Sexual coercion, consent and negotiation: processes of change amongst couples participating in the Indashyikirwa programme in Rwanda.
Sexual coercion among married or cohabitating couples is a complex phenomenon with few effective strategies for prevention. This paper explores sexual coercion among couples from rural Rwanda who participated in Indashyikirwa, a 4-year intimate partner violence prevention programme that included a 5-month couples curriculum to promote equalitarian, non-violent relationships. Drawing on three rounds of longitudinal qualitative interviews with partners from 14 couples (28 individuals), this paper explores processes of change in experiences and conceptualisations of coerced sex over the course of the intervention and 1 year after. The data were analysed using thematic and dyadic analysis. Both partners of couples reported significant changes in their sexual relationship, including reduced experiences of coerced sex, greater communication about sex and increased acceptability for women to initiate sex. Men and women became more willing to disclose sexual coercion over the course of the interviews, both current and past experiences, and couples' accounts generally became more concordant. Findings yield insights to inform programming to prevent coerced sex among spouses. These include grounding discussion of sexual coercion in an analysis of gendered power and norms, reflecting on the consequences of broader forms of sexual coercion and employing a benefits-driven, skills-based approach.


[Pharmacotherapy of the cognitive sequelae secondary to traumatic brain injury].
To review and correlate the most common cognitive disorders secondary to traumatic brain injuries (TBI), the neurobiology of these deficits and their possible modulation by neuropharmacological means. As of a complex cascade of injuries to the brain, patients with TBI may experience alterations that affect the cognitive domain on different levels and to varying degrees, the most common being alteration of the level of alertness; slowing of the speed at which information is processed; attention, memory and learning deficits; language and communication disorders; and impaired executive functions. Brain damage may be caused by a range of pathological mechanisms, such as focal bruising, diffuse axonal damage, cytotoxic damage and neurotransmitter excitotoxicity. Certain pharmacological agents have an effect on the cognitive functions. Pharmacological agents that improve cognitive performance include dopaminergic agents, psychostimulants, some antidepressants and cholinesterase inhibitors. Studies into the pharmacological neuromodulation of the cognitive disorders secondary to TBI are currently in the early stages. The information we have available on the neurochemical bases of cognition and cognitive disorders due to TBI suggest that the most important goals of pharmacological intervention in this group of patients are the stimulation of the catecholaminic and cholinergic functions.


An automatic sequential recognition method for cortical auditory evoked potentials.
The detection of cortical auditory evoked potentials (CAEP), which are part of the electroencephalogram (EEG) in reaction to acoustic stimuli, has important applications such as determining objective audiograms. The detection is usually performed by a human operator, with support from often basic signal processing methods. This paper presents a novel mechanism for the detection of CAEPs, which is fully automatic and stops the measurement when a given confidence is reached. This proposed detector comprises of three stages. First, a feature extraction by a wavelet transform parameterizes the time domain EEG signal by only few transform coefficients. This feature vector is then classified by a neural network which yields a binary vote on every EEG segment. Finally, a sequential statistical test is performed on successive classifications; this stops the measurement if a specified decision confidence has been reached. The adjustment of the detector according to a clinical database is discussed. Thus adjusted, the proposed CAEP detection scheme is applied to a study, and compared with a human operator. The results demonstrate that this method can attain similar results, but outperforms the human expert for stimulation levels close to the hearing threshold.


Local excision of rectal cancer: review of literature.
In selected patients, local excision of rectal cancer may be an alternative to radical surgery such as abdominoperineal excision of the rectum or anterior resection. Local excision carries lower mortality and morbidity, without the functional disturbance or alteration in body image that can be associated with radical surgery. There are several techniques of local therapy for rectal cancer, with most experience being available in transanal excision. Transanal endoscopic microsurgery is also used but experience with this newer technique is limited. Patient selection is the most important factor in successful local excision, however specific criteria for selecting patients have not been universally accepted. Review of the published literature is difficult because of the variation in adjuvant therapy regimes and follow-up strategies, as well as results reported in terms of local recurrence and survival rates. There is increasing evidence to suggest that local excision should be restricted to patients with T1 stage rectal cancer without high-risk factors. The place for local excision in patients with T2 or high-risk T1 tumours requires prospective, randomised multi-centre trials comparing radical surgery with local excision, with or without adjuvant therapy.


[Teenagers with piercing and tattooing].
The search for social identity seems important to young people's efforts at finding a social practice that fulfills their own needs. "Body art", i.e. tattoos and piercing, could be understood as a way of demonstrating a personal identity, though it is doubtful whether this practice over time could fill such needs in a modern society. This study addresses the question of whether young people that acquire tattoos or piercings have special characteristics in terms of social integration and behaviour. A cross-sectional questionnaire was administered to junior high school students (6th, 8th and 10th grade, age 11-15) in a Norwegian town (population: 40,000). A total of 1237 students filled in the questionnaire. The social integration and health-impacting behaviour of those with body art was compared to those without. Adjustments were made for age and sex through linear and logistic regression analysis. Teenagers with body art are just as active in their spare time as their peers without such decorations and they are just as close to and trusting of their friends (relational quality), but they are more integrated with their friends in terms of time spent with them (relational quantity). Teenagers with body art see themselves as less well integrated in school than their peers. Moreover, they assess the support they get from their parents and their closeness to them lower than do those without body art. Having body art is strongly associated with health-compromising behaviour. Health-promoting efforts in schools would benefit from recognition of young people's need for expressing their personal identity and that so-called risk behaviour may be an expression of personal identity. A focus on mastering experiences and inter-generational dialogue could be as fruitful as a focus on risk behaviour.


Promoter insertion leads to polyembryony in mango - a case of convergent evolution with citrus.
Sexual reproduction in plants is the main pathway for creating new genetic combinations in modern agriculture. In heterozygous plants, after the identification of a plant with desired traits, vegetative propagation (cloning) is the primary path to create genetically uniform plants. Another natural plant mechanism that creates genetically uniform plants (clones) is apomixis. In fruit crops like citrus and mango, sporophytic apomixis results in polyembryony, where seeds contain multiple embryos, one of which is sexually originated and the others are vegetative clones of the parent mother tree. Utilizing the mango genome and genetic analysis of a diverse germplasm collection, we identified MiRWP as the gene that causes polyembryony in mango. There is a strong correlation between a specific insertion in the gene's promoter region and altered expression in flowers and developing fruitlets, inducing multiple embryos. The MiRWP gene is an ortholog of CitRWP that causes polyembryony in citrus. Based on the data, we speculate that promoter insertion events, which occurred independently in citrus and mango, induced nucellar embryogenesis. The results suggest convergent evolution of polyembryony in the two species. Further work is required to demonstrate the utility of these genes (mango and citrus) in other biological systems as a tool for the clonal production of other crops.


Dentists' education, knowledge, and professional behavior concerning the diagnosis and treatment of dentin hypersensitivity: an exploration.
Dentin hypersensitivity (DH) affects patients' oral health-related quality of life, but is not always optimally treated in dental offices. The objectives were to assess dentists' DH-related education, knowledge, and professional behavior and explore relationships between education, knowledge, and behavior. Survey data were collected from 220 ADA members in the United States. Descriptive and correlational analyses were performed. About half of the respondents agreed/strongly agreed that their dental school had educated them well about diagnosing DH in classroom-based (53.6%) and clinical settings (48.9%). Lower percentages agreed being well educated about treating DH (40.9%/37.3%). The majority self-educated themselves about DH after dental school by attending continuing education courses in person or online (60.6%/36.8%), reading articles (64.1%), or consulting with colleagues (59.6%). The majority knew that patients with DH describe their pain as stimulated (91.4%) and that recessed gingiva (89.6%), abrasion lesions (72.3%), tooth whitening (63.1%), erosion lesions (58.6%), and abfraction lesions (51.4%) are risk factors for DH. The majority diagnosed DH with patient self-reporting, confirmed by exams (81.8%), applying air blasts (53.7%), or cold-water (52.3%). They treated patients with DH often/very often with over-the-counter desensitizing agents (90%), and prescribing fluoride formulations toothpaste (82.8%) and/or potassium nitrate toothpastes (60.9%). In their offices, the majority (73.2%) educated their patients often/very often about DH and used fluoride dental varnish for treating DH (71.8%). The more recently respondents had graduated from dental school, the more positively they described their dental school education (r = 0.14; p < 0.05), the more ways to diagnose DH they used (r = 0.16; p < 0.05) and the more often they used fluoride dental varnish in their offices (r = 0.23; p < 0.001). The more dentists had educated themselves, the more methods for diagnosing DH they used (r = 0.23; p < 0.001) and the more often they used potassium oxalate products (r = 0.19; p < 0.01), Arginine/calcium products (r = 0.19; p < 0.01) and dentin bonding (r = 0.22; p < 0.001). More recently graduating from dental school correlates with more positive evaluations of DH-related dental school education. The finding that most dentists engage in self-education about DH after dental school should motivate dental educators to increase education about this topic not only in dental school, but also in continuing education courses.


Efficacy of amiodarone for the termination of persistent atrial fibrillation.
The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64+/-9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9+/-7.2 vs 50.4+/-5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.


Accelerated longitudinal cortical atrophy in OEF/OIF/OND veterans with severe PTSD and the impact of comorbid TBI.
Veterans who deployed in support of Operation Enduring Freedom (OEF), Iraqi Freedom (OIF), and New Dawn (OND) commonly experience severe psychological trauma, often accompanied by physical brain trauma resulting in mild traumatic brain injury (mTBI). Prior studies of individuals with posttraumatic stress disorder (PTSD) have revealed alterations in brain structure, accelerated cellular aging, and impacts on cognition following exposure to severe psychological trauma and potential interactive effects of military-related mTBI. To date, however, little is known how such deployment-related trauma changes with time and age of injury of the affected veteran. In this study, we explored changes in cortical thickness, volume, and surface area after an average interval of approximately 2 years in a cohort of 254 OEF/OIF/OND Veterans ranging in age from 19 to 67 years. Whole-brain vertex-wise analyses revealed that veterans who met criteria for severe PTSD (Clinician-Administered PTSD Scale ≥60) at baseline showed greater negative longitudinal changes in cortical thickness, volume, and area over time. Analyses also revealed a significant severe-PTSD by age interaction on cortical measures with severe-PTSD individuals exhibiting accelerated cortical degeneration with increasing age. Interaction effects of comorbid military-related mTBI within the severe-PTSD group were also observed in several cortical regions. These results suggest that those exhibiting severe PTSD symptomatology have accelerated atrophy that is exacerbated with increasing age and history of mTBI.


Synthesis and Characterization of Tellurium Catecholates and Their N-Oxide Adducts.
Tellurium catecholate complexes were investigated to probe the redox chemistry of tellurium, whose oxidation state can span from -2 to +6. Treating TeO2 with catechols resulted in tellurium coordination complexes in high yields within minutes to hours at room temperature or with extended heating, depending on the ligand substituents, giving Te(IV) complexes of the form Te(C)2, where C = 3,5-di-tert-butylcatecholate, o-catecholate, or tetrachlorocatecholate. The redox behavior of these complexes was investigated through addition of organic oxidants, giving nearly quantitative adducts of pyridine N-oxide or N-methylmorpholine N-oxide with each tellurium complex, the latter set leading to ligand oxidation upon heating. Each compound was characterized crystallographically and computationally, providing data consistent with a mostly electrostatic interaction and very little covalent character between the N-oxide and Te complex. The Te N-oxide bond orders are consistently lower than those with the catechol derivatives, as characterized with the Mayer, Gopinathan-Jug (G-J), and first Nalewajski-Mrozek (N-M1) bond indices. The tellurium lone pair is energetically buried by 1.93-2.81 eV, correlating with the observation that the ligands are more reactive than the tellurium center toward oxidation. This combined experimental and theoretical study finds structure-property relationships between ligand design and reactivity that will aid in future efforts for the recovery of tellurium.


The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.
The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identify over 300 PYHIN interactions reflective of diverse functions, including DNA damage response, transcription regulation, intracellular signaling, and antiviral response. In view of the IFIX interaction with antiviral factors, including nuclear PML bodies, we further characterize IFIX and demonstrate its function in restricting herpesvirus replication. We discover that IFIX detects viral DNA in both the nucleus and cytoplasm, binding foreign DNA via its HIN domain in a sequence-non-specific manner. Furthermore, IFIX contributes to the induction of interferon response. Our results highlight the value of integrative proteomics in deducing protein function and establish IFIX as an antiviral DNA sensor important for mounting immune responses.


[Clinical aptitude in occupational medicine residents].
To determine clinical aptitude (AC) in occupational medicine residents. An instrument based on real clinical cases was built and validated to assess AC, which was composed by surveillance indicators of the workers health (SIWH) and occupational-medical evaluation indicators (0ME) In the study participated 22 undergraduate students (UE), 40 residents of first year (R1) and 36 of second year (R2). The instrument was validated by experts. Internal consistency of the instrument was 0.93 by Kuder-Richardson. Regarding global AC, 96 % of UE were situated in a random level and 4 % in a very low level. 15 % of R1 was situated in a random level, 50 % in a very low level, 30 % low level and 5 % in medium level; whereas R2 3 % was positioned in a random level, 28 % in a very low level, 50 % in low level and 19 % in medium level. A significant difference was found between R1 and R2 in occupational-medical evaluation (p < 0.009), but not in SIWH. Two centers showed statistical difference in both indicators.


Islet antigen-specific Th17 cells can induce TNF-α-dependent autoimmune diabetes.
Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells. Although Th1 cells are key orchestrators of T1D, the function(s) of the more recently identified Th17 subset are unclear due to inherent plasticity. In this study, we analyzed Th17 cells for stability and diabetogenicity in NOD mice. We found that like Th1 cells, Th17 are a distinct population throughout the prediabetic phase. At diabetes onset, there were marked increases in IL-17-producing Th17 cells and IFN-γ-producing Th1 cells in the pancreas as well as in the serum levels of these cytokines, indicating that these proinflammatory mediators serve as biomarkers of advanced autoimmunity. Although naturally occurring Th17 cells in diabetic mice did not contribute to diabetes development in transfer models, islet-specific Th17 cells were diabetogenic independently of IL-17 and displayed inflammation-induced Th17-to-Th1 reprogramming that could be elicited by Th1 cells. However, an inability to generate Th1 cells because of Stat4, Ifngr, and Ifng deficiencies did not prevent diabetes. Instead, TNF-α could mediate diabetes in response to either Th17 cells or Th1 cells. The results identify a previously unknown mechanism by which Th17 cells can contribute to T1D. Our studies also suggest that when developing interventions for T1D, it will be potentially advantageous to focus on mechanisms common to effector T cells rather than on the signature cytokines of various subsets.


Isolation and molecular characterization of a mouse renal microvascular endothelial cell line.
Murine endothelial cells (ECs) have proven difficult to obtain and maintain in culture. Long-term maintenance of normal ECs remains a difficult task. In this article we report the establishment of the first cellular line of renal microvascular endothelium obtained from normal tissue. Cells were isolated, cloned, and maintained by serial passages for longer than 24 mo, using endothelial cell growth supplement (ECGS) and gelatin-coated plates. Their morphology and ultrastructure, expression of von Willebrand factor, presence of smooth muscle alpha-actin, vimentin, cytokeratin filaments, capillary structures formed on Matrigel, and some typical ECs surface molecules were the criteria used to characterize cultured ECs. When examined for responsiveness to Shiga toxin-1, 13-20% of cytotoxicity was observed when coincubated with lipopolysaccharides. This cytotoxicity was not observed for normal lung ECs (1G11). Consequently, REC-A4 line retains characteristics of resting microvascular ECs and represents a useful in vitro model to study biological and physiopathological properties of renal endothelium.


PeerWise and Pathology: Discontinuing a teaching innovation that did not achieve its potential.
This article was migrated. The article was marked as recommended. Introduction Writing and answering multiple choice questions (MCQs) is a learning activity that potentially engages deep learning. We conducted three year-long case studies of MCQ writing and answering in PeerWise to engage students in learning Pathology. Methods Overall, an instrumental case-study design with the structure of sequential multiple case studies was used. Across three years fourth year medical students were required to write and answer MCQs. In 2016 students were provided with advice for writing questions and were encouraged to adhere to Bloom's taxonomy. In 2017, to reduce cognitive load, students were provided with a MCQ template and allocated topics. In 2018, to encourage engagement, students were informed that the top forty MCQs would be in the final exam. Results An evaluation survey was used to measure each student's perception of the MCQ exercise. In 2016 most students had a negative opinion of the MCQ exercise. Students found writing MCQs too time consuming and demanding. In 2017 student's attitudes to the MCQ exercise were more positive. In 2018 there were insufficient responses to the survey but informal student feedback suggested the MCQ exercise was considered an inefficient use of student study time. There were minimal changes in student's activity levels from 2016 to 2017. However, in 2018 when students were informed that the top forty MCQs generated would be included in their final exam they answered a greater number of MCQs than in previous years. Conclusions Providing students with templates and assigning topics for MCQs may improve student attitudes toward MCQ writing and including student generated MCQs in the final exam encourages students to answer more MCQs. However, due to high demands on their time, medical students' prioritised efficiency and MCQ writing may not be an efficient strategy for deep learning.


Current trends in quantitative proteomics.
It was inevitable that as soon as mass spectrometrists were able to tell biologists which proteins were in their samples, the next question would be how much of these proteins were present. This has turned out to be a much more challenging question. In this review, we describe the multiple ways that mass spectrometry has attempted to address this issue, both for relative quantitation and for absolute quantitation of proteins. There is no single method that will work for every problem or for every sample. What we present here is a variety of techniques, with guidelines that we hope will assist the researcher in selecting the most appropriate technique for the particular biological problem that needs to be addressed. We need to emphasize that this is a very active area of proteomics research-new quantitative methods are continuously being introduced and some 'pitfalls' of older methods are just being discovered. However, even though there is no perfect technique--and a better technique may be developed tomorrow--valuable information on biomarkers and pathways can be obtained using these currently available methods.


Estimation of urinary concentration of aflatoxin M1 in Chinese pregnant women.
Aflatoxin M1 (AFM1 ) is a main cause of hepatocarcenogenoma in Chinese population. Measurement of aflatoxin exposure in human may help in providing clear evidence for the exposure of specific environmental pollutants in certain population. "One child policy" in China offered parents more careful to choose safe food during pregnancy, but no reports published on the efficacy of their endeavor. In present study, we aimed to assess the exposure of AFM1 in Chinese pregnant women. The urine samples were collected from 600 volunteers from Zhejiang province, China and the urinary concentration of AFM1 was measured using ELISA kit. AFM1 was detected in 84% of the pregnant women. The geometric mean and 95th percentile concentration of AFM1 in pregnant women were 50.3 ng/L and 633.5 ng/L, respectively. Our results point out that pregnant women especially are at the high risk of exposure to AFM1 . Our results also indicate that although "one child policy" offered parents to pay more attention for the selection of safe food, but detection of AFM1 in urine of pregnant women indicate that more foods containing AFM1 still need to be detected. Highest exposure of AFM1 in pregnant women indicates that awareness campaigns must be started especially in the rural areas of China regarding the possible hazardous effects of AFM1 exposure in pregnant women.


[Thromboembolic risk factors in atrial flutter. Transesophageal echocardiographic study].
The thromboembolic risk of atrial flutter (AFL) is not well defined. On the other hand, in atrial fibrillation (AF), the echocardiographic demonstration of thrombus or spontaneous echo contrast in the left atria or its appendage, a lower flow velocity in the left atrial appendage, and its reduced mobility, are well known risk factors of thromboembolism. To study the incidence of these echocardiographic risk factors in patients with AFL. We prospectively studied 50 consecutive patients with AFL comparing them with two groups of patients with a well known increased risk of thromboembolism: 54 patients with AF and 24 patients with sinus rhythm and severe mitral stenosis (RSEMS). The group of patients with AFL was also compared with a control group of 27 patients with sinus rhythm and no increased risk of thromboembolism. In each group, we studied the presence of thrombi and spontaneous echo contrast in the left atria and left atrial appendage, emptying velocity (Vel A), filling flow (Vel B) and motility of the left atrial appendage and left atrial dimensions. When compared with control patients, AFL subjects had a higher incidence of spontaneous echo contrast in the left atria and left atrial appendage (11 and 42% respectively, p < 0.05); slower flow velocity in the left atrial appendage (Vel A 69.25 +/- 25 and 41 +/- 19 cm/s respectively, Vel B 55 +/- 16 and 46 +/- 20 cm/s respectively, p < 0.05); lower atrial appendage wall motility (4 and 84% respectively, p < 0.001) and a larger left atrium (40 +/- 10 and 45 +/- 0.6 mm respectively, p < 0.05). Patients with AFL had a lower incidence of echocardiographic abnormalities than subjects with AF or RSEMS. Thrombi were found in 2 patients with AFL, 12 patients with AF, 4 patients with RSEMS and in no control patient. In AFL, there are echocardiographic markers of increased thromboembolic risk in comparison with a control group. Nevertheless, the incidence of these factors is lower than in patients with AF or with RSEMS.


Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial.
The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS.


Structural and magnetic characterization of batch-fabricated nickel encapsulated multi-walled carbon nanotubes.
We report on the growth and fabrication of Ni-filled multi-walled carbon nanotubes (Ni-MWNTs) with an average diameter of 115 nm and variable length of 400 nm-1 µm. The Ni-MWNTs were grown using template-assisted electrodeposition and low pressure chemical vapor deposition (LPCVD) techniques. Anodized alumina oxide (AAO) templates were fabricated on Si using a current controlled process. This was followed by the electrodeposition of Ni nanowires (NWs) using galvanostatic pulsed current (PC) electrodeposition. Ni NWs served as the catalyst to grow Ni-MWNTs in an atmosphere of H2/C2H2 at a temperature of 700 °C. Time dependent depositions were carried out to understand the diffusion and growth mechanism of Ni-MWNTs. Characterization was carried out using scanning electron microscopy (SEM), focused ion beam (FIB) milling, transmission electron microscopy (TEM), Raman spectroscopy and energy dispersive x-ray spectroscopy (EDX). TEM analysis revealed that the Ni nanowires possess a fcc structure. To understand the effects of the electrodeposition parameters, and also the effects of the high temperatures encountered during MWNT growth on the magnetic properties of the Ni-MWNTs, vibrating sample magnetometer (VSM) measurements were performed. The template-based fabrication method is repeatable, efficient, enables batch fabrication and provides good control on the dimensions of the Ni-MWNTs.


Impact of Metabolic Surgery on Renal Injury in Pre-Clinical Models of Diabetic Kidney Disease.
Surgical approaches to the treatment of obesity and type 2 diabetes, most notably the Roux-en-Y gastric bypass (RYGB) procedure, have been shown to be renoprotective, reducing the incidence of albuminuria and end-stage kidney disease over 15- to 20-year follow-up in patients with obesity. The tissue level effects of metabolic surgery on the diabetic kidney are not easily interrogated in clinical samples. However, elucidation of the cellular and molecular basis for the renoprotective effects of metabolic surgery is now emerging from a body of pre-clinical work in rodent models of diabetic kidney disease (DKD). Experimental metabolic surgery (RYGB, sleeve gastrectomy [SG], Roux-en-Y oesophagojejunostomy, and duodenojejunal bypass) exerts a pronounced albuminuria-lowering effect in rat models of DKD. Following RYGB in the Zucker diabetic fatty rat, glomerular histology is improved as demonstrated by reductions in podocyte stress, glomerulomegaly, and glomerulosclerosis. Glomerular ultrastructure improves after RYGB and after SG, manifested by quantifiable reductions in podocyte foot process effacement. The transcriptional programme underpinning these structural improvements has been characterized at the pathway level using RNA sequencing and is associated with a significant reduction in the activation of inflammatory and fibrotic responses. Key Messages: Experimental metabolic surgery reduces biochemical, histological, and molecular indices of DKD. These pre-clinical data support a growing interest in the potential utility of metabolic surgery as a therapeutic approach to slow renal functional decline in patients with obesity and DKD.


Solution structure of the c-terminal dimerization domain of SARS coronavirus nucleocapsid protein solved by the SAIL-NMR method.
The C-terminal domain (CTD) of the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP) contains a potential RNA-binding region in its N-terminal portion and also serves as a dimerization domain by forming a homodimer with a molecular mass of 28 kDa. So far, the structure determination of the SARS-CoV NP CTD in solution has been impeded by the poor quality of NMR spectra, especially for aromatic resonances. We have recently developed the stereo-array isotope labeling (SAIL) method to overcome the size problem of NMR structure determination by utilizing a protein exclusively composed of stereo- and regio-specifically isotope-labeled amino acids. Here, we employed the SAIL method to determine the high-quality solution structure of the SARS-CoV NP CTD by NMR. The SAIL protein yielded less crowded and better resolved spectra than uniform (13)C and (15)N labeling, and enabled the homodimeric solution structure of this protein to be determined. The NMR structure is almost identical with the previously solved crystal structure, except for a disordered putative RNA-binding domain at the N-terminus. Studies of the chemical shift perturbations caused by the binding of single-stranded DNA and mutational analyses have identified the disordered region at the N-termini as the prime site for nucleic acid binding. In addition, residues in the beta-sheet region also showed significant perturbations. Mapping of the locations of these residues onto the helical model observed in the crystal revealed that these two regions are parts of the interior lining of the positively charged helical groove, supporting the hypothesis that the helical oligomer may form in solution.


[Oxidative stress in porphyria and carriers].
We sought to establish a causal relationship between oxidative stress and porphyria in patients and carriers. We reported changes in urinary porphyrin concentrations related to 8-hydroxy-2'-deoxyguanosine. We measured urinary 8-hydroxy-2'-deoxyguanosine concentration in porphyria patients and carriers with multifactorial inheritance as a possible marker of attack. The porphyria types included 10 patients with porphyria cutanea tarda, 5 with variegate porphyria, 8 with hereditary coproporphyria, 7 with congenital erythropoietic porphyria, 5 with erythropoietic protoporphyria, 5 with acute intermittent porphyria, 7 erythropoietic protoporphyria carriers, and 7 acute intermittent porphyria carriers. Urinary porphyrin concentrations in these patients were significantly higher than those in healthy subjects (p<0.001). Urinary 8-hydroxy-2'-deoxyguanosine concentrations were significantly high in dermatopathy porphyria types namely porphyria cutanea tarda (p<0.001), variegate porphyria (p<0.05), hereditary coproporphyria (p<0.05), congenital erythropoietic phyria (p<0.05), and erythropoietic protoporphyria (p<0.001). These results reveal that urinary 8-hydroxy-2'-deoxyguanosine concentration in cutis porphyria types is a good predictor of attack and abatement.


Evaporative Cooling Does Not Prevent Vertical Dispersion of Effervescent Seawater Aerosol for Brightening Clouds.
Marine cloud brightening (MCB) is a potential intervention to mitigate the effects of climate change by increasing the reflectance of low-level maritime clouds, including those over the Great Barrier Reef. The technique involves dispersing a plume of submicrometer seawater droplets over the ocean, which evaporate, generating nanosized sea-salt aerosols (SSAs) that disperse through the atmosphere with some fraction incorporated into clouds. Droplet evaporation, which occurs in the immediate vicinity (meters to tens of meters) of the source, has been theorized to produce a negatively buoyant plume hindering the mixing of the sea-salt aerosol to cloud height and compromising the effectiveness of MCB. We characterized in situ for the first time the nearfield aerosol dispersion from a point source of atomized seawater produced using the effervescent technique. We observed consistent vertical mixing of the plume up to 150 ± 5 m height at 1 km downwind. The extent of vertical dispersion was influenced by wind velocity and atmospheric stability. We found no evidence that negative buoyancy due to the evaporation of the 0.068 kg/s water fraction significantly suppressed vertical mixing. Our results can be attributed to the small droplet sizes generated by the effervescent spray technology and associated low flow rates required to generate around 1014 droplets s-1. We estimate that, for a hypothetical implementation producing up to 1016 s-1 similarly sized SSAs, evaporative cooling is unlikely to significantly suppress the vertical dispersion of aerosol for MCB.


Phase shifts to light are altered by antagonists to neuropeptide receptors.
The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor, while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for the photic phase shifting of the hamster circadian clock by examining two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([d-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on their own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP; phase shifts to light are only impaired when signalling in both pathways are inhibited. Additionally, the unexpected potentiation of light-induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications.


Interactions among the glucocorticoid receptor, lipoprotein lipase, and adrenergic receptor genes and plasma insulin and lipid levels in the Quebec Family Study.
The aim of the study was to investigate the possible interactions among the glucocorticoid receptor (GRL), lipoprotein lipase (LPL), and adrenergic receptor (ADR) genes on plasma insulin and lipid levels. The study was cross-sectional and based on 742 individuals from phase 2 of the Quebec Family Study (QFS) cohort. Gene markers were identified by Southern blot analysis or polymerase chain reaction (PCR). Plasma glucose and insulin in the fasted state and during an oral glucose tolerance test (OGTT) were determined and insulin and glucose areas were computed. Triglyceride (TG) and cholesterol concentrations in plasma and lipoprotein fractions were determined enzymatically. The results show that GRL and LPL variants had independent effects on plasma high-density lipoprotein cholesterol (HDL-C) and two beta2-ADR variants were related to total cholesterol concentrations. The alpha2-ADR gene Dral polymorphism was the only variant that had an independent effect on the plasma insulin area. Gene-gene interaction effects were found between GRL and alpha2-ADR genes for low-density lipoprotein cholesterol ([LDL-C] P = .013) and between GRL and LPL genes for HDL-C (P = .045). Higher-order interaction effects involving GRL, LPL, and ADR markers were observed for the plasma insulin area (P = .001 to .025) but not the glucose area. After correction for multiple tests, the findings remained essentially unchanged for the insulin area but became nonsignificant for the lipid phenotypes. In conclusion, multiple interactions among GRL, LPL, and ADR gene markers contribute to insulin metabolism and perhaps to lipid levels, while no significant effect is found for each gene separately. The LPL locus appears to determine the pattern of interactions with ADR and GRL loci. These results suggest that gene-gene interaction effects could play a role in the etiology of risk factors for common chronic diseases.


All-terrain vehicle use in agriculture: exposure to whole body vibration and mechanical shock.
Whole body vibration (WBV) and mechanical shock were measured in 12 New Zealand farmers during their daily use of all-terrain vehicles (ATVs). As per the International Organization for Standardization (ISO) guidelines for WBV exposure, frequencies between 0 and 100Hz were recorded via a seat-pad tri-axial accelerometer during 20min of ATV use. The farmers were also surveyed to estimate seasonal variation in daily ATV usage as well as 7-day and 12-month prevalence of spinal pain. Frequency-weighted vibration exposure and total riding time were calculated to determine the daily vibration dose value (VDV). The daily VDV of 16.6m/s(1.75) was in excess of the 9.1m/s(1.75) action limit set by ISO guidelines suggesting an increased risk of low back injury from such exposure. However, the mean shock factor R, representing cumulative adverse health effects, was 0.31 indicating that these farmers were not exposed to excessive doses of mechanical shock. Extrapolation of daily VDV data to estimated seasonal variations of farmers in ATV riding time demonstrated that all participants would exceed the ISO recommended maximum permissible limits during the spring lambing season, as compared to lower exposures calculated for summer, autumn and winter. Low back pain was the most commonly reported complaint for both 7 day (50%) and 12 month prevalence (67%), followed by the neck (17% and 42%) and the upper back (17% and 25%) respectively. The results demonstrate high levels of vibration exposure within New Zealand farmers and practical recommendations are needed to reduce their exposure to WBV.


Selective stimulation of somatostatin receptor subtypes: differential effects on Ras/MAP kinase pathway and cell proliferation in human neuroblastoma cells.
In previous studies we have showed that somatostatin (SST) inhibits cell division, mitogen-activated protein (MAP) kinase and Ras activity in the human neuroblastoma cell line SY5Y. In the present study, we have assessed the role of a series of SST analogs, three of which were selective for SSTR1, SSTR2 or SSTR5, in these cellular events. All the analogs inhibited forskolin-induced cAMP accumulation. Selective stimulation of SSTR1 or SSTR2 but not of SSTR5 inhibited platelet-derived growth factor (PDGF)-induced [(3)H]thymidine incorporation. The three analogs inhibited PDGF-stimulated MAP kinase activity, at least at an early time. In contrast, none of the analogs used individually was able to inhibit PDGF-stimulated Ras activity. A combined stimulation of SSTR2 and SSTR5 was necessary to obtain a significant inhibitory effect, suggesting the possibility of receptor heterodimerization. These results indicate that SST inhibition of Ras and MAP kinase activities takes place via different pathways and that SST inhibition of PDGF-induced cell proliferation occurs via a Ras-independent pathway.


Morphologic and functional evaluation of coronary artery bypass conduits.
There is clear evidence in the literature that conventional spin-echo and gradient-echo magnetic resonance imaging (MRI) is capable of assessing patency of coronary artery vein grafts. With more recently introduced breath-hold two-dimensional (2D) and contrast-enhanced 3D techniques, the predictive accuracy has further improved, with sensitivities and specificities in the 90% range. Limitations arise with regard to assessing obstructive disease and evaluating distal segments of sequential grafts, due to insufficient spatial resolution, low signal-to-noise ratio, and cardiac motion. Imaging of arterial grafts is complicated by the metallic clip artifacts. Adding information on graft flow patterns and flow reserve using velocity-encoded cine MRI may help to reduce some of the problems. Clinically, these functional measurements may become of use in non-invasive monitoring of gradually increasing graft narrowing. However, apart from a few exceptions, most patients undergo evaluation of their grafts because they are considered for a re-intervention by angioplasty or coronary artery bypass graft surgery. In these cases information on the status of the native coronary arteries is required. A broader clinical use of MRI in the evaluation of patients with coronary artery bypass grafts may therefore only be expected with further improvement in MR techniques for coronary angiography. J. Magn. Reson. Imaging 1999;10:734-740.


Two Photolyases Repair Distinct DNA Lesions and Reactivate UVB-Inactivated Conidia of an Insect Mycopathogen under Visible Light.
Fungal conidia serve as active ingredients of fungal insecticides but are sensitive to solar UV irradiation, which impairs double-stranded DNA (dsDNA) by inducing the production of cytotoxic cyclobutane pyrimidine dimers (CPDs) and (6-4)-pyrimidine-pyrimidine photoproducts (6-4PPs). This study aims to elucidate how CPD photolyase (Phr1) and 6-4PP photolyase (Phr2) repair DNA damage and photoreactivate UVB-inactivated cells in Beauveria bassiana, a main source of fungal insecticides. Both Phr1 and Phr2 are proven to exclusively localize in the fungal nuclei. Despite little influence on growth, conidiation, and virulence, singular deletions of phr1 and phr2 resulted in respective reductions of 38% and 19% in conidial tolerance to UVB irradiation, a sunlight component most harmful to formulated conidia. CPDs and 6-4PPs accumulated significantly more in the cells of Δphr1 and Δphr2 mutants than in those of a wild-type strain under lethal UVB irradiation and were largely or completely repaired by Phr1 in the Δphr2 mutant and Phr2 in the Δphr1 mutant after optimal 5-h exposure to visible light. Consequently, UVB-inactivated conidia of the Δphr1 and Δphr2 mutants were much less efficiently photoreactivated than were the wild-type counterparts. In contrast, overexpression of either phr1 or phr2 in the wild-type strain resulted in marked increases in both conidial UVB resistance and photoreactivation efficiency. These findings indicate essential roles of Phr1 and Phr2 in photoprotection of B. bassiana from UVB damage and unveil exploitable values of both photolyase genes for improved UVB resistance and application strategy of fungal insecticides.IMPORTANCE Protecting fungal cells from damage from solar UVB irradiation is critical for development and application of fungal insecticides but is mechanistically not understood in Beauveria bassiana, a classic insect pathogen. We unveil that two intranuclear photolyases, Phr1 and Phr2, play essential roles in repairing UVB-induced dsDNA lesions through respective decomposition of cytotoxic cyclobutane pyrimidine dimers and (6-4)-pyrimidine-pyrimidine photoproducts, hence reactivating UVB-inactivated cells effectively under visible light. Our findings shed light on the high potential of both photolyase genes for use in improving UVB resistance and application strategy of fungal insecticides.


The Use of Image-Guided Navigation Systems During Spine Surgeries in Saudi Arabia: A Cross-Sectional Study.
We used a cross-sectional study design (questionnaire) to investigate the use of image-guided navigation (IGN) in Saudi Arabia and explore possible differences in implementing IGN for daily practice. An internet-based survey was sent to all spine surgeons who are practicing in Saudi Arabia (orthopedics or neurosurgery). The survey is composed of 12 items that collected demographic and academic data. Ninety-nine answered the questionnaire from 197; 80% were from Riyadh, the capital, and 50% were consultants (attending physicians). Orthopedic surgeons were almost 60% of responders compared to 40% neurosurgeons. The use of navigation in Saudi hospitals was high (76.8%). There was a significant difference between specialties in the preference of using navigation (23.2% for orthopedics versus 81.4% for neurosurgery, P < .001) and routine use in surgical spine cases (88.4% for neurosurgery versus 50.0% orthopedics, P < .001). The majority of responders from neurosurgery learned to use navigation during residency compared to orthopedics responders (51.2% versus 28.6%, P = .001). More than 30% of orthopedics responders expressed they never learned navigation compared to only 4% of neurosurgery responders. The comfort level of > 75% with performing surgery using navigation was significantly different between specialties (25% for orthopedics versus 46.5% for neurosurgery, P < .001). Saudi spine surgeons are among the highest users of IGN systems. The strong healthcare infrastructure and the availability of these devices across the country are among the most important factors for its prevalence. Enhancing surgical exposure and education of postgraduate trainees to use these tools, especially within orthopedics, could increase use and comfort level rates.


Quasicrystals - A Paradigm Shift in Crystallography?
The discovery of quasicrystals had important consequences for our understanding of long-range order in thermodynamic equilibrium, the definition of the term 'crystal' as well as diffraction theory. Quasicrystals have been observed not only at the atomic scale in binary and ternary intermetallic systems, but also at the mesoscale in self-assembled colloids and block-copolymers, and even at the macroscale in packings of hard polyhedra. How important was the discovery of quasicrystals for crystallography? Did it usher in a scientific revolution and a paradigm shift? These questions are discussed following a short overview of the status of quasicrystal research.


"When Will Your Program Be Available in Spanish?" Adapting an Early Parenting Intervention for Latino Families.
This paper describes the Spanish adaptation of PACE-Parenting Our Children to Excellence. Successfully offered in preschools and daycare centers since 2002, PACE is a research-based preventive intervention to support families in their parenting task through discussions and activities that address practical childrearing issues and promote child coping-competence. Developed in response to community calls, the new program is known as CANNE -Criando a Nuestros Niños hacia el Éxito. The paper makes the processes linking original and adapted versions explicit by accounting for the conceptual and practical decisions that were made as CANNE was being developed. We begin by summarizing the challenges of adapting and translating a behavioral intervention, and by describing the coping-competence model that informs both versions of the program. We turn then to a detailed account of the adaptation itself and of its results. Specifically, we describe: (a) the consultation process at the origin of this adaptation, (b) the adaptation of the manual and the steps taken to establish the extent to which the English and Spanish versions correspond (adaptation fidelity), and (c) the translation of the manual and the cross-language comparison of measures to demonstrate that they yield comparable data when administered in English and Spanish.


Peak expiratory flow rate and sarcopenia risk in older Indonesian people: A nationwide survey.
Reduced peak expiratory flow is a common physiological change in older individuals and age is an important predictor for sarcopenia. We analyzed nationwide survey data to determine the relationship between peak expiratory flow rate and sarcopenia in older Indonesians. Community-dwelling Indonesian individuals aged ≥60 years (n = 2422; mean age = 67.21 y) from the fifth-wave data of the Indonesian Family Life Survey was selected. Sarcopenia was diagnosed based on handgrip strength, gait speed, and appendicular skeletal muscle mass measurements. Peak expiratory flow rates (PEFRs) were categorized according to their percentage of predicted flow rates as <50%, 50% to 80%, and >80%. Confounders previously determined to be associated with sarcopenia occurrence were included. Sarcopenia prevalence was 50.25%. After adjustment for confounders, PEFRs of <50% and 50% to 80% were associated with an increased sarcopenia risk (odds ratio = 5.22 and 1.88, respectively) compared with PEFRs of >80%. Poor lung function was independently associated with sarcopenia occurrence. Future studies should explore the usefulness of PEFR as a risk factor of sarcopenia.


Effect of dietary calcium on the colonic luminal environment.
Dietary supplementation with calcium may prevent the development of colorectal cancer. This mechanism may be related to fatty acid and bile salt chelation in the small bowel forming non-toxic calcium-soap compounds. Calcium may also act locally or systemically on the colonic mucosa. Faecal concentrations of free fatty acids and free bile acids were measured in 17 Sprague-Dawley rats (weighing 472 (39 g)) whose daily calcium intake had been trebled by enriching the chow and adding calcium lactate (24 g/l) to the drinking water. Mean (SEM) faecal concentrations of free bile acids were 33% less than in 19 controls (1.23 (0.15) v 1.82 (0.20) mg/g; p less than 0.001), whereas free fatty acid concentrations were 117% higher (14.68 (3.59) v 6.76 (2.41) mg/g; p less than 0.02). The 'direct' effect of calcium was assessed by organ culture of rat colonic explants in three different concentrations of calcium. Crypt cell production rate (measured by a stathmokinetic technique), which was (mean (SEM)) 4.80 (0.23) cells/crypt/h in control medium (Ca2+ = 2.14 mmol/l), fell by 43% when calcium concentration was doubled (p less than 0.05) and by a further 43% when the concentration was trebled (p less than 0.02). Calcium binds free fatty acids but not free bile acids intraluminally. Calcium has a direct antitropic action on colonic crypts.


Pharmacologic study of muscarinic receptor subtypes and arteriolar dilations: a comparison of conducted and local responses.
Arteriolar relaxation caused by the application of muscarinic agonists is mediated by multiple factors. One factor causes dilation only at the point of drug microapplication (local response), and a second factor causes responses remote (500 microm away) from the site of application (conducted response). This study was performed to determine if different muscarinic subtypes mediate the two responses. Arterioles of anesthetized hamster cheek pouch were studied with videomicroscopy. Muscarinic antagonists methscopolamine, scopolamine, pirenzepine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide), and AFDX-116 [(11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepin-6-one)] were cumulatively applied, and the K(B) for each antagonist was determined for the local and conducted responses caused by methacholine microapplication (10(-4) M, 5 s). The pK(B) (local, conducted) were not significantly different for the two responses when using scopolamine (10.5, 10.4). When the antagonist AFDX-116 (5.6, 6.3), selective for muscarinic receptor (m2) subtype was applied, the K(B) was greater for the conducted response. The pK(B) was greater, however, for the local response when the m1 subtype-selective pirenzepine (7.7, 6.9) or m3 subtype-selective 4-DAMP (10.1, 9.8) was applied. Thus the antagonist pK(B) ratio for on the local and conducted responses depends on the subtype selectivity of the antagonist. These data strongly suggest that different receptors are involved in the two responses.


Enzyme-labeled Antigen Method: Development and Application of the Novel Approach for Identifying Plasma Cells Locally Producing Disease-specific Antibodies in Inflammatory Lesions.
In chronic inflammatory lesions of autoimmune and infectious diseases, plasma cells are frequently observed. Antigens recognized by antibodies produced by the plasma cells mostly remain unclear. A new technique identifying these corresponding antigens may give us a breakthrough for understanding the disease from a pathophysiological viewpoint, simply because the immunocytes are seen within the lesion. We have developed an enzyme-labeled antigen method for microscopic identification of the antigen recognized by specific antibodies locally produced in plasma cells in inflammatory lesions. Firstly, target biotinylated antigens were constructed by the wheat germ cell-free protein synthesis system or through chemical biotinylation. Next, proteins reactive to antibodies in tissue extracts were screened and antibody titers were evaluated by the AlphaScreen method. Finally, with the enzyme-labeled antigen method using the biotinylated antigens as probes, plasma cells producing specific antibodies were microscopically localized in fixed frozen sections. Our novel approach visualized tissue plasma cells that produced 1) autoantibodies in rheumatoid arthritis, 2) antibodies against major antigens of Porphyromonas gingivalis in periodontitis or radicular cyst, and 3) antibodies against a carbohydrate antigen, Strep A, of Streptococcus pyogenes in recurrent tonsillitis. Evaluation of local specific antibody responses expectedly contributes to clarifying previously unknown processes in inflammatory disorders.


Neuron-astrocyte interactions in the medial nucleus of the trapezoid body.
The calyx of Held (CoH) synapse serves as a model system to analyze basic mechanisms of synaptic transmission. Astrocyte processes are part of the synaptic structure and contact both pre- and postsynaptic membranes. In the medial nucleus of the trapezoid body (MNTB), midline stimulation evoked a current response that was not mediated by glutamate receptors or glutamate uptake, despite the fact that astrocytes express functional receptors and transporters. However, astrocytes showed spontaneous Ca(2+) responses and neuronal slow inward currents (nSICs) were recorded in the postsynaptic principal neurons (PPNs) of the MNTB. These currents were correlated with astrocytic Ca(2+) activity because dialysis of astrocytes with BAPTA abolished nSICs. Moreover, the frequency of these currents was increased when Ca(2+) responses in astrocytes were elicited. NMDA antagonists selectively blocked nSICs while D-serine degradation significantly reduced NMDA-mediated currents. In contrast to previous studies in the hippocampus, these NMDA-mediated currents were rarely synchronized.


Counting the Toll of Smoking-Attributable Hospitalisations.
Aim In Ireland, 20% of adults smoke. Many current and ex-smokers live with ill-health and disability as a result of smoking, and this study aimed to quantify the extent of smoking-related hospitalisations in Irish publicly-funded hospitals. Methods A population attributable fractions approach was used in this analysis utilising smoking prevalence data from the Healthy Ireland Survey and combining this with internationally-recognised relative-risks for current and past smoking, and hospitalisation data and hospital base costs data sourced from HIPE, for the years 2011-2016. Results In 2016, there were 21,486 day case admissions, 33,615 inpatient hospital admissions consuming 309,117 bed days, attributable to smoking and exposure to second-hand smoke, with an estimated cost of €172 million in publicly funded hospitals. This represents 2% of day case admissions, 5% of inpatient admissions, and 8% of inpatient bed days for that year. Conclusion Smoking continues to cause a considerable impact on hospital services in Ireland.


Ferulic acid, a phenolic phytochemical, inhibits UVB-induced matrix metalloproteinases in mouse skin via posttranslational mechanisms.
Matrix metalloproteinases MMP-2 and -9 are known to be overexpressed in ultraviolet B (UVB)-irradiated skin tissues and contribute to the acceleration of photoaging and the development of skin cancer. But the specific molecular mechanisms that can control or interfere with the expression and regulation of these MMP-2 and -9 activities in skin are not clearly understood. The aim of the present study was to analyze the suppressive effects of ferulic acid (FA), an abundant phenolic compound present in various dietary and medicinal plants, on UVB radiation-induced MMP-2 and -9 activities in mouse skin. For attenuation of chronic UVB irradiation damage to skin, inhibition of MMP-2 and -9 protein expression was detected using immunohistochemistry analysis. However, the in situ suppressive effects of FA did not interfere with the transcription or translation of MMP-2 and -9, suggesting that its action could be mediated via the proteasome pathway. Histological analyses showed that FA attenuates the degradation of collagen fibers, abnormal accumulation of elastic fibers and epidermal hyperplasia induced by UVB, demonstrating the functional and physiological relevance of FA effects in UVB-irradiated skin tissues. Together, our findings provide a novel and increased insight into the in vivo action of FA and suggest a possible clinical application in skin pathophysiological conditions associated with overexpression of MMP-2 and -9.


How subtle differences in MHC class II affect the severity of experimental myasthenia gravis.
Myasthenia gravis is an autoimmune disorder characterized by muscle weakness, due to an antibody-mediated deficit of acetylcholine receptors (AChRs) at neuromuscular junctions. We analyzed the factors that determine the severity of experimental myasthenia gravis (EAMG) induced by immunization with Torpedo AChR, in two congenic strains of mice--B6 mice, which are highly susceptible to EAMG; and bm12 mice, which are relatively resistant, and differ only in a change of three amino acids in MHC Class II. We prepared large numbers of AChR-specific T cell hybridomas from each strain and characterized their epitope specificities and T cell receptor (TCR) gene usage: Half the B6 hybridomas responded to a single AChR peptide (alpha 146-162), and their TCR genes encoded restricted V alpha and V beta chains and CDR3 motifs. bm12 hybridomas had different epitope specificities and different, less restricted TCR genes. APCs were able to present AChR or AChR-derived peptides virtually exclusively to hybridomas of their own strain. Levels of antibodies to Torpedo and autoantibodies to mouse AChR were higher in B6 mice, and were biased toward the IgG2b isotype. We conclude that the "better fit" of MHC II, peptide, and TCR in the B6 mice enhanced cognate interactions of APCs with T cells, and T cells with B cells, resulting in a more abundant and pathogenic AChR antibody response, and thus more severe EAMG.


Thirty-eight cases of acute pancreatitis in pregnancy: a 6-year single center retrospective analysis.
Thirty-eight pregnant inpatients with acute pancreatitis (AP) were retrospectively reviewed from 2006 to 2012 in our hospital. The incidence of pregnancy-associated AP was 2.27‰. Most (78.95%) of the attack occurred in the third trimester. The median of APACHE II score was 6 and severe AP accounted for 31.58% (12 cases). Primary diseases were absent in most cases (57.89%). The most common clinical presentations were abdominal pain (89.47%) and vomiting (68.42%). Pleural effusion and ascites were found only in the third trimester. Elevated white blood cell count, amylase and lipase were commonly found in biochemical examinations. Eleven cases required intensive care in ICU and 21 cases received caesarean section. There were 2 maternal deaths and 12 fetal losses including 4 abortions. It is concluded that AP is a rare entity in pregnancy. The incidence of pancreatitis increases with the gestational age. However, the severity is not necessarily related with the pregnancy trimesters. The diagnosis is based on clinical presentations, laboratory tests and imaging examinations. Although the treatment strategy of a pregnant woman with pancreatitis is similar to the general non-pregnant patient with AP, a multidisciplinary team consisting of gastroenterologist, gastrointestinal surgeon, radiologist, obstetrician, and ICU doctor should be set up.


Comparison between erbium-doped yttrium aluminum garnet laser therapy and sling procedures in the treatment of stress and mixed urinary incontinence.
Stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) lead to poor quality of life. In Japan, urinary incontinence is treated with tension-free vaginal tape (TVT) or transobturator tape (TOT) sling procedures, which involves inserting a synthetic material; however, problems arise with artificial mesh in some instances, requiring new treatment methods. Hence, laser therapy, whereby an erbium-doped yttrium aluminum garnet laser is directed into the vagina and urethra, may be useful. The study aimed to compare the effects of these three treatments. Subjects included patients who received TVT, TOT, or laser therapy (n = 50 each). The 1-h pad test, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and overactive bladder symptom score were used to assess the patients before and 12 months after treatment. For laser therapy, a probe was inserted into the vagina after applying a local anesthetic to the vaginal wall, and irradiation was performed for 20 min at a wavelength of 2940 nm. This treatment was performed three times every alternate month. As per the 1-h pad test and ICIQ-SF, the TVT, TOT, and laser therapy groups showed comparable improvements in SUI. For patients with MUI, some in the TVT and TOT groups showed exacerbation; however, all patients in the laser therapy group tended to improve. The efficacy of laser therapy for urinary incontinence was confirmed. This is the first study to report on the effect of laser therapy on urinary incontinence in Japanese women.


Prognostic implications of non-culprit plaques in acute coronary syndrome: non-invasive assessment with coronary CT angiography.
Non-culprit plaques are responsible for a substantial number of future events in patients with acute coronary syndrome (ACS). In this study, we evaluated the prognostic implications of non-culprit plaques seen on coronary computed tomography angiography (CTA) in patients with ACS. Coronary CTA was performed in 169 patients (mean 59 ± 11 years, 129 males) admitted with ACS. Data sets were assessed for the presence of obstructive non-culprit plaques (>50% luminal narrowing), segment involvement score, and quantitative measures of plaque burden, after censoring initial culprit plaques. Follow-up was performed for the occurrence of major adverse cardiovascular events (MACEs) unrelated to the initial culprit plaque; cardiac death, second ACS, or coronary revascularization after 90 days. After a median follow-up of 4.8 (IQR 2.6-6.6) years, MACE occurred in 36 (24%) patients: 6 cardiac deaths, 16 second ACS, and 14 coronary revascularizations. Dyslipidaemia (hazard ratio [HR] 3.1 [95% confidence interval 1.5-6.6]) and diabetes mellitus (HR 4.8 [2.3-10.3]) were univariable clinical predictors of MACE. Patients with remaining obstructive non-culprit plaques (HR 3.66 [1.52-8.80]) and higher plaque burden index (HR 1.22 [1.01-1.48]) had a more risk of MACE. In multivariate analysis, with diabetes, dyslipidaemia, and plaque burden index, obstructive non-culprit plaques (HR 3.76 [1.28-11.09]) remained an independent predictor of MACE. Almost a quarter of the study population experienced a new event arising from a non-culprit plaque during a follow-up of almost 5 years. ACS patients with remaining obstructive non-culprit plaques or high plaque burden have an increased risk of future MACE.


The patient journey in Chronic Obstructive Pulmonary Disease (COPD): a human factors qualitative international study to understand the needs of people living with COPD.
Chronic obstructive pulmonary disease (COPD) is a common condition that causes irreversible airway obstruction. Fatigue and exertional dyspnoea, for example, have a detrimental impact on the patient's daily life. Current research has revealed the need to empower the patient, which can result in not only educated and effective decision-making, but also a considerable improvement in patient satisfaction and treatment compliance. The current study aimed to investigate the perspectives and requirements of people living with COPD to possibly explore new ways to manage their disease. Adults with COPD from 8 European countries were interviewed by human factor experts to evaluate their disease journey through the gathering of information on the age, performance, length, and impact of diagnosis, symptoms progression, and family and friends' reactions. The assessment of present symptoms, services, and challenges was performed through a 90-min semi-structured interview. To identify possible unmet needs of participants, a generic thematic method was used to explore patterns, themes, linkages, and sequences within the data collected. Flow charts and diagrams were created to communicate the primary findings. Following analysis, the data was consolidated into cohesive insights and conversation themes relevant to determining the patient's unmet needs. The 62, who voluntarily accepted to be interviewed, were patients (61% females, aged 32-70 years) with a COPD diagnosis for at least 6 months with stable symptoms of different severity. The main challenges expressed by the patients were the impact on their lifestyle, reduced physical activity, and issues with their mobility. About one-fourth had challenges with their symptoms or medication including difficulty in breathing. Beyond finding a cure for COPD was the primary goal for patients, their main needs were to receive adequate information on the disease and treatments, and to have adequate support to improve physical activity and mobility, helpful both for patients and their families. These results could aid in the creation of new ideas and concepts to improve our patient's quality of life, encouraging a holistic approach to people living with COPD and reinforcing the commitment to understanding their needs.


Tanshinone IIA and Cryptotanshinone Counteract Inflammation by Regulating Gene and miRNA Expression in Human SGBS Adipocytes.
Inflammation of the adipose tissue contributes to the onset and progression of several chronic obesity-related diseases. The two most important lipophilic diterpenoid compounds found in the root of Salvia milthorrhiza Bunge (also called Danshen), tanshinone IIA (TIIA) and cryptotanshinone (CRY), have many favorable pharmacological effects. However, their roles in obesity-associated adipocyte inflammation and related sub-networks have not been fully elucidated. In the present study, we investigated the gene, miRNAs and protein expression profile of prototypical obesity-associated dysfunction markers in inflamed human adipocytes treated with TIIA and CRY. The results showed that TIIA and CRY prevented tumor necrosis factor (TNF)-α induced inflammatory response in adipocytes, by counter-regulating the pattern of secreted cytokines/chemokines associated with adipocyte inflammation (CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, IL-6, IL-8, MIF and PAI-1/Serpin E1) via the modulation of gene expression (as demonstrated for CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, and IL-8), as well as related miRNA expression (miR-126-3p, miR-223-3p, miR-124-3p, miR-155-5p, and miR-132-3p), and by attenuating monocyte recruitment. This is the first demonstration of a beneficial effect by TIIA and CRY on adipocyte dysfunction associated with obesity development and complications, offering a new outlook for the prevention and/or treatment of metabolic diseases.


Vascular remodeling alters adhesion protein and cytoskeleton reactions to inflammatory stimuli resulting in enhanced permeability increases in rat venules.
Vascular remodeling has been implicated in many inflammation-involved diseases. This study aims to investigate the microvascular remodeling-associated alterations in cell-cell adhesion and cytoskeleton reactions to inflammatory stimuli and their impact on microvessel permeability. Experiments were conducted in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp), and endothelial intracellular calcium concentration, [Ca(2+)](i), was measured in fura-2-perfused vessels. Alterations in VE-cadherin and F-actin arrangement were examined by confocal imaging. Vascular wall cellular composition and structural changes were evaluated by electron microscopy. Vessels exposed to platelet activating factor (PAF) on day 1 were reevaluated 3 days later in rats that had undergone survival surgery. Initial PAF exposure and surgical disturbance increased microvascular wall thickness along with perivascular cell proliferation and altered F-actin arrangement. Although basal permeability was not changed, upon reexposure to PAF, peak endothelial [Ca(2+)](i) was augmented and the peak Lp was 9.3 ± 1.7 times higher than that of day 1. In contrast to patterns of PAF-induced stress fiber formation and VE-cadherin redistribution observed in day 1 vessels, the day 4 vessels at the potentiated Lp peak exhibited wide separations of VE-cadherin between endothelial cells and striking stress fibers throughout the vascular walls. Confocal images and ultrastructural micrographs also revealed that the largely separated VE-cadherin and endothelial gaps were completely covered by F-actin bundles in extended pericyte processes at the PAF-induced Lp peak. These results indicate that inflammation-induced vascular remodeling increased endothelial susceptibility to inflammatory stimuli with augmented Ca(2+) response resulting in upregulated contractility and potentiated permeability increase. Weakened adhesions between the endothelial cells and contractile mechanisms are both involved in increasing permeability in the intact microvessels and are aggravated during remodeling. The perivascular cells play important roles in stabilizing the microvessel wall, while lessening an otherwise much greater magnitude of leakage during cytoskeletal contraction.


Diagnostic performance of body mass index to detect obesity in patients with coronary artery disease.
Emerging evidence suggests that a mildly elevated body mass index (BMI), is related to improved survival and fewer cardiovascular events in patients with coronary artery disease (CAD). We hypothesize that these results are related to the poor diagnostic performance of BMI to detect adiposity, especially in the intermediate BMI ranges. A cross-sectional study of 95 patients with CAD referred to phase II cardiac rehabilitation. Body fat (BF)% was estimated by air displacement plethysmography. Height, weight, BMI and waist circumference were measured the same day. We calculated the correlation between BMI and both, BF% and lean mass and assessed the diagnostic performance of BMI to detect obesity defined as a BF% > 25% in men and > 35% in women. Although BMI had a good correlation with BF% (rho = 0.66, P < 0.0001), it also had a good correlation with lean mass (rho = 0.41, P < 0.0001), and BMI failed to discriminate between both (P-value = 0.72). A BMI >or= 30 kg/m2 had a good specificity (95%; 95% CI, 83-100) but a poor sensitivity (43%; 95% CI, 32-54) while a BMI >or= 25 kg/m2 had a good sensitivity (91%; 95% CI, 84-97) but a poor specificity (65%; 95% CI, 42-88) to detect BF%-obesity. In patients with CAD, BMI does not discriminate between BF% and lean mass, and a BMI < 30 kg/m(2) is a poor index to diagnose obesity. These findings may explain the controversial findings that link mild elevations of BMI to better survival and fewer cardiovascular events in patients with CAD. Body composition techniques to accurately diagnose obesity in patients with CAD might be necessary.


Urea supplementation in rumen and post-rumen for cattle fed a low-quality tropical forage.
We evaluated the differences between the supplementation of urea in rumen and/or abomasum on forage digestion, N metabolism and urea kinetics in cattle fed a low-quality tropical forage. Five Nellore heifers were fitted with rumen and abomasum fistulas and assigned to a Latin square design. The treatments were control, continuous infusion of urea in the abomasum (AC), continuous infusion of urea in the rumen, a pulse dose of urea in the rumen every 12 h (PR) and a combination of PR and AC. The control exhibited the lowest (P < 0·10) faecal and urinary N losses, which were, overall, increased by supplementation. The highest urinary N losses (P < 0·10) were observed when urea was either totally or partially supplied as a ruminal pulse dose. The rumen N balance was negative for the control and when urea was totally supplied in the abomasum. The greatest microbial N production (P < 0·10) was obtained when urea was partially or totally supplied in the abomasum. Urea supplementation increased (P < 0·10) the amount of urea recycled to the gastrointestinal tract and the amount of urea-N returned to the ornithine cycle. The greatest (P < 0·10) amounts of urea-N used for anabolism were observed when urea was totally and continuously infused in the abomasum. The continuous abomasal infusion also resulted in the highest (P < 0·10) assimilation of microbial N from recycling. The continuous releasing of urea throughout day either in the rumen or abomasum is able to improve N accretion in the animal body, despite mechanism responsible for that being different.


Neurobrucellosis in an endemic area of brucellosis.
Central nervous system involvement occurs less than 5% of patients with brucellosis. A prospective analysis of 73 patients with brucellosis identified 13 (17.8%) neurobrucellosis cases from February 2001 to May 2002. 10 patients had chronic meningitis and 3 acute meningitis. Two patients had only psychiatric disorders. Cranial nerve involvement was observed in 3 patients (6th, 7th and 8th nerves). Three patients had positive blood cultures and 3 others had positive cerebrospinal fluid (CSF) cultures. 12 patients had positive agglutination titres in CSF. All patients received antibiotic therapy with ceftriaxone, rifampicin and doxycycline initially, and after 1 month they were continued with rifampicin and doxycycline up to 4 months. All patients were completely cured. Hearing loss developed in 1 patient as a sequela.


The impact of computerized provider order entry systems on medical-imaging services: a systematic review.
Computerized provider order entry (CPOE) systems have been strongly promoted as a means to improve the quality and efficiency of healthcare. This systematic review aimed to assess the evidence of the impact of CPOE on medical-imaging services and patient outcomes. Fourteen studies met the inclusion criteria, most of which (10/14) used a pre-/postintervention comparison design. Eight studies demonstrated benefits, such as decreased test utilization, associated with decision-support systems promoting adherence to test ordering guidelines. Three studies evaluating medical-imaging ordering and reporting times showed statistically significant decreases in turnaround times. The findings reveal the potential for CPOE to contribute to significant efficiency and effectiveness gains in imaging services. The diversity and scope of the research evidence can be strengthened through increased attention to the circumstances and mechanisms that contribute to the success (or otherwise) of CPOE and its contribution to the enhancement of patient care delivery.


Effect of the Base-Pair Sequence on B-DNA Thermal Conductivity.
The thermal conductivity of double-stranded (ds) B-DNA was systematically investigated using classical molecular dynamics (MD) simulations. The effect of changing the base pair (bp) on the thermal conductivity of dsDNA needed investigation at a molecular level. Hence, four sequences, viz., poly(A), poly(G), poly(CG), and poly(AT), were initially analyzed in this work. First, the length of these sequences was varied from 4 to 40 bp at 300 K, and the respective thermal conductivity (κ) was computed. Second, the temperature-dependent thermal conductivities between 100 and 400 K were obtained in 50 K steps at 28 bp length. The Müller-Plathe reverse nonequilibrium molecular dynamics (RNEMD) was employed to set a thermal gradient and obtain all thermal conductivities in this work. Moreover, mixed sequences using AT and CG sequences, namely, A(CG)nT (n = 3-7), ACGC(AT)mGCGT (m = 0-5), and ACGC(AT)nAGCGT (n = 1-4), were investigated based on the hypothesis that these sequences could be better thermoelectrics. One-dimensional lattices are said to have diverging thermal conductivities at longer lengths, which violate the Fourier law. These follow the power law, where κ ∝ Lβ. At longer lengths, the exponent β needs to satisfy the condition β > 1/3 for divergent thermal conductivity. We find no such significant Fourier law violation through divergence of thermal conductivities at 80 bp lengths or 40 bp lengths. Also, in the case of the second study, the presence of short (m ≤ 2) encapsulated AT sequences within CG sequences shows an increasing trend. These results are important for engineering DNA-based thermal devices.


HIV sequence databases.
Two important databases are often used in HIV genetic research, the HIV Sequence Database in Los Alamos, which collects all sequences and focuses on annotation and data analysis, and the HIV RT/Protease Sequence Database in Stanford, which collects sequences associated with the development of viral resistance against anti-retroviral drugs and focuses on analysis of those sequences. The types of data and services these two databases offer, the tools they provide, and the way they are set up and operated are described in detail.


Impact of a tenofovir disoproxil fumarate plus ritonavir-boosted protease inhibitor-based regimen on renal function in HIV-infected individuals: a prospective, multicenter study.
The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients. Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start (baseline, week 0) and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared. Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 μmol/L, P<0.001) and a lower rate of eGFR (93.0 vs. 101.6 ml/min/1.73 m², P=0.009) at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control (-8.8 vs. 6.4 ml/min/1.73 m², P<0.001). Compared to baseline renal function of the control group, the TDF+PI/r group exhibited a greater median decline in eGFR at the end of week 48 (P<0.001). We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r. ClinicalTrials.gov identifier: NCT00872417.


The systemic theory of living systems and relevance to CAM: the theory (Part III).
Western medical science lacks a solid philosophical and theoretical approach to disease cognition and therapeutics. My first two articles provided a framework for a humane medicine based on Modern Biophysics. Its precepts encompass modern therapeutics and CAM. Modern Biophysics and its concepts are presently missing in medicine, whether orthodox or CAM, albeit they probably provide the long sought explanation that bridges the abyss between East and West. Key points that differentiate Systemic from other systems' approaches are 'Intelligence', 'Energy' and the objective 'to survive'. The General System Theory (GST) took a forward step by proposing a departure from the mechanistic biological concept-of analyzing parts and processes in isolation-and brought us towards an organismic model. GST examines the system's components and results of their interaction. However, GST still does not go far enough. GST assumes 'Self-Organization' as a spontaneous phenomenon, ignoring a causative entity or central controller to all systems: Intelligence. It also neglects 'Survive' as the directional motivation common to any living system, and scarcely assigns 'Energy' its true inherent value. These three parameters, Intelligence, Energy and Survive, are vital variables to be considered, in our human quest, if we are to achieve a unified theory of life.


[Risk-group patients due to the administration of iodine and gadolinium preparations for diagnostic clinical study].
The paper discusses the concept of risk-group patients who have an increased probability of immediate systemic adverse reactions to contrast agents used clinically in various radiodiagnostic techniques. It analyzes the pathogenesis of allergoid reactions to X-ray and magnetic resonance, contrast media. On this basis, the authors describe the abnormalities and nosological entities the patients had in their medical history before diagnostic studies will be indicative of the increased risk of these complications to the administration of a contrast agent.


Response inhibition deficit is involved in poor decision making under risk in nonamnesic individuals with alcoholism.
Individuals with alcoholism exhibit poor decision making as reflected by their continued alcohol use despite encountering problems and by low performance in laboratory tasks of decision making. Here, the authors investigated the relative contribution of several distinct processes of executive functions in performance on the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) in recently detoxified individuals with alcoholism. Compared to matched healthy participants, individuals with alcoholism showed below-normal scores in the last 20 trials of the IGT as well as on other tasks of executive functions, specifically those assessing the capacity to manipulate information stored in working memory, detect abstract rules, or inhibit prepotent responses. Prepotent response inhibition best predicted performance in the late trials of the IGT, that is, when participants have likely acquired knowledge about the reward/punishment contingencies of the task. These results underline the important role that response inhibition plays in decision making, especially in risky situations, when knowledge of the probability of a given outcome becomes available (i.e. decisions under risk).


[Associated changes in recombination length, number of exchanges, and interference in Drosophila chromosome 2].
A set of eight strains differing in recombinational length of the left arm of chromosome 2(2L) was obtained by means of inserting genetic material of the Y chromosome into the 34A region and two inversions, In(1)dl-49 + BM1 and In(3LR)D, demonstrating interchromosomal effects on crossing over. The length of 2L ranged from 15.0 to 64.9 cM. Interchromosomal effects on crossing over differed in extent and in distribution over 2L between females carrying wild-type chromosome 2 and the chromosome with inserts. Tetrad analysis showed that the 2L recombinational length was increased up to the normal level (females +/+; +/+, +/+) or more due to increased proportions of single- or double-exchange tetrads, respectively. A model of pairing and crossing over proposed earlier was used to interpret crossing-over patterns. The model implies that initial pairing of homologous chromosomes involves the formation of local contacts between them. The number of exchanges in a bivalent is determined by the number of local contacts at the onset of an event termed the determination of crossing-over sites (DCS). Interference is determined by the mechanism of contact formation. The extent of interference varies both temporally and spatially (within a chromosome), decreasing from the periphery to a contact site as the time from contact formation increases.


Lack of health insurance is associated with delays in PrEP initiation among young black men who have sex with men in Atlanta, US: a longitudinal cohort study.
Delays between receiving a PrEP prescription and taking a first dose increase the risk of HIV infection. This is especially relevant in populations with high HIV incidence, such as young black men who have sex with men (YBMSM) in the United States. Additionally, YBMSM have relatively low levels of health insurance. We investigated whether lack of health insurance and reliance on PrEP funding through the manufacturer assistance programme (MAP) leads to delays in initiation of PrEP. HIV-negative YBMSM were offered PrEP as part of a prospective cohort. Enrolment began in June 2015 with follow-up through February 2019. Interested participants attended a PrEP clinician visit and received a prescription. Those with health insurance received a copay assistance card; those without insurance accessed PrEP using the MAP. The primary outcome was the days between prescription and initiation. The effect of insurance status on this delay was modelled using a Cox proportional hazards model. The median delay between receipt of a PrEP prescription and taking a first dose was 12 days (IQR 3 to 32). Compared to uninsured participants, the adjusted hazard ratio for PrEP initiation for those with insurance was 2.72 (95% CI 1.82 to 4.06). The adjusted median time to initiation for insured participants was 5 days versus 21 days for those without insurance (p < 0.0001). Older age and STI diagnosis were also associated with faster PrEP initiation. Despite equivalent access to PrEP provided by the study, YBMSM without insurance had longer delays in initiation after receipt of a prescription. Overall, the observed delay in PrEP initiation increases the chances of HIV infection and the possibility of PrEP initiation after undetected seroconversion. The extended time period between PrEP prescription and taking a first dose increases the risk of HIV transmission. Younger YBMSM and those without health insurance had longer delays in PrEP initiation. Immediate PrEP initiation programmes could decrease the likelihood of this occurrence and mitigate the disparity in initiation between those with and without health insurance. Clinical Trial Number: NCT02503618.


Transcriptomics and interactomics during the primary infection of an SfNPV baculovirus on Spodoptera frugiperda larvae.
The fall armyworm (FAW), Spodoptera frugiperda, has been the most devastating pest of corn as well as of other crops in America, and more recently in Africa and Asia. The development of resistance to chemical insecticides led the search for environmentally friendly biological alternatives such as baculoviruses. This study focuses on the primary infection of the baculovirus SfNPV-Ar in the FAW's midgut epithelium, by analyzing the differential expression of transcripts in excised midguts at 6, 12, and 24 h post-infection (hpi), and predicted their interactions. Interaction of viral factors with the infected midgut tissue could alters various cellular processes, such as the apoptotic system due to the up-regulation observed of FABP at 6 hpi and of HSP90 at 24 hpi, along with the down-regulated PRX at 6 hpi and FABP transcripts between 12 and 24 hpi. Changes in transcript regulation could affect the cellular architecture of infected cells due to up-regulation of ARP 2/3 at 6 and 12 hpi, followed by down-regulation at 24 hpi. In relation to protein folding proteins, HSP90 was up-regulated at 24 hpi and PDI was down-regulated between 6 and 12 hpi. With respect to metabolism and cellular transport, AcilBP and ATPS0 were up regulated at 6 hpi and 12 hpi, respectively. In reference to transcription and translation up-regulation of RPL11 at 6 hpi and of FPN32 and RPL19 at 24 hpi was detected, as well as the down-regulation of RPL19 at 6 hpi, of PDI and RPL7 at 12 hpi, and of FABP at 24 hpi. In conclusion, gene regulation induced by viral infection could be related to the cytoskeleton and cellular metabolism as well as to oxidative stress, apoptosis, protein folding, translation, and ribosomal structure. The results presented in this work are an approach to understanding how the virus takes control of the general metabolism of the insect host during the primary infection period.


Reducing Preventable Hospitalizations With Two Models of Transitional Care.
Transitional care is an emerging model of health care designed to decrease preventable adverse events and associated utilization of health care through temporary follow-up after hospital discharge. This study describes the approaches and outcomes of two distinct transitional care programs serving different populations: one is provided by master's-prepared clinical nurse specialists (CNS) with a chronic disease self-management focus, another by physicians specializing in palliative care (PPCs). Existing research has shown that transitional care programs with intensive follow-up reduce hospitalizations, emergency department (ED) visits, and costs. Few studies, however, have included side-by-side descriptions of the efficacy of transitional care programs varying by healthcare providers or program focus. This is a retrospective cohort study comparing the number of ED visits and hospitalizations in the 120 days before and after the intervention for patients enrolled in each transitional care program. Each program included post-hospitalization home visits, but included differences in program focus (chronic disease vs. palliative), assessment and interventions, and population (rural vs. urban). Data from participants in the CNS program (September 2014 to December 2014) were analyzed (n = 98). The average age of participants was 69 years and 65% were female. Data were collected from patients from the PPC program from September 2014 to April 2015 (n = 71). Thirty participants died within 120 days after the intervention and were excluded; the remaining 41 were included in the analysis. Participants had an average age of 81 years and 63% were female. For the CNS program, a secondary analysis of existing data was performed. For the PPC program, a review of patient charts was done to collect data on encounters. A Wilcoxon matched-pairs signed-rank test was performed to test for significance. Patients in the CNS intervention had significantly fewer ED visits (p < .005) and hospitalizations (p < .005) in the 4 months after the intervention than in the 4 months before the intervention. Patients in the PPC program had a nonsignificant reduction in ED visits (p = .327) and a significant reduction in hospitalizations postintervention (p = .03). Both transitional programs have value in decreasing rehospitalizations. The CNS intervention also significantly reduced ED visits for their target population. Further study with randomized controlled trials is needed to allow for a better understanding of the healthcare workforce best fitted to enhance transitional care outcomes. Future study to examine the cost savings of each of the interventions is also needed. Transitional care programs have the potential to prevent unnecessary utilization of health care at the critical periods of transition that leave patients vulnerable to adverse events and poor outcomes.


Interleukin-6 Stimulates Defective Angiogenesis.
The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here, we show that IL6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies, there was an association between levels of IL6 mRNA, Jagged1, and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease, and stroke.