Tetanus Immunoglobulin G Assessment in Adults Trauma Patients.
Clostridium tetani is an anaerobic, gram-positive bacillus that causes tetanus infection. It usually enters the body through injury with contaminated objects. Tetanus differs from other diseases that can be prevented by vaccination in that it is not contagious and does not spread from person to person. The aim of this study is to evaluate the levels of Tetanus IgG in trauma patients admitted to the emergency department (ED). The study was planned as cross-sectional, prospective, and single-center. The study was conducted from January to July 2018 in the Kahramanmaraş Sütçü İmam University Hospital. Totally, 178 patients aged ≥18 years were included. For measurement of the level of Tetanus IgG, Clostridium tetani toxin 5S IgG kit (NovaLisa, NOVATEC) was used to quantitatively detect IgG type antibodies by micro-ELISA method in accordance with the manufacturer's recommendation. In total, 143 cases were male and 35 were female. The mean age of the cases was 40 ± 16 years. Tetanus IgG levels were found to be 0.29 ± 0.6 IU/mL in cases from rural areas and 2.14 ± 1.64 IU/mL in cases from urban areas (P < 0.001). There was a negative correlation between age and Tetanus IgG level (r: (-) 0.479; P < 0.001). The protective level of Tetanus IgG was observed to be even lower, especially in patients aged ≥40 years (n = 43, 78.9%). Measurements of Tetanus IgG levels should be performed as far as possible in the ED. In this way, unnecessary vaccination can be avoided.


Photoerasable and photorewritable spatially-tunable laser based on a dye-doped cholesteric liquid crystal with a photoisomerizable chiral dopant.
This study investigates, for the first time, a photoerasable and photorewritable spatially-tunable laser using a dye-doped cholesteric liquid crystal (DDCLC) with a photoisomerizable chiral dopant (AzoM). UV illumination via a photomask with a transmittance-gradient can create a pitch gradient in the cell such that the lasing wavelength can be spatially tuned over a wide band of 134nm. The pitch gradient is generated by the UV-irradiation-induced gradient of the cis-AzoM concentration and therefore the induced gradient of the cell HTP value, resulting in the spatial tunability of the laser. Furthermore, the laser has advantages of photoerasability and photorewritability. The spatial tunability of the laser can undergo more than 100 cycles of photoerasing and photorewriting processes without decay or damage.


Age-independent association of pulse pressure with cerebral white matter lesions in asymptomatic elderly individuals.
Brachial pulse pressure (PP) is a marker of arterial stiffness in the elderly and a useful tool for measuring vascular aging. The presence of cerebral white matter lesions (WMLs) is a radiological marker of sub-clinical ischemic brain damage. WMLs may be age-related degenerative change, but few studies have addressed the relationship between vascular aging and WMLs. In this study, we assessed whether brachial PP is associated with the presence of WMLs in the elderly. Six hundred and ninety-two asymptomatic elderly individuals (>55 years) who visited for routine health check-up were included. Brachial blood pressure (BP) was measured and brain MRI used to determine the presence of advanced WMLs. Ninety-six (13.9%) were found to have advanced WMLs. In the highest PP quartile (≥54 mmHg), 55 (32.9%) had advanced WMLs, and this was significantly higher than in other quartiles. After controlling for age, hypertension, systolic BP, diastolic BP, aspirin use, C-reactive protein, and other vascular risk factors, the highest quartile of PP was significantly associated with advanced WMLs compared with the lowest quartile [adjusted odds ratio (OR) 2.55; 95% confidence interval (CI) 1.03-6.30]. The authors report for the first time that increased brachial PP is an age-independently associated with WMLs in asymptomatic elderly individuals. This result suggests that PP as a presumed marker of vascular aging may predict the presence of sub-clinical cerebrovascular diseases.


Predicting performance in contracting of basic health care to NGOs: experience from large-scale contracting in Uttar Pradesh, India.
Escalating costs and increasing pressure to improve health services have driven a trend toward contracting with the private sector to provide traditionally state-run services. Such contracting is seen as an opportunity to combine theorized advantages of contracting with the efficiency of the private sector. There is still a limited understanding of the preconditions for successful use of contracting and the resources needed for their appropriate use and sustainability. This study assesses the large-scale contracting of 294 non-governmental organizations (NGOs) for delivery of basic health services in Uttar Pradesh, a state with almost 170 million in India. Due to high rates of discontinuation or non-renewal of contracts based on poor performance in the project, a better method for selecting partners was requested. Data on characteristics of the NGOs (intake data) and performance/outcome monitoring indicators were combined to identify correlations. The results showed that NGOs selected were generally small but well-established, had implemented at least two large projects, and had more non-health experience than health experience. Bivariate regressions of outcome score on each input variable showed that training experience, proposal quality and having 'health' contained in the objectives of the organization were statistically significant predictors of good performance. Factors relating to financial capacity, staff qualification, previous experience with health or non-health projects, and age of establishment were not. A combined training plus proposal score was highly predictive of outcome score (β = 1.37, P < 0.001). The combined score was found to be a much better predictor of outcome scores than a total score used to select NGOs (β = 0.073, P = 0.539). The study provides valuable information from large-scale contracting. Conclusions on criteria for selecting NGOs for providing basic health care could guide other governments choosing to contract for such services.


Nanotechnology and animal health.
Nanotechnology, as a new enabling technology, has the potential to revolutionise agriculture and food systems in the United States of America and throughout the world. Examples of potential applications of nanotechnology in the science and engineering of agriculture and food systems include disease treatment delivery systems, new tools for molecular and cellular biology, the security of agricultural and food systems, new materials for pathogen detection, and protection of the environment. Existing research has clearly demonstrated the feasibility of introducing nanoshells and nanotubes into animal systems to seek out and destroy targeted cells. Nanoparticles smaller than one micron have been used to deliver drugs and genes into cells. Thus, some building blocks do exist in isolation and are expected to be integrated into systems over the next 10 to 15 years. It is reasonable to presume over the next couple of decades that nanobiotechnology industries and unique developments will revolutionise animal health and medicine.


Case Report: Lung Ultrasound for the Guidance of Adjunctive Therapies in Two Invasively Ventilated Patients with COVID-19.
Two patients with respiratory failure due to confirmed COVID-19 were examined using bedside lung ultrasound (LUS) shortly after intubation and start of invasive ventilation. In the first patient, LUS revealed extensive atelectatic areas. A recruitment maneuver was applied, resulting in some reaeration of areas that showed atelectasis, and some improvement in oxygenation was observed. Oxygenation improved further with the use of prone positioning. In the second patient, LUS showed diffuse abnormalities without atelectatic areas, and ventilation proceeded without a recruitment maneuver but with prone positioning. These two cases illustrate how LUS could be useful in identifying different lung morphologies early after the start of invasive ventilation and help decide on adjunctive therapies. This has possible implications for ventilator management in resource-limited settings, with limited availability of chest computed tomography and blood gas analyzers. Tailoring invasive ventilation based on LUS findings early after the start of invasive ventilation is feasible, but this should be further evaluated in future studies.


Investigation of the toxicokinetics of petroleum hydrocarbon distillates with the earthworm Eisenia andrei.
The Canada-wide standards for petroleum hydrocarbons in soils regulate petroleum hydrocarbons based on four distillate ranges: F1 (C6-C10), F2 (>C10-C16), F3 (>C16-C34), and F4 (>C34). Previous toxicity tests with earthworms and F2, as well as two subfractions of F3, F3a (>C16-C23) and F3a (>C23-C34), indicate that test durations might not be sufficiently long to reach threshold effect concentrations, likely because of the differing toxicokinetics for each distillate. A study was conducted to determine the toxicokinetics of both aliphatic and aromatic fractions of F2, F3a, and F3b with the earthworm Eisenia andrei. Peak accumulation curves were observed for F2 aliphatics and aromatics and F3a aromatics, likely as a result of changes in exposure concentration over the test duration via loss or a decrease in the bioavailable fraction. Biota-soil accumulation factors were >1 for total F2 aliphatics and aromatics and F3a aromatics as well as for several individual polyaromatic hydrocarbons for each distillate. Aromatics were disproportionately accumulated over aliphatics and were the main contributors to toxicity; therefore, aromatics and aliphatics should be regulated separately. The toxicokinetics were used to interpret previous toxicity data. Higher molecular weight distillates need longer-than-standard test durations to determine toxicity, so toxicity test results from fixed, standard-duration tests are not strictly comparable for these petroleum distillates.


Transvaginal hydrolaparoscopy and laparoscopy.
To evaluate the findings of outpatient transvaginal hydrolaparoscopy (THL) in comparison with diagnostic laparoscopy combined with chromopertubation in subfertile women. In a retrospective study in four large teaching hospitals, all subfertile women who underwent a THL and a conventional laparoscopy as part of their fertility work-up in the period between 2000 and 2011 were studied. Findings at THL were compared with findings at diagnostic and therapeutic laparoscopies. Tubal occlusion, endometriosis and adhesions were defined as abnormalities. Out of 1119 women, 1103 women underwent THL. A complete evaluation or incomplete but diagnostic procedure could be performed in 989 (89.7%) and 28 (2.5%), respectively. An incomplete non-diagnostic procedure was performed in 11 (1.0%) women. Failure of THL occurred in 75 women (6.8%) and 40 of these women (3.6%) subsequently underwent laparoscopy. Laparoscopy was performed in a total of 126 patients with a median time interval of 7 weeks (interquartile range [IQR] 3-13 weeks). Of 64 patients who successfully underwent both THL and laparoscopy, concordant findings were found in 53 women and discordant results in 11 women, 6 of which were caused by tubal spasm. Sensitivity of THL in detecting abnormalities was 100% and specificity was 22.2%, with a likelihood ratio of 1.29. THL in an outpatient setting can detect anatomical abnormalities comparable to the more invasive reference standard diagnostic laparoscopy. If THL succeeds, there is no need to add a diagnostic laparoscopy in the work-up.


Prevalence of portopulmonary hypertension among liver transplant candidates in a region highly endemic for viral hepatitis.
Portopulmonary hypertension (POPH) is rarely encountered in the setting of end-stage liver disease (ESLD) and, if severe, may preclude patients from undergoing liver transplantation. The aim of the present study was to determine the prevalence of POPH in the setting of ESLD for patients who were referred to King Abdulaziz Medical City-Riyadh (Riyadh, Saudi Arabia) for assessment for liver transplantation. The medical records of all patients evaluated for liver transplantation between 1993 and 2009 were retrospectively reviewed. Pulmonary hypertension (PH) was defined as an echocardiographically estimated right ventricular systolic pressure ≥40 mmHg and a mean pulmonary arterial pressure >25 mmHg measured using right heart catheterization. A total of 542 consecutive subjects with ESLD who underwent assessment for liver transplantation were identified; however, medical records for 18 were missing. The final cohort, therefore, consisted of 524 subjects with a mean (±SD) age of 49±13.9 years, 60% were male, and 70% had viral hepatitis. PH was detected by echocardiography in 64 (12%) of the 524 subjects. Hemodynamic data obtained from intraoperative right heart catheterization or as part of the pre-transplantation evaluation were available for 248 subjects, including 57 of the 64 who had echocardiographically defined PH. PH was confirmed in 30 subjects and ruled out in 27, and only 4 (0.76%) subjects fulfilled the criteria for POPH. The prevalence of POPH determined in the present study was lower than previously reported. Further prospective research is needed to confirm this finding and to explore possible clinical, genetic, and environmental factors that contribute to the low prevalence of POPH in regions highly endemic for viral hepatitis.


Distractive Auditory Stimuli in the Form of Music in Individuals With COPD: A Systematic Review.
Music has been used as a distractive auditory stimulus (DAS) in patients with COPD, but its effects are unclear. This systematic review aimed to establish the effect of DAS on exercise capacity, symptoms, and health-related quality of life (HRQOL) under three conditions: (1) during exercise training, (2) during exercise testing, and (3) for symptom management at rest. Randomized controlled or crossover trials as well as cohort studies of DAS during exercise training, during formal exercise testing, and for symptom management among individuals with COPD were identified from a search of seven databases. Two reviewers independently assessed study quality. Weighted mean differences (WMDs) with 95% CIs were calculated using a random-effects model. Thirteen studies (12 of which were randomized controlled or crossover trials) in 415 participants were included. DAS increased exercise capacity when applied over at least 2 months of exercise training (WMD, 98 m; 95% CI, 47-150 m). HRQOL improved only after a training duration of 3 months. Less dyspnea was noted with DAS during exercise training, but this was not consistently observed in short-term exercise testing or as a symptom management strategy at rest. DAS appears to reduce symptoms of dyspnea and fatigue when used during exercise training, with benefits observed in exercise capacity and HRQOL. When applied during exercise testing, the effects on exercise capacity and symptoms and as a strategy for symptom management at rest are inconsistent.


Antibacterial and Anti-Inflammatory pH-Responsive Tannic Acid-Carboxylated Agarose Composite Hydrogels for Wound Healing.
pH-sensitive hydrogels play an important role in controlled drug release applications and have the potential to impact the management of wounds. In this study, we report the fabrication of novel carboxylated agarose/tannic acid hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of tannic acid. The resulting hydrogels exhibited negligible release of tannic acid at neutral and alkaline pH and sustained release at acidic pH, where they also displayed maximum swelling. The hydrogels also displayed favorable antibacterial and anti-inflammatory properties, and a lack of cytotoxicity toward 3T3 fibroblast cell lines. In simulated wound assays, significantly greater cell migration and proliferation was observed for cells exposed to tannic acid hydrogel extracts. In addition, the tannic acid hydrogels were able to suppress NO production in stimulated human macrophages in a concentration-dependent manner, indicating effective anti-inflammatory activity. Taken together, the cytocompatibility, antibacterial, and anti-inflammatory characteristics of these novel pH-sensitive hydrogels make them promising candidates for wound dressings.


Aquatic exercise training for fibromyalgia.
Exercise training is commonly recommended for individuals with fibromyalgia. This review examined the effects of supervised group aquatic training programs (led by an instructor). We defined aquatic training as exercising in a pool while standing at waist, chest, or shoulder depth. This review is part of the update of the 'Exercise for treating fibromyalgia syndrome' review first published in 2002, and previously updated in 2007. The objective of this systematic review was to evaluate the benefits and harms of aquatic exercise training in adults with fibromyalgia. We searched The Cochrane Library 2013, Issue 2 (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, NHS Economic Evaluation Database), MEDLINE, EMBASE, CINAHL, PEDro, Dissertation Abstracts, WHO international Clinical Trials Registry Platform, and AMED, as well as other sources (i.e., reference lists from key journals, identified articles, meta-analyses, and reviews of all types of treatment for fibromyalgia) from inception to October 2013. Using Cochrane methods, we screened citations, abstracts, and full-text articles. Subsequently, we identified aquatic exercise training studies. Selection criteria were: a) full-text publication of a randomized controlled trial (RCT) in adults diagnosed with fibromyalgia based on published criteria, and b) between-group data for an aquatic intervention and a control or other intervention. We excluded studies if exercise in water was less than 50% of the full intervention. We independently assessed risk of bias and extracted data (24 outcomes), of which we designated seven as major outcomes: multidimensional function, self reported physical function, pain, stiffness, muscle strength, submaximal cardiorespiratory function, withdrawal rates and adverse effects. We resolved discordance through discussion. We evaluated interventions using mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (95% CI). Where two or more studies provided data for an outcome, we carried out meta-analysis. In addition, we set and used a 15% threshold for calculation of clinically relevant differences. We included 16 aquatic exercise training studies (N = 881; 866 women and 15 men). Nine studies compared aquatic exercise to control, five studies compared aquatic to land-based exercise, and two compared aquatic exercise to a different aquatic exercise program.We rated the risk of bias related to random sequence generation (selection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), blinding of outcome assessors (detection bias), and other bias as low. We rated blinding of participants and personnel (selection and performance bias) and allocation concealment (selection bias) as low risk and unclear. The assessment of the evidence showed limitations related to imprecision, high statistical heterogeneity, and wide confidence intervals. Aquatic versus controlWe found statistically significant improvements (P value < 0.05) in all of the major outcomes. Based on a 100-point scale, multidimensional function improved by six units (MD -5.97, 95% CI -9.06 to -2.88; number needed to treat (NNT) 5, 95% CI 3 to 9), self reported physical function by four units (MD -4.35, 95% CI -7.77 to -0.94; NNT 6, 95% CI 3 to 22), pain by seven units (MD -6.59, 95% CI -10.71 to -2.48; NNT 5, 95% CI 3 to 8), and stiffness by 18 units (MD -18.34, 95% CI -35.75 to -0.93; NNT 3, 95% CI 2 to 24) more in the aquatic than the control groups. The SMD for muscle strength as measured by knee extension and hand grip was 0.63 standard deviations higher compared to the control group (SMD 0.63, 95% CI 0.20 to 1.05; NNT 4, 95% CI 3 to 12) and cardiovascular submaximal function improved by 37 meters on six-minute walk test (95% CI 4.14 to 69.92). Only two major outcomes, stiffness and muscle strength, met the 15% threshold for clinical relevance (improved by 27% and 37% respectively). Withdrawals were similar in the aquatic and control groups and adverse effects were poorly reported, with no serious adverse effects reported. Aquatic versus land-basedThere were no statistically significant differences between interventions for multidimensional function, self reported physical function, pain or stiffness: 0.91 units (95% CI -4.01 to 5.83), -5.85 units (95% CI -12.33 to 0.63), -0.75 units (95% CI -10.72 to 9.23), and two units (95% CI -8.88 to 1.28) respectively (all based on a 100-point scale), or in submaximal cardiorespiratory function (three seconds on a 100-meter walk test, 95% CI -1.77 to 7.77). We found a statistically significant difference between interventions for strength, favoring land-based training (2.40 kilo pascals grip strength, 95% CI 4.52 to 0.28). None of the outcomes in the aquatic versus land comparison reached clinically relevant differences of 15%. Withdrawals were similar in the aquatic and land groups and adverse effects were poorly reported, with no serious adverse effects in either group. Aquatic versus aquatic (Ai Chi versus stretching in the water, exercise in pool water versus exercise in sea water)Among the major outcomes the only statistically significant difference between interventions was for stiffness, favoring Ai Chi (1.00 on a 100-point scale, 95% CI 0.31 to 1.69). Low to moderate quality evidence relative to control suggests that aquatic training is beneficial for improving wellness, symptoms, and fitness in adults with fibromyalgia. Very low to low quality evidence suggests that there are benefits of aquatic and land-based exercise, except in muscle strength (very low quality evidence favoring land). No serious adverse effects were reported.


Numerical assessment of induced ELF currents in the human head due to the battery current of a digital mobile phone.
In this study, the extremely low frequency (ELF) fields induced in the human head by the battery currents of a mobile phone are considered. The magnetic field induced by the phone was measured, and this data was used to calculate the resulting currents induced in the human head and brain. Both the finite element method (FEM) and finite integration technique (FIT) were used for numerical computations. The computed current density values were then compared with the guidelines given by the International Commission on Non-Ionising Radiation Protection (ICNIRP). The comparison showed that the computed exposure is well within the limits of those guidelines.


Hierarchical multifunctional composites by conformally coating aligned carbon nanotube arrays with conducting polymer.
A novel method for the fabrication of carbon nanotube (CNT)-conducting polymer composites is demonstrated by conformally coating extremely high aspect ratio vertically aligned-CNT (A-CNT) arrays with conducting polymer via oxidative chemical vapor deposition (oCVD). A mechanical densification technique is employed that allows the spacing of the A-CNTs to be controlled, yielding a range of inter-CNT distances between 20 and 70 nm. Using this morphology control, oCVD is shown to conformally coat 8-nm-diameter CNTs having array heights up to 1 mm (an aspect ratio of 10(5)) at all inter-CNT spacings. Three phase CNT-conducting polymer nanocomposites are then fabricated by introducing an insulating epoxy via capillary-driven wetting. CNT morphology is maintained during processing, allowing quantification of direction-dependent (nonisotropic) composite properties. Electrical conductivity occurs primarily along the CNT axial direction, such that the conformal conducting polymer has little effect on the activation energy required for charge conduction. In contrast, the conducting polymer coating enhanced the conductivity in the radial direction by lowering the activation energy required for the creation of mobile charge carriers, in agreement with variable-range-hopping models. The fabrication strategy introduced here can be used to create many multifunctional materials and devices (e.g., direction-tailorable hydrophobic and highly conducting materials), including a new four-phase advanced fiber composite architecture.


Twelve years' experience of the mini-Bankart repair for recurrent anterior dislocation of the shoulder.
Stabilization for recurrent anterior shoulder dislocation can be achieved through either an open or arthroscopic approach. The former tends to have a lower recurrence rate but longer rehabilitation.The technique of mini-Bankart repair has been used at this establishment since 1996. We retrospectively reviewed the patients that had undergone this procedure. We describe our experience of the mini-Bankart procedure and the results in 24 patients with a mean follow-up of 56 months (range, 12-144 months).The technique is a direct mini-approach to the shoulder joint, preserving the inferior portion of subscapularis. Where present, a Bankart lesion is repaired with two GII Mitek anchors (Ethicon) and the capsule reefed. There were no incidences of repeat anterior dislocation, and the average time period taken to return to work was 8.8 weeks. We recommend this technique due to its low recurrence rate and satisfactory return to normal function.


Evaluation of a vision-related utility instrument: the German vision and quality of life index.
Multi-attribute utility instruments (MAUIs), which contain a descriptive system, including several health dimensions with associated levels of increasing severity, are used commonly to measure utilities. However, the validity of the descriptive systems rarely is examined using modern psychometric theory. Therefore, we evaluated the psychometric properties of the German version of the Vision and Quality of Life Index (VisQol), a six-item vision-related MAUI. The German VisQol was self-administered to 340 patients and 280 controls. All subjects underwent a full ophthalmologic examination, including best-corrected visual acuity (VA) testing. The psychometric properties of the VisQoL were assessed using Rasch analysis. The VisQoL's descriptive system did not function in controls. In patients, after collapsing response categories to resolve disordered thresholds and omitting misfitting persons, the measurement properties (i.e., precision, unidimensionality, and targeting) of the German VisQoL were satisfactory. Most person misfit related to unexpected responses to item 4 ("organizing assistance"). Rasch-generated person estimates were not different between age categories, sex, or underlying ocular condition, but decreased significantly with presence of visual impairment in the better eye (LogMAR ≥ 0.5, 1.20 ± 4.62 compared to 3.46 ± 3.52, P < 0.001). The German VisQoL's descriptive system displayed adequate fit to the Rasch model after removal of a large proportion of patients with poor fit statistics. However, the wording of item four should be revised to reduce respondent confusion and measurement "noise." The scale's descriptive system does not function in a sample of visually unimpaired persons, most likely due to a lack of variance in the measured trait.


Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.
Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.


Sex predilection in patients with acute frontal sinusitis.
We performed a retrospective analysis of 50 patients with acute frontal sinusitis who came to the Albert Einstein College of Medicine affiliated hospitals between 1981 and 1984. Cases were analyzed for age and sex in an attempt to determine the sex predilection for this disease in various age groups. Of the 50 patients studied, 38 (76%) were male and 12 (24%) were female. When subdivided into adult (older than 21 years of age) and adolescent (11 to 21 years of age) subgroups, a similar male predominance was noted. Among adults (28 patients), 21 (75%) were male and 7 (25%) were female. Among adolescents (22 patients), 17 (77%) were male and 5 (23%) were female. Of the 50 patients studied, 3 developed intracranial complications. All of these latter patients (all males) were in the adolescent group. Our findings indicate that male adolescents may be a high risk subgroup for developing intracranial complications secondary to their sinus infections.


Expression of aquaporins in the rat ocular tissue.
The aquaporins (AQPs) are a rapid growing family of water channel proteins found in animals, plants and microorganisms that raise plasma membrane water permeability required for efficient isosmotic fluid transport. Five homologs of aquaporins (AQP1, AQP2, AQP3, AQP4 and AQP5) have been identified from various mammalian tissues; the expression of these aquaporins in ocular tissues was studied. Semiquantitative expression levels of these aquaporins were determined in ciliary body, cornea, lens, retina, iris and choroid using RT-PCR. Expression levels of AQP1 are highest among the known aquaporins in each rat ocular tissue examined. In cornea, AQP1 is expressed approximately three-fold higher than AQP3 and 2.5 fold higher than AQP5. However, the highest intraocular expressions of AQP3 and AQP5 are in the cornea. In the iris, expression levels of AQP1 are approximately 600-700 fold higher than AQP4 and AQP5. In the ciliary body, the expression levels of AQP1 are approximately ten-fold higher than AQP4, the only other aquaporin expressed. In the lens, the major water channel is AQP1 with detectable levels of AQP4 and AQP5 that are approximately 1000-fold lower than AQP1. In choroid, AQP1 is the only water channel expressed. In retin, AQP1 is expressed approximately six-fold higher than AQP4, the only other aquaporin expressed. However, the highest ocular expression of AQP4 is in retina. AQP2 is not detected in the eye. Finally, the possible physiological roles of aquaporins in maintaining and regulating the aqueous flow, and corneal and lens transparency are discussed.


New insights on the antidepressant discontinuation syndrome.
Antidepressants are at best 50–55% effective. Non-compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non-compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology. The relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. This review raises awareness of the long-term negative aspects of non-compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to "design-out" a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long-term outcome.


Depth-encoded all-fiber swept source polarization sensitive OCT.
Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of conventional OCT and can assess depth-resolved tissue birefringence in addition to intensity. Most existing PS-OCT systems are relatively complex and their clinical translation remains difficult. We present a simple and robust all-fiber PS-OCT system based on swept source technology and polarization depth-encoding. Polarization multiplexing was achieved using a polarization maintaining fiber. Polarization sensitive signals were detected using fiber based polarization beam splitters and polarization controllers were used to remove the polarization ambiguity. A simplified post-processing algorithm was proposed for speckle noise reduction relaxing the demand for phase stability. We demonstrated systems design for both ophthalmic and catheter-based PS-OCT. For ophthalmic imaging, we used an optical clock frequency doubling method to extend the imaging range of a commercially available short cavity light source to improve polarization depth-encoding. For catheter based imaging, we demonstrated 200 kHz PS-OCT imaging using a MEMS-tunable vertical cavity surface emitting laser (VCSEL) and a high speed micromotor imaging catheter. The system was demonstrated in human retina, finger and lip imaging, as well as ex vivo swine esophagus and cardiovascular imaging. The all-fiber PS-OCT is easier to implement and maintain compared to previous PS-OCT systems and can be more easily translated to clinical applications due to its robust design.


Prevalence of anxiety following adult traumatic brain injury: A meta-analysis comparing measures, samples and postinjury intervals.
Anxiety following a traumatic brain injury (TBI) is a common problem; however, disparate prevalence estimates limit the clinical utility of research. The purpose of the current study was to examine how differences in methodological variables and sample characteristics impact on the prevalence of anxiety. Data from 41 studies that examined either the prevalence of generalized anxiety disorder (GAD) diagnoses or clinically significant "cases" of self-reported anxiety following adult, nonpenetrating TBI were analyzed, and the impact of diagnostic criteria, measure, postinjury interval and injury severity was evaluated. Overall, 11% of people were diagnosed with GAD and 37% reported clinically significant levels of anxiety following TBI. Prevalence estimates varied for different diagnostic criteria (range: 2%-19%), interview schedules (range: 2%-28%), and self-report measures (range: 36%-50%). GAD and "cases" of anxiety were most prevalent 2 to 5 years postinjury. The rates of GAD increased with injury severity (mild: 11%, severe 15%), but "cases" decreased (mild: 53%, severe: 38%), although neither difference was significant. Anxiety is common after a TBI and ongoing monitoring and treatment should be provided. Methodological and sample characteristics should be clear and well-defined, as differences across studies (e.g., how anxiety is conceptualized, which measure is used, time since injury, injury severity) impact prevalence rates.


ENCODE whole-genome data in the UCSC Genome Browser: update 2012.
The Encyclopedia of DNA Elements (ENCODE) Consortium is entering its 5th year of production-level effort generating high-quality whole-genome functional annotations of the human genome. The past year has brought the ENCODE compendium of functional elements to critical mass, with a diverse set of 27 biochemical assays now covering 200 distinct human cell types. Within the mouse genome, which has been under study by ENCODE groups for the past 2 years, 37 cell types have been assayed. Over 2000 individual experiments have been completed and submitted to the Data Coordination Center for public use. UCSC makes this data available on the quality-reviewed public Genome Browser (http://genome.ucsc.edu) and on an early-access Preview Browser (http://genome-preview.ucsc.edu). Visual browsing, data mining and download of raw and processed data files are all supported. An ENCODE portal (http://encodeproject.org) provides specialized tools and information about the ENCODE data sets.


Carpel size, grain filling, and morphology determine individual grain weight in wheat.
Individual grain weight is a major yield component in wheat. To provide a comprehensive understanding of grain weight determination, the carpel size at anthesis, grain dry matter accumulation, grain water uptake and loss, grain morphological expansion, and final grain weight at different positions within spikelets were investigated in a recombinant inbred line mapping population of bread wheat (Triticum aestivum L.)×spelt (Triticum spelta L.). Carpel size, grain dry matter and water accumulation, and grain dimensions interacted strongly with each other. Furthermore, larger carpels, a faster grain filling rate, earlier and longer grain filling, more grain water, faster grain water absorption and loss rates, and larger grain dimensions were associated with higher grain weight. Frequent quantitative trait locus (QTL) coincidences between these traits were observed, particularly those on chromosomes 2A, 3B, 4A, 5A, 5DL, and 7B, each of which harboured 16-49 QTLs associated with >12 traits. Analysis of the allelic effects of coincident QTLs confirmed their physiological relationships, indicating that the complex but orderly grain filling processes result mainly from pleiotropy or the tight linkages of functionally related genes. After grain filling, distal grains within spikelets were smaller than basal grains, primarily due to later grain filling and a slower initial grain filling rate, followed by synchronous maturation among different grains. Distal grain weight was improved by increased assimilate availability from anthesis. These findings provide deeper insight into grain weight determination in wheat, and the high level of QTL coincidences allows simultaneous improvement of multiple grain filling traits in breeding.


Protein myristoylation as an intermediate step during signal transduction in macrophages: its role in arachidonic acid metabolism and in responses to interferon gamma.
The role of macrophages in the regulation of inflammation and immunity is, in part, due to their secretory repertoire. Among the important mediators released by macrophages are the products of both the cyclooxygenase and lipoxygenase pathways of arachidonic acid (20:4) metabolism. The principal focus of this paper is the mechanism by which bacterial lipopolysaccharides (LPS) regulate 20:4 metabolism in macrophages. LPS has the capacity to prime macrophages for greatly enhanced 20:4 metabolism when the cells are subsequently challenged with a spectrum of triggers. Concomitant with priming, LPS also promotes the covalent attachment of myristic acid to a set of macrophage proteins. The time and concentration dependence of LPS-induced protein myristoylation is consistent with a role for myristoylation in LPS priming of the 20:4 cascade. One of the myristoylated proteins is a 68K (K = 10(3) Mr) protein kinase C substrate which associates with membranes upon myristoylation. LPS-primed macrophages show greatly increased phosphorylation of the 68K protein when the cells are subsequently treated with protein kinase C activating phorbol esters. It is proposed that the myristoylation of the 68K protein promotes its attachment to the membrane where it is more closely associated with activated protein kinase C (PKC), an association which would ensure more efficient catalysis during the mobilization and oxygenation of 20:4. This paper also examines protein myristoylation during T-cell-mediated activation of macrophages. Immune-activated macrophages have an enhanced capacity to kill several infectious agents by oxidative mechanisms. The lymphokine gamma-interferon (IFN gamma) rapidly induces the myristoylation of a 48K protein. This 48K protein is also myristoylated in murine macrophages that have been activated in vivo by intraperitoneal injection of Corynebacterium parvum, suggesting that it may be an important intermediate in the activation of macrophages for enhanced microbicidal capacity.


Analysis of Diagnoses, Symptoms, Medications, and Admissions Among Patients With Cancer Presenting to Emergency Departments.
Better understanding of the emergency care needs of patients with cancer will inform outpatient and emergency department (ED) management. To provide a benchmark description of patients who present to the ED with active cancer. This multicenter prospective cohort study included 18 EDs affiliated with the Comprehensive Oncologic Emergencies Research Network (CONCERN). Of 1564 eligible patients, 1075 adults with active cancer were included from February 1, 2016, through January 30, 2017. Data were analyzed from February 1 through August 1, 2018. The proportion of patients reporting symptoms (eg, pain, nausea) before and during the ED visit, ED and outpatient medications, most common diagnoses, and suspected infection as indicated by ED antibiotic administration. The proportions observed, admitted, and with a hospital length of stay (LOS) of no more than 2 days were identified. Of 1075 participants, mean (SD) age was 62 (14) years, and 51.8% were female. Seven hundred ninety-four participants (73.9%; 95% CI, 71.1%-76.5%) had undergone cancer treatment in the preceding 30 days; 674 (62.7%; 95% CI, 59.7%-65.6%) had advanced or metastatic cancer; and 505 (47.0%; 95% CI, 43.9%-50.0%) were 65 years or older. The 5 most common ED diagnoses were symptom related. Of all participants, 82 (7.6%; 95% CI, 6.1%-9.4%) were placed in observation and 615 (57.2%; 95% CI, 54.2%-60.2%) were admitted; 154 of 615 admissions (25.0%; 95% CI, 21.7%-28.7%) had an LOS of 2 days or less (median, 3 days; interquartile range, 2-6 days). Pain during the ED visit was present in 668 patients (62.1%; 95% CI, 59.2%-65.0%; mean [SD] pain score, 6.4 [2.6] of 10.0) and in 776 (72.2%) during the prior week. Opioids were administered in the ED to 228 of 386 patients (59.1%; 95% CI, 18.8%-23.8%) with moderate to severe ED pain. Outpatient opioids were prescribed to 368 patients (47.4%; 95% CI, 3.14%-37.2%) of those with pre-ED pain, including 244 of 428 (57.0%; 95% CI, 52.2%-61.8%) who reported quite a bit or very much pain. Nausea in the ED was present in 336 (31.3%; 95% CI, 28.5%-34.1%); of these, 160 (47.6%; 95% CI, 12.8%-17.1%) received antiemetics in the ED. Antibiotics were administered in the ED to 285 patients (26.5%; 95% CI, 23.9%-29.2%). Of these, 209 patients (73.3%; 95% CI, 17.1%-21.9%) were admitted compared with 427 of 790 (54.1%; 95% CI, 50.5%-57.6%) not receiving antibiotics. This initial prospective, multicenter study profiling patients with cancer who were treated in the ED identifies common characteristics in this patient population and suggests opportunities to optimize care before, during, and after the ED visit. Improvement requires collaboration between specialists and emergency physicians optimizing ED use, improving symptom control, avoiding unnecessary hospitalizations, and appropriately stratifying risk to ensure safe ED treatment and disposition of patients with cancer.


Some properties of acetylcholine receptors in human cultured myotubes.
The distribution and single channel properties of acetylcholine (ACh) receptors in human myotubes grown in tissue culture have been examined. Radioautography of myotubes labelled with [125I]alpha-bungarotoxin showed that ACh receptors are distributed uniformly over the myotube surface at a density of 3.9 +/- 0.5 receptors per square micrometre. Accumulations of ACh receptors (hot spots) were found rarely. The conductance and kinetics of ACh-activated channels were investigated with the patch-clamp technique. Cell-attached membrane patches were used in all experiments. A single channel conductance in the range 40-45 pS was calculated. No sublevels of conductance (substates) of the activated channel were observed. The distribution of channel open-times varied with ACh concentration. With 100 nM ACh, the distribution was best fitted by the sum of two exponentials, whereas with 1 microM ACh a single exponential could be fitted. The mean channel open-time at the myotube resting potential (ca. -70 mV, 22 degrees C) was 8.2 ms. The distribution of channel closed-times was complex at all concentrations of ACh studied (100 nM to 10 microM). With desensitizing doses of ACh (10 microM), channel openings occurred in obvious bursts; each burst usually appeared as part of a 'cluster' of bursts. Both burst duration and mean interval between bursts increased with membrane hyperpolarization. Individual channel open-times and burst durations showed similar voltage dependence (e-fold increase per 80 mV hyperpolarization), whereas both the channel closed-times within a burst and the number of openings per burst were independent of membrane potential.


The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association.
Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.


GPER activation protects against epithelial barrier disruption by Staphylococcus aureus α-toxin.
Sex bias in innate defense against Staphylococcus aureus skin and soft tissue infection (SSTI) is dependent on both estrogen production by the host and S. aureus secretion of the virulence factor, α-hemolysin (Hla). The impact of estrogen signaling on the immune system is most often studied in terms of the nuclear estrogen receptors ERα and ERβ. However, the potential contribution of the G protein-coupled estrogen receptor (GPER) to innate defense against infectious disease, particularly with respect to skin infection, has not been addressed. Using a murine model of SSTI, we found that GPER activation with the highly selective agonist G-1 limits S. aureus SSTI and Hla-mediated pathogenesis, effects that were absent in GPER knockout mice. Specifically, G-1 reduced Hla-mediated skin lesion formation and pro-inflammatory cytokine production, while increasing bacterial clearance. In vitro, G-1 reduced surface expression of the Hla receptor, ADAM10, in a human keratinocyte cell line and increased resistance to Hla-mediated permeability barrier disruption. This novel role for GPER activation in skin innate defense against infectious disease suggests that G-1 may have clinical utility in patients with epithelial permeability barrier dysfunction or who are otherwise at increased risk of S. aureus infection, including those with atopic dermatitis or cancer.


The determinants of first sex by age 14 in a high-risk adolescent population.
A study using data for mothers from the National Longitudinal Survey of Youth and their children aged 14 or older indicates that, after accounting for a wide range of demographic and socioeconomic antecedents, children are significantly more likely to become sexually active before age 14 if their mother had sex at an early age and if she has worked extensively. In addition, early sexual debut is eight times as likely among black boys as among non-Hispanic white boys. Children who use controlled substances at an early age are more than twice as likely to have sex before age 14 as those who do not, although the type of substance having an effect is different for girls (cigarettes) and boys (alcohol). Church attendance is an important determinant of delayed sexual activity, but only when a child's friends attend the same church.


Ciliary reversal without rotation of axonemal structures in ctenophore comb plates.
We have used a newly discovered reversal response of ctenophore comb plates to investigate the structural mechanisms controlling the direction of ciliary bending. High K+ concentrations cause cydippid larvae of the ctenophore Pleurobrachia to swim backward. High-speed cine films of backward-swimming animals show a 180 degree reversal in beat direction of the comb plates. Ion substitution and blocking experiments with artificial seawaters demonstrate that ciliary reversal is a Ca++-dependent response. Comb plate cilia possess unique morphological markers for numbering specific outer-doublet microtubules and identifying the sidedness of the central pair. Comb plates of forward- and backward-swimming ctenophores were frozen in different stages of the beat cycle by an "instantaneous fixation" method. Analysis of transverse and longitudinal sections of instantaneously fixed cilia showed that the assembly of outer doublets does not twist during ciliary reversal. This directly confirms the existence of radial switching mechanism regulating the sequence of active sliding on opposite sides of the axoneme. We also found that the axis of the central pair always remains perpendicular to the plane of bending; more importantly, the ultrastructural marker showed that the central pair does not rotate during a 180 degree reversal in beat direction. Thus, the orientation of the central pair does not control the direction of ciliary bending (i.e., the pattern of active sliding around the axoneme). We discuss the validity of this finding for three-dimensional as well as two-dimensional ciliary beat cycles and conclude that models of central-pair function based on correlative data alone must now be re-examined in light of these new findings on causal relations.


Antimicrobial Activity of Chestnut Extracts for Potential Use in Managing Soilborne Plant Pathogens.
Chestnut extracts were studied for antimicrobial activity against selected microorganisms, including plant pathogens. Chestnut extract on paper discs was applied to an agar medium to evaluate the inhibition to multiple microorganisms or the extract was added at various concentrations to a culture medium to evaluate the growth of target microorganisms. Chestnut type, tissue of plants (shell, pellicle, and leaf), extraction methods, and physical characteristics were studied to determine antimicrobial activity. Most test microorganisms were inhibited by the extracts at different effective concentrations for 50% growth inhibition (EC50). Pseudomonas fluorescens was the most sensitive (EC50 = 4.4 μg/μl), Phytophthora cambivora was one of the least inhibited (EC50 = 185 μg/μl), and Cryphonectria parasitica was not inhibited. Extracts of the Japanese × European chestnut (Castanea crenata × C. sativa) 'Colossal' showed a greater inhibition than those of wild trees of the Chinese species (C. mollissima). High temperature did not affect the inhibitory effect. Extracts from chestnut pellicle had the highest concentration of antimicrobial compound, compared with leaf and shell. The active fraction contained several substances with molecular masses consistent with one flavonol glycoside and several terpenoid substances. Pellicle and shell tissue reduced radish scab disease caused by Streptomyces scabies in the greenhouse.


Resolving structural variability in network models and the brain.
Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling--in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity) do not in general simultaneously display a second (e.g., hierarchy). This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful starting point for the statistical inference of brain network structure from neuroimaging data.


The EGFR ligands amphiregulin and heparin-binding egf-like growth factor promote peritoneal carcinomatosis in CXCR4-expressing gastric cancer.
Peritoneal carcinomatosis, often associated with malignant ascites, is the most frequent cause of death in patients with advanced gastric cancer. We previously showed that the CXCR4/CXCL12 axis is involved in the development of peritoneal carcinomatosis from gastric cancer. Here, we investigated whether epidermal growth factor receptor (EGFR) ligands are also involved in the development of peritoneal carcinomatosis from gastric cancer. The functional involvement of expression of the ErbB family of receptors and/or EGFR ligands was examined in CXCR4-expressing human gastric cancer cells and fibroblasts, clinical samples (primary tumors and ascites), and an animal model. High concentration of the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF), as well as of CXCL12, were present in malignant ascites. Human gastric cancer cell lines and primary gastric tumors, with high potential to generate peritoneal carcinomatosis, expressed high levels of EGFR and CXCR4 mRNA and protein. Both amphiregulin and HB-EGF enhanced the proliferation, migration, and functional CXCR4 expression in highly CXCR4-expressing gastric cancer NUGC4 cells. Amphiregulin strongly enhanced the proliferation of NUGC4 cells, whereas HB-EGF markedly induced the migration of fibroblasts. Moreover, HB-EGF and CXCL12 together enhanced TNFα-converting enzyme (TACE)-dependent amphiregulin shedding from NUGC4 cells. In an experimental peritoneal carcinomatosis model in mice, cetuximab effectively reduced tumor growth and ascites formation. Our results strongly suggest that the EGFR ligands amphiregulin and HB-EGF play an important role, interacting with the CXCL12/CXCR4 axis, in the development of peritoneal carcinomatosis from gastric cancer, indicating that these two axes may be potential therapeutic targets for peritoneal carcinomatosis of gastric carcinoma.


Human stem cell therapy in ischaemic stroke: a review.
Stroke is a leading cause of death and disability. Globally, 15 million people suffer a stroke each year, of whom more than 5 million die, and a further 5 million are left permanently disabled. Current treatment options offer modest benefits, and there is a pressing need for new and effective treatments. Stem cell therapy is a well-established treatment modality for various haematological diseases, with its use now being explored in different disease processes, including various neurological diseases, as well as vascular conditions such as ischaemic heart disease and peripheral vascular disease. Promising results have been seen in animal models of stroke, with evidence of significant functional benefits. Translation to the bedside, however, is in its early stages. This review will discuss the scientific background to stem cell therapy in ischaemic stroke, including evidence from current clinical trials.


Does enrollment in multidisciplinary team-based primary care practice improve adherence to guideline-recommended processes of care? Quebec's Family Medicine Groups, 2002-2010.
We investigated whether multidisciplinary team-based primary care practice improves adherence to process of care guidelines, in the absence of financial incentives related to pay-for-performance. We conducted a natural experiment including 135,119 patients, enrolled with a general practitioner (GP) in a multidisciplinary team Family Medicine Group (FMG) or non-FMG practice, using longitudinal data from Quebec's universal insurer over the relevant time period (2000-2010). All study subjects had diabetes, chronic obstructive pulmonary disease, or heart failure and were followed over a 7-year period, 2 years prior to enrollment and 5 years after. We constructed indicators on adherence to disease-specific guidelines and composite indicators across conditions. We evaluated the effect of FMGs using propensity score methods and Difference-in-Differences (DD) models. Rates of adherence to chronic disease guidelines increased for both FMG and non-FMG patients after enrollment, but not differentially so. Adherence to prescription-related guidelines improved less for FMG patients (DD [95% CI]=-2.83% [-4.08%, -1.58%]). We found no evidence of an FMG effect on adherence to consultation-related guidelines, (DD [95% CI]=-0.24% [-2.24%; 1.75%]). We found no evidence that FMGs increased adherence to the guidelines we evaluated. Future research is needed to assess why this reform did not improve performance on these quality-of-care indicators.


Use of butterfly needles to draw blood is independently associated with marked reduction in hemolysis compared to intravenous catheter.
Hemolysis of blood samples drawn in the emergency department (ED) is a common problem that can interfere with timely diagnosis and appropriate treatment. The objective of this study was to identify the smallest number of remediable factors that independently increases the risk of hemolysis to design an effective strategy to address this issue. This was a prospective, observational, cross-sectional study of blood specimens obtained by ED staff in an urban, academic, adult ED in a tertiary care center. The staff member who drew the specimen recorded data on a standardized data collection instrument about device (intravenous [IV] catheter or butterfly needle), needle size, anatomic site, fullness of collection tube, tourniquet time, and difficulty of venipuncture. Specimens were sent to the laboratory by a vacuum-powered tube system. A standard automated process that measures free hemoglobin was used to identify hemolysis. A multivariable logistic regression and a tabular analysis stratified by device were performed. Ninety-five percent confidence intervals (CIs) were calculated around the odds ratios (ORs) and around the difference between hemolysis rates. Data were collected on 5,118 blood specimens. There were 4,513 specimens with complete data on all characteristics of the blood draw included in the analyses. The overall hemolysis rate was 12.5% (95% CI = 11.6% to 13.5%), 14.6% in blood drawn from IV catheters and 2.7% from butterfly needles (difference = 11.9%; 95% CI = 10.2% to 13.4%). Device was the strongest independent predictor of hemolysis (OR = 7.7; 95% CI = 4.9 to 12.0). In specimens drawn by IV catheter, hemolysis was significantly higher when blood was drawn from locations other than the antecubital fossa, with small-gauge catheters, collection tubes ≤ half full, tourniquet time ≥ 1 minute, and difficult venipuncture. In contrast, none of these factors was associated with hemolysis when blood was drawn by butterfly needle. The device used to collect blood was the strongest independent predictor of hemolysis in blood samples drawn in the ED in this study. This finding suggests that the most effective strategy to reduce the rate of hemolysis in the ED is to use butterfly needles for phlebotomy rather than IV catheters.


The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy.
To determine whether the use of mild soap and aloe vera gel versus mild soap alone would decrease the incidence of skin reactions in patients undergoing radiation therapy. Prospective, randomized, blinded clinical trial. Radiation therapy outpatient clinic in a cancer center affiliated with a major teaching medical facility. The mean age of the participants was 56 years. The group consisted of Caucasians (74%) and African Americans (26%). The ethnic mix was non-Hispanic (65%) and Hispanic (35%). Prophylactic skin care began on the first day of radiation therapy. Patients cleansed the area with mild, unscented soap. Patients randomized into the experimental arm of the trial were instructed to liberally apply aloe vera gel to the area at various intervals throughout the day. At low cumulative dose levels < or = 2,700 cGy, no difference existed in the effect of adding aloe. When the cumulative dose was high (> 2,700 cGy), the median time was five weeks prior to any skin changes in the aloe/soap arm versus three weeks in the soap only arm. When the cumulative dose increases over time, there seems to be a protective effect of adding aloe to the soap regimen. Skin products used to treat radiation dermatitis vary among institutions. Nurses should be aware that some patients may be predisposed to skin problems. Nurses must be aware of newly developed products and research regarding these products so that effective treatment can be instituted.


Cannabidiol attenuates mechanical allodynia in streptozotocin-induced diabetic rats via serotonergic system activation through 5-HT1A receptors.
Most diabetic patients describe moderate to severe pain symptoms whose pharmacological treatment is palliative and poorly effective. Cannabidiol (CBD) has shown promising results in painful conditions. Then, we aimed to investigate the potential antinociceptive effect of CBD over the mechanical allodynia in streptozotocin-induced diabetic (DBT) rats, as well as its involved mechanisms. Wistar adult male diabetic rats were treated acutely or sub-chronically (for 14 days) with CBD (0.1, 0.3 or 3 mg/kg, intraperitoneal; i.p.) and had their mechanical threshold assessed using the electronic Von Frey. Acute treatment with CBD (at doses of 0.3 and 3 mg/kg) exerted a significant anti-allodynic effect, which is not associated with locomotor impairment. The antinociceptive effect of CBD (3 mg/kg) was not altered by the pre-treatment with CB1 or CB2 receptor antagonists (AM251 and AM630; respectively; both at a dose of 1 mg/kg, i.p.) nor by glycine receptor antagonist (strychnine hydrochloride, 10 μg/rat, intrathecal, i.t.). However, this effect was completely prevented by the pre-treatment with the selective 5-HT1A receptor antagonist WAY 100135 (3 μg/rat, i.t.). Sub-chronic treatment with CBD (0.3 or 3 mg/kg) induced a sustained attenuation of the mechanical allodynia in DBT rats. DBT rats presented significantly lower spinal cord levels of serotonin, which was prevented by the daily treatment with CBD (0.3 mg/kg). Taken together, our data suggest that CBD may be effective in the treatment of painful diabetic neuropathy and this effect seems to be potentially mediated by the serotonergic system activation through 5-HT1A receptors.


Unusual Presentation of Porencephalic Cyst in an Adult.
Porencephalic cyst is quite a rare entity in adults with only a few cases reported so far. It is usually congenital and seen in neonates. Here, we report a 28-year-old female who presented with post-ictal confusion following a new onset of focal seizures with secondary generalisation. She was diagnosed to have porencephalic cyst in left posterior parietal lobe on brain imaging. She was started on anti-epileptic drugs and is on follow up.


Two 6-minute Walk Tests Are Required During Hospitalisation for Acute Exacerbation of COPD.
The 6-minute walk test (6MWT) is recommended to be performed twice to accurately assess exercise performance in stable chronic obstructive pulmonary disease (COPD) due to the presence of a learning effect. It is unknown whether a learning effect exists when the 6MWT is performed during hospitalisation for acute exacerbation of COPD (AECOPD). This study investigated whether repeat 6MWTs are necessary when conducted in inpatients with AECOPD. Pooled analysis was undertaken of data from two studies (Australia and Brazil) involving 46 participants (25 males, mean age 67.2 years, FEV1 43% predicted) admitted with AECOPD. Two 6MWTs, separated by ≥20 minutes, were performed on the day of discharge. Six-minute walk distance (6MWD; primary outcome), perceived dyspnoea (Borg scale), heart rate and oxyhaemoglobin saturation were recorded. 6MWD data from tests one (T1) and two (T2) were analysed via visual inspection of Bland-Altman plots. Factors associated with test improvement or decline were explored. Mean 6MWD difference between T1 and T2 was 6.2 m, however limits of agreement were wide (-92.2 m to 104.5 m). 32 (70%) participants improved (by any distance) from T1 to T2 by a mean (± standard deviation) of 32 m ± 28 m. Of these, 14 (30%) improved by a distance > 30 m. Fourteen (30%) participants recorded poorer 6MWD at T2 by a mean of 52 m ± 36 m. No factors were able to identify participants who improved or declined upon repeat testing. When performed in patients admitted to hospital with AECOPD, the 6MWT needs to be conducted twice in order to better estimate 6MWD.


Anaemia in schoolchildren in eight countries in Africa and Asia.
To report on the haemoglobin concentrations and prevalence of anaemia in schoolchildren in eight countries in Africa and Asia. Blood samples were collected during surveys of the health of schoolchildren as a part of programmes to develop school-based health services. Rural schools in Ghana, Indonesia, Kenya, Malawi, Mali, Mozambique, Tanzania and Vietnam. Nearly 14 000 children enrolled in basic education in three age ranges (7-11 years, 12-14 years and > or =15 years) which reflect the new UNICEF/WHO thresholds to define anaemia. Anaemia was found to be a severe public health problem (defined as >40% anaemic) in five African countries for children aged 7-11 years and in four of the same countries for children aged 12-14 years. Anaemia was not a public health problem in the children studied in the two Asian countries. More boys than girls were anaemic, and children who enrolled late in school were more likely to be anaemic than children who enrolled closer to the correct age. The implications of the four new thresholds defining anaemia for school-age children are examined. Anaemia is a significant problem in schoolchildren in sub-Saharan Africa. School-based health services which provide treatments for simple conditions that cause blood loss, such as worms, followed by multiple micronutrient supplements including iron, have the potential to provide relief from a large burden of anaemia.


Advanced MR imaging techniques for skeletal muscle evaluation.
Diagnostic imaging procedures for muscle evaluation have typically provided basic information concerning gross anatomical change resulting from pathology. Up until recently the musculoskeletal radiologist has been fairly limited to using simple proton-density weighted fat-saturated and short tau inversion recovery magnetic resonance imaging scans for assessment of skeletal muscle. Recent advances, however, have resulted in development of newer scans and postprocessing methods that provide much more than gross muscle structure. Scans providing fine structure, muscle function, and metabolism can easily be done using clinical scanners. Here we describe how diffusion tensor imaging (DTI) and blood oxygenation level-dependent (BOLD) imaging together can provide detailed information on muscle structural and functional changes. DTI is useful for visualizing muscle tears, and BOLD can be used for vascular insufficiency (e.g., compartment syndrome). In clinical sites that are gaining experience using these techniques, imaging of muscle pathology is becoming increasingly thorough. In the future, these methods will reduce the need for invasive approaches to study muscle pathology.


Inflectional bootstrapping in 2-year-olds.
The theory of syntactic bootstrapping proposes that children can use syntax to infer the meanings of words. This paper presents experimental evidence that children are also able to use word inflections to infer word reference. Twenty-four- and 30-month-olds were tested in a preferential looking experiment. Children were shown a pair of novel images, one showing a single object, the other a pair of objects, whilst they heard novel words with and without the English plural inflection. Word-image associations were then assessed. Analyses revealed that the older group of children had learnt to associate the words with the appropriate pictures. These results demonstrate that early in the third year, children are readily able to identify whether a spoken word is a singular or plural form, that they have a proper understanding of the significance of plural morphology and that they can deploy this knowledge inferentially to aid the process of word learning--a strategy we call inflectional bootstrapping.


Influence of Stiles-Crawford effect on visual performance after laser in situ keratomileusis.
We evaluated the impact of the Stiles-Crawford effect (SCE) on visual performance following laser in situ keratomileusis procedures. This prospective study included 71 eyes of 36 consecutive myopic patients (mean age, 20.94±3.69 years). Ocular aberrations and contrast sensitivity were measured one month after surgery. The SCE was modeled optically as a filter placed in front of the eye, and then the modulation transfer functions (MTFs) and the predicted log contrast sensitivity were calculated from the measured wavefront aberration data. Then the visual Strehl ratio for MTF (VSMTF) was calculated. The results indicated that the computed MTF with SCE were superior to that without SCE. The predicted contrast sensitivity functions were underestimated about 20% when the SCE was not taken into account for the scotopic pupil. Moreover, the measured contrast sensitivity was not significantly different from that with SCE at 6, 12, and 18 cycles/deg spatial frequencies. According to the obtained VSMTF ratio, optical qualities of all eyes were underestimated with the range from 5% (0.02 log unit) to 65% (0.22 log unit) without SCE, and the average value is 41% (0.15 log unit). When only taking higher-order aberrations into account, the predicted postoperative visual performance would be different from the real values. The evaluation of postoperative visual performance from wavefront aberrations should consider not only the compensation relationship between defocus and spherical aberration but also the SCE.


Pest categorisation of Liriomyza sativae.
The EFSA Panel on Plant Health performed a pest categorisation of Liriomyza sativae (Diptera: Agromyzidae) for the EU. L. sativae (the cabbage or vegetable leaf miner; EPPO code: LIRISA) is a polyphagous pest native to the Americas which has spread to Africa, Asia and Oceania. L. sativae can have multiple overlapping generations per year. Eggs are inserted in the leaves of host plants. Three larval instars, which feed internally on field vegetables (leaves and stems), follow. Then, the larva jumps into the soil where a fourth larval instar occurs immediately before pupation, which takes place in the soil. L. sativae is regulated in the EU by Commission Implementing Regulation (EU) 2019/2072 (Annex IIA). Within this Regulation, import of soil or growing medium as such or attached to plants for planting from third countries other than Switzerland is regulated. Therefore, entry of L. sativae pupae is prevented. However, immature stages on plants for planting (excluding seeds) and fresh leafy hosts for consumption, cut branches, flowers and fruit with foliage provide potential pathways for entry into the EU. L. sativae has been repeatedly intercepted in the EU, especially in basil (Ocimum spp.). Climatic conditions and the wide availability of host plants provide conditions to support establishment in the EU, both in open fields and greenhouses. Impacts on field vegetables and ornamentals as well as hosts in greenhouses would be possible. Phytosanitary measures are available to reduce the likelihood of entry. L. sativae satisfies the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest. Although human-assisted movement of vegetables is considered the main spread way for L. sativae, this agromyzid does not meet the criterion of occurring in the EU for it to be regarded as a potential Union regulated non-quarantine pest.


Vitamin E reduction of protein glycosylation in diabetes. New prospect for prevention of diabetic complications?
This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA1, and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients. Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA1 levels, stable HbA1, and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration. These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.


Drop-by-drop chemical reaction and sample introduction for capillary electrophoresis.
In this paper, we report a novel sample introduction and chemical reaction strategy by drop-by-drop inkjet injection for an electrophoretically mediated microanalysis (EMMA). This method makes it possible to achieve an on-line introduction of reactant solutions by alternately ejecting small plugs, with an overlapping region of the plugs for mixing the reactants by electrophoresis, supporting chemical reactions, followed by electrophoretic separation of the final compounds. As a proof-of-concept of the method, the EMMA of an inkjetted mixture of 4-fluoro-7-nitrobenzofurazan (NBD-F) and amino acids was carried out as a model chemical reaction. The product NBD-amino acids were quantified by detection with laser induced fluorescence. The optimal conditions for the procedure were: inkjet driving voltage: +40-44 V; pulse width: 20-24 μs; drop-by-drop injection of reactant solutions: alternately 2 drops × 25 times for the amino acid solution and the NBD-F solution; zone overlapping voltage and time: 3 kV and 2 s; incubation time after overlapping: 5 min; separation voltage: 18 kV. Under the optimized conditions, a significant enhancement in sensitivity and a sensitive quantitative analysis were realized. The results obtained were comparable with those using the off-line labeling method. This method is rapid, cost-effective, and readily automated for EMMA.


Magnetic resonance imaging of coronary arteries: technique and preliminary results.
Coronary artery imaging is an important investigation for the management of coronary artery disease. The only reliable technique presently available, x ray contrast angiography, is invasive and is associated with a small morbidity and mortality. Alternative non-invasive imaging would be useful, but the small calibre and tortuosity of the coronary vessels, and cardiac and respiratory motion create formidable imaging problems. The development of rapid magnetic resonance imaging of the coronary arteries. 21 healthy controls and five patients with coronary artery disease established by x ray contrast angiography, of whom two had undergone bypass grafting. Magnetic resonance imaging was performed with gradient echoes and a segmented k-space technique, such that a complete image was acquired in 16 cardiac cycles during a breathhold. The signal from fat was suppressed and images were acquired in late diastole to reduce artefact from cardiac motion. An imaging strategy was developed for the proximal arteries, including longitudinal imaging from oblique planes defined according to the origins and the continuation of the arteries in the atrioventricular grooves or interventricular sulcus. Of the 26 subjects studied, 22 were imaged successfully. Identification of the artery was possible for the left main stem, left anterior descending, right coronary, and left circumflex arteries respectively in 95%, 91%, 95%, and 76%. The arterial diameter at the origin could be measured in 77%, 77%, 81%, and 63%. The mean (SD) arterial diameter in each case (4.8 (0.8), 3.7 (0.5), 3.9 (0.9), and 2.9 (0.6) mm) was not significantly different from reference values. The mean length of artery visualised was 10.4 (5.2), 46.7 (22.8), 53.7 (27.9), and 26.3 (17.5) mm. In 12 healthy men the total coronary area was 30.9 (9.2) mm2 and the ratio compared with body surface area was 16.4 (4.4) mm2m2 (both p = NS compared with reference values). In seven patients in whom x ray contrast coronary angiography was available, the proximal arterial diameter was 3.9 (1.1) mm measured by magnetic resonance and 3.7 (1.0) mm by x ray contrast angiography (p = NS). The mean difference between the measurements was 0.2 (0.5) mm, and the coefficient of variation was 13.7%. All five occluded coronary arteries were identified, as were all three vein grafts. In two patients insertion of the graft into the native arteries was identified. Magnetic resonance coronary angiography is feasible. Good results were obtained by a breath-hold, fat suppression technique, gated to late diastole. Arterial occlusions and vein grafts were readily identified. Further studies are required to establish its value in the detection of coronary stenosis and to develop the measurement of coronary flow velocity which could be used to quantify the severity of the stenosis.


Impaired respiratory muscle function in chemical plant workers producing chlorfenvinphos.
All employees of a chemical plant division producing chlorfenvinphos were studied, i.e. 35 males aged 25-57 years (mean 42.1); their employment period ranged from 1-15 years (mean 9.0). Chronic bronchitis was diagnosed in 13 workers (37.1%). Mean air chlorfenvinphos concentrations in the work environment estimated with gas-liquid chromatography were from 0.0008-0.0018 mg/m3 (maximum allowable concentration according to Polish standards is 0. 01 mg/m3). The activity of erythrocyte acetylcholinesterase was similar to that observed in people who were not exposed to chemicals, however, a slightly lowered activity of plasma cholinesterase in the studied population was evidently the result of mild liver impairment. Spirometric investigations performed in the studied workers revealed slight alterations manifested by increased intrathoracic gas volume (ITGV) (the value of the index was 138.6% of the mean value, 24 workers with an abnormally high index), as well as by decreased specific airway conductance (sGaw); its mean value in the studied group was 58.5% of the mean standard (11 people showed an abnormal index). Substantial functional changes were found in the respiratory muscles. Maximal inspiratory pressures (MIP = 97. 2 +/- 28.3 cm H2O) as well as maximal expiratory pressures (MEP = 113.9 +/- 44.2 cm H2O) in the studied group were significantly lower (p < 0.01) as compared to those observed in the control group (MIP = 120.7 +/- 31.7; MEP = 154.4 +/- 40.2 cm H2O) of 22 males having similar cigarette smoking habit, without occupational exposure to chemicals. It was also found that the people who had worked for more than 10 years under conditions of exposure to chlorfenvinphos showed significantly lower (p < 0.05) values of maximal inspiratory pressure (87.2 +/- 28.06 cm H2O, n = 17) compared to the workers whose period of employment was shorter than 10 years (106.6 +/- 26.8 cm H2O, n = 18). The two groups were comparable with regard to age and smoking habits. The values of maximal expiratory pressures were similar in both groups. No essential disturbances in neuro-muscular transmission were observed; only in 3 workers (8.5%) the electrostimulating myasthenic test showed some disturbances in neuro-muscular transmission. It seems that respiratory muscles impairment in humans exposed to chlorfenvinphos results from changes in the metabolism and structure of muscles, and partly from lung hyperinflation.


Chromosome instability modulated by BMI1-AURKA signaling drives progression in head and neck cancer.
Chromosomal instability (CIN) is widely considered a hallmark of cancer, but its precise roles in cancer stem cells (CSC) and malignant progression remain uncertain. BMI1 is a member of the Polycomb group of chromatin-modifier proteins that is essential for stem cell self-renewal. In human cancers, BMI1 overexpression drives stem-like properties associated with induction of epithelial-mesenchymal transition (EMT) that promotes invasion, metastasis, and poor prognosis. Here, we report that BMI1 mediates its diverse effects through upregulation of the mitotic kinase Aurora A, which is encoded by the AURKA gene. Two mechanisms were found to be responsible for BMI1-induced AURKA expression. First, BMI1 activated the Akt pathway, thereby upregulating AURKA expression through activation of the β-catenin/TCF4 transcription factor complex. Second, BMI1 repressed miRNA let-7i through a Polycomb complex-dependent mechanism, thereby relieving AURKA expression from let-7i suppression. AURKA upregulation by BMI1 exerts several effects, including centrosomal amplification and aneuploidy, antiapoptosis, and cell-cycle progression through p53 degradation and EMT through stabilization of Snail. Inhibiting Aurora A kinase activity attenuated BMI1-induced tumor growth in vivo. In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis. Together, our results link CSCs, EMT, and CIN through the BMI1-AURKA axis and suggest therapeutic use from inhibiting Aurora A in head and neck cancers, which overexpress BMI1.


NCCN Task Force Report: breast cancer in the older woman.
Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.


Low frequency (1-Hz), right prefrontal repetitive transcranial magnetic stimulation (rTMS) compared with venlafaxine ER in the treatment of resistant depression: a double-blind, single-centre, randomized study.
Previous studies have shown effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. This double-blind study compared efficacy of l Hz rTMS over the right prefrontal dorsolateral cortex with venlafaxine ER in the treatment of resistant depression. A total of 60 inpatients with depressive disorder (DSM-IV criteria), who previously did not respond to at least one antidepressant treatment, were randomly assigned to 1 Hz rTMS with placebo and venlafaxine ER with sham rTMS for 4 weeks. The primary outcome measure was score change in the Montgomery-Asberg Depression Rating Scale (MADRS). We also used Clinical Global Impression (CGI) and Beck Depressive. Inventory-Short Form (BDI-SF). The response was defined as a >or=50% reduction of MADRS score. There were no significant differences between treatment groups in MADRS (p=0.38), BDI-SF (p=0.56) and CGI (p=0.17) scores from baseline to endpoint. Response rates for rTMS (33%) and venlafaxine (39%) as well as remission (MADRS score<or=10 points) rates (19% vs. 23%) and drop-out rate did not differ between treatment groups. There were significant reductions of MADRS, CGI and BDI-SF scores in both groups. Small sample size. No placebo arm was included for ethical reasons, because both treatments have previously been reported to be more effective than placebo. Relatively short duration of antidepressant treatment. The findings of this study suggest that, at least in the acute treatment, the right sided rTMS produces clinically relevant reduction of depressive symptomatology in patients with resistant depression comparable to venlafaxine ER. Larger sample sizes are required to confirm these results.


Random mutagenesis of the human immunodeficiency virus type-1 trans-activator of transcription (HIV-1 Tat).
A new method is described for the direct construction of randomly mutagenized genes by applying the polymerase chain reaction (PCR) to an oligonucleotide synthesized using doped nucleotide reservoirs. We have demonstrated the utility of this method by generating a library of mutant HIV-1 tat genes. Several arbitrarily selected, inactive tat clones were sequenced to evaluate the extent of the mutagenesis. Moreover, fourteen recombinants encoding varying levels of transcriptional trans-activator activity were isolated by transient transfection of sub-library pools into a HeLa cell line bearing an HIV-LTR-chloramphenicol acetyltransferase (CAT) reporter gene. Sequence data revealed a spectrum of alterations including nucleotide substitutions, insertions, and deletions, suggesting that mutations arose from both the doped DNA synthesis and the subsequent PCR 'rescue' of full-length product. Sequence comparison between inactive and active Tat clones revealed a selection pressure against amino-acid substitutions within the N-terminal domains of Tat, indicating the importance of this region to trans-activation competence. In addition, single and double missense mutations within the basic-rich, TAR RNA-binding domain were seen to be tolerated within active Tat clones.


A new twist on a very old binary similarity coefficient.
Pairwise similarity coefficients are downward biased when samples only record presences and sampling is partial. A simple but forgotten index proposed by Stephen Forbes in 1907 can help solve this problem. His original equation requires knowing the number of species absent in both samples that could have been present. It is proposed that this count should simply be ignored and that the coefficient should be adjusted using a simple heuristic correction. Four analyses show that the corrected equation outperforms the Dice and Simpson indices, which are highly correlated with many others. In two-sample simulations, similarity is almost always closer to the assumed value when the species pool size and sampling intensity are varied, regardless of whether the underlying abundance distribution is uniform, log-normal, or geometric. The index is also much more robust when sampling is unequal. An analysis of bat samples from peninsular Malaysia buttresses these conclusions. The corrected coefficient also indicates that local assemblages of North American mammals are random subsamples of larger species pools by returning similarity of values of around 1, and it suggests a more consistent relationship between biome-scale comparisons and local-scale comparisons. Finally, it yields a better-dispersed pattern when the biome-scale inventories are ordinated. If these results are generalizable, then the new and old equation should see wide application, potentially taking the place of the two most commonly used alternatives (the interrelated Dice and Jaccard indices) whenever sampling is incomplete.


State-specific prevalence of smoke-free home rules--United States, 1992-2003.
Secondhand smoke (SHS) causes premature death and disease in children and nonsmoking adults. The home is the primary source of exposure to SHS for infants and children and a major source of SHS exposure for nonsmoking adults. To assess trends in national and state-specific prevalence of home "no smoking" rules (i.e., smoke-free home rules), CDC analyzed data from the Tobacco Use Supplement to the Current Population Survey for 1992-1993, 1998-1999, and 2003. This report summarizes the results of that analysis, which indicated that the national prevalence of households with smoke-free home rules in the United States increased significantly, from 43.2% during 1992-1993 to 72.2% in 2003. During this period, the national prevalence of such rules increased from 9.6% to 31.8% among households with at least one smoker and from 56.8% to 83.5% among households with no smoker. A regression analysis of the rate of change over time indicated that the increase in smoke-free homes during this period was not significantly different for households with at least one smoker compared with households with no smoker. Statistically significant increases in the prevalence of smoke-free home rules were also observed in all states, although variation was observed among states. Comprehensive tobacco-control measures, including 1) evidence-based interventions to help smokers quit, 2) policies making workplaces and public places smoke-free, 3) voluntary rules making homes smoke-free, and 4) initiatives to educate the public regarding the health effects of SHS, are needed to further reduce exposure of nonsmokers to SHS.


Social stigma and disclosure about induced abortion: results from an exploratory study.
It is well recognised that unsafe abortions have significant implications for women's physical health; however, women's perceptions and experiences with abortion-related stigma and disclosure about abortion are not well understood. This paper examines the presence and intensity of abortion stigma in five countries, and seeks to understand how stigma is perceived and experienced by women who terminate an unintended pregnancy and influences her subsequent disclosure behaviours. The paper is based upon focus groups and semi-structured in-depth interviews conducted with women and men in Mexico, Nigeria, Pakistan, Peru and the United States (USA) in 2006. The stigma of abortion was perceived similarly in both legally liberal and restrictive settings although it was more evident in countries where abortion is highly restricted. Personal accounts of experienced stigma were limited, although participants cited numerous social consequences of having an abortion. Abortion-related stigma played an important role in disclosure of individual abortion behaviour.


Migraine-induced epistaxis and sporadic hemiplegic migraine: unusual features in the same patient.
Since the mid-19th century, epistaxis and migraine have been occasionally associated with each other. Nevertheless, we found only two cases in the contemporary medical literature. Sporadic hemiplegic migraine is a subtype of migraine with reversible motor deficits, without similar episodes in relatives. We describe a 47-year-old male with a history of migraine with a scintillating scotoma starting at the age of 20. In some of the episodes, he developed epistaxis in the resolution phase of migraine. At the age of 35, he experienced a visual aura followed by transient aphasia, left crural weakness and headache. Contralateral similar episodes occurred in the subsequent months. Neurological examination and MRI were normal. Mutations in CACNA1A, ATP1A2, SCN1A and NOTCH3 were excluded. Three distinct aspects deserve our consideration. This is the first report of migraine-induced epistaxis involving aura; the scarcity of similar reports may be due to the lack of a guided anamnesis. The complex aura presented had a peculiar topography, inconsistent with the classical analytical neurological semiology. This may suggest that the spreading depression affects the brain bilaterally but in an uneven and elective manner. Lastly, the present report conveys that the late appearance of complex auras requires improbable interactions between environmental and endogenous conditions in individuals with a genetic predisposition.