The prognostic significance of serum glucose levels after the onset of ventricular arrhythmia on in-hospital mortality of patients with acute coronary syndrome.
Several studies have illustrated the role played by serum glucose levels in cardiovascular morbidity and mortality in general and, more particularly, after an acute coronary event. The aim of this study was to evaluate the impact of serum potassium and glucose levels on in-hospital mortality in patients with ischemic heart disease, who exhibited severe ventricular arrhythmia. We enrolled 162 consecutive patients who were referred to our institution for an acute coronary event and presented with sustained ventricular tachycardia or ventricular fibrillation during the first 24 hours of hospitalization. Serum potassium and glucose levels were measured in all patients at the onset of tachycardia and after 2, 4, 6, 12, 36, 48 hours. During hospitalization, 23 out of 162 patients died (61% males). Serum glucose levels at the onset of the arrhythmia, as well as after 2, 12, 36 and 48 hours, were higher in the deceased (onset: 228.8 +/- 108 vs. 158 +/- 68 mg/dl, p = 0.0001, 2 h: 182 +/- 109 vs. 149 +/- 59 mg/dl, p = 0.03, 12 h: 155.5 +/- 72 vs. 128 +/- 48 mg/dl, p = 0.025, 36 h: 163.8 +/- 63 vs.116 +/- 42 mg/dl, p = 0.002, and 48 h: 138 +/- 64 vs. 122 +/- 42 mg/dl, p = 0.05, respectively), even after adjustment for age, sex, diabetes, left ventricular ejection fraction, type of acute coronary syndrome and site of infarction and medication intake. There was no difference in serum potassium levels between the deceased and survivors. Serum glucose levels at the onset of arrhythmia and 2, 36 and 48 hours later seem to have prognostic significance for in-hospital mortality in patients hospitalized for an acute coronary event, who exhibit severe ventricular arrhythmia.


'Candidatus Branchiomonas cysticola' is a common agent of epitheliocysts in seawater-farmed Atlantic salmon Salmo salar in Norway and Ireland.
The prevalence and geographical distribution of the recently described endosymbiont 'Candidatus Branchiomonas cysticola' in Atlantic salmon Salmo salar gill epithelial cell cysts was investigated in seawater-farmed fish suffering proliferative gill inflammation (PGI). To this end, we developed a specific and sensitive real-time PCR assay for detection of the bacterium. 'Ca. B. cysticola' was found to be highly prevalent in Atlantic salmon gills sampled over 7 yr and from 17 geographically distant seawater locations in Norway and Ireland. 'Ca. B. cysticola' was found in significantly greater quantities in fish with large numbers of epitheliocysts, and fluorescence in situ hybridization confirmed its localisation within cysts. 'Ca. Piscichlamydia salmonis', a bacterium previously linked to epitheliocysts, was identified at relatively low levels of infection, apparently independent of epitheliocyst prevalence. These results suggest that 'Ca. B. cysticola' is the main cyst-forming bacterium in seawater-farmed Atlantic salmon in the studied countries. Our results also suggest a relationship between load of 'Ca. B. cysticola' and extent of pathological changes. Taken together with a previously described association between epitheliocyst load and severity of PGI in Norwegian salmon, the results could indicate a role for 'Ca. B. cysticola' in gill diseases such as PGI.


Synthetic access to isoxazoline-functionalized isoquinolines via microwave-assisted iminoxyl radical-participated cascade cyclization of vinyl isocyanides.
A convenient microwave-assisted method for the synthesis of isoxazoline-functionalized isoquinolines via the n-Bu4NI (TBAI) catalyzed radical cascade cyclization of vinyl isocyanides with β,γ-unsaturated ketoximes has been described. The methodology presented here achieves a wide substrate scope and good to excellent yields. A radical mechanism is proposed, which is supported by the intermolecular competing kinetic isotope effect (KIE) experiment and the radical trapping experiment.


Differential roles of kinesin and dynein in translocation of neurofilaments into axonal neurites.
Neurofilament (NF) subunits translocate within axons as short NFs, non-filamentous punctate structures ('puncta') and diffuse material that might comprise individual subunits and/or oligomers. Transport of NFs into and along axons is mediated by the microtubule (MT) motor proteins kinesin and dynein. Despite being characterized as a retrograde motor, dynein nevertheless participates in anterograde NF transport through associating with long MTs or the actin cortex through its cargo domain; relatively shorter MTs associated with the motor domain are then propelled in an anterograde direction, along with any linked NFs. Here, we show that inhibition of dynein function, through dynamitin overexpression or intracellular delivery of anti-dynein antibody, selectively reduced delivery of GFP-tagged short NFs into the axonal hillock, with a corresponding increase in the delivery of puncta, suggesting that dynein selectively delivered short NFs into axonal neurites. Nocodazole-mediated depletion of short MTs had the same effect. By contrast, intracellular delivery of anti-kinesin antibody inhibited anterograde transport of short NFs and puncta to an equal extent. These findings suggest that anterograde axonal transport of linear NFs is more dependent upon association with translocating MTs (which are themselves translocated by dynein) than is transport of NF puncta or oligomers.


Selective removal of 2,4-dichlorophenoxyacetic acid from water by molecularly-imprinted amino-functionalized silica gel sorbent.
A molecularly-imprinted amino-functionalized sorbent for selective removal of 2,4-dichlorophenoxyacetic acid (2,4-D) was prepared by a surface imprinting technique in combination with a sol-gel process. The 2,4-D-imprinted amino-functionalized silica sorbent was characterized by FT-IR, nitrogen adsorption and static adsorption experiments. The selectivity of the sorbent was investigated by a batch competitive binding experiment using an aqueous 2,4-D and 2,4-dichlorophenol (2,4-DCP) mixture or using an aqueous 2,4-D and 2,4-dichlorophenylacetic acid (DPAC) mixture. The largest selectivity coefficient for 2,4-D in the presence of 2,4-DCP was found to be over 18, the largest relative selectivity coefficient between 2,4-D and 2,4-DCP over 9. The static uptake capacity and selectivity coefficient of the 2,4-D-imprinted functionalized sorbent are higher than those of the non-imprinted sorbent. The imprinted functionalized silica gel sorbent offered a fast kinetics for the extraction/stripping of 2,4-D, 73% of binding capacity (200 mg/L 2,4-D onto 20 mg of imprinted sorbent) was obtained within 5 min and the adsorbed 2,4-D can be easily stripped by the mixture solution of ethanol and 6 mol/L HCl (V:V = 1:1). In a test of five extraction/stripping cycles, the adsorption capacity of the sorbent was all above 93% of that of the fresh sorbent. Experimental result showed the potential of molecularly-imprinted amino-functionalized sorbent for selective removal of 2,4-D.


[Present status of pediatric living-donor liver transplantation in National Center for Child Health and Development].
We reviewed our initial experience of pediatric living-donor liver transplantation (LDLT) in National Center for Child Health and Development and report the results herein. We have done 103 cases of LDLT during November 2005 through September 2009 in National Center for Child Health and Development. Variables including indication of liver transplantation/infectious/immunological outcome were reviewed. The indication for liver transplantation was cholestatic liver disease in 43.76%, followed by metabolic liver disease 24.3% and acute liver failure 18.5%. The mean age of recipient was 3.6 +/- 4.2 years and body weight was 14.4 +/- 11.1kg. Immunosuppression consisted of tacrolimus and low-dose steroids. The incidence of acute cellular rejection was 33.3%. The graft and patient survival were 92.2%. Satisfactory result can be achieved on LDLT program in National Center for Child Health and Development. The follow-up period was too short to make definitive conclusion, however, long-term observation may be necessary to collect sufficient data for the establishment of the treatment modality.


Lymph node assessment in colorectal cancer surgery: laparoscopic versus open techniques.
The aim of our study is to compare the outcomes of laparoscopic resection (LR) and open resection (OR) for colorectal cancer surgery evaluating lymph node assessment. It may be important to remove and examine an adequate number of lymph nodes because a more extensive nodal resection has been associated to higher survival rate and lower recurrences. 150 patients (74 females and 76 males) with colorectal cancer were enrolled and analyzed from January 2006 to March 2010 in our Unit. 100 procedures were performed with traditional laparotomy and 50 procedures laparoscopically. A strict follow-up was scheduled every 1-3-6 months after surgery and, therefore, every year. Laparoscopic techniques require a longer operating time. 2484 total lymph nodes examined with a mean of 16,56 removed per resection in all procedures. 1632 lymph nodes were removed during open procedures and 852 removed during laparoscopy. The scheduled follow-up demonstrated that local recurrence and distant metastasis presented with no significant differences between two groups and overall survival and disease-free survival were assessed over 5 year in 80% of patients. According to our experience, laparoscopic colorectal surgery is safe and feasible, with better short-term outcomes and oncological adequacy comparable to open approach.


IgG4 immunostaining and its implications in orbital inflammatory disease.
IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.


Predictors of elevations in fasting lipid levels in adults with epilepsy on a modified Atkins diet.
Ketogenic diet therapies can improve seizure control in patients with drug-resistant epilepsy (DRE). The current study investigated whether dietary fat composition is associated with elevations in serum lipid levels in adults with epilepsy who began a modified Atkins diet (MAD). Adults with DRE were instructed to follow the MAD. Food records collected at baseline and follow-up were analyzed to extract median daily macro- and micronutrient composition. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, triglyceride (TG), high-density lipoprotein (HDL) cholesterol, non-HDL and TC/HDL ratio were measured at baseline and follow-up. Study participants initiating MAD showed higher fat intake at 1 month (p<0.001) and 2 months (p<0.001) and lower carbohydrate intake at 1 month (p<0.001) and 2 months (p<0.001) compared to baseline. Study participants also showed higher intake of cholesterol (p<0.001), saturated fatty acid (p<0.001) and monounsaturated fatty acid (p<0.001) over time. Following MAD initiation, study participants showed significant increases in levels of TC (p = 0.007), LDL (p<0.001), and non-HDL (p = 0.009) over time. Dietary intake variables, including cholesterol and fat subtypes, were significantly associated with difference in 1 month TC and LDL levels from baseline but not absolute 1 month lipid values. In a sub-analysis, participants with baseline dyslipidemia showed smaller changes in lipid values during diet use. Adults with DRE starting MAD increased fat intake, particularly saturated and monounsaturated fat subtypes, and reduced carbohydrate intake. Changes in TC and LDL levels 1 month after MAD initiation are associated with dietary intake of cholesterol and fat.


Attitudes towards suicide among nurses and doctors working with children and young people who self-harm.
This paper presents a study investigating the attitudes towards suicide in nurses and doctors who work with children and young people who self-harm. The effect of basic demographic factors on attitudes towards suicide in the staff group is explored. The Suicide Opinion Questionnaire was implemented to collect data on attitudes towards suicide. A 5-point Likert Scale was used to score responses and attitudes were measured on eight clinical scales. Participants were 179 nurses and doctors working in three clinical areas: accident and emergency; paediatric medicine and adolescent inpatient mental health services. Nurses and doctors indicated agreement on the Mental Illness, Cry for Help, Right to Die, Impulsivity, Normality and Aggression scales, and less agreement on the Religion and Moral Evil scale. Only the scores for Mental Illness were statistically different in relation to professional group. There were no other significant differences on the other clinical scales in relation to gender, age clinical speciality and length of experience in current post. It is argued that complex attitudes need to be taken into account in training for healthcare professionals and in the development of contemporary suicide prevention policy.


[Antigenic and biological characteristics of influenza virus A strains isolated in 1985].
The antigenic structure of hemagglutinin of influenza A virus (H3N2) strains isolated in 1985 was studied using a series of monoclonal antibody to A/Dunedin/4/73/A (H3N2) and A/Bangkok/1/79/A (H3N2), and biological and physico-chemical properties of these strains were compared with those of influenza A (H3N2) virus of 1983 and reference A (H3N2) of 1979-1984 (the rate of adsorption on chick erythrocytes and eluting activity, thermostability of hemagglutinin and neuraminidase, sensitivity to nonionic detergents, sensitivity to remantadine, analysis of virion polypeptide composition). A high degree of heterogeneity of the 1985 strain population of influenza A (H3N2) virus was revealed both in the antigenic structure of hemagglutinin and in all the biological and physico-chemical parameters tested. It was suggested that the A/Caen/1/84 strain originated not from A/Philippines/2/82 but directly from A/Texas/1/77.


Naming the illness: the power of words.
A key part of the doctor-patient encounter is the giving of a name to the patient's illness by the physician. Personal, professional, societal, and bureaucratic factors influence physicians in their choice of a name and the manner in which they present these words to the patient. The effect of the illness name on the individual patient may be determined not only by individual experience and knowledge, but also by social, cultural, and economic factors. Citing examples from medical practice from its origins in ancient Greece to the present day, this paper draws attention to the crucial significance of medical language in doctor-patient communication. A heightened awareness by physicians of communication style is suggested, both in encounters with patients and in the training of medical students and residents.


Highly Polarized Upconversion Emissions from Lanthanide-Doped LiYF4 Crystals as Spatial Orientation Indicators.
Polarized emission, an inherent characteristic that correlated with structure and morphology, is very sensitive to orientation. For the upconversion (UC) emission of lanthanides, the mechanism of polarization is rarely discussed, and the highly polarized UC emissions are poorly developed. Herein, with the benefit of the strong anisotropic crystal field, well-resolved emissions from lanthanide-doped LiYF4 crystals were studied, and highly polarized UC emissions from Er3+ and Ho3+ were investigated. With multiple sub-energy level transitions, the UC emissions are classified into two sets, with transition dipoles being either parallel or perpendicular to the c-axis of the LiYF4 crystal. An optical three-dimensional orientation sensor was further investigated, in which the in-plane angle is referenced from the orientation of the transition dipoles. In contrast, the out-of-plane angle can be deduced from the change in the degree of polarization. This research deepens our understanding of the polarized photoluminescence, and it opens up an avenue toward unique UC orientation sensors.


Cord blood cardiac troponin I as an early predictor of short-term outcome in perinatal hypoxia.
In most perinatal-hypoxia survivors, myocardial dysfunction can be reversed with appropriate inotropic support and oxygenation. The main problem related to outcome is cerebral damage. We tested the hypothesis that cardiac troponin I (cTnI), a known marker of myocardial injury, is also an early predictor of severity of cerebral damage and mortality in intrauterine hypoxia. Venous and arterial cord blood samples were collected at delivery from 54 consecutive newborns with hypoxic-ischemic encephalopathy and from 50 consecutive healthy controls. Arterial blood gas analysis was performed and levels of cTnI, creatine kinase and creatine kinase-MB in venous cord blood were measured. The same serum parameters were also measured on the 3rd and 7th day of life. Infants with hypoxia had a significantly higher cord blood cTnI levels than controls (p < 0.0001). Cord blood and 3rd and 7th day serum cTnI values showed a significant increase with severity of HIE (p < 0.0001). In non-survivors cord blood cTnI levels were significantly higher than the survivors (5.9 ng/ml, range 2.1-12.8, and 1.6 ng/ml, range 0.4-5.8, respectively; p < 0.0001). Receiver-operator curve analysis revealed cord cTnI as the most sensitive factor for predicting early death (area under curve = 0.956; SE: 0.028; 95% CI: 0.9-1.01). Cord blood cTnI of 4.6 ng/ml was identified as the optimal cut-off level for predicting serious risk of early mortality. The results suggest that significant elevation of cord cTnI is an excellent early predictor of severity of hypoxic-ischemic encephalopathy and mortality in term infants.


Prevalence of antiretroviral drug resistance in the HIV-1-infected urban indigent population in San Francisco: a representative study.
We determined the prevalence of antiretroviral (ARV) resistance in HIV-1 infected indigent persons in San Francisco, California. Three hundred and twenty-seven subjects (159 (49%) ARV naïve, and 168 (51%) ARV-experienced), were recruited during 1996-97 and 1999-2000. Plasma HIV-1 viral load quantification and genotypic resistance testing were performed. Twice as many subjects received nucleoside reverse transcriptase inhibitors (NRTIs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs); resistance mutation prevalences were 30%, 14% and 16% respectively. Risk of any resistance mutations was strongly and independently associated with prior ARV exposure (OR = 1.3 per year of exposure, P < 0.0001) and with ARV exposure prior to HAART (OR = 2.5, P = 0.015). Prevalences of primary ARV resistance mutations among both treatment-naive and treatment-experienced subjects in this indigent urban population are low compared to other observational cohorts, are directly related to length and type of prior ARV exposure, and did not increase significantly between recruitment periods.


The practice of evidence-based medicine involves the care of whole persons.
In this issue of the Journal, Dr. Fava posits that evidence-based medicine (EBM) was bound to fail. I share some of the concerns he expresses, yet I see more reasons for optimism. Having been on rounds with both Drs. Engel and Sackett, I reckon they would have agreed more than they disagreed. Their central teaching was the compassionate and well-informed care of sick persons. The model that emerged from these rounds was that patient care could be both person-centered and evidence-based, that clinical judgment was essential to both, and the decisions could and should be shared. Both clinicians and patients can bring knowledge from several sources into the shared decision making process in the clinical encounter, including evidence from clinical care research. I thank Dr. Fava for expressing legitimate doubts and providing useful criticism, yet I am cautiously optimistic that the model of EBM described here is robust enough to meet the challenges and is not doomed to fail.


Bayesian cost-effectiveness analysis for censored data: an application to antiplatelet therapy.
Cost-effectiveness analysis (CEA) on trial-based data has played an important role in pharmacoeconomics. A regression model can be used to account for patient-level heterogeneity throughout covariates adjustment in CEA. However, the estimates from CEA could be biased if ignoring the censoring issue on effectiveness and costs. This study is to propose a regression model to account for both time-to-event effectiveness and cost. A bivariate regression model was proposed to analyze both effectiveness and cost simultaneously, while censored observations were also taken into account. The regression coefficients were estimated using a Bayesian approach by drawing a random sample from their posterior distribution derived from the Markov chain Monte Carlo (MCMC) method. The proposed method was illustrated using empirical data of anti-platelet therapies to the management of cardiovascular diseases for those patients with high risk of gastrointestinal (GI) bleeding, where cost-effectiveness between different therapies was analyzed under both censored and non-censored circumstances, where the effectiveness was defined as the time to re-hospitalization due to GI complications, and the cost was measured by the total drug expenditure. Under censored circumstances, aspirin plus proton-pump inhibitors (PPIs) was considered more cost-effective than clopidogrel with/without PPIs, as shown in the cost-effectiveness acceptability curve, and clopidogrel was preferred to aspirin for a willingness-to-pay of 89 NTD for delaying 1 day to hospitalization due to GI complications. Ignoring censoring problems could possibly bias the results in CEA. This study has provided an appropriate method to conduct regression-based CEA to improve the estimation which serves its purpose for CEA concerns. The normality assumption for the cost and effectiveness in the bivariate normal regression needs to be examined, and the conclusions may be biased if this assumption is violated. However, when sample size is sufficiently large, a slight deviation from normality would not be a serious problem.


Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes.
All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter cells. Simian immunodeficiency virus (SIV) infection of non-human primates has served as a useful model for understanding AIDS pathogenesis in humans. Research on several genetically divergent SIV isolates has revealed that SIV uses CCR5, and not CXCR4, for entry. CEM x174, a human lymphoid cell line, has been routinely used to cultivate and maintain various SIV strains. However, questions have arisen about how CEM x174, which reportedly was unable to express detectable amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching for an answer, we resorted to a sensitive competitive reverse transcriptase-polymerase chain reaction procedure in an attempt to detect as well as quantify the amount of CCR5 expression. Here we present our findings, which indicate that CEM x174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells pretreated with morphine. These results correlate well with our previous observations that morphine treatment causes CEM x174 cells to be more susceptible to SIV infection. Similar morphine effect was not observed on CEM x174 cells infected with simian retroviruses, which do not depend on CCR5 for entry. These findings suggest a plausible mechanism whereby opiate drug users render themselves more susceptible to HIV infection, thereby explaining the vast prevalence of HIV infection among endemic drug use populations.


Biofilm formation and toxin production provide a fitness advantage in mixed colonies of environmental yeast isolates.
Microbes can engage in social interactions ranging from cooperation to warfare. Biofilms are structured, cooperative microbial communities. Like all cooperative communities, they are susceptible to invasion by selfish individuals who benefit without contributing. However, biofilms are pervasive and ancient, representing the first fossilized life. One hypothesis for the stability of biofilms is spatial structure: Segregated patches of related cooperative cells are able to outcompete unrelated cells. These dynamics have been explored computationally and in bacteria; however, their relevance to eukaryotic microbes remains an open question. The complexity of eukaryotic cell signaling and communication suggests the possibility of different social dynamics. Using the tractable model yeast, Saccharomyces cerevisiae, which can form biofilms, we investigate the interactions of environmental isolates with different social phenotypes. We find that biofilm strains spatially exclude nonbiofilm strains and that biofilm spatial structure confers a consistent and robust fitness advantage in direct competition. Furthermore, biofilms may protect against killer toxin, a warfare phenotype. During biofilm formation, cells are susceptible to toxin from nearby competitors; however, increased spatial use may provide an escape from toxin producers. Our results suggest that yeast biofilms represent a competitive strategy and that principles elucidated for the evolution and stability of bacterial biofilms may apply to more complex eukaryotes.


A design-based model of the aortic valve for fluid-structure interaction.
This paper presents a new method for modeling the mechanics of the aortic valve and simulates its interaction with blood. As much as possible, the model construction is based on first principles, but such that the model is consistent with experimental observations. We require that tension in the leaflets must support a pressure, then derive a system of partial differential equations governing its mechanical equilibrium. The solution to these differential equations is referred to as the predicted loaded configuration; it includes the loaded leaflet geometry, fiber orientations and tensions needed to support the prescribed load. From this configuration, we derive a reference configuration and constitutive law. In fluid-structure interaction simulations with the immersed boundary method, the model seals reliably under physiological pressures and opens freely over multiple cardiac cycles. Further, model closure is robust to extreme hypo- and hypertensive pressures. Then, exploiting the unique features of this model construction, we conduct experiments on reference configurations, constitutive laws and gross morphology. These experiments suggest the following conclusions: (1) The loaded geometry, tensions and tangent moduli primarily determine model function. (2) Alterations to the reference configuration have little effect if the predicted loaded configuration is identical. (3) The leaflets must have sufficiently nonlinear material response to function over a variety of pressures. (4) Valve performance is highly sensitive to free edge length and leaflet height. These conclusions suggest appropriate gross morphology and material properties for the design of prosthetic aortic valves. In future studies, our aortic valve modeling framework can be used with patient-specific models of vascular or cardiac flow.


Measurement of Murine Single-Kidney Glomerular Filtration Rate Using Dynamic Contrast-Enhanced MRI.
To develop and validate a method for measuring murine single-kidney glomerular filtration rate (GFR) using dynamic contrast-enhanced MRI (DCE-MRI). This prospective study was approved by the Institutional Animal Care and Use Committee. A fast longitudinal relaxation time (T1 ) measurement method was implemented to capture gadolinium dynamics (1 s/scan), and a modified two-compartment model was developed to quantify GFR as well as renal perfusion using 16.4T MRI in mice 2 weeks after unilateral renal artery stenosis (RAS, n = 6) or sham (n = 8) surgeries. This approach was validated by comparing model-derived GFR and perfusion to those obtained by fluorescein isothiocyanante (FITC)-inulin clearance and arterial spin labeling (ASL), respectively, using the Pearson's and Spearman's rank correlations and Bland-Altman analysis. The compartmental model provided a good fitting to measured gadolinium dynamics in both normal and RAS kidneys. The proposed DCE-MRI method offered assessment of single-kidney GFR and perfusion, comparable to the FITC-inulin clearance (Pearson's correlation coefficient r = 0.95 and Spearman's correlation coefficient ρ = 0.94, P < 0.0001, and mean difference -7.0 ± 11.0 μL/min) and ASL (r = 0.92 and ρ = 0.84, P < 0.0001, and mean difference 4.4 ± 66.1 mL/100 g/min) methods. The proposed DCE-MRI method may be useful for reliable noninvasive measurements of single-kidney GFR and perfusion in mice. Magn Reson Med 79:2935-2943, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Validation of Two Short Personality Inventories Using Self-Descriptions in Natural Language and Quantitative Semantics Test Theory.
If individual differences are relevant and prominent features of personality, then they are expected to be encoded in natural language, thus manifesting themselves in single words. Recently, the quantification of text data using advanced natural language processing techniques offers innovative opportunities to map people's own words and narratives to their responses to self-reports. Here, we demonstrate the usefulness of self-descriptions in natural language and what we tentatively call Quantitative Semantic Test Theory (QuSTT) to validate two short inventories that measure character traits. In Study 1, participants (N 1 = 997) responded to the Short Character Inventory, which measures self-directedness, cooperativeness, and self-transcendence. In Study 2, participants (N 2 = 2373) responded to Short Dark Triad, which measures Machiavellianism, narcissism, and psychopathy. In both studies, respondents were asked to generate 10 self-descriptive words. We used the Latent Semantic Algorithm to quantify the meaning of each trait using the participants' self-descriptive words. We then used these semantic representations to predict the self-reported scores. In a second set of analyses, we used word-frequency analyses to map the self-descriptive words to each of the participants' trait scores (i.e., one-dimensional analysis) and character profiles (i.e., three-dimensional analysis). The semantic representation of each character trait was related to each corresponding self-reported score. However, participants' self-transcendence and Machiavellianism scores demonstrated similar relationships to all three semantic representations of the character traits in their respective personality model. The one-dimensional analyses showed that, for example, "loving" was indicative of both high cooperativeness and self-transcendence, while "compassionate," "kind," and "caring" was unique for individuals high in cooperativeness. The words "kind" and "caring" indicated low levels of Machiavellianism and psychopathy, whereas "shy" or "introvert" indicated low narcissism. We also found specific keywords that unify or that make the individuals in some profiles unique. Despite being short, both inventories capture individuals' identity as expected. Nevertheless, our method also points out some shortcomings and overlaps between traits measured with these inventories. We suggest that self-descriptive words can be quantified to validate measures of psychological constructs (e.g., prevalence in self-descriptions or QuSTT) and that this method may complement traditional methods for testing the validity of psychological measures.


Electrically conductive [Fe4S4]-based organometallic polymers.
Tailoring the molecular components of hybrid organic-inorganic materials enables precise control over their electronic properties. Designing electrically conductive coordination materials, e.g. metal-organic frameworks (MOFs), has relied on single-metal nodes because the metal-oxo clusters present in the vast majority of MOFs are not suitable for electrical conduction due to their localized electron orbitals. Therefore, the development of metal-cluster nodes with delocalized bonding would greatly expand the structural and electrochemical tunability of conductive materials. Whereas the cuboidal [Fe4S4] cluster is a ubiquitous cofactor for electron transport in biological systems, few electrically conductive artificial materials employ the [Fe4S4] cluster as a building unit due to the lack of suitable bridging linkers. In this work, we bridge the [Fe4S4] clusters with ditopic N-heterocyclic carbene (NHC) linkers through charge-delocalized Fe-C bonds that enhance electronic communication between the clusters. [Fe4S4Cl2(ditopic NHC)] exhibits a high electrical conductivity of 1 mS cm-1 at 25 °C, surpassing the conductivity of related but less covalent materials. These results highlight that synthetic control over individual bonds is critical to the design of long-range behavior in semiconductors.


Minimising the risk of infection: a peri-operative checklist.
The purpose of this article is to provide the reader with a seven-step checklist that could help in minimising the risk of PJI. The check list includes strategies that can be implemented pre-operatively such as medical optimisation, and reduction of the bioburden by effective skin preparation or actions taking during surgery such as administration of timely and appropriate antibiotics or blood conservation, and finally implementation of post-operative protocols such as efforts to minimise wound drainage and haematoma formation.


Long-term impact of obesity on patient-reported outcomes and patient satisfaction after lumbar spine surgery: an observational study.
Obese body habitus is a challenging issue to address in lumbar spine surgery. There is a lack of consensus on the long-term influence of BMI on patient-reported outcomes and satisfaction. This study aimed to examine the differences in patient-reported outcomes over the course of 12 and 24 months among BMI classifications of patients who underwent lumbar surgery. A search was performed using the Quality Outcomes Database (QOD) Spine Registry from 2012 to 2018 to identify patients who underwent lumbar surgery and had either a 12- or 24-month follow-up. Patients were categorized based on their BMI as normal weight (≤ 25 kg/m2), overweight (25-30 kg/m2), obese (30-40 kg/m2), and morbidly obese (> 40 kg/m2). Outcomes included the Oswestry Disability Index (ODI) and the visual analog scale (VAS) for back pain (BP) and leg pain (LP), and patient satisfaction was measured at 12 and 24 months postoperatively. A total of 31,765 patients were included. At both the 12- and 24-month follow-ups, those who were obese and morbidly obese had worse ODI, VAS-BP, and VAS-LP scores (all p < 0.01) and more frequently rated their satisfaction as "I am the same or worse than before treatment" (all p < 0.01) compared with those who were normal weight. Receiver operating characteristic curve analysis revealed that the BMI cutoffs for predicting worsening disability and surgery dissatisfaction were 30.1 kg/m2 and 29.9 kg/m2 for the 12- and 24-month follow-ups, respectively. Higher BMI was associated with poorer patient-reported outcomes and satisfaction at both the 12- and 24-month follow-ups. BMI of 30 kg/m2 is the cutoff for predicting worse patient outcomes after lumbar surgery.


Spermatocytic Tumor With Sarcoma: A Rare Testicular Neoplasm.
Spermatocytic tumor, formerly known as spermatocytic seminoma, is an uncommon testicular neoplasm which is a distinct clinicopathologic entity from classic seminoma. These tumors are not associated with germ cell neoplasia in situ, other germ cell tumors, or isochromosome 12p. Although typically, these tumors have an excellent prognosis occasional cases are associated with sarcoma and have a very poor prognosis. We present a case of spermatocytic tumor with sarcoma showing a chondrosarcomatous component, discuss the pathologic findings and differential diagnosis and provide follow-up information.


Batch tautomer generation with MolTPC.
Besides all their conformational degrees of freedom, drug-like molecules and natural products often also undergo tautomeric interconversions. Compared to the huge efforts made in experimental investigation of tautomerism, open and free algorithmic solutions for prototropic tautomer generation are surprisingly rare. The few freely available software packages limit their output to a subset of the possible configurational space by sometimes unwanted prior assumptions and complete neglection of ring-chain tautomerism. Here, we describe an adjustable fully automatic tautomer enumeration approach, which is freely available and also incorporates the detection of ring-chain variants. The algorithm is implemented in the MolTPC framework and accessible on SourceForge.


Using Clinical Vignettes to Assess Quality of Care for Acute Respiratory Infections.
Overprescribing of antibiotics for acute respiratory infections (ARIs) is common. Our objective was to develop and validate a vignette-based method to estimate clinician ARI antibiotic prescribing. We surveyed physicians (n = 78) and retail clinic clinicians (n = 109) between January and September 2013. We surveyed clinicians using a set of ARI vignettes and linked the responses to electronic health record data for all ARI visits managed by these clinicians during 2012. We then created a new measure of antibiotic prescribing, the comprehensive ARI management rate. This was defined as not prescribing antibiotics for antibiotic-inappropriate diagnoses and prescribing guideline-concordant antibiotics for antibiotic-appropriate diagnoses (and also included appropriate use of streptococcal testing for the pharyngitis vignettes). We compared the vignette-based and chart-based comprehensive ARI management at the clinician level. We then identified the combination of vignettes that best predicted comprehensive ARI management rates, using a partitioning algorithm. Responses to 3 vignettes partitioned clinicians into 4 groups with chart-based comprehensive ARI management rates of 61% (n = 121), 50% (n = 47), 31% (n = 12), and 22% (n = 7). Responses to 3 clinical vignettes can identify clinicians with relatively poor quality ARI antibiotic prescribing. Vignettes may be a mechanism to target clinicians for quality improvement efforts.


"We Need a System that's Not Designed to Fail Māori": Experiences of Racism Related to Kidney Transplantation in Aotearoa New Zealand.
Reported experiences of racism in Aotearoa New Zealand are consistently associated with negative measures of health, self-rated health, life satisfaction, and reduced access to high-quality healthcare with subsequent poor health outcomes. In this paper, we report on perceptions and experiences of prejudice and racism by Indigenous Māori with kidney disease and their family members and donors who took part in a wider study about experiences of kidney transplantation. We conducted semi-structured interviews with 40 Māori between September and December 2020. Participants included those with kidney disease who had considered, were being worked up for, or who had already received a kidney transplant as well as family members and potential or previous donors. We examined the data for experiences of racism using a theoretical framework for racism on three levels: institutionalised racism, personally mediated racism, and internalised racism. We identified subthemes at each level of racism: institutional (excluded and devalued by health system; disease stigmatization; discriminatory body weight criteria, lack of power), personally mediated (experiencing racial profiling; explicit racism), and internalized racism (shame and unworthiness to receive a transplant). The wide-reaching experiences and perceptions of racism described by participants with kidney disease and their families in this research point to an unfair health system and suggest that racism may be contributing to kidney transplantation inequity in Aotearoa New Zealand. Addressing racism at all levels is imperative if we are to address inequitable outcomes for Māori requiring kidney transplantation.


Analysis of feeder bus network design and scheduling problems.
A growing concern for public transit is its inability to shift passenger's mode from private to public transport. In order to overcome this problem, a more developed feeder bus network and matched schedules will play important roles. The present paper aims to review some of the studies performed on Feeder Bus Network Design and Scheduling Problem (FNDSP) based on three distinctive parts of the FNDSP setup, namely, problem description, problem characteristics, and solution approaches. The problems consist of different subproblems including data preparation, feeder bus network design, route generation, and feeder bus scheduling. Subsequently, descriptive analysis and classification of previous works are presented to highlight the main characteristics and solution methods. Finally, some of the issues and trends for future research are identified. This paper is targeted at dealing with the FNDSP to exhibit strategic and tactical goals and also contributes to the unification of the field which might be a useful complement to the few existing reviews.


Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells' vulnerability to DNA-damaging agents.
Genomic instability plays a pathological role in various malignancies, including acute myeloid leukemia (AML), and thus represents a potential therapeutic target. Recent studies demonstrate that SIRT6, a NAD+-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity in different tumor cells. Here, we demonstrate that also CD34+ blasts from AML patients show ongoing DNA damage and SIRT6 overexpression. Indeed, we identified a poor-prognostic subset of patients, with widespread instability, which relies on SIRT6 to compensate for DNA-replication stress. As a result, SIRT6 depletion compromises the ability of leukemia cells to repair DNA double-strand breaks that, in turn, increases their sensitivity to daunorubicin and Ara-C, both in vitro and in vivo In contrast, low SIRT6 levels observed in normal CD34+ hematopoietic progenitors explain their weaker sensitivity to genotoxic stress. Intriguingly, we have identified DNA-PKcs and CtIP deacetylation as crucial for SIRT6-mediated DNA repair. Together, our data suggest that inactivation of SIRT6 in leukemia cells leads to disruption of DNA-repair mechanisms, genomic instability and aggressive AML. This synthetic lethal approach, enhancing DNA damage while concomitantly blocking repair responses, provides the rationale for the clinical evaluation of SIRT6 modulators in the treatment of leukemia.


Randomized study of the effects of cocoa-rich chocolate on the ventricle-arterial coupling and vascular function of young, healthy adults.
The aim of this study was to evaluate and explore the benefits of long-term dark chocolate intake in young, healthy adults by measuring cardiovascular function. A randomized study was conducted with 30 healthy participants ages 18 to 27 y. Half of the participants ingested a 20-g dose of lower cocoa chocolate (LCC; ∼55%; 12.6 ± 1.4 mg equivalent of epicatechin/g) and the others ingested a daily dose of 20 g of higher cocoa chocolate (HCC; ∼90%; 18.2 ± 2.6 mg equivalent of epicatechin/g). A baseline evaluation was performed before the participants started ingesting the assigned chocolate for a 30-d period, after which a final evaluation was performed. Each evaluation included heart ultrasonography, carotid-femoral pulse wave velocity (PWV) and carotid pulse wave analysis, flow-mediated slowing (FMS), and an analysis of the ventricular-arterial coupling (VAC), which reflects the matching between the aorta and the left ventricle (ratio of arterial elastance to left ventricle elastance). The baseline evaluation presented similar values within normal range in both groups. The positive vascular effects were overall more distinct in the group eating the HCC. No structural modifications on the heart were found after the intervention, notwithstanding cardiac function was improved on certain functional parameters in the HCC group only. A statistically significant improvement was depicted over the brachial and central systolic and pulse pressures in the HCC group, and a trend for improvement in the reflected waves component (Aix) and the FMS was also observed in the HCC, but not in the LCC group. VAC parameters were similar at baseline between groups, but showed a significant improvement in the HCC group after intervention, increasing from 0.674 to 0.719 (P = 0.004), so that the post-intervention VAC was significantly higher in the HCC group than in the LCC group (P < 0.05). In addition, significant variation was observed in both groups regarding arterial and left ventricle elastances, stroke work, and potential energy, with greater mean differences identified in the HCC group. This study demonstrated that regular consumption of HCC has beneficial effects on the cardiovascular system in young, healthy adults, improving vascular function by reducing central brachial artery pressures and promoting vascular relaxation, and thus enhancing the matching of the arterial system with the left ventricle.


A Digital Hardware Realization for Spiking Model of Cutaneous Mechanoreceptor.
Inspired by the biology of human tactile perception, a hardware neuromorphic approach is proposed for spiking model of mechanoreceptors to encode the input force. In this way, a digital circuit is designed for a slowly adapting type I (SA-I) and fast adapting type I (FA-I) mechanoreceptors to be implemented on a low-cost digital hardware, such as field-programmable gate array (FPGA). This system computationally replicates the neural firing responses of both afferents. Then, comparative simulations are shown. The spiking models of mechanoreceptors are first simulated in MATLAB and next the digital neuromorphic circuits simulated in VIVADO are also compared to show that obtained results are in good agreement both quantitatively and qualitatively. Finally, we test the performance of the proposed digital mechanoreceptors in hardware using a prepared experimental set up. Hardware synthesis and physical realization on FPGA indicate that the digital mechanoreceptors are able to replicate essential characteristics of different firing patterns including bursting and spiking responses of the SA-I and FA-I mechanoreceptors. In addition to parallel computation, a main advantage of this method is that the mechanoreceptor digital circuits can be implemented in real-time through low-power neuromorphic hardware. This novel engineering framework is generally suitable for use in robotic and hand-prosthetic applications, so progressing the state of the art for tactile sensing.


Pulsed laser imaging of Ca(2+) influx in a neuroendocrine terminal.
The surge of Ca(2+) that triggers vesicle fusion is shaped by the distribution of Ca(2+) channels and the physical relationship between those channels and the exocytotic apparatus. Although channels and the release apparatus are thought to be tightly associated at fast synapses, the arrangement at neuroendocrine cells is less clear. The distribution of Ca(2+) influx near release sites is difficult to determine because of spatial and temporal limitations on Ca(2+) imaging techniques. We now present spatially resolved images of Ca(2+) influx into rat neuroendocrine terminals on a millisecond time scale. Images of voltage-dependent Ca(2+) influx into neurohypophysial terminals were captured after excitation of Ca(2+)-sensitive dyes with pulses of laser light lasting a fraction of a microsecond. Submembranous Ca(2+) increases were detected during the first millisecond of an evoked Ca(2+) tail current. Steep gradients of Ca(2+) were evident, with concentrations near the membrane reaching above 1 microM during a 30 msec depolarization. Ca(2+) influx appeared evenly distributed, even when diffusion was restricted with an exogenous Ca(2+) chelator. During longer depolarizations, mean and peak Ca(2+) concentrations reached an asymptote in parallel, suggesting that Ca(2+) binding proteins near the membrane rapidly buffer Ca(2+) and do not become saturated during prolonged influx. These data support the hypothesis that exocytosis is activated in these terminals by the summation of influx through multiple, randomly spaced Ca(2+) channels.


Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons.
The central pattern generator can generate locomotor-like rhythmic activity in the spinal cord in the absence of descending and peripheral inputs, but the motor pattern is regulated by feedback from peripheral sensory inputs that adjust motor outputs to external stimuli. To elucidate the possible role of Hb9-expressing interneurons (Hb9 INs) in the locomotor circuitry, we investigated whether their induced oscillatory activity is modulated by low-threshold afferents in the isolated spinal cords of neonatal Hb9:eGFP transgenic mice. Low-intensity stimulation of segmental afferents generated short-latency, monosynaptic excitatory responses in 62% of Hb9 INs. These were associated with longer-latency (approximately 13 ms) excitatory postsynaptic currents that were evoked in all Hb9 INs, probably by slow conducting afferents that synapse directly onto them. Concomitant morphological analysis confirmed that afferent axons with immunoreactive expression of vesicular glutamate transporter-1 and parvalbumin, presumably from primary afferents, contacted somata and dendrites of all Hb9 INs. Most of the putative synaptic contacts were on distal dendrites that extended to an area with profuse afferent projections. We next examined whether low-threshold afferents in upper (flexor-related) and lower (extensor-related) lumbar segments altered the timing of neurochemically induced locomotor-like rhythms in Hb9 INs and motoneurons. Excitation of flexor-related afferents during the flexor phase delayed the onset of subsequent cycles in both Hb9 INs and segmental motoneurons while maintaining the phase relationship between them. The in-phase correlation between voltage oscillations in Hb9 INs and motor bursts also persisted during the two- to threefold increase in cycle period triggered by extensor-related afferents. Our findings that low-threshold, presumably muscle afferents, synapse directly onto these interneurons and perturb their induced locomotor-like membrane oscillations in a pattern that remains phase-locked with motor bursts support the hypothesis that Hb9 INs are part of the sensorimotor circuitry that regulates the pattern of locomotor rhythms in the isolated cord.


Phospho-regulation of KIBRA by CDK1 and CDC14 phosphatase controls cell-cycle progression.
KIBRA (kidney- and brain-expressed protein) is a novel regulator of the Hippo pathway, which controls tissue growth and tumorigenesis by regulating both cell proliferation and apoptosis. In mammals, KIBRA is associated with memory performance. The physiological function and regulation of KIBRA in non-neuronal cells remain largely unclear. We reported recently that KIBRA is phosphorylated by the mitotic kinases Aurora-A and -B. In the present study, we have expanded our analysis of KIBRA's role in cell-cycle progression. We show that KIBRA is also phosphorylated by CDK1 (cyclin-dependent kinase 1) in response to spindle damage stress. We have identified KIBRA Ser(542) and Ser(931) as main phosphorylation sites for CDK1 both in vitro and in vivo. Moreover, we found that the CDC (cell division cycle) 14A/B phosphatases associate with KIBRA, and CDK1-non-phosphorylatable KIBRA has greatly reduced interaction with CDC14B. CDC14A/B dephosphorylate CDK1-phosphorylated KIBRA in vitro and in cells. By using inducible-expression cell lines, we show further that phospho-regulation of KIBRA by CDK1 and CDC14 is involved in mitotic exit under spindle stress. Our results reveal a new mechanism through which KIBRA regulates cell-cycle progression.


Hemochromatosis and iron-overload screening in a racially diverse population.
Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 mug per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites.


Future trends in managing hepatitis C.
Despite recent improvements in the treatment of patients who have chronic hepatitis C, a large proportion of patients do not achieve viral clearance. Treatment regimens are also costly, associated with significant morbidity, require substantial patient commitment, and are not appropriate for all patients. Therefore, it is important to maximize and enhance current therapeutic approaches and to investigate new approaches and therapies. Because the ability to maintain adherence to current treatment is associated with higher sustained virologic response rates (particularly in patients infected with genotype 1), strategies directed at patients and support staff to promote treatment adherence are important. Other strategies to enhance current therapy include alternative interferons (IFNs)/cytokines and new IFN delivery systems. Current therapy may also be enhanced by new ribavirin (RBV) analogs with an improved safety profile or by the addition of other immunomodulatory agents such as inosine 5'-monophosphate dehydrogenase inhibitors, histamine dihydrochloride, thymosin alfa 1, and amantadine. Some of these agents have demonstrated promising results, although further evaluation is required. Greater knowledge of the molecular biology of the hepatitis C virus (HCV) holds promise for the development of targeted therapies such as specific inhibitors of HCV polymerase, protease, or helicase, as well as therapeutic vaccines. Other potential molecular-based therapies include antisense oligonucleotides, ribozymes, and short interfering ribonucleic acid (RNA) molecules. Therapies aimed at reducing or preventing the development of fibrosis are also under investigation. Multiple-drug regimens will likely be required to enhance viral clearance and reduce viral resistance, while providing greater tolerability.


Biological rhythms and epilepsy treatment.
Approximately one-third of patients with epilepsy are drug-refractory, necessitating novel treatment approaches. Chronopharmacology, which adjusts pharmacological treatment to physiological variations in seizure susceptibility and drug responsiveness, offers a promising strategy to enhance efficacy and tolerance. This narrative review provides an overview of the biological foundations for rhythms in seizure activity, clinical implications of seizure patterns through case reports, and the potential of chronopharmacological strategies to improve treatment. Biological rhythms, including circadian and infradian rhythms, play an important role in epilepsy. Understanding seizure patterns may help individualize treatment decisions and optimize therapeutic outcomes. Altering drug concentrations based on seizure risk periods, adjusting administration times, and exploring hormone therapy are potential strategies. Large-scale randomized controlled trials are needed to evaluate the efficacy and safety of differential and intermittent treatment approaches. By tailoring treatment to individual seizure patterns and pharmacological properties, chronopharmacology offers a personalized approach to improve outcomes in patients with epilepsy.


Development of a self-cleaning sensor membrane for implantable biosensors.
Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature-modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self-cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles ( approximately 219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33-34 degrees C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature-modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP-H2B 3T3 fibroblast cells.


Identification of highly synchronized subnetworks from gene expression data.
There has been a growing interest in identifying context-specific active protein-protein interaction (PPI) subnetworks through integration of PPI and time course gene expression data. However the interaction dynamics during the biological process under study has not been sufficiently considered previously. Here we propose a topology-phase locking (TopoPL) based scoring metric for identifying active PPI subnetworks from time series expression data. First the temporal coordination in gene expression changes is evaluated through phase locking analysis; The results are subsequently integrated with PPI to define an activity score for each PPI subnetwork, based on individual member expression, as well topological characteristics of the PPI network and of the expression temporal coordination network; Lastly, the subnetworks with the top scores in the whole PPI network are identified through simulated annealing search. Application of TopoPL to simulated data and to the yeast cell cycle data showed that it can more sensitively identify biologically meaningful subnetworks than the method that only utilizes the static PPI topology, or the additive scoring method. Using TopoPL we identified a core subnetwork with 49 genes important to yeast cell cycle. Interestingly, this core contains a protein complex known to be related to arrangement of ribosome subunits that exhibit extremely high gene expression synchronization. Inclusion of interaction dynamics is important to the identification of relevant gene networks.


Vitamin C and immunity: an assessment of the evidence.
The high concentration of ascorbate in leucocytes and its rapid expenditure during infection and phagocytosis suggests a role for the vitamin in the immune process. Evidence published to date shows an involvement in the migration and phagocytosis by macrophages and leucocytes, as well as the induction and expression of delayed hypersensitivity. Its effect on antibody production and complement levels is controversial but probably minimal. This study suggests there is room for further investigation into the effect of ascorbate on immunity, particularly with defined populations, but cautions the use of megadose therapy.


Transforming-growth-factor-beta activation elements in the distal promoter regions of the rat alpha 1 type I collagen gene.
We have located a cis-acting element (alpha 1-TAE) within the promoter sequences of the rat collagen alpha 1(I) gene (COL1A1) 1600 bases upstream of the transcription start site which mediates transcriptional activation by transforming growth factor beta (TGF-beta). The functional significance of this region was established by (1) deletion analysis of the alpha 1(I) promoter cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and (2) by co-transfection of promoter constructs with double-stranded oligonucleotides. DNA-mobility-shift assays with radiolabelled alpha 1-TAE demonstrated increased nuclear binding activity after TGF-beta stimulation. Oligonucleotides encoding the alpha 1-TAE, additional upstream regions within the alpha 1(I) promoter, as well as consensus nuclear-factor-1 (NF-1) sequences, competed with the alpha 1-TAE sequence. The two collagen type I genes are stimulated by TGF-beta through different regions of their promoters.


Is Language Production Planning Emergent From Action Planning? A Preliminary Investigation.
The nature of syntactic planning for language production may reflect language-specific processes, but an alternative is that syntactic planning is an example of more domain-general action planning processes. If so, language and non-linguistic action planning should have identifiable commonalities, consistent with an underlying shared system. Action and language research have had little contact, however, and such comparisons are therefore lacking. Here, we address this gap by taking advantage of a striking similarity between two phenomena in language and action production. One is known as syntactic priming-the tendency to re-use a recently produced sentence structure-and the second is hysteresis-the tendency to re-use a previously executed abstract action plan, such as a limb movement. We examined syntactic priming/hysteresis in parallel language and action tasks intermixed in a single experimental session. Our goals were to establish the feasibility of investigating language and action planning within the same participants and to inform debates on the language-specific vs. domain-general nature of planning systems. In both action and language tasks, target trials afforded two alternative orders of subcomponents in the participant's response: in the language task, a picture could be described with two different word orders, and in the action task, locations on a touch screen could be touched in two different orders. Prime trials preceding the target trial promoted one of two plans in the respective domain. Manipulations yielded higher rates of primed behavior in both tasks. In an exploratory cross-domain analysis, there was some evidence for stronger priming effects in some combinations of action and language priming conditions than others. These results establish a method for investigating the degree to which language planning is part of a domain-general action planning system.


Alternating carboplatin and doxorubicin as adjunctive chemotherapy to amputation or limb-sparing surgery in the treatment of appendicular osteosarcoma in dogs.
Thirty-two dogs with appendicular osteosarcoma treated by amputation or limb sparing had adjuvant chemotherapy of alternating doses of carboplatin (300 mg/m2 IV) and doxorubicin (30 mg/m2 IV) every 21 days for a total of 3 cycles. Efficacy, toxicity, and previously identified prognostic factors for osteosarcoma were evaluated. The median progression free survival was 227 days (range 180-274), and the median overall survival was 320 days (range 153-487). The 1-year survival rate was 48%, and the 2-year survival rate was 18%. Age, sex, surgical procedure, and alkaline phosphatase activity above the reference ranges were not prognostic for survival. There was minimal toxicity associated with the chemotherapy. This protocol could be useful for the adjuvant treatment of appendicular osteosarcoma of dogs.


Drugs for preventing tuberculosis in HIV infected persons.
People with HIV have a increased risk of developing tuberculosis. Preventive therapy may help prevent progression of tuberculosis infection to disease. The objective of this review was to assess the effects of preventive therapy with anti-tuberculosis drugs in people with HIV infection. The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Researchers in the field were contacted. Randomised trials of anti-tuberculosis drugs in people with HIV infection but without evidence of active tuberculosis. One reviewer assessed eligibility and trial quality. Study authors were contacted for additional information. Six trials were included. Compared to placebo, preventive therapy was associated with a lower incidence of active tuberculosis (relative risk 0.54, 95% confidence interval 0.39 to 0.76). Risk of death (relative risk 0.96, 95% confidence interval 0.82 to 1.13) was not significantly different in the two groups. Incidence of tuberculosis was reduced in people with a positive tuberculin skin test (relative risk 0.24, 95% confidence interval 0.14 to 0.40), but was not significantly lower in those with a negative skin test (relative risk 0.87, 95% confidence interval 0.56 to 1.36). Similarly death was less frequent in those with a positive skin test who received preventive therapy (relative risk 0.77, 95% confidence interval 0.58 to 1.03), but this difference was not observed among those with a negative skin test (relative risk 1.07, 95% confidence interval 0.88 to 1.30). Each regimen (isoniazid alone, isoniazid plus rifampicin, isoniazid plus rifampicin plus pyrazinamide, rifampicin plus pyrazinamide) had similar protective effects against active tuberculosis for people with positive skin tests. Preventive therapy appears to be effective in reducing incidence of tuberculosis, and death from tuberculosis in HIV infected adults with a positive tuberculin skin test, at least in the short to medium term.


Sexual trauma and post-traumatic stress among African female refugees and migrants in South Africa.
While there is considerable research in developed countries on the nature and extent of post-traumatic stress among refugees and migrants, few report on female Africans migrating within Africa. The aim of this study was to investigate the association between exposure to traumatic life events and post-traumatic stress disorder risk in refugees and migrants in Durban, South Africa, with specific focus on sexual trauma events among women. Interviews were conducted on 157 consenting non-South African adults using a sociodemographic questionnaire, Life Events Checklist (documenting traumatic events experienced) and the Harvard Trauma Questionnaire (measuring post-traumatic symptomatology). Associations between total number of traumatic events and post-traumatic stress were explored using adjusted regression models. The results of one model indicated that greater numbers of traumatic life events experienced by women were associated with raised odds of post-traumatic stress disorder risk (β = 1.48; p < 0.001). Another model indicated that exposure to sexual trauma events were associated with greater odds of post-traumatic stress disorder risk (β = 4.09; p = 0.02). Our findings highlight the critical importance of mental health service for females with history of sexual traumatic events for this vulnerable population.


Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.
To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism. ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1β, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1β, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB. Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation. Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.


Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in Facioscapulohumeral Muscular Dystrophy.
Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD.


Investigation of the impact of radiation dose on hormones, biologically active metabolites and immunoglobulins in Chernobyl accident recovery workers.
One hundred twenty-five Chernobyl accident recovery workers (liquidators) who were exposed to low-dose radiation were studied over a period of 4-6 years for changes in levels of hormones, arachidonic acid metabolites and cyclic nucleotides. Some significant changes were observed, especially in the levels of metabolites that are regulators of cell functions. In comparison to controls, there were increased levels of thyroxin, cortisol, thromboxane B2, and immunoglobulins G, A and M, and reduced levels of growth hormone, cyclic nucleotides and 6-keto-prostaglandin F1. The degree or presence of these metabolite imbalances did not correlate with the level of the radiation dose received. The only change found that did relate to the radiation dose received was a statistically significant increase in levels of biomarkers for oxidative stress, seen in workers who received higher doses.


The effect of crop protection strategy on pest and beneficials incidence in protected crops.
This study took place in the Oeste region from 1996-1999 and it intended to analyse if the crop protection strategy followed by the farmer influenced the arthropod incidence and the natural control in protected vegetable crops under Mediterranean conditions. The observations were made fortnightly (Autumn/Winter) or weekly (Spring/Summer) in 30-60 plants/parcel (1 plant/35 m2) in order to evaluate incidences. Samples of pests and natural enemies were collected for systematic identification in two greenhouses for each protection strategy (traditional chemical control (TCC), integrated pest management (IPM) and pest control allowed in organic farming (OF)) in lettuce, tomato, green beans and cucumber. Data on incidence of mites, aphids, caterpillars, leafminers, whiteflies, thrips and respective natural enemies were registered as well as phytosanitary treatments performed (farmers' information and/or in loco traces). The leafminers were the pest whose incidence more often presented significant statistical differences between the studied protection strategies. In relation to this pest, the main results obtained were: a higher feeding punctures incidence in TCC than in IPM; higher incidence of adults, mines and feeding punctures in TCC than in OF; and a higher mines' incidence in IPM than in OF. Both in TCC and IPM high percentages of plants with mines were found although without an adult proportional presence. In the first case this was due to the repeatedly phytosanitary treatments applied; in the second case it was due to the natural control, since in IPM and OF greenhouses the collected larvae were mostly parasitized or dead. In spite of the fact these two strategies have as final result a similar mines and adults incidence, their production and environmental costs are quite different. Significant differences at the beneficials' population level between TCC greenhouses and IPM or OF greenhouses were found. As the farmers did no biological treatments these differences are related to different levels of beneficial populations due to different secondary effects of the pesticides applied.


The World Health Organization African regional training course for mid-level immunization managers: lessons and future directions.
The World Health Organization (WHO) African regional training course for mid-level managers (MLM) of immunization programs launched in 2004, has undergone revisions across the years, to accommodate new developments in the field. In 2016, the WHO African regional office conducted a thorough review of the course materials and delivery methods to document lessons to help improve the course. Some of the gaps included inappropriate selection of trainees, inadequate focus on skills development, heavy reliance on text and presentations, as well as resource limitations to reach a critical mass of learners. The regional office worked with Bull City Learning to redesign the course materials along carefully crafted course objectives and curricula, and to assist facilitators to better deliver the course. In addition, the materials were converted into online learning tools. Within 10 months, a total of 3011 learners were enrolled in the online MLM training platform and earned a total of 9209 certificates. The MLM course will continue to be highly relevant as the immunization area of work expands significantly, with the addition of new vaccines, introduction of new technologies, and expanding opportunities for online learning.


Invalid Baseline Testing with ImPACT: Does Sandbagging Occur with High School Athletes?
The aim of this large-scale research was to determine the frequency of valid, invalid, and sandbagging results in ImPACT baseline testing of high school athletes. This retrospective study identified valid, invalid (identified by five embedded Invalidity Indicators), and sandbagging (identified by three "red flags") results in the ImPACT baseline test scores of 6,346 high school athletes. In addition, the ImPACT postconcussion scores of 266 athletes who sustained a concussion during the school year were evaluated to compare the baseline-to-postconcussion changes of valid versus a combined group of invalid and sandbagging scorers. There were 3,299 (51.99%) athletes who had valid baseline scores, 269 (4.24%) had invalid scores, and 3,009 (47.42%) had sandbagging scores. (There were 231 who obtained both invalidity and sandbagging scores.) The overall difference in baseline-to-postconcussion changes between the valid scorers and the combined group of invalid and sandbagging scorers was statistically significant. The high rate of athletes who had invalid and sandbagging scores raised concern that the underperformance of baseline testing occurs more commonly than is probably realized by those who utilize computerized neuropsychological testing with high school athletes. Accordingly, efforts are needed to improve test administration procedures so that maximal attention and effort can be maintained among the test takers. In the meantime, increased caution is called for in employing the baseline-to-postconcussion paradigm when return-to-play decisions are made.


Serum-mediated depression of neutrophil chemiluminescence following blunt trauma.
To investigate one possible mechanism responsible for decreased neutrophil bactericidal activity following trauma, the chemiluminescence response of normal neutrophils was measured following incubation in nonseptic and septic serum from 19 blunt trauma patients. Incubation of normal neutrophils in septic patients' sera (61 studies) resulted in a marked decrease in the chemiluminescence response (36 +/- 26% of control), compared to incubation in nonseptic sera (92 studies, 80 +/- 53% of control; p less than 0.005). This difference between nonseptic and septic serum was apparent immediately after injury, prior to the development of sepsis (47 +/- 4% versus 77 +/- 12%; p less than 0.05). The depression of the CL response was due to a suppressive factor present in septic patients' sera. This factor was nondialyzable and was present in high performance liquid chromatography (HPLC) fractions containing protein of molecular weight 50 to 100,000. Removal of albumin using Affigel-blue did not remove the suppressive factor. In contrast to the suppressive effect of septic trauma serum, septic patients' neutrophils had a normal chemiluminescence response after their isolation and washing. We conclude that trauma results in the generation of a serum factor that suppresses neutrophil chemiluminescence and that is present in greater amounts in patients who eventually become septic. This factor may be responsible for the decreased bactericidal activity and depressed host defense following injury.


Relationships among neurocognition, symptoms, and functioning in treatment-resistant depression.
Treatment-resistant depression (TRD) refers to a condition where individuals with major depressive disorder have inadequate or no response to treatment. Although functional disability is a prominent and costly feature of treatment resistance, very little is known about the factors that contribute to and maintain functional impairment in TRD. This is the first study to report the neurocognitive profile of TRD and the relationships among neurocognition, symptoms, and functioning in this syndrome. Results indicated that patients with TRD (N = 33) exhibit mildly reduced performance across all neurocognitive domains with a superimposed moderate impairment in verbal working memory. Neurocognition was associated with functional competence (what one can do), whereas depressive symptoms were associated with functional performance (what one actually does). Understanding the psychological mechanisms related to functioning may help us move toward recovery in this chronically ill group.


Photoinduced intramolecular electron transfer in ruthenium and osmium polyads: insights from theory.
Ru(II) and Os(II) complexes (P) of [4'-(p-phenyl)]terpyridyl ligand (ptpy) derivatized with an electron acceptor (A) of the triphenylpyridinium (H3TP+) type have been recently proposed as functional models for electron-transfer (ET) processes in the context of artificial photosynthesis. These inorganic dyads, P-A, are expected to undergo intramolecular photoinduced ET to form a charge separated (CS) state of pivotal interest. To draw a complete picture of possible ET processes, the ground- and excited-state properties of these complexes, both in their native and monoreduced forms, have been studied by the means of density functional theory (DFT). A time-dependent-DFT approach (TDDFT) was used to interpret the electronic spectra, while additional spectroscopic measurements have been carried out in order to complete the available experimental information and to further confirm the theoretical issues. Besides the noticeable quantitative agreement between computed and experimental absorption spectra, our results allow us to clarify, by first principles, the actual nature and interplay of the electronic and geometrical coupling between the acceptor moiety and the photosensitizer. The possibility of a direct (optical) ET from the ground state to the targeted *[P+-A-] CS state is theoretically postulated and found to be consistent with available photophysical data (transient absorption spectroscopy). Concerning backward ET (from the CS state), the occurrence of a quinoidal-like electronic redistribution inherent to the photoreduced acceptor-ligand is proposed to favor efficient charge recombination.


Asthma terminology and classification in hospital records.
Asthma is a national health priority area in Australia, and there is significant interest in capturing relevant detail about hospitalisations as a result of asthma. A public submission received by the National Centre for Classification in Health from a large teaching hospital in Victoria suggested that current classification terminology in ICD-10-AM did not adequately reflect the terms recorded in clinical inpatient records, and that patterns and severity of asthma better reflected current clinical terminology in Australian hospitals. The purpose of this study was to determine the validity of the public submission and inform future changes to ICD-10-AM. A representative sample of over 3000 asthma records across Australia and New Zealand were extracted, and the asthma terminology documented and codes assigned were recorded and analysed. The study concluded that there was little support for either pattern terminology or the current classification terminology; however, severity of asthma was commonly used in asthma documentation.


Protein depletion and replenishment in mice: different roles of muscle and liver.
Fully grown male CD-1 mice, fed a protein-free diet for 3 days, received 1 g of starch with or without 300 mg casein by intragastric intubation. We surveyed the acute effects of these nutrients on protein synthesis in all tissues (by extrapolating to infinity the incorporation of radioactive leucine after its injection in massive doses) and protein degradation in skeletal muscle and liver (by the accumulation of bestatin-induced peptide intermediates). Muscle proteolysis was the major source of N during depletion. Compared with postabsorptive animals, starch suppressed muscle protein loss (synthesis +21%, degradation -24%, P < 0.01) and stimulated hepatic proteolysis (degradation +28%, P < 0.01). Addition of casein to the starch was anabolic in liver (synthesis +41%, degradation -33%, P < 0.01), gastrointestinal tract, pancreas, and skin (synthesis +38, +69 and +38%, respectively, P < 0.01) but had no effect on muscle. Protein turnover proved uniquely sensitive to the dietary supply of carbohydrates in muscle and to the endogenous or exogenous supply of amino acids in liver.


Inverse Relationship between Adherence to the Mediterranean Diet and Serum Cystatin C Levels.
The aim of the present study was to examine serum cystatin C levels in association with the Mediterranean diet in a healthy Greek population. Cystatin C together with basic clinical chemistry tests was measured in a total of 490 adults (46±16 years, 40% of males), who underwent an annual health check. Demographic, anthropometric and lifestyle characteristics were recorded, while adherence to the Mediterranean diet was evaluated through the MedDietScore (0-55). The mean level of serum cystatin C was 0.84 mg/L, while men had increased serum cystatin C levels compared to women (0.86 mg/L vs. 0.83 mg/L, respectively, 0.017). After adjusting for age, gender, body mass index, smoking status, hypertension, diabetes, hypercholesterolemia, estimated glomerular filtration rate (eGFR), albumin and ferritin levels, each unit increase in MedDietScore led to 0.002 mg/dL drop off in cystatin C serum levels. We have demonstrated an inverse relationship between the MedDietScore and serum cystatin C levels. Our finding that increases in MedDietScore are associated with decreases in serum cystatin C levels could imply that adherence to the Mediterranean diet may reduce the cardiovascular risk, as assessed by cystatin C, a prognostic marker of the cardiometabolic risk. This notion could have a great impact on public health.


Defining regulatory elements in the human KAI1 (CD 82) metastasis suppressor gene.
The human KAI1 metastasis suppressor gene encodes for a 267 amino acid plasma membrane glycoprotein, which has four transmembrane domains and one large and one small extracellular domain. Plasma membrane expression of KAI1 is downregulated during the progression of several cancers to a metastatic state, including prostate, lung, and pancreatic cancers. To elucidate the mechanisms for this downregulation, an understanding of its transcriptional regulation is critical. Therefore, a set of luciferase reporter gene plasmid constructs were generated containing various 5' flanking regions to the transcription initiation site, with or without the first exon and a portion of the first intron of the KAI1 gene. These constructs were transfected into a series of normal and malignant prostate cell lines as well as fibroblasts and the resultant luciferase activities used to define the regulatory elements for expression of the KAI1 gene. Using this approach, the minimal KAI1 promoter was found to be 0.5 kb in size and contains two regions. The first region includes the 197 bp 5' to the transcription initiation site and the second region includes the first exon and a portion of first intron (i.e., +1 to +351 bp). This combined region result in positively regulated strong, but not epithelial specific, luciferase expression. In addition to this minimal promoter element from -197 to +351 bp, there is a second regulatory element further upstream (i.e., -735 to -197 bp), which negatively regulates luciferase expression. Additional studies of Marreiros et al. (Gene 302:155, 2003) have documented that a third regulatory element even further 5' (i.e., -922 to -846 bp) encodes an enhancer for the KAI1 gene.


The Madreporic cementless total hip arthroplasty: short-term North American experience.
Forty-four Madreporic, cementless, total hip arthroplasties performed on 41 patients were reviewed, with special attention to overall clinical results and radiologic findings. Follow-up averaged 17 months (range from 6 to 27 months). Subjectively, 87% of patients rated the results of their operation as being excellent or good; objectively, 92.5% were in the excellent or good category, using the Harris hip scale rating system. Short-term radiologic findings were of major interest, with proximal medial calcar reabsorption (7 hips), thickening of the lateral cortex at the tip of the femoral stem (2 hips) and sclerosis at the tip of the femoral component (15 hips) all being present. Complications were associated with 11 operations, but adversely affected long-term results in only two hips. The authors conclude that short-term clinical results using Madreporic total hip replacement are satisfactory. However, long-term biomechanical effects of stress shielding and use of a large, rigid, femoral component in the uncemented total hip replacement are unknown. A long-term, follow-up study is necessary to demonstrate whether the early radiologic findings in this series are progressive and whether they will result in serious morbidity with time. The authors strongly believe that the Madreporic cementless total hip arthroplasty should be used only in centres dealing with a large volume of hip conditions where staff are committed to documenting and reporting the results of surgery regularly.


Evaluation of a school-based reproductive health education program in rural South Western, Nigeria.
This quasi-experimental study compared the relative efficacy of teacher instructions alone, peer education alone, and a combination of these two on reproductive health knowledge, attitude, perceived self-efficacy and sexual practices among secondary schools students in the Ibarapa district of Southwestern Nigeria. A baseline questionnaire was administered to a systematic sample of students in four schools that were randomized into four treatment arms: teacher instructions alone (E1), peer education alone (E2), combination of teacher instruction and peer education (E3), and control. The results were used to design the contents of the interventions, which were implemented for one academic session. A follow-up survey using the same sampling procedures as baseline was conducted to measure the outcome of the intervention. The control group had superior reproductive health knowledge at baseline. By follow-up survey however, all three intervention schools showed significant knowledge gains, while the control school students' mean score increased slightly. Increase in knowledge was greatest among E3 (+5.0 points), followed by E2 (+3.4), E1 (+1.4) and C (0.3). The intervention schools showed a significant positive shift in attitude towards use of contraceptives with mean increase of 0.6, 0.5, and 0.9 points in E1, E2 and E3 respectively. Scores that measured the students' perceived self-efficacy for safe sex increased significantly among E1 (from 10.8 to 11.8) and E3 (from 10.4 to 12.6). Reported condom use was significantly higher among E2 (from 16.7 % to 62.8%) (p < 0.05) and E3 (from 22.8% to 53%) (p < 0.05) compared to El (28.6% to 47.40%) (p > 0.05) and control (from 25% to 45.8%) (p > 0.05). Overall, the students from E3 showed more improvement in knowledge, attitude and self-efficacy, than their counterparts from E2 and E3 and control. Multiple intervention strategies have greater potential of improving reproductive health of students.


Activation of nuclear factor kappa B inflammatory bowel disease.
Expression of pro-inflammatory cytokines is increased in the intestinal lamina propria of patients with inflammatory bowel disease (IBD). Nuclear factor kappa B (NF kappa B) controls transcription of inflammation genes. On activation, NF kappa B is rapidly released from its cytoplasmic inhibitor (I kappa B), transmigrates into the nucleus, and binds to DNA response elements in gene promoter regions. To investigate whether increased activation of NF kappa B is important in IBD and may be down-regulated by anti-inflammatory treatment. Activation of NF kappa B was determined by western blot assessment and electrophoretic mobility shift assay in nuclear extracts of colonic biopsy samples as well as lamina propria mononuclear cells. Nuclear levels of NF kappa B p65 are increased in lamina propria biopsy specimens from patients with Crohn's disease in comparison with patients with ulcerative colitis and controls. Increased activation of NF kappa B was detected in lamina propria mononuclear cells from patients with active IBD. Corticosteroids strongly inhibit intestinal NF kappa B activation in IBD in vivo and in vitro by stabilising the cytosolic inhibitor I kappa B alpha against activation induced degradation. In both IBDs, but particularly Crohn's disease, increased activation of NF kappa B may be involved in the regulation of the inflammatory response. Inhibition of NF kappa B activation may represent a mechanism by which steroids exert an anti-inflammatory effect in IBD.


Chronic ethanol reduces immunologically detectable Gq alpha/11 alpha in NG108-15 cells.
Recent work has shown that chronic ethanol treatment inhibits receptor-stimulated phosphoinositide hydrolysis in NG108-15 cells and that ethanol exerts this effect primarily at the level of the guanine-nucleotide binding protein (G protein). Here we investigated the effects of ethanol exposure on the expression of Gq alpha/11 alpha, two highly homologous G protein alpha-subunits that have been implicated as regulators of phosphoinositidase C. Addition of ethanol (10-200 mM) to the culture medium for 48 h caused a concentration-dependent decrease in the immunologically detectable levels of Gq alpha/11 alpha. A small (approximately 15%) reduction in Gq alpha/11 alpha was observed after only 6 h of exposure to 200 mM ethanol, but membrane levels were reduced by 31% at 48 h. The ethanol-induced loss of Gq alpha/11 alpha was apparently independent of factors present in the foetal calf serum component of the culture medium. These results suggests that the decrease in receptor-mediated phosphoinositide hydrolysis following chronic ethanol treatment of NG108-15 cells may be mediated in part by a reduction in the membrane levels of Gq alpha/11 alpha.


A rural community moves closer to sustainable obesity prevention - an exploration of community readiness pre and post a community-based participatory intervention.
Understanding levels of community readiness can result in prevention efforts that align with communities' ability and capacity for change and, therefore, be more effective and sustainable. Our study aimed to use baseline (pre-intervention) community readiness scores to assist with the development of obesity prevention strategies, and to assess changes in community readiness over time (pre/post- intervention), to provide evidence of intervention impact. Our study was located in a rural and remote area of Victoria, Australia. Community readiness was part of a broader obesity prevention intervention designed to create healthier food and physical activity environments through the combination of systems thinking and collaborative community-led solutions. Interviews were conducted using the community readiness to change tool in 2016 (pre) and 2018 (post) with a community representative sample. Baseline data informed the development of community relevant strategies and the pre/post results formed part of the overall evaluation. The tool generated both quantitative and qualitative (quotes) data. A final readiness score was calculated that corresponded to one of the nine stages of readiness. Four of the five domains of the community readiness to change tool showed statistically significant improvements over time (p < 0.05): knowledge of effort, knowledge of issue, community climate, and leadership. The resources domain that did not improve pre/post intervention. Community readiness to change interviews, pre- and post- intervention, provided essential information related to the appropriate targeting and pitch of the prevention strategies, as well as providing an overall evaluation of the positive movement in the community's readiness to implement change.