Factors predictive of successful retention in care among HIV-infected men in a universal test-and-treat setting in Uganda and Kenya: A mixed methods analysis.
Previous research indicates clinical outcomes among HIV-infected men in sub-Saharan Africa are sub-optimal. The SEARCH test and treat trial (NCT01864603) intervention included antiretroviral care delivery designed to address known barriers to HIV-care among men by decreasing clinic visit frequency and providing flexible, patient-centered care with retention support. We sought to understand facilitators and barriers to retention in care in this universal treatment setting through quantitative and qualitative data analysis. We used a convergent mixed methods study design to evaluate retention in HIV care among adults (age > = 15) during the first year of the SEARCH (NCT01864603) test and treat trial. Cox proportional hazards regression was used to evaluate predictors of retention in care. Longitudinal qualitative data from n = 190 in-depth interviews with HIV-positive individuals and health care providers were analyzed to identify facilitators and barriers to HIV care engagement. There were 1,863 men and 3,820 women who linked to care following baseline testing. Retention in care was 89.7% (95% CI 87.0-91.8%) among men and 89.0% (86.8-90.9%) among women at one year. In both men and women older age was associated with higher rates of retention in care at one year. Additionally, among men higher CD4+ at ART initiation and decreased time between testing and ART initiation was associated with higher rates of retention. Maintaining physical health, a patient-centered treatment environment, supportive partnerships, few negative consequences to disclosure, and the ability to seek care in facilities outside of their community of residence were found to promote retention in care. Features of the ART delivery system in the SEARCH intervention and social and structural advantages emerged as facilitators to retention in HIV care among men. Messaging around the health benefits of early ART start, decreasing logistical barriers to HIV care, support of flexible treatment environments, and accelerated linkage to care, are important to men's success in ART treatment programs. Men already benefit from increased social support following disclosure of their HIV-status. Future efforts to shift gender norms towards greater equity are a potential strategy to support high levels of engagement in care for both men and women.


Early results with the thrust plate prosthesis in young patients with osteoarthritis of the hip.
The purpose of this study was to evaluate the results of the Thrust Plate Prosthesis as a treatment option for osteoarthritis of the hip in young patients. Of the fifty patients (63 hips) reviewed, 31 (62%) were males and 19 (38%) females. Pre-operative diagnosis included primary osteoarthritis (23), developmental dysplasia (8), avascular necrosis (7), Perthes (4), post-traumatic arthritis (3), rheumatoid arthritis (2), ankylosing spondylitis (1), psoriatic arthropathy (1) and slipped upper femoral epiphysis (1). All components were implanted uncemented with metal-on-metal articulation. The average follow-up was 4.04 years (range 12 months-8.5 years). The mean age of the patients was 42.3 years (range 21-57 years). The mean pre-operative Harris Hip Score was 41.9 (range 12-89) and at final follow-up 89.91 (range 41-100). In 25 hips with > or = 5 yr follow-up, the average HHS at final follow-up was 84.5 (range 50-100). Complications included dislocation (2), transient sciatic nerve palsy (1), discomfort from lateral strap (2), implantation of wrong femoral head (1), revision (3 = 4.76%) and implant loosening (4) (6.35%). The thrust plate prosthesis is a useful alternative in young patients with hip arthritis and the results are comparable with other uncemented hip replacements. The added advantage is preservation of the proximal femoral bone stock, which can prove useful in future revisions.


Low phase noise optoelectronic oscillator based on an electroabsorption modulated laser.
An optoelectronic oscillator (OEO) scheme based on an electroabsorption modulated laser (EML) is proposed and experimentally demonstrated. The oscillation conditions and a complete phase noise model for the EML-based OEO are detailed. A 20-GHz microwave signal with a side-mode suppression ratio of 42 dB is generated and evaluated. The corresponding single sideband phase noise with a 1-km and 4-km fiber used in the loop is respectively measured to be -110.2 dBc/Hz and -114.8 dBc/Hz at 10 kHz offset frequency. The experimental phase noise results agree well with the theoretical results in an offset frequency range from 100 Hz to 10 MHz.


Engaging underrepresented youth populations in community youth development: tapping social capital as a critical resource.
For youth who are the most vulnerable to challenging community conditions, more limited opportunities, and poor health, educational and economic trajectories derive especially strong benefits from engagement in community youth development efforts. Although communities can benefit in powerful ways from the knowledge and insight of these youth populations, the experiences of vulnerable youth are often underrepresented in planning and decision making. This article draws on lessons learned from two communities that successfully engaged such youth in a community change initiative over four years. Key elements in creating the types of safe, supportive, and meaningful settings that promote young people's ongoing participation and leadership were intentionality and commitment; local knowledge of vulnerable populations; adult allies with key capacities; meaningful focus; resources for intensive outreach, relationship building, and youth support; and continuity of key adults. Each of these elements is described, identifying the ways they build on often underrecognized forms of social capital and offering lessons learned about engaging underserved youth populations in community youth development.


Sphincter of Oddi manometry: comparison of microtransducer and perfusion methods.
There are two approaches to endoscopic sphincter of Oddi manometry, the microtransducer method and the perfusion method. Data reported by us and others are reviewed, with the aim of comparing the two techniques. Biliary pressure, pancreatic duct pressure, and sphincter of Oddi phasic wave activity can be measured by both of these methods. Easy handling and the capability of recording the mode of phasic wave propagation with a multilumen catheter are present advantages of perfusion manometry over the microtransducer method. Because there is no need for perfusion of fluid, the equipment needed for microtransducer manometry is simpler than that needed for the perfusion method, and the microtransducer technique may be more suitable for prolonged recording. An inter-study comparison of manometric data is easier with microtransducer manometry, but must await the collection of more data. Manometric differences between various diseases are still inconsistent, whereas there is no question of the effect of sphincterotomy on pressure values, with the exception of pancreatic duct and sphincter pressures. The possibilities of diagnosing sphincter of Oddi dysfunction, and of predicting the response to sphincterotomy have been received with enthusiasm. However, whether the findings obtained by endoscopic manometry over relatively short periods of time can be considered representative of overall sphincter function is now being questioned since the presence of physiologic cyclic changes in sphincter of Oddi phasic activity in phase with the migrating motor complex of the duodenum was demonstrated. Hormonal or pharmacological stimulation of sphincter activity may help us overcome this problem.


Insights into the function of opioid receptors from molecular dynamics simulations of available crystal structures.
The opioid receptors are key targets in the treatment of acute and chronic pain, and the development of novel analgesics with reduced side effects is crucial in the search for more effective medications. The crystal structures of opioid receptors have provided a wealth of knowledge on many aspects of opioid receptor pharmacology and function, including ligand binding poses, location of the sodium allosteric binding site, conformational changes associated with activation and putative dimeric interfaces. These crystal structures also offer a starting point for molecular dynamics (MD) simulations to capture one aspect of drug design that static structures cannot resolve, namely protein dynamics. With the increase in computing power, MD simulations of crystal structures have become an influential tool in understanding the function of GPCRs in general. Here, we discuss lessons learned from MD simulations of opioid receptor crystal structures with reference to (i) the binding pathway of sodium to its crystallographic allosteric site, (ii) the dynamics of ligand-receptor and receptor-receptor interactions, both at the ligand- and G protein-binding sites, (iii) the binding pathway and binding pose of novel ligands, and (iv) opioid receptor oligomerization. This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.


Clinical results with ProDisc: European experience and U.S. investigation device exemption study.
This study is based on a review of the literature related to the use of the ProDisc device and a report of the preliminary results of a prospective randomized study. To review European results related to the use of the ProDisc device and compare the results of this device to lumbar fusion in a prospective, randomized study being performed as part of a Food and Drug Administration-approved investigational study. There are two devices that have been used on a large-scale basis for total disc replacement. These are the SB Charitè and the ProDisc. Both devices were created in Europe and have been used there for more than 10 years. Reported results for these devices have been favorable, but there have been no prospective studies evaluating the outcome. The literature related to the ProDisc was reviewed. The preliminary study data were based on one center's experience participating in the Food and Drug Administration Investigation Device Exemption study. There were 39 patients with a minimum 6-month follow-up. Patients were randomly assigned to receive either the ProDisc or undergo a combined anterior-posterior lumbar fusion in a ratio of 2:1 (ProDisc to fusion). Patients completed standardized questionnaires before surgery and at 6 weeks, 3 months, and 6 months after surgery. Data collection is continuing for the 12- and 24-month follow-up. RESULTS Operative time, blood loss, and length of hospitalization were significantly less in the disc replacement group (P < 0.05). At the 3-month follow-up, the disc replacement group had a significantly greater improvement in Oswestry scores than did the fusion group. There were no differences in pain scores as measured by visual analog scales. Disc replacement patients had greater motion and there was a trend for this group to have greater satisfaction at the 6-month follow-up. The preliminary results of this prospective randomized study found that peri-operative factors were more favorable in the disc replacement group than in the fusion group. There was a trend to greater patient satisfaction in this group. These early results suggest that total disc replacement may be a viable alternative to lumbar spinal fusion in patients with symptomatic disc disruption unresponsive to nonoperative care. Long-term follow-up is needed and is currently being collected for this study group.


Development of a methacholine challenge method to minimize methacholine waste.
The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded. To develop a method with reduced methacholine waste and to compare it to the standard method. Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation. There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification. The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.


Incidence and Risk Factors of Inferior Rectus Muscle Palsy in Pediatric Orbital Blowout Fractures.
The aim of this study was to evaluate the incidence, clinical features, and risk factors of sustaining inferior rectus (IR) palsy in a group of pediatric patients with orbital floor blowout fractures. We performed a retrospective case review of sequential cases of pediatric orbital floor blowout fractures (<18 years old) from 2000 to 2013 in a tertiary ophthalmic center in Singapore. A total of 48 patients were included in our study, of whom 5 had IR palsy (10.4%). Patients with IR palsy had a higher mean age (16.4 ± 1.5 years) compared with patients without IR palsy (12.4 ±3.3 years), had significantly ( p < 0.05) worse preoperative motility, and had significantly greater proportion developing postoperative hypertropia (100%) compared with patients without IR palsy (4.7%). Our series of pediatric blowout fractures demonstrated IR palsy prevalence and clinical features for IR palsy which may be distinct to the pediatric group.


Food addiction: an evolving nonlinear science.
The purpose of this review is to familiarize readers with the role that addiction plays in the formation and treatment of obesity, type 2 diabetes and disorders of eating. We will outline several useful models that integrate metabolism, addiction, and human relationship adaptations to eating. A special effort will be made to demonstrate how the use of simple and straightforward nonlinear models can and are being used to improve our knowledge and treatment of patients suffering from nutritional pathology. Moving forward, the reader should be able to incorporate some of the findings in this review into their own practice, research, teaching efforts or other interests in the fields of nutrition, diabetes, and/or bariatric (weight) management.


[Longitudinal changes of pulmonary function in workers with high wood dust exposure levels].
It is well know that wood dust exposure can induce sino-nasal cancers, rhinitis and asthma; induction of chronic bronchial obstruction, pulmonary fibrosis and lung cancer are also suggested, but data are often inconclusive and in disagreement. The study evaluated the decrease in lung function in a group of 31 non-smokers exposed to high levels of wood dust (> 5 mg/m3 also) and in 2 non-smokering control groups with comparable lung function tests at first examination: 39 mechanical workers without respiratory hazards (group 1) and 30 forestry workers (group 2). Assessment of lung function was repeated at least 5 times during 11.2 +/- 2.4 years for wood workers and 12.3 +/- 4.2 years for group 1 (n.s.) and 15.0 +/- 2.6 years for group 2 (p < 0.0005). Linear regression for annual loss of VC and FEV1 was calculated from observed data for each subject. No significant differences were observed in VC loss or FEV1 loss between woodworkers and control group1 (20.67 +/- 16.9 vs 19.0 +/- 23.2 and 31.37 +/- 22.3 vs 36.2 +/- 22.4 ml/year respectively), while control group 2 showed an accelerated (p < 0.005) VC and FEV1 loss (32.8 +/- 22.1 and 46.6 +/- 21.2 ml/years respectively). In conclusion, the study did not show any alterations in the longitudinal decrease in pulmonary function due to high wood dust exposure levels, perhaps due to the poor inhalability of wood particles that are mostly trapped in the nose; further studies are needed to investigate chronic effects of wood dust exposure on development of Chronic Obstructive Pulmonary Disease, pulmonary fibrosis and also lung cancer.


Generalized muscle pseudo-hypertrophy and stiffness associated with the myotilin Ser55Phe mutation: a novel myotilinopathy phenotype?
Myotilinopathies are a group of muscle disorders caused by mutations in the MYOT gene. It was first described in two families suffering from limb girdle muscle dystrophy type 1 (LGMD 1A), and later identified in a subset of dominant or sporadic patients suffering from myofibrillar myopathy, as well as in a family with spheroid body myopathy. Disease phenotypes associated with MYOT mutations are clinically heterogeneous and include pure LGMD forms as well as late-onset distal myopathies. We report here on a 53-year-old male suffering from a unique clinical profile characterized by generalized symmetrical increase in muscle bulk leading to a Herculean appearance. Muscle weakness and stiffness in the lower extremities were the patient's main complaints. Muscle MRI showed extensive fatty infiltration in the thigh and leg muscles and a muscle biopsy showed a myofibrillar myopathy with prominent protein aggregates. Gene sequencing revealed a Ser55Phe missense mutation in the myotilin gene. The mutation was identified in his older brother, who presented a mild hypertrophic appearance and had a myopathic pattern in EMG, despite not presenting any of the complaints of the proband and having normal muscle strength. This finding, and his deceased father and paternal aunt's similar gait disorders, suggest that this is in fact a new autosomal dominant kindred. The present observations further expand the spectrum of clinical manifestations associated with mutations in the myotilin gene.


Indirect activation of adenosine A1 receptors in cultured rat hippocampal neurons by volatile anaesthetics.
Volatile anaesthetics depress excitatory signal transmission by potentiating the inhibitory action of GABAA receptors and there is strong evidence that this is related with anaesthesia. Using primary hippocampal cultures we analyzed the possibility that the volatile anaesthetics enflurane and sevoflurane depress excitatory signal transmission by activation of adenosine A1 receptors. Primary rat hippocampal cultures on 4 cm poly-L-lysine coated glass coverslips were loaded with the Ca2+-indicator fluo-3 and incorporated in a gastight, temperature-controlled perfusion chamber. The intracellular Ca2+-concentration was monitored with a confocal laser-scanning microscope (BioRad) using the 488 nm laser line of a krypton-argon laser for excitation and the Lasersharp Acquisition software for analysis. Continuous perfusion in Mg2+-free medium generated spontaneous synchronized calcium oscillations, which were dose dependently depressed by the volatile anaesthetics enflurane and sevoflurane (0.25-1 minimum alveolar concentration). Addition of 100 nmol of 2-chloro-N6-cyclopentyladenosine, a specific adenosine A1 receptor antagonist, partly reversed the anaesthetic-induced inhibition of the oscillation amplitude of the oscillating cells. The effect of the anaesthetics was mimicked by the addition of S-(p-nitrobenzyl)-6-thioguanosine, an adenosine transport inhibitor and by the addition of 5-amino-5-deoxyadenosine, an inhibitor of adenosine kinase. The volatile anaesthetics sevoflurane and enflurane activate adenosine A1 receptors in primary rat hippocampal cultures. This effect is mediated by liberation of adenosine most likely by an interaction of the volatile anaesthetics with adenosine transport or key enzymes in adenosine metabolism.


Why Only Humans Shed Emotional Tears : Evolutionary and Cultural Perspectives.
Producing emotional tears is a universal and uniquely human behavior. Until recently, tears have received little serious attention from scientists. Here, we summarize recent theoretical developments and research findings. The evolutionary approach offers a solid ground for the analysis of the functions of tears. This is especially the case for infant crying, which we address in the first part of this contribution. We further elaborate on the antecedents and (intra- and interpersonal) functions of emotional tears in adults. The main hypothesis that emerges from this overview is that crying evolved as an emotional expression that signals distress and promotes prosocial behaviors in conspecifics. Further, shedding tears may influence the mood of the crier and his/her outlook on life primarily as a consequence of fulfillment of the proposed signaling function of tears. We also describe how cultural phenomena such as ritual weeping nicely fit within this framework, as they often aim to support a request for help to a powerful person or deity and promote social bonding.


Post-traumatic membranous obstruction of the inferior vena cava associated with a hypercoagulable state.
It has been hypothesized that abdominal trauma may be one of the factors involved in membranous obstruction of the inferior vena cava. We present two cases of membranous obstruction of the inferior vena cava associated with trauma. One asymptomatic case, associated with an occult myeloproliferative disorder, developed within 3 years of a violent abdominal trauma. The other case, associated with familial plasminogen deficiency, was discovered at surgery 3 days after a road accident with obvious abdominal trauma, since superimposed extensive thrombosis of the inferior vena cava caused acute Budd-Chiari syndrome. We conclude that underlying prothrombotic conditions are probably necessary for the development of membranous obstruction of the inferior vena cava and that minor trauma may contribute to the development of thrombosis through indirect mechanisms.


Cell lysis and protein extraction in a microfluidic device with detection by a fluorogenic enzyme assay.
A critical requirement for achieving a micro total analytical system for the analysis of cells and their constituent proteins is to integrate the lysis and fractionation steps on-chip. Here, an experimental microfluidic system integrating the lysis of bacterial cells and the extraction of a large intracellular enzyme, beta-galactosidase, is demonstrated. The beta-galactosidase is detected and quantified using a fluorogenic enzyme assay and a numerical model. While the focus is on the lysis of typical gram-negative bacterial cells (E. coli), the techniques described here could, in principle, be applied to a variety of different cell types.


CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.
The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.


Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development.
The epicardium, the outermost layer of the heart, is an essential source of cells and signals for the formation of the cardiac fibrous skeleton and the coronary vasculature, and for the maturation of the myocardium during embryonic development. The molecular factors that control epicardial mobilization and differentiation, and direct the epicardial-myocardial cross-talk are, however, insufficiently understood. The T-box transcription factor gene Tbx18 is specifically expressed in the epicardium of vertebrate embryos. Loss of Tbx18 is dispensable for epicardial development, but may influence coronary vessel maturation. In contrast, over-expression of an activator version of TBX18 severely impairs epicardial development by premature differentiation of epicardial cells into SMCs indicating a potential redundancy of Tbx18 with other repressors of the T-box gene family. Here, we show that Tbx2 and Tbx20 are co-expressed with Tbx18 at different stages of epicardial development. Using a conditional gene targeting approach we find that neither the epicardial loss of Tbx2 nor the combined loss of Tbx2 and Tbx18 affects epicardial development. Similarly, we observed that the heterozygous loss of Tbx20 with and without additional loss of Tbx18 does not impact on epicardial integrity and mobilization in mouse embryos. Thus, Tbx18 does not function redundantly with Tbx2 or Tbx20 in epicardial development.


Production and validation of the use of gamma phage for identification of Bacillus anthracis.
Gamma phage specifically lyses vegetative cells of Bacillus anthracis and serves as part of the basis for identification of isolates from agar cultures. We report our study to standardize gamma phage production and preparation and to validate the assay for routine use. Unstable phage preparations were largely reduced through propagation of phage on blood agar cultures of the avirulent B. anthracis strain CDC684 and were adequately stable for extended storage beyond 1 to 2 years at 4 degrees C, provided that the preparation initially gave rise to clearly discernible plaques (macroplaques, 5 to 10 mm in diameter) on dilution at 1:8 or greater during potency testing with the Sterne strain or its equivalent. The primary intent of the assay was to test nonhemolytic, ground-glass-appearing bacterial B. anthracis-like colonies arising from culture of clinical or nonclinical samples on 5% sheep blood agar. Specifically, the assay was designed to show clear or primarily clear circular zones of lysis on bacterial lawns at the site of gamma phage inoculation after incubation at 35 degrees C +/- 2 degrees C for 20 h. When tested with 51 B. anthracis strains and 49 similar non-B. anthracis Bacillus species, the analytical specificity was >95%, a value that is intentionally low because our study design included two rare nonsusceptible B. anthracis strains as well as a rare susceptible non-B. anthracis strain, B. cereus ATCC 4342. Repeatability, day-to-day precision, and analyst-to-analyst precision were superior. The assay was rugged to variations among phage lots, phage concentration, amounts of bacterial inoculum, and incubation times as short as 6 to 8 h. System suitability evaluation showed improved robustness when bacterial lawns were tested with high- and low-density inoculum using the first and second quadrants of a serial four-quadrant streak on 5% sheep blood agar plates.


Advancements of vitreoretinal surgical machines.
This article reviews current advancements in vitreoretinal surgical machines. The most recent advancement in vitreoretinal surgical machines include 27-gauge vitrectomy probes, new cutter designs, higher cut rate, improved intraocular pressure control, new endoillumination technologies, and combined anterior/posterior segment capabilities. With recent advancements in vitreoretinal surgical machines, surgical incisions have become less traumatic and fluidics control has led to a more controlled posterior segment vitrectomy.


Prospective study on long-term dietary patterns and incident depression in middle-aged and older women.
Although individual nutrients have been investigated in relation to depression risk, little is known about the overall role of diet in depression. We examined whether long-term dietary patterns derived from a food-frequency questionnaire (FFQ) predict the development of depression in middle-aged and older women. We conducted a prospective study in 50,605 participants (age range: 50-77 y) without depression in the Nurses' Health Study at baseline (1996) who were followed until 2008. Long-term diet was assessed by using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high in meats) patterns were identified by using a principal component analysis. We used 2 definitions for clinical depression as follows: a strict definition that required both a reported clinical diagnosis and use of antidepressants (3002 incident cases) and a broad definition that further included women who reported either a clinical diagnosis or antidepressant use (7413 incident cases). After adjustment for age, body mass index, and other potential confounders, no significant association was shown between the diet patterns and depression risk under the strict definition. Under the broad definition, women with the highest scores for the Western pattern had 15% higher risk of depression (95% CI: 1.04, 1.27; P-trend = 0.01) than did women with the lowest scores, but after additional adjustment for psychological scores at baseline, results were no longer significant (RR: 1.09; 95% CI: 0.99, 1.21; P-trend = 0.08). Overall, results of this large prospective study do not support a clear association between dietary patterns from factor analysis and depression risk.


Effect of dietary sodium restriction on patients receiving antihypertensive medication.
Twenty-four patients receiving medication for moderate to severe hypertension were studied during a six week normal diet and a six week low sodium period. Mean urinary sodium excretion was reduced from 169 +/- 13 to 92 +/- 7 mmol/24 hour yet with the exception of a small reduction in the mean erect systolic blood pressure 140.7 +/- 2.5 to 135.1 +/- 2.6; p less than 0.05) no significant alteration in the patients blood pressure was noted. Urinary potassium excretion and body weight remained unaltered. However, evaluation of the patient data when the patients were grouped into those taking thiazide diuretics (n = 14) and those not taking diuretics (n = 10) revealed a significant reduction in the mean supine systolic and diastolic and erect systolic blood pressure in the thiazide group. Significant changes in blood pressure were not recorded in the non-diuretic group. It is suggested that moderate dietary sodium restriction in combination with thiazide diuretics is of value in the treatment of moderate to severe hypertension.


[Substitution of care: what do we know, what should we know, and what should we do?]
In order to contain rising healthcare expenditure, the Dutch minister of Health, Welfare, and Sport has agreed with various stakeholders to shift care as much as possible from the expensive specialised care sector to the cheaper primary care sector. Such a shift is only desirable if it constitutes a permanent shift to the primary care sector thereby reducing costs while simultaneously increasing quality of care and the health of the population. In order to prove the success of substitution initiatives, their effects must be compared with the national trend at population level. Longitudinal research is necessary as substitution constitutes a transitional process that requires continuous monitoring and interaction between patients, healthcare providers, insurers, and scientists.


Incidence of Venous Thromboembolism After Different Modes of Gynecologic Surgery.
To evaluate the incidence of postoperative venous thromboembolism after gynecologic surgery by mode of incision. We conducted a retrospective cohort study of all patients who underwent gynecologic surgery from May 2006 to June 2015 at two tertiary care academic hospitals in Massachusetts. Billing and diagnosis codes were used to identify surgeries and cases of venous thromboembolism. A total of 43,751 surgical encounters among 37,485 individual patients were noted during the study. The overall incidence of venous thromboembolism is 0.2% for all gynecologic surgeries, 0.7% for hysterectomy, and 0.2% for myomectomy. Compared with patients undergoing laparotomy, patients who underwent minimally invasive gynecologic surgery were less likely to develop venous thromboembolism (laparoscopy risk ratio 0.22, 95% CI 0.13-0.37; vaginal surgery risk ratio 0.07, 95% CI 0.04-0.12). This effect persisted when data were adjusted for other known venous thromboembolism risk factors such as age, race, cancer, medical comorbidities, use of pharmacologic thromboprophylaxis, admission status, and surgical time. Minimally invasive surgery is associated with a decreased risk of venous thromboembolism in patients undergoing gynecologic surgery, including hysterectomy and myomectomy. Although society guidelines and risk assessment tools do not currently account for mode of surgery when assessing venous thromboembolism risk and recommendations for prevention, there is a small but growing body of evidence in both general and gynecologic surgery literature that surgical approach affects a patient's risk of postoperative venous thromboembolism. Mode of surgery should be considered when assessing venous thromboembolism risk and planning venous thromboembolism prophylaxis for patients undergoing gynecologic surgery.


A Clinical Prediction Model Based on Post Large Artery Atherosclerosis Infarction Pneumonia.
Stroke-associated pneumonia (SAP) has been found as a common complication in acute ischemic stroke (AIS) patients. Large artery atherosclerosis (LAA) infarct is a major subtype of AIS. This study aimed to build a clinical prediction model for SAP of LAA type AIS patients. This study included 295 patients with LAA type AIS. Univariate analyses and logistic regression analyses were conducted to determine the independent predictors for the modeling purpose. Nomogram used receiver operating characteristics to assess the accuracy of the model, and the calibration plots were employed to assess the fitting degree between the model and the practical scenario. One hundred and five patients were employed for the external validation to test the stability of the model. From the univariate analysis, patients' ages, neutrophil-to-lymphocyte ratios, National Institute of Health Stroke scale (NIHSS) scores, red blood cell, sex, history of coronary artery disease, stroke location and volume-viscosity swallow test showed statistical difference in the development group for the occurrence of SAP. By incorporating the factors above into a multivariate logistic regression analysis, patients' ages, neutrophil-to-lymphocyte ratios, NIHSS, and volume-viscosity swallow test emerged as the independent risk factors of the development of SAP. The nomogram based on the mentioned 4 variables above achieved a receiver operating characteristic of 0.951 and a validation group of 0.946. The proposed nomogram is capable of predicting predict the occurrence of SAP in LAA type AIS patients, and it may identify high-risk patients in time and present information for in-depth treatment.


Bi-allelic CAMSAP1 variants cause a clinically recognizable neuronal migration disorder.
Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and severe hypoplasia or absence of the corpus callosum; dysplasia of the basal ganglia, hippocampus, and midbrain; and cerebellar hypodysplasia, similar to the tubulinopathies, a group of monogenic tubulin-associated disorders of cortical dysgenesis. Neural cell rosette lineages derived from affected individuals displayed findings consistent with these phenotypes, including abnormal morphology, decreased cell proliferation, and neuronal differentiation. Camsap1-null mice displayed increased perinatal mortality, and RNAScope studies identified high expression levels in the brain throughout neurogenesis and in facial structures, consistent with the mouse and human neurodevelopmental and craniofacial phenotypes. Together our findings confirm a fundamental role of CAMSAP1 in neuronal migration and brain development and define bi-allelic variants as a cause of a clinically distinct neurodevelopmental disorder in humans and mice.


Seasonal influence on thyroidal response to thyrotrophin-releasing hormone in cattle and buffaloes.
The effect of thyrotrophin-releasing hormone (TRH) on the circulating plasma levels of tri-iodothyronine (T3) and thyroxine (T4) was determined in the same group of animals (four cattle and four Murrah buffaloes) during hot dry (HD), hot humid (HH) and cold environmental conditions. Plasma T3 and T4 concentrations were measured during 2 h before and up to 12 h after the administration of TRH (200 micrograms i.v.). In the preinjection period in both cattle and buffaloes T3 levels were significantly lower in HH conditions. No significant difference in basal (preinjection) T3 levels was observed during HD and cold seasons in cattle. The highest T3 levels were obtained in buffaloes during HD season with intermediate values during the cold months. Plasma T4 levels in these animals were reversed during HD and HH months. In both cattle and buffaloes there was a biphasic response of T3 and T4 to TRH treatment and this varied with time and in size. The season significantly affected the T3 response to TRH in cattle and buffaloes but the T4 response differed in the two species. The ratio of T4/T3 was higher during HH condition compared with other seasons in both cattle and buffaloes. The climate significantly affected the thyroidal response to TRH.


Open distal femur fractures treated with lateral locked implants: union, secondary bone grafting, and predictive parameters.
Nonunion and secondary reduction loss complicate open distal femur fractures with bone loss. The authors hypothesized that locking plates decrease subsequent bone grafting yet maintain alignment and immediate postfixation radiographic features predict primary union. A retrospective chart/radiographic review was performed at a Level 1 university trauma center. Thirty-four adults with 36 open AO/Orthopaedic Trauma Association (AO/OTA) C-type distal femur fractures were studied. All fractures were treated with open reduction, internal fixation with a lateral locked implant with or without antibiotic beads, and subsequent bone grafting. Union required radiographic bridging callus on at least 2 of 4 cortices. Alignment was assessed on initial and united radiographs. Antibiotic beads within a metaphyseal defect defined clinically important bone loss. Eleven (55%) of 20 fractures with bone loss underwent staged bone grafting to achieve union vs 2 (13%) of 16 fractures without bone loss. Antibiotic bead presence was associated with staged bone grafting (P<.01). Of those with bone loss and grafting, 3 had posterior cortical bone loss only, 3 had medial and posterior cortical bone loss, and 5 had segmental defects. Of 9 fractures with bone loss not requiring grafting, all had radiographic posterior cortical contact and 7 had radiographic medial cortical contact. Posterior cortical continuity was associated with injuries not requiring bone graft (P<.001). Thirty-four had accurate frontal plane reductions and 35 had accurate sagittal plane reductions. Despite metaphyseal bone loss, locking plates obviate the need for routine bone grafting of some open distal femur fractures. Those with radiographic posterior cortical contact are strongly correlated with primary union.


Predictive value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for primary patency of percutaneous transluminal angioplasty in hemodialysis arteriovenous fistula stenosis.
The aim of this study is to investigate the potential association of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula (AVF) stenosis. This study conducted a retrospective review of patients with end-stage renal disease referred for hemodialysis AVF stenosis in one center. The study consisted of 114 patients with significant (significant stenosis was defined as a reduction in the caliber of the fistula vein of > 50% with respect to the non-aneurysmal venous segment). AVF stenosis patients were treated with PTA, with conventional balloon angioplasty. The NLR and PLR were calculated from the pre-interventional blood samples. The patients were classified into two groups: group A, primary patency < 12 months (n = 35) and group B, and primary patency ≥ 12 months (n = 79). Comparisons between the groups were performed using the Mann-Whitney U test. Kaplan-Meier analysis was performed to compare the factors, NLR and PLR, for association with primary patency AVFs. A receiver-operating characteristic curve analysis was performed to identify the sensitivity and specificity of the NLR and PLR cut-off values in the prediction of primary patency time. There was no difference in gender; age; side of AVF; AVF type; comorbid diseases such as diabetes mellitus and hypertension; or blood parameters such as white cell count, erythrocytes, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils, basophils, C-reactive protein, NLR, or PLR between the two groups (p > 0.05). There was also no significant difference in the patency rate between the NLR < 4.13 and NLR ≥ 4.13 groups at 12 months (NLR cut-off point = 4.13, p = 0.273). There were statistically significant differences between the primary patency rates of the PLR < 187.86 and PLR ≥ 187.86 groups at 12 months (PLR cut-off point = 187.86, p = 0.023). The cut-off value for PLR for the determination of primary patency was 187.86, with a sensitivity of 57.0% and specificity of 34.4%. An increased level of PLR may be a risk factor for the development of early AVF restenosis after successful PTA. However, more studies are needed to validate this finding.


Effect of copulation on estrus duration and ovulation time in goats.
The objective of the present study was to evaluate the effect of copulation on estrus duration and ovulation in goats. During the fall season, 14 multiparous Boer does were estrous synchronized with controlled internal drug release (300 mg), maintained in the vagina for 7 days, and received 50 μg of intramuscular GnRH device insertion and 5 mg of natural intramuscular PGF2α at device removal. The does were randomly divided into two equal groups: a treatment group (TRE; n = 7) and a control group (CON; n = 7). The TRE group received two copulas by fertile bucks within the first 4 hours of estrus onset, and the CON group received only mounts by the same males equipped with canvas aprons. Estrus detection was performed every 12 hours after controlled internal drug release removal within the first 24 hours and then every 4 hours for 5 days. Estrus was defined when a doe accepted mounting by the bucks equipped with canvas aprons. Each doe in estrus got the first transrectal ultrasonography at 24 hours after estrus onset and then every 4 hours until all the preovulatory follicles ovulated. Estrus onset for the TRE and CON groups was 40.3 ± 17.4 (mean ± standard deviation) and 43.3 ± 12.2 hours (P = 0.72), respectively. Estrus duration for the same groups was 28.6 ± 5.4 and 36.7 ± 5.3 hours (P = 0.02), respectively. The mean ovulation time for the TRE and CON groups was 31.4 ± 2.2 and 35.7 ± 3.7 hours (P = 0.04), respectively. The proportion of ovulations that occurred after the end of estrus in the TRE group was higher than in the CON group (86% vs. 33%, respectively; P = 0.05). The number of ovulations for the TRE group was 2.1 ± 0.7; for the CON group, there were 2.2 ± 0.5 ovulations (P = 0.92). It was concluded that copulation by a buck at the beginning of estrus reduced estrus duration and hastened the ovulation time in Boer goats.


The relation of clinical saccadic eye movement testing to reading in kindergartners and first graders.
Although a substantial body of research has demonstrated an association between reading and eye movements, this association has not been examined in kindergartners. Therefore, the relation between psychometric eye movement scores and reading skill was studied in a masked investigation with 181 kindergartners and first graders (mean age 6.25 years) from a middle class, suburban, elementary school near Cleveland, Ohio. Eye movements were evaluated with the New York State Optometric Association King-Devick (NYSOA K-D; Bernell Corporation, South Bend, IN) and the Developmental Eye Movement tests (DEM; Bernell Corporation, South Bend, IN). Digit knowledge was assessed with Reversals Frequency Test Execution subtest (Gardner). Reading performance was measured with Metropolitan Achievement Test 6 (MAT6) Reading Test and teachers' assessments. The number of unknown or reversed numbers on Gardner was significantly related to test times on the NYSOA K-D and DEM, but not the DEM ratio. Outcome on NYSOA K-D, determined by errors in conjunction with test time, was significantly related to reading ability in 5-year-olds (p = 0.0129), 6-year-olds (p = 0.0167), and the entire subject group when controlling for age (p = 0.0008). Our findings suggest that: (1) DEM factors out automaticity of number knowledge; (2) the NYSOA K-D can be completed by kindergartners; (3) the DEM is too difficult for many kindergarteners; and (4) performance on the NYSOA K-D is related to reading performance in 5- and 6-year-olds in kindergarten.


Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disorder. The etiology of this disease is still not fully clear, but free radicals have been proposed to cause neuronal injury. Metals play a key role in the intracellular oxidative balance. However their implication in the degeneration process remains unknown. To assess Cu, Zn and Se concentrations in serum of a group of PD patients in order to determinate, in comparison with age-matched controls, whether alteration in their levels could be involved in PD. A serum level of 3 trace elements (Cu, Zn and Se) was investigated in 48 patients with PD and 36 matched controls using plasma atomic absorption spectrometry. We compared these parameters in PD patients with controls, and we also compared the variations within the PD group according to age, illness duration, stage of the disease and levodopa intake. Patients with PD had significantly lower Cu levels compared to controls. The mean Zn and Se levels in PD patients did not differ significantly from those of controls. Levodopa therapy, age, stage, and illness duration did not significantly influence the measured parameters. These results suggest that a disturbance of the plasmatic rate of Cu could be a marker of PD or at least, a risk factor for the development of this disease. Although zinc participates to the reduction of oxidative stress and the antioxidant role of the selenium, their implication in the onset of PD is not clearly established. Perspectives for the future could include antioxidant therapy. For this reason, other prospective studies should be conducted on this subject to elucidate the implication of trace elements in PD.


Recent Progress in Surface-Enhanced Raman Scattering for the Detection of Chemical Contaminants in Water.
Water is a matter of vital importance for all developed countries due to the strong impact on human health and aquatic, wetlands and terrestrial environments. Therefore, the monitoring of water quality is of tremendous importance. The enormous advantages that Surface-enhanced Raman scattering (SERS) spectroscopy offers, such as fingerprint recognition, multiplex capabilities, high sensitivity, and selectivity or non-destructive testing, make this analytical tool very attractive for this purpose. This minireview aims to provide a summary of current approaches for the implementation of SERS sensors in monitoring organic and inorganic pollutants in water. In addition, we briefly highlight current challenges and provide an outlook for the application of SERS in environmental monitoring.


[Prevalence of various voiding disorders].
The article presents the data of Russian and international epidemiological studies on the prevalence of various lower urinary tract symptoms (LUTS) among male and female populations. The overall summary of these data highlights the need for the national data on LUTS prevalence, severity and impact on quality of life to project the spending for LUTS management.


Recent advances in the neurochemical pathology of Alzheimer's disease. Studies of neuropeptides, cholinergic function and Alzheimer's disease-associated protein.
Our findings from three postmortem tissue studies in Alzheimer's disease (AD) are presented. We investigated (1) alterations in somatostatin (SRIF) and corticotropin-releasing factor (CRF) in AD; (2) regulatory changes in presynaptic cholinergic function in AD; and (3) use of Alzheimer's disease-associated protein (ADAP) as a diagnostic test for AD in postmortem tissue. Taken together, these findings reveal marked reductions in SRIF and CRF concentrations in many cerebrocortical areas in AD, a marked up-regulation of cholinergic neuronal activity in surviving cholinergic neurons in AD, and excellent specificity and sensitivity for the use of the ADAP assay as a diagnostic test for AD in postmortem tissue.


Four Pentasaccharide Resin Glycosides from Argyreia acuta.
Four pentasaccharide resin glycosides, acutacoside F-I (1-4), were isolated from the aerial parts of Argyreia acuta. These compounds were characterized as a group of macrolactones of operculinic acid A, and their lactonization site of 11S-hydroxyhexadecanoic acid was esterified at the second saccharide moiety (Rhamnose) at C-2. The absolute configuration of the aglycone was S. Their structures were elucidated by established spectroscopic and chemical methods.


Immune Response and Protective Efficacy of a Heterologous DNA-Protein Immunization with Leishmania Superoxide Dismutase B1.
Growing evidence shows that antioxidant proteins of Leishmania could be used as vaccine candidates. In this study, we report the efficacy of Leishmania donovani iron superoxide dismutase B1 (LdFeSODB1) as a vaccine antigen in BALB/c mice in a DNA-protein prime-boost immunization regimen in the presence or absence of murine granulocyte macrophage colony stimulating factor (mGMCSF) DNA adjuvant. The expression study confirmed that LdFeSODB1 is expressed in mammalian cells and mGMCSF fusion mediates the secretion of the recombinant protein. Heterologous immunization with LdFeSODB1 induced a strong antibody- and cell-mediated immune response in mice. Immunization triggered a mixed Th1/Th2 response as evidenced by the ratio of IgG2a to IgG1. Antigen-stimulated spleen cells from the immunized mice produced high level IFN-γ. Multiparametric flow cytometry data showed that immunization with LdFeSODB1 induced significantly higher expression of TNF-α or IL-2 by antigen-stimulated T cells. Eight weeks after L. major infection, immunization with the antigen shifted the immune response to a more Th1 type than the controls as demonstrated by IgG2a/IgG1 ratio. Moreover, IFN-γ production by antigen-stimulated spleen cells from immunized mice remained high. The footpad swelling experiment showed that immunization with LdFeSODB1 resulted in partial protection of mice from a high dose L. major infection.


Impact of disease-causing mutations on inter-domain interactions in cMyBP-C: a steered molecular dynamics study.
The molecular interactions of the sarcomeric proteins are essential in the regulation of various cardiac functions. Mutations in the gene MYBPC3 coding for cardiac myosin-binding protein-C (cMyBP-C), a multi-domain protein, are the most common cause of hypertrophic cardiomyopathy (HCM). The N-terminal complex, C1-motif-C2 is a central region in cMyBP-C for the regulation of cardiac muscle contraction. However, the mechanism of binding/unbinding of this complex during health and disease is unknown. Here, we study possible mechanisms of unbinding using steered molecular dynamics simulations for the complex in the wild type, in single mutations (E258K in C1, E441K in C2), as well as in a double mutation (E258K in C1 + E441K in C2), which are associated with severe HCM. The observed molecular events and the calculation of force utilized for the unbinding suggest the following: (i) double mutation can encourage the formation of rigid complex that required large amount of force and long-time to unbind, (ii) C1 appears to start to unbind ahead of C2 regardless of the mutation, and (iii) unbinding of C2 requires larger amount of force than C1. This molecular insight suggests that key HCM-causing mutations might significantly modify the native affinity required for the assembly of the domains in cMyBP-C, which is essential for normal cardiac function.


Influence of surface cell structures on physicochemical properties of Escherichia coli.
The partition of cells in a polyethylene glycol-dextran two phase system was used to compare the relative hydrophobicity of E. coli strains expressing different surface structures. The role of fimbriae and surface antigens on the behavior partition was investigated. The strains expressing PAP fimbriae and/or O-antigen showed a higher surface hydrophobicity than strains which express only type 1 fimbriae and/or R-antigen. No relation was found between K and H antigen and hydrophobicity measurements. The influence of surface structures on electrophoretic mobility has been evaluated. The polysaccharide capsules of AL 213 and AL 499 strains generated a high EPM. For non capsulated E. coli the EPM of rough strains (AL 46, 382) is higher than smooth strain (AL52).


Dihydrotestosterone in human ovarian venous plasma.
Androstenedione (delta), oestradiol-17beta (Oe2), 5alpha-dihydrotestosterone (DHT), progesterone (P) and testosterone (T) concentrations have been measured by radioimmunoassay in ovarian and peripheral venous blood from 15 women in the luteal phase of the cycle. The ovarian blood samples were obtained during surgical intervention from 15 ovaries containing the corpus luteum and from 5 contralateral ovaries. The mean concentration of DHT in ovarian venous blood was not higher than that found in the cubital vein. However in some cases with high concentrations of testosterone in ovarian venous blood, a small but significant DHT gradient was found.


A noncrystallographic screw axis parallel to a twin axis can corrupt intensity statistics.
A number of methods to detect twinning are based upon the assumption that the statistical properties of diffracted intensities are different for twinned and untwinned specimens. This may not be true for a large portion of the reflections in a twinned specimen if a noncrystallographic screw axis parallel to the twinning axis is present. In this case, up to half of all reflections can obey Wilson statistics, which are typical of untwinned crystals. The distribution corresponding to a whole set of observed intensities is biased towards the Wilson distribution in this case.


Siberian subtype tickborne encephalitis virus, Finland.
We isolated 11 Siberian subtype tickborne encephalitis virus (TBEV) strains from Ixodes persulcatus ticks from a TBEV-endemic focus in the Kokkola Archipelago, western Finland. Thus I. persulcatus and the Siberian TBEV are reported in a focus considerably northwest of their previously known range in eastern Europe and Siberia.


Dynamic assessment of the load distribution on the plantar surface of the foot using the University of Cape Town walkway and its clinical application.
The dynamic assessment of the plantar pressure profile is now possible, and an immediate visual display without the necessity for complicated computer-assisted analysis has been developed using a walkway designed at the University of Cape Town. Using the walkway, the author assessed the feet of 10 normal children and 10 normal adults. They showed consistently similar profiles with very minor variations. Using the walkway, the author also showed in four abnormal cases the effects of corrective surgical procedures and of an orthotic device.


Mistreatment at work and musculoskeletal pain in male and female working Syrian refugee children.
Since the Syrian war in 2011, Syrian refugees in Lebanon have continued to experience socioeconomic deprivation, resorting many families to child labour as a form of survival. Adopting a gender-sensitive analysis, this study explores the relationship between psychosocial adversities and musculoskeletal pain among male and female Syrian refugee children in Lebanon, using data from a cross-sectional survey of working Syrian refugee children between 8 and 18 years in informal tented settlements in the Bekaa Valley of Lebanon. The majority of working children (4090) worked in agriculture (75.8%). Of the children who experienced musculoskeletal pain, 27.4% worked despite severe pain, three-quarters of the children worked under time pressure, over a third (37.4%) were physically abused at work, and the majority (95.8%) had a good relationship with their co-workers. Logistic regression models revealed a significant association between exposure to psychosocial stressors at work and musculoskeletal pain among male and female children.Practitioner summary: This study is the first to obtain direct testimony on musculoskeletal pain and psychosocial risk factors, among Syrian refugee children in Lebanon. Using a gender-sensitive analysis, the survey results demonstrated associations between exposure to psychosocial stressors and musculoskeletal pain among male/female Syrian refugee children enduring strenuous working conditions.


Health benefits, risks, and cost-effectiveness of influenza vaccination of children.
We estimated cost-effectiveness of annually vaccinating children not at high risk with inactivated influenza vaccine (IIV) to range from US $12,000 per quality-adjusted life year (QALY) saved for children ages 6-23 months to $119,000 per QALY saved for children ages 12-17 years. For children at high risk (preexisting medical conditions) ages 6-35 months, vaccination with IIV was cost saving. For children at high risk ages 3-17 years, vaccination cost $1,000-$10,000 per QALY. Among children notat high risk ages 5-17 years, live, attenuated influenza vaccine had a similar cost-effectiveness as IIV. Risk status was more important than age in determining the economic effects of annual vaccination, and vaccination was less cost-effective as the child's age increased. Thus, routine vaccination of all children is likely less cost-effective than vaccination of all children ages 6-23 months plus all other children at high risk.


Reactions of 1-hydroxy-1-methylethyl radicals with NO2-: time-resolved electron spin resonance.
The reaction of the alpha-hydroxyalkyl radical of 2-propanol (1-hydroxy-1-methylethyl radical) with nitrite ions was characterized. A product of the reaction was assigned as the adduct nitro radical anion, [HO-C(CH(3))(2)NO(2)](*-). This radical was identified using time-resolved electron spin resonance (TRESR). The radical's magnetic parameters, the nitrogen hyperfine coupling constant (a(N) = 26.39 G), and its g-factor (2.0052) were the same as those of the nitro radical anion previously discovered in (*)OH spin-trapping experiments with the aci-anion of (CH(3))(2)CHNO(2). Production of [HO-C(CH(3))(2)NO(2)](*-) was determined to be 38% +/- 4% of the reaction of (CH(3))(2)C(*)-OH with nitrite. The reason why this fraction was less than 100% was rationalized by invoking the competitive addition at oxygen, which forms [HO-C(CH(3))(2)ONO](*-), followed by a rapid loss of (*)NO. Furthermore, by taking this mechanism into account, the bimolecular rate constant for the total reaction of (CH(3))(2)C(*)-OH with nitrite at reaction pH 7 was determined to be 1.6 x 10(6) M(-1) s(-1), using both decay traces of (CH(3))(2)C(*)-OH and growth traces of [HO-C(CH(3))(2)NO(2)](*-). This correspondence further confirms the nature of the reaction. The reaction mechanism is discussed with guidance by computations using density functional theory.


GraphPart: homology partitioning for biological sequence analysis.
When splitting biological sequence data for the development and testing of predictive models, it is necessary to avoid too-closely related pairs of sequences ending up in different partitions. If this is ignored, performance of prediction methods will tend to be overestimated. Several algorithms have been proposed for homology reduction, where sequences are removed until no too-closely related pairs remain. We present GraphPart, an algorithm for homology partitioning that divides the data such that closely related sequences always end up in the same partition, while keeping as many sequences as possible in the dataset. Evaluation of GraphPart on Protein, DNA and RNA datasets shows that it is capable of retaining a larger number of sequences per dataset, while providing homology separation on a par with reduction approaches.


Paracetamol ecotoxicological bioassay using the bioindicators Lens culinaris Med. and Pisum sativum L.
Paracetamol is one of the most widely used drugs worldwide, yet its environmental presence and hazardous impact on non-target organisms could rapidly increase. In this study, the possible cytotoxic effects of paracetamol were evaluated using two bioindicator plants Lens culinaris and Pisum sativum. Concentrations of 500, 400, 300, 200, 100, 50, 25, 5, 1 mg L-1, and a control (distilled water) were used for a total of 10 treatments, which were subsequently applied on seeds of Lens culinaris Med. and Pisum sativum L.; after 72 h of exposure, root growth, mitotic index, percentage of chromosomal abnormalities, and the presence of micronucleus were evaluated. The cytotoxic effect of paracetamol on L. culinaris and P. sativum was demonstrated, reporting the inhibition of root growth, the presence of abnormalities, and a significant micronucleus index at all concentrations used, which shows that this drug has a high degree of toxicity.


fac-Specific syntheses of homochiral [Fe(NN)3]2+ complexes (NN = pyridine keto-hydrazone); origins of the stereoselectivity.
The 2-pyridinehydrazones (from condensation of pyridine-2-carbaldehyde and hydrazines) have previously been noted to have poor ligating ability as a result of a sterically demanding planar conformation. Destabilisation of this conformation is achieved through simple use of the ketohydrazones, and as a result the diamagnetic chiral tris-bidentate diimine complexes fac-[FeL3]2+ are readily isolated. In the solid state, inter-ligand - stacking and complex/counter-ion H-bonding are apparent, and these features persist in solution according to dynamic NMR spectra, which also indicate extremely high stereoselectivity for the fac isomers (>200:1). The compounds crystallise as conglomerates, and time-resolved CD spectra of non-racemic samples indicate a high degree of persistence of chirality (racemisation t1/2 ca 77 min). Variations of solvent and counter-ion indicate that H-bonding is unimportant in determining the structure of the cation. The fac-selectivity arises in the induction of a chiral conformation in the coordinated ligand, and the fact that such non-planar ligands can only be accommodated about the Fe(II) centre if they all have the same absolute configuration. Adding a hydrazine N-methyl group increases the steric demand further, while retaining the novel non-planar conformation, and as a result paramagnetic chiral bis-bidentate complexes such as [FeL72(CH3CN)2]2+ are readily available.


Women's leadership in the Public Dental Service in Finland.
This study aimed to examine how leadership positions in the Public Dental Service (PDS) were distributed between women and men and how the female and male lead dentists perceived themselves as managers or leaders and whether their superiors, the leading doctors and municipal decision makers or their subordinates, the public dentists, found differences between female and male lead dentists as leaders. Gender aspects on the leadership qualities of the lead dentists in the Public Dental Service were evaluated by four professional groups using a questionnaire. The groups surveyed were: lead dentists (in charge of the municipal PDS clinics), leading doctors (lead dentists'line managers), the directors of municipal health boards, and the PDS dentists (subordinates to the lead dentists). Factor analysis, chi-square and non-parametric tests were used to analyse the data gathered. Women made up 50% (96/192) of the lead dentists, 80% (211/263) of the public dentists, 31% (47/152) of the leading doctors, and 27% (33/124) of directors of the municipal health boards (P<0.001). Nearly all female (92%; 86/93) and 78% (70/90) of the male lead dentists considered themselves to be good people-oriented leaders (P<0.01) and three-quarters of the men (74%; 67/90) and 59% (54/92) of the women good goal-oriented managers (P<0.05). In the eyes of their nearest superiors, the female and male lead dentists were rated equally; they were given scores as goal-oriented managers, people-oriented leaders (both medians= 3.2 on a scale from 1 to 4), and their ability (median=3.5) to take care of their tasks. Their decision authority, power in municipal decision-making (median=2.8), was considered weaker. Most, 67% (70/105), of the PDS dentists evaluated their female superiors and 50% (75/150) their male superiors good as goal-oriented managers (P<0.001), and 51% (54/105) considered their female superiors and 35% (53/150) their male superiors good as people-oriented leaders (P<0.05). Female dentists had not become lead dentists in proportion to their numbers in the PDS. Those who had a leading position felt that they were good leaders, their superiors considered them as good as their male colleagues, and their subordinates felt they were better.


Two-dimensional echocardiography in acute transmural and non-transmural myocardial infarction.
Left ventricular wall motion abnormalities in acute myocardial infarction and their changes during hospitalisation were investigated in 40 patients by means of two-dimensional echocardiography (2-D-E). It was confirmed that two-dimensional echocardiography can detect segmental left ventricular asynergy, follow up its development during hospitalisation and provide on the basis of this information on the extent of infarction. Differences were found between transmural and non-transmural infarctions, in particular as regards the duration of impaired wall motion (in non-transmural infarctions it was only temporary). Suggested indicators of the extent of this disorder ("index of asynergy" and "extent of asynergy") seem to be valuable for the evaluation of the extent of infarction and of its clinical impact. The sensitivity and specificity of echocardiography, as compared with postmortem findings, is satisfactory.


[Usefulness of Vacuum-Assisted Biopsy(VAB)at Initial Biopsy].
In recent years, breast micro-lesions such as ductal carcinoma in situ(DCIS)were detected with progress of the image diagnosis. We investigated the usefulness of vacuum-assisted biopsy(VAB)for initial biopsy of breast tumors. We analyzed 32 cases of VAB performed for breast tumors. The pathological diagnosis of the biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and benign lesions in 21 cases. 11 cases underwent surgery and the final histopathological diagnosis was the same in 10 of them. One case histopathology varied from DCIS to invasive ductal carcinoma(IDC). It was suggested that VAB at initial biopsy was a useful biopsy method.


[THC-YAG laser sclerostomy ab externo in monkey eyes].
THC-YAG laser sclerostomy was performed in 7 eyes of 6 monkeys. The 26-gauge optic probe, which delivers energy perpendicularly to the long axis of the probe, was inserted through a 1-mm conjunctival stab incision, 6-7 mm away from the limbus, and the probe tip was positioned at the sclerostomy site. Pulse energy of 80 mJ or 100 mJ was used with a repetition rate of 5 pulses per second. Total energy levels to produce a new outflow pathway ranged from 1.2 to 6.6 J (2.8 +/- 1.2 J). After the surgery, 5-fluorouracil (0.1 mg daily) was injected subconjunctivally for 7 days, and intraocular pressure measurements and ophthalmic examination were performed for 4 weeks. Eyes were enucleated just after surgery or 1 week or 4 weeks after surgery. Intraocular pressures in operated eyes at 1 week and 4 weeks after surgery were reduced to 7-10 (9 +/- 1.2) mmHg, and 0-11 (3.5 +/- 4.3) mmHg, respectively, in comparison with intraocular pressures in nonoperated eyes. Histological examination revealed that the sclerostomy hole with a diameter of 150 microns just after surgery had narrowed at 1 week, and was closed by subconjunctival proliferative tissues at 4 weeks after surgery.


Adult psychiatric status of hyperactive boys grown up.
Numerous studies have examined the adolescent and young adult fate of children with attention deficit hyperactivity disorder (ADHD). In marked contrast, relatively little is known about the adult outcome of these children. There have been only two controlled, prospective studies of psychiatric status into adulthood. The present study was conducted to gain further understanding of the natural course of this common childhood condition. This was a prospective follow-up of clinically diagnosed, white boys of average intelligence who were referred by teachers to a child psychiatric research clinic at an average age of 7.3 years. At a mean age of 24.1 years, 85 probands (82% of the childhood cohort) and 73 comparison subjects (94% of adolescent comparison subjects) were directly interviewed by trained clinicians who were blind to group status. Evaluations of the probands and comparison subjects indicated significantly higher prevalences of antisocial personality disorder (12% versus 3%) and nonalcohol substance abuse (12% versus 4%) in the probands, whereas mood disorders (4% versus 4%) and anxiety disorders (2% versus 7%) were not significantly different. At adult follow-up, ADHD was rare, occurring in only 4% of the probands (no comparison subjects). The results of the present study are consistent with the authors' previously reported major findings. They strongly suggest that children with ADHD are at significantly higher risk for a specific negative course marked by antisocial and substance-related disorders.


Comparison of Hydroxyapatite-coated stems in total hip arthroplasty after a minimum 10-years follow-up.
PURPOSE OF THE STUDY Hydroxypatite coating (HAC) was introduced into total hip arthroplasty (THA) practice to improve the fixation interface between bone and prosthesis. To test this assumption however, long-term follow-up investigations are needed. In this study, we present data for two consecutive series of THA stems with HAC and a minimum ten-year follow-up. MATERIAL Overall, 249 patients (271 hips) were included in the study, of these 122 (135 hips) had Walter hip arthroplasty (WHA group) with a two-layered TiO2/HAC at the proximal part of the stem and 127 (136 hips) had ABG I prostheses (ABG I group) with a single-layered HAC at the proximal part of the stem. Mean length of follow-up was 11.4 years (0.8-13) and 9.8 years (4-12) in WHA and ABG I groups, respectively. Mean age at the time of surgery was 62 years (23-79) and 47 years (21-65) in WHA and ABG I groups, respectively. METHODS Probabilities of implant survival were estimated using the Kaplan-Meier method. Radiographic data were included to construct the worst-case scenario. Differences in survival curves were evaluated by Gehan's Wilcoxon test. Harris hip score was used to compare preoperative status with that of final follow-up. RESULTS The overall survival of WHA was significantly better than the ABG I (0.85 versus 0.66; p < 0.05). The main reason for a high revision rate in ABG I was periprosthetic osteolysis followed by aseptic loosening. With regard to stems, the survivorship curve for the Walter stem was significantly better than for the ABG I stem even when radiographic results were included (p = 0.0002). In the WHA group, two stems (1.5%) were revised due to sepsis, in contrast to thirty-one stems (23.5%) revised in the ABG I group due to osteolysis and aseptic loosening (p < 0.05). Significant improvement was achieved in both groups under study in terms of Harris hip score. DISCUSSION Data presented here appear surprising at first glance because the differences between the stems under study are only minor. The failure in ABG I was most probably caused by poor polyethylene quality and poor locking mechanism of polyethylene liner in the metallic shell. In addition, HAC used in ABG I prosthesis was not able to prevent the development of polyethylene disease stimulated by high wear rate. CONCLUSION This study revealed excellent survivorship for WHA stems after a minimum ten-year survival and significantly poorer survivorship for the ABG I stems.This may be explained at least particularly by combined two-layered HAC used in WHA stems which provide simultaneously endurable bone interlocking and effective barrier against expansion of polyethylene disease.


Emotional and adjustment issues faced by cardiac patients seen in clinical practice: a qualitative survey of experienced clinicians.
Many cardiac patients experience psychological difficulties after a cardiac event including anxiety, depressed mood, adjustment difficulties, and feelings of grief and loss. There is a vast literature on the psychological adjustment of cardiac patients including reports by individual practitioners into the emotional difficulties of these patients. However, no previous study has surveyed therapists collectively about their experiences working with cardiac patients. In this study, clinical practitioners were surveyed to identify specific emotional issues faced by cardiac patients and to explore potential relationships between these issues. Semistructured interviews were conducted with 14 psychologists and cardiac social workers who had extensive experiences with cardiac patients. Responses were collated by means of a qualitative thematic analysis. Participants described the interrelationships of anxiety, depression, grief and loss, and denial that were observed in cardiac patients. Participants also identified trauma, guilt, and anger as issues of concern. The findings supply a richness of detail that is often absent in quantitative studies. This detail may give cardiac rehabilitation professionals additional insight into the complexity of patients' emotional reactions and the interrelationships of these reactions. The results highlight the importance of the identification and referral of patients who present with more than transient emotional difficulties.


Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy.
Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m(2); mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years.


The prophage-encoded transcriptional regulator AppY has pleiotropic effects on E. coli physiology.
Bacterial genome diversity is influenced by prophages, which are viral genomes integrated into the bacterial chromosome. Most prophage genes are silent but those that are expressed can provide unexpected properties to their host. Using as a model E. coli K-12 that carries 9 defective prophages in its genome, we aimed at highlighting the impact of genes encoded by prophages on host physiology. We focused our work on AppY, a transcriptional regulator encoded on the DLP12 prophage. By performing RNA-Seq experiments, we showed that AppY production modulates the expression of more than 200 genes. Among them, 11 were identified by ChIP-Seq as direct AppY targets. AppY directly and positively regulates several genes involved in the acid stress response including the master regulator gene gadE but also nhaR and gadY, two genes important for biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favoring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increases acid stress resistance and biofilm formation while also causing a strong defect in motility. Our research shed light on the importance to consider the genetic interactions occurring between prophages and bacteria to fully understand bacterial physiology. It also highlights how a prophage-encoded transcriptional regulator integrates in a complex manner into the host regulatory network and how it benefits its host, allowing it to cope with changing environmental conditions.


Physicochemical interaction of local anesthetics with lipid model systems--correlation with in vitro permeation and in vivo efficacy.
In dermal/transdermal drug administration stratum corneum (SC) is often the rate-limiting step. Furthermore, the intercellular lipid domain of SC is nowadays widely accepted as the major contributor to the skin barrier. The current work investigates whether the difference in the level of topical efficacy of local anesthetic compounds correlates with the type of interaction between the drug and the intercellular lipids of SC. Therefore, local anesthetics of varying topical efficacy were evaluated with respect to their effect on the morphology of various model lipid systems using small and wide angle X-ray diffraction (SWAXD) and differential scanning calorimetry (DSC). The model lipids used were glyceryl monooleate, sphingomyelin and lipids isolated from human SC. Furthermore, partitioning into isolated human SC as well as permeation through isolated human SC and human tape-stripped skin were investigated in vitro. The results indicate that local anesthetics may act as their own permeation enhancers by increasing the degree of hydrocarbon chain fluidity of the intercellular lipids. Eventually these interactions may induce non-lamellar reversed types of liquid crystalline structures locally in SC, which further facilitate the drug mobility. The large difference in topical efficacy of the investigated local anesthetics could not be explained simply by looking at their effect on the phase behavior of lipid model systems. Despite the similarities in physicochemical properties of these substances, the in vitro skin permeability differed markedly (AD>EMLA>lidocaine>prilocaine>sameridine). Thus, it was concluded that sufficient drug permeability over SC is essential to obtain local anesthesia by blocking the superficial nociceptors.


Chitosan-Based Composite Membranes with Different Biocompatible Metal Oxide Nanoparticles: Physicochemical Properties and Drug-Release Study.
Chitosan (CS) composite membranes were prepared using different biocompatible metal oxide nanoparticles (NPs): titanium dioxide (TiO2); iron oxide (Fe3O4); and aluminum oxide (Al2O3). For each nanoparticle, the CS-based composite membranes were prepared with two NPs contents in the CS solution, high (H) and low (L) NPs concentrations. To establish both concentrations, the NPs saturation point in the CS polymeric matrix was determined. The influence of NP concentrations on the physicochemical properties of the CS films was assessed. The prepared CS membranes were characterized with different techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and zeta potential. It was found that the addition of NPs in the CS matrix improved both swelling and mechanical properties. Nanocomposite CS membranes could be prepared using Al2O3 NPs. Swelling experiments revealed different pH-sensitive mechanisms, which might be beneficial in biomedical applications since solute permeation through CS-based composite membranes could be controlled by adjusting environmental conditions. When aspirin transport (ASA) through the prepared membranes was carried out in different release media, SGF (simulating gastric fluid) and SIF (simulating intestinal fluid without enzymes), it was observed that the Fickian diffusion coefficient (D) was conditioned by the pH of the release solution. In SGIT (simulating gastrointestinal transit) medium, a transition time (ttrans) was detected due to the shrinkage of the CS polymeric chains, and the drug release depended not only on the Fickian's diffusion but also on the shrinkage of the biopolymer, obeying Peppas and Sahlin equation.


Clonidine in the treatment of hypertension.
Clonidine has clearly been shown to be effective in the treatment of all grades of hypertension. Clonidine by itself, when compared with placebo, has proved its worth in the treatment of essential hypertension; it has also been found to be more effective than diuretic treatment alone. When clonidine and a diuretic have been combined, the combination has proved superior to either clonidine or the diuretic given alone. The combination of clonidine with a diuretic is equal in efficacy to combinations of a diuretic with a beta-blocker, alpha-methyldopa, or prazosin. Combinations of a diuretic, a vasodilator, and clonidine were useful in patients with refractory hypertension that failed to respond to a two-drug regimen. Clonidine has also been shown to be effective in patients with renal failure or in hypertensive crisis.


A theoretical experimental method to determine the locus of desensitization.
Consider a ligand-gated channel with n agonist binding sites which can undergo desensitization. We present a theoretical experimental procedure for pinpointing the principal receptor state from which there is a transition to the desensitized state. The method is based on the observation that the dependence of the slope of the time constant of desensitization vs agonist concentration, at low concentrations, represents the state from which desensitization occurs. In those receptors where desensitization occurs from the open state (or the one immediately preceding it), the method also enables us to determine the number of binding sites.


Biofluid 1H NMR-based metabonomic techniques in nutrition research - metabolic effects of dietary isoflavones in humans.
A metabonomic approach to nutrition research may provide an insight into in vivo mechanisms of action following nutritional intervention. This approach was applied to investigate changes in the (1)H NMR spectral profile of urine collected from controlled dietary intervention studies conducted in premenopausal women before and following soy or miso consumption. The aim of the study was to identify the biochemical effects of a diet rich in soy isoflavones, phytochemicals which are receiving significant attention because of their potential importance to human health and wide bioactivity in vitro. By applying various chemometric techniques to the data the biochemical effects of conjugated and unconjugated isoflavones were determined. The biochemical changes observed suggest that soy isoflavone ingestion had significant effects on several metabolic pathways associated with osmolyte fluctuation and energy metabolism. These biochemical changes were more significant following ingestion of the unconjugated soy isoflavone (miso) diet suggesting that the chemical composition of the isoflavones present in soy-based foods may have an effect on their biological efficacy in vivo. This study describes a novel application for (1)H NMR analysis by determining subtle differences in biochemical profiles following dietary intervention and providing further insight into the mechanisms of action of phytochemicals in vivo.


MRP4-mediated cAMP efflux is essential for mouse spermatozoa capacitation.
Mammalian spermatozoa must undergo biochemical and structural changes to acquire the capacity for fertilization, in a process known as capacitation. Activation of PKA enzymes is essential for capacitation, and thus cAMP levels are tightly regulated during this process. Previously, we demonstrated that during capacitation, bovine spermatozoa extrude cAMP through multidrug resistance-associated protein 4 (MRP4, also known as ABCC4), which regulates intracellular levels of the nucleotide and provides cAMP to the extracellular space. Here, we report the presence of functional MRP4 in murine spermatozoa, since its pharmacological inhibition with MK571 decreased levels of extracellular cAMP. This also produced a sudden increase in PKA activity, with decreased tyrosine phosphorylation at the end of capacitation. Blockade of MRP4 inhibited induction of acrosome reaction, hyperactivation and in vitro fertilization. Moreover, MRP4 inhibition generated an increase in Ca2+ levels mediated by PKA, and depletion of Ca2+ salts from the medium prevented the loss of motility and phosphotyrosine inhibition produced by MK571. These results were supported using spermatozoa from CatSper Ca2+ channel knockout mice. Taken together, these results suggest that cAMP efflux via MRP4 plays an essential role in mouse sperm capacitation.This article has an associated First Person interview with the first author of the paper.


Good Sanctuary Doctoring for Undocumented Patients.
Clinicians whose practice includes a significant immigrant population report a climate of fear adversely affecting their current patients. Increased immigration enforcement targeting undocumented immigrants increases these patients' stress and negatively affects their willingness to seek medical care. To address these concerns, this article draws upon the literature and the authors' experience to develop guidance on sanctuary doctoring. These materials provide opportunities for patients to open a dialogue about their immigration concerns and can assist clinicians in connecting patients to networks and resources that can address their needs. The materials are designed to be used in single, brief clinical encounters.


Long Term Effects of Hazard Anticipation Training on Novice Drivers Measured on the Open Road.
(a) The purpose of this study was to determine whether novice drivers that were trained to anticipate hazards did so better than novice drivers who were not so trained immediately after training and up to one year after training occurred. (b) Novice drivers who had held their restricted license for about one month were randomly assigned to a PC-based hazard anticipation training program (RAPT) or a placebo (control) training program. The programs took about one hour to complete. The effects of training were assessed in a field drive by using patterns of eye movements to assess whether drivers anticipated a potential unseen hazard. (c) The effects of training persisted over time. In the field test immediately after training, the RAPT group anticipated the hazards 65.8% of the time whereas; the control group anticipated them only 47.3% of the time. Six or more months later, the groups were brought back for a second field test and the effects of training did not diminish; the RAPT group anticipated the hazards 61.9% of the time compared to 37.7% for the control group.


Incident-angle dependence of the sensitivity of second-harmonic generation of an oxacyanine dye in an LB film.
The second-harmonic generation of a cyanine dye in an LB film was investigated by varying the incident angle of the excitation laser. There was a clear dependence on the incident angle, which was simulated by a simple model. Thus, a highly sensitive determination should be carried out at such an angle where the efficiency of the second-harmonic generation shows its maximum.


Chronic Tobacco-Smoking on Psychopathological Symptoms, Impulsivity and Cognitive Deficits in HIV-Infected Individuals.
HIV-infected individuals (HIV+) has 2-3 times the rate of tobacco smoking than the general population, and whether smoking may lead to greater psychiatric symptoms or cognitive deficits remains unclear. We evaluated the independent and combined effects of being HIV+ and chronic tobacco-smoking on impulsivity, psychopathological symptoms and cognition. 104 participants [27 seronegative (SN)-non-Smokers, 26 SN-Smokers, 29 HIV+ non-Smokers, 22 HIV+ Smokers] were assessed for psychopathology symptoms (Symptom Checklist-90, SCL-90), depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), impulsivity (Barratt Impulsiveness Scale, BIS), decision-making (The Iowa Gambling Task, IGT, and Wisconsin Card Sorting Test, WCST), and cognition (seven neurocognitive domains). Both HIV+ and Smoker groups had higher SCL-90 and CES-D scores, with highest scores in HIV+ Smokers. On BIS, both HIV+ and Smokers had higher Total Impulsiveness scores, with higher behavioral impulsivity in Smokers, highest in HIV+ Smokers. Furthermore, across the four groups, HIV+ Smokers lost most money and made fewest advantageous choices on the IGT, and had highest percent errors on WCST. Lastly, HIV+ had lower z-scores on all cognitive domains, with the lowest scores in HIV+ Smokers. These findings suggest that HIV-infection and chronic tobacco smoking may lead to additive deleterious effects on impulsivity, psychopathological (especially depressive) symptoms and cognitive dysfunction. Although greater impulsivity may be premorbid in HIV+ and Smokers, the lack of benefits of nicotine in chronic Smokers on attention and psychopathology, especially those with HIV-infection, may be due to the negative effects of chronic smoking on dopaminergic and cardio-neurovascular systems. Tobacco smoking may contribute to psychopathology and neurocognitive disorders in HIV+ individuals.


Dissociation between manipulation and conceptual knowledge of object use in the supramarginalis gyrus.
Because tool naming activates motor-related areas in the posterior parietal cortex, it has been suggested that conceptual knowledge of tools relies on their unique manipulation patterns. However, this view is questioned by the finding that some patients impaired in retrieving manipulation knowledge of man-made objects are still able to perform conceptual judgments on them. To address this issue, we used repetitive transcranial magnetic stimulation (rTMS) to interfere with the functioning of the anterior part of the right or left supramarginalis gyrus (SMG), a region critically involved in object-directed actions. rTMS was delivered in healthy participants performing four judgment tasks designed to explore different aspects of manipulation and conceptual knowledge of man-made objects. The two manipulation judgment tasks consisted in determining whether (1) two objects displayed on a computer screen are normally used by adopting a comparable hand posture, or (2) a given hand posture is appropriate to use an object. In the two conceptual judgment tasks, subjects had to decide whether (1) two objects displayed on the computer screen are normally used in the same context or (2) they are functionally related. We found that virtual lesions of left SMG interfere only with the performance of the manipulation judgment task in which subjects had to decide whether two different objects are used by adopting the same hand posture, all the other tasks being unaltered. rTMS applied over the right SMG had no effect. These results challenge the assumption that conceptual knowledge of tools is grounded upon motor representations.


Embolism of cerebral tissue to lungs: report of two cases and review of the literature.
Two patients with head injury and pulmonary emboli of brain tissue are described. Both patients developed persistent bleeding with elevations of prothrombin time, partial thromboplastin time, and decreased platelet counts. Postmortem examination identified multiple skull fractures, subdural and subarachnoid blood, cortical tears, and intraparenchymal hemorrhages. Lacerations of dural venous sinuses were documented in each case. Multiple pulmonary arteries contained plugs of cerebral tissue, including fragments of cerebral and cerebellar cortex, and white matter. The literature concerning brain tissue emboli is reviewed. In neonates, three patients who survived longer than 1 hour were found to have evidence of persistent hemorrhage. Among both children and adults, our two cases are the only ones reported with associated clotting abnormalities. Brain tissue embolism in neonates occurs after difficult vaginal deliveries, often in conjunction with the use of forceps. Tears of the tentorium cerebelli or falx cerebri have been documented at postmortem examination in the majority of these cases. By contrast, brain tissue embolism in children and adults occurs in association with severe closed or penetrating head injury. In several cases, as in the two reported here, postmortem examination has demonstrated a large cerebral venous defect as the probable site of entry of brain tissue into the systemic circulation.


Activation of the wt1 Wilms' tumor suppressor gene by NF-kappaB.
The Wilm's tumor suppressor gene, wt1, is expressed in a very defined spatial-temporal fashion and plays a key role in development of the urogenital system. Transacting factors governing wt1 expression are poorly defined. The presence of putative kappa-B binding sites within the wt1 gene prompted us to investigate whether members of the NF-kappaB/Rel family of transcription factors are involved in regulating wt1 expression. In transient transfection assays, ectopic expression of p50 and p65 subunits of NF-kappaB stimulated wt1 promoter activity 10-30-fold. Deletion mutagenesis revealed that NF-kappa-B responsiveness is mediated by a short DNA fragment located within promoter proximal sequences of the major transcription start site. Two kappaB-binding sites are present in this region and form specific complexes with purified NF-kappaB proteins, as revealed by electrophoretic mobility gel shift assays. Ectopic expression of p50 and p65 resulted in increased transcription of the endogenous wt1 gene, as revealed by nuclear run-on experiments. Taken together, these results indicate that members of the NF-kappaB/Rel family are important for activating expression of wt1 and reside upstream of the regulatory cascade leading to wt1 activation.