A simple and fast UHPLC-MS-MS assay for rapid determination of vilazodone in plasma sample.
Vilazodone is a novel antidepressant agent, approved by the US Food and Drug Administration (US FDA) for the treatment of major depressive disorder. In this study, a fast sensitive ultra-high performance liquid chromatography-tandem mass spectroscopy method was developed and validated for the determination of vilazodone in human plasma. After a simple protein precipitation by acetonitrile, both vilazodone and risperidone (internal standard, IS) were separated on an Acquity UPLC BEH™ C18 column (50 × 2.1 mm, 1.7 µm). An isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v) was used at the 0.3 mL/min flow rate. Both vilazodone and IS were eluted at 0.44 and 0.47 min, respectively, having a run time of 1.0 min. Detection and quantification were performed using an electrospray ionization source in positive mode by multiple reaction monitoring. The precursor to product ion transitions were monitored at m/z 442.19 > 154.99 for vilazodone and m/z 411.18 > 191.07 for IS, respectively. The standard curve (0.40-500 ng/mL) was found to be linear with a lower limit of quantification 0.40 ng/mL. All validation results were found to be within acceptable limits as per guidelines for bioanalytical method validation (US FDA and European Medicines Agency). To the best of our knowledge, this is the first fully validated assay for the determination of vilazodone in human plasma and was successfully applied to an oral pharmacokinetic study in rats.


Long-lasting catch-up growth under bio-methionyl growth hormone treatment in an infant with isolated growth hormone deficiency type 1A.
This case report concerns a 7-month-old infant with severe height retardation (-5.0 SD), typical growth hormone (GH)-deficient phenotype, and undetectable GH serum levels in response to three pharmacological stimuli. Diagnosis of isolated GH deficiency type 1A was confirmed by restriction endonuclease analysis of genomic DNA which pointed out GH-N gene deletion. The introduction of bio-methionyl-GH therapy in this patient was followed by a transient and clinically irrelevant appearance of low binding capacity GH antibodies as well as by a long-lasting catch-up growth (42.2 cm) which is continuing 44 months after beginning of treatment. This atypical pattern confirms that immune and growth response to exogenous GH in isolated GH deficiency 1A may be very heterogeneous.


Successful medical management of renal zygomycosis: a summary of two cases and a review of the Indian literature.
We present two cases of renal zygomycosis caused by Apophysomyces elegans and Mycocladus corymbifer in previously healthy immunocompetent males and an overview of the disease in India. In both cases a percutaneous nephrostomy (PCN) was performed and the etiologic agents were identified by direct microscopy and culture. Amphotericin B was administered and both patients recovered completely. A review of the literature revealed 42 cases of renal zygomycosis in India. The majority of them were from the Postgraduate Institute of Medical Education and Research, Chandigarh, in North India. In contrast to cases from the developed world where transplant recipients and patients with hematological malignancies seem to be most vulnerable to zygomycosis, the most common risk factor in India is uncontrolled diabetes mellitus. However, renal zygomycosis is an exception and the patients in both of our cases had no identifiable underlying disorder and recovered successfully without nephrectomy. It is important to emphasize that treatment of A. elegans must be aggressive and lipid formulations of antifungals are typically favored due to their limited side effects profile and ability of the clinician to use higher doses. A high index of clinical suspicion and knowledge of the varied manifestations in diagnosing this condition cannot be overemphasized.


Molecular epidemiology of hospital-acquired vancomycin-resistant enterococci.
Vancomycin-resistant Enterococcus faecium strains are a significant cause of nosocomial infections in predisposed patients. Multiple-locus variable-number tandem repeat analysis (MLVA) has been validated recently by use of a global strain collection. In this report, we applied MLVA together with multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to type 14 isolates from three clusters of patients colonized or infected with vancomycin-resistant Enterococcus faecium and another 10 epidemiologically unrelated isolates from the same hospital. The clusters could be distinguished by all three typing methods, which proved to be concordant. PFGE patterns provided the highest resolution. We observed seven sequence types (ST), six MLVA types (MT), and nine distinct ST/MT combinations. The combination of MLST and MLVA may be an alternative to PFGE in hospital epidemiology, providing the benefits of high accuracy, reproducibility, and portability.


Malassezia pachydermatis isolated from normal and diseased external ear canals in dogs: a comparative analysis.
To investigate the role of Malassezia pachydermatis as a pathogenic agent in canine otitis, a comparative analysis of isolates from normal and diseased external ear canals in dogs was undertaken. Specimens were collected from the ears of dogs with unilateral or bilateral otitis and from healthy dogs. Mycological analysis was by direct microscopy and fungal culture on Sabouraud's dextrose agar and Dixon's agar. Of the otitis specimens, 63.7% showed typical Malassezia cells on cytological examination. In samples taken from the healthy ears of dogs with unilateral otitis, only 21.43% (P<0.05) showed evidence of Malassezia. M. pachydermatis was identified cytologically and culturally in 57.53% (P<0.05), 14.29% and 30.0% of samples from the ears of dogs with otitis, from the healthy ears of dogs with unilateral otitis and from the ears of healthy dogs with no otitis. In the group with otitis associated with M. pachydermatis, the poodle was the most common breed (39.29%; P<0.05), whereas in the group without otitis, the German Shepherd breed was prominent (although this observation was not statistically significant). In both groups, the majority of dogs with M. pachydermatis were aged between 1 and 3 years (P<0.05). The higher incidence of M. pachydermatis isolated from the ears of dogs with otitis externa suggests a putative pathogenic role of this yeast in this condition.


Metallic artifacts in magnetic resonance imaging of patients with spinal fusion. A comparison of implant materials and imaging sequences.
Devices for spinal fusion were compared with respect to their influence on magnetic resonance images. In addition, different magnetic resonance pulse sequences were evaluated to elicit their susceptibility to imaging artifacts. To determine the implants with the least imaging artifacts as a recommendation for the spine surgeon and to assess the best imaging strategy for the radiologist. For patients who have had surgical spinal fusion with instrumentation, magnetic resonance imaging is the most favorable diagnostic method. Unfortunately, metallic implants lead to severe degradation of image quality. These artifacts depend on the material of the implant and on the choice of the pulse sequence. The fusion devices were mounted on a simple plastic phantom in various combinations and were imaged on 1.5-T magnetic resonance units. Frequently used types of plates and screws made of titanium or steel in various alloys were examined on the phantom with routinely used pulse sequences. The results of these examinations were compared with those in patient studies involving the same implants as well as the same pulse sequences. The least imaging artifacts were caused by titanium implants, especially when using shorter screws, wider screw placement, and thinner titanium plates. Nevertheless, there were distinct image distortions that could lead to erroneous image interpretation. The best images were acquired by spin echo (T1), turbo spin echo (T1, T2), and half Fourier single shot turbo spin echo (HASTE) sequences. Sequences containing any gradient echo components (gradient echo or turbo gradient and spin echo sequence or frequency-selective fat saturation techniques) resulted in the highest amount of image degradation. By choosing appropriate spinal fusion devices as well as pulse sequences, postoperative magnetic resonance imaging examinations can give acceptable results, in spite of the presence of metallic implants.


Host enzymes in gingival crevicular fluid as diagnostic indicators of periodontitis.
Host responses to periodontal infections include the production of several families of enzymes that are released by stromal, epithelial or inflammatory cells. Study of these enzymes in gingival crevicular fluid may lead to insights into pathogenesis and may provide a rational basis for the development of novel diagnostic tests. However, analogous to other diagnostic interventions in dentistry and medicine, validation of host enzymes as diagnostic indicators is dependent on clear-cut demonstrations of the identity of the enzyme, reproducibility, diagnostic accuracy and clinical utility. The enzyme of interest should be readily measured over a broad range of disease severity and in varied clinical settings. Ideally, the enzyme should also be an essential component of proposed pathogenic mechanisms. In this context, the connective tissue matrix degrading enzymes elastase, collagenase and gelatinase are promising because of their apparently central role in periodontal attachment loss and disease progression. Sensitive and specific assays are also available to quantify these enzymes. Other work on enzymes associated with cell death (aspartate aminotransferase, lactate dehydrogenase) and several neutrophil lysosomal enzymes (beta glucuronidase, arylsulphatase, cathepsins) has demonstrated positive associations between enzyme levels and attachment loss and inflammation. While numerous cross-sectional studies have indicated that the levels of hydrolytic enzymes in gingival crevicular fluid parallel the severity of periodontal lesions, there are much less data on reproducibility, diagnostic accuracy and clinical utility in longitudinal studies. As appropriate study design is an essential prerequisite for establishing the efficacy of host enzymes as diagnostic tests, future clinical investigations should include: (1) individuals who would most likely benefit by early diagnosis, i.e., rapidly progressive and recurrent periodontitis cases; (2) longitudinal, cohort study designs to show that attachment loss is temporally linked with large increases in enzyme activity; (3) the use of a battery of tests to overcome intrinsic problems of low predictive values when prevalence of active disease is low. In the final analysis, the utility of host enzymes as diagnostic indicators will need to be examined in randomized controlled trials in which the question is asked: are patients better off as a result of testing?


The pathophysiology, diagnosis, and management of foot stress fractures.
There is an increasing prevalence of osteoporosis, and with it a rise in the diagnosis of stress fractures. Postmenopausal women are particularly at risk of stress fractures. This review article describes the pathophysiology of foot stress fractures and the latest diagnostic and treatment strategies for these common injuries. There are numerous risk factors for stress fractures that have been identified in the literature. Reduced bone mineral density is an independent risk factor for delayed union. Prevention of stress fractures with training periodization and nutritional assessment is essential, especially in females. Diagnosis of stress fractures of the foot is based on history and diagnostic imaging, which include radiographs, ultrasound, therapeutic ultrasound, computed tomography, and bone scans; however, magnetic resonance imaging is still the gold standard. Treatment depends on the bone involved and the risk of nonunion, with high-risk fractures requiring immobilization or surgical intervention. Patients presenting with underlying bone mineral deficiency treated without surgery require a longer period of activity modification. Training rehabilitation protocols are described for those with low-risk stress fractures. A useful algorithm is presented to guide the clinician in the diagnosis and management of such injuries.


The Comparative Effectiveness and Provider-induced Demand Collaboration Project: A Pioneering Military-Civilian Academic Partnership to Build Health Services Research Capacity for the Military Health System.
Like civilian health systems, the United States Military Health System (MHS) confronts challenges in achieving the aims of reducing cost, and improving quality, access, and safety, but historically has lacked coordinated health services research (HSR) capabilities that enabled knowledge translation and iterative learning from its wealth of data. A military-civilian academic partnership called the Comparative Effectiveness and Provider-Induced Demand Collaboration (EPIC), formed in 2011, demonstrated early proof-of-concept in using the MHS claims database for research focused on drivers of variation in health care. This existing partnership was reorganized in 2015 and its topics expanded to meet the need for HSR in support of emerging priorities and to develop current and HSR capacity within the MHS. A Donabedian framework of structure, process, and outcomes was applied to support the project, through a core of principal investigators, researchers, analysts, and administrators. Within this framework, new researchers and student trainees learn foundations of HSR while performing secondary analysis of claims data from the MHS Data Repository (MDR) focusing on Health and Readiness, Pediatrics, Policy, Surgery, Trauma, and Women's Health. Since 2015, the project has trained 25 faculty, staff, and providers; 51 students and residents; 21 research fellows across multiple disciplines; and as of 2022, produced 107 peer-reviewed publications and 130 conference presentations, across all five themes and six cores. Research results have been incorporated into Federal and professional policy guidelines. Major research areas include opioid usage and prescribing, value-based care, and racial disparities. EPIC researchers provide direct support to MHS leaders and enabling expertise to clinical providers. EPIC, through its Donabedian framework and utilization of the MHS Data Repository as a research tool, generates actionable findings and builds capacity for continued HSR across the MHS. Eight years after its reorganization in 2015, EPIC continues to provide a platform for capacity building and knowledge translation.


Prognostic factors in diabetes: Comparison of Chi-square automatic interaction detector (CHAID) decision tree technology and logistic regression.
This study aimed to develop a diabetes prediction model. The model performance was compared with logistic regression, and the decision tree Chi-square automatic interaction detection (CHAID) was used to predict diabetes. In total, 3233 patients were included in the analysis. Of these, 589 patients with diabetes and 2644 patients without diabetes were included after analyzing the study sample from the Korean Genome and Epidemiology Study (KoGES)-8 data. In this study, Diabetes Mellitus (DM) diagnosis prediction was compared with logistic regression and prediction through machine learning (ML) using the CHAID decision classification tree. We performed statistical analysis using the CHAID method with International Business Machine (IBM) statistical program SPSS®. We performed logistic regression analysis to predict the classification of diabetes accurately, and the total classification accuracy of the analysis was 81.7%, and the CHAID decision tree classification accuracy was 81.8%. A diabetes diagnosis decision tree was created, which included seven terminal nodes and three depth levels. This analysis showed that a blood pressure problem and hospital visits were the most decisive variables at the time of classification, and two risk levels were created for diabetes diagnosis. The suggested method is a valuable tool for predicting diabetes. Patients who visit the hospital because of blood pressure problems are more likely to develop diabetes than under-treating hyperlipidemia. The diabetes prediction model can help doctors make decisions by detecting the possibility of diabetes early; however, it is impossible to diagnose diabetes using only the model without the doctor's opinion.


Molecular signature of pancreatic adenocarcinoma: an insight from genotype to phenotype and challenges for targeted therapy.
Pancreatic adenocarcinoma remains one of the most clinically challenging cancers despite an in-depth characterization of the molecular underpinnings and biology of this disease. Recent whole-genome-wide studies have elucidated the diverse and complex genetic alterations which generate a unique oncogenic signature for an individual pancreatic cancer patient and which may explain diverse disease behavior in a clinical setting. In this review article, we discuss the key oncogenic pathways of pancreatic cancer including RAS-MAPK, PI3KCA and TGF-β signaling, as well as the impact of these pathways on the disease behavior and their potential targetability. The role of tumor suppressors particularly BRCA1 and BRCA2 genes and their role in pancreatic cancer treatment are elaborated upon. We further review recent genomic studies and their impact on future pancreatic cancer treatment. Targeted therapies inhibiting pro-survival pathways have limited impact on pancreatic cancer outcomes. Activation of pro-apoptotic pathways along with suppression of cancer-stem-related pathways may reverse treatment resistance in pancreatic cancer. While targeted therapy or a 'precision medicine' approach in pancreatic adenocarcinoma remains an elusive challenge for the majority of patients, there is a real sense of optimism that the strides made in understanding the molecular underpinnings of this disease will translate into improved outcomes.


Gang membership and student behavior: nursing's involvement with prevention, intervention, and suppression.
Gangs are alive, and growing stronger each day, as they infiltrate all socioeconomic levels of most towns, cities, and metropolitan areas. This is the first of two articles in this issue discussing students and gang membership and a school nurse's involvement with gang prevention, intervention, and suppression. It is also about a large metropolitan school district's proactive approach to gang prevention, which includes a meaningful partnership involving the family, community, and school. The program is a comprehensive developmental guidance program to promote pro-social behaviors, equip students with refusal skills, and encourage problem-solving strategies that enable students to avoid engaging in high-risk activities.


[Diagnosis of human hydatidosis by hemagglutination and complement fixation (Weinberg) tests].
397 sera were tested by passive hemaglutination and weinberg reactions to diagnose hydatid cysts. 5 of 211 sera (2.53%) gave positive and 206 sera (97.63%) gave negative results by passive hemagglutination test, whereas in weinberg reaction 204 of them (96.68%) were negative and 7 (3.32%) anticomplementary. 13 sera (14.13%) from another batch of 92 sera gave negative results and 79 of them (85.87%) remained negative by passive hemagglutination test, when 6 of them (6.52%) were positive and 96 (93.48%) negative by weinberg reaction. 56 (91.80%) of 61 sera taken from patients operated on for hydatid cysts gave positive and 5 (8.20%) of them negative by passive hemagglutination test. 29 (47.54%) were positive, and 32 (52.46%) negative by weinberg reaction. In another batch of 15 sera taken from patients, 3 were positive and 12 were negative by passive hemagglutination, 2 were positive and 13 were negative by weinberg test. When the two tests are compared, passive hemagglutination test gave better results both qualitatively and quantitatively than weinberg so that it may be preferred in laboratories having improved facilities.


Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer.
A phase I clinical trial and molecular correlative studies were conducted to evaluate preclinical evidence for combinatorial activity of the proteasome inhibitor bortezomib, the epidermal growth factor receptor (EGFR) inhibitor cetuximab, and radiation therapy. Patients with radiotherapy-naive stage IV or recurrent squamous cell carcinoma of the head and neck (SCCHN) were studied. Escalating doses of bortezomib (0.7, 1.0, and 1.3 mg/m²) were given intravenously twice weekly on days 1, 4, 8, and 11, every 21 days, with weekly cetuximab beginning 1 week prior and concurrently with intensity-modulated radiotherapy, delivered in 2 Gy fractions to 70 to 74 Gy. Molecular effects were examined in serial serum and SCCHN tumor specimens and the cell line UMSCC-1. Seven patients were accrued before the study was terminated when five of six previously untreated patients with favorable prognosis oropharyngeal SCCHN progressed within 1 year (progression-free survival = 4.8 months; 95% CI, 2.6-6.9). Three patients each received bortezomib 0.7 or 1.0 mg/m², without dose-limiting toxicities; one patient treated at 1.3 mg/m² was taken off study due to recurring cetuximab infusion reaction and progressive disease (PD). Expected grade 3 toxicities included radiation mucositis (n = 4), dermatitis (n = 4), and rash (n = 1). SCCHN-related cytokines increased in serial serum specimens of patients developing PD (P = 0.029). Bortezomib antagonized cetuximab- and radiation-induced cytotoxicity, degradation of EGFR, and enhanced prosurvival signal pathway activation in SCCHN tumor biopsies and UMSCC-1. Combining bortezomib with cetuximab and radiation therapy showed unexpected early progression, evidence for EGFR stabilization, increased prosurvival signaling, and SCCHN cytokine expression, warranting avoidance of this combination.


The surface structure and thermal properties of novel polymer composite films based on partially phosphorylated poly(vinyl alcohol) with aluminum phosphate.
Partially phosphorylated polyvinyl alcohol (PPVA) with aluminum phosphate (ALPO4) composites was synthesized by solution casting technique to produce (PPVA)(100-y) - (ALPO4)(y) (y = 0, 1, and 2). The surface structure and thermal properties of the films were characterized using Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The results showed that the films have higher thermal stability with strong bonding between PPVA and ALPO4.


Procedure Cost Comparison of Outpatient and Inpatient Shoulder Arthroplasty and Lower-Extremity Arthroplasty Within a Managed-Care Organization.
Introduction The authors sought to evaluate cost differences between shoulder arthroplasties and lower-extremity joint replacements in the outpatient and inpatient setting within a large health-maintenance organization. Methods A cross-sectional study of 100 total hip arthroplasties (THA), 100 total knee arthroplasties (TKA), and 100 shoulder arthroplasties (50 anatomical total shoulder arthroplasties and 50 reverse shoulder arthroplasties [RTSA]) was performed at a single regional health care center within an integrated health care maintenance organization. A time-driven activity-based costing methodology was used to obtain total cost of each episode for outpatient (vs) inpatient surgery. Results are presented by procedure type. Results Compared to their respective inpatient procedure, outpatient surgery was less expensive by 20% for RTSA, 22% for total shoulder arthroplasties, 29% for THA, and 30% for TKA. The cost of implants was the highest proportion of cost for all joint procedures across inpatient and outpatient settings, ranging from 28% of the total cost for inpatient THA to 63% of the cost for outpatient RTSA. Discussion Although many factors influence the total cost for arthroplasty surgery, including rate of hospitalization, duration of stay, operative time, complexity of cases, patient factors, equipment, and resource utilization, the implant cost remains the most expensive factor, with hospital bed admission status being the second costliest contribution. Conclusion Outpatient total arthroplasty substantially reduced procedure expenses in a managed-care setting by 20%-30%, although savings for outpatient shoulder arthroplasty was lower than savings for THA or TKA. Implant costs remain the largest portion of shoulder arthroplasty procedure expenses.


Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma.
Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.


Free to lead, free to care.
Supporting ward managers not only improves patient outcomes, but saves the NHS money too. Some trusts are achieving good results by giving ward managers supervisory status, training and greater authority. And for this the Royal College of Physicians recommends a salary of 75,000 sterling pounds.


Hot flashes--physiology, hormonal therapy, and alternative therapies.
Hormone replacement therapy should be discussed with every postmenopausal woman and should be the first therapy offered to treat hot flashes owing to its high efficacy and other beneficial properties. Women who are ineligible for or uncomfortable with estrogen replacement therapy and who suffer from hot flashes that interfere with the quality of life should be offered other regimens as discussed in this article.


Pharmacokinetics of theophylline after administration of suppositories formulation.
Asthma is a public health problem for developed countries. It attacks all age groups but often starts in childhood. Theophylline ethanoate of piperazine in a suppository form is one of the treatments of asthmatic children. The pharmacokinetics of theophylline were evaluated in 24 healthy male subjects after administration of theophylline ethanoate of piperazine suppositories (PR) (Minophylline 500 mg. Alexandria Co.) and single injection intravenous (IV) of theophylline ethanoate of piperazine (Minophylline ampoules 500 mg Alexandria Co.). The theophylline serum levels were determined by an ELISA method. Peak theophylline plasma concentration, Cmax, (mean +/- S.D) was 21.5 +/- 2.10 microg/mL & 14 +/- 0.90 microg/mL; AUC(0-t), values were 80.9 and 67. 4 microg x ml x hr for the reference IV preparation and suppositories, respectively. The median peak time, Tmax, was 0.5 hr for theophylline rectal administration. The above mentioned results demonstrate the possibilities of using theophylline (Minophylline Suppositories--500 mg Alexandria Co.) in asthmatic children in rural and desert areas away from health care personnel.


A micelle-mediated approach enables facile access to bridged oxabicyclo[n.3.1]alkene scaffolds.
Oxabicyclo[n.3.1]alkene scaffolds present in a diverse range of complex natural products have been accessed by reacting 2-cycloalkenones with 1,3-cycloalkadiones in a micellar medium. This reaction occurring in a micellar confinement environment operates through a Michael addition/enolization/oxygen addition cascade to furnish highly functionalized constructs using a sustainable organic synthesis protocol. NMR analysis confirms that the locus of the solubilizates is within the palisade and stern regions of the micellar cavity.


Triethyllead inhibits gamma-aminobutyric acid binding to uptake sites in synaptosomal membranes.
Triethyllead (TEL), the active metabolite of tetraethyllead, was shown previously to inhibit selectively high-affinity Na+-dependent uptake of gamma-aminobutyric acid (GABA) into cerebrocortical synaptosomes. Such inhibition was not related to the Na+ gradient, Na+,K+-ATPase activity, [Cl-], or energy charge. We report here that TEL inhibits GABA binding to the presynaptic transporter involved in Na+-dependent uptake. Scatchard plot analysis of Na+-dependent [3H]GABA binding to a highly purified synaptic plasma membrane preparation revealed that 25 microM TEL reduced the Bmax by 44%, leaving the KD unchanged. This binding was reversible and predominantly involved membrane uptake sites, as characterized by pharmacological specificity to GABA ligands. Approximately 85% of specific GABA binding was considered membrane uptake site binding, as indicated by sensitivity to nipecotic acid and diaminobutyric acid, with relative insensitivity to muscimol, bicuculline methiodide, baclofen, and beta-alanine. With respect to previous data, these finding suggest that TEL inhibits Na+-sensitive high-affinity GABA uptake by interfering with GABA binding to its presynaptic transporter.


Neuronal avalanches in Watts-Strogatz networks of stochastic spiking neurons.
Networks of stochastic leaky integrate-and-fire neurons, both at the mean-field level and in square lattices, present a continuous absorbing phase transition with power-law neuronal avalanches at the critical point. Here we complement these results showing that small-world Watts-Strogatz networks have mean-field critical exponents for any rewiring probability p>0. For the ring (p=0), the exponents are the same from the dimension d=1 of the directed-percolation class. In the model, firings are stochastic and occur in discrete time steps, based on a sigmoidal firing probability function. Each neuron has a membrane potential that integrates the signals received from its neighbors. The membrane potentials are subject to a leakage parameter. We study topologies with a varied number of neuron connections and different values of the leakage parameter. Results indicate that the dynamic range is larger for p=0. We also study a homeostatic synaptic depression mechanism to self-organize the network towards the critical region. These stochastic oscillations are characteristic of the so-called self-organized quasicriticality.


Overexpression of miR-146a and miR-155 are Potentially Biomarkers and Predict Unfavorable Relationship between Gastric Cancer and Helicobacter pylori Infection.
Gastric Cancer (GC) is one of the most dangerous malignancies in the world. This study aims to evaluate the relationship between miR-146a and miR-155 in patients with H. pylori infections with GC compared to H. pylori-infected patients and healthy subjects. Forty patients with H. pylori and GC positive diagnoses and 40 patients with H. pylori positive and GC negative diagnoses, and 40 healthy persons were selected. The expression of miR-146a and miR-155 genes in the whole blood was examined using qRT-PCR. Moreover, ROC curves were drawn to represent the sensitivity and specificity of miR-146a and miR-155 expression as biomarkers. The results showed the expression of miR-146a and miR-155 in the whole blood of patients with H. pylori and GC positive diagnoses are significantly higher than in healthy individuals and are non-significantly enhanced compared to H. pylori positive and GC negative. Also, the results stated miR-146a and miR-155 expression in the whole blood of patients who are H. pylori positive and GC negative are significantly increased compared to healthy individuals. Furthermore, the ROC curve analysis of miR-146a and miR-155 RNA level demonstrated the two miRNAs have an appropriate sensitivity and specificity for diagnostic goals. In conclusion, H. pylori infection may increase the expression of miR-146a and miR-155 in patients with H. pylori and GC positive diagnoses, which can be effective in the curbing the progression of GC. For this reason, up-regulation of miR-146a and miR-155 along with H. pylori infection might contribute to the pathogenesis of GC, and also can be suggested as biomarkers for GC diagnosis and treatment.


Communicative action, a path through the dissonance between nursing and corporate healthcare values.
There is tension in the US healthcare system due to conflicting goals of maximizing the public's health and at the same time ensuring shareholder profit among the many private organizations that provide care to those in need. As a result, nurses (often the frontline workers in this mixed public/private and economized system) may experience dissonance between their professional values and the capitalistic values embodied in the healthcare system. Beyond the workplace, nurses are also committed to championing health and wellness, to advocating for social justice, and driving health policy. Yet, constrained by the conflicts between neoliberal values in an economized system and the values of care that inspire many to join the healthcare profession, nurses may lose the ability to live up to their moral ideals, to champion social justice, and to improve public health outcomes. In this paper, we use the critical theory of Juergen Habermas to explore these tensions and to suggest a path forward for nurses. We suggest that by engaging in dialog with each other and the public, and working for greater inclusivity, nurses can find ways to deconstruct ideologies inherent in our current healthcare system, to consider alternatives, and liberate healthcare from the dominance of market forces.


Inframammary Fold Reconstruction: A Biomechanical Analysis.
Inframammary fold reconstruction has scarcely been evaluated in literature. No biomechanical analyses have been performed comparing different reconstructive methods. This evaluation compares the gold-standard suture reconstruction with an intrarib anchor system (Micro BioComposite SutureTak, Arthrex). Three analysis groups were compared including 8 Sawbone blocks, 22 embalmed cadaver, and 27 regular cadaver specimens (N = 57). Transient mechanical analysis was performed at 5 N/s using an Instron 5565 test frame. Ultimate load favored the anchor system (compared with the gold-standard suture) by a factor of 9.8 (P < 0.0001) for the regular cadaver group and a factor of 1.7 (P < 0.038) for the embalmed cadaver group. A similar statistically significant benefit was shown for stiffness and load at 2-mm displacement. This analysis showed an anchor system to be the biomechanically superior fixation method in terms of ultimate load, fixation stiffness, and displacement at failure when compared with the gold-standard suture method in inframammary fold reconstruction. Because of superior stability in every aspect, an anchor system may be considered for inframammary fold reconstruction.


Surrogacy and women's right to health in India: issues and perspective.
The human body is a wonderful machine. The future of child birth in the form of test tube babies, surrogate motherhood through new reproductive and cloning technology will introduce undreamt of possibilities in the sexual arena. Surrogacy is a method of assisted reproduction whereby a woman agrees to become pregnant for the purpose of gestating and giving birth to a child for others to raise. In some jurisdictions the possibility of surrogacy has been allowed and the intended parents may be recognized as the legal parents from birth. Commercial surrogacy, or "Womb for rent", is a growing business in India. In our rapidly globalizing world, the growth of reproductive tourism is a fairly recent phenomenon. Surrogacy business is exploiting poor women in country like India already having with an alarmingly high maternal death rate. This paper talks about paternity issues and women's right to health in context of surrogacy. Government must seriously consider enacting a law to regulate surrogacy in India in order to protect and guide couples going in for such an option. Without a foolproof legal framework, patients will invariably be misled and the surrogates exploited.


Methodological triangulation in healthcare research.
Sue Bradley gives a critical appraisal of the process of methodological triangulation as described in the literature, emphasising its utilisation in healthcare research.


Including dietary fiber and resistant starch to increase satiety and reduce aggression in gestating sows.
Aggression during mixing of pregnant sows impacts sow welfare and productivity. The aim of this study was to increase satiety and reduce aggression by including dietary fiber and fermentable carbohydrates. Sows were housed in individual stalls 7 to 14 d after breeding (moving day was considered d 0 of treatment) and were fed (at 0700 h) with a CONTROL (corn-soybean meal based with no additional fiber sources), RSTARCH (10.8% resistant starch), BEETPULP (27.2% sugar beet pulp), SOYHULLS (19.1% soybean hulls), or INCSOY (14.05% soybean hulls) for 21 d (5 sows/diet × 5 diets × 8 replications = 200 sows). The CONTROL diet was targeted to contain 185 g(d∙sow) NDF and the other diets were targeted to contain 350 g(d∙sow) NDF. The INCSOY diet was fed at 2.2 kg/(d∙sow) and the other diets were fed at 2 kg(d∙sow). On d 22, sows were mixed in groups of 5 (at 1200 h). Behaviors in stalls (on d 1, 7, 14, and 21) and after mixing (d 22 and 23), heart rate (on d 1, 7, 14, and 21), blood metabolites (on d 2, 8, 15, 22, and 25), and the effects of diets on production were collected and analyzed. Sows stood more ( < 0.01) and rested less ( < 0.001) over time irrespective of the diet. Sows on BEETPULP stood more ( < 0.01) and sows on SOYHULLS rested more ( < 0.01). Sham chewing increased over days irrespective of the diet. Chewing behavior (bar and feeder) increased with days on diet ( < 0.001) and was lowest in sows on the SOYHULLS diet ( = 0.045). When mixed, biting frequency in the first hour was highest for sows on the CONTROL diet (236.5 ± 62.6) and lowest for sows on the RSTARCH diet (90.5 ± 30.5). Skin lesions increased ( < 0.001) 24 h after mixing sows irrespective of diet. Blood urea nitrogen (BUN) concentration was lowest in sows fed BEETPULP and SOYHULLS ( < 0.001). Serum glucose concentration was highest in sows fed RSTARCH and BEETPULP ( = 0.04), but there was no day effect ( = 0.62) or diet × day interaction ( = 0.60). The NEFA was greatest in sows fed RSTARCH, BEETPULP, and SOYHULLS ( < 0.001). Lactate ( < 0.001) and BUN concentrations were greatest on d 2 but dropped and remained constant after d 8. Average heart rate was lowest for sows on SOYHULLS and INCSOY compared with sows on the other diets ( = 0.03). Number of piglets born and average weaning weight were not affected by diets ( > 0.05). Average birth weight was lowest in the INCSOY diet ( = 0.02). This study demonstrates that RSTARCH and SOYHULLS can improve the welfare of sows by reducing aggression and increasing satiety in limit-fed pregnant sows without affecting production.


Tranexamic Acid: Promise or Panacea: The Impact of Air Medical Administration of Tranexamic Acid on Morbidity, Mortality, and Length of Stay.
The MATTERs and CRASH-2 studies demonstrate that tranexamic acid (TXA) reduces mortality in patients with traumatic hemorrhage. However, their results, conducted in foreign countries and with U.S. military soldiers, provoke concerns over generalizability to civilian trauma patients in the United States was reported. The evaluation of patient outcomes following treatment with TXA by a civilian air medical program. A retrospective chart review of trauma patients transported by air service to a Level 1 trauma center was conducted. For the purposes of intervention evaluation, patients meeting this criterion for the 2 years (2012-2014) prior to therapy implementation were compared with patients treated during the 2-year study period (2014-2016). Goals were to evaluate morbidity, mortality, and length of stay. During the review, 82 control and 49 study patients were identified as meeting inclusion criteria. Patients in the control group were found to be less acute, which correlated with shorter hospital stays and better discharge outcomes. Multiple patients in the study group who should have expired according to a significantly elevated Trauma Revised Injury Severity Score (TRISS) survived, whereas multiple patients in the control group expired despite a low TRISS calculation. This is the first outcome-based study conducted in a U.S. trauma system. The outcomes in civilian trauma patients in the United States do not follow that of the previous MATTERs and CRASH-2 studies. However, this study still shows benefit to TXA administration and reduced risk for administration to patients with head trauma and occurrence of venous thromboembolism. Randomized control trials are needed to evaluate the role of TXA administration in the United States.


Aripiprazole for the treatment of pediatric bipolar I disorder: a 30-week, randomized, placebo-controlled study.
To evaluate the long-term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. A randomized, double-blind, 30-week, placebo-controlled study of aripiprazole (10 or 30 mg/day) in youths (10-17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double-blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Of the 210 subjects who entered the 26-week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol-specified last observation carried forward analyses, but not in observed case or mixed-model repeated measures at week 30. Overall time to all-cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children's Global Assessment of Functioning and Clinical Global Impressions-Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.


[Dental management of hemorrhage-prone patients].
The authors present a proposal of dental treatment and management of anticoagulated patients and of patients on antiplatelet therapy, with the approval by the Hungarian Association of Oral and Maxillofacial Surgeons and by the Dental Implantology Association of Hungarian Dentists. This current guide was based on recent Hungarian and on several foreign national guidelines and considers significant publications from international literature.


Aerobic oxidation of hydrogen sulfide by Thiobacillus denitrificans.
It has been demonstrated that Thiobacillus denitrificans may be readily cultured aerobically in batch and continuous flow reactors on H(2)S(g) under sulfide limiting conditions. Under these conditions sulfide concentrations in the culture medium were less than 1muM resulting in very low concentrations of H(2)S in the reactor outlet gas. Biomass yield under aerobic conditions was much lower than previously reported for anaerobic conditions, presumably because of oxygen inhibition of growth. However, biomass yield was not affected by steady state oxygen concentration in the range of 45muM-150muM. Biomass yield was also observed to be essentially independent of specific growth rate in the range of 0.030-0.053 h(-1). Indicators of reactor upset were determined and recovery from upset conditions demonstrated. Maximum loading of the biomass for H(2)S oxidation under aerobic conditions was observed to be 15.1-20.9 mmol/h/g biomass which is much higher than previously reported for aerobic conditions. Other aspects of the stoichiometry of aerobic H(2)S oxidation are also reported.


The efficacy of intra-alveolar 0.2% chlorhexidine gel on alveolar osteitis: a meta-analysis.
The objective of this meta-analysis was to assess the effect of 0.2% chlorhexidine gel in preventing alveolar osteitis following mandibular third molar extraction(s). PubMed, Cochrane Library, Embase, Web of Science, Science Direct and the references of identified articles were searched for relevant studies that met our eligibility criteria. Treatment effects were combined by meta-analysis using RevMan 5.3 and Stata 12.0 software. We included 11 trials in this meta-analysis. Compared to the control, 0.2% chlorhexidine gel reduced the risk of alveolar osteitis by 62% (RR = 0.38, 95% CI = 0.28-0.53, P < 0.00001) following mandibular third molar extraction(s). The subgroup analysis results indicated that 0.2% chlorhexidine gel reduced the risk of alveolar osteitis after mandibular third molar extraction(s) by 75% (RR = 0.25, 95% CI = 0.11-0.58) and 56% (RR = 0.44, 95% CI = 0.30-0.63) compared to no treatment and placebo, respectively. However, the occurrence of alveolar osteitis following mandibular third molar extraction(s) was not significantly different between 0.2% chlorhexidine gel and 0.12% chlorhexidine mouthwash (RR = 0.24, 95% CI = 0.06-1.00). The results showed that 0.2% chlorhexidine gel was effective in preventing alveolar osteitis after lower third molar extraction(s).


Analyzing disavowed action: the fundamental resistance of analysis.
Several detailed analytic hours illustrate how, with the analyst's full participation, patients use the words, setting, and activity of analysis to gratify the very wishes they are analyzing, and so disavow the work of analysis. These gratifications, which are hidden in plain sight, are themselves disavowed in the apparent pursuit of analytic understanding. In this way the patient's and the analyst's use of the analytic situation becomes the fundamental resistance to the work itself. This process shares features in common with perversion. The painful but necessary task for both analyst and patient is to analyze this process as it is occurring, moment by moment, in the real time of the hour.


Artificial intelligence and radiomics in magnetic resonance imaging of rectal cancer: a review.
Rectal cancer (RC) is one of the most common tumours worldwide in both males and females, with significant morbidity and mortality rates, and it accounts for approximately one-third of colorectal cancers (CRCs). Magnetic resonance imaging (MRI) has been demonstrated to be accurate in evaluating the tumour location and stage, mucin content, invasion depth, lymph node (LN) metastasis, extramural vascular invasion (EMVI), and involvement of the mesorectal fascia (MRF). However, these features alone remain insufficient to precisely guide treatment decisions. Therefore, new imaging biomarkers are necessary to define tumour characteristics for staging and restaging patients with RC. During the last decades, RC evaluation via MRI-based radiomics and artificial intelligence (AI) tools has been a research hotspot. The aim of this review was to summarise the achievement of MRI-based radiomics and AI for the evaluation of staging, response to therapy, genotyping, prediction of high-risk factors, and prognosis in the field of RC. Moreover, future challenges and limitations of these tools that need to be solved to favour the transition from academic research to the clinical setting will be discussed.


Pathology-specific experimental antivenoms for haemotoxic snakebite: The impact of immunogen diversity on the in vitro cross-reactivity and in vivo neutralisation of geographically diverse snake venoms.
Snakebite is a neglected tropical disease that causes high global rates of mortality and morbidity. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms are the mainstay therapeutic for treating the toxic effects of snakebite, but despite saving thousands of lives annually, these therapies are associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility to particular geographical regions. In this study we explored the feasibility of generating globally effective pathology-specific antivenoms to counteract the haemotoxic signs of snakebite envenoming. Two different immunogen mixtures, consisting of seven and twelve haemotoxic venoms sourced from geographically diverse and/or medically important snakes, were used to raise ovine polyclonal antibodies, prior to characterisation of their immunological binding characteristics and in vitro neutralisation profiles against each of the venoms. Despite variability of the immunogen mixtures, both experimental antivenoms exhibited broadly comparable in vitro venom binding and neutralisation profiles against the individual venom immunogens in immunological and functional assays. However, in vivo assessments using a murine preclinical model of antivenom efficacy revealed substantial differences in venom neutralisation. The experimental antivenom generated from the seven venom immunogen mixture outperformed the comparator, by providing protective effects against venom lethality caused by seven of the eight geographically diverse venoms tested, including three distinct venoms that were not used as immunogens to generate this antivenom. These findings suggest that a core set of venom immunogens may be sufficient to stimulate antibodies capable of broadly neutralising a geographically diverse array of haemotoxic snake venoms, and that adding additional venom immunogens may impact negatively on the dose efficacy of the resulting antivenom. Although selection of appropriate immunogens that encapsulate venom toxin diversity without diluting antivenom potency remains challenging and further optimisation is required, the findings from this pilot study suggest that the generation of pathology-specific antivenoms with global utility is likely to feasible, thereby highlighting their promise as future modular treatments for the world's tropical snakebite victims.


Transmission risk assessment of HIV/AIDS epidemic resulting from sexual transmission in China, 2013-2017.
To estimate the risk of human immunodeficiency virus (HIV) infection through sexual transmission in China from 2013 to 2017 accurately, we divide the total population into three groups, namely, men who have sex with men (MSM) group; non-marital and commercial sex group: female sex workers (FSW) and their clients (FSWC); non-marital and non-commercial sex group: general women (GW) and general men (GM). First, the risks of HIV infection among men who have contacts with infected men or infected women decrease annually. Second, the number of contacts between susceptible FSWC and infected FSW per unit time is greater than that between susceptible MSM and infected MSM, and also greater than that between susceptible FSW and infected FSWC, which suggests that the intervention for commercial sex of heterosexual men should be strengthened. Third, the effective reproduction numbers of the MSM group and non-commercial sex group decrease annually, while the effective reproduction number of the commercial sex group decreases first, then increases, because the risk of women being infected by men decreases first, then increases. Additionally, the effective reproduction number of the commercial sex group exceeds that of the MSM group after 2015, which indicates that commercial sex contributes more and more to the HIV/AIDS epidemic.


Circular Photogalvanic Current in Ni-Doped Cd3As2 Films Epitaxied on GaAs(111)B Substrate.
Magnetic element doped Cd3As2 Dirac semimetal has attracted great attention for revealing the novel quantum phenomena and infrared opto-electronic applications. In this work, the circular photogalvanic effect (CPGE) was investigated at various temperatures for the Ni-doped Cd3As2 films which were grown on GaAs(111)B substrate by molecular beam epitaxy. The CPGE current generation was found to originate from the structural symmetry breaking induced by the lattice strain and magnetic doping in the Ni-doped Cd3As2 films, similar to that in the undoped ones. However, the CPGE current generated in the Ni-doped Cd3As2 films was approximately two orders of magnitude smaller than that in the undoped one under the same experimental conditions and exhibited a complex temperature variation. While the CPGE current in the undoped film showed a general increase with rising temperature. The greatly reduced CPGE current generation efficiency and its complex variation with temperature in the Ni-doped Cd3As2 films was discussed to result from the efficient capture of photo-generated carriers by the deep-level magnetic impurity bands and enhanced momentum relaxation caused by additional strong impurity scattering when magnetic dopants were introduced.


Individual and Environmental Factors Associated with Tobacco Smoking, Alcohol Abuse and Illegal Drug Consumption in University Students: A Mediating Analysis.
Substance abuse is a major and prevalent public health concern among university students. Tobacco smoking, risky alcohol behavior, and illegal drug consumption may lead to health problems and behavioral and academic issues. Several individual and environmental factors associate with substance abuse in this population, and the mediating effect of alcohol abuse in the relationship between tobacco smoking and drug consumption is yet to be explored. The purposes of this study were to evaluate the association of individual and environmental factors and substance use, and to analyze the relationship between tobacco smoking, alcohol abuse, and drug consumption, considering alcohol abuse as a possible mediator. A total of 550 Spanish undergraduate and postgraduate students completed several questionnaires regarding their smoking status, alcohol use, and drug consumption during the last six months. Bivariate and multivariate analyses were conducted to explore associations between factors. Direct, indirect and mediating effects were tested using a partial least squares approach (PLS-SEM). The results indicated that substance abuse is associated with being male, living with other students, and combined substance consumption. PLS-SEM showed a significant effect of tobacco smoking and alcohol abuse on drug consumption. Alcohol abuse plays a mediating role in the relationship between tobacco smoking and drug use.


Complementary usage of Rhodiola crenulata (L.) in chronic obstructive pulmonary disease patients: the effects on cytokines and T cells.
Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age-matched, and sex-matched non-COPD control subjects. Our results showed that serum levels of IL-2, IL-10, and IFN-γ in COPD patients before treatment are significantly higher than levels in non-COPD controls (p < 0.05). A significant decrease in IFN-γ was seen in the Rhodiola treatment group (p < 0.05) but not in the placebo group (p > 0.05). The results suggested that Rhodiola treatment had beneficial antiinflammation effects, lower COPD assessment test score and decreased high-sensitivity C-reactive protein, on COPD patients (p < 0.05). The effects of Rhodiola treatment on COPD patients were shown to decrease the IFN-γ concentration and CD8(+) count but increase the expressions of CD4(+) CD25(+) FOXP3(+) and CD4(+) CD25(+) CD45(+) FOXP3(+) in the blood significantly (p < 0.05). This is the first trial using Rhodiola as a complementary therapy for COPD patients. T cells play an important role in the pathogenesis of COPD through the increased expression of CD8(+) T cells and IFN-γ and may be a viable target for potential therapy.


Do epidermal cells produce thymic hormones in vivo? An immunohistochemical study using anti-thymic hormone antibodies.
Cultured human epidermal cells have been shown to produce soluble factors endowed with T cell differentiating activities. In addition, the presence of thymopoietin and FTS/thymulin-like factors has been reported in normal human and mouse epidermis using immunohistochemical methods and anti-thymic hormone antibodies. The present study was conducted to re-evaluate the presence of thymic hormones in normal epidermal cells using a panel of monoclonal antibodies (mAbs) and rabbit antisera to several well characterized thymic factors. The reactivity of the following antibodies was tested by indirect immunofluorescence on human and mouse tissue sections: a) two anti-FTS/thymulin mAbs; b) one anti-FTS/thymulin rabbit antiserum; c) one anti-thymopoietin rabbit antiserum; d) one anti-thymosin alpha 1 mAb. Our results show that: 1) all five antibodies reacted with human and/or mouse thymic epithelial cells; 2) none of the 3 antithymic hormone mAbs (2 anti-FTS/thymulin and 1 anti-thymosin alpha 1 mAbs) reacted with normal skin; 3) only 2 out of 5 antibodies, namely the anti-FTS and anti-thymopoietin antisera cross-reacted with mouse and human epidermis and labeled keratinocytes, as previously reported; these latter 2 antibodies also stained nude mouse epidermal cells and labeled non-thymic, non-epidermal normal mouse epithelial tissues, suggesting that the cross-reactive epitope is common to a number of epithelial cells; 4) the antigen defined by the anti-FTS and anti-thymopoietin antisera was not related to keratins, since absorption experiments using purified human epidermal keratins failed to abolish staining of the epidermis. We conclude from this study that epidermal cells do not produce in vivo the well characterized thymic hormones: FTS/thymulin, thymopoietin and thymosin alpha 1. The precise nature of the antigenic structure recognized within epidermis by the anti-FTS and anti-thymopoietin antibodies remains to be defined.


Successful Treatment of Cannabinoid Hyperemesis Syndrome with Topical Capsaicin.
Cannabinoid hyperemesis syndrome (CHS) is a clinical entity in which marijuana users develop nausea, vomiting, and abdominal pain that improves with hot water bathing or cannabis cessation. Previous models suggest that CHS arises solely from the derangement of cannabinoid receptor type 1 signaling. However, involvement of transient receptor potential vanilloid subtype 1 (TRPV1) receptor, which is activated by marijuana, capsaicin, and heat, could fill gaps in existing models, including the enigmatic role of hot water bathing. We propose that chronic cannabis use decreases TRPV1 signaling and alters gastric motility, and we report the case of a CHS patient whose symptoms improved after topical capsaicin.


Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines.
Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19-0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations focusing on the detection of DSB for predicting individual response to radiation therapy for dogs, regardless of tumor type.


The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer.
Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.


The influence of a fructooligosaccharide prebiotic combined with alfalfa molt diets on the gastrointestinal tract fermentation, Salmonella enteritidis infection, and intestinal shedding in laying hens.
Molting is a natural process, which birds undergo to rejuvenate their reproductive organs. The US poultry egg production industry has used feed withdrawal to effectively induce molt; however, susceptibility of Salmonella Enteritidis has encouraged the development of alternative methods. Previous research conducted in our laboratory showed that alfalfa is effective at molt induction and provides equivalent postmolt production numbers and quality when compared with feed withdrawal. In the attempt to further increase the efficacy of alfalfa molt diet and decrease the chicken susceptibility to Salmonella Enteritidis during molt, fructooligosaccharide (FOS) was added to a combination of 90% alfalfa and 10% layer ration in 2 levels (0.750 and 0.375%). Ovary and liver colonization by Salmonella Enteritidis in 3 and 2 of the 4 trials, respectively, were reduced (P <or= 0.05) in hens fed FOS-containing diets compared with hens subjected to feed withdrawal. Significant decreases in ce-cal Salmonella Enteritidis counts were also observed in 2 of the 4 trials. In 3 of the 4 trials, the same diets did not affect (P > 0.05) the production of cecal total volatile fatty acids when compared with hens undergoing feed withdrawal. However, in all 3 alfalfa molt diets, the concentrations of lactic acid were greater (P <or= 0.05) than hens with feed withdrawal, but no differences (P > 0.05) were observed among hens fed alfalfa combined with FOS and hens fed alfalfa/layer ration without FOS. Overall, given the similarities between hens fed 0.750% FOS (H) and 0.375% FOS (L), molt diets combined with the lower level of FOS should be sufficient.


Comparison of two commonly used methods in measurement of cancer volume in prostate biopsy.
Currently, cancer volume in prostate biopsy samples is commonly calculated as linear length of carcinoma divided by total core length and reported as percentage involvement. The measurement of the linear length of carcinoma can be problematic particularly when there are two or more separate foci of carcinoma in a single core. There are two most methods commonly used by practicing pathologists. One method is to measure the exact linear extent of each discrete carcinoma foci in millimeters and then add up the linear length (the exact method, E method). The other method is to measure the core length encompassing all carcinoma foci including the intervening benign prostate tissue (glands and/or stroma) (the scattered method, S method). In this study, we used digital pathology to compare the site-specific and overall cancer volumes measured with the E and S methods and analyzed their correlation with the cancer volume in the corresponding prostatectomy specimens. Our results showed that prostate-cancer volumes estimated with both E and S methods on biopsy samples positively correlate with cancer volume at radical prostatectomy. However, the cancer volumes measured with both E and S methods in the majority of biopsy samples were significantly larger than that in prostatectomy (P<0.001). The E method more closely predicts the cancer volume compared to the S method. The overall cancer volume is better than site-specific cancer volume at biopsy in predicting cancer volume at prostatectomy.


Using Post Transplant 1 Week Tc-99m DPTA Renal Scan as Another Method for Predicting Renal Graft Failure.
The aims of this study were to determine whether post transplant renal scan performed at around 1 week can predict graft failure, and to identify the best predictive factors among easy-to-measure variables. We retrospectively evaluated patients who underwent Tc-99m DTPA renal scan at approximately 1 week after renal transplantation. They were separated into two categories at 3 months after the operation; graft failure and non-failure. Graft failure was confirmed by biopsy (rejection). Non-failure was confirmed either by biopsy or clinical follow-up with serum creatine (Cr). Scan parameters including glomerular filtration rate (GFR), Hilson perfusion index, peaks of the iliac and graft perfusion curves were analyzed. Clinical variables including age, sex, height, weight, systolic blood pressure, serum Cr, type of donated kidney, side of transplant, and immunosuppressant were also analyzed. Among total 45 patients, graft failure was present in 11 cases. The serum Cr level was significantly higher in the failure group. Among scan variables, only the GFR was significantly different between groups. GFR of <44.48 mL/min was predictive of graft failure (sen 88.9%). Serum Cr level >2.13 mg/dL was also predictive (sen 72.7%). GFR on renal scan at approximately 1 week after kidney transplant can predict graft failure.


Afferent motor feedback determines the perceived location of tactile stimuli in the external space presented to the moving arm.
People make systematic errors when localizing a brief tactile stimulus in the external space presented on the index finger while moving the arm. Although these errors likely arise in the spatiotemporal integration of the tactile input and information about arm position, the underlying arm position information used in this process is not known. In this study, we tested the contributions of afferent proprioceptive feedback and predictive arm position signals by comparing localization errors during passive vs. active arm movements. In the active trials, participants were instructed to localize a tactile stimulus in the external space that was presented to the index finger near the time of a self-generated arm movement. In the passive trials, each of the active trials was passively replayed in randomized order, using a robotic device. Our results provide evidence that the localization error patterns of the passive trials are similar to the active trials and, moreover, did not lag but rather led the active trials, which suggests that proprioceptive feedback makes an important contribution to tactile localization. To further test which kinematic property of this afferent feedback signal drives the underlying computations, we examined the localization errors with movements that had differently skewed velocity profiles but overall the same displacement. This revealed a difference in the localization patterns, which we explain by a probabilistic model in which temporal uncertainty about the stimulus is converted into a spatial likelihood, depending on the actual velocity of the arm rather than involving an efferent, preprogrammed movement.NEW & NOTEWORTHY We show that proprioceptive feedback of arm motion rather than efferent motor signals contributes to tactile localization during an arm movement. Data further show that localization errors depend on arm velocity, not displacement per se, suggesting that instantaneous velocity feedback plays a role in the underlying computations. Model simulation using Bayesian inference suggests that these errors depend not only on spatial but also on temporal uncertainties of sensory and motor signals.


Radical scavenging activities of niacin-related compounds.
We investigated whether niacin-related compounds had radical-scavenging activity by electron spin resonance methods. Many compounds, but not trigonelline, had radical-scavenging activity against hydroxyl radicals. However, for the nitric oxide radical and 1,1-diphenyl-2-picrylhydrazyl radical, only nicotinic acid hydrazide and isonicotinic acid hydrazide had scavenging activities. These results suggest that the moiety of hydrazide might have an important role in scavenging abilities of various radicals.


An attempt to predict graduation from medical school.
Although there is less attrition from medical school now than in prior years, 500 or more students can be expected to withdraw from American medical schools during each academic year. Continuing study of the problem is, therefore, warranted. Personality inventory, cognitive, and application data, all gathered at the time of admission, were examined for 1,014 graduates and 57 dropouts; separate analyses were conducted for the 17 who departed for academic reasons and the 40 whose attrition was attributable to other causes. Correlational analyses were also conducted in which graduates, nonacademic dropouts, and academic dropouts were scaled in a 4-3-1 continuum. The best predictor of this graduation versus dropout hierarchy was given by a six-variable combination, including scores on the Quantitative ability subtest of the Medical College Admission Test and premedical grades for the last two terms, with positive weightings; personality inventory scales for status potential, socialization, and communality, also with positive weightings; and a personality scale for conformist achievement drive, weighted negatively.


Dose-response of spinal manipulation for cervicogenic headache: study protocol for a randomized controlled trial.
Cervicogenic headache is a prevalent and costly pain condition commonly treated by chiropractors. There is evidence to support the effectiveness for spinal manipulation, but the dose of treatment required to achieve maximal relief remains unknown. The purpose of this paper is to describe the methodology for a randomized controlled trial evaluating the dose-response of spinal manipulation for chronic cervicogenic headache in an adult population. This is a mixed-methods, two-site, prospective, parallel groups, observer-blind, randomized controlled trial conducted at university-affiliated research clinics in the Portland, OR and Minneapolis, MN areas. The primary outcome is patient reported headache frequency. Other outcomes include self-reported headache intensity, disability, quality of life, improvement, neck pain intensity and frequency, satisfaction, medication use, outside care, cervical motion, pain pressure thresholds, health care utilization, health care costs, and lost productivity. Qualitative interviews are also conducted to evaluate patients' expectations of treatment. With growing concerns regarding the costs and side effects of commonly used conventional treatments, greater numbers of headache sufferers are seeking other approaches to care. This is the first full-scale randomized controlled trial assessing the dose-response of spinal manipulation therapy on outcomes for cervicogenic headache. The results of this study will provide important evidence for the management of cervicogenic headache in adults. ClinicalTrials.gov (Identifier: NCT01530321).


Conducting Polymers Crosslinked with Sulfur as Cathode Materials for High-Rate, Ultralong-Life Lithium-Sulfur Batteries.
Low electrical conductivity and a lack of chemical confinement are two major factors that limit the rate performances and cycling stabilities of cathode materials in lithium-sulfur (Li-S) batteries. Herein, sulfur is copolymerized with poly(m-aminothiophenol) (PMAT) nanoplates through inverse vulcanization to form the highly crosslinked copolymer cp(S-PMAT) in which approximately 80 wt % of the feed sulfur is bonded chemically to the thiol groups of PMAT. A cp(S-PMAT)/C-based cathode exhibits a high discharge capacity of 1240 mAh g-1 at 0.1 C and remarkable rate capacities of 880 mAh g-1 at 1 C and 600 mAh g-1 at 5 C. Moreover, it can retain a capacity of 495 mAh g-1 after 1000 deep discharge-charge cycles at 2 C; this corresponds to a retention of 66.9 % and a decay rate of only 0.040 % per cycle. Such a remarkable rate performance is attributed to the highly conductive pathways of PMAT nanoplates, and the excellent cycling stability is ascribed mainly to the chemical confinement of sulfur through a large number of stable covalent bonds between sulfur and the thiol groups of PMAT. The results suggest that this strategy is a viable paradigm for the design and engineering of conducting polymers with reactive functional groups as effective electrode materials for high-performance Li-S batteries.


Adapting chromophore-assisted laser inactivation for high throughput functional proteomics.
Recent advances in genomics and proteomics have generated a change in emphasis from hypothesis-based to discovery-based investigations. Genomic and proteomic studies based on differential expression microarrays or comparative proteomics often provide many potential candidates for functionally important roles in normal and diseased cells. High throughput technologies to address protein and gene function in situ are still necessary to exploit these emerging advances in gene and protein discovery in order to validate these identified targets. The pharmaceutical industry is particularly interested in target validation, and has identified it as the critical early step in drug discovery. An especially powerful approach to target validation is a direct protein knockdown strategy called chromophore-assisted laser inactivation (CALI) which is a means of testing the role of specific proteins in particular cellular processes. Recent developments in CALI allow for its high throughput application to address many proteins in tandem. Thus, CALI may have applications for high throughput hypothesis testing, target validation or proteome-wide screening.


Association between hepatic triacylglycerol accumulation induced by administering orotic acid and enhanced phosphatidate phosphohydrolase activity in rats.
Orotic acid is known to cause fatty liver, but it is unclear whether this is caused partly by stimulation of the enzymes for triacylglycerol (TG) synthesis. To understand the change of hepatic TG metabolism in fatty liver induced by orotic acid, we determined the liver tissue TG level and phosphatidate phosphohydrolase (PAP) activity over time in rats fed on a diet containing orotic acid (OA). A dietary lipid content of 10% was achieved by using n-6 fatty acid-rich corn oil in experiment 1, and n-6 fatty acid-rich safflower oil (SO) and n-3 fatty acid-rich fish oil (FO) with the same polyunsaturated fatty acid/monounsaturated fatty acid/saturated fatty acid (P/M/S) ratio in experiment 2. In experiment 1, an increase in the hepatic TG level due to OA intake was observed from day 5 onwards, the level rising approximately 6-fold by day 10. The activity of hepatic microsomal PAP, the rate-limiting enzyme in TG synthesis, increased markedly from day 5 onwards, concurrent with the liver diacylglycerol concentration. A strong correlation (r = 0.974) was observed between the hepatic TG level and microsome-bound PAP activity. In experiment 2, we investigated the effects of dietary fatty acid on OA-induced fatty liver. Compared with the n-6 fatty acid-rich vegetable oil diet, the relative increase in hepatic TG was smaller with the n-3 fatty acid-rich FO diet, and hepatic PAP activity fell markedly to the level for an OA-free diet. In addition, the hepatic TG accumulation and serum TG concentration were lower in the FO group than in the SO group. Nevertheless, because the hepatic TG level was low, it seems that the inhibition of liver PAP activity by FO possibly had a strong influence on the accumulation of TG in the liver. In conclusion, enhanced TG synthesis mediated by changes in liver PAP activity was involved in the hepatic TG accumulation induced by OA administration, this change being markedly suppressed by dietary n-3 fatty acids.


["Menouria", a symptom of vesico-cervicalfistulae (author's transl)].
In the paper rare clinical picture is presented as a possible clinical manifestation of vesico-cervical fistulae, the cardinal symptom being cyclic vesical haematuria - "menouria". The author discusses the cause being at the bottom of the symptomatology, and elaborates on the differential diagnosis. The author considers operative treatment necessary in all cases, and prefers the abdominaltransperitioneal access for the operation.


Tumoral calcinosis form of hydroxyapatite deposition disease in related red-bellied short-necked turtles, Emydura subglobosa.
Ten of 12 red-bellied short-necked turtles from a single clutch presented at 9 months of age with multiple white to tan nodules on their feet. Histologically, the nodules were composed of large periarticular deposits of mineralized crystalline material that extended into the joint spaces of interphalangeal joints and was surrounded by granulomatous inflammation and fibrosis. Crystallographic analysis determined the material to be apatite (calcium phosphate hydroxide) consistent with the tumoral calcinosis form of hydroxyapatite deposition disease (HADD). HADD has previously been described in aquatic turtles and rarely lizards and must be differentiated from gout in reptiles. A cause for the tumoral calcinosis lesions in these turtles could not be determined; however, based on previous reports in this species, a species-specific predilection, in conjunction with unknown environmental factors, is suspected. The use of the terms HADD, pseudogout (calcium pyrophosphate crystal deposition disease), and calcinosis circumscripta has been inconsistent, creating confusion in the literature.


Condensed-matter energetics from diatomic molecular spectra.
Analyses of molecular spectra and compression data from crystals show that a single function successfully describes the dependence on interatomic separation of both the potential energy of diatomic molecules and the cohesive binding energy of condensed matter. The empirical finding that one function describes interatomic energies for such diverse forms of matter and over a wide range of conditions can be used to extend condensed-matter equations of state but warrants further theoretical study.


Treatment outcome of alcoholics with and without cocaine disorders.
The treatment outcome literature suggests that alcoholics with coexisting drug dependence have worse prognoses. We compared three groups of inpatients treated on the same hospital unit for disorders of alcohol only (n = 51), cocaine only (n = 27), or both disorders (dual group, n = 27). At follow-up, we contacted 105 (81%) of 129 patients at a mean of 13.4 +/- 4.1 months after discharge. The three groups significantly and equivalently decreased their consumption of substances at follow-up, and they also had equivalent improvements in employment and in medical and psychiatric well-being. A nonsignificant trend existed for greater abstinence in the alcohol group (53%) than in the dual group (35%), and with regression analysis diagnostic group and stable residence predicted abstinence in the past 30 days. Elapsed time before using alcohol was equivalent for the two alcohol groups, and relapse to alcohol preceded relapse to cocaine by 1 month on average. In sum, outcomes were more similar than different for the three groups. Although specific treatments to enhance abstinence for cocaine users are indicated, clinicians should approach cocaine-using alcoholics with equal optimism for improvement as with other alcoholics.


NGO Code of Practice released.
Renewing Our Voice: Code of Good Practice for NGOs Responding to HIV/AIDS was launched on World AIDS Day 2004, with the endorsement of over 150 NGOs from around the world. Eleven NGOs collaborated on the project.


Numerical identification of teeth in Japanese shrew-moles, Urotrichus talpoides and Dymecodon pilirostris.
Numerical determination of the teeth of two species of Japanese shrew moles, Urotrichus talpoides and Dymecodon pilirostris (Talpidae, Insectivora), was based on the position of the premaxillo-maxillary suture, comparison of the dentitions of the two species with those of their relatives and the supernumerary tooth. The premaxillo-maxillary suture is situated between the fifth and sixth tooth anterior to the M1, and the fifth tooth anterior to the M1 was determined to be C both in the two species. The supernumerary tooth which appears in the gap between the third and fourth anterior to the M1 of the lower jaw of Urotrichus talpoides was considered as a relic of pdl which seems to have been lost relatively recently in the evolution of this species. It was also shown that the first premolar of the upper jaw of the Urotrichus talpoides and the first premolars of the Dymecodon pilirostris are dihyodont. Retention of the dihyodont first premolars in these species seems to be a primitive character and is significant in determining the phylogenetical positions of these species.


Mouse models to study wound closure and topical treatment of infected wounds in healing-impaired and normal healing hosts.
Full-thickness wounds were made on the backs of wound healing-impaired diabetic mice and their normally healing litter mates. The wounds were then inoculated with 10(4) colony-forming units of Pseudomonas aeruginosa. In both cases, the inoculum increased rapidly to between 10(9) and 10(10) colony-forming units/wound area. The infection caused a significant decrease in wound closure in the normally healing mice. In the wound healing-impaired diabetic mice, infection increased the size of the wound area over 100% by day 21. The wound became filled with inflammatory cells and serous fluid, and the mice lost significant amounts of weight, an additional sign of severe, ongoing infection. Early antimicrobial treatment of infected wounds in diabetic mice (1 hour after wounding and microbial inoculation) reversed the increase in wound size area, improved wound closure, and reduced to a significant degree the weight loss observed in untreated control mice. Delay in treatment for as little as 8 hours significantly reduces the efficacy of antimicrobial treatment. These models can be used to study the effects of infection as well as to determine the efficacy of topical antimicrobial and/or wound healing-enhancing substances on these wounds in both normally healing and healing-impaired hosts.


Lack of insurance coverage for testing supplies is associated with poorer glycemic control in patients with type 2 diabetes.
Public insurance for testing supplies for self-monitoring of blood glucose is highly variable across Canada. We sought to determine if insured patients were more likely than uninsured patients to use self-monitoring and whether they had better glycemic control. We used baseline survey and laboratory data from patients enrolled in a randomized controlled trial examining the effect of paying for testing supplies on glycemic control. We recruited patients through community pharmacies in Alberta and Saskatchewan from Nov. 2001 to June 2003. To avoid concerns regarding differences in provincial coverage of self-monitoring and medications, we report the analysis of Alberta patients only. Among our sample of 405 patients, 41% had private or public insurance coverage for self-monitoring testing supplies. Patients with insurance had significantly lower hemoglobin A(1c) concentrations than those without insurance coverage (7.1% v. 7.4%, p = 0.03). Patients with insurance were younger, had a higher income, were less likely to have a high school education and were less likely to be married or living with a partner. In multivariate analyses that controlled for these and other potential confounders, lack of insurance coverage for self-monitoring testing supplies was still significantly associated with higher hemoglobin A(1c) concentrations (adjusted difference 0.5%, p = 0.006). Patients without insurance for self-monitoring test strips had poorer glycemic control.


Benefits of using a chemotherapy symptom assessment scale.
'Medical Intervention aims to eliminate disease, mitigate disease effect, and maximise quality of life' (Ingham and Portenoy, 1998). Diseases present with signs and symptoms: signs can be measured objectively, symptoms cannot. It is not just disease processes that cause symptoms but also the treatment of the disease.


Post-lithography pattern modification and its application to a tunable wire grid polarizer.
This study reports a simple and cost-effective post-lithography solution for reducing the characteristic dimensions of structures on the nanometer scale using an external mechanical force without any modification of the existing exposure system. In particular, this study presents a tunable aluminum wire grid polarizer (WGP) made by a laser interference lithography and i-line (365 nm) exposure setup on polyethylene naphthalate. The WGP achieves a 58% maximum linewidth shrinkage of the metal nanowire on the polymer substrate, and further improved the polarization extinction ratio by 83% with a defined operation window and optimized strain. The simulations in this study prove the rise of the extinction ratio with the modulation of the WGP pattern. Physical evidence explains the fall of the extinction ratio for both the increase of the metal crack volume and the delaminated randomly oriented fall-on fragments under extensive operation.


Depletion interaction mediated by semiflexible polymers.
We present a simple mean-field theory to describe the polymer-mediated depletion attraction between colloidal particles that accounts for the polymer's chain stiffness. We find that for fixed polymer radius of gyration and volume fraction, the strength of this attraction increases with increasing chain stiffness in both dilute and semidilute concentration regimes. In contrast, the range of attraction monotonically decreases with chain stiffness in the dilute regime, while it attains a maximum in the semidilute regime. The obtained analytical expressions for the depletion interaction were compared with numerical self-consistent field lattice computations and shown to be in quantitative agreement. From the interaction potential between two spheres, we calculated the second osmotic virial coefficient B2, which appears to be a convex function of chain stiffness. A minimum of B2 as a function of chain stiffness was observed both in the numerical self-consistent field computations and the analytical theory. These findings help explain the general observation that semiflexible polymers are more effective depletants than flexible polymers and give insight into the phase behavior of mixtures containing spherical colloids and semiflexible polymers.


Health promotion and intellectual disability: listening to men.
Taking responsibility for your own health has been a central tenet of public health policy internationally for a number of decades. Governments in the UK and internationally continue to promote a plethora of health promotion strategies, encouraging individuals and communities to adopt healthy lifestyle choices. Although it is widely recognised that men are not as proactive in seeking out medical help or taking on health promotion advice as women, limited gender-sensitive research exists in the field of intellectual disability. Despite many health promotion policy and practice strategies targeted at this population, little research exists exploring whether men with intellectual disability acknowledge health promotion advice. The study aimed to explore how men with mild-to-moderate intellectual disability understood and perceived their health and what health promotion messages they acted upon. The study was based on a participatory approach which enabled 11 men with intellectual disability to contribute as steering group members and as participants through one-to-one interviews. Data were collected between September 2011 and July 2012. Thematic analysis was undertaken. The participants demonstrated a capacity to understand their own health. This was inclusive of a concern about associating being obese with being unhealthy. The participants reported good relationships with their general practitioners (GPs) and felt valued, in particular when the GP was prepared to offer specific intellectual disability and health promotion advice. More gendered research inclusive of the views of this male population is required and the study reiterates the importance of promoting the health of men and women with intellectual disability.


Preferences for paper bedding material of the laboratory mice.
In order to identify indicators of the preferences for bedding materials, the paper bedding material preferences of laboratory mice were investigated in the present study. Four cages, each containing a different structure of paper bedding material were connected to allow free access to each cage. The preferences for paper bedding materials of laboratory mice were judged by the differences in the length of stay and sleep in each cage. The mice preferred the bedding material that allowed them to easily hide and build nests and was soft. We conclude that the comfort and well-being of laboratory mice can be increased through the appropriate selection of bedding material.


Biochemical analysis of the regulatory T cell protein lymphocyte activation gene-3 (LAG-3; CD223).
Lymphocyte activation gene-3 (LAG-3; CD223) is a CD4-related transmembrane protein that binds to MHC class II molecules. We have recently shown that LAG-3 is required for maximal regulatory T cell function, and that ectopic expression of LAG-3 is sufficient to confer regulatory activity. In this study we show that LAG-3 is cleaved within the D4 transmembrane domain connecting peptide into two fragments that remain membrane associated: a 54-kDa fragment that contains all the extracellular domains and oligomerizes with full-length LAG-3 (70 kDa) on the cell surface via the D1 domain, and a 16-kDa peptide that contains the transmembrane and cytoplasmic domains. This NH(2)-terminal fragment is subsequently released as soluble LAG-3 (sLAG-3), a process that is increased after T cell activation in vitro and in vivo, and is found in the sera of C57BL/6 and RAG-1(-/-) mice. Modulation of LAG-3 cleavage may contribute to the function of this key regulatory T cell protein.


Fast track genetic improvement of ascochyta blight resistance and double podding in chickpea by marker-assisted backcrossing.
Ascochyta blight (AB) caused by the fungus Ascochyta rabiei Pass. Lab. is one of the major diseases of chickpea worldwide and a constraint to production in western Canada. The use of varieties with high levels of resistance is considered the most economical solution for long-term ascochyta blight management in chickpea. QTL for resistance to ascochyta blight have been identified in chickpea. The availability of molecular markers associated with QTL for ascochyta blight resistant and double podding provides an opportunity to apply marker-assisted backcrossing to introgress the traits into adapted chickpea cultivars. In the present study, molecular markers that were linked to the QTL for ascochyta blight resistance and the double podding trait, and those unlinked to the resistance were used in foreground and background selection, respectively, in backcrosses between moderately resistant donors (CDC Frontier and CDC 425-14) and the adapted varieties (CDC Xena, CDC Leader and FLIP98-135C). The strategy included two backcrosses and selection for two QTL for ascochyta blight resistance and a locus associated with double podding. The fixation of the elite genetic background was monitored with 16-22 SSR markers to accelerate restoration of the genetic background at each backcross. By the BC2F1 generation, plants with improved ascochyta blight resistance and double podding were identified. The selected plants possessed the majority of elite parental type SSR alleles on all fragments analyzed except the segment of LG 4, LG 6 and LG 8 that possessed the target QTL. The results showed that the adapted variety could be efficiently converted into a variety with improved resistance in two backcross generations.


Cholesterol-modified poly(lactide-co-glycolide) nanoparticles for tumor-targeted drug delivery.
Poly(lactide-co-glycolide)-cholesterol (PLGA-C)-based nanoparticles (NPs) were developed for the tumor-targeted delivery of curcumin (CUR). PLGA-C/CUR NPs with ∼200nm mean diameter, narrow size distribution, and neutral zeta potential were fabricated by a modified emulsification-solvent evaporation method. The existence of cholesterol moiety in PLGA-C copolymer was confirmed by proton nuclear magnetic resonance ((1)H NMR) analysis. In vitro stability of developed NPs after 24h incubation was confirmed in phosphate buffered saline (PBS) and serum media. Sustained (∼6days) and pH-responsive drug release profiles from PLGA-C NPs were presented. Blank PLGA and PLGA-C NPs exhibited a negligible cytotoxicity in Hep-2 (human laryngeal carcinoma) cells in the tested concentration range. According to the results of flow cytometry and confocal laser scanning microscopy (CLSM) studies, PLGA-C NPs presented an improved cellular accumulation efficiency, compared to PLGA NPs, in Hep-2 cells. Enhanced in vivo tumor targetability of PLGA-C NPs, compared to PLGA NPs, in Hep-2 tumor-xenografted mouse model was also verified by a real-time near-infrared fluorescence (NIRF) imaging study. Developed PLGA-C NPs may be a candidate of efficient and biocompatible nanosystems for tumor-targeted drug delivery and cancer imaging.


Immune globulin and hepatitis B immune globulin. Prophylactic measures for intimate contacts exposed to acute type B hepatitis.
We studied the relative prophylactic efficacies of recently derived immune globulin containing antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B immune globulin in 60 intimate contacts exposed to acute type B hepatitis. Forty susceptible contacts were randomly assigned to treatment with either a single intramuscular dose of immune globulin or hepatitis B immune globulin (0.06 mL/kg of body weight), following which observation was maintained over a 12-month period. Twenty additional contacts received the equivalent of twice the dose of immune globulin given to the first group, and follow-up was maintained for six months. Neither the hepatitis B virus (HBV) attack rates (11% to 19%) nor the frequency of clinical illness (0% to 4.8%) was substantially different in the three groups. When compared with average frequencies reported in the literature, significantly lower illness rates were noted for immune globulin recipients. These data indicate that currently derived immune globulin as well as hepatitis B immune globulin may confer protection from illness (le, passive-active immunity) in the setting of intimate exposure to HBV.