Modeling a Dielectrophoretic Microfluidic Device with Vertical Interdigitated Transducer Electrodes for Separation of Microparticles Based on Size.
This article conceptualizes and mathematically models a dielectrophoretic microfluidic device with two sets of interdigitated transducer vertical electrodes for separation of a binary heterogeneous mixture of particles based on size; each set of electrodes is located on the sidewalls and independently controllable. To achieve separation in the proposed microfluidic device, the small microparticles are subjected to positive dielectrophoresis and the big microparticles do not experience dielectrophoresis. The mathematical model consists of equations describing the motion of each microparticle, fluid flow profile, and electric voltage and field profiles, and they are solved numerically. The equations of motion take into account the influence of phenomena, such as inertia, drag, dielectrophoresis, gravity, and buoyancy. The model is used for a parametric study to understand the influence of parameters on the performance of the microfluidic device. The parameters studied include applied electric voltages, electrode dimensions, volumetric flow rate, and number of electrodes. The separation efficiency of the big and small microparticles is found to be independent of and dependent on all parameters, respectively. On the other hand, the separation purity of the big and small microparticles is found to be dependent on and independent of all parameters, respectively. The mathematical model is useful in designing the proposed microfluidic device with the desired level of separation efficiency and separation purity.


A Comparative Evaluation of Efficacy of Gingival Retraction Using Polyvinyl Siloxane Foam Retraction System, Vinyl Polysiloxane Paste Retraction System, and Copper Wire Reinforced Retraction Cord in Endodontically Treated Teeth: An in vivo Study.
The purpose of the study is to evaluate the efficacy of three gingival retraction systems such as polyvinyl siloxane foam retraction system (magic foam cord; Coltene/WhaledentInc), polysiloxane paste retraction system (GingiTrac; Centrix), and aluminum chloride impregnated twisted retraction cord (Stay-Put; Roeko) in endodontically treated teeth. Patients who were endodontically treated for molars and requiring crown for the same, were selected for the present study with sample size of 45. The 45 participants were divided into three groups. Group 1 was treated with Stay-Put, Group 2 with Magic Foam, and Group 3 with GingiTrac. About 90 elastomeric impressions of the participants were taken-45 impressions before retraction and 45 impressions after retraction. The sulcus width was measured on the die obtained from the elastomeric impressions by placing the dies under OVI-200 optical microscope in combination with X soft imaging system software attached to a computer. The study indicated 0.465627 mm ± 0.063066 mm of gingival retraction for aluminum chloride impregnated retraction cord, 0.210993 mm ± 0.067358 mm of gingival retraction for GingiTrac paste, and 0.294147 mm ± 0.056697 mm of gingival retraction for magic foam cord. The study data indicated that the new retraction systems are not as effective as the standard retraction cord; however, of the two new systems the Magic Foam system did prove to be effective enough for clinical use. The GingiTrac system failed to achieve the minimum gingival retraction required and hence may not be suitable for clinical use.


Measuring perceived efficacy for coping with posttraumatic stress disorder in the workplace.
PTSD is associated with high levels of vocational difficulty, and research on relationships between PTSD and vocational adjustment may be relevant to vocational rehabilitation services to achieve optimal outcomes. Veteran perception of ability to cope with stressors in the workplace setting may play a role in rehabilitation outcome. This article outlines preliminary steps in the development of the Vocational Efficacy in Trauma Survivors Scale (VETSS), to measure perceived efficacy in managing PTSD symptoms in the workplace. This has potential to expand future options for research in vocational rehabilitation for veterans with PTSD. Veterans in outpatient treatment for PTSD at a large, mid-western Veterans Affairs Health Care System facility responded to items on the proposed instrument and items on other measures of vocational and psychological functioning to assess the potential validity of items for an instrument to measure vocational self-efficacy among veterans managing PTSD. In a sample of 63 working veterans who receive outpatient care for PTSD, exploratory factor analysis identified two viable subscales, one tapping Workplace Coping, and another tapping Self-Disclosure. Preliminary findings indicate that the measure demonstrated acceptable indications of reliability and validity, suggesting promise for future use in vocational rehabilitation research.


Determination of proanthocyanidins in grape products by liquid chromatography/mass spectrometric detection under low collision energy.
A method has been established for the identification of proanthocyanidins and quantification of individual monoproanthocyanidins using liquid chromatography/electrospray ionization-mass spectrometric detection (LC/ESI-MSD) for raw grape products. The separated monoproanthocyanidins and oligoproanthocyanidins were individually analyzed and identified by their molecular ion peaks using LC/MS. Using HPLC/ESI-MSD, the proanthocyanidin monomers, (+)-catechin (C), (-)-epicatechin (EC), (-)-catechin gallate (CG), and (-)-epicatechin gallate (ECG) in grape products were successfully quantified by LC/MS/MS detection of protonated molecular ions and characteristic fragment ions for each component under the optimized low collision energy level of 20%. For the investigated concentration ranges of C (21.88-11,200 ng/mL), EC (21.10-10,800 ng/mL), CG (36.72-18,800 ng/mL), and ECG (39.84-20,400 ng/mL), good linearities (r2 > 0.99) for standard curves were obtained. Validation of this method showed an accuracy that was well below 15% and precision (RSD) within 8% for the four compounds. The method proposed here is simple, sensitive, and allows a direct sample preparation procedure. This is the first method that enables the determination of individual monoproanthocyanidins in grape products without any solid-phase extraction.


Estimation of genomic breeding values for residual feed intake in a multibreed cattle population.
Residual feed intake (RFI) is a measure of the efficiency of animals in feed utilization. The accuracies of GEBV for RFI could be improved by increasing the size of the reference population. Combining RFI records of different breeds is a way to do that. The aims of this study were to 1) develop a method for calculating GEBV in a multibreed population and 2) improve the accuracies of GEBV by using SNP associated with RFI. An alternative method for calculating accuracies of GEBV using genomic BLUP (GBLUP) equations is also described and compared to cross-validation tests. The dataset included RFI records and 606,096 SNP genotypes for 5,614 Bos taurus animals including 842 Holstein heifers and 2,009 Australian and 2,763 Canadian beef cattle. A range of models were tested for combining genotype and phenotype information from different breeds and the best model included an overall effect of each SNP, an effect of each SNP specific to a breed, and a small residual polygenic effect defined by the pedigree. In this model, the Holsteins and some Angus cattle were combined into 1 "breed class" because they were the only cattle measured for RFI at an early age (6-9 mo of age) and were fed a similar diet. The average empirical accuracy (0.31), estimated by calculating the correlation between GEBV and actual phenotypes divided by the square root of estimated heritability in 5-fold cross-validation tests, was near to that expected using the GBLUP equations (0.34). The average empirical and expected accuracies were 0.30 and 0.31, respectively, when the GEBV were estimated for each breed separately. Therefore, the across-breed reference population increased the accuracy of GEBV slightly, although the gain was greater for breeds with smaller number of individuals in the reference population (0.08 in Murray Grey and 0.11 in Hereford for empirical accuracy). In a second approach, SNP that were significantly (P < 0.001) associated with RFI in the beef cattle genomewide association studies were used to create an auxiliary genomic relationship matrix for estimating GEBV in Holstein heifers. The empirical (and expected) accuracy of GEBV within Holsteins increased from 0.33 (0.35) to 0.39 (0.36) and improved even more to 0.43 (0.50) when using a multibreed reference population. Therefore, a multibreed reference population is a useful resource to find SNP with a greater than average association with RFI in 1 breed and use them to estimate GEBV in another breed.


Current status of safety and efficacy of calcium channel blockers in cardiovascular diseases: a critical analysis based on 100 studies.
Recently, serious concerns have been expressed about the long-term safety of the calcium channel blockers (CCBs) as a group. Safety and efficacy are, however, ultimately linked to each other; therefore both must be evaluated especially in the therapy of angina and hypertension, the main clinical indications for CCBs. The structural, functional, and pharmacokinetic heterogeneity of CCBs means that the efficacy and dangers of one subclass, such as the short-acting dihydropyridines (DHPs), in one situation, such as unstable angina, do not necessarily apply in other clinical situations. One hundred studies are reviewed according to their methods of data collection: case series, case control, cohort, randomized controlled trials (RCTs), and meta-analyses. Large, well-designed RCTs and the meta-analyses based on these trials remain the gold standard. Observational studies, though potentially less reliable sources of information because of selection bias, may nevertheless produce hypotheses that must then be tested in RCTs. Regarding safety, both observational studies and RCTs suggest that adverse effects of CCBs may be linked to short-acting agents, specifically short-acting nifedipine. Two good studies favor the safety of verapamil, even in short-acting form. Incomplete but increasing overall evidence favors the safety of longer-acting DHPs. Heart failure remains a class contraindication to the use of all CCBs, with some exceptions. Regarding efficacy, there are positive results of RCTs with CCBs in 2 specific clinical situations, namely, verapamil in postinfarct protection in the absence of pre-existing heart failure, and 2 outcome studies on hypertension with longer acting DHPs. These results cannot automatically be applied to other clinical situations and to other CCBs. For example, there is no evidence for the safety or efficacy of DHPs used without beta blockers in postinfarct patients. In diabetic hypertensives, 2 relatively large RCTs show that the blood pressure can be reduced by DHP-based therapy in diabetics, with a reduction in hard end points. To achieve current blood pressure goals, combination therapy is almost always necessary, and in diabetics there is strong evidence that 1 essential component should be an angiotensin converting enzyme inhibitor. The future aim with CCBs must be to obtain a large database gathered from RCTs, which will give the same certainty about efficacy and safety that already holds for use of the diuretics in hypertension, beta-blockers in postmyocardial infarction patients, and the angiotensin converting enzyme inhibitors in heart failure.


Recurrent brief depression and personality traits in allergy, anxiety and premenstrual syndrome patients: a general practice survey.
Recurrent brief depression (RBD) is a common disorder, poorly characterised in clinical studies. Some problems associated with the diagnosis and treatment of RBD may be improved if patients are easier to identify. This study investigates the distribution of RBD and personality types within three common syndromes. A survey of adult patients in one general practice. Patients with anxiety, PMS or an allergy condition (n=1094) were screened for exclusion criteria, including depression. Of the study sample (n=384) 159 patients were interviewed. RBD patients were identified by DSM-IV criteria. The Hospital Anxiety and Depression Scale was used to categorise RBD (symptom scores of at least moderate severity) and RBD-res (milder symptoms) patients. Trait anxiety and personality dimensions were measured with the State-Trait Anxiety Inventory (STAI) and Eysencks' Personality Questionnaire (EPQ-R). In the syndrome groups, 40% of anxiety or PMS patients and 21% of allergy patients had a recurrent problem with brief depression, with half reporting symptoms of at least moderate severity. Patients with brief depression showed syndrome specific symptom and impairment differences for sleep, cognition, medication and suicide ideation. There were significant differences in the distribution of STAI, neuroticism (N) and extraversion (E) scores between patients in the RBD and no depression categories. In the anxiety group, high STAI or N scores, and low E scores identified all patients with RBD. This study reveals a substantial burden of RBD in a practice population who were not receiving treatment nor consulting for depression. Trait scores were useful markers of RBD in patients with an anxiety condition.


The Human Proteoform Project: Defining the human proteome.
Proteins are the primary effectors of function in biology, and thus, complete knowledge of their structure and properties is fundamental to deciphering function in basic and translational research. The chemical diversity of proteins is expressed in their many proteoforms, which result from combinations of genetic polymorphisms, RNA splice variants, and posttranslational modifications. This knowledge is foundational for the biological complexes and networks that control biology yet remains largely unknown. We propose here an ambitious initiative to define the human proteome, that is, to generate a definitive reference set of the proteoforms produced from the genome. Several examples of the power and importance of proteoform-level knowledge in disease-based research are presented along with a call for improved technologies in a two-pronged strategy to the Human Proteoform Project.


Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells.
Patients with mutations in the Artemis gene display a complete absence of T- and B lymphocytes, together with increased cellular radiosensitivity; this leads to a radiosensitive severe combined immunodeficiency (RS-SCID). Allogenic hematopoietic stem-cell (HSC) transplantation is only partially successful in the absence of an human leukocyte antigen-genoidentical donor, and this has prompted a search for alternative therapeutic approaches such as gene therapy. In this study, a self-inactivated lentiviral vector expressing Artemis was used to complement the Artemis knockout mouse (Art(-/-)). Transplantation of Artemis-transduced HSCs into irradiated Art(-/-) mice restored a stable (over a 15-month period of follow-up) and functional T- and cell repertoire that was comparable to that of control mice. The success of secondary transplantations demonstrated that the HSCs had been transduced. One of thirteen mice developed a thymoma 6 months after gene therapy. Although thymic cells were seen to be carrying two lentiviral integration sites, there was no evidence of lentivirus-driven oncogene activation. The Art(-/-) mice were found to be prone to develop T-cell lymphomas, either spontaneously or after irradiation. These data indicate that the observed lymphoproliferation was probably the consequence of the chromosomal instability associated with the Artemis-deficient background. As a whole, our work provides a basis for supporting the gene therapy approach in Artemis-deficient SCID.


Detection of Philadelphia chromosome-positive cells by the polymerase chain reaction following bone marrow transplant for chronic myelogenous leukemia.
Sixteen patients treated by allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr/abl-specific RNA transcripts at various time points after BMT. In reconstitution experiments, one CML cell per million normal mononuclear cells could be detected by direct agarose gel visualization of a bcr/abl-specific band following PCR. Bcr/abl message was found in ten out of 16 patients post-BMT. PCR-positive bcr/abl was present only transiently in three patients and correlated with relapse in three. One patient died in clinical remission, while two patients remain in remission despite persistence of bcr/abl-positive abl-positive cells at 180 days. Long-term follow-up of bcr/abl-positive patients in clinical remission may provide insight into the fate or residual Ph+ cells after BMT. This approach may aid in the identification of high-risk patients likely to relapse post-BMT.


What to expect when girls are expecting: psychosocial support challenges and opportunities in the context and aftermath of teenage pregnancy in Kenya.
An understanding of the psychosocial support challenges and opportunities in the context of teenage pregnancy is important for developing appropriate interventions for pregnant and parenting girls. This qualitative study was conducted in Homa Bay County, Kenya, to examine the experience of teenage pregnancy and the resultant psychosocial support needs from the perspectives of both pregnant/parenting girls and their own parents, who are typically expected to provide various forms of support. The study used a descriptive case study design, drawing on counseling case notes documented by psychologists who held counseling sessions with 20 pregnant or parenting girls and 6 of their parents as part of a psychosocial support intervention. The counseling case notes formed a qualitative data set, which was analyzed thematically. Emerging master themes were related to pregnant and parenting girls' experience of sexual violence and adverse childbirth outcomes; psychological trauma confronted by girls and their parents alike; parental need for support in communicating with pregnant/parenting girls about sex and sexuality; and the availability of family support as a resource for teenage mothers. Pregnant and parenting teenage girls require a range of psychosocial support responses that recognize the realities of sexual violence and other challenges in the lives of the girls themselves, as well as in the lives of their parents and caregivers. While parents and other caregivers can serve as an important resource for supporting affected girls, they often need assistance as well, in order to support pregnant/parenting girls effectively. These realities need to be taken into account to maximize the effectiveness of health and development programs for pregnant and parenting girls. Furthermore, emerging themes from actual counseling sessions with affected girls and parents can provide important insights into the potential psychosocial support needs of the broader population of pregnant and parenting girls.


Prospective one-year cost-of-illness study in a cohort of patients with dementia of Alzheimer's disease type in Spain: the ECO study.
In this study, we analyzed the economic impact of one-year healthcare and non-healthcare resources utilization by patients with dementia of Alzheimer's disease (AD) under usual medical practice in Spain. A one-year, prospective, naturalistic, multicenter cohort study was designed to recruit patients with mild, moderate to severe, and severe AD according to Clinical Dementia Rating scale: the ECO study. Healthcare resources (medical visits, drugs and concomitant treatments, complementary and diagnostic tests, institutionalization and use of home-nursing facilities) and non-healthcare resources (inventory materials, consumables, professional and non-professional caregivers' time for care and supervision) were recorded and valued at 2006 prices. A total of 560 patients with possible/probable AD by DSM-IV-NINCDS-ADRDA criteria were included in the study: 68% women, 77 +/- 6 years old, 29% treatment naïve. Monthly average cost per patient was 1,425.73 euro, and increased 10.08% at the end of the study (baseline monthly cost; 1,316.22 euro). Non-healthcare costs 1059.00 euro, 74.30% of total cost) decreased 4.30 euro/month (0.40%) at the end of the year, while healthcare costs, which presented a total average of 366.66 euro, grew by 136.94 euro in the period (54.06%), mainly due to cost of drugs, nursing home utilization, and institutionalization. The 87.26% of the overall cost (1,244.22 euro) was not financed by National Health Service (NHS), and the majority of this cost corresponded to caregiver-associated cost. The caregiver's total burden represented 70.86% of the overall cost-of-illness. In conclusion, monthly overall mean cost of dementia of AD type was high in Spain (1,412.73 euro). Almost 88% of the cost-of-illness is funded by the patient's own family, adding a financial burden to the suffering of these families.


Subtercola boreus gen. nov., sp. nov. and Subtercola frigoramans sp. nov., two new psychrophilic actinobacteria isolated from boreal groundwater.
Psychrophilic actinobacterial isolates from permanently cold groundwater in Finland were characterized using a polyphasic approach. Growth on agar plates was observed at temperatures down to -2 degrees C, with an optimum at 15-17 degrees C, but no growth was observed at 30 degrees C. The peptidoglycan type was B2y and the characteristic diamino acid was diaminobutyric acid. The cell wall sugars of strain K265T were rhamnose, ribose, xylose and mannose and those of strain K300T were glucose, rhamnose and xylose. The polar lipids included phosphatidylglycerol, diphosphatidylglycerol, one unknown phospholipid and two glycolipids. The main whole-cell fatty acids were 12-methyltetradecanoic acid, 14-methylpentadecanoic acid and 14-methylhexadecanoic acid. Large amounts of anteiso-1,1-dimethoxy-pentadecane and also iso-1,1-dimethoxyhexadecane were present as diagnostic markers. The predominant menaquinones were MK-9 and MK-10. The G+C content of the DNA of strains K265T and K300T was 64.4 and 67.8 mol%, respectively. Comparison of 16S rRNA gene sequences revealed that strains K265T and K300T represent a new lineage among the type-B-peptidoglycan actinomycetes. The closest relatives were Clavibacter michiganensis, Frigoribacterium faeni and Rathayibacter rathayi. On the basis of 16S rDNA sequence, G+C content and chemotaxonomical and physiological characteristics, K265T and K300T clearly represent a new genus. The genus Subtercola gen. nov. is described, together with two species, namely Subtercola boreus sp. nov. (type strain K300T = DSM 13056T = CCUG 43135T) and Subtercola frigoramans sp. nov (type strain K265T = DSM 13057T = CCUG 43136T).


Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects.
To systematically develop dietary strategies based on resistant starch (RS) that modulate the human gut microbiome, detailed in vivo studies that evaluate the effects of different forms of RS on the community structure and population dynamics of the gut microbiota are necessary. The aim of the present study was to gain a community wide perspective of the effects of RS types 2 (RS2) and 4 (RS4) on the fecal microbiota in human individuals. Ten human subjects consumed crackers for three weeks each containing either RS2, RS4, or native starch in a double-blind, crossover design. Multiplex sequencing of 16S rRNA tags revealed that both types of RS induced several significant compositional alterations in the fecal microbial populations, with differential effects on community structure. RS4 but not RS2 induced phylum-level changes, significantly increasing Actinobacteria and Bacteroidetes while decreasing Firmicutes. At the species level, the changes evoked by RS4 were increases in Bifidobacterium adolescentis and Parabacteroides distasonis, while RS2 significantly raised the proportions of Ruminococcus bromii and Eubacterium rectale when compared to RS4. The population shifts caused by RS4 were numerically substantial for several taxa, leading for example, to a ten-fold increase in bifidobacteria in three of the subjects, enriching them to 18-30% of the fecal microbial community. The responses to RS and their magnitudes varied between individuals, and they were reversible and tightly associated with the consumption of RS. Our results demonstrate that RS2 and RS4 show functional differences in their effect on human fecal microbiota composition, indicating that the chemical structure of RS determines its accessibility by groups of colonic bacteria. The findings imply that specific bacterial populations could be selectively targeted by well designed functional carbohydrates, but the inter-subject variations in the response to RS indicates that such strategies might benefit from more personalized approaches.


Novel and versatile reactions of trifluoroamine oxide: a new route to polyfluorinated ethers.
A series of pyrimidine methyl and polyfluoroalkyl ethers were synthesized from the reactions of trifluoroamine oxide (1) with several 5-substituted uracils in the presence of tetrabutylammonium hydroxide and methanol, 2,2,2-trifluoroethanol (6), or 1H,1H-pentafluoropropanol (7). With 5-(trifluoromethyl)uracil (2), the new ethers formed were 5-fluoro-5-(trifluoromethyl)-6-methoxypyrimidine-2,4-dione (8), 5-fluoro-5-(trifluoromethyl)-6-(trifluoroethoxy)pyrimidine-2,4-dione (9), and 5-fluoro-5-(trifluoromethyl)-6-(1H,1H- pentafluoropropoxy)pyrimidine-2,4-dione (10). With 5-chlorouracil (3), the new ethers 5-chloro-5-fluoro-6-methoxypyrimidine-2,4-dione (11), 5-chloro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (12), and 5-chloro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (13) were obtained. With 5-fluorouracil (4), the new ethers 5,5-difluoro-6-methoxypyrimidine-2,4-dione (14), 5,5-difluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (15) and 5,5 difluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (16) were found. By reaction of 5-nitrouracil (5), the new ethers 5-nitro-5-fluoro-6 methoxypyrimidine-2,4-dione (17), 5-nitro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (18), and 5-nitro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (19) were obtained. Each of the new compounds was characterized by using IR, 19F and 1H NMR, and mass spectroscopy, and elemental analysis. A single-crystal X-ray diffraction study of 8 was helpful in confirming compound structure.


NIH consensus development conference statement: Lactose intolerance and health.
To provide health care providers, patients, and the general public with a responsible assessment of currently available data on lactose intolerance and health. A non-DHHS, nonadvocate 14-member panel representing the fields of internal medicine, pediatrics, pediatric and adult endocrinology, gastroenterology, hepatology, neonatology and perinatology, geriatrics, racial/ethnic disparities, radiology, maternal and fetal nutrition, vitamin and mineral metabolism, nutritional sciences, bone health, preventive medicine, biopsychology, biostatistics, statistical genetics, epidemiology, and a public representative. In addition, 22 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the University of Minnesota Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. • Lactose intolerance is a real and important clinical syndrome, but its true prevalence is not known. • The majority of people with lactose malabsorption do not have clinical lactose intolerance. Many individuals who think they are lactose intolerant are not lactose malabsorbers. • Many individuals with real or perceived lactose intolerance avoid dairy and ingest inadequate amounts of calcium and vitamin D, which may predispose them to decreased bone accrual, osteoporosis, and other adverse health outcomes. In most cases, individuals do not need to eliminate dairy consumption completely. • Evidence-based dietary approaches with and without dairy foods and supplementation strategies are needed to ensure appropriate consumption of calcium and other nutrients in lactose-intolerant individuals. • Educational programs and behavioral approaches for individuals and their healthcare providers should be developed and validated to improve the nutrition and symptoms of individuals with lactose intolerance and dairy avoidance.


A multizone cerebellar chip for bioinspired adaptive robot control and sensorimotor processing.
The cerebellum is a neural structure essential for learning, which is connected via multiple zones to many different regions of the brain, and is thought to improve human performance in a large range of sensory, motor and even cognitive processing tasks. An intriguing possibility for the control of complex robotic systems would be to develop an artificial cerebellar chip with multiple zones that could be similarly connected to a variety of subsystems to optimize performance. The novel aim of this paper, therefore, is to propose and investigate a multizone cerebellar chip applied to a range of tasks in robot adaptive control and sensorimotor processing. The multizone cerebellar chip was evaluated using a custom robotic platform consisting of an array of tactile sensors driven by dielectric electroactive polymers mounted upon a standard industrial robot arm. The results demonstrate that the performance in each task was improved by the concurrent, stable learning in each cerebellar zone. This paper, therefore, provides the first empirical demonstration that a synthetic, multizone, cerebellar chip could be embodied within existing robotic systems to improve performance in a diverse range of tasks, much like the cerebellum in a biological system.


High frequency spikes in long period blood cell oscillations.
Several hematological diseases are characterised by oscillations of various blood cell populations. Two of these are a variant of chronic myelogenous leukemia (CML) and cyclical neutropenia (CN). These oscillations typically have long periods ranging from 20 to 60 days, despite the fact that the stem cell cycling time is thought to be of the order of 2-3 days. Clinical data from humans and laboratory data from the grey collie animal model of CN is suggestive of the idea that these long period oscillations may also contain higher frequency spiky oscillations. We show how such oscillations can be understood in the context of slow periodic stem cell oscillations, by analysing a two component differential-delay equation model of stem cell and neutrophil populations.


[A case of chemical colitis caused by hydrogen peroxide enema].
Hydrogen peroxide is commonly used as a disinfectant that has been reported to cause chemical colitis. We report a case of 49 year-old man who presented with chemical colitis caused by self-inflicted hydrogen peroxide enema. In the sigmoidoscopic examination, diffuse erythematous and edematous mucosal change with multiple ulcerations and easy touch bleeding was noted from the rectum to the proximal sigmoid colon. Abdominal computed tomography showed diffuse wall thickening of the rectum and the sigmoid colon with inflammatory and reactive change at surrounding. The patient was treated with NPO, intravenous fluid, and antibiotic therapy. On 5th hospital day, abdominal pain and bloody stool disappeared, and the patient started oral feeding. He discharged on 6th hospital day with fully recovered state.


The Metabolic Activity of Caudate and Prefrontal Cortex Negatively Correlates with the Severity of Idiopathic Parkinson's Disease.
Positron emission tomography (PET) scan with tracer [18F]-fluorodeoxy-glucose (18F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson's disease (IPD). Previous studies using 18F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.


Gender differences in minor morbidity among full time employees of a British university.
To examine gender differences in minor morbidity among men and women working in similar circumstances, and to test whether the relation between reported working conditions and health is similar for men and women. Multivariate analysis of data collected from a postal questionnaire distributed to full time employees in white collar jobs within a single organisation. A British university. 1641 employees (1009 men and 632 women) working full time in white collar occupations in the university. Overall, female university employees reported more "physical" symptoms (2.0 v 1.7, p < 0.001) and more "malaise" symptoms (1.4 v 1.1, p < 0.001) than male employees, but mean scores on a measure of minor psychiatric morbidity did not differ by gender. Poor perceived working conditions (and particularly lack of job stimulation, job drain and poor physical conditions) were consistently related to all three measures of minor morbidity, and these variables accounted for most of the variance in these health measures in this sample. When the analysis controlled for occupational grade, perceived working conditions and orientation to gender roles, there was no difference between men and women for any of the health measures. The relations for the predictor variables were generally the same for men and women (and there were no interactions with gender for any of the work related variables). Although small gender differences in recent experience of malaise and physical symptoms remain when examining men and women in as similar working circumstances as possible, these differences are cumulatively eroded by taking account of occupational grade, reported working conditions and orientation to gender. These results lend support to a differential exposure, rather than a differential vulnerability, model of gender differences in health.


Efficient sex pheromone trapping: catching the sweetpotato weevil, Cylas formicarius.
The sweetpotato weevil, Cylas formicarius (Fabricius) (Coleoptera: Brentidae), is the most serious pest of sweetpotato around the world, damaging sweetpotatoes in the field and in storage, as well as being a quarantine pest. Because the larval period is spent within vines or tubers, and the adults are nocturnal, chemical control frequently is not effective. In addition, there are few natural enemies, and pheromone-based trapping does not appear to reduce the damage level. In the present study, we evaluated a number of parameters that affect pheromone-based trap catch, including trap design, trap size, trap color, and height at which the traps are placed. Pherocon unitraps caught higher numbers than ground, funnel water, or delta traps. Medium-sized traps (13 × 17.5 cm) were more effective than larger or smaller traps. In a color-choice test, C. formicarius preferred red over gray, brown, blue, white, yellow, black, or red traps; light red was more attractive than other shades of red. Maximum catches were obtained when the traps were set 50 cm above the crop canopy. Light-red unitraps with pheromone lures caught more adults than identical traps without lures, suggesting that C. formicarius is influenced by both visual and olfactory cues. Pheromone-baited light-red unitraps, 13 × 17.5 cm, installed 50 cm above the crop canopy, were the most effective at catching C. formicarius adults, and they appear to have the greatest potential for use in trap-and-kill strategies and eradication programs.


Primary human testicular PDGFRα+ cells are multipotent and can be differentiated into cells with Leydig cell characteristics in vitro.
Is it possible to differentiate primary human testicular platelet-derived growth factor receptor alpha positive (PDGFRα+) cells into functional Leydig cells? Although human testicular PDGFRα+ cells are multipotent and are capable of differentiating into steroidogenic cells with Leydig cell characteristics, they are not able to produce testosterone after differentiation. In rodents, stem Leydig cells (SLCs) that have been identified and isolated using the marker PDGFRα can give rise to adult testosterone-producing Leydig cells after appropriate differentiation in vitro. Although PDGFRα+ cells have also been identified in human testicular tissue, so far there is no evidence that these cells are true human SLCs that can differentiate into functional Leydig cells in vitro or in vivo. We isolated testicular cells enriched for interstitial cells from frozen-thawed fragments of testicular tissue from four human donors. Depending on the obtained cell number, PDGFRα+-sorted cells of three to four donors were exposed to differentiation conditions in vitro to stimulate development into adipocytes, osteocytes, chondrocytes or into Leydig cells. We compared their cell characteristics with cells directly after sorting and cells in propagation conditions. To investigate their differentiation potential in vivo, PDGFRα+-sorted cells were transplanted in the testis of 12 luteinizing hormone receptor-knockout (LuRKO) mice of which 6 mice received immunosuppression treatment. An additional six mice did not receive cell transplantation and were used as a control. Human testicular interstitial cells were cultured to Passage 3 and FACS sorted for HLA-A,B,C+/CD34-/PDGFRα+. We examined their mesenchymal stromal cell (MSC) membrane protein expression by FACS analyses. Furthermore, we investigated lineage-specific staining and gene expression after MSC trilineage differentiation. For the differentiation into Leydig cells, PDGFRα+-sorted cells were cultured in either proliferation or differentiation medium for 28 days, after which they were stimulated either with or without hCG, forskolin or dbcAMP for 24 h to examine the increase in gene expression of steroidogenic enzymes using qPCR. In addition, testosterone, androstenedione and progesterone levels were measured in the culture medium. We also transplanted human PDGFRα+-sorted testicular interstitial cells into the testis of LuRKO mice. Serum was collected at several time points after transplantation, and testosterone was measured. Twenty weeks after transplantation testes were collected for histological examination. From primary cultured human testicular interstitial cells at Passage 3, we could obtain a population of HLA-A,B,C+/CD34-/PDGFRα+ cells by FACS. The sorted cells showed characteristics of MSC and were able to differentiate into adipocytes, chondrocytes and osteocytes. Upon directed differentiation into Leydig cells in vitro, we observed a significant increase in the expression of HSD3B2 and INSL3. After 24 h stimulation with forskolin or dbcAMP, a significantly increased expression of STAR and CYP11A1 was observed. The cells already expressed HSD17B3 and CYP17A1 before differentiation but the expression of these genes were not significantly increased after differentiation and stimulation. Testosterone levels could not be detected in the medium in any of the stimulation conditions, but after stimulation with forskolin or dbcAMP, androstenedione and progesterone were detected in culture medium. After transplantation of the human cells into the testes of LuRKO mice, no significant increase in serum testosterone levels was found compared to the controls. Also, no human cells were identified in the interstitium of mice testes 20 weeks after transplantation. N/A. This study was performed using tissue from only four donors because of limitations in donor material. Because of the need of sufficient cell numbers, we first propagated cells to passage 3 before FACS of the desired cell population was performed. We cannot rule out this propagation of the cells resulted in loss of stem cell properties. A lot of information on Leydig cell development is obtained from rodent studies, while the knowledge on human Leydig cell development is very limited. Our study shows that human testicular interstitial PDGFRα+ cells have different characteristics compared to rodent testicular PDGFRα+ cells in gene expression levels of steroidogenic enzymes and potential to differentiate in adult Leydig cells under comparable culture conditions. This emphasizes the need for confirming results from rodent studies in the human situation to be able to translate this knowledge to the human conditions, to eventually contribute to improvements of testosterone replacement therapies or establishing alternative cell therapies in the future, potentially based on SLCs. This study was funded by Amsterdam UMC, location AMC, Amsterdam, the Netherlands. All authors declare no competing interests.


Selective recognition of alkyl pyranosides in protic and aprotic solvents.
The design and synthesis of receptors capable of selective, noncovalent recognition of carbohydrates continues to be a signature challenge in bioorganic chemistry. We report a new generation of tripodal receptors incorporating three pyridine (compound 2) or quinoline (compound 3) rings around a central cyclohexane core for use in molecular recognition of monosaccharides in apolar and polar protic solvents. These tripodal receptors were investigated using (1)H NMR, UV, and fluorescence titrations in order to determine their binding abilities toward a set of octyl glycosides. Receptor 2 displayed the highest binding affinity reported to date for noncovalent 1:1 binding of an alpha-glucopyranoside in chloroform (Ka = 212,000 +/- 27,000 M(-1)) and an approximately 8-fold selectivity for the alpha anomer over the beta anomer of the glucopyranoside. Most importantly, 2 retained its micromolar range of affinities toward monosaccharides in a polar and highly competitive solvent (methanol). The quinoline variant 3 also displayed micromolar binding affinities for selected monosaccharides in methanol (as measured by fluorescence) that were generally smaller than those of 2. Compound 3 was found to follow a selectivity pattern similar to that of 2, displaying higher affinities for glucopyranosides than for other monosaccharides. The binding stoichiometry was estimated to be 1:1 for the complexes formed by both 2 and 3 with glucopyranosides, as determined by Job plots. Nuclear Overhauser effect spectroscopy allowed for the derivation of a binding model consistent with the observed selectivities.


Evaluation the quality of bag-mask ventilation by E/C, T/E and hook technique (a new proposed technique).
Bag-Mask Ventilation (BMV) is a crucial skill in managing emergency airway situations and induction of general anesthesia. Ensuring proficient BMV execution is imperative for healthcare providers. Various techniques exist for performing BMV. This study aims to compare the quality of ventilation achieved using the E/C technique, Thenar Eminence (T/E) technique and a novel approach referred to as the hook technique. The goal is to identify the most effective single-person BMV method. We conduct a pilot study on manikins involving 63 medical staff members who used the hook technique for ventilation. Subsequently, we obtained ethical approval and patient guardian consent to perform the study on 492 emergency department (ED) patients. These patients were randomly divided into three groups, with each group subjected to one three ventilation techniques. The study focused on patients requiring reliable airway management for rapid sequence intubation (RSI). Ventilation was administrated using bag-mask device connected to the capnograph. End-tidal CO2 (ETCO2) levels were recorded. Demographic data were collected and analyzed by SPSS software version 22. Success rates were reported as frequency (percentage) as well as mean ± standard deviation. Comparing partial pressure of CO2 (PCO2) results obtained via capnography between T/E, E/C and hook techniques, we found that the successful ventilation rate was 87.2% for T/E, 89.6% for E/C, and 93.3% for the hook methods. The hook method demonstrated significantly higher success rate compared to the other two techniques (P-value = 0.038). Furthermore, we observed statistically significant trends in PCO2 changes between measurements both within and between groups (P-value < 0/001). Our study indicates that the hook method achieved notably higher success rate in ventilation compared to the T/E and E/C methods. This suggests that the hook method, which involves a chin lift maneuver while securely fitting the mask, could serve as a novel BMV technique, particularly for resuscitation with small hands for a prolonged use without fatigue and finger discomfort. Our finding contributes to the development of a new BMV method referred to as the hook technique. IRCT registration number: IRCT20121010011067N5. URL of trial registry record: https://www.irct.ir/trial/57420 .


Analytical refinements in animal calorimetry.
An analysis is presented of a system for indirect calorimetric measurement. Emphasis has been placed upon problems associated with the use of large climate-controlled chambers. The dynamics of gas exchange and the influence of ambient conditions on various parameters have been subjected to physical analysis which has led to the following conclusions: 1) Fast-response measurement of heat production can be achieved even if the size and hence washout time of the chamber is large. 2) Accurate continuous measurement of heat production over long periods, without correction for changes in barometric pressure, is possible if suitable instrumentation is chosen. 3) A method for calibration of a paramagnetic oxygen analyzer achieved high accuracy at low cost. 4) The entire system has been checked by simulation of gas exchange in the chamber, by injection of nitrogen at a known rate.


Socioeconomic status and cancer survival in Ontario.
It is known that the socioeconomic status (SES) of the patient is associated with cancer survival in the United States. The purpose of this study was to determine whether the association between SES and survival is also present in Canada, a society with a comprehensive, universal, health insurance program. A population-based cancer registry was used to identify the 357,530 cases of invasive cancer diagnosed in the Canadian province of Ontario between 1982 and 1991. Information from the 1986 Canadian census was linked to the registry and used to describe the SES of the area in which each patient resided. Cox regression was used to describe the association between median household income and survival while controlling for age, sex, and the region in which the patient resided. The Cox model was fitted in a competing risk framework to assess the association between income and the probability of specific causes of death. Lung cancer and cancers of the head and neck region were relatively more common in poor-income communities, and cancers of the breast, CNS, and testis were relatively more common in richer communities. A strong and statistically significant association between community income and survival was observed in cancers of the head and neck region, cervix, uterus, breast, prostate, bladder, and esophagus. Smaller, but significant associations were seen in cancers of the lung and rectum. No significant association between community income and survival was observed in cancers of the stomach, colon, pancreas, or ovary. Analysis of the cause of death showed that community income is associated both with the probability of death from cancer and with the probability of death from other causes. Although Canada's health care system was designed to provide equitable access to equivalent standards of care, it does not prevent a difference in cancer survival between rich and poor communities.


Cervical Evaluation in Pregnancy: Proper Measurement, Evaluation, and Management.
Preterm birth is the leading cause of perinatal morbidity and mortality in developed nations. The heterogeneous causes of spontaneous preterm birth make prediction and prevention difficult. The primary importance of transvaginal cervical sonography and cervicovaginal fetal fibronectin lies in their high negative predictive values in assessing risk for preterm birth. Cervical length may be useful in identifying women who are candidates for cervical cerclage or progesterone therapy for preterm birth prevention. Together, cervical length and fibronectin can be used in the triaging of women symptomatic for preterm labor.


Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II.
Recent observations in our laboratory suggest that angiotensin II (Ang II) is a bifunctional vascular smooth muscle cell (VSMC) growth modulator capable of inducing hypertrophy or inhibiting mitogen-stimulated DNA synthesis. Because transforming growth factor-beta 1 (TGF beta 1) has similar bifunctional effects on VSMC growth, we hypothesized that autocrine production of TGF beta 1 may mediate the growth modulatory effects of Ang II. Indeed, this study demonstrates that Ang II induces a severalfold increase in TGF beta 1 mRNA levels within 4 h that is dependent on de novo protein synthesis and appears to be mediated by activation of protein kinase C (PKC). Ang II not only stimulates the synthesis of latent TGF beta 1, but also promotes its conversion to the biologically active form as measured by bioassay. The coincubation of VSMCs with Ang II and control IgG has no significant mitogenic effect. However, the co-administration of Ang II and the anti-TGF beta 1 antibody stimulates significantly DNA synthesis and cell proliferation. We conclude that: (a) Ang II induces increased TGF beta 1 gene expression via a PKC dependent pathway involving de novo protein synthesis; (b) Ang II promotes the conversion of latent TGF beta 1 to its biologically active form; (c) Ang II modulates VSMC growth by activating both proliferative and antiproliferative pathways; and (d) Autocrine active TGF beta 1 appears to be an important determinant of VSMC growth by hypertrophy or hyperplasia.


The Roles of Long Noncoding RNA in Depression.
Depression is a common psychiatric disorder that brings great pain and burden to patients and their families. However, the pathogenesis underlying the development of depression remains unclear, limiting the development of diagnostic and therapeutic approaches for the disease. Recently, an increasing number of studies have shown that long noncoding RNAs (lncRNAs) play modulatory roles in depression. Here, we summarize the general mechanism of action and their roles in depression. LncRNAs are suggested to exert regulatory functions in depression in various ways, including competing endogenous RNA (ceRNA) networks, interacting with epigenetic modifications, interacting with single-nucleotide polymorphisms (SNPs), acting in cis or trans on target genes and regulating the immune system. A total of 13 lncRNAs (involving 16 ceRNA regulatory axes) have been revealed to have regulatory mechanisms. The potential relationship between methylation modification and lncRNA was also analyzed through lncRNA expression profile data. Functional annotation analysis showed that methylation-related lncRNAs were mainly enriched in postsynaptic specialization, neuron-to-neuron synapses, asymmetric synapses, and postsynaptic density. This indicates that methylation-related lncRNAs may have an impact on the synaptic microenvironment and may thus contribute to the development of depression. Moreover, we predicted potential interactions between SNP sites and lncRNAs in depression by querying the database. Through this review, we hope to deepen the understanding of the regulatory landscape of lncRNAs in depression and propose that future efforts should focus on establishing comprehensive and robust diagnostic models and further revealing the exact mechanism of lncRNA action in depression by experimental evidence.


Nramp1 gene expression in different tissues of Meishan piglets from newborn to weaning.
Natural resistance-associated macrophage protein gene 1 (Nramp1) plays an important role in the innate immune response of swine, and is believed to influence disease resistance. In this study, a real-time quantitative polymerase chain reaction technique was used to investigate Nramp1 expression in 12 different tissues in newborn and 7-, 14-, 21-, 28-, and 35-day-old Meishan piglets. Results indicated that Nramp1 was expressed to varying degrees in all sample tissues, although expression differed among growth stages. For example, Nramp1 was highly expressed in the spleen, but minimally expressed in heart, liver, and muscle tissues among the various piglet age classes. Overall, Nramp1 expression increased with age, reaching significant levels in 21- and 28-day-old animals. Nramp1 was expressed in all 12 tissues tested; however, expression in spleen, lung, kidney, and thymus tissues was highest among newborns, which is consistent with this gene's role in innate immunity improvement. Before and after weaning, Nramp1 was highly expressed in digestive (stomach) and intestinal (duodenum, jejunum, and ileum) tissues, further indicating a genetic role in both immune regulation to compensate for weaning stress and enhanced development of intestinal immunity.


Beth Lanham on Six Sigma in healthcare. Interview by Luc R. Pelletier.
Beth Lanham, BSN RN, is a Six Sigma Coordinator in the department of quality management, staff development and safety, at Froedtert Hospital in Milwaukee, WI. Ms. Lanham received her bachelor's degree from Otterbein College in Westerville, OH and has an extensive clinical and management background in critical care nursing. In April 2000, Ms. Lanham completed the Six Sigma Black Belt training program through the American Society for Quality. She is currently working as a Six Sigma Black Belt and is actively involved with numerous committees and projects aimed at reducing medical errors and enhancing patient safety. Ms. Lanham has presented Six Sigma initiatives at the International Quality Congress sponsored by the American Society for Quality, the University Healthcare Consortium National Conference, the International Quality and Productivity Center National Conference on Six Sigma for Healthcare Providers, and the American Hospital Association Patient Safety Leadership Fellowship Retreat. Six Sigma projects at Froedtert Hospital are aimed at reducing errors associated with patient controlled analgesia pumps, continuous intravenous infusions, narcotic sedation in postoperative patients, insulin therapy, and handling of laboratory specimens. Six Sigma has also been applied toward reducing falls on a rehabilitation unit.


Establishing and validating an ADCP-related prognostic signature in pancreatic ductal adenocarcinoma.
With the progress of precision medicine treatment in pancreatic ductal adenocarcinoma (PDAC), individualized cancer-related examination and prediction is of great importance in this high malignant tumor, and antibody-dependent cell phagocytosis (ADCP) with changed pathways highly enrolled in the carcinogenesis of PDAC. High-throughput data of pancreatic ductal adenocarcinoma were downloaded and 160 differentially expressed ADCP-related genes (ARGs) were obtained. Secondly, GO and KEGG enrichment analyses show that ADCP is a pivotal biologic process in pancreatic carcinogenesis. Next, CALB2, NLGN2, NCAPG and SERTAD2 are identified through multivariate Cox regression. These 4 genes are confirmed with significant prognostic value in PDAC. Then, a risk score formula is constructed and tested in PDAC samples. Finally, the correlation between these 4 genes and M2 macrophage polarization was screened. Some pivotal differentially expressed ADCP-related genes and biologic processes, four pivotal subgroup was among identified in the protein-protein network, and hub genes was found in these sub group. Then, an ADCP-related formula was set: CALB2* 0.355526 + NLGN2* -0.86862 + NCAPG* 0.932348 + SERTAD2* 1.153568. Additionally, the significant correlation between M2 macrophage-infiltration and the expression of each genes in PDAC samples was identified. Finally, the somatic mutation landscape and sensitive chemotherapy drug between high risk group and low risk group was explored. This study provides a potential prognostic signature for predicting prognosis of PDAC patients and molecular insights of ADCP in PDAC, and the formula focusing on the prognosis of PDAC can be effective. These findings will contribute to the precision medicine of pancreatic ductal adenocarcinoma treatment.


Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages B and C patients.
Urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for colorectal cancer (CRC) patient survival. However, CRC uPAR expression remains controversial, especially regarding cell types where uPAR is overexpressed (e.g., epithelium (uPARE) or stroma-associated cells (uPARS)) and associated prognostic relevance. In this study, two epitope-specific anti-uPAR monoclonal antibodies (MAbs) could discriminate expression of uPARE from uPARS and were used to examine this association with survival of stages B and C rectal cancer (RC) patients. Using immunohistochemistry, MAbs #3937 and R4 were used to discriminate uPARE from uPARS respectively in the central and invasive frontal regions of 170 stage B and 179 stage C RC specimens. Kaplan-Meier and Cox regression analyses were used to determine association with survival. uPAR expression occurred in both epithelial and stromal compartments with differential expression observed in many cases, indicating uPARE and uPARS have different cellular roles. In the central and invasive frontal regions, uPARE was adversely associated with overall stage B survival (HR = 1.9; p = 0.014 and HR = 1.5; p = 0.031, respectively) reproducing results from previous studies. uPARS at the invasive front was associated with longer stage C survival (HR = 0.6; p = 0.007), reflecting studies demonstrating that macrophage peritumoural accumulation is associated with longer survival. This study demonstrates that different uPAR epitopes should be considered as being expressed on different cell types during tumour progression and at different stages in RC. Understanding how uPARE and uPARS expression affects survival is anticipated to be a useful clinical prognostic marker of stages B and C RC.


Digestive characteristics of astaxanthin oil in water emulsion stabilized by a casein-caffeic acid-glucose ternary conjugate.
To overcome the barrier of poor oral bioavailability of astaxanthin, a stable oil-in-water emulsion was constructed using casein-caffeic acid-glucose ternary conjugates (CSC) to deliver astaxanthin, and its gastrointestinal behavior was evaluated in vitro with sodium caseinate (CSN) as a control. Results showed that, CSC-stabilized emulsion shower better resistance to the adverse conditions of the gastric environment than CSN-stabilized emulsion, and exhibited lower average particle size and aggregation (4972.33 nm, -5.93 mv) after simulated gastric digestion. Besides, after simulated intestinal digestion, the reducing capacity and astaxanthin transfer efficiency of CSC emulsion into the micellar phase were 686.74 μmol Trolox/100 mL and 26.2 %, which were 2.6 and 4.05-fold higher than that of CSN emulsion. The above results suggest that CSC can be used for better delivery of astaxanthin, which could be useful in designing foods such as functional beverages, pharmaceuticals and nutritional supplements for delivery of lipophilic bioactives.


Electrically and thermally conductive underwater acoustically absorptive graphene/rubber nanocomposites for multifunctional applications.
Graphene is ideal filler in nanocomposites due to its unique mechanical, electrical and thermal properties. However, it is challenging to uniformly distribute the large fraction of graphene fillers into a polymer matrix because graphene is not easily functionalized. We report a novel method to introduce a large fraction of graphene into a styrene-butadiene rubber (SBR) matrix. The obtained graphene/rubber nanocomposites were mechanically enhanced, acoustically absorptive under water, and electrically and thermally conductive. The Young's modulus of the nanocomposites was enhanced by over 30 times over that for rubber. The electrical conductivity of nanocomposites was ≤219 S m-1 with 15% volume fraction of graphene content, and exhibited remarkable electromagnetic shielding efficiency of 45 dB at 8-12 GHz. The thermal conductivity of the nanocomposites was ≤2.922 W m-1 k-1, which was superior to the values of thermally conductive silicone rubber thermal interface materials. Moreover, the nanocomposites exhibited excellent underwater sound absorption (average absorption coefficient >0.8 at 6-30 kHz). Notably, the absorption performance of graphene/SBR nanocomposites increased with increasing water pressure. These multifunctional graphene/SBR nanocomposites have promising applications in electronics, thermal management and marine engineering.


Computational prediction of SEG (single exon gene) function in humans.
Human genes are often interrupted by non-coding, intragenic sequences called introns. Hence, the gene sequence is divided into exons (coding segments) and introns (non-coding segments). Consequently, a majority of them are multi exon genes (MEG). However, a considerable amount of single exon genes (SEG) are present in the human genome (approximately 12%). This amount is sizeable and it is important to probe their molecular function and cellular role. Hence, we performed a genome wide functional assignment to 3750 SEG sequences using PFAM (protein family database), PROSITE (database of biologically meaningful signatures or motifs) and SUPERFAMILY (a library covering all proteins of known 3 dimensional structure). PFAM assigned 13% SEG to trans-membrane receptor genes of the G-protein coupled receptor (GPCR) family and showed that a majority of SEG proteins have DNA binding function. PROSITE identified 336 unique motif types in them and this accounts for 25% of all known patterns, with a majority having PHOSPHORYLATION and ACETYLATION signals. SUPERFAMILY assigned 33% SEG to the membrane all alpha (proteins containing alpha helix structural elements according to SCOP (structural classification of proteins) definition). Functional assignment of SEG proteins at multiple levels (sequence signals, sequence families, 3D structures) using PFAM, PROSITE and SUPERFAMILY is envisioned to suggest their selective and predominant molecular function in cellular systems. Their function as DNA binding, phosphorylating, acetylating and house-keeping agents is intriguing. The analysis also showed evidence of SEG expression and retro-transposition. However, this information is inadequate to draw concerted conclusion on the prevalent role played by these proteins in cellular biology. A complete understanding of SEG function will help to explore their role in cellular environment. The derived datasets from these analyses are available at http://sege.ntu.edu.sg/wester/intronless/human/.


The needle in the haystack: international consortia and the return of individual research results.
Returning individual results to participants in research studies is gaining acceptance and policy guidance is now available for investigators to develop a plan for returning results at the local level. However, returning results discovered through the work of an international scientific research consortium presents additional ethical and procedural difficulties. No general guidance is available for international consortia that wish to consider this issue, but there are examples of internal policies that are being used by consortia such as the International Cancer Genome Consortium (ICGC) and the Type 1 Diabetes Genetics Consortium (T1DGC). This paper presents the policy stance these studies have adopted regarding returning individual research results and their reasons behind it, and gives specific examples from their policy documents and project consent materials. Finally, it suggests an oversight mechanism these and other international consortia can use to ensure that this important issue is addressed appropriately.


Serum beta-HCG and CA-125 as tumor markers in a patient with osteosarcoma: case report.
Elevated beta-HCG serum levels are usually an indication of pregnancy or pregnancy-related disorders, but beta-HCG can also be elevated in testis and germ cell tumors. HCG expression by osteosarcoma is a rare phenomenon, with a few documented cases. CA-125 is commonly used to monitor disease progression and treatment response in ovarian cancer. CA-125 expression in patients with osteosarcoma has not previously been documented. Elevated beta-HCG and CA-125 serum levels were observed in a female patient of 57 years of age with metastatic osteosarcoma during screening investigations prior to participation in a phase I clinical trial. Pregnancy was excluded. Immunohistochemical studies revealed the tumor to be the source of the elevated beta-HCG serum levels. We found no CA-125 expression in tumor tissue. The patient was treated with E7080, a novel oral multi-targeted tyrosine kinase inhibitor. We measured serum beta-HCG and CA-125 to monitor treatment response. She had a significant clinical and radiological response after two cycles of treatment, but developed progressive disease after the third cycle. The beta-HCG serum levels seemed to better reflect her disease status than those of the other tumor marker, CA-125. When elevated, beta-HCG serum levels in patients with osteosarcoma might be used to monitor treatment. Treatment of advanced osteosarcoma with tyrosine kinase inhibitors, including E7080, warrants further investigation.


Long-term follow-up of deep brain stimulation of peduncolopontine nucleus in progressive supranuclear palsy: Report of three cases.
Progressive supranuclear palsy (PSP) is a neurodegenerative disease due to mitochondrial dysfunction. The PSP syndrome presents generally with gait disorder, Parkinsonism, ophthalmoparesis and cognitive alteration. Few reports exist on deep brain stimulation (DBS) in patients with atypical Parkinsonism. The aim of our study was to evaluate further the potential role of DBS in PSP. We report three patients with PSP with long-term follow up undergoing DBS. Two patients had right peripedunculopontine nucleus (PPN) stimulation and one patient had simultaneous right PPN and bilateral globus pallidus internus DBS. DBS of the PPN alone or combined with globus pallidus internus (GPi) determined an improvement in gait and a reduction in falls sustained over time. Combined target stimulation (GPi-PPN) was correlated with better clinical outcome than single target (PPN) DBS for PSP. Although few data on DBS for PSP exist, reported clinical results are encouraging. DBS might be considered as an alternative therapeutic option for patients with PSP presenting with relevant gait imbalance and frequent falls, who fail to respond to pharmacological treatment. Larger cohorts with longer follow-ups are needed to evaluate more exhaustively the efficacy of DBS in PSP.


Repetitive intrathecal VEGF(165) treatment has limited therapeutic effects after spinal cord injury in the rat.
Neuropathic pain and motor deficits are detrimental consequences of injury to the spinal cord. In experimental settings, numerous neuroprotective agents are being explored for their therapeutic benefits. Vascular endothelial growth factor (VEGF) is an interesting candidate molecule in this respect since it is not only associated with angiogenesis, but also with neuroprotection and neurite growth. Other investigators have reported improved motor outcomes following intraparenchymal VEGF treatment. Here we demonstrate the therapeutic effects of daily intrathecal treatment of the contused thoracic rat spinal cord with the 165-isoform of VEGF during the first week after injury. We show that VEGF treatment resulted in a statistically significant attenuation of mechanical, but not thermal, hypersensitivity of the hindpaws, while motor deficits remained unaffected. Tissue sparing was also unchanged by VEGF treatment. Microglial responses at the lumbar spinal cord, which have been linked with spinal cord injury-induced hypersensitivity, were found to be unaffected by VEGF treatment. We conclude that repetitive intrathecal VEGF delivery has limited therapeutic effects on spinal cord injury outcome.


Characteristics of 275 patients with bulimia.
The authors present data on 275 patients who met DSM-III criteria for bulimia. The mean age of the patients was 24.8 years, and the average duration of illness was approximately 7 years. These patients reported a variety of abnormal eating-related behaviors: binge eating (100%), self-induced vomiting (88.1%), laxative abuse (60.6%), diuretic abuse (33.1%), and chewing and spitting out food (64.5%). Over one-third reported a history of problems with alcohol or other drugs and most indicated substantial social impairment.


Electrically driven flow near a colloidal particle close to an electrode with a Faradaic current.
To elucidate the nature of processes involved in electrically driven particle aggregation in steady fields, flows near a charged spherical colloidal particle next to an electrode were studied. Electrical body forces in diffuse layers near the electrode and the particle surface drive an axisymmetric flow with two components. One is electroosmotic flow (EOF) driven by the action of the applied field on the equilibrium diffuse charge layer near the particle. The other is electrohydrodynamic (EHD) flow arising from the action of the applied field on charge induced in the electrode polarization layer. The EOF component is proportional to the current density and the particle surface (zeta) potential, whereas our scaling analysis shows that the EHD component scales as the product of the current density and applied potential. Under certain conditions, both flows are directed toward the particle, and a superposition of flows from two nearby particles provides a mechanism for aggregation. Analytical calculations of the two flow fields in the limits of infinitesimal double layers and slowly varying current indicate that the EOF and EHD flow are of comparable magnitude near the particle whereas in the far field the EHD flow along the electrode is predominant. Moreover, the dependence of EHD flow on the applied potential provides a possible explanation for the increased variability in aggregation velocities observed at higher field strengths.


Immunomodulation of surface biofunctionalized 3D printed porous titanium implants.
Additive manufacturing (AM) techniques have provided many opportunities for the rational design of porous metallic biomaterials with complex and precisely controlled topologies that give rise to unprecedented combinations of mechanical, physical, and biological properties. These favorable properties can be enhanced by surface biofunctionalization to enable full tissue regeneration and minimize the risk of implant-associated infections (IAIs). There is, however, an increasing need to investigate the immune responses triggered by surface biofunctionalized AM porous metals. Here, we studied the immunomodulatory effects of AM porous titanium (Ti-6Al-4V) printed using selective laser melting, and of two additional groups consisting of AM implants surface biofunctionalized using plasma electrolytic oxidation (PEO) with/without silver nanoparticles. The responses of human primary macrophages and human mesenchymal stromal cells (hMSCs) were studied in terms of cell viability, cell morphology and biomarkers of macrophage polarization. Non-treated AM porous titanium triggered a strong pro-inflammatory response in macrophages, albeit combined with signs of anti-inflammatory effects. The PEO treatment of AM porous titanium implants showed a higher potential to induce polarization towards a pro-repair macrophage phenotype. We detected no cytotoxicity against hMSCs in any of the groups. However, the incorporation of silver nanoparticles resulted in strong cytotoxicity against attached macrophages. The results of this study indicate the potential immunomodulatory effects of the AM porous titanium enhanced with PEO treatment, and point towards caution and further research when using silver nanoparticles for preventing IAIs.


A case of adrenocortical oncocytic carcinoma arising in ectopic adrenal tissue: a multidisciplinary diagnostic challenge.
Adrenocortical oncocytic neoplasm arising in ectopic adrenal tissue is a rare finding and presents as a unique diagnostic challenge. We report a case of a 26-year-old female who presented with vague left-sided abdominal pain and a large left retroperitoneal mass. She underwent exploratory laparotomy and resection of the mass and was diagnosed with extra-adrenal adrenocortical oncocytic carcinoma.


Nutritional support for wound healing.
Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome.


Desynchronizing Embryonic Cell Division Waves Reveals the Robustness of Xenopus laevis Development.
The early Xenopus laevis embryo is replete with dynamic spatial waves. One such wave, the cell division wave, emerges from the collective cell division timing of first tens and later hundreds of cells throughout the embryo. Here, we show that cell division waves do not propagate between neighboring cells and do not rely on cell-to-cell coupling to maintain their division timing. Instead, intrinsic variation in division period autonomously and gradually builds these striking patterns of cell division. Disrupting this pattern of division by placing embryos in a temperature gradient resulted in highly asynchronous entry to the midblastula transition and misexpression of the mesodermal marker Xbra. Remarkably, this gene expression defect is corrected during involution, resulting in delayed yet normal Xbra expression and viable embryos. This implies the existence of a previously unknown mechanism for normalizing mesodermal gene expression during involution.


Vitamin D deficiency and outcomes in pediatric hematopoietic stem cell transplantation.
Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are frequently diagnosed with vitamin D deficiency, which may impact outcomes. To estimate the prevalence of vitamin D deficiency and examine its association with short-term survival in pediatric HSCT patients. Patients undergoing HSCT at Phoenix Children's Hospital were retrospectively identified. Routine serum 25-hydroxyvitamin D measurements were described prior to transplant and at 100 days and 1-year post-HSCT. Associations of pre-HSCT vitamin D groups (i.e., normal ≥30 ng/ml, insufficient 20-29 ng/ml, and deficient <30 ng/ml) with demographics, clinical factors, and outcomes were examined using nonparametric tests and Cox proportional hazards analyses. Among 72 study subjects, the median vitamin D pre-HSCT was 26 ng/ml (range: 19-34 ng/ml). Levels were insufficient and deficient in 25 (35%) and 20 (28%) patients, respectively, with only two (3%) patients on supplemental therapy pre-HSCT. Despite supplemental therapy provided to 46 (74%) subjects, insufficient/deficient rates did not significantly change between pre-HSCT and 100 days post-HSCT, but mean vitamin D levels significantly increased by 1-year post-HSCT (P = 0.01).Vitamin D pre-HSCT was not associated with the development of acute or chronic graft-versus-host disease (GVHD) or delayed engraftment. Overall 1-year survival was significantly lower for patients with deficient (65%) compared to normal (93%) pre-HSCT vitamin D (P = 0.001). Suboptimal vitamin D levels are common in pediatric patients scheduled to receive HSCT and are associated with lower overall 1-year survival. Further study is warranted to delineate the mechanisms underlying the role of vitamin D in successful HSCT.


Dietary adherence and mealtime behaviors in young children with type 1 diabetes on intensive insulin therapy.
Diet is an important component of diabetes treatment and integral to successful management. While intensive insulin therapy can allow patients to eat more freely, it is not known how the rapid uptake of intensive therapy in young children with type 1 diabetes has impacted their diet and if diet and healthful eating in young children correlates with mealtime behaviors and glycemic control. This study examined diet, mealtime behaviors, and glucose control in a sample of 39 young children on intensive therapy. This was a one-sample, cross-sectional study. Children had a mean age of 5.1 ± 1.1 years. Children's 3-day diet diaries were assessed using a deviation scale (measure of adherence) and a healthy eating index. Mealtime behaviors were assessed using the Behavioral Pediatric Feeding Assessment Scale. Children's glucose control was measured using continuous glucose monitoring. Children's mean carbohydrate intake was 72% ± 24% of the recommended levels based on their age, sex, size, and activity level, and children exceeded national guidelines for percentage of calories from fat and saturated fat. A more healthful diet correlated with fewer child mealtime behavior problems, but better dietary adherence correlated with more parent mealtime behavior problems. Even in the context of intensive management, diet can be problematic for young children with type 1 diabetes. Parent-reported problems with mealtime behaviors seem to correlate with healthy eating and dietary adherence.


Exophiala dermatitidis fungal infective endocarditis on prosthetic mitral valve.
Fungal infective endocarditis, although rare, carries a high mortality risk. We present a case of successful multidisciplinary management of Exophiala dermatitidis infective endocarditis in an immunocompetent male with a bio-prosthetic mitral valve. This case highlights the clinical presentation and provides valuable treatment insights into this rare fungal entity. Prompt consideration of fungal pathogens in predisposed patients, expedited detection through non-culture-based tests, and a combined surgical and prolonged antifungal approach are pivotal.


A CMP-based method for tunable, cell-mediated gene delivery from collagen scaffolds.
The use of collagen-based biomaterials in regenerative medicine has rapidly increased over the past decade. The unique structural and biochemical properties of collagen make it a particularly promising material for delivering both protein and DNA-based therapeutics. Although many collagen modification techniques have been developed, the majority of them require multi-step chemical treatments that can modify the natural favourable properties of collagen. We have developed a promising biomimetic modification technique employing collagen-mimetic peptides (CMP)s to control the retention and delivery of DNA polyplexes from collagen structures, including both monomeric 2-D collagen films and fibrous, 3-D gels. Variations in the concentration of CMPs displayed on polyplexes enabled tuning of polyplex retention vs. release over periods of at least 2 weeks on films and a month on gels. Retention of CMP-modified polyplexes (20 days) was substantially improved compared to non-modified polyplexes, which were retained for only 2 days. The activity of bound polyplex in collagen gels was shown, through a series of transfection studies, to be maintained in the presence of serum for a minimum of 2 weeks. Only matrix metalloproteinase (MMP)-stimulated cells exhibited significant levels of transfection suggesting that cell mobility within the gel was vital and that collagen remodelling played a role in stimulating gene release and expression. To our knowledge, this study is the first to deliver genes with CMP-modified polyplexes and to examine the effects of CMP display on DNA release. The results suggest that this technique may be used more broadly to create tuneable, collagen-based delivery systems.


Institutional review board approaches to the incidental findings problem.
Institutional Review Boards (IRBs) are confronted with new challenges in the face of expanding technologies while fulfilling their existing regulatory mandate to ensure that plans are in place to protect subjects and to inform them of risks and benefits of research participation. Existing regulations and guidance do not address the issue of incidental findings (IFs), thus leaving awareness of the issue and the application of ethical principles to IRB judgment alone. In order to assure that researchers are aware of the potential for IFs, IRBs must identify which studies are likely to identify IFs and establish what plans should be put into place prior to study initiation to assure the subjects are appropriately informed of the likelihood of IFs, how IFs will be communicated to subjects, and whether the burden of follow-up falls on the researchers or is the subject's responsibility.


Early-stage cervical cancer: agreement between ultrasound and histopathological findings with regard to tumor size and extent of local disease.
To determine the agreement between ultrasound and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. Eighteen patients with histologically proven cervical cancer Stage IB1-IIA according to traditional clinical staging (FIGO 1988) who were scheduled for radical surgery underwent a standardized transvaginal ultrasound examination. The maximum tumor length, anteroposterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor-free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease within the parametria and vagina were evaluated. The surgical specimens were examined using a specifically devised method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. Limits of agreement were wide and the intraclass correlation coefficient (ICC) was low (0.51-0.58) for three of the four measurements taken to represent the minimal depth of tumor-free cervical stroma, i.e. the results of the measurements taken posteriorly and laterally. However, the limits of agreement were narrower and the ICC values were higher (0.74-0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients, which was detected during ultrasound examination, with no false-positive results. Transvaginal sonography is acceptably accurate for evaluation of tumor size and depth of cervical stroma invasion in clinical practice.


Boundary work as a buffer against burnout: Evidence from healthcare workers during the COVID-19 pandemic.
Burnout represents a significant problem for many modern-day workers, but perhaps none more acutely than those in healthcare. Imbued with the chronic stressors that often accompany high-risk, interpersonal work, the healthcare industry is rife with stories of burnout, and the addition of a pandemic has intensified the challenges of an already demanding work environment. With an aim toward understanding the root causes of pandemic-exacerbated burnout, we document the experiences of 93 healthcare workers during the COVID-19 pandemic and, in doing so, explore an important link between burnout and work-nonwork boundaries. We find the contextual shock of the pandemic resulted in an increased incidence of boundary violations-undesired disruptions between work and other important life domains such as personal and family life. These boundary violations-which we classify as physical, temporal, or knowledge-based-frequently corresponded to greater reports of burnout manifested by exhaustion, detachment, and inefficacy. We detail specific patterns within the broader context of boundary violations whereby intrusion events are associated with increased job-related demands and distancing events are associated with reduced job-related resources. In addition to documenting the connection between burnout and boundary violations, we also reveal how workers utilized specific boundary work tactics in response to specific types of boundary violations to redefine boundaries and forestall burnout. Our grounded theorizing points to theoretical and practical implications for the impact of boundary work tactics on burnout and other stress-related phenomena. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Bilateral inguinal hernia repair and male fertility: a randomized clinical trial comparing Lichtenstein versus laparoscopic transabdominal preperitoneal (TAPP) technique.
The effects of hernia repair on testicular function remain uncertain, regardless of the technique used. Studies that analyze testicular volume and flow after hernia repair or hormonal measurements are scarce and show contradictory results. This study aimed to evaluate the impact of bilateral inguinal hernia repair on male fertility in surgical patients in whom the Lichtenstein and laparoscopic transabdominal preperitoneal (TAPP) techniques were used. A randomized clinical trial comparing open (Lichtenstein) versus laparoscopic (TAPP) hernia repair using polypropylene mesh was performed in 48 adult patients (20 to 60 years old) with primary bilateral inguinal hernia. Patients were evaluated preoperatively and 90 and 180 postoperative (PO) days. Sex hormones (Testosterone, FSH, LH and SHGB) analysis, testicular ultrasonography, semen quality sexual activity changes and quality of life (QoL) were performed. Postoperative pain was evaluated using the visual analog scale (VAS). Thirty-seven patients with aged of 44 ± 11 years were included, 19 operated on Lichtenstein and 18 operated on TAPP. The surgical time was similar between techniques. The pain was greater in the Lichtenstein group on the 7th PO day. The biochemical and hormonal analyses, testicular ultrasonography (Doppler, testicular volume, and morphological findings) and sperm quality were similar between groups. However, the sperm morphology was better in the Lichtenstein group after 180 days (p < 0.05 vs. preoperative) and two patients who underwent Lichtenstein hernia repair had oligospermia after 180 days. The QoL evaluation showed a significant improvement after surgery in the following domains: physical function, role emotional, bodily pain and general health (p < 0.05). On comparison of Lichtenstein vs. TAPP none of the domains showed statistically significant differences. No patient reported sexual changes. Bilateral inguinal hernia repair with polypropylene mesh, whether using Lichtenstein or TAPP, does not impair male fertility in terms of long-term outcomes. Approved by the Ethics Committee for the Analysis of Research Projects (CAPPesq) of the HC/FMUSP, Number 2.974.457, in June 2015, Registered on Plataforma Brasil in October 2015 under Protocol 45535015.4.0000.0068. Registered on Clinicaltrials.gov, NCT05799742. Enrollment of the first subject in January 2016.


Evaluation of a Remote Symptom Assessment and Management (SAM) System for People Receiving Adjuvant Chemotherapy for Breast or Colorectal Cancer: Mixed Methods Study.
The Symptom Assessment and Management (SAM) program is a structured, online, nurse-supported intervention to support symptom self-management in people receiving adjuvant chemotherapy post surgery for breast or colorectal cancer. The objective of this study was to describe the development, implementation strategy, and evaluation of the SAM system. The development of the SAM program involved 3 phases. In phase 1, the web app was developed through consultation with consumers and clinicians and of the literature to ensure that the system was evidence-based and reflected the realities of receiving treatment and supporting patients through treatment. In phase 2, 7 participants recorded the severity of 6 symptoms daily over the course of 1 cycle of chemotherapy. In phase 3, 17 participants recorded their symptoms daily over the course of 3 cycles of chemotherapy. Once symptoms were recorded, participants received immediate feedback on the severity of their symptoms and self-management recommendations, which could include seeking immediate medical attention. Data on quality of life, symptom burden, anxiety and depression, distress, and self-efficacy were collected during treatment; participants' perceptions of the SAM program were evaluated following participation via interview. The outcomes of the SAM project include the development of a system that is reliable and easy to use and navigate. Participants reported benefits related to using the SAM program that included feeling more in control of managing their symptoms and feeling reassured. Engagement with the system on a daily basis was variable, with some participants completing the symptom tracker daily and others engaging some of the time. The feedback from all participants was that the system was easy to navigate and the information was relevant and supportive. The SAM program has the potential to enhance the management of symptoms for people receiving chemotherapy treatment. The system creates an accurate repository of symptoms that can be accessed easily and highlight patterns in symptom experience. These can be shared with clinicians, with patient permission, to inform and support treatment plans. The potential to predict the risk of developing severe symptoms can be developed to anticipate the need for care and support. Further considerations on how to increase engagement with the system, the value of the system for people diagnosed with other tumor types and treatment regimes, and the incorporation of the system into everyday clinical practice are needed.


P300 clinical utility and control of variability.
The P300 event-related brain potential (ERP) has been used to study normal aging as well as patient populations with a variety of neurologic and psychiatric disorders. The P300 has demonstrated reasonable success as a means to assess disturbances in cognitive function, and its clinical utility has been enhanced by the identification of factors that contribute to the variability of ERP measurements. In this article, the neuropsychological theory of P300 is reviewed, ways in which this brain potential can be used as a measure of cognitive efficiency are defined, and methodologic issues that must be considered for successful clinical ERP applications are outlined. This approach is then extended to specific recommendations concerning the technical and practical aspects of P300 recording, so that a well-defined normative database can be developed for evaluating individual patients. When appropriate procedures are used, the P300 can provide a highly useful means to quantify human cognitive capability.


Molecular studies of linkage group XIX of Chlamydomonas reinhardtii: evidence against a basal body location.
Linkage group XIX (also known as the UNI linkage group) in the green alga, Chlamydomonas reinhardtii, exhibits a number of unusual properties that have lead to the suggestion that it represents a basal body-associated chromosome. To begin a molecular analysis of this linkage group, we have identified DNA sequences from it and used them to determine the copy number of linkage group XIX within the cell. We find that linkage group XIX is present in the same copy number per cell as nuclear linkage groups in both haploid and diploid strains. We also find that the copy number of linkage group XIX is unchanged in mutants lacking basal bodies. We conclude that there is no convincing evidence that linkage group XIX localizes to the basal bodies of Chlamydomonas reinhardtii cells.


Rifampin and rifabutin and their metabolism by human liver esterases.
1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2. In experiments with human liver slices and human liver microsomes, the 25 deacetylated derivatives of these drugs were the main metabolites observed. Slices and microsomes metabolized rifabutin 3-6-fold faster than rifampin, in agreement with their relative clearance in patients. Rifabutin partitioned into slices more avidly than rifampin. 3. In microsomal incubations, deacetylation did not require NADPH, but the amount of metabolite at the end of incubation was affected by NADPH. With NADPH the amount of 25 deacetyl rifabutin decreased, whereas the amount of 25 deacetyl rifampin increased slightly. A panel of liver microsomes from seven donors showed a 3-4-fold difference in the formation of 25 deacetyl rifabutin or 25 deacetyl rifampin, with strong correlation between the production of the two metabolites (r2 = 0.94). 4. The production of 25 deacetyl rifabutin and 25 deacetyl rifampin by human liver microsomes was not significantly affected by 1 microM 4 chloromercuricbenzoic acid or bis-(4-nitrophenyl) phosphate, but was completely inhibited by 1 microM paraoxon or 1 microM diisopropylfluorophosphate. These results indicate that in man rifampin and rifabutin are deacetylated to their main metabolites by B-esterases.


Acrylonitrile-induced reversible inhibition of uridine uptake by isolated rat intestinal epithelial cells.
Isolated rat intestinal epithelial cells (IEC) were used to investigate the mechanism(s) of acrylonitrile (VCN)-induced gastro-intestinal damage. The isolated cells were 93% structurally intact for 60 min, as indicated by trypan blue exclusion. Uridine uptake by isolated IEC was linear from 6-20 min, after which a steady state was reached for up to 40 min. Exposure of isolated IEC to various concentrations of VCN reduced the ability of the cells to take up uridine in a concentration-dependent manner. A concentration of 82 mum VCN inhibited the [(3)H]uridine uptake of the cells by 50% (IU(50)). A time-course study indicated that the maximal inhibition of uridine uptake occurred at 15 min after exposure to VCN. The VCN-induced inhibition of uridine uptake was found to be reversible. IEC exposed to two sublethal doses of VCN (41 and 82 mum) for 15 min regained normal uridine uptake activity within 50 min after removal of VCN. The present study provides a sensitive approach for the detection and evaluation of cytotoxic risk of sublethal doses of the gastro-intestinal toxin VCN using IEC as target cells. The observed in vitro cytotoxicity of sublethal doses of VCN will be used to investigate further the mechanism of VCN-induced gastro-intestinal damage.