 to 6.30 and Cronbach's alpha from 0.63 to 0.85. The concordance between these dimensions and those in the proposed framework indicated that two dimensions required minor modifications and six were confirmed, providing evidence of good construct validity for this portion of the framework. The same dimensions were also evident at follow-up except that the first two above-listed loaded on one combined factor, clinician interaction (eigenvalues 1.83-7.92; Cronbach's alpha from 0.64 to 0.86). This provides evidence of the construct's stability over time. Clinical communication and patient-clinician relationship were associated (odds ratio [OR] 2.79, 2.31-3.36). Better clinician communication correlated with somewhat better personal acceptance (OR 1.10,1.02-1.19), and a better patient-clinician relationship correlated with less psychological distress (OR 0.84, 0.75-0.95). We conclude that: (1) Personally meaningful aspects of patients' experience of terminal illness can be represented in valid, multidimensional constructs that are stable over time; (2) They are measurable; and (3) Aspects of the therapeutic relationship appear to correlate with patients' experience of the dying process.


[Importance of the therapeutic alliance experience for the differential psychotherapeutic indication].
The influence of the therapeutic alliance experience on the recommendation for psychotherapy and prognosis was examined in a retrospective study. Three hundred seventy-four of 3270 patients who presented at the psychosomatic-psychotherapeutic outpatient service at the Benjamin Franklin Hospital of the Free University of Berlin between July 1994 and December 1999 were selected based on the fact that they had been examined only by a psychoanalyst and recommended for individual psychoanalytical outpatient therapy, nondirective therapy (according to Rogers) or behavioral therapy. Results of the unifactorial variance analysis: The better the alliance is assessed, the sooner procedures for psychoanalytical therapy are recommended (F = 35.85; p < 0.000) and the better the assessment of the prognosis (r = 0.68; p < 0.000). The results confirm the importance of the therapeutic working relationship and correct the assumption that the indication and prognosis are exclusively diagnosis or patient-related, clearly showing that they are the result of an interactive process.


End-to-end multimodal system for depression detection from online recordings.
Depression is one of the most occurring civilizational diseases. In this paper, we propose a new approach for detecting depression through the analysis of social media content using face analysis, emotion recognition neural networks, and speech processing. We utilized audio-visual analysis and acquired more than 605 features in the time domain. Those are fed to machine learning and deep learning models for depression classification. Our approach outperforms the other state-of-the-art models, achieving the F1-score 0.77. The results have the potential to provide valuable insights for mental health professionals, offer early detection and intervention, and serve as a resource for individuals seeking help with their mental health. This study enables real-time analysis and represents a significant advancement in mental health and technology and has the potential to impact society.Clinical relevance-The system aims to provide a fast and accurate way to detect depression in individuals through online recordings. The use of multimodal information (e.g. audio, image) enhances the performance of the non-verbal behavioral analysis. The end-to-end system reduces the need for manual analysis by mental health professionals and increases the efficiency of depression screening. The system can potentially help identify individuals who are at risk for depression, enabling early intervention and treatment. The results from the system can complement traditional assessments and support mental health professionals in making a diagnosis. The system can be used in real-time processing, f.e. during online calls, and provide objective measurements summarizing the overall behavior based on computer vision and audio analysis.


Weird people, yes, but also weird experiments.
While we agree that the cultural imbalance in the recruitment of participants in psychology experiments is highly detrimental, we emphasize the need to complement this criticism with a warning about the "weirdness" of some cross-cultural studies showing seemingly deep cultural differences. We take the example of economic games and suggest that the variety of results observed in these games may not be due to deep psychological differences per se, but rather due to different interpretations of the situation.


The use of a hyperosmolar irrigation solution is safe in an equine stifle joint model but does not reduce joint swelling.
To determine the following: (1) whether an irrigation solution that is hyperosmolar (HYPER) relative to synovial fluid decreases tissue extravasation during an arthroscopic protocol when compared to a relatively hypoosmolar solution, (2) the safety of a HYPER solution based on viability of joint tissues following joint irrigation, and (3) if the use of a HYPER solution decreases water content in stifle joint tissue. 8 adult horses. A prospective, blinded, randomized controlled trial was performed to compare lactated Ringer's solution (LRS; 273 mOsm/L) and a HYPER (600 mOsm/L) irrigation solution for routine medial femorotibial joint (MFTJ) arthroscopy. Primary outcomes included quantification of periarticular fluid retention based on measured changes in defined stifle joint girth and ultrasonographic (US) criteria. Water content of tissue samples was assessed. The viability of articular cartilage was determined using a microscopic fluorescent cell viability staining system. No significant difference in postprocedural joint swelling was observed between LRS and HYPER treatment groups. Percent increments in femorotibial joint dimensions (mean ± SD) were seen in both treatment groups based on US (LRS, 83.9 ± 84.6%; HYPER, 131.2 ± 144.9%) and caliper measurements (LRS 5.5 ± 4.3%; HYPER 7.5 ± 5.8%) (P ≤ .05). Chondrocyte viability and tissue water content were maintained in both treatment groups, and differences were not statistically significant. Doubling the osmolarity of an irrigation solution used routinely for arthroscopy does not result in detrimental effects on chondrocyte viability or tissue water content. However, use of a relatively HYPER irrigation solution did not attenuate procedural tissue swelling of the equine stifle joint.


Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual.
Sera from individuals infected by HIV-1 usually neutralize multiple viral isolates. To determine the extent to which these neutralizing antibodies recognize a principal neutralizing determinant in the V3 region of the envelope protein gp120 (amino acids 308-332), one broadly neutralizing serum was fractionated by affinity chromatography on immobilized peptide columns. Antibodies that neutralize one isolate (HTLV-IIIMN) were substantially but not completely absorbed by the peptide corresponding to a portion of its V3 determinant, whereas the antibodies that neutralize two other isolates (HTLV-IIIB and HTLV-IIIRF) were not absorbed by homologous peptides corresponding to their neutralizing determinants. Neutralizing antibodies also failed to be absorbed by full length envelope protein gp160 and by two other envelope peptides previously reported to be broadly neutralizing epitopes (amino acids 254-274 and 735-752). We conclude that the infected individual had raised a type-restricted neutralizing response targeted at a linear epitope in the V3 region, and that broad neutralization resulted from recognition of epitopes not yet identified.


Quantum chemistry and molecular dynamics studies of the entropic elasticity of localized molecular kinks in polyisoprene chains.
We investigate the thermodynamic consequences of the distribution of rotational conformations of polyisoprene on the elastic response of a network chain. In contrast to the classical theory of rubber elasticity, which associates the elastic force with the distribution of end-to-end distances, we find that the distribution of chain contour lengths provides a simple mechanism for an elastic force. Entropic force constants were determined for small contour length extensions of chains constructed as a series of localized kinks, with each kink containing between one and five cis-1,4-isoprene units. The probability distributions for the kink end-to-end distances were computed by two methods: (1) by constructing a Boltzmann distribution from the lengths corresponding to the minimum energy dihedral rotational conformations, obtained by optimizing isoprene using first principles density functional theory, and (2) by sampling the trajectories of molecular dynamics simulations of an isolated molecule composed of five isoprene units. Analogous to the well-known tube model of elasticity, we make the assumption that, for small strains, the chain is constrained by its surrounding tube, and can only move, by a process of reptation, along the primitive path of the contour. Assuming that the chain entropy is Boltzmann's constant times the logarithm of the contour length distribution, we compute the tensile force constants for chain contour length extension as the change in entropy times the temperature. For a chain length typical of moderately crosslinked rubber networks (78 isoprene units), the force constants range between 0.004 and 0.033 N/m, depending on the kink size. For a cross-linked network, these force constants predict an initial tensile modulus of between 3 and 8 MPa, which is comparable to the experimental value of 1 MPa. This mechanism is also consistent with other thermodynamic phenomenology.


Three little words--vision, perception, seeing.
Vision, perception and seeing are everyday words, especially important to those in the image creation business. Vision, here, is used to describe the physiological process of image formation in the eye, and its subsequent projection to the brain for further action. Visual perception is a process driven by sensation with its outcome dependent on judgements based on the perceiver's situational experiences. It is a complex involving cerebral interpretations of a series of retinal images. Seeing is an intellectual exercise strongly influenced by perceptions and cultural experiences. It may be expressed in several ways, among them, verbally and pictorially. Some individuals acquire these expressions at an early age, but for most it must be learned. In the sciences, clarity is important, while in the fine arts, subtlety, and sometimes obscurity, are often sought. In all instances, the image maker is a communicator; and if the message is not received by a prepared viewer, the creator has failed. An understanding of seeing is an important mechanism in the process of image creation. An attempt will be made in this paper to advance an understanding of this process.


Many drugs and phytochemicals can be activated to biological reactive intermediates.
The metabolism of drugs and other xenobiotics is exemplified by cytochrome P450-mediated oxidation to more hydrophilic compounds. Enzymatic oxidation of some functional groups, however, can result in transient reactive intermediates--a transformation that is common in nature. Some drugs and many phytochemicals that contain, for example, a thiophene ring are oxidized by cytochrome P450 to reactive intermediates, such as sulfoxides, that can covalently bond to thiol nucleophiles in macromolecules, such as proteins. Many other functional groups can be oxidized to reactive intermediates--for instance, olefins, alkynes, alkylamines, furans, and p-aminophenols. Because any consequence of a biological reactive intermediate (BRI) is dependent on many factors a number of BRIs are benign. Toxicity is determined by complex and specific arrays of parallel and/or serial pathways and cellular states, not by entities or individual reactions. Because the formation of reactive intermediates can correlate with unacceptable toxicity, it is important to understand if or how a compound may undergo this type of transformation. Not all substances that form reactive intermediates are toxic; many are not. Therefore, it is critical to understand the mechanism of metabolism in considering any toxicity relevance and in evaluating animal models. Indeed, the complex nature of these many interactions and entities underscores the fact that the presence of a BRI is not an accurate indicator of human toxicity. A BRI is neither good nor a priori bad. It is a potential detoxication product and an incidental fate of the xenobiotic.


Influence of sodium pyrophosphate on the physicochemical and gelling properties of myofibrillar proteins under hydroxyl radical-induced oxidative stress.
Porcine myofibrillar proteins (MP) with or without sodium pyrophosphate (PP) were oxidatively stressed in hydroxyl radical (˙OH)-generating systems (10 μM FeCl3, 100 μM ascorbic acid, and 0, 0.5, 3, 10 mM H2O2) at 4 °C for 12 h. The results showed significant protein oxidation under the ˙OH stress, indicated by the modification of amino acid side chain groups and the aggregation of MP, which led to losses in gelling properties of MP especially at high dosages of H2O2 (3-10 mM). The PP addition effectively suppressed ˙OH induced lipid oxidation (as evidenced by TBARS values) in MP, but the inhibitory effect on protein oxidation was limited. In fact, the PP treatment with a high level of H2O2 (10 mM) tended to promote protein unfolding and aggregation in the tested systems. However, a significantly (P < 0.05) improved protein solubility was found in all tested systems with added PP. The PP treated MP gels exhibited a more compact and orderly microstructure, which may explain the reduced cooking loss and improved gel strength.


The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model.
The endoplasmic reticulum (ER) has a major role in protein folding. The accumulation of unfolded proteins in the ER induces a stress, which can be resolved by the unfolded protein response (UPR). Chronicity of ER stress leads to UPR-induced apoptosis and in turn to an unbalance of tissue homeostasis. Although ER stress-dependent apoptosis is observed in a great number of devastating human diseases, how cells activate apoptosis and promote tissue homeostasis after chronic ER stress remains poorly understood. Here, using the Drosophila wing imaginal disc as a model system, we validated that Presenilin overexpression induces chronic ER stress in vivo. We observed, in this novel model of chronic ER-stress, a PERK/ATF4-dependent apoptosis requiring downregulation of the antiapoptotic diap1 gene. PERK/ATF4 also activated the JNK pathway through Rac1 and Slpr activation in apoptotic cells, leading to the expression of Dilp8. This insulin-like peptide caused a developmental delay, which partially allowed the replacement of apoptotic cells. Thanks to a novel chronic ER stress model, these results establish a new pathway that both participates in tissue homeostasis and triggers apoptosis through an original regulation.


Relevance of Activity Tracking With Mobile Devices in the Relationship Between Physical Activity Levels and Satisfaction With Physical Fitness in Older Adults: Representative Survey.
Physical activity has been shown to positively affect many aspects of life, and the positive relationship between physical activity levels and health is well established. Recently, research on the interrelationship between physical activity levels and subjective experiences has gained attention. However, the underlying mechanisms that link physical activity levels with subjective experiences of physical fitness have not been sufficiently explained. This study aimed to explore the role of physical activity tracking (PAT) in the relationship between physical activity levels and satisfaction with physical fitness in older adults. It is hypothesized that higher levels of physical activity are associated with a higher satisfaction with physical fitness in older adults and that this positive association is stronger for older people who use mobile devices for PAT. As part of this study, 1013 participants aged 50 years or older and living in Switzerland were interviewed via computer-assisted telephone interviews. Bivariate and multivariate analyses were applied. The interaction effects between physical activity levels and PAT were evaluated using multiple linear regression analysis. Descriptive analyses showed that 719 participants used at least 1 mobile device and that 136 out of 719 mobile device users (18.9%) used mobile devices for PAT. In the multivariate regression analysis, frequent physical activity was found to have a positive effect on satisfaction with physical fitness (beta=.24, P<.001). A significant interaction effect between physical activity levels and PAT (beta=.30, P=.03) provides some first evidence that the positive effects of physical activity on satisfaction with physical fitness can be enhanced by PAT. The results indicate the potential of PAT to enhance the physical fitness of older adults. However, the results also raise new issues in this context. Recommendations for further research and practice include the acquisition of longitudinal data, a more detailed observation of durations of use, and the development of devices for PAT considering health psychology and gerontology theories.


Racial/ethnic disparities in ADHD diagnosis by kindergarten entry.
Whether and to what extent racial/ethnic disparities in attention-deficit/hyperactivity disorder (ADHD) diagnosis occur by kindergarten entry is currently unknown. We investigated risk factors associated with an ADHD diagnosis by kindergarten entry generally, and specifically whether racial/ethnic disparities in ADHD diagnosis occur by this very early time period. Secondary analysis of data from children enrolled in the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B), a large, nationally representative cohort of U.S. children born in 2001. Data include information from birth certificates, parent and teacher questionnaires, and in-person developmental assessments conducted with children at intervals from 9 months through kindergarten entry. The analytic sample included children enrolled in the ECLS-B at the 60-month assessment (N = 6,550). Black children in the United States were 70% (1 - OR of .30) less likely to receive an ADHD diagnosis than otherwise similar White children. Hispanic children initially appeared to be underdiagnosed for ADHD. However, their disparity with Whites became statistically nonsignificant after controlling for whether a language other than English was primarily spoken in the home. Analyses of kindergarten teacher-reported classroom behavior indicated that neither Black nor Hispanic children displayed less frequent ADHD-related behaviors than Whites. Although they are not less likely to display ADHD-related behaviors, children who are Black or being raised in households where non-English is primarily spoken are less likely than otherwise similar White children to be diagnosed with ADHD in the US.


Variations of capitate morphology in the wrist.
This anatomical study details and categorizes variations in capitate morphology and associated structures in the human cadaveric wrist. We dissected 107 cadaveric wrists. Capitate morphology, the presence of capitate and hamate ridges, the lunate types, and the width of the medial hamate facet of type II lunates and 4th carpometacarpal joint types were recorded. Three types of capitate were identified. The flat type (69/107, or 65%) was characterized by a horizontally oriented (radio-ulnar) lunate-capitate articulation and a longitudinally oriented (proximal-distal) scaphoid-capitate articulation. The flat type was associated with type I lunates or type II lunates with a smaller facet. The spherical type (23/107, or 22%) was associated with a concave articulation formed by the scaphoid and lunate articulations, with an indistinct border between the scaphoid and lunate facets. The width of the medial hamate facet of type II lunates in wrists with a spherical-type capitate was <or=4 mm. The V-shaped type (15/107, or 14%) was characterized by separate lunate and scaphoid facets that converge, forming a V-shape. All the V-shaped capitates had a type II lunate with a large facet. A relationship was found between the 3 capitate types and both the lunate types and the width of the medial hamate facet of the type II lunates. Further study is warranted to determine if these differences in capitate morphology influence the development or progression of various wrist pathologic conditions, such as Kienböck's disease and post-traumatic arthritis associated with scapholunate dissociation and scaphoid nonunion, and the outcome of certain surgical procedures, such as a proximal row carpectomy.


Applying Risk Society Theory to findings of a scoping review on caregiver safety.
Chronic Illness represents a growing concern in the western world and individuals living with chronic illness are primarily managed at home by family caregivers. A scoping review of the home-care literature (2004-2009; updated with review articles from 2010 to January 2013) on the topic of the caregiver revealed that this group experiences the following safety-related concerns: caregivers are conscripted to the role, experience economic hardship, risk being abused as well as abusing, and may well become patients themselves. Methodology and methods used in the scoping review are presented as well as a brief overview of the findings. The concepts of risk and safety are defined. Risk Society Theory is introduced and used as a lens to view the findings, and to contribute to an understanding of the construction of risk in contemporary health-care.


Clinical proteomics of the cerebrospinal fluid: Towards the discovery of new biomarkers.
The cerebrospinal fluid (CSF) circulates within the CNS where it plays an essential physiological role in homeostasis of neuronal cells. This biological fluid has an important protein diversity that results from both filtration of serum through the blood-brain barrier and production/secretion of neuronal peptides and proteins. Changes in CSF composition depend on blood proteome, CSF circulation alterations, as well as physiological or pathological brain status. Hence, CSF proteomic analysis gives a unique opportunity to detect and describe biomarkers in neurological affections. Although lumbar puncture is considered as invasive, post lumbar puncture events remain rare and minor. Nevertheless, CSF biological analysis is currently limited to a small number of parameters and clinical situations suggesting mainly meningitis, malignancies or dementia. Few CSF proteomic studies have been performed in comparison to those on blood. In this review, we will provide a proteomics description of the CSF, summarize the current clinical use of this fluid and describe its clinical proteomics examination.