[Role of extra- and intracellular Ca2+ in changes of NO2- and H2O2 production by endometrium].
The work is aimed to find out the role of extra- and intracellular Ca2+ in cyclic mechanisms of NO2- and H2O2 metabolism in the stroma cells of endometrium activated by acetylcholine. High activity of Mg2+, Ca(2+)-ATP-ase is characteristic of stroma cells of the endometrium. This activity is tested in the presence of 0.01% of the Triton X-100 (36 +/- +/- 2 mumole Pi/mg of protein for 1 hour). The acetylcholinesterase activity in these systems is equal to 9.8 +/- 0.2 mumole thiocholinebromide/mg of protein for 1 hour. Acetylcholine (10 microM) elevated essentially the concentration of cytosolic Ca2+ in them. It was established, that in the control the suspension of stroma cells produced 1 nmol/NO2-/10(6) of cells, this value being constant for the experimental period of time in the range of 5-60 s. The activation of cells (1 microM acetylcholine + 10 microM Ca2+) results in the appearance of cyclicity (maxima on 5, 15 and 60 s) and 5-fold intensification of NO2- production. The rise of extracellular concentration of Ca2+ up to 0.1-1--10 mM results in essential change of the character of the time dependence of NO2- metabolism and only in inappreciable intensification of the response amplitude. Such a pattern is observed for H2O2: 0.77 mumol H2O2/10(6) of cells in the control, at 10 microM Ca2+ maxima of production on the 5 and 30 s, change of the form of the time response, instead of the amplitude under the increase of concentration of extracellular Ca2+. Preincubation of cells with modifiers endoplasmic reticulum ryanodine, caffeine (1 mM) and heparine (10 mM) results in essential drop of NO2- production and infringement of cyclicity, the effect of ryanodine being more expressed on 5 s, than on 15 s, and heparine--also on 5 s, and on 15 s. Preincubation of cells with methylene blue (10 mM), which inhibits guanilate cyclase, result in considerable intensification of NO2- and H2O2 formation and cyclicity losses. Dynamics of NO2- formation (is controversy) reciprocated with cGMP, whereas nitrosoglutathione production and NO3- tends to saturation in the course of time. Thus, acetylcholine-dependent variations of NO2- and H2O2 concentrations in the suspension of stroma cells depend on the state of extra- and intracellular Ca(2+)-stores, are controlled by cGMP. It may be assumed, that the NO2- production minima are caused by its transfer in NO3- and its binding with glutathione.


Effects of prepartum roughage neutral detergent fiber levels on periparturient dry matter intake, metabolism, and lactation in heat-stressed dairy cows.
Heat stress of lactating cattle results in dramatic reductions in dry matter intake (DMI). As a result, energy input cannot satisfy energy needs and thus accelerates body fat mobilization. Decreasing the level of roughage neutral detergent fiber (NDF) in prepartum diets, and thereby increasing the amount of nonfiber carbohydrates, may provide an adequate supply of energy and glucose precursors to maintain and minimize the decrease in DMI while reducing mobilization of adipose tissue. The effects of 3-wk prepartum diets containing different amounts of roughage NDF on DMI, blood metabolites, and lactation performance of dairy cows were investigated under summer conditions in Thailand. Thirty cross-bred cows (87.5% Holstein x 12.5% Sahiwal) were dried off 60 d before their expected calving date and were assigned immediately to a nonlactating cow diet containing the net energy for lactation recommended by the National Research Council (2001) model. The treatment diets contained 17.4, 19.2, and 21.0% DM as roughage NDF from bana grass (Pennisetum purpureum x Pennisetum glaucum) silage. Levels of concentrate NDF were 39.8, 40.2, and 38.6% of dietary NDF, so the levels of dietary NDF were 28.9, 32.1, and 34.2% of DM. After parturition, all cows received a lactating cow diet containing 12.7% roughage NDF and 23% dietary NDF. During the entire experiment, the minimum and maximum temperature-humidity index averaged 77.7 and 86.8, respectively, indicating conditions appropriate for the induction of extreme heat stress. As parturition approached, DMI decreased steadily, resulting in a 12.9, 25, and 32.8% decrease in DMI from d -21 until calving for nonlactating cows fed prepartum diets containing 17.4, 19.2, and 21% roughage NDF, respectively. During the 3-wk prepartum period, intakes of DM and net energy for lactation and concentrations of plasma glucose and serum insulin were higher for cows fed diets containing less roughage NDF. In cows fed the 3-wk prepartum diets containing less roughage NDF, calf birth weights, milk yield, and 4% fat-corrected milk were higher, whereas periparturient concentrations of serum nonesterified fatty acids and plasma beta-hydroxybutyrate were lower. There was a carryover effect of the prepartum diet on serum nonesterified fatty acids and plasma beta-hydroxybutyrate during the first 7 d in milk, and therefore on milk production. These results suggest that feeding diets containing decreased amounts of roughage NDF during the 3-wk prepartum period may minimize the decrease in DMI and lipid mobilization as parturition approaches. This strategy may thus minimize the effect of hormonal factors and heat stress on periparturient cows.


A comparison of isokinetic and isotonic predictions of a functional task.
Controversy still exists regarding the use of isokinetic and isotonic exercise in rehabilitation. Many authors have compared these two types of training methods on various strength measures and functional activity, but have used open kinetic chain training. The purposes of this investigation were to determine: 1) which form of closed kinetic chain training, isokinetic or isotonic, would produce the greatest increase in one-legged jump reaction force, and 2) which training method most accurately predicts peak force produced during a one-legged jump. Forty-two legs from 21 female volunteer subjects were used. Each subject had her dominant and nondominant extremities identified, and then each extremity was randomly assigned to either isokinetic training, isotonic training, or control. Both training groups trained using a leg press exercise 3 days a week for 5 weeks, while the control extremities did not train. The isokinetic extremities were trained using a velocity spectrum (two sets of 10 repetitions at each speed: 60 degrees , 180 degrees and 240 degrees /sec) and the isotonic extremities trained using the DAPRE technique. Data were analyzed with an analysis of variance (ANOVA). There was no difference between the three groups for change in one-legged jump force. Both isokinetic and isotonic groups increased strength after training, but these changes did not correlate with changes in one-legged jump reaction force. These results suggest that changes in neither isokinetic force nor isotonic weight lifted developed in a nonweight-bearing closed kinetic chain, directly translate into increased force production during a functional activity.


How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials.
Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA.


Rapid Ex-Vivo Ciliogenesis and Dose-Dependent Effect of Notch Inhibition on Ciliogenesis of Respiratory Epithelia.
Background: Cilia are actin based cellular protrusions conserved from algae to complex multicellular organisms like Homo sapiens. Respiratory motile cilia line epithelial cells of the tracheobronchial tree, beat in a synchronous, metachronal wave, moving inhaled pollutants and pathogens cephalad. Their role in both congenital disorders like primary ciliary dyskinesia (PCD) to acquired disorders like chronic obstructive pulmonary disease (COPD) continues to evolve. In this current body of work we outline a protocol optimized to reciliate human nasal epithelial cells and mouse tracheal cells in vitro. Using this protocol, we knocked down known cilia genes, as well as use a small molecule inhibitor of Notch, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl Ester (DAPT), to assess the effect of these on ciliogenesis in order to show the validity of our protocol. Methods: Tracheas were harvested from wild-type, adult C57B6 mice, pronase digested and sloughed off epithelial cells grown to confluence in stationary culture on rat-tail collagen coated wells. Upon reaching confluence, collagen was digested and cells placed suspension culture protocol to reciliate the cells. Using this suspension culture protocol, we employed siRNA gene knockdown to assay gene functions required for airway ciliogenesis. Knock down of Dynein axonemal heavy chain 5 (Dnah5), a ciliary structural protein, was confirmed using immunostaining. Mouse tracheal cells were treated in suspension with varying doses of DAPT, an inhibitor of Notch, with the purpose of evaluating its effect and dose response on ciliogenesis. The optimum dose was then used on reciliating human nasal epithelial cells. Results: siRNA knockdown of Foxj1 prevented ciliation, consistent with its role as a master regulator of motile cilia. Knockdown of Dnai1 and Dnah5 resulted in immotile cilia, and Cand1 knockdown, a centrosome protein known to regulate centrosome amplification, inhibited airway ciliogenesis. Dnah5 knockdown was confirmed with significantly decreased immunostaining of cilia for this protein. Inhibiting Notch signaling by inhibiting gamma secretase with DAPT enhanced the percentage of ciliation, and resulted in longer cilia that beat with higher frequency in both mouse and human airway epithelia. Conclusions: Modifying existing reciliation protocols to suit both human nasal epithelial and mouse tracheal tissue, we have shown that knockdown of known cilia-related genes have the expected effects. Additionally, we have demonstrated the optimal dosage for significantly improving reciliation of airway epithelia using DAPT. Given that cilia length and function are significantly compromised in COPD, these findings open up interesting avenues for further exploration.


Use of Endophytic and Rhizosphere Actinobacteria from Grapevine Plants To Reduce Nursery Fungal Graft Infections That Lead to Young Grapevine Decline.
Endophytic and rhizosphere actinobacteria isolated from the root system of 1-year-old grafted Vitis vinifera plants were evaluated for their activities against fungi that cause grapevine trunk diseases. A total of 58 endophytic and 94 rhizosphere isolates were tested. Based on an in vitro bioassay, 15.5% of the endophytic isolates and 30.8% of the rhizosphere isolates exhibited antifungal activity against the fungal pathogen Diplodia seriata, whereas 13.8% of the endophytic isolates and 16.0% of the rhizosphere isolates showed antifungal activity against Dactylonectria macrodidyma (formerly Ilyonectria macrodidyma). The strains which showed the greatest in vitro efficacy against both pathogens were further analyzed for their ability to inhibit the growth of Phaeomoniella chlamydospora and Phaeoacremonium minimum (formerly Phaeoacremonium aleophilum). Based on their antifungal activity, three rhizosphere isolates and three endophytic isolates were applied on grafts in an open-root field nursery in a 3-year trial. The field trial led to the identification of one endophytic strain, Streptomyces sp. VV/E1, and two rhizosphere isolates, Streptomyces sp. VV/R1 and Streptomyces sp. VV/R4, which significantly reduced the infection rates produced by the fungal pathogens Dactylonectria sp., Ilyonectria sp., P. chlamydospora, and P. minimum, all of which cause young grapevine decline. The VV/R1 and VV/R4 isolates also significantly reduced the mortality level of grafted plants in the nursery. This study shows that certain actinobacteria could represent a promising new tool for controlling fungal trunk pathogens that infect grapevine plants through the root system in nurseries.IMPORTANCE Grapevine trunk diseases are a major threat to the wine and grape industry worldwide. They cause a significant reduction in yields as well as in grape quality, and they can even cause plant death. Trunk diseases are caused by fungal pathogens that enter through pruning wounds and/or the root system. Although different strategies have recently been developed to protect pruning wounds using antifungal compounds (natural or synthetic) or biocontrol agents, no tools are yet available for controlling soil pathogens that infect plants through their root system. This study shows that different actinobacterial isolates, when applied to grafts in a nursery, can significantly reduce the infection rate caused by fungal pathogens that enter through the root system. This is a new, promising, and green alternative for preventing the decline of young grapevines in nurseries and vineyards.


[Conservative management in severe pre-eclampsia].
A total of 58 women with severe preeclampsia between 28-33 weeks of gestation were studied during the period from 1 October 1996 to 1 October 1997. Twenty-four women (42%) developed maternal or fetal indications necessitating early delivery within 48 hours, meanwhile the other 34 patients (58%) received expectant management. The average pregnancy prolongation period in the conservative management group was 6.4 days (range 3 to 18). The primary indications for delivery in this group were maternal indications 16 (47%), fetal compromise 13 (39%), 34 weeks of gestation 3 (8%), abruption placentae 1 (3%) and preterm labor 1 (3%). The mean birth weight and Apgar score at 5 minutes were 1520 +/- 310 g and 8, respectively. Expectant management was not associated with fetal death or maternal complications. The only neonatal death was related with sepsis and prematurity. The women in the early delivery group totaled two stillbirths and three neonatal deaths.


Purohit technique of vaginal hysterectomy: a new approach.
To ease intra-operative access to laterally at vaginal hysterectomy, we have developed the 'Purohit technique of vaginal hysterectomy' using a right angle forceps, electrocautery and 10 mm telescope with light source. A prospective study on consecutive 214 women with benign disease of the uterus without prolapse, including cases with relative contraindications (excluding endometriosis and uteri above 20 weeks size), demonstrated it to be easy, safe and effective. Vaginal hysterectomy was successfully completed in 213 (99.53%) cases, with one failure (0.46%) which needed laparoscopic assistance. Vaginal salpingo-oophorectomy was completed in all indicated cases. We believe that many abdominal and laparoscopic hysterectomies could be avoided by this technique. Details of the technique can be seen on the following website http://www.purohittechnique.com


Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation.
The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells. We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells. We found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-ɑ and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults. In a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01's impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging.


Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.
To assess the effects of rivastigmine on the core domains of Alzheimer's disease. Prospective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks. 45 centres in Europe and North America. 725 patients with mild to moderately severe probable Alzheimer's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. Cognitive subscale of the Alzheimer's disease assessment scale, rating on the clinician interview based impression of change incorporating caregiver information scale, and the progressive deterioration scale. At the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer's disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events. Rivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.


Significantly Enhanced Energy Density in Nanocomposite Capacitors Combining the TiO2 Nanorod Array with Poly(vinylidene fluoride).
A novel inorganic/polymer nanocomposite, using 1-dimensional TiO2 nanorod array as fillers (TNA) and poly(vinylidene fluoride) (PVDF) as matrix, has been successfully synthesized for the first time. A carefully designed process sequence includes several steps with the initial epitaxial growth of highly oriented TNA on the fluorine-doped tin oxide (FTO) conductive glass. Subsequently, PVDF is embedded into the nanorods by the spin-coating method followed by annealing and quenching processes. This novel structure with dispersive fillers demonstrates a successful compromise between the electric displacement and breakdown strength, resulting in a dramatic increase in the electric polarization which leads to a significant improvement on the energy density and discharge efficiency. The nanocomposites with various height ratios of fillers between the TNA and total film thickness were investigated by us. The results show that nanocomposite with 18% height ratio fillers obtains maximum increase in the energy density (10.62 J cm-3) at a lower applied electric field of 340 MV m-1, and it also illustrates a higher efficiency (>85%) under the electric field less than 100 MV m-1. Even when the electric field reached 340 MV m-1, the efficiency of nanocomposites can still maintained at ∼70%. This energy density exceeds most of the previously reported TiO2-based nanocomposite values at such a breakdown strength, which provides another promising design for the next generation of dielectric nanocomposite material, by using the highly oriented nanorod array as fillers for the higher energy density capacitors. Additionally, the finite element simulation has been employed to analyze the distribution of electric fields and electric flux density to explore the inherent mechanism of the higher performance of the TNA/PVDF nanocomposites.


Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women.
Urinary tract infection (UTI) is one of the most common adult bacterial infections and exhibits high recurrence rates, especially in postmenopausal women. Studies in mouse models suggest that cyclooxygenase-2 (COX-2)-mediated inflammation sensitizes the bladder to recurrent UTI (rUTI). However, COX-2-mediated inflammation has not been robustly studied in human rUTI. We used human cohorts to assess urothelial COX-2 production and evaluate its product, PGE2, as a biomarker for rUTI in postmenopausal women. We found that the percentage of COX-2-positive cells was elevated in inflamed versus uninflamed bladder regions. We analyzed the performance of urinary PGE2 as a biomarker for rUTI in a controlled cohort of 92 postmenopausal women and PGE2 consistently outperformed all other tested clinical variables as a predictor of rUTI status. Furthermore, time-to-relapse analysis indicated that the risk of rUTI relapse was 3.6 times higher in women with above median urinary PGE2 levels than with below median levels. Taken together, these data suggest that urinary PGE2 may be a clinically useful diagnostic and prognostic biomarker for rUTI in postmenopausal women.


Changing functionality of surfaces by directed self-assembly using oligonucleotides--the Oligo-Tag.
A method is presented to modify surfaces for biotechnological applications. Oligonucleotides have been coupled covalently to a pre-activated surface. Complementary oligonucleotides hybridize to the surface, which are conjugated with functionalities. The oligonucleotides serve as "Oligo-Tags" for these functionalities that now are linked specifically and reversibly. The approach might be used to change DNA-arrays into arrays of arbitrary ligands. We demonstrate the method with an optical wave guide grating coupler as a sensing surface using two different haptens as examples for a variety of functionalities. The haptens were 2,4-dichlorophenoxyacetic acid and atrazin and are recognized by specific antibodies. The surface created was completely regenerable by alkaline washing or temperature increase without any loss of binding capacity. Specificity was demonstrated by competitive binding of antibody in presence and absence of analyte; unspecific binding has not been observed.


Clinical experience, infection control practices and diagnostic algorithms for poxvirus infections - an Emerging Infections Network survey.
In order to determine how best to tailor outreach messages about poxvirus diagnosis and infection control for health practitioners, we surveyed infectious disease physicians in the Infectious Diseases Society of America's Emerging Infections Network. Surveys consisting of two unknown case scenarios designed to raise suspicion for monkeypox and orf were distributed to the 1,080 members of the EIN. The surveys contained questions pertaining to which diagnostic tests, points of contact, and transmission precautions they would likely utilize during patient evaluation. Basic response rates and frequencies of responses were calculated. Comparisons of the survey responses were made using the chi-square test. Of the 212 members who responded (20% response rate), significantly more respondents indicated that they would request diagnostic testing in the context of the monkeypox case scenario as compared to the orf case scenario. A significantly higher number of respondents indicated they would institute droplet or airborne precautions for the monkeypox case as opposed to the orf case scenario. This survey provided an opportunity for public health practitioners to gain insight into physician approaches to evaluation, diagnosis and reporting of suspected poxvirus-associated infections. This survey identified key areas in which public health practitioners can better serve physicians by focusing on education. As a result we were able to identify potential knowledge gaps and deficits in the availability of useful resources to facilitate accurate case identification and management.


Addition of Vision Impairment to a Life-Course Model of Potentially Modifiable Dementia Risk Factors in the US.
Dementia prevention is a high priority, given the large impact of dementia on the well-being of individuals and society. The number of older adults with dementia in the US and globally is projected to increase as a result of population aging and growth. Thus, it is vital to identify potentially modifiable dementia risk factors. Vision impairment has been identified as a risk factor for accelerated cognitive decline and incident dementia. An estimated 90% of vision impairment is preventable or has yet to be treated. Nevertheless, vision impairment has not been included in the dominant life-course models of dementia risk factors used to shape public health policy and research priorities. To strengthen an existing model of potentially modifiable dementia risk factors through the inclusion of vision impairment and to estimate the contributions of those risk factors in the US population. Population-based, cross-sectional study using data from the 2018 round of the Health and Retirement Study. Analyses were conducted from March 11 through September 24, 2021. The study population was a probability sample of US adults aged 50 years and older. Potentially modifiable dementia risk factors, including vision impairment. The estimated population attributable fractions (PAFs) of dementia associated with vision impairment and other dementia risk factors were calculated. The PAF represents the number of cases of dementia that would potentially be prevented if a risk factor were eliminated. The probability sample from the Health and Retirement Study included 16 690 participants (weighted demographic characteristics: 54.0% female, 52.0% age ≥65, 10.6% Black, 80% White, and 9.2% identified as other [including American Indian or Alaska Native, Asian, and Hawiian Native or Pacific Islander, although specific data were not available]). The 12 dementia risk factors in the PAF model were associated with an estimated 62.4% of dementia cases in the US. The risk factor with the highest weighted PAF for dementia was hypertension (12.4%). The PAF of vision impairment was 1.8%, suggesting that more than 100 000 prevalent dementia cases in the US could potentially have been prevented through healthy vision. Existing life-course models of potentially modifiable dementia risk factors may consider including vision impairment. Since a large majority of vision impairment can be treated with cost-effective but underused interventions, this may represent a viable target for future interventional research that aims to slow cognitive decline and prevent incident dementia.


Development and Initial Validation of a Frailty Score for Pediatric Patients with Congenital and Acquired Heart Disease.
Frailty is a multi-dimensional clinical syndrome that is associated with increased morbidity and mortality and decreased quality of life. Children/adolescents with heart disease (HD) perform significantly worse for each frailty domain compared to non-HD peers. Our study aimed to create a composite frailty score (CFS) that can be applied to children/adolescents with HD and evaluate associations between the CFS and outcomes. Children and adolescents (n = 30) with HD (73% single ventricle, 20% heart failure, 7% pulmonary hypertension) were recruited from 2016 to 2017 (baseline). Five frailty domains were assessed at baseline using measures validated for pediatrics: (1) Slowness: 6-min walk test; (2) Weakness: handgrip strength; (3) Fatigue: PedsQL Multi-dimensional Fatigue Scale; (4) Body composition: triceps skinfold thickness; and (5) Physical activity questionnaire. Frailty points per domain (range = 0-5) were assigned based on z-scores or raw questionnaire scores and summed to produce a CFS (0 = least frail; 25 = most frail). Nonparametric bootstrapping was used to identify correlations between CFS and cross-sectional change in outcomes over 2.2 ± 0.2 years. The mean CFS was 12.5 ± 3.5. In cross-sectional analyses of baseline data, correlations (|r|≥ 0.30) were observed between CFS and NYHA class, the number of ancillary specialists, total prescribed medications, heart failure medications/day, exercise test derived chronotropic index and percent predicted VO2peak, and between child and parent proxy PEDsQL. At follow-up, CFS was correlated with an increase in the number of heart failure medications (r = 0.31). CFS was associated with cross-sectional outcomes in youth with heart disease. Longitudinal analyses were limited by small sample sizes due to loss to follow-up.


[Participatory development of indicators for assessing mental health].
The specialized literature frequently cites the inclusion of different interest groups in evaluative research, referred to generically as "participatory evaluation". However, there is a lack of an empirical basis for discussion on ways to operate and (especially) qualify such participation. This article discusses the participatory development of mental health indicators for use in the Centers for Psychosocial Care (CAPS) in Brazil. The process included participation by 58 health workers and managers from 26 CAPS through regular meetings over a year. The meetings were intermediated by a course on mental health evaluation and workshops in subgroups, supported by facilitators throughout the year. The creation of spaces for the qualification of their participation, through the course and other collective activities, proved effective for guaranteeing participation at various levels in the process (such as definition of issues, pre-test indicators, and data analysis) as well as for stimulating ownership of the final product by the participants.


A Single-Dose Intramuscular Nanoparticle Vaccine With or Without Prior Intrauterine Priming Triggers Specific Uterine and Colostral Mucosal Antibodies and Systemic Immunity in Gilts but Not Passive Protection for Suckling Piglets.
An effective single-dose vaccine that protects the dam and her suckling offspring against infectious disease would be widely beneficial to livestock animals. We assessed whether a single-dose intramuscular (i.m.) porcine epidemic diarrhea virus (PEDV) vaccine administered to the gilt 30 days post-breeding could generate mucosal and systemic immunity and sufficient colostral and mature milk antibodies to protect suckling piglets against infectious challenge. The vaccine was comprised of polymeric poly-(lactide-co-glycolide) (PGLA)-nanoparticle (NP) encapsulating recombinant PEDV spike protein 1 (PEDVS1) associated with ARC4 and ARC7 adjuvants, a muramyl dipeptide analog and a monophosphoryl lipid A (MPLA) analog, respectively (NP-PEDVS1). To establish whether prior mucosal exposure could augment the i.m. immune response and/or contribute to mucosal tolerance, gilts were immunized with the NP-PEDVS1 vaccine via the intrauterine route at breeding, followed by the i.m. vaccine 30 days later. Archived colostrum from gilts that were challenged with low-dose PEDV plus alum was used as positive reference samples for neutralizing antibodies and passive protection. On day 100 of gestation (70 days post i.m. immunization), both vaccinated groups showed significant PEDVS1-specific IgG and IgA in the serum, as well as in uterine tissue collected on the day of euthanasia. Anti-PEDVS1 colostral IgG antibody titers collected at farrowing were significantly higher relative to the negative control gilts indicating that the NP vaccine was effective in contributing to the colostral antibodies. The PEDVS1-specific colostral IgA and anti-PEDVS1 IgG and IgA antibodies in the mature milk collected 6 days after farrowing were low for both vaccinated groups. No statistical differences between the vaccinated groups were observed, suggesting that the i.u. priming vaccine did not induce mucosal tolerance. Piglets born to either group of vaccinated gilts did not receive sufficient neutralizing antibodies to protect them against infectious PEDV at 3 days of age. In summary, a single i.m. NP vaccine administered 30 days after breeding and a joint i.u./i.m. vaccine administered at breeding and 30 days post-breeding induced significant anti-PEDVS1 immunity in systemic and mucosal sites but did not provide passive protection in suckling offspring.


Foot and ankle surgery--the Achilles heel of medical students and doctors.
Numerous studies have shown that deficiencies exist in orthopaedic and musculoskeletal medical training resulting in students and doctors regularly failing basic orthopaedic exams. However, there have not been any studies addressing the attitudes of medical students towards the orthopaedic subspecialties. This study aimed (i) to determine if foot and ankle surgery was the orthopaedic specialty with which students and doctors have the most difficulty, (ii) to appraise attitudes towards teaching of foot and ankle surgery, and (iii) to suggest ways teaching might be improved. A questionnaire on orthopaedic teaching was given to 238 medical students in Ireland. Perceived difficulties with foot and ankle surgery were compared to seven other orthopaedic subspecialties and the results were analysed. Other aspects of teaching were assessed including why foot and ankle surgery is perceived as difficult and ways teaching could be improved. Foot and ankle surgery is the orthopaedic subspecialty with which medical students and doctors have the most difficulty, least confidence and poorest knowledge in. This was due to: perceived complexity; insufficient exposure; and a lack of teaching. Foot and ankle surgery is the least popular of the orthopaedic subspecialties and considerable deficiencies exist in its education.


[Use of tamoxifen in the treatment of Riedel's thyroiditis: report of a case].
Treatment of Riedel's thyroiditis (RT) consists of surgery in cases of local limited fibrosis. In most cases, however, it is required the use of anti-inflammatory agents like glucocorticoids or, in those who fail to respond or relapse, tamoxifen can be useful. We report a case of RT in a 55-year-old black woman associated with hypothyroidism and hypoparathyroidism. We evaluated the treatment with tamoxifen, 20 mg twice a day, for eleven months. After sixty days of therapy, patient had no compressive symptoms previously presented. However, in a follow-up of eleven months, there was little objective improvement by regular ultrasonography and computed tomography of the cervical region. Tamoxifen can be useful in RT, mainly when glucocorticoids are not indicated. The ideal duration of this therapy remains to be established.


Isomer specific product detection in the reaction of CH with acrolein.
The products formed in the reaction between the methylidene radical (CH) and acrolein (CH2═CHCHO) are probed at 4 Torr and 298 K employing tunable vacuum-ultraviolet synchrotron light and multiplexed photoionization mass-spectrometry. The data suggest a principal exit channel of H loss from the adduct to yield C4H4O, accounting for (78 ± 10)% of the products. Examination of the photoionization spectra measured upon reaction of both CH and CD with acrolein reveals that the isomeric composition of the C4H4O product is (60 ± 12)% 1,3-butadienal and (17 ± 10)% furan. The remaining 23% of the possible C4H4O products cannot be accurately distinguished without more reliable photoionization spectra of the possible product isomers but most likely involves oxygenated butyne species. In addition, C2H2O and C3H4 are detected, which account for (14 ± 10)% and (8 +10, -8)% of the products, respectively. The C2H2O photoionization spectrum matches that of ketene and the C3H4 signal is composed of (24 ± 14)% allene and (76 ± 22)% propyne, with an upper limit of 8% placed on the cyclopropene contribution. The reactive potential energy surface is also investigated computationally, and specific rate coefficients are calculated with RRKM theory. These calculations predict overall branching fractions for 1,3-butadienal and furan of 27% and 12%, respectively, in agreement with the experimental results. In contrast, the calculations predict a prominent CO + 2-methylvinyl product channel that is at most a minor channel according to the experimental results. Studies with the CD radical strongly suggest that the title reaction proceeds predominantly via cycloaddition of the radical onto the C═O bond of acrolein, with cycloaddition to the C═C bond being the second most probable reactive mechanism.


Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units.
This study was specifically focused on para-professional healthcare workers (PHCWs) who handle cytotoxic drugs and contaminated wastes at the Public Teaching Hospitals of Marseille (AP-HM), France. It first aimed at evaluating the knowledge and professional practice of the PHCWs who belong to a personnel category among the less informed and protected in hospitals. In a second time, this study also proposed to raise awareness, educate and train the staff on protective measures to minimise the exposure of the PHCWs to the potential toxicity of anticancer chemotherapy agents (or metabolites) when cleaning and handling both cytotoxic drugs and wastes. Among the 11 oncology units evaluated, 82% completed an assessment survey, 63% of which were PHCWs. Out of nine oncology units assessed, 89% reported limited knowledge of the general risk and of the safe handling of cytotoxic drugs, 89% reported using vinyl gloves which are the less protective ones. Forty-four per cent of the units used wet sweeping techniques for cleaning the floors, and 11% of the units did not have specific procedures for cleaning the equipments used for collecting contaminated excreta. Protective outer apparel was not always worn and chemotherapy wastes were not managed consistently between all units. Standardized procedures and guidelines to prevent occupational exposure were not used by PHCWs. More education and training are needed to improve safety.


[Effect of the inhibition of prostaglandin biosynthesis on the hematopoietic status of irradiated mice].
The administration to mice of preparations inhibiting prostaglandin synthesis was shown to reduce the post-irradiation cytopenia in the peripheral blood and to increase the total cellularity of the bone marrow and the yield of splenic endocolonies. When the exposed mice were injected with intact myelocaryocytes, at the background of the inhibited prostaglandin biosynthesis, the number of exogenous colonies increased.


Future directions for nursing administration.
As the age of centralization wanes, nurse executives must look ahead. The author, noting a terrain obscured by the increasing complexity of nursing practice, points out the advantages of decentralizing decision making and of providing a distinctive nursing stamp to research and administration theory. Nurse executives, trained in management from early in their professional formation, can provide enlightened direction and flexible support for tomorrow's opportunities.


What Does the Chinese Public Care About with Regard to Primary Care Physicians: Trustworthiness or Competence?
Background and Objective: China has launched a series of reforms to enhance primary care. The aims of these reforms are to strengthen the functionality of primary care to encourage patients to use primary care. Patients' trust in physicians is important in clinical medicine; however, little is known about how Chinese patients' preferences relate to their trust in primary care physicians. This study's objectives are to measure the Chinese public's trust in primary care physicians and to characterize reasons of their preferences for health care. Materials and Methods: This quantitative study comprises a face-to-face survey with a convenience sample (n = 273) of people visiting community health centers or stations (CHCSs) in Wuhan, China. We measured the patients' preferences for the different level of hospitals and their trust in physicians, as well as the reasons of the patients' preferences, using a Chinese version of the Wake Forest Physician Trust Scale and other variables (such as demographics, health status, and hospital preference). Results: Approximately two thirds (68.6%) of the participants had experienced a mild or chronic disease in the year before the survey, but only 26.4% preferred to visit CHCSs in such cases. The negative factors related to this lack of preference are the physicians' competence (odds ratio [OR] = 0.250), the medical equipment (OR = 0.301), and the popularity of hospitals (OR = 0.172). The positive factors were ease of access (OR = 2.218) and affordability (OR = 1.900). The participants expressed a moderate trust in physicians in CHCSs (score of 3.02 out of 5). There is no association between the patients' trust and their hospital preference (r = 0.019, p = 0.859). Of the participants, 92 suggested that the physicians in CHCSs should improve in terms of their competence (n = 53), attitude (n = 35), and/or medical ethics (n = 16). Conclusions: This study's results suggest that patients consider improving physicians' competence to be more important and urgent than improving those physicians' trustworthiness in terms of reconstructing Chinese primary care. Improving the physicians' competence would not only reduce the barriers that patients experience regarding CHCSs, but would also increase their trust in the physicians.


Mutation in the beta adducin subunit causes tissue-specific damage to myogenic tone.
Damage to renal artery myogenic tone is universally associated with progressive kidney damage. Recently, we have observed that mutations in the beta adducin subunit are associated with proteinuria in the Milan rat. Because of the role of adducin as a component of the cytoskeleton we hypothesized that this mutation may be associated with changes in myogenic tone. Congenic rats were generated with beta adducin subunit mutation (NB rats) and compared with a previously studied rat model with alpha adducin subunit mutation (NAs rats). Blood pressure and urinary protein excretion were studied at two time points: 6 weeks and 4 months of age, and at these time points, small renal, middle cerebral and skeletal (cremaster) arteries were isolated and studied using pressure myography. Agonist-induced vasoconstriction was not different between the two groups at any age. However, myogenic tone in renal arteries was significantly damaged in the NB rat compared to its NAs counterpart and this was associated with a decrease in vascular distensibility. There was a smaller reduction in myogenic tone in the middle cerebral arteries from the NB rat, whereas in the skeletal arteries there was no difference between the two strains. In the NB rat, this tissue-specific damage to myogenic tone was associated with progressive proteinuria despite lower blood pressure than the NAs rat. Mutations in the beta subunit of the adducin protein result in damage to renal artery myogenic tone and this is associated with renal damage as manifest by proteinuria.


The Detection of Spontaneous Venous Pulsation with Smartphone Video Ophthalmoscopy.
Spontaneous venous pulsation (SVP) has a high negative predictive value for raised intracranial pressure and is a useful sign when assessing patients with headache. The objective was to determine if smartphone-based video ophthalmoscopy can detect SVP. In total 233 patients and 291 eyes were recruited from the Dunedin Hospital eye clinic from July to November 2018. Patients were examined by a clinician and graded for SVP with a slit lamp and 78 Dioptre lens. Videos were taken with a smartphone ophthalmoscope and graded by two separate clinicians blinded to the slit lamp findings. Only 272 eyes of 215 patients were included, as others failed in the inclusion criteria for overall video quality. Sensitivity was calculated as how likely the presence of SVP on video was indicative of the presence of SVP on slit lamp. Sensitivity was 84.77% for Observer 1, with 128 videos graded as positive for SVP on video ophthalmoscopy of the 151 identified as positive on slit lamp examination. Sensitivity was 76.82% for Observer 2 with 116 videos correctly identified. The false positive rate was calculated as the number of videos graded positive for SVP that had been graded as negative on slit lamp examination. This was 10.74% for observer 1 and 31.40% for observer 2. This study demonstrates that SVP is detected by video ophthalmoscopy. This may be a useful triage, telemedicine and referral tool to be used for patients with headache in a primary care setting.


From hepatitis C virus infection to B-cell lymphoma.
In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.


Further evidence for differences between cardiac atypical beta-adrenoceptors and brown adipose tissue beta3-adrenoceptors in the pithed rat.
1. We have previously shown (Malinowska & Schlicker, 1996) that the atypical beta-adrenoceptor involved in the positive chronotropic effect of the so-called non-conventional partial beta-adrenoceptor agonists CGP 12177 and cyanopindolol in the pithed rat possesses properties markedly different from those observed for beta3-adrenoceptors in the literature. In the present study, we have directly compared the pharmacological properties of the atypical cardiostimulant beta-adrenoceptor and of the beta3-adrenoceptor mediating the thermogenic response in the brown adipose tissue in pithed and vagotomized rats. 2. Heart rate was dose-dependently increased by CGP 12177 and cyanopindolol by maximally 150 and 100 beats min(-1), yielding pED50 values of 8.0 and 7.3, respectively (pED50, -log10 of the dose in mol kg(-1) body weight i.v. causing the half-maximum effect), but not affected by the selective beta3-adrenoceptor agonist CL 316243 (pED50 > 6.0). 3. CGP 12177, cyanopindolol and CL 316243 increased temperature in the brown adipose tissue by maximally 1 degree C (pED50 values 7.4, 6.3 and 8.6, respectively). 4. The beta1-adrenoceptor antagonist CGP 20712 10 micromol kg(-1), attenuated the cardiostimulatory effect of CGP 12177 and, at a still higher dose (30 micromol kg(-1)), also antagonized its thermogenic effect. The -log10 values of the doses causing a two fold shift of the dose-response curves (DRCs) of CGP 12177 to the right were 6.1 and 5.2, respectively, and were much lower than the corresponding value for the antagonism of CGP 20712 against the beta1-adrenoceptor-mediated positive chronotropic effect which was 8.6. 5. The cardiostimulant and the thermogenic effect of CGP 12177 were not affected by the beta2-adrenoceptor antagonist ICI 118551 10 micromol kg(-1). 6. The beta3-adrenoceptor antagonist SR 59230A (which, by itself, caused a beta1-adrenoceptor-mediated increase in heart rate and, for this reason, was studied after administration of a low dose of CGP 20712) attenuated the cardiostimulant and the thermogenic effect of CGP 12177 to a similar extent. The -log10 values of the doses causing two fold rightward shifts of the DRCs of CGP 12177 were 5.9 and 5.7, respectively. 7. The non-selective beta-adrenoceptor antagonist bupranolol diminished the cardiostimulant and thermogenic response to a very similar extent. The -log10 values causing two fold rightward shifts of the DRCs of CGP 12177 were 5.6 and 5.7, respectively, and were much lower than the corresponding values for the antagonism of bupranolol against the beta1-adrenoceptor-mediated positive chronotropic effect and the beta2-adrenoceptor-mediated decrease in diastolic blood pressure which were 7.6 and 8.3, respectively. 8. The rank order of agonistic potencies for the cardiostimulant effect (CGP 12177 > cyanopindolol > CL 316243) differs from that for the thermogenic response in the brown adipose tissue (CL 316243 > CGP 12177 > cyanopindolol); furthermore, there is a difference with respect to the rank orders of antagonistic potencies for cardiostimulation (CGP 20712 > or = SR 59230A > or = bupranolol > ICI 118551) and thermogenesis (SR 59230A = bupranolol > CGP 20712 > ICI 118551). 9. In conclusion, our study provides further evidence that the atypical cardiostimulant beta-adrenoceptors (causing an increase in heart rate) and beta3-adrenoceptors are pharmacologically different.


Selective Growth and Contact Gap-Fill of Low Resistivity Si via Microwave Plasma-Enhanced CVD.
Low resistivity polycrystalline Si could be selectively grown in the deep (~200 nm) and narrow patterns (~20 nm) of 20 nm pitch design rule DRAM (Dynamic Random Access Memory) by microwave plasma-enhanced chemical vapor deposition (MW-CVD). We were able to achieve the high phosphorus (CVD gap-fill in a large electrical contact area which does is affected by line pitch size) doping concentration (>2.5 × 1021 cm-3) and, thus, a low resistivity by adjusting source gas (SiH4, H2, PH3) decomposition through MW-CVD with a showerhead controlling the decomposition of source gases by using two different gas injection paths. In this study, a selective growth mechanism was applied by using the deposition/etch cyclic process to achieve the bottom-up process in the L-shaped contact, using H2 plasma that simultaneously promoted the deposition and the etch processes. Additionally, the cyclic selective growth technique was set up by controlling the SiH4 flow rate. The bottom-up process resulted in a uniform doping distribution, as well as an excellent filling capacity without seam and center void formation. Thus, low contact resistivity and higher transistor on-current could be achieved at a high and uniform phosphorus (P)-concentration. Compared to the conventional thermal, this method is expected to be a strong candidate for the complicated deep and narrow contact process.


Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors.
The molecular pathology of thymic epithelial tumors (TETs) is largely unknown. Using array comparative genomic hybridization (CGH), we evaluated 59 TETs and identified recurrent patterns of copy number (CN) aberrations in different histotypes. GISTIC algorithm revealed the presence of 126 significant peaks of CN aberration, which included 13 cancer-related genes. Among these peaks, CN gain of BCL2 and CN loss of CDKN2A/B were the only genes in the respective regions of CN aberration and were associated with poor outcome. TET cell lines were sensitive to siRNA knockdown of the anti-apoptotic molecules BCL2 and MCL1. Gx15-070, a pan-BCL2 inhibitor, induced autophagy-dependent necroptosis in TET cells via a mechanism involving mTOR pathways, and inhibited TET xenograft growth. ABT263, an inhibitor of BCL2/BCL-XL/BCL-W, reduced proliferation in TET cells when administered in combination with sorafenib, a tyrosine kinase inhibitor able to downregulate MCL1. Immunohistochemistry on 132 TETs demonstrated that CN loss of CDKN2A correlated with lack of expression of its related protein p16(INK4) and identified tumors with poor prognosis. The molecular markers BCL2 and CDKN2A may be of potential value in diagnosis and prognosis of TETs. Our study provides the first preclinical evidence that deregulated anti-apoptotic BCL2 family proteins may represent suitable targets for TET treatment.


Morphology of the genital organs of male and female giant anteaters (Myrmecophaga tridactyla).
The giant anteater belongs to the supraorder Xenarthra which occupies a systematically isolated position among placental mammals. The species is categorized as Vulnerable by the International Union for Conservation of Nature, and understanding its reproductive characteristics is critical for future conservation efforts. Gross and microscopic anatomy of the genital organs of 23 male and 21 female adult and young roadkill giant anteaters in Brazil were studied. Male giant anteaters presented a short conical penis, intraabdominal testes, and prostate, vesicular and bulbourethral glands. A tubular remnant of the partially fused Müllerian ducts extended from the seminal colliculus through the prostate gland, continued cranially in the genital fold, bifurcated, and attached with one elongation each to the left and right epididymal corpus. The structure presented a total length of up to 10 cm and contained a yellowish liquid in its lumen. Histologically, the caudal section of this structure resembled the female vagina, the middle portion corresponded to the uterus, and the extensions showed characteristics of uterine tubes. In adult female giant anteaters, ovoid ovaries with occasional seminiferous cord-like structures were observed. The animals possessed a simple uterus, which was directly continuous with the vaginal canal. The caudal portion of the vagina had two lumina, separated by a longitudinal septum and opening into two apertures into the vaginal vestibule, cranial to the urethral opening. In the urethral and the lateral vestibular wall, glandular structures with characteristics of male prostate and bulbourethral glands, respectively, were found. The vestibule opened through a vertical vulvar cleft to the exterior. A pair of well-differentiated Wolffian ducts with a central lumen originated ventrally at the vaginal opening into the vestibule and passed in a cranial direction through the ventral vaginal and uterine wall. Each duct extended highly coiled along the ipsilateral uterine tube until the lateral pole of the ovaries where it merged with the rete ovarii. The reproductive morphology of giant anteaters reveals characteristics shared with other Xenarthrans: intraabdominal testes, a simple uterus, and a double caudal vagina. The persistence of well-differentiated genital ducts of the opposite sex in both males and females, however, singles them out among other species. These structures are the results of an aberration during fetal sexual differentiation and possess secretory functions. The possibility of a pathological degeneration of these organs should be considered in reproductive medicine of the species. Knowledge of the unique reproductive characteristics of the giant anteater is essential for future reproductive management of the species. Additionally, further research on the peculiarities of the persisting genital duct structures might help to understand sexual differentiation in placental mammals in general.


Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial.
A VLCK diet supplemented with DHA, commercially available, was tested against an isocaloric VLCK diet without DHA. The main purpose of this study was to compare the effect of DHA supplementation in classic cardiovascular risk factors, adipokine levels, and inflammation-resolving eicosanoids. A total of obese patients were randomized into two groups: a group supplemented with DHA (n = 14) (PnK-DHA group) versus a group with an isocaloric diet free of supplementation (n = 15) (control group). The follow-up period was 6 months. The average weight loss after 6 months of treatment was 20.36 ± 5.02 kg in control group and 19.74 ± 5.10 kg in PnK-DHA group, without statistical differences between both groups. The VLCK diets induced a significant change in some of the biological parameters, such as insulin, HOMA-IR, triglycerides, LDL cholesterol, C-reactive protein, resistin, TNF alpha, and leptin. Following DHA supplementation, the DHA-derived oxylipins were significantly increased in the intervention group. The ratio of proresolution/proinflammatory lipid markers was increased in plasma of the intervention group over the entire study. Similarly, the mean ratios of AA/EPA and AA/DHA in erythrocyte membranes were dramatically reduced in the PnK-DHA group and the anti-inflammatory fatty acid index (AIFAI) was consistently increased after the DHA treatment (p < 0.05). The present study demonstrated that a very low-calorie ketogenic diet supplemented with DHA was significantly superior in the anti-inflammatory effect, without statistical differences in weight loss and metabolic improvement.


Electrical stimulation of osteogenesis.
The three electrical stimulation systems available for treating nonunion of long bones are successful in approximately 85% of cases. The percutaneous direct current bone growth stimulator is partially invasive, allows patient mobility, can be used with magnetic fixation devices, and can be monitored for proper function, but it requires an operation, cannot be used where infection exists, and is subject to breakage. The implantable direct current bone growth stimulator is similar, but is totally invasive. The external pulsing electromagnetic field bone growth stimulator is noninvasive and can be used where infection exists, but it requires long, exact patient compliance and cannot be used with magnetic fixation devices or at certain sites. None of the systems can be used where synovial pseudarthrosis or a sizeable gap between bone ends exists, nor are they more effective than bone grafting. Whether their use might evoke malignant transformation or might accelerate or retard epiphyseal growth patterns is not known. Many controlled studies are needed before it is clear how commonly electrical stimulation should be used to treat bony ununion.


[Metabolic correction of bile outflow in patients with obstructive jaundice].
The purpose of research is to study the influence of infusion therapy structure on the of metabolic disorders and biliary excretion correction in patients with obstructive jaundice. The study was carried out in 139 patients divided into 3 groups with the same volume of infusion therapy (1600 ml/day). In 1-St group (54 patients) infusion therapy included ringer's lactate and 10% glucose solution in the ratio of 1:1. In the 2nd group (37 patients) infusion therapy was sterofundine - G-5. In the 3rd group (48 patients) in infusion therapy have included remaxol with dosage of 800 ml/day. The inclusion of remaxol and sterofundin in infusion therapy leads to the improvement of biliary excretion in the early postoperative period versus ringer's lactate and 10% glucose solution. Remaxol has the advantage in metabolic disorders and biliary excretion correction versus sterofundine-G-5.


[Current use of ECT in the treatment of depressive disorders].
If used with correct indication, electroconvulsive therapy (ECT) is a very effective and safe treatment for some forms of major depression, provided due consideration is given to possibly concomitant somatic conditions and that the cardiovascular reactions during and after the ECT treatments are managed carefully. Despite this, ECT remains controversial, especially in Germany. This article provides an overview of the current state of the art in ECT: appropriate indications, best practice in conducting ECT, side effects and recent developments in the use of ECT as maintenance therapy. This, it is hoped, will contribute to a more factually grounded discussion of the use of ECT.


Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration.
Aa robust inflammatory response to tissue damage and infection is conserved across almost all animal phyla. Neutrophils and macrophages, or their equivalents, are drawn to the wound site where they engulf cell and matrix debris and release signals that direct components of the repair process. This orchestrated cell migration is clinically important, and yet, to date, leukocyte chemotaxis has largely been studied in vitro. Here, we describe a genetically tractable in vivo wound model of inflammation in the Drosophila melanogaster embryo that is amenable to cinemicroscopy. For the first time, we are able to examine the roles of Rho-family small GTPases during inflammation in vivo and show that Rac-mediated lamellae are essential for hemocyte motility and Rho signaling is necessary for cells to retract from sites of matrix- and cell-cell contacts. Cdc42 is necessary for maintaining cellular polarity and yet, despite in vitro evidence, is dispensable for sensing and crawling toward wound cues.


Frequent shopping by men and women increases survival in the older Taiwanese population.
Active ageing is a key to healthy ageing; shopping behaviour is an economically relevant activity of the elderly. Analysis was based on the NAHSIT 1999-2000 dataset. A total of 1841 representative free-living elderly Taiwanese people were selected and information included demographics, socioeconomic status, health behaviours, shopping frequencies, physical function and cognitive function. These data were linked to official death records. Cox proportional hazard models were used to evaluate shopping frequency on death from 1999-2008 with possible covariate adjustment. Highly frequent shopping compared to never or rarely predicted survival (HR 0.54, 95% CI 0.43 to 0.67) with adjustment for physical function and cognitive function and other covariates HR was 0.73 (95% CI 0.56 to 0.93). Elderly who shopped every day have 27% less risk of death than the least frequent shoppers. Men benefited more from everyday shopping than women with decreased HR 28% versus 23% compared to the least. Shopping behaviour favourably predicts survival. Highly frequent shopping may favour men more than women. Shopping captures several dimensions of personal well-being, health and security as well as contributing to the community's cohesiveness and economy and may represent or actually confer increased longevity.


A prospective, randomized platelet-function study of heparinized oxygenators and cardiotomy suction.
The purpose of this study was to determine if substitution of a heparin-coated oxygenator and salvaged autologous blood for cardiotomy suction would improve platelet function. A prospective, randomized trial. A large academic medical center. Sixty adult patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (CPB). Patients were randomized into 1 of 4 groups in a 2 x 2 factorial design by oxygenator (heparinized v nonheparinized) and blood salvage during CPB (cardiotomy suction v salvaged autologous blood). Primary outcome measures were platelet function, glass-bead retention, platelet dense-body adenosine triphosphate secretion, platelet-rich plasma (PRP) aggregometry, Plateletworks platelet-function analyzer (Helena Laboratories Corp, Allen Park, MI), and platelet count. Secondary outcome measures were chest-tube drainage and allogeneic blood transfusion requirements. All platelet-function tests except thrombin-receptor activator peptide-induced PRP aggregometry showed a reduction in platelet function during and immediately after CPB (all p < 0.05). The only statistically significant difference in platelet-function tests between the groups was the glass-bead assay at 5 minutes before discontinuation of CPB (p < 0.05). This difference resolved 10 minutes after protamine administration. There were no differences between the groups in the amount of blood transfused, chest-tube drainage, and routine laboratory test results. The authors concluded that the effects of these changes to the CPB circuit were small and inconsequential in this cohort of patients.


Tubuloglomerular feedback during elevated renal venous pressure.
Interstitial hydrostatic and oncotic pressures are believed to influence the sensitivity of the tubuloglomerular feedback (TGF) control. To further investigate this hypothesis, three groups of experiments with elevated renal venous pressure (Prv) were conducted. We investigated 1) the stop-flow pressure (Psf) feedback response; 2) urine flow rate, glomerular filtration rate (GFR), subcapsular interstitial hydrostatic pressure (Psc), and interstitial oncotic pressure (pi int); and 3) the proximal-distal single nephron glomerular filtration rate (SNGFR). The results showed that the Psf feedback response was unaffected by Prv elevation. Psc increased from 0.5 to 3.5 mmHg and pi int increased from 2.1 to 5.8 mmHg; thus, no change in net interstitial pressure (Psc - pi int) was found during elevated Prv. There was a significant proximal-distal SNGFR difference during both control and elevated Prv (8.0 and 6.3 nl/min, respectively). A 20% reduction in total GFR and SNGFR was observed at increased Prv. In separate experiments using the same protocol, a 5% body wt/h volume expansion with saline was induced before Prv was elevated. During volume expansion, TGF sensitivity declined and net interstitial pressure increased, both of which were normalized by increasing Prv. The results show that the TGF sensitivity is normal during elevated Prv to 20 mmHg and that the increase in Psc during this condition is counter-balanced by an increase in pi int. In addition, the decrease in GFR and SNGFR during increased Prv cannot be explained by a change in TGF activity. However, these findings indicate that both interstitial hydrostatic and oncotic pressures may influence the resetting of the TGF sensitivity.


Agroforestry systems and environmental quality: introduction.
Investments in agroforestry research during the past three decades-albeit modest-have yielded significant gains in understanding the role of trees on farmlands, and the ecological and economic advantages of integrated farming systems. While early research focused mostly on farm or local levels, broader-level ecosystem services of agroforestry systems (AFS) have raised high expectations in recent years. The nine papers included in this special collection deal with three of such environmental benefits of AFS: water-quality enhancement, carbon sequestration, and soil improvement. These benefits are based on the perceived ability of (i) vegetative buffer strips (VBS) to reduce surface transport of agrochemical pollutants, (ii) large volumes of aboveground and belowground biomass of trees to store high amounts of C deeper in the soil profile, and (iii) trees to enhance soil productivity through biological nitrogen fixation, efficient nutrient cycling, and deep capture of nutrients. The papers included have, in general, substantiated these premises and provided new insights. For example, the riparian VBS are reported to increase the reservoir life, in addition to reducing transport of agrochemicals; the variations in C storage in different soil-fraction sizes suggest that microaggregate (250-53 μm) dynamics in the soil could be a good indicator of its C-storage potential; and the use of vector analysis technique is recommended in AFS to avoid consequences of inaccurate and overuse of fertilizers. The papers also identified significant knowledge gaps in these areas. A common theme across all three environmental quality issues covered is that more and varied research datasets across a broad spectrum of conditions need to be generated and integrated with powerful statistical tools to ensure wide applicability of the results. Furthermore, appropriate management practices that are acceptable to the targeted land users and agroforestry practitioners need to be designed to exploit these environmental benefits. The relative newness of research in environmental quality of AFS will pose some additional challenges as well. These include the lack of allometric equations for tree-biomass determination, absence of standardized norms on soil sampling depth, and limitations of fixed-effect models arising from issues such as pseudo-replication and repeated measures that are common in studies on preexisting field plots. Overall, this special collection is a timely effort in highlighting the promise of AFS in addressing some of the environmental quality issues, and the challenges in realizing that potential.


A Primer on Chimeric Antigen Receptor T-cell Therapy-related Toxicities for the Intensivist.
Chimeric antigen receptor (CAR) T-cell therapy is an innovative treatment approach that has shown remarkable efficacy against several hematologic malignancies. However, its use can be associated with unique and sometimes severe toxicities that require admission to intensive care unit in 30% of patients, and intensivists should be aware of immune-mediated toxicities of CAR T-cell therapy and management of adverse events. We will review available literature on current diagnostic criteria and therapeutic strategies for mitigating these most common toxicities associated with CAR T-cell therapy including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the post-infusion period. The authors will also review other toxicities associated with CAR T-cell therapy including cytopenias, acquired immunocompromised states, and infections, and discuss the available literature on best supportive care and prophylaxis recommendations. Critical care medicine specialists play a crucial role in the management of patients undergoing CAR T-cell therapies. With the expanding use of these products in increasing numbers of treating centers, intensivists' roles as part of the multidisciplinary team caring for these patients will have an outsized impact on the continued success of these promising therapies.


Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals.
Although an organizational model for syncope management facilities was proposed in the 2004 guidelines of the European Society of Cardiology (ESC), its implementation in clinical practice and its effectiveness are largely unknown. This prospective study enrolled 941 consecutive patients referred to the Syncope Units of nine general hospitals from 15 March 2008 to 15 September 2008. A median of 15 patients per month were examined in each unit, but the five older units had a two-fold higher volume of activity than the four newer ones (instituted <1 year before): 23 vs. 12, P = 0.02. These figures give an estimated volume of 163 and 60 patients per 100,000 inhabitants per year, respectively. Referrals: 60% from out-of-hospital services, 11% immediate and 13% delayed referrals from the Emergency Department, and 16% hospitalized patients. A diagnosis was established on initial evaluation in 191 (21%) patients and early by means of 2.9 +/- 1.6 tests in 541 (61%) patients. A likely reflex cause was established in 67%, orthostatic hypotension in 4%, cardiac in 6% and non-syncopal in 5% of the cases. The cause of syncope remained unexplained in 159 (18%) patients, despite a mean of 3.5 +/- 1.8 tests per patient. These latter patients were older, more frequently had structural heart disease or electrocardiographic abnormalities, unpredictable onset of syncope due to the lack of prodromes, and higher OESIL and EGSIS risk scores than the other groups of patients. The mean costs of diagnostic evaluation was 209 euro per outpatient and 1073 euro per inpatient. The median cost of hospital stay was 2990 euro per patient. We documented the current practice of syncope management in specialized facilities that have adopted the management model proposed by the ESC. The results are useful for those who wish to replicate this model in other hospitals. Syncope remains unexplained during in-hospital evaluation in more complex cases at higher risk.


Identification of N-acetylgalactosamine-containing glycoproteins PEB3 and CgpA in Campylobacter jejuni.
It was demonstrated recently that there is a system of general protein glycosylation in the human enteropathogen Campylobacter jejuni. To characterize such glycoproteins, we identified a lectin, Soybean agglutinin (SBA), which binds to multiple C. jejuni proteins on Western blots. Binding of lectin SBA was disrupted by mutagenesis of genes within the previously identified protein glycosylation locus. This lectin was used to purify putative glycoproteins selectively and, after sodium dodecyl sulphatepolyacrylamide gel electrophoresis (SDS-PAGE), Coomassie-stained bands were cut from the gels. The bands were digested with trypsin, and peptides were identified by mass spectrometry and database searching. A 28kDa band was identified as PEB3, a previously characterized immunogenic cell surface protein. Bands of 32 and 34kDa were both identified as a putative periplasmic protein encoded by the C. jejuni NCTC 11168 coding sequence Cj1670c. We have named this putative glycoprotein CgpA. We constructed insertional knockout mutants of both the peb3 and cgpA genes, and surface protein extracts from mutant and wild-type strains were analysed by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE). In this way, we were able to identify the PEB3 protein as a 28 kDa SBA-reactive and immunoreactive glycoprotein. The cgpA gene encoded SBA-reactive and immunoreactive proteins of 32 and 34 kDa. By using specific exoglycosidases, we demonstrated that the SBA binding property of acid-glycine extractable C. jejuni glycoproteins, including PEB3 and CgpA, is a result of the presence of alpha-linked N-acetylgalactosamine residues. These data confirm the existence, and extend the boundaries, of the previously identified protein glycosylation locus of C. jejuni. Furthermore, we have identified two such glycoproteins, the first non-flagellin campylobacter glycoproteins to be identified, and demonstrated that their glycan components contain alpha-linked N-acetylgalactosamine residues.


Regulation of the Brain Neural Niche by Soluble Molecule Akhirin.
In the central nervous system (CNS), which comprises the eyes, spinal cord, and brain, neural cells are produced by the repeated division of neural stem cells (NSCs) during the development of the CNS. Contrary to the notion that the CNS is relatively static with a limited cell turnover, cells with stem cell-like properties have been isolated from most neural tissues. The microenvironment, also known as the NSC niche, consists of NSCs/neural progenitor cells, other neurons, glial cells, and blood vessels; this niche is thought to regulate neurogenesis and the differentiation of NSCs into neurons and glia. Although it has been established that neurons, glia, and blood vessels interact with each other in a complex manner to generate neural tissues in the NSC niche, the underlying molecular mechanisms in the CNS niche are unclear. Herein, we would like to introduce the extracellular secreted protein, Akhirin (AKH; Akhi is the Bengali translation for eye). AKH is specifically expressed in the CNS niche-the ciliary body epithelium in the retina, the central canal of the spinal cord, the subventricular zone, and the subgranular zone of the dentate gyrus of the hippocampus-and is supposedly involved in NSC niche regulation. In this review, we discuss the role of AKH as a niche molecule during mouse brain formation.


Δ9-Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3/S100A8.
MDSCs are potent immunosuppressive cells that are induced during inflammatory responses, as well as by cancers, to evade the anti-tumor immunity. We recently demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the current study, we investigated the epigenetic mechanisms through which THC, an exogenous cannabinoid, induces MDSCs and compared such MDSCs with the naïve MDSCs found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs, which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore, promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs, and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding protein associated with accumulation of MDSCs in cancer models. Neutralization of S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the suppressive function of MDSCs. Together, the current study demonstrates that THC mediates epigenetic changes to promote MDSC differentiation and function and that S100A8 plays a critical role in this process.


Cluster of Enterobacter cloacae pseudobacteremias associated with use of an agar slant blood culturing system.
From 1 February through 12 October 1990, 27 blood cultures processed at Shiprock Hospital were positive for Enterobacter cloacae; only 3 had been reported in the preceding 12 months. Twenty (74%) of the cultures were obtained from patients without clinical evidence of gram-negative septicemia. The increase in E. cloacae-positive blood cultures was temporally associated with the introduction of a new blood culturing system. To evaluate potential risk factors for an E. cloacae-positive blood culture (case-culture), we conducted a case-control study. Case-cultures were compared with 81 randomly selected cultures that were processed during the epidemic period and that were not positive for E. cloacae (controls). Because several factors suggested the possibility of pseudoinfection, we limited our analysis to the 20 blood cultures that appeared to be contaminants. Blood samples received in the laboratory during the midnight shift (5 of 20 [25%] versus 5 of 81 [6%]; odds ratio, 5.1; 95% confidence intervals, 1.01 to 24.6; P = 0.02) or present in the incubator with other E. cloacae-positive samples (17 of 20 [85%] versus 29 of 81 [36%]; odds ratio, 10.2, 95% confidence interval, 2.6 to 57.3; P < 0.001) were at increased risk for contamination. During mock experiments of the procedures for processing blood samples for culture, several breaks in aseptic technique and leakage from the blood culturing system were observed. Cultures of samples obtained from several environmental sites in the laboratory and the hand washings of two laboratory technicians grew E. cloacae. Plasmid and restriction enzyme analyses of E. cloacae isolates recovered from the patients' blood cultures, the two technicians' hand washings, and environmental sites in the laboratory indicated that all had identical plasmid profiles. Our findings suggest that the breaks in aseptic technique and the environmental contamination that occurred in association with the use of the new blood culturing system resulted in contamination of the blood cultures. This outbreak highlights the importance of routine environmental cleaning, periodic quality control assessments, and adherence to aseptic practices in clinical laboratories, particularly when new methods or equipment are introduced and/or new personnel are hired.


Acceptability, feasibility and affordability of infant feeding options for HIV-infected women: a qualitative study in south-west Nigeria.
The objective of this study was to explore the acceptability, feasibility, affordability, safety and sustainability of replacement feeding options for HIV-infected mothers in Ile-Ife, in south-west Nigeria. Six focus group discussions were conducted with a purposive sample of mothers, fathers and grandmothers. The HIV status of all participants was unknown to investigators. All text data were analysed using the Text-based Beta Software program. With regard to the acceptability of replacement feeds, respondents perceived the stigma associated with not breastfeeding to be an important consideration. In this community, breastfeeding is the norm--even though it is not necessarily exclusive. For infected mothers who choose to breastfeed exclusively and then to wean their infants before 6 months of age, respondents did not anticipate early cessation of breastfeeding to be problematic. Respondents noted that acceptable replacement foods included infant formula, soy milk and cow's milk. Barriers to replacement feeding that were mentioned included: the high costs of replacement foods and fuel for cooking; an unreliable supply of electrical power; poor access to safe water; and poor access to storage facilities. The research confirms the difficulty of replacement feeding for HIV-infected mothers in sub-Saharan Africa. The results also provide the basis for new issues and hypothesis for future research in other communities with similar socio-cultural and economic characteristics.


Root Microbiome Modulates Plant Growth Promotion Induced by Low Doses of Glyphosate.
Glyphosate is a commonly used herbicide with a broad action spectrum. However, at sublethal doses, glyphosate can induce plant growth, a phenomenon known as hormesis. Most glyphosate hormesis studies have been performed under microbe-free or reduced-microbial-diversity conditions; only a few were performed in open systems or agricultural fields, which include a higher diversity of soil microorganisms. Here, we investigated how microbes affect the hormesis induced by low doses of glyphosate. To this end, we used Arabidopsis thaliana and a well-characterized synthetic bacterial community of 185 strains (SynCom) that mimics the root-associated microbiome of Arabidopsis We found that a dose of 3.6 × 10-6 g acid equivalent/liter (low dose of glyphosate, or LDG) produced an ∼14% increase in the shoot dry weight (i.e., hormesis) of uninoculated plants. Unexpectedly, in plants inoculated with the SynCom, LDG reduced shoot dry weight by ∼17%. We found that LDG enriched two Firmicutes and two Burkholderia strains in the roots. These specific strains are known to act as root growth inhibitors (RGI) in monoassociation assays. We tested the link between RGI and shoot dry weight reduction in LDG by assembling a new synthetic community lacking RGI strains. Dropping RGI strains out of the community restored growth induction by LDG. Finally, we showed that individual RGI strains from a few specific phyla were sufficient to switch the response to LDG from growth promotion to growth inhibition. Our results indicate that glyphosate hormesis was completely dependent on the root microbiome composition, specifically on the presence of root growth inhibitor strains.IMPORTANCE Since the introduction of glyphosate-resistant crops, glyphosate has become the most common and widely used herbicide around the world. Due to its intensive use and ability to bind to soil particles, it can be found at low concentrations in the environment. The effect of these remnants of glyphosate in plants has not been broadly studied; however, glyphosate 1,000 to 100,000 times less concentrated than the recommended field dose promoted growth in several species in laboratory and greenhouse experiments. However, this effect is rarely observed in agricultural fields, where complex communities of microbes have a central role in the way plants respond to external cues. Our study reveals how root-associated bacteria modulate the responses of Arabidopsis to low doses of glyphosate, shifting between growth promotion and growth inhibition.


Socially responsible investing. Is it successful?
Socially responsible investing (SRI) has been defined as "the integration of social or ethical criteria into the investment decision-making process." Based on the values they hold, investors distinguish socially responsible investments from those which are not by implementing social screens: nonfinancial criteria applied in the decision-making process. Socially responsible investors typically follow one of three approaches to ethical investing: avoidance of businesses whose activities they do not support, a positive approach where they seek investments that will enhance the quality of life, and an activist approach where they attempt to influence the company's activities. In addition to individuals, many institutional investors are heavily involved with SRI. Activist investors can judge their investments' performance by the success of their shareholder activities. Investors might also look at the societal effects of their investments. If investors are seeking to change the corporation or society, SRI has proven to be successful. Empirical studies have shown mixed results with respect to the financial performance of SRI, but the findings tend to show that SRI has minimal impact, either positively or negatively, on investment returns. Nevertheless, many factors indicate that SRI may be here to stay.


Electrical stimulation of the lingual musculature in obstructive sleep apnea.
The influence of lingual muscle activity on airflow dynamics in the upper airway was examined in nine patients with obstructive sleep apnea. Muscles that retract the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus) were selectively stimulated electrically during sleep with fine wire electrodes placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and 40-microseconds pulse duration did not elicit changes in electroencephalographic patterns or heart rate or alter airflow after the stimulation burst had ceased. The highest stimulus intensity that did not arouse patients from sleep was then utilized to examine the effect of lingual muscle recruitment on airflow dynamics during steady-state periods of inspiratory airflow limitation. When applying a stimulus burst during single inspirations, maximal inspiratory airflow decreased by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P < 0.001) compared with breaths immediately before and after the stimulated breath. When consecutive inspirations were stimulated repeatedly, protrusor stimulation decreased the frequency of obstructive breathing episodes in four patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest that stimulation of the lingual muscles can increase or decrease airflow depending on the specific muscles stimulated without arousing patients from sleep.


Posttraumatic syringomyelia: a technical note.
Previous studies have not identified a preferred surgical technique to treat posttraumatic syringomyelia. Both syringopleural shunting and arachnoidolysis are used in neurosurgery practice for the surgical treatment of posttraumatic syringomyelia. In this study, we present a new technique designed to achieve a better outcome following surgery. A 33-year-old man, who exhibited pain and spasticity below the thoracic region after a traffic accident that occurred 16 years ago, was treated with a new technique. He also had paraparesis and urinary incontinency before the surgery. The initial cervicothoracic Magnetic Resonance Imaging (MRI) scans showed the development of a syrinx in the T4-5 region. A syringopleural shunt and bilateral subarachnoid to subarachnoid catheters from proximal to distal zones of the syrinx were performed under surgical microscope. The operative time was 90 minutes, and the blood loss was approximately 100 mL. The patient was mobilized on postoperative day 2 and was discharged 4 days after surgery with mild improvement of his preoperative symptoms. Postoperative MRI scans revealed partial regression at 6 months and complete decompression of the syrinx at 3 years follow-up without any clinical symptoms. This is a report of minimal-access insertion combining syringopleural with subarachnoid-subarachnoid bypass shunt insertion. This minimally invasive technique seems to be an effective and safe method.


Comparison of filter media materials for heavy metal removal from urban stormwater runoff using biofiltration systems.
The filter media in biofiltration systems play an important role in removing potentially harmful pollutants from urban stormwater runoff. This study compares the heavy metal removal potential (Cu, Zn, Cd, Pb) of five materials (potting soil, compost, coconut coir, sludge and a commercial mix) using laboratory columns. Total/dissolved organic carbon (TOC/DOC) was also analysed because some of the test materials had high carbon content which affects heavy metal uptake/release. Potting soil and the commercial mix offered the best metal uptake when dosed with low (Cu: 44.78 μg/L, Zn: 436.4 μg/L, Cd, 1.82 μg/L, Pb: 51.32 μg/L) and high concentrations of heavy metals (Cu: 241 μg/L, Zn: 1127 μg/L, Cd: 4.57 μg/L, Pb: 90.25 μg/L). Compost and sludge also had high removal efficiencies (>90%). Heavy metal leaching from these materials was negligible. A one-month dry period between dosing experiments did not affect metal removal efficiencies. TOC concentrations from all materials increased after the dry period. Heavy metal removal was not affected by filter media depth (600 mm vs. 300 mm). Heavy metals tended to accumulate at the upper 5 cm of the filter media although potting soil showed bottom-enriched concentrations. We recommend using potting soil as the principal media mixed with compost or sludge since these materials perform well and are readily available. The use of renewable materials commonly found in Singapore supports a sustainable approach to urban water management.


White Collars, Dark Histories: The Factors That Lead Women to Commit Corporate Crimes.
The literature on white-collar crimes committed by women is sparse, dealing mostly with their motivations, the incidence of the phenomenon, and differences between the women who commit them and those who commit other types of offenses. This qualitative study maps factors leading women to commit such crimes, with particular focus on their family and personal histories, and on the various roles they played as children and adults, which prepared and "trained" them for future illegal behavior. Data were collected using semi-structured interviews with 18 women convicted and imprisoned for white-collar crimes. A relationship was found between problematic family background and difficulty in help seeking and a nearly obsessive need for love in adulthood, and between the latter and white-collar crime. Theoretical and practical conclusions are discussed and future directions proposed.


Ex-Vivo Method to Quantifiably Evaluate the Staining Effectiveness of Anterior Lens Capsule Dyes.
High frequency of cataracts and the requirements of new European Union regulations for medical devices require the availability of preclinical models to adequately evaluate anterior lens capsule dyes before their use in patients. Herein, we describe an ex vivo method to quantifiably evaluate the macroscopic and microscopic staining effectiveness of anterior lens capsule dyes using porcine eyes. Commercially available trypan blue-based products or physiological saline solution (negative control) was injected into porcine eyes. Anterior pole and lens (after extraction) were macroscopically photographed, and the images were quantitatively analyzed. Lenses were histologically processed, and the staining intensity microscopically was semiquantified. Macroscopic evaluation of the anterior pole revealed bluish staining of the anterior capsule; however, this coloring cannot be macroscopically discerned after lens extraction. Quantitative image analyses showed significant (P < 0.01) staining of the lens capsule compared to the negative control, but not significant (P > 0.05) between the products tested. Quantitative analysis of dying on lens images could not be performed. Microscopic semiquantification of the capsule staining intensity allows us to appreciate differences between products. The described method is a quick and useful tool for macroscopic evaluation by surgeons to choose an anterior capsule staining for use during everyday surgeries, and a more specific microscopic evaluation also allows us to determine the effectiveness and usefulness of these products. This method satisfies preclinical effectiveness evaluations required by European Union regulations and complements the safety and toxicity evaluations that new products must guarantee before they enter the market and are used in clinical practice.


High mobility of flap endonuclease 1 and DNA polymerase eta associated with replication foci in mammalian S-phase nucleus.
Originally detected in fixed cells, DNA replication foci (RFi) were later visualized in living cells by using green fluorescent protein (GFP)-tagged proliferating cell nuclear antigen (PCNA) and DNA ligase I. It was shown using fluorescence redistribution after photobleaching (FRAP) assay that focal GFP-PCNA slowly exchanged, suggesting the existence of a stable replication holocomplex. Here, we used the FRAP assay to study the dynamics of the GFP-tagged PCNA-binding proteins: Flap endonuclease 1 (Fen1) and DNA polymerase eta (Pol eta). We also used the GFP-Cockayne syndrome group A (CSA) protein, which does associate with transcription foci after DNA damage. In normal cells, GFP-Pol eta and GFP-Fen1 are mobile with residence times at RFi (t(m)) approximately 2 and approximately 0.8 s, respectively. GFP-CSA is also mobile but does not concentrate at discrete foci. After methyl methanesulfonate (MMS) damage, the mobile fraction of focal GFP-Fen1 decreased and t(m) increased, but it then recovered. The mobilities of focal GFP-Pol eta and GFP-PCNA did not change after MMS. The mobility of GFP-CSA did not change after UV-irradiation. These data indicate that the normal replication complex contains at least two mobile subunits. The decrease of the mobile fraction of focal GFP-Fen1 after DNA damage suggests that Fen1 exchange depends on the rate of movement of replication forks.


Assessing heteroplasmic load in Leber's hereditary optic neuropathy mutation 3460G->A/MT-ND1 with a real-time PCR quantitative approach.
To quantify the amount of the 3460G-->A/ND1 point mutation responsible for Leber's hereditary optic neuropathy, we developed a quantitative real-time polymerase chain reaction method based on the SYBR Green assay and a new approach using the TaqMan assay. Both methods were based on the amplification refractory mutation system, comparing the heteroplasmic load quantified by restriction fragment length polymorphism in 15 Leber's hereditary optic neuropathy family members, with the results obtained using quantitative real-time polymerase chain reaction methods. The comparative evaluation of mitochondrial DNA (mtDNA) heteroplasmy from blood samples showed significant correlation between restriction fragment length polymorphism analysis, real-time SYBR Green assay, and TaqMan assay. We validated the last method by measuring experimental samples composed by a known proportion of cloned plasmids containing either the wild-type or mutant sequence, giving a correlation coefficient of 0.999 (P < 0.0001). The real-time amplification refractory mutation system polymerase chain reaction by TaqMan assay provides a rapid, reliable, sensitive, reproducible, and one-step quantitative method to detect heteroplasmic mutant mtDNA. This method allows the quantitation of a broad range of mutational load (up to 100%, down to 0.01%) on the basis of in vitro calibration, thus rendering the TaqMan assay suitable for the diagnostic analysis of heteroplasmic load in mtDNA-related disorders.


The isolation of illness.
Reading the illness narratives of my professional collogues was a moving experience, which reminded me of my own vulnerability and made clear the wisdom of connecting the dots between lived experience and scholarship. Though this wisdom is compelling, it is far from clear how it might be done. Including lived-sexperience in medical humanities scholarship exposes researchers to the vulnerability and isolation that goes with illness. Disability studies analysis offers powerful tools for understanding this vulnerability and isolation. The next step is to take that analysis into applied medical scholarship. These articles provide a valuable start in that direction.