AIDS awareness and attitudes among Yemeni young people living in high-risk areas.
Despite te low rate of infection in Yemen, there are concerns about the possible spread of HIV among high-risk and vulnerable groups. A community-based study was made in 2005 of AIDS awareness and attitudes among 601 young people aged 15-24 years from low-income, high-risk neighbourhoods in Aden. Young people lacked proper information about HIV/AIDS. Although 89% had heard of AIDS, fewer (46%) could name 3 ways of transmission or 3 ways to avoid infection (28%). Misconceptions about modes of transmissions were prevalent and many young people believed that they faced little or no risk. There were intolerant attitudes towards AIDS patients. About half the young people knew that prostitution and homosexuality existed in their area.


Mitochondrial morphology and cardiovascular disease.
Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a variety of biological processes including embryonic development, metabolism, apoptosis, and autophagy, although the majority of studies have been largely confined to non-cardiac cells. Despite the unique arrangement of mitochondria in the adult heart, emerging data suggest that changes in mitochondrial morphology may be relevant to various aspects of cardiovascular biology-these include cardiac development, the response to ischaemia-reperfusion injury, heart failure, diabetes mellitus, and apoptosis. Interestingly, the machinery required for altering mitochondrial shape in terms of the mitochondrial fusion and fission proteins are all present in the adult heart, but their physiological function remains unclear. In this article, we review the current developments in this exciting new field of mitochondrial biology, the implications for cardiovascular physiology, and the potential for discovering novel therapeutic strategies for treating cardiovascular disease.


Supervised dosing with a long-acting opioid medication in the management of opioid dependence.
Opioid dependence (OD) is an increasing clinical and public health problem worldwide. International guidelines recommend opioid substitution treatment (OST), such as methadone and buprenorphine, as first-line medication treatment for OD. A negative aspect of OST is that the medication used can be diverted both through sale on the black market, and the unsanctioned use of medications. Daily supervised administration of medications used in OST has the advantage of reducing the risk of diversion, and may promote therapeutic engagement, potentially enhancing the psychosocial aspect of OST, but costs more and is more restrictive on the client than dispensing for off-site consumption. The objective of this systematic review is to compare the effectiveness of OST with supervised dosing relative to dispensing of medication for off-site consumption. We searched in Cochrane Drugs and Alcohol Group Specialised Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science from inception up to April 2016. Ongoing and unpublished studies were searched via ClinicalTrials.gov (www.clinicaltrials.gov) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (http://www.who.int/ictrp/en/).All searches included non-English language literature. We handsearched references on topic-related systematic reviews. Randomised controlled trials (RCTs), controlled clinical trials (CCTs), and prospective controlled cohort studies, involving people who are receiving OST (methadone, buprenorphine) and comparing supervised dosing with dispensing of medication to be consumed away from the dispensing point, usually without supervision. We used the standard methodological procedures expected by Cochrane. Six studies (four RCTs and two prospective observational cohort studies), involving 7999 participants comparing supervised OST treatment with unsupervised treatment, met the inclusion criteria. The risk of bias was generally moderate across trials, but the results reported on outcomes that we planned to consider were limited. Overall, we judged the quality of the evidence from very low to low for all the outcomes.We found no difference in retention at any duration with supervised compared to unsupervised dosing (RR 0.99, 95% CI 0.88 to 1.12, 716 participants, four trials, low-quality evidence) or in retention in the shortest follow-up period, three months (RR 0.94; 95% CI 0.84 to 1.05; 472 participants, three trials, low-quality evidence). Additional data at 12 months from one observational study found no difference in retention between groups (RR 0.94, 95% CI 0.77 to 1.14; n = 300).There was no difference in abstinence at the end of treatment (self-reported drug use) (67% versus 60%, P = 0.33, 293 participants, one trial, very low-quality evidence); and in diversion of medication (5% versus 2%, 293 participants, one trial, very low-quality evidence).Regarding our secondary outcomes, we did not found a difference in the incidence of adverse effects in the supervised compared to unsupervised control group (RR 0.63; 96% CI 0.10 to 3.86; 363 participants, two trials, very low-quality evidence). Data on severity of dependence were very limited (244 participants, one trial) and showed no difference between the two approaches. Data on deaths were reported in two studies. One trial reported two deaths in the supervised group (low-quality evidence), while in the cohort study all-cause mortality was found lower in regular supervision group (crude mortality rate 0.60 versus 0.81 per 100 person-years), although after adjustment insufficient evidence existed to suggest that regular supervision was protective (mortality rate ratio = 1.23, 95% CI = 0.67 to 2.27).No studies reported pain symptoms, drug craving, aberrant opioid-related behaviours, days of unsanctioned opioid use and overdose. Take-home medication strategies are attractive to treatment services due to lower costs, and place less restrictions on clients, but it is unknown whether they may be associated with increased risk of diversion and unsanctioned use of medication. There is uncertainty about the effects of supervised dosing compared with unsupervised medication due to the low and very low quality of the evidence for the primary outcomes of interest for this review. Data on defined secondary outcomes were similarly limited. More research comparing supervised and take-home medication strategies is needed to support decisions on the relative effectiveness of these strategies. The trials should be designed and conducted with high quality and over a longer follow-up period to support comparison of strategies at different stages of treatment. In particular, there is a need for studies assessing in more detail the risk of diversion and safety outcomes of using supervised OST to manage opioid dependence.


Emergency Department Vital Signs and Outcomes After Discharge.
Vital signs are critical markers of illness severity in the emergency department (ED). Providers need to understand the abnormal vital signs in older adults that are problematic. We hypothesized that in patients age > 65 years discharged from the ED, there are abnormal vital signs that are associated with an admission to an inpatient bed within 7 days of discharge. We conducted a retrospective cohort study using data from a regional integrated health system of members age > 65 years during the years 2009 to 2010. We used univariate contingency tables to assess the relationship between hospital admission within 7 days of discharge and vital sign (including systolic blood pressure [sBP], heart rate [HR], body temperature, and pulse oximetry [SpO2 ] values measured closest to discharge) using standard thresholds for abnormal and thresholds derived from the study data. Of 104,025 ED discharges, 4,638 (4.5%) were followed by inpatient admission within 7 days. Vital signs had a greater odds of admission beyond a single cutoff. The vital signs with at least twice the odds of admission were sBP < 97 mm Hg (odds ratio [OR] = 2.02, 95% CI = 1.57-2.60), HR > 101 beats/min (OR = 2.00 95% CI = 1.75-2.29), body temperature > 37.3°C (OR = 2.14, 95% CI = 1.90-2.41), and pulse oximetry < 92 SpO2 (OR = 2.04, 95% CI = 1.55-2.68). Patients with two vital sign abnormalities per the analysis had the highest odds of admission. A majority of patients discharged with abnormal vital signs per the analysis were not admitted within 7 days of ED discharge. While we found a majority of patients discharged with abnormal vital signs as defined by the analysis, not to be admitted after discharge, we identified vital signs associated with at least twice the odds of admission.


Alpha2B adrenergic receptor 301-303 deletion polymorphism and vascular alpha2 adrenergic receptor response.
Postsynaptic alpha2B adrenergic receptors (ARs) mediate vasoconstriction. There is more than 1000-fold variability in vascular sensitivity to an alpha2-AR agonist. Genetic variability may contribute to such interindividual differences in sensitivity. A 301-303 deletion (del) polymorphism has been identified in the coding region of the alpha2B-AR gene and has functional effects in vitro. Thus, we examined the hypothesis that the del301-303 polymorphism contributes to variability in vascular alpha2-AR responses in vivo. Healthy subjects were recruited based on their alpha2B-AR genotype. Their vascular sensitivity was determined using a linear variable differential transformer following the infusion of increasing doses (range 0.01-1000 ng/min) of the alpha2-AR agonist, dexmedetomidine, into a dorsal hand vein. The dose that produced 50% (ED50) of maximum venoconstriction (Emax) was determined for each subject. Vascular response was compared among the three genotypes. Forty-nine subjects were studied [28 wild-type wt/wt, 13 wt/del, 8 del/del]. There was no difference in dexmedetomidine ED50 and Emax among the alpha2B-AR del301-303 genotypes. The ED50 was 1.39 ng/min [95% confidence interval (CI) 0.03-63.0 ng/min] in wt/wt subjects, 1.63 ng/min (95% CI 0.01-177.8 ng/min) in wt/del and 2.37 ng/min (95% CI 0.17-33.7 ng/min) in del/del (P=0.80). The average Emax was 75.4+/-14.9% in wt/wt, 75.7+/-21.3% in wt/del and 82.2+/-12.9% in del/del subjects (P=0.26). These findings suggest that the del301-303 polymorphism does not contribute significantly to interindividual in vivo variability in response to alpha2-AR activation in the hand vein.


Breed does not affect the association between murmur intensity and disease severity in dogs with pulmonic or subaortic stenosis.
To determine whether breed affects the ability of murmur intensity to predict the severity of stenosis in dogs with pulmonic stenosis or subaortic stenosis. Retrospective multi-investigator study of dogs with pulmonic stenosis or subaortic stenosis. Murmur intensity, assessed by a four-level classification scheme, was compared with echocardiographically-determined pressure gradient across the affected valve. Breeds represented by at least 10 dogs at any murmur intensity were compared to determine the effect, if any, of breed. A total of 1088 dogs (520 with pulmonic stenosis and 568 with subaortic stenosis, representing 106 breeds and the mixed breed group) were included; 208 dogs had soft, 210 had moderate, 283 had loud and 387 had palpable murmurs. Fifteen breeds were represented by at least 10 dogs: five breeds with at least 10 dogs had soft murmurs (132 dogs), nine breeds had moderate murmurs (149 dogs), 10 breeds had loud murmurs (188 dogs), and 11 breeds had palpable murmurs (286 dogs). No breeds differed in stenosis severity from any other breeds within any murmur grade. Post hoc power calculations suggested that we would have been able to detect at least a moderate or large effect size, had one existed. Several dogs with soft murmurs had more-than-mild disease severity. Despite anecdotally perceived differences in the detection of heart murmurs between breeds, which have been proposed to potentially affect the interpretation of stenosis severity, we found no obvious breed effect in the ability to predict severity of stenosis.


Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?
Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction. To date, no effective therapy has been developed to restore the cardiac energy metabolism of the failing myocardium, mainly due to the metabolic complexity and intertwining of the involved processes. Recent years have witnessed a growing scientific interest in natural molecules that play a pivotal role in energy metabolism with promising therapeutic effects against heart failure. Among these molecules, B vitamins are a class of water soluble vitamins that are directly involved in energy metabolism and are of particular interest since they are intimately linked to energy metabolism and HF patients are often B vitamin deficient. This review aims at assessing the value of B vitamin supplementation in the treatment of heart failure.


Application of new tissue microarrayer-ZM-1 without recipient paraffin block.
The ZM-1 tissue microarrayer designed by our groups is manufactured in stainless steel and brass and contains many features that make TMA (tissue microarray) paraffin blocks construction faster and more convenient. By means of ZM-1 tissue microarrayer, biopsy needles are used to punch the donor tissue specimens respectively. All the needles with the punched specimen cylinders are arrayed into the array-board, with an array of small holes dug to fit the needles. All the specimen cylinders arraying and the TMA paraffin block shaping are finished in only one step so that the specimen cylinders and the paraffin of the TMA block can very easily be incorporated and the recipient paraffin blocks need not be made in advance, and the paraffin used is the same as that for conventional pathology purpose. ZM-1 tissue microarrayer is easy to be manufactured, does not need any precision location system, and so is much cheaper than the currently used instrument. Our method's relatively cheap and simple ZM-1 tissue microarrayer technique of constructing TMA paraffin block may facilitate popularization of the TMA technology.


A leader sequence capable of enhancing RNA expression and protein synthesis in mammalian cells.
Many applications in biotechnology require human proteins generated from human cells. Stable cell lines commonly used for this purpose are difficult to develop, and scaling to large numbers of proteins can be problematic. Transient expression can circumvent this problem, but protein yields are generally too low for most applications. Here we report a novel 37-nucleotide leader sequence that promotes rapid and high transgene expression in mammalian cells. This sequence was identified by in vitro selection and functions in a transient vaccinia-based cytoplasmic expression system. Vectors containing this sequence produce microgram levels of protein in just 6 h from a small-scale expression in 10(6) cells. This level of protein synthesis is ideal for high throughput production of human proteins, and could be scaled to generate milligram quantities of protein. The technology is compatible with a broad range of cell lines, accepts plasmid and linear DNA, and functions with viruses that are approved for use under BSL1 conditions. We suggest that these advantages provide a powerful method for generating human protein in mammalian cells.


Nuclear Quantum Effects in Liquid Water at Near Classical Computational Cost Using the Adaptive Quantum Thermal Bath.
We demonstrate the accuracy and efficiency of a recently introduced approach to account for nuclear quantum effects (NQEs) in molecular simulations: the adaptive quantum thermal bath (adQTB). In this method, zero-point energy is introduced through a generalized Langevin thermostat designed to precisely enforce the quantum fluctuation-dissipation theorem. We propose a refined adQTB algorithm with improved accuracy and report adQTB simulations of liquid water. Through extensive comparison with reference path integral calculations, we demonstrate that it provides excellent accuracy for a broad range of structural and thermodynamic observables as well as infrared vibrational spectra. The adQTB has a computational cost comparable to that of classical molecular dynamics, enabling simulations of up to millions of degrees of freedom.


Development of Colloidal Gold Test Strips for the Detection of Oxamyl Residues in Tobacco.
In this study, monoclonal antibodies against oxamyl were prepared, and colloidal gold immunochromatography was used to design a rapid test strip product for the detection of oxamyl in tobacco with high specificity, accuracy and stability without cross-reactivity to commonly used tobacco fungicides based on the optimization of conditions such as pH value of diluent, diluent dosage, concentration of antibody marker, type of confining solution and complex solution. 5 The results of five samples of post-harvest ready-to-bake tobacco and first-harvest tobacco were consistent with the gas chromatographic method, which proved the reliability of the test strips. The limits of detection for the post-harvest and first-harvest tobacco samples were 0.1 mg/kg, and the test strips developed in this study are suitable for mass testing in tobacco laboratories with good application prospects because of their short detection time, simple pre-treatment and detection methods.


Preparation of Progressive Antibacterial LDPE Surface via Active Biomolecule Deposition Approach.
The use of polymers in all aspects of daily life is increasing considerably, so there is high demand for polymers with specific properties. Polymers with antibacterial properties are highly needed in the food and medical industries. Low-density polyethylene (LDPE) is widely used in various industries, especially in food packaging, because it has suitable mechanical and safety properties. Nevertheless, the hydrophobicity of its surface makes it vulnerable to microbial attack and culturing. To enhance antimicrobial activity, a progressive surface modification of LDPE using the antimicrobial agent grafting process was applied. LDPE was first exposed to nonthermal radio-frequency (RF) plasma treatment to activate its surface. This led to the creation of reactive species on the LDPE surface, resulting in the ability to graft antibacterial agents, such as ascorbic acid (ASA), commonly known as vitamin C. ASA is a well-known antioxidant that is used as a food preservative, is essential to biological systems, and is found to be reactive against a number of microorganisms and bacteria. The antimicrobial effect of grafted LDPE with ASA was tested against two strong kinds of bacteria, namely, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), with positive results. Surface analyses were performed thoroughly using contact angle measurements and peel tests to measure the wettability or surface free energy and adhesion properties after each modification step. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the surface morphology or topography changes of LDPE caused by plasma treatment and ASA grafting. Surface chemistry was studied by measuring the functional groups and elements introduced to the surface after plasma treatment and ASA grafting, using Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). These results showed wettability, adhesion, and roughness changes in the LDPE surface after plasma treatment, as well as after ASA grafting. This is a positive indicator of the ability of ASA to be grafted onto polymeric materials using plasma pretreatment, resulting in enhanced antibacterial activity.


Nerve repair and cable grafting for facial paralysis.
Facial nerve injury and facial paralysis are devastating for patients. Although imperfect, primary repair is currently the best option to restore facial nerve function. Cable, or interposition, nerve grafting is an acceptable alternative when primary repair is not possible. Several donor nerves are at the surgeon's disposal. Great auricular, sural, or medial and lateral antebrachial cutaneous nerves are all easily obtained. Both primary repair and interposition grafting typically result in better facial function than do other dynamic and static rehabilitation strategies. Proficient anastomotic technique and, when necessary, selection of an appropriate interposition graft will optimize patient outcomes. Promising research is under way that will enhance future nerve repair and grafting efforts.


The metamorphosis of hemoglobin in the bullfrog.
1. Tadpole and adult hemoglobin do not differ significantly in molecular weight. The molecular weight of both is in the neighborhood of 68,000. 2. Heme-heme interaction as measured by the value of n in Hill's equation is virtually the same-about 2.8-in both tadpole and adult. 3. There appears to be no significant effect of pH upon the oxygen equilibrium of tadpole hemoglobin, in contrast to large Bohr and reverse Bohr effects in the adult. This is taken to mean that during metamorphosis acid groups of globin become sensitive to the oxygenation of heme by some change in the mode of linkage between heme and globin. 4. The oxygen affinity of tadpole hemoglobin is about seven times as great as that of the adult at pH 6 and twice as great at pH 9.


Desflurane pharmacokinetics during cardiopulmonary bypass.
To describe the washin and washout of desflurane when first administered during cardiopulmonary bypass (CPB) for cardiac surgery. A single-arm prospective study. University-affiliated hospital operating room. Ten adult patients presenting for cardiac surgery. Consenting patients presenting for cardiac surgery received anesthesia with midazolam and fentanyl. Patients were cooled to 32 degrees C on CPB, then desflurane 6% was administered and blood samples drawn repeatedly from the arterial and venous bypass cannulae as well as from the membrane oxygenator inlet and exhaust from 2 to 32 minutes of desflurane administration. Just before rewarming, final (maximum) washin samples were taken. On rewarming, desflurane was discontinued, and blood and gas samples were taken 2 to 24 minutes thereafter. CPB time was 116 +/- 10 minutes, and ischemic time was 81 +/- 6 minutes. Mean pump flow was 4.49 +/- 0.03 L/min, and mean arterial pressure was 70.1 +/- 1 mmHg during the study period. Arterial washin of desflurane was initially rapid; arterial concentrations reached 50% of administered concentrations within 4 minutes, but then slowed, reaching 68% of inspired concentrations at 32 minutes (desflurane concentration 4.0% +/- 0.3%). Arterial washout of desflurane was more rapid; arterial concentrations fell to 18% of the maximum concentration reached within 4 minutes, and only 8% of the maximum arterial concentration was present in blood 20 minutes later. Desflurane showed rapid initial washin and washout on CPB when administration was started at 32 degrees C and stopped at time of rewarming.


Carbon biogeochemistry and climate change.
The rapid increase of atmospheric CO2 resulting from anthropogenic activites has stimulated a great deal of interest in the carbon cycle. Important decisions need to be made about future tolerable levels of atmospheric CO2 content, as well as the land and fossil fuel use strategies that will permit us to achieve these goals. The vast amount of new data on atmospheric CO2 content and ancillary properties that has become available during the last decade, and the development of models to interpret these data, have led to significant advances in our capacity to deal with such issues. However, a major continuing source of uncertainty is the role of photosynthesis in providing a sink for anthropogenic emissions. It is thus appropriate that a new evaluation of the status of our understanding of this issue should be made at this time.The aim of this paper is to provide a setting for the papers that follow by giving an overview of the role of carbon dioxide in climate, the biogeochemical processes that control its distribution, and the evolution of carbon dioxide through time from the origin of the earth to the present. We begin with a discussion of relevant processes. We then proceed to a more detailed discussion of the time periods that are best documented: the late Pleistocene (during which time large continental ice sheets waxed and waned) and the modern era of anthropogenic impact on the carbon cycle.


Radial dependence diagnosis of inductively coupled Ar plasma based upon optical emission spectroscopic measurement with spectral reflectance compensation.
This study proposed a simple method to evaluate the spectral reflectance of the inner wall of a vacuum chamber. A method for calculating spectral emission coefficients by taking the spectral reflectance of the chamber inner wall into account was proposed. Furthermore, plasma diagnosis based on optical emission spectroscopic (OES) measurement was performed so as to obtain radial dependence of electron temperature Te and density Ne of a radio frequency inductively coupled Argon (Ar) plasma by applying a collisional-radiative model to radially resolved emission spectra of the Ar plasma assuming axial symmetry. In addition, Langmuir probe measurement and electromagnetic simulation were performed and compared with the OES-based plasma diagnosis results. The spectral radiance compensation improved the diagnostic result by 0.6% and 3.1% for Te and Ne, respectively.


Heparin versus 0.9% saline solution to maintain patency of totally implanted venous access ports in cancer patients: A systematic review and meta-analysis.
The use of heparin and 0.9% saline solution is always controversial for central venous catheters. However, there is no systematic review or guideline about whether saline solution can replace heparin solution in adult cancer patients with totally implantable venous access ports (TIVAPs). The purpose of this review is to evaluate whether saline solution can replace heparin saline to lock TIVAPs. The following databases were searched: PubMed, the Cochrane Library, Web of Science, Embase, CINAHL and Ovid (January 1, 1982, and February 21, 2020). All statistical analyses of the meta-analysis were completed using the Review Manager 5.3. A total of 201 studies were identified from these databases after initial review, and four studies met inclusion criteria, including 2652 cases. There was little heterogeneity among the included studies (I2 < 30%), and all analyses were conducted by the fixed-effects model. The total complications, catheter occlusions, catheter-related bloodstream infections and other complication rates in the heparin solution group were higher than in the saline solution group. In the subgroup analysis of heparin concentration, total complication rates in the saline solution group were higher than with 50 U of heparin and lower than with 100 U of heparin. However, the differences in these complications were small, and no significant difference was observed (all P > 0.05). Based on existing clinical studies, we recommend that saline solution can replace 50 or 100 U/ml of heparin as a safe and effective flush solution for TIVAPs.


The squash-and-stretch stylization for character motions.
The squash-and-stretch describes the rigidity of the character. This effect is the most important technique in traditional cartoon animation. In this paper, we introduce a method that applies the squash-and-stretch effect to character motion. Our method exaggerates the motion by sequentially applying the spatial exaggeration technique and the temporal exaggeration technique. The spatial exaggeration technique globally deforms the pose in order to make the squashed or stretched pose by modeling it as a covariance matrix of joint positions. Then, the temporal exaggeration technique computes a time-warping function for each joint, and applies it to the position of the joint allowing the character to stretch its links appropriately. The motion stylized by our method is a sequence of squashed and stretched poses with stretching limbs. By performing a user survey, we prove that the motion created using our method is similar to that used in 2D cartoon animation and is funnier than the original motion for human observers who are familiar with 2D cartoon animation.


Use of a plastic eraser for ear reconstruction training.
Microtia reconstruction is a challenging procedure, especially in developing nations. The most complex part is learning how to fabricate a framework from costal cartilage. We herein propose a training regimen for ear reconstruction with the use of a plastic eraser. The texture of a plastic eraser made from polyvinyl chloride is similar to that of human costal cartilage. The first step of the training is carving out the sixth through eighth rib cartilages from a block of plastic eraser. The second step is a fabrication of the framework from plastic rib cartilages, referring to a template from the intact auricle. As plastic erasers are inexpensive and universally available, inexperienced surgeons can repeatedly perform this framework training. Following several of these training sessions in developing nations, the co-authors and local surgeons successfully performed their microtia reconstructions in a reasonable operative time. This realistic carving model allows surgeons to gain experience before performing an actual ear reconstruction, even in resource-constrained circumstances.


Does the septic shock interfere experimental acute pancreatitis in rats?
Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response. The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats. The study was performed on rats using the ceruleine pancreatitis model. The activation status of polymorphonuclear cells, blood IL-6 concentration, oxidative stress parameters, pancreatic enzymes concentration and microscopic alterations were determined at 5th and 9th h observations. In acute pancreatitis and acute pancreatitis with LPS groups, the peripheral polymorphonuclear cells activity was lower than in control one. Authors noticed the same neutrophil activation in acute pancreatitis after lipopolysaccharide administration although the peripheral blood polymorphonuclear cells count was significantly higher at the 9th h observation. LPS neither changed the oxidative stress within pancreatic gland, nor amylase or serum lipase activity. LPS given to acute pancreatitis animals resulted in significant increase of serum IL-6 concentration at 5th observation turning normal after 9th h. Collected data supports thesis of early polymorphonuclear cells involvement in acute pancreatitis and oxidative stress evidence in pancreatic parenchyma. However, results did not reveal that administration of LPS amplified inflammatory response during the course of acute pancreatitis.


The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome.
Antiphospholipid (Hughes) syndrome (APS) is recognised as a systemic autoimmune disease defined by recurrent thromboembolic events and/or pregnancy morbidity. Little is known about the psychological burden of this long-term condition. This study aims to explore the relationship between social support and health-related quality of life (HRQoL) in patients with APS. A total of 270 patients with a clinical diagnosis of APS participated in a cross-sectional online questionnaire survey. Data included demographics, disease-related information, social support and HRQoL. Both perceived and ideal social support were associated with HRQoL in APS. Patients reported receiving insufficient social support. Perceived emotional support was related to physical functioning (B = 7.77, p = .006, 95% CI: 2.25, 13.29); perceived instrumental support was associated with bodily pain (B = 17.52, p < .001, 95% CI: 11.15, 23.90) and perceived informational support with physical and social functioning (B = -6.30, p = .05, 95% CI: -12.52, -0.08; B = 8.06, p = .02, 95% CI: 1.17, 14.94). Ideal emotional support was related to physical and social functioning (B = 5.80, p = .04, 95% CI: 0.26, 11.34; B = 7.53, p = .04, 95% CI: 0.55, 14.51); ideal instrumental support was associated with mental health (B = 4.73, p = .03, 95% CI: 0.38, 9.07) and ideal informational support with vitality (B = 5.85, p = .01, 95% CI: 1.23, 10.46). Social support was linked to HRQoL in patients with APS. Insufficient social support was associated with limitations in various HRQoL domains. Increasing social support especially through provision of disease-specific education might contribute to improving HRQoL in patients with APS. Patient-tailored interventions addressing psychosocial aspects of living with APS are needed to improve patients' psychological and physical status.


Characterization of cuckoo-pint (Arum maculatum) mitochondrial adenosine triphosphatases.
The catalytic properties of cuckoo-pint (Arum maculatum) mitochondrial adenosine triphosphatase have been analysed. The pH profile, effect of inhibitors, cold-stability and substrate specificity are characteristic of mitochondrial adenosine triphosphatases, although a high guanosine triphosphatase activity does appear to be restricted to plant mitochondrial adenosine triphosphatases. The kinetic properties of nucleoside 5'-triphosphate hydrolysis by membrane-bound and soluble enzymes have been studied by means of double-reciprocal plots. These plots were linear in the absence of an activating anion, which may indicate that the catalytic and/or regulatory mechanism of Arum maculatum adenosine triphosphatase is different from that of other enzyme preparations. It is suggested that the differences in subunit composition of plant and mammalian adenosine triphosphatases reported previously [Dunn, Slabas & Moore (1985) Biochem. J. 225, 821-824] are structurally, rather than functionally, significant.


Two mechanisms of constructive recollection: Perceptual recombination and conceptual fluency.
Recollection is constructive and prone to distortion, but the mechanisms through which recollections can become embellished with rich yet illusory details are still debated. According to the conceptual fluency hypothesis, abstract semantic or conceptual activation increases the familiarity of a nonstudied event, causing one to falsely attribute imagined features to actual perception. In contrast, according to the perceptual recombination hypothesis, details from actually perceived events are partially recollected and become erroneously bound to a nonstudied event, again causing a detailed yet false recollection. Here, we report the first experiments aimed at disentangling these 2 mechanisms. Participants imagined pictures of common objects, and then they saw an actual picture of some of the imagined objects. We next presented misinformation associated with these studied items, designed to increase conceptual fluency (i.e., semantically related words) or perceptual recombination (i.e., perceptually similar picture fragments). Finally, we tested recollection for the originally seen pictures using verbal labels as retrieval cues. Consistent with conceptual fluency, processing-related words increased false recollection of pictures that were never seen, and consistent with perceptual recombination, processing picture fragments further increased false recollection. We also found that conceptual fluency was more short-lived than perceptual recombination, further dissociating these 2 mechanisms. These experiments provide strong evidence that conceptual fluency and perceptual recombination independently contribute to the constructive aspects of recollection. (PsycINFO Database Record


Chemical enhancers of cytokine signaling that suppress microfilament turnover and tumor cell growth.
The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell proliferation, morphogenesis, and specialized cell functions in metazoans. Herein, we screened a compound library for modifiers of TGF-beta signaling in NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear translocation. We identified five enhancers of TGF-beta signaling that share a core structure of diethyl 2-(anilinomethylene)malonate (DAM), and D(50) values of 1 to 4 micromol/L. Taking advantage of the Mgat5 mutant phenotype of accelerated receptor loss to endocytosis, we determined that DAM-1976 restored the sensitivity of Mgat5(-/-) carcinoma cells to both TGF-beta and epidermal growth factor (EGF). In Mgat5 mutant and wild-type carcinoma cells, DAM-1976 enhanced and prolonged TGF-beta- and EGF-dependent Smad2/3 and Erk activation, respectively. DAM-1976 reduced ligand-dependent EGF receptor endocytosis, actin microfilament turnover, and cell spreading, suggesting that the compound attenuates vesicular trafficking. Hyperactivation of intracellular signaling has the potential to suppress tumor cell growth and, in this regard, DAM-1976 represents a new pharmacophore that increases basal activation of Smad2/3 and Erk, inhibits microfilament remodeling, and suppresses carcinoma cell growth.


International migration of doctors from developing countries: need to follow the Commonwealth Code.
There is an ongoing debate on the migration of doctors, especially psychiatrists, from developing countries. It is argued that these countries, which are already running short of psychiatrists, will further be jeopardized and their health systems will collapse if this migration and subsequent recruitment continue. In this paper the author presents a personal view of the ethics and human rights of this matter. He emphasises the importance of migration of doctors in view of the current situation in developing countries and advises that the Commonwealth Code be followed to address the problem of the shortage of psychiatrists in developing countries and psychiatrists' basic right to avail themselves of the opportunities in the developed world.


Updating during reading comprehension: why causality matters.
The present set of 7 experiments systematically examined the effectiveness of adding causal explanations to simple refutations in reducing or eliminating the impact of outdated information on subsequent comprehension. The addition of a single causal-explanation sentence to a refutation was sufficient to eliminate any measurable disruption in comprehension caused by the outdated information (Experiment 1) but was not sufficient to eliminate its reactivation (Experiment 2). However, a 3 sentence causal-explanation addition to a refutation eliminated both any measurable disruption in comprehension (Experiment 3) and the reactivation of the outdated information (Experiment 4). A direct comparison between the 1 and 3 causal-explanation conditions provided converging evidence for these findings (Experiment 5). Furthermore, a comparison of the 3 sentence causal-explanation condition with a 3 sentence qualified-elaboration condition demonstrated that even though both conditions were sufficient to eliminate any measurable disruption in comprehension (Experiment 6), only the causal-explanation condition was sufficient to eliminate the reactivation of the outdated information (Experiment 7). These results establish a boundary condition under which outdated information will influence comprehension; they also have broader implications for both the updating process and knowledge revision in general.


Health care resources consumed to treat postoperative infections: cost saving by perioperative immunonutrition.
The objectives of the study were to calculate the costs of postoperative complications and to evaluate whether the use of perioperative enteral immunonutrition, may lead to a saving in health care resources consumed. The economic analysis was based on data from a randomized double-blind trial that include 206 cancer patients who received perioperatively either enteral immunonutrition (treatment group, n = 102) or a standard enteral diet (control group, n = 104). Estimates of costs were based on resource use for treatment of complications, which were valued according to the National List of Sanitary Costs of the Italian Ministry of Health and on the medical Diagnosis-Related-Group (DRG) reimbursement rates. Costs of nutrition were also calculated. Cost comparison and cost effectiveness analyses were then carried out. Intent-to-treat analysis showed that the total costs of 52 postoperative complications were 322,218 euros, with a consumption of the DRG reimbursement rate of 15.4%. The costs of nutrition were 35,437 euros in the treatment group versus 10,768 euros in the control group. The total costs (nutrition plus treating complications) amounted to 113,778 euros in the treatment group versus 254,450 euros in the control group. The mean total costs per patient were 1,115 euros in the treatment group versus 2,447 euros in the control group (P = 0.04). Effectiveness was 83.3% in the treatment group versus 68.3% in the control group (P = 0.009). Cost effectiveness analysis showed a net saving of 2,386 euros per complication-free patient in favor of the treatment group. In conclusion, the perioperative use of immunonutrition appears cost effective due to a substantial saving of resources used to treat postoperative complications.


Donor race does not predict graft failure after liver transplantation.
Donor race has been proposed to predict graft failure after liver transplantation. We evaluated the extent to which the center where the transplantation surgery was performed and other potential confounding factors might account for the observed association between donor race and graft failure. We analyzed data from the Organ Procurement and Transplantation Network (January 2003-December 2005) for adult patients undergoing primary liver transplantation in the United States. We examined the association between graft failure and the donor races of African American (AA), Caucasian, Asian/Pacific Islander (API), or those classified as other. Of 10,874 livers that were donated for transplantation, 7631 came from Caucasians, 1579 from AAs, 243 from APIs, and 1421 from others. After 36 months of follow-up evaluation, 2687 grafts failed. Without any adjustments, AA donors (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.00-1.24), API donors (HR, 1.41; 95% CI, 1.12-1.77), and other donors (HR, 1.16; 95% CI, 1.04-1.29) were associated with graft failure. After stratification by center and adjustments for age, height, and hepatitis B core antibody status of donors as well as serum creatinine and hepatitis C status of recipients, donor race was no longer statistically significant for AA (HR, 1.06; 95% CI, 0.95-1.20) and API (HR, 1.15; 95% CI, 0.89-1.49) donors. However, livers donated from members of other race still had an increased risk of graft failure (HR, 1.19; 95% CI, 1.05-1.35), although the effect was not uniform across donor-recipient pairs. Donor race is not a uniform predictor of graft failure and should not be construed as an indicator of donor quality.


The CORE Service Improvement Programme for mental health crisis resolution teams: study protocol for a cluster-randomised controlled trial.
As an alternative to hospital admission, crisis resolution teams (CRTs) provide intensive home treatment to people experiencing mental health crises. Trial evidence supports the effectiveness of the CRT model, but research suggests that the anticipated reductions in inpatient admissions and increased user satisfaction with acute care have been less than hoped for following the scaling up of CRTs nationally in England, as mandated by the National Health Service (NHS) Plan in 2000. The organisation and service delivery of the CRTs vary substantially. This may reflect the lack of a fully specified CRT model and the resources to enhance team model fidelity and to improve service quality. We will evaluate the impact of a CRT service improvement programme over a 1-year period on the service users' experiences of care, service use, staff well-being, and team model fidelity. Twenty-five CRTs from eight NHS Trusts across England will be recruited to this cluster-randomised trial: 15 CRTs will be randomised to receive the service improvement programme over a 1-year period, and ten CRTs will not receive the programme. Data will be collected from 15 service users and all clinical staff from each participating CRT at baseline and at the end of the intervention. Service use data will be collected from the services' electronic records systems for two 6-month periods: the period preceding and the period during months 7-12 of the intervention. The study's primary outcome is service user satisfaction with CRT care, measured using a client satisfaction questionnaire. Secondary outcomes include the following: perceived continuity of care, hospital admission rates and bed use, rates of readmission to acute care following CRT support, staff morale, job satisfaction, and general health. The adherence of the services to a model of best practice will be assessed at baseline and follow-up. Outcomes will be compared between the intervention and control teams, adjusting for baseline differences and participant characteristics using linear random effects modelling. Qualitative investigations with participating CRT managers and staff and programme facilitators will explore the experiences of the service improvement programme. Our trial will show whether a theoretically underpinned and clearly defined package of resources are effective in supporting service improvement and improving outcomes for mental health crisis resolution teams. Current Controlled Trials ISRCTN47185233.


Percutaneous vesicolithotomy: an alternative to open bladder surgery in patients with an impassable or surgically ablated urethra.
Although vesical calculi are routinely treated transurethrally, open vesicolithotomy is generally performed in patients with an impassable or surgically ablated urethra. We describe a technique of percutaneous vesicolithotomy which we used in patients who had undergone urethral ablation and concomitant continent diversion by appendicovesicostomy. Bladder stones were detected in 3 patients with neurogenic bladder who had undergone continent urinary diversion with bladder neck closure and appendicovesicostomy. To treat the stones access to the bladder was achieved percutaneously and the tract was enlarged using a balloon dilator. An Amplatz sheath was slipped over the inflated balloon and after the dilator was removed the sheath provided a working channel through which stones were fragmented and removed using a nephroscope. Each patient was rendered stone-free and discharged home the same day as the procedure. Percutaneous vesicolithotomy provides an alternative approach for bladder stone removal in patients with an impassable urethra with decreased morbidity compared to open procedures.


The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients.
Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2 (BioNTech) and mRNA-1273 (Moderna) vaccines. Plasma and peripheral blood mononuclear cells samples were collected before vaccination, post the second and the third doses and tested for spike-specific antibodies, ACE2/RBD antibody inhibition binding activity and spike-specific B cells. The third vaccine dose significantly increased the spike-specific IgG titers in both ruxolitinib-treated and untreated patients, and strongly enhanced the percentage of subjects with antibodies capable of in vitro blocking ACE2/RBD interaction, from 50% up to 80%. While a very low frequency of spike-specific B cells was measured in blood 7 days after the second vaccination dose, a strong and significant increase was elicited by the third dose administration, generating a B cell response similar to the one detected in healthy controls. Despite the overall positive impact of the third dose in MF patients, two patients that were under active concomitant immunosuppressive treatment at the time of vaccination, and a patient that received lymphodepleting therapies in the past, remained low responders. The third mRNA vaccine dose strongly increases the SARS-CoV-2 specific humoral and B cell responses in MF patients, promoting a reactivation of the immune response similar to the one observed in healthy controls.


Adherence to surveillance guidelines following colonic polypectomy is abysmal.
Surveillance guidelines following excision of colonic tubular adenomas are well established. However, adherence to the guidelines are rarely audited. The aim of our study was to evaluate the rate of compliance to the recommended guidelines following polyp removal. A review of a prospectively collected colonoscopy database in a single tertiary institution was conducted for all patients who underwent polypectomy in 2008. We excluded patients who were diagnosed with or had prior history of colorectal malignancy. The frequency of subsequent colonoscopic were evaluated against the recommended guidelines based on the clinico-histological characteristics of the removed polyps. There were 419 colonoscopies with polypectomies performed in 2008. The patient cohort had a median age of 60 years (range, 26-95 years), with the most common diagnosis being tubular adenoma with low grade dysplasia (n=291, 69.5%). Adherence to Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) post-polypectomy surveillance guidelines, based on the factors such as the characteristics of the colonic polyps and bowel preparation at initial colonoscopy, was only 13.8% (n=58). There were 107 (25.5%) patients who had their surveillance endoscopy performed earlier than recommended. None of them were diagnosed with malignancy. The majority of patients (n=192, 45.8%), had surveillance scopes later than recommended or were lost to follow-up. Amongst these patients, two actually were diagnosed to have malignancy 3 and 5 years after their recommended surveillance scope date, respectively. There is a very low compliance to post-polypectomy surveillance guidelines. More needs to be done to improve compliance to guidelines.


Detection of nonesterified (free) fatty acids in bovine serum: comparative evaluation of two methods.
A method comparison study for the determination and quantitation of nonesterified fatty acids (NEFAs) in serum, using the commercial "NEFA C" enzymatic test kit, was performed using the spectrophotometric method recommended by the manufacturer and a modified procedure optimized for the use of a microplate reader, a 96-well microtiter plate, and small sample volumes (10 microl). Linearity, sensitivity, and precision using the test kit were determined for each method of detection. The assay was linear from 0 to 1.97 mEq/liter for both procedures, and the limits of detection were determined to be 0.22 (+/- 0.074) and 0.05 (+/- 0.002) mEq/liter for the spectrophotometer and microplate reader, respectively. Pairs of measurements for bovine serum samples were compared and evaluated by a mean difference plot method and not regression analysis, a method that has been shown to be inappropriate for method comparison studies. The difference plot was used to evaluate the systematic bias between the 2 methods. Random error is reported on the basis of SD differences, and "limits of agreement" are used to describe the maximum differences likely to occur between the 2 methods. Results suggest that the microplate reader method can be used reliably in place of the recommended spectrophotometric method. The microplate reader method is preferred because of its high throughput capabilities, simultaneous analysis of all the standards and samples, use of small sample and reagent volumes, and reduction in labor requirements and costs.


Morphometric analysis of nonadult characters of common species of American gordiids (Nematomorpha: Gordioidea).
The nonadult stages, egg strings, eggs, larvae, and cysts of Gordius robustus, Paragordius varius, and Chordodes morgani are described morphometrically. The goal was to document the differences between species and to evaluate the usefulness of morphometrics in species identification. In concert, multivariate analysis of variance (MANOVA) and univariate analysis of variance (ANOVA, a posteriori contrasts) statistical tests demonstrated that each species is morphometrically distinguishable from all others. Additionally, discriminant function analysis indicated that postseptum length, pseudointestine length, and stylet width were the most important variables in the discrimination of species based on larval characters. Finally, differences in oviposition behaviors among these 3 species were found. It is suggested that ovipositioning differences may place larvae into distinct niches and may ultimately lead to the use of different paratenic hosts by different gordiid species.


Clinical outcomes of patients with breast cancer relapsing after (neo)adjuvant trastuzumab and receiving trastuzumab rechallenge or lapatinib-based therapy: a multicentre retrospective cohort study.
In the prepertuzumab era, we evaluated the clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who underwent first-line trastuzumab-based or lapatinib-based therapy according to prior exposure to (neo)adjuvant trastuzumab. In this multicentre retrospective cohort study conducted in 14 Italian centres of the Gruppo Italiano Mammella, consecutive patients undergoing first-line trastuzumab or lapatinib-based therapy were included. Analyses were performed according to the type of first-line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analysed using logistic regression and time-to-event outcomes using Cox proportional hazard models controlling for relevant demographic, clinicopathological and therapy characteristics. Out of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the lapatinib cohort had a trastuzumab-free interval <1 month (37% vs 13.9%; p=0.017) and brain metastasis as first site of relapse (38.2% vs 9.4%; p<0.001). Among the 128 patients who relapsed after prior (neo)adjuvant trastuzumab, 101 (78.9%) received first-line trastuzumab and 27 (21.1%) first-line lapatinib. The following outcomes were observed with first-line lapatinib or trastuzumab, respectively: overall response rate 45.5% vs 61.3% (p=0.184), clinical benefit rate 68.2% vs 72.5% (p=0.691), median progression-free survival (PFS) 11.4 vs 12.0 months (p=0.814) and median overall survival (OS) 34.7 vs 48.2 months (p=0.722). In patients with brain metastasis as first site of relapse, median PFS was 12.2 vs 9.9 months (p=0.093) and median OS 33.7 vs 28.5 months (p=0.280), respectively. In patients with HER2-positive breast cancer relapsing after prior (neo)adjuvant trastuzumab, first-line treatment with trastuzumab or lapatinib was not associated with a significant difference in the clinical outcomes. A non-significant trend favouring the use of lapatinib was observed in patients with brain metastasis as the first site of relapse.


[Silicification of silk fibroin and their application in bone tissue engineering].
In bone tissue engineering, fabrication of scaffold materials that are biodegradable with regenerative functions is one of the most important research fields. Silk fibroin exhibits many favorable characteristics used as scaffold materials. Among them, hybrid silk fibroin/inorganic composites prepared by biomimetic mineralization have better biocompatibility, biomechanical properties, and biodegradability. At the same time, the hybrid silk fibroin/inorganic materials have much better osteoinduction and conduction properties than silk fibroin. Here, the recent advances in the preparation of silk fibroin/silica hybrid materials by combination or biomimetic silicification are reviewed, and the future research prospects of silicification of silk fibroin are discussed.


[Phospholipid turnover in the liver mitochondria of rats on a diet with a varying fat and protein ratio].
Using the method of pulse introduction of labeled precursors the authors studied metabolism of rat liver mitochondrial phospholipids. The animals received high-protein diets (36% protein) containing 20% (diet II) and 36% (diet III) of fat as compared with the control (I) diet (18% protein and 20% fat). It appeared that the increase of protein in the diet (diet II) led to a reduction in the efficacy of 14C-palmitic acid incorporation into mitochondrial phospholipids, to a fall in the rate of metabolism of mitochondrial phospholipids and to a rise of their half-life within mitochondrial membranes, with the half-life of phospholipids labeled with 14C-palmitic acid in the fatty acid part being increased to a far greater degree as compared with that of phospholipids labeled with 3H-glycerin in the polar part of the molecules. However, in the presence of a high protein quota in the diet the fat/protein ratio agreed with the control level (diet III), whereas the metabolism of mitochondrial phospholipids remained close to the control values.


Histopathological typing in diffuse malignant epithelioid mesothelioma: implication for prognosis and molecular basis.
The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.


Characterization of a novel differentiation antigen complex recognize by a monoclonal antibody (A-1A5): unique activation-specific molecular forms on stimulated T cells.
By using a single monoclonal antibody, a novel glycoprotein complex composed of at least three distinct bands was defined on the surface of mitogen- or alloantigen-stimulated T cells. These bands (210,000, 165,000, and 130,000 Mr) were not disulfide linked and could be radio-labeled with 125I or 35S-methionine and readily detected by immunoprecipitation with the monoclonal antibody A-1A5. Only approximately 20% of normal T cells (E rosette positive) and approximately 47% non-T cells (E rosette negative) were reactive with A-1A5. However, upon activation of T cells, the amount of A-1A5 binding per cell and the percentage of positive cells significantly increased. This increase was most pronounced in the activated cell subpopulations currently undergoing cell division (S, G2, and M phases), which became 79% A-1A5 positive (after PHA stimulation) and 99% A-1A5 positive (in long-term culture with alloantigen and IL2). Resting lymphocytes contained only the 130,000 Mr band reactive with A-1A5. The two other bands (210,000 and 165,000 Mr) were markers for T cell activation and only appeared several days after T cell stimulation and became especially prominent after the addition of exogenous IL 2. All T lymphoblastoid cell lines tested expressed at least the lower bands (130,000 Mr), and the T cell line HSB also expressed one of the activation-related larger proteins (165,000 Mr). B lymphoblastoid cell lines expressed only a very weak lower band (130,000 Mr), and the cell line U-937 (in the monocyte-macrophage lineage) expressed only a single band (145,000 Mr) not aligned with any of the bands found on lymphoid cells. The estimated number of A-1A5 binding sites per cell was much higher on U-937 (11 X 10(5)), and generally higher on other cell lines of myeloid lineage (1 to 4 X 10(5)) than on lymphoid cell lines (0.2 to 1.3 X 10(5)).


Electrophoretic variation in multiple recessive tester, T, stock mice.
The multiple recessive tester stock, homozygous for seven recessive visible markers, has been used since the 1950s in the specific locus test of mutagenicity in the mouse. The stock was developed by W.L. Russell in Oak Ridge, sent to the MRC Radiobiology Unit (Harwell) in 1953 and then passed to Research Triangle Institute (RTI) in 1988. Stocks are maintained by random mating in all three centres. and in addition stocks that have been selected for homozygosity at certain enzyme and protein markers are kept at both Harwell and RTI. The extent of electrophoretic variation was investigated in the random bred tester stocks at Harwell in 1981 and 1990, and in both random bred and fixed tester stocks at RTI in 1990. Altogether 44 loci were scored and eight of these (Acy-1, Es-3, Gpi-1, Hba, Hbb, Idh-1, Mod-1 and Pgd) have been polymorphic in one or more colonies at various times. Three loci (Es-3, Hbb and Mod-1) had low levels of polymorphism in 1981 and had become monomorphic by 1990. Despite this slight loss of variation, overall the tester stocks show considerable variability. The proportion of polymorphic loci and mean heterozygosity is of the same order of magnitude as island populations of wild mice or other isolated random bred laboratory populations. Contamination of tester stocks with other stocks can be ruled out, and thus tester stocks can be considered to be characteristic island populations. The retention of an appreciable amount of genetic variability in tester stocks is of practical importance in designing new mutation tests involving these mice. When using these stocks, care must be taken to ensure that they are homozygous for the loci under test.


Effects of direct-fed microbial supplementation on performance and immune parameters of lactating dairy cows.
We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. One-hundred and 14 multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14-d covariate (pre-experimental sample and data collection) and 91-d of experimental period. Cows were blocked based on energy-corrected milk yield during the covariate period and the following treatments were randomly assigned within each block: 1) Control (CON): Corn silage-based total mixed ration (TMR) without DFM; 2) PRO-A: Basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/day; and 3) PRO-B: Basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis and B. licheniformis at 11.8 × 109 cfu/day. Milk yield, DMI, and BW were measured daily while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total VFA concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive.


Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats.
Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.


"The cord is the child": meanings and practices related to umbilical cord care in Central Uganda.
Infections account for a quarter of all newborn deaths and the umbilical cord has been identified as a major route of newborn infections. To explore the meanings and practices related to the umbilical cord among caretakers of newborns in central Uganda. This was a qualitative study, designed to inform the design, and interpretation of a randomized controlled trial assessing the effectiveness of chlorhexidine use for the umbilical cord. We conducted 22 in-depth interviews exploring umbilical cord care practices among ten mothers, four health workers, five traditional birth attendants, and three men. We also conducted three focus group discussions with young mothers and elderly women. We used qualitative content analysis to analyze our findings and we borrow upon Mary Douglas' concepts of dirt to present our findings. The umbilical cord had a symbolic position in newborn care. The way it was perceived and handled had far reaching consequences for the survival and wellbeing of the baby. The umbilical cord was a centre of anxiety, a possible gate to illness, a test of fatherhood and a signifier of parental responsibility. Hence, the umbilical cord and the way it was cared for played a part in the present and future survival of the baby, as well as the survival and wellbeing of the household. Persons other than the mother such as older female relatives were very influential in the care of the umbilical cord. The umbilical cord carried symbolic meanings, which extended beyond the newborn and the newborn period, and in turn influenced the various practices of umbilical cord care. The important position of the cord in local newborn care practices should be recognized and taken into consideration when scaling up newborn care interventions in the country.


Modeling and numerical simulations of the influenced Sznajd model.
This paper investigates the effects of independent nonconformists or influencers on the behavioral dynamic of a population of agents interacting with each other based on the Sznajd model. The system is modeled on a complete graph using the master equation. The acquired equation has been numerically solved. Accuracy of the mathematical model and its corresponding assumptions have been validated by numerical simulations. Regions of initial magnetization have been found from where the system converges to one of two unique steady-state PDFs, depending on the distribution of influencers. The scaling property and entropy of the stationary system in presence of varying level of influence have been presented and discussed.


Mild and selective labeling of malondialdehyde with 2-aminoacridone: assessment of urinary malondialdehyde levels.
Malondialdehyde (MDA) has become a well-established biomarker for oxidative stress. The most commonly used way to determine urinary MDA levels is the thiobarbituric acid (TBA) assay, which suffers from several drawbacks. In this manuscript, we describe a novel derivatization strategy for the highly sensitive and selective fluorescence-based determination of MDA in urinary samples. The methodology is based on the mild labeling of MDA with 2-aminoacridone, which can be carried out in aqueous citrate buffer at 40 °C, yielding a highly fluorescent substance. No further sample preparation than mixing with the necessary chemicals is necessary. The formed MDA derivative can conveniently be separated from the label itself and matrix constituents by gradient LC in less than 5 minutes on a cyano-based reversed-phase material. The method was validated with respect to matrix effects, linearity, selectivity and sensitivity (values as low as 1.8 nM for the LOD and 5.8 nM for the LOQ could be achieved). Standard addition quantitation was applied for the determination of MDA in human urine samples. Additionally, the protocol was applied to the measurement of a stability indicating analysis of MDA in urine at different storage conditions.


Enhancing MS(n) mass spectrometry strategy for carbohydrate analysis: A b2 ion spectral library.
Searchable mass spectral libraries for glycans may be enhanced using a B2 ion library. Using a quadrupole ion-trap mass spectrometer, successive fragmentations of sodiated oligosaccharides were carried out in the positive ion mode. In B,Y-type fragmentation, disaccharide B2 ions are generated which correspond to specific glycosidic linkages using progressive MS stages. Fragmentation of "B2 ions" corresponding to glycosidic linkages such as Hex-Fuc, Hex-Hex, Hex-HexNAc, HexNAc-Hex and HexNAc-HexNAc, were systematically studied in low energy CID and collected to form a "B2 library". Linkages produce characteristic fragmentation patterns in the absence of cross-ring fragmentation. Patterns of "B2 ions" rely on relative stability of glycosidic bonds and carbohydrate-metal complexes in the gas phase. MS(n) studies of linear, branched trisaccharides and tetrasaccharides show that isomers for which B2 ion information is not available are rarely a problem in practice by their absence in an isomeric sequence or by their scarcity in nature. This MS strategy for linkage determination of carbohydrates aided by a "B2 library" was developed with a scope for expansion, providing an improved tool for glycomics. We validated this method examining levels of expressed activities of two glycosyl transferases in cancer cell lines: β3(B3GALNT2) and β4GalNAcT(B4GALNT3&4) that generate GalNAcβ3GlcNAcβ and GalNAcβ4GlcNAcβ. Glycosylation is an important class of the "postranslationome", which includes manifold aspects of post-translational protein modification, affecting protein conformation, providing ligands for protein receptors [1-5], and encoding unique haptenic [6,7] or antigenic markers for oncology [8-11] and other applications. Identification of individual monomeric units, linkages, ring size, branching and anomerity has posed significant challenges to mass spectrometrists. MS(n) is a growing key instrumental method to differentiate among isomers [12]. While the potential isomers in oligosaccharides are impossibly large [12], likely possibilities can be limited by the biological system, including the expressed glycosyl transferases [13-20]. Mass spectra from sequential stages of collision activation (MS(n)) can supply structural details for precise characterization of linkage, monomer ID, substitutions, anomerity and branching [21-25]. There is a fundamental need for high throughput tools in glycomics to complement proteome studies. In that regard, nothing could be more important than searchable spectral library files for structural confirmation. The National Academy of Science (NAS) report (http://glyco.nas.edu) recommends the need of more than 10,000 synthetic structures of carbohydrates to advance the field of glycomics. This study demonstrates that the general reproducibility of ion trap spectra, and energy independence from modes of ionization and collisional activation, make compiling an MS(n) library for carbohydrate identification an achievable research target [26]. We intend to use the new B2 library for carbohydrate differences found on cancers, where we profile the glycosyltransferases to predict classes of potential structures, and use the library for MS identification of the expected cohort of altered structures.


Pregnancy suppression by an antiserum to the sperm specific lactate dehydrogenase.
An antiserum induced against the isozyme of lactate dehydrogenase (LDH-X) that is unique to spermatozoa reduced significantly the number of pregnancies in mice treated at varying times after they had mated. This effect of the antiserum occurred both prior to and following implantation. The fecundity of treated animals appeared to be normal in subsequent matings.


Bone marrow transplantation induces either clonal deletion or infectious tolerance depending on the dose.
The concept of immunologic tolerance arose from bone marrow transplantation in neonatal or irradiated mice, in which the predominant mechanism is clonal deletion of donor-specific T cells by donor hemopoietic cells in the recipient thymus. A short term treatment with nonlytic CD4 and CD8 mAbs can induce tolerance to tissue allografts or reversal of spontaneous autoimmunity. Such tolerance to skin or heart allografts is dependent on "infectious" tolerance mediated by regulatory CD4+ T cells. We show here, for multiple minor Ag differences, that while a large inoculum of donor marrow produces significant deletion of Ag-reactive cells as expected, a low marrow dose generates tolerance with little evidence of clonal deletion. Only this low dose tolerance can be transferred to unmanipulated recipients via CD4+ T cells, can be passed onto naive T cells as if infectious, and can act to suppress rejection of third party Ags when "linked" on F1 grafts.


Early-Life Iron Deficiency and Subsequent Repletion Alters Development of the Colonic Microbiota in the Pig.
Background: Iron deficiency is the most prevalent micronutrient deficiency worldwide, affecting over two billion people. Early-life iron deficiency may alter the developing microbiota, which may or may not be reversible with subsequent dietary iron repletion. Thus, the aim of this study was to determine whether early-life iron deficiency and subsequent repletion alter colonic microbial composition and fermentation end-product concentrations in pigs. Methods: Forty-two male pigs received either control (CONT, 21.3 mg Fe/L) or iron-deficient (ID, 2.72 mg Fe/L) milk replacer treatments from postnatal day (PND) 2 to 32. Subsequently, 20 pigs continued through a series of age-appropriate, iron-adequate diets from PND 33 to 61. Contents from the ascending colon (AC) and rectum (feces) were collected at PND 32 and/or 61. Assessments included microbiota composition by 16S rRNA sequencing and volatile fatty acid (VFA) concentrations by gas chromatography methods. Data were analyzed using a 1-way ANOVA and PERMANOVA to assess the main effects of early-life iron status on all outcomes. Results: In AC samples, 15 genera differed (P < 0.05) between ID and CONT pigs, while 27 genera differed (P < 0.05) in fecal samples at PND 32. Early-life ID pigs had higher (P = 0.012) relative abundance of Lactobacillus in AC samples compared with CONT pigs. In feces, ID pigs had lower (P < 0.05) relative abundances of Bacteroides and Clostridium from the families of Clostridiaceae, Lachnospiraceae, and Ruminococcaceae. At PND 61, only two genera differed between treatment groups in AC samples, with ID pigs having a higher (P = 0.043) relative abundance of Bifidobacterium and lower (P = 0.047) relative abundance of Prevotella. Beta diversity differed at PND 32 in both AC and feces between CONT and ID pigs but no differences remained at PND 61. At PND 32, the total VFA concentration was higher in ID pigs compared with CONT pigs in both AC (P = 0.003) and feces (P = 0.001), but no differences in VFA concentrations persisted to PND 61. Conclusion: Early-life iron status influenced microbial composition and VFA concentrations within the large intestine, but these differences were largely normalized following subsequent dietary iron repletion.


Preliminary evidence of early bone resorption in a sheep model of acute burn injury: an observational study.
Treatment with bisphosphonates within the first 10 days of severe burn injury completely prevents bone loss. We therefore postulated that bone resorption occurs early post burn and is the primary explanation for acute bone loss in these patients. Our objective was to assess bone for histological and biomechanical evidence of early resorption post burn. We designed a randomized controlled study utilizing a sheep model of burn injury. Three sheep received a 40 % total body surface area burn under isoflurane anesthesia, and three other sheep received cotton-smoke inhalation and served as control. Burned sheep were killed 5 days post procedure and controls were killed 2 days post procedure. Backscatter scanning electron microscopy was performed on iliac crests obtained immediately postmortem along with quantitative histomorphometry and compression testing to determine bone strength (Young's modulus). Blood ionized Ca was also determined in the first 24 h post procedure as was urinary CTx. Three of three sheep killed at 5 days had evidence of scalloping of the bone surface, an effect of bone resorption, whereas none of the three sheep killed at 2 days post procedure had scalloping. One of the three burned sheep killed at 5 days showed quantitative doubling of the eroded surface and halving of the bone volume compared to sham controls. Mean values of Young's modulus were approximately one third lower in the burned sheep killed at 5 days compared to controls, p = 0.08 by unpaired t test, suggesting weaker bone. These data suggest early post-burn bone resorption. Urine CTx normalized to creatinine did not differ between groups at 24 h post procedure because the large amounts of fluids received by the burned sheep may have diluted urine creatinine and CTx and because the urine volume produced by the burned sheep was threefold that of the controls. We calculated 24 h urinary CTx excretion, and with this calculation CTx excretion/24 h in the burned sheep was nearly twice that of the controls. Moreover, whole blood ionized Ca measured at 3- to 6-h intervals over the first 24 h in both burn and control sheep showed a 6 % reduction versus baseline in the burned sheep with <1 % reduction in the control animals. This sheep model was previously used to demonstrate upregulation of the parathyroid calcium-sensing receptor within the timeframe of the present study. Because both early bone resorption, supported by this study, and calcium-sensing receptor upregulation, consistent with the observed reduction in blood ionized Ca, are mediated by proinflammatory cytokines that are present as part of the post-burn systemic inflammatory response, we may postulate that post-burn upregulation of the parathyroid calcium-sensing receptor may be an adaptive response to clear the blood of excess calcium liberated by cytokine-mediated bone resorption.


Measurement of albumin synthesis in humans: a new approach employing stable isotopes.
A new method for measuring albumin synthesis in humans with stable isotopes is presented. This can readily be applied in most clinical conditions, even when albumin losses are occurring or when repeated assessment is required. After rapid intravenous injection of a large dose of [13C]leucine (57 mg/kg body wt, 19.4 atoms%), plasma samples were taken at intervals up to 90 min. The enrichment of free leucine in plasma measured by gas chromatography-mass spectrometry rose to a peak at 10 min and then fell slowly, whereas that in liver biopsies (from surgical patients) ranged from 101.5 to 80.5% of the plasma value between 10 and 90 min after injection. The fractional synthesis rate (FSR) was calculated by dividing the increase in enrichment of leucine in albumin, measured by gas isotope ratio mass spectrometry, by the area under the plasma free leucine enrichment vs. time curve after allowing for the period between synthesis of the protein and its secretion into the plasma. The FSR in healthy postabsorptive males was 7.2 +/- 1.3%/day, and the absolute synthesis rate was 157 +/- 39 mg.kg body wt-1.day-1. These rates are comparable to those obtained by other methods.


Intranuclear trafficking of plasmid DNA is mediated by nuclear polymeric proteins lamins and actin.
Functions of nuclear polymeric proteins such as lamin A/C and actin in transport of plasmid DNA were studied. The results show that the lamina plays an important role in plasmid DNA's entry into the cell nucleus from the cytoplasm. Selective disruption of lamin A/C led to a halt in plasmid DNA transport through the nuclear envelope. Inside the nucleus, plasmid DNA was frequently localized at sites with impaired genome integrity, such as DNA double-strand breaks (DSBs), occurring spontaneously or induced by ionizing radiation. Polymeric actin obviously participates in nuclear transport of plasmid DNA, since inhibition of actin polymerization by latrunculin B disturbed plasmid transport inside the cell nucleus. In addition, precluding of actin polymerization inhibited plasmid co-localization with newly induced DSBs. These findings indicate the crucial role of polymeric actin in intranuclear plasmid transport.


Detecting awareness in children by using an auditory intervention.
The incidence of awareness has been reported to be higher in children than in adults. Accurately assessing awareness in children is difficult, and the lack of a specific measure of awareness makes it difficult to determine exactly how many and why children are aware. The aim of this study was to determine the incidence and timing of awareness in children by using auditory stimuli applied during anesthesia. Three easily identified animal noises were played repeatedly through headphones during three specific phases of anesthesia in 539 children aged 5-12 yr. Children were not told that this would happen. Awareness was determined with a structured interview on days 1 and 3 after the anesthetic. All positive responses were sent to four adjudicators for assessment, and awareness was defined as having occurred if all adjudicators agreed that the child was aware. Five hundred children were interviewed at least once after the anesthetic. Thirty-five reports were sent to the adjudicators, and one child was classified as aware. This child was deemed to be aware even though he did not report hearing an animal. The incidence of awareness in this study is less than reported previously.


Major repeat components covering one-third of the ginseng (Panax ginseng C.A. Meyer) genome and evidence for allotetraploidy.
Ginseng (Panax ginseng) is a famous medicinal herb, but the composition and structure of its genome are largely unknown. Here we characterized the major repeat components and inspected their distribution in the ginseng genome. By analyzing three repeat-rich bacterial artificial chromosome (BAC) sequences from ginseng, we identified complex insertion patterns of 34 long terminal repeat retrotransposons (LTR-RTs) and 11 LTR-RT derivatives accounting for more than 80% of the BAC sequences. The LTR-RTs were classified into three Ty3/gypsy (PgDel, PgTat and PgAthila) and two Ty1/Copia (PgTork and PgOryco) families. Mapping of 30-Gbp Illumina whole-genome shotgun reads to the BAC sequences revealed that these five LTR-RT families occupy at least 34% of the ginseng genome. The Ty3/Gypsy families were predominant, comprising 74 and 33% of the BAC sequences and the genome, respectively. In particular, the PgDel family accounted for 29% of the genome and presumably played major roles in enlargement of the size of the ginseng genome. Fluorescence in situ hybridization (FISH) revealed that the PgDel1 elements are distributed throughout the chromosomes along dispersed heterochromatic regions except for ribosomal DNA blocks. The intensity of the PgDel2 FISH signals was biased toward 24 out of 48 chromosomes. Unique gene probes showed two pairs of signals with different locations, one pair in subtelomeric regions on PgDel2-rich chromosomes and the other in interstitial regions on PgDel2-poor chromosomes, demonstrating allotetraploidy in ginseng. Our findings promote understanding of the evolution of the ginseng genome and of that of related species in the Araliaceae.


Physician preferences for accredited online continuing medical education.
The need for up-to-date and high-quality continuing medical education (CME) is growing while the financial investment in CME is shrinking. Despite online technology's potential to efficiently deliver electronic CME (eCME) to large numbers of users, it has not yet displaced traditional CME. The purpose of this study was to explore what health care providers want in eCME and how they want to use it. This was a qualitative study. Two 3-hour focus groups were held with physicians in both academic and community practices as well as trainees knowledgeable in the hypertension clinical practice guidelines with a willingness to discuss eCME. Content/thematic analysis was used to examine the data. Three main themes emerged: credibility, content/context, and control. Credibility was the most consistent and dominant theme. Affiliations with medical organizations and accreditation were suggested as methods by which eCME can gain credibility. The content and need for discussion of the content emerged as a key pivot point between eCME and traditional CME: a greater need for discussion was linked to a preference for traditional face-to-face CME. Control over the content and how it was accessed was an emergent theme, giving learners the ability to control the depth of learning and the time spent. They valued the ability to quickly find information that was in a format (podcast, video, mobile device) that best suited their learning needs or preferences at the time. This study provides insight into physician preferences for eCME and hypotheses that can be used to guide further research.


Where's the Disconnect? Exploring Pathways to Healthcare Coordinated for Youth Experiencing Homelessness in Toronto, Canada, Using Grounded Theory Methodology.
About 900 youth experiencing homelessness (YEH) reside at an emergency youth shelter (EYS) in Toronto on any given night. Several EYSs offer access to healthcare based on youths' needs, including access to primary care, and mental health and addictions support. However, youth also require healthcare from the broader health system, which is often challenging to navigate and access. Currently, little is known about healthcare coordination efforts between the EYS and health systems for YEH. Using grounded theory methodology, we interviewed 24 stakeholders and concurrently analyzed and compared data to explore pathways to healthcare coordinated for youth who reside at an EYS in Toronto. We also investigated fundamental parts (i.e., norms, resources, regulations, and operations) within the EYS and health systems that influence these pathways to healthcare using thematic analysis. A significant healthcare coordination gap was found between these two systems, typically when youth experience crises, often resulting in a recurring loop of transition and discharge between EYSs and hospitals. Several parts within each system act interdependently in hindering adequate healthcare coordination between the EYS and health systems. Incorporating training for system staff on how to effectively coordinate healthcare and work with homeless populations who have complex health needs, and rethinking information-sharing policies within circles of care are examples of how system parts can be targeted to improve healthcare coordination for YEH. Establishing multidisciplinary healthcare teams specialized to serve the complex needs of YEH may also improve healthcare coordination between systems, and access and quality of healthcare for this population.


Genomic loci involved in sensing environmental cues and metabolism affect seasonal coat shedding in Bos taurus and Bos indicus cattle.
Seasonal shedding of winter hair at the start of summer is well studied in wild and domesticated populations. However, the genetic influences on this trait and their interactions are poorly understood. We use data from 13,364 cattle with 36,899 repeated phenotypes to investigate the relationship between hair shedding and environmental variables, single nucleotide polymorphisms, and their interactions to understand quantitative differences in seasonal shedding. Using deregressed estimated breeding values from a repeated records model in a genome-wide association analysis (GWAA) and meta-analysis of year-specific GWAA gave remarkably similar results. These GWAA identified hundreds of variants associated with seasonal hair shedding. There were especially strong associations on chromosomes 5 and 23. Genotype-by-environment interaction GWAA identified 1,040 day length-by-genotype interaction associations and 17 apparent temperature-by-genotype interaction associations with hair shedding, highlighting the importance of day length on hair shedding. Accurate genomic predictions of hair shedding were created for the entire dataset, Angus, Hereford, Brangus, and multi-breed datasets. Loci related to metabolism and light-sensing have a large influence on seasonal hair shedding. This is one of the largest genetic analyses of a phenological trait and provides insight for both agriculture production and basic science.


PA.NET International Quality Certification Protocol for blood pressure monitors.
Although standard validation protocols provide assurance of the accuracy of blood pressure monitors (BPMs), there is no guidance for the consumer as to the overall quality of a device. The PA.NET International Quality Certification Protocol, developed by the Association for Research and Development of Biomedical Technologies and for Continuing Medical Education (ARSMED), a nonprofit organization, with the support of the Italian Society of Hypertension-Italian Hypertension League, and the dabl Educational Trust denotes additional criteria of quality for BPMs that fulfilled basic validation criteria, published in full in peer-reviewed medical journals. The certification is characterized by three phases: (i) to determine that the device fulfilled standard validation criteria; (ii) to determine the technical and functional characteristics of the device (e.g. operativity, display dimension, accessory functions, memory availability, etc.) and (iii) to determine the commercial characteristics (e.g. price-quality ratio, after-sale service, guarantee, etc.). At the end of the certification process, ARSMED attributes a quality index to the device, based on a scale ranging from 1 to 100, and a quality seal with four different grades (bronze, silver, gold and diamond) according to the achieved score. The seal is identified by a unique alphanumeric code. The quality seal may be used on the packaging of the appliance or in advertising. A quality certification is released to the manufacturer and published on www.pressionearteriosa.net and www.dableducational.org. The PA.NET International Quality Certification Protocol represents the first attempt to provide health care personnel and consumers with an independent and objective assessment of BPMs based on their quality.


Pyruvate:ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia.
The mechanism of action of, and resistance to, metronidazole in the anaerobic (or micro-aerotolerant) protozoan parasite Giardia lamblia has long been associated with the reduction of ferredoxin (Fd) by the enzyme pyruvate:ferredoxin oxidoreductase (PFOR) and the subsequent activation of metronidazole by Fd to toxic radical species. Resistance to metronidazole has been associated with down-regulation of PFOR and Fd. The aim of this study was to determine whether the PFOR/Fd couple is the only pathway involved in metronidazole activation in Giardia. PFOR and Fd activities were measured in extracts of highly metronidazole-resistant (MTR(r)) lines and activities of recombinant G. lamblia thioredoxin reductase (GlTrxR) and NADPH oxidase were assessed for their involvement in metronidazole activation and resistance. We demonstrated that several lines of highly MTR(r) G. lamblia have fully functional PFOR and Fd indicating that PFOR/Fd-independent mechanisms are involved in metronidazole activation and resistance in these cells. Flavin-dependent GlTrxR, like TrxR of other anaerobic protozoa, reduces 5-nitroimidazole compounds including metronidazole, although expression of TrxR is not decreased in MTR(r) Giardia. However, reduction of flavins is suppressed in highly MTR(r) cells, as evidenced by as much as an 80% decrease in NADPH oxidase flavin mononucleotide reduction activity. This suppression is consistent with generalized impaired flavin metabolism in highly MTR(r) Trichomonas vaginalis. These data add to the mounting evidence against the dogma that PFOR/Fd is the only couple with a low enough redox potential to reduce metronidazole in anaerobes and point to the multi-factorial nature of metronidazole resistance.


Electroretinogram Changes Following Sequential Panretinal Photocoagulation for Proliferative Diabetic Retinopathy.
To evaluate changes in electroretinogram (ERG) response over the course of multiple sessions of panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PRP). A prospective cohort study of 11 patients with PDR who required PRP was conducted. PRP was completed over three sessions. Each patient had five ERGs done: baseline, 1 week after each PRP session, and 6 weeks after the last session of PRP. Dark-adapted 0.01 ERG, Dark-adapted 3 ERG, Dark-adapted 10 ERG, Light- adapted 3 ERG, and Light-adapted 30 Hz flicker ERG were done. The mean change in a- and b-wave amplitudes as well as implicit times compared to baseline was analyzed. A significant reduction in peak amplitudes of both a- and b-waves and delay in latencies were observed in all responses (p<0.05). The absolute amplitude reduction and delay in latency were higher for scotopic b-waves (p<0.05). The root mean square (RMS) of Dark-adapted 10.0 ERG (p<0.05) and total mean amplitude changes of a- and b-waves (p<0.001) were reduced after each laser session; however, the magnitude of change was not different between the first, second, or third sessions of PRP, and each session showed a similar deterioration rate of ERG parameters comparing to each other (p=0.4 for RMS and p=0.2 for total mean amplitude changes). In addition, the results indicated recovery of the amplitude and latency of ERG waves after 6 weeks from the final treatment (p<0.001) although not to baseline levels. ERG findings following PRP show reduced retinal function after each session which partially recovers by 6 weeks after the completion of therapy. Clinicians should be mindful of these changes when planning the treatment course for patients with PDR.