A Unique High-Throughput Assay to Identify Novel Small Molecule Inhibitors of Chemotaxis and Migration.
Chemotaxis and cell migration play pivotal roles in normal physiological processes such as embryogenesis, inflammation, and wound healing, as well as in pathological processes including chronic inflammatory disease and cancer metastasis. Novel chemotaxis/migration inhibitors are desirable for developing effective therapeutics and probing molecular mechanisms. We describe a fluorescence-based phenotypic assay in a 1536-well plate format for high-throughput screening of novel inhibitors of chemotaxis/migration within complex libraries of thousands of compounds. Although the assay utilizes the unique cellular response properties of Dictyostelium, the compounds identified are able to inhibit chemotaxis of mammalian cells. In addition, a parallel cell cytotoxicity counter-screen with an ATP content assay is described that eliminates cytotoxic compounds from the screen. This novel compound screening approach enables rapid identification of novel lead compounds that inhibit chemotaxis in human and other cells for drug development and research tools. © 2017 by John Wiley & Sons, Inc.


Breast cancer prevention.
Breast cancer is the most common cancer in women with 232,670 new cases estimated in the USA for 2014. Approaches for reducing breast cancer risk include lifestyle modification, chemoprevention, and prophylactic surgery. Lifestyle modification has a variety of health benefits with few associated risks and is appropriate for all women regardless of breast cancer risk. Chemoprevention options have expanded rapidly, but most are directed at estrogen receptor positive breast cancer and uptake is low. Prophylactic surgery introduces significant additional risks of its own and is generally reserved for the highest risk women.


Hemagglutinin activity and heterogeneity of related Porphyromonas gingivalis proteinases.
Thiol-dependent proteinases that are expressed and released by Porphyromonas gingivalis are considered virulence factors in periodontitis because of their potential to effect matrix degradation and inflammation. A number of P. gingivalis thiol-proteinases have been described, however, with similar biochemical characteristics. In this report we demonstrate that an isolate P. gingivalis proteinase consists of noncovalently associated peptides and that slight variations in the association pattern of these peptides could result in different proteinases with different affinities and activities. We also describe the co-purification of thiol-proteinase activity with hemagglutinin activity and demonstrate that each type of activity has similar inhibition profiles. With the use of monoclonal antibodies against the P. gingivalis proteinase we follow proteinase released into the culture medium over the course of 10 days and, by Western blot analysis, demonstrate that many of the proteinases with varying molecular weight are related. The identification of a single, immunoreactive, 140 kDa proteinase detected early in the culture and in association with the P. gingivalis cells suggests that multiple proteinase may originate from a single 140 kDa proteinase.


Mother-infant interactions in two strains of rats: implications for dissociating mechanism and function of a maternal pattern.
Mother-infant interaction was observed in Long-Evans and Fischer 344 rats after fostering within or across strains. Interactions immediately following introduction of foster pups to the cage as well as undisturbed interactions with resident litters were examined. Some differences were related to alien status, some to strain of pups, and others to strain of dams. Greater responsiveness to pups of the maternal strain was exhibited in retrieval and body licking. Long-Evans pups received more crouching from dams of both strains 3-12 days postpartum, perhaps because they are significantly larger. Regardless of pup strain, Long-Evans dams engaged in more maternal licking than did F344 dams, and this was more likely directed to the anogenital region. Dams of both strains were more likely to lick male than female pups, regardless of pup strain. The strain difference in maternal licking is consistent with adult strain differences in water and salt appetite and may contribute developmentally to the superior copulatory performance of Long-Evans males.


Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of reproductive function in immature female Japanese quail (Coturnix japonica).
In a previous study, we found that 3-methyl-4-nitrophenol (PNMC), a component of diesel exhaust particles and also a degradation product of the insecticide fenitrothion, exhibits reproductive toxicity in the adult male Japanese quail. The present study investigated the toxicity of PNMC in the female Japanese quail and its ability to influence reproduction in immature females. The quail (21-day-old) were injected intramuscularly (im) with PNMC at doses 0.1, 1 or 10 mg/kg body weight daily for 3 days. There was no significant difference in body growth between the PNMC-administered and control birds. However, the weights of the oviducts were significantly lower in the PNMC-treated birds at all doses. Furthermore, the plasma concentrations of luteinizing hormone (LH) and estradiol-17 beta were significantly decreased with 1 and 10 mg/kg of PNMC. These findings suggest that PNMC might influence the hypothalamo-pituitary-gonadal axis with decreasing in secretion of GnRH, LH and ovarian steroid hormones and subsequently disturb growth of the reproductive organs of immature female quail. This study indicates that PNMC induces reproductive toxicity at the central level and disrupts reproductive function in the immature female quail.


Protoporphyrin IX induces a necrotic cell death in human THP-1 macrophages through activation of reactive oxygen species/c-Jun N-terminal protein kinase pathway and opening of mitochondrial permeability transition pore.
Protoporphyrin IX (PpIX) and its derivatives are widely used in photodynamic therapy (PDT) to kill cancer cells. Studies showed that the application of these drugs could cause systemic toxic effects in human. However, the molecular pathways involved in PpIX-induced cytotoxicity are not well-defined. Macrophages represent the primary system for protecting tissues from toxicants and initiating the resolution of inflammation. Thus, this study aims to investigate the toxicity of PpIX on macrophages and provide strategies to prevent the toxic effects. THP-1 macrophages were incubated with PpIX and cell death was measured by MTT assay and Annexin V-PI staining. Intracellular reactive oxygen species (ROS) were evaluated by 2', 7'-Dichlorodihydrofluorescin diacetate (DCFH-DA) and MitoSOX® Red staining and mitochondrial membrane potential (ΔΨm) was detected by tetramethylrhodamine methyl ester (TMRM) staining. Mitogen-activated protein (MAP) kinase activation was assayed by western blotting. Mitochondrial permeability transition pore (mPTP) opening was measured by calcein loading/Co(2+) quenching technique and evaluating the release of mitochondrial content. PpIX reduced cell viability in a dose- and time-dependent manner. The cell death was characterized by increasing PI-positive cells, ATP depletion, LDH releasing and rapid ΔΨm loss favoring necrotic features. In addition, PpIX successively induced ROS production, c-Jun N-terminal protein kinase (JNK) activation and mPTP opening. ROS scavengers, N-acetylcysteine (NAC) and deferoxamine (DFX), JNK inhibitor, SP600125, and mPTP inhibitor, cyclosporin A (CsA), all significantly rescued this cell death. Furthermore, mPTP opening was directly regulated by ROS/JNK pathway. PpIX induces a necrotic cell death in THP-1 macrophages through ROS production, JNK activation, and mPTP opening. It is tempting to speculate that blocking the pathways involved in the cytotoxic effects of PpIX will alleviate its side effects.


Current controversies in the initial post-surgical radioactive iodine therapy for thyroid cancer: a narrative review.
Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the fifth most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post-thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Before 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease, and 175-200 mCi for distant metastases. Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies. A significant controversy has thus arisen regarding the use of RAI, particularly in the management of the low-risk DTC patient. This debate includes the definition of the low-risk patient, RAI dose selection, and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.


From the aerospace medicine residents' teaching file. Pulmonary arteriovenous malformations.
A USAF transport pilot was referred to the Aeromedical Consult Service for a cardiology work-up. During his evaluation for an abnormal treadmill, a chest X-ray showed a probable pulmonary arteriovenous malformation (PAVM). A CT scan of his chest and a shunt study confirmed this diagnosis. The aviator was referred for treatment and later underwent successful balloon embolization therapy. A discussion of PAVM presentation, diagnosis, treatment, and aeromedical aspects follows.


Promoter of Arabidopsis thaliana phosphate transporter gene drives root-specific expression of transgene in rice.
The PHT1 promoter::GUS fusion gene was constructed and introduced into Arabidopsis and rice by Agrobacterium-mediated transformation. Strong beta-glucuronidase (GUS) activity was detected in roots and showed phosphate starvation induction both in Arabidopsis and rice. In contrast, GUS activity in aerial tissues such as those of the leaf and stem was low. In situ GUS staining of root tissue indicated that PHT1 was expressed in root hairs and the outer layer of the main roots, but not in root tips. The PHT1 promoter has a desirable character for biotechnological transgene expression in monocot rice plants.


Influence of virtual reality training on the roadside crossing judgments of child pedestrians.
The roadside crossing judgments of children aged 7, 9, and 11 years were assessed relative to controls before and after training with a computer-simulated traffic environment. Trained children crossed more quickly, and their estimated crossing times became better aligned with actual crossing times. They crossed more promptly, missed fewer safe opportunities to cross, accepted smaller traffic gaps without increasing the number of risky crossings, and showed better conceptual understanding of the factors to be considered when making crossing judgments. All age groups improved to the same extent, and there was no deterioration when children were retested 8 months later. The results are discussed in relation to theoretical arguments concerning the extent to which children's pedestrian judgments are amenable to training.


Novel quantitative assessment of metamorphopsia in maculopathy.
Patients with macular disease often report experiencing metamorphopsia (visual distortion). Although typically measured with Amsler charts, more quantitative assessments of perceived distortion are desirable to effectively monitor the presence, progression, and remediation of visual impairment. Participants with binocular (n = 33) and monocular (n = 50) maculopathy across seven disease groups, and control participants (n = 10) with no identifiable retinal disease completed a modified Amsler grid assessment (presented on a computer screen with eye tracking to ensure fixation compliance) and two novel assessments to measure metamorphopsia in the central 5° of visual field. A total of 81% (67/83) of participants completed a hyperacuity task where they aligned eight dots in the shape of a square, and 64% (32/50) of participants with monocular distortion completed a spatial alignment task using dichoptic stimuli. Ten controls completed all tasks. Horizontal and vertical distortion magnitudes were calculated for each of the three assessments. Distortion magnitudes were significantly higher in patients than controls in all assessments. There was no significant difference in magnitude of distortion across different macular diseases. There were no significant correlations between overall magnitude of distortion among any of the three measures and no significant correlations in localized measures of distortion. Three alternative quantifications of monocular spatial distortion in the central visual field generated uncorrelated estimates of visual distortion. It is therefore unlikely that metamorphopsia is caused solely by retinal displacement, but instead involves additional top-down information, knowledge about the scene, and perhaps, cortical reorganization.


Microarray RNA transcriptional profiling: part II. Analytical considerations and annotation.
This review summarizes the various data filtration, transformation and normalization processes for different array platforms (cDNA, oligos, one- and two-color), data analysis methods and their validation, and databases and annotation for RNA transcriptional profiling microarrays. This review is intended to introduce the beginner to the analyses and interpretation of gene expression studies using a nonmathematical approach for easier comprehension. Microarray analysis is not a trivial undertaking as there is no single method that works well for all, and results obtained from these analyses should be considered as a complement to other approaches.


Intraventricular cryptococcal granuloma.
A case is reported of a cryptococcal granuloma occurring within the lateral ventricle. The findings on angiography and brain-scanning led to a preoperative diagnosis of intraventricular meningioma. There are no previous reports of an isotope brain-scan in this condition and angiography usually shows an avascular swelling.


Allelopathic potential of Artemisia arborescens: isolation, identification and quantification of phytotoxic compounds through fractionation-guided bioassays.
The aerial part of Artemisia arborescens L. (Asteraceae) was extracted with water and methanol, and both extracts were fractionated using n-hexane, chloroform, ethyl acetate and n-butanol. The potential phytotoxicity of both crude extracts and their fractions were assayed in vitro on seed germination and root growth of lettuce (Lactuca sativa L.), a sensitive species largely employed in the allelopathy studies. The inhibitory activities were analysed by dose-response curves and the ED 50 were estimated. Crude extracts strongly inhibited both germination and root growth processes. The fraction-bioassay indicated the following hierarchy of phytotoxicity for both physiological processes: ethyl acetate ≥ n-hexane > chloroform ≥ n-butanol. On the n-hexane fraction, GC-MS analyses were carried out to characterise and quantify some of the potential allelochemicals. Twenty-one compounds were identified and three of them, camphor, trans-caryophyllene and pulegone were quantified.


Evaluation of Appropriate Venous Thromboembolism Prophylaxis in Patients With Orthopaedic Trauma With Symptom-Driven Vascular and Radiographic Studies.
To evaluate venous thromboembolism (VTE) prophylaxis adherence and effectiveness in orthopaedic trauma patients who had vascular or radiographic studies showing deep vein thromboses or pulmonary emboli. Retrospective review. A level I trauma center that independently services a 5-state region. Four hundred seventy-six patients with orthopaedic trauma who underwent operative treatments for orthopaedic injuries and had symptom-driven diagnostic VTE studies. The medical records of patients treated surgically between July 2010 and March 2013 were interrogated using a technical tool that electronically captures thrombotic event data from vascular and radiologic imaging studies by natural language processing. Patients were evaluated for hospital guideline-directed VTE prophylaxis adherence with mechanical or chemical prophylaxis. Patient demographics, associated injuries, mechanism of injury, and symptoms that led to imaging for a VTE were also assessed. Of the 476 orthopaedic patients who met inclusion criteria, 100 (mean age 52.3 median 52, SD 18.3, 70% men) had positive VTE studies. Three hundred seventy-six (age 47.3, SD 17.3, 69% men) had negative VTE studies. Of the 100 patients with VTE, 63 deep vein thromboses, and 49 pulmonary emboli were found. Eight-five percent of all patients met hospital guideline-VTE prophylaxis standards. The study population had better than previously reported VTE prophylaxis adherence, however, patients still developed VTEs. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Exertional dyspnoea and cortical oxygenation in patients with COPD.
This study was designed to investigate the association of perceived dyspnoea intensity with cortical oxygenation and cortical activation during exercise in patients with chronic obstructive pulmonary disease (COPD) and exertional hypoxaemia.Low-intensity exercise was performed at a constant work rate by patients with COPD and exertional hypoxaemia (n=11) or no hypoxaemia (n=16), and in control participants (n=11). Cortical oxyhaemoglobin (oxy-Hb) and deoxyhaemoglobin (deoxy-Hb) concentrations were measured by multichannel near-infrared spectroscopy. Increased deoxy-Hb is assumed to reflect impaired oxygenation, whereas decreased deoxy-Hb signifies cortical activation.Exercise decreased cortical deoxy-Hb in control and nonhypoxaemic patients. Deoxy-Hb was increased in hypoxaemic patients and oxygen supplementation improved cortical oxygenation. Decreased deoxy-Hb in the pre-motor cortex (PMA) was significantly correlated with exertional dyspnoea in control participants and patients with COPD without hypoxaemia. In contrast, increased cortical deoxy-Hb concentration was correlated with dyspnoea in patients with COPD and hypoxaemia. With the administration of oxygen supplementation, exertional dyspnoea was correlated with decreased deoxy-Hb in the PMA of COPD patients with hypoxaemia.During exercise, cortical oxygenation was impaired in patients with COPD and hypoxaemia compared with control and nonhypoxaemic patients; this difference was ameliorated with oxygen supplementation. Exertional dyspnoea was related to activation of the pre-motor cortex in COPD patients.


An Infant Diagnosed With Hydrocephalus by Point-of-Care Ultrasound.
Point-of-care ultrasound has become a valuable tool for pediatric emergency physicians, with an increasing number of indications being described. In this case presentation, we demonstrate the use of point-of-care ultrasound in the pediatric emergency department to diagnose ventriculomegaly in an infant presenting with a seizure.


Houston Recovery Initiative: A Rich Case Study of Building Recovery Communities One Voice at a Time.
Recovery from alcohol and drug problems is a process of change through which an individual achieves control and improved quality of life. Recovery is a primary goal for individuals with substance use disorder as it provides hope that treatment and overall health are possible for every individual. More than 23 million Americans are in recovery from addiction to alcohol and other drugs.Recovery-oriented systems of care (ROSC) are networks of community services and peer support that help individuals and families achieve recovery from substances and improve overall health. ROSC is a strengths-based and person-centered model that leverages existing community resources to address the needs of individuals and families as they progress through the journey of recovery. The ROSC model serves as the foundation of the Houston Recovery Initiative (HRI).The purpose of this article is to describe the history, development, and infrastructure of the HRI, which is a volunteer collaboration whose main goal is to educate the community on recovery and broaden the recovery safety net for people with substance use disorder in Houston, Texas. Since 2010, the HRI has grown to include more than 200 agencies across the spectrum of treatment and recovery support services in Houston so as to provide a resource for the community. Herein, we detail efforts to grow the HRI, lessons learned, future plans, and resources needed to move the HRI forward.


State-specific changes in cholesterol screening--behavioral risk factor surveillance system, 1988-1991.
High blood cholesterol (HBC) is an important risk factor for coronary heart disease (1)--the leading cause of death in the United States. To reduce the prevalence of elevated cholesterol levels in the United States, in 1985 the National Heart, Lung, and Blood Institute initiated the National Cholesterol Education Program (NCEP). The NCEP recommends that all adults aged > or = 20 years be screened for HBC at least once every 5 years. One of the national health objectives for the year 2000 is to increase to 75% the percentage of adults screened for HBC within the preceding 5 years (objective 15.14). To measure progress toward this objective, data from CDC's Behavioral Risk Factor Surveillance System (BRFSS) were used to examine state-specific trends in cholesterol screening from 1988 through 1991. This report summarizes the results of this analysis and provides a projected estimate of the 1994 screening rates for HBC in each state.


Effectiveness of a steam cleaning unit for disinfection in a veterinary hospital.
To evaluate whether the application of steam to a variety of surface types in a veterinary hospital would effectively reduce the number of bacteria. 5 surface types. Steam was applied as a surface treatment for disinfection to 18 test sites of 5 surface types in a veterinary hospital. A pretreatment sample was obtained by collection of a swab specimen from the left side of each defined test surface. Steam disinfection was performed on the right side of each test surface, and a posttreatment sample was then collected in the same manner from the treated (right) side of each test surface. Total bacteria for pretreatment and posttreatment samples were quantified by heterotrophic plate counts and for Staphylococcus aureus, Pseudomonas spp, and total coliforms by counts on selective media. Significant reductions were observed in heterotrophic plate counts after steam application to dog runs and dog kennel floors. A significant reduction in counts of Pseudomonas spp was observed after steam application to tub sinks. Bacterial counts were reduced, but not significantly, on most other test surfaces that had adequate pretreatment counts for quantification. Development of health-care-associated infections is of increasing concern in human and veterinary medicine. The application of steam significantly reduced bacterial numbers on a variety of surfaces within a veterinary facility. Steam disinfection may prove to be an alternative or adjunct to chemical disinfection within veterinary practices.


Biosensor technology: technology push versus market pull.
Biosensor technology is based on a specific biological recognition element in combination with a transducer for signal processing. Since its inception, biosensors have been expected to play a significant analytical role in medicine, agriculture, food safety, homeland security, environmental and industrial monitoring. However, the commercialization of biosensor technology has significantly lagged behind the research output as reflected by a plethora of publications and patenting activities. The rationale behind the slow and limited technology transfer could be attributed to cost considerations and some key technical barriers. Analytical chemistry has changed considerably, driven by automation, miniaturization, and system integration with high throughput for multiple tasks. Such requirements pose a great challenge in biosensor technology which is often designed to detect one single or a few target analytes. Successful biosensors must be versatile to support interchangeable biorecognition elements, and in addition miniaturization must be feasible to allow automation for parallel sensing with ease of operation at a competitive cost. A significant upfront investment in research and development is a prerequisite in the commercialization of biosensors. The progress in such endeavors is incremental with limited success, thus, the market entry for a new venture is very difficult unless a niche product can be developed with a considerable market volume.


Men with hip fractures have poorer nutritional status and survival than women: a prospective study of 165 patients.
Many hip fracture patients have a poor nutritional status which may be one explanation for their increased mortality. We studied nutritional status and other mortality-related factors prospectively in 165 patients with hip fractures (85 women). We concentrated on differences between death rates and survival rates at 3 months and at 1 year, and between those patients who died within 3 months and those who died later. In general, men had a poorer nutritional status and a larger number of comorbidities. Also, there were more smokers and alcohol abusers amongst the men. Of the patients who died during the first 3 months, most were men, and their initial nutritional status was poorer than that of women. Multivariate logistic regression analysis revealed a correlation between mortality and total serum protein, retinol binding protein and the number of comorbidities. Among patients who died after 3 months, mortality was associated with the number of comorbidities and smoking. The higher mortality rate in men than in women after hip fracture may in part be explained by the poor nutritional status in men.


Impact of the COVID-19 pandemic on surgical practice, training, and research in Nigeria.
the rising rate of SARS-CoV-2 infections has caused perceptible strain on the global health system. Indeed, this disease is also a litmus test for the resilience of the structures in the African health system including surgery. Therefore, this study aimed to determine the impact of the COVID-19 pandemic on surgical practice, training and research in Nigeria. it was a cross-sectional study conducted over three weeks in Nigeria among doctors in 12 surgery-related specialties. Consenting participants filled a pre-tested online form consisting of 35 questions in 5 sections which assessed demographics, infection control measures, clinical practice, academic training, research program, and future trends. Data were analyzed using Statistical Package for Social Sciences Version 20. a total of 384 respondents completed the form. Their mean age was 38.3 years. Lockdown measures were imposed in the state of practice of 89.0% of respondents. Most participants reported a decrease in patient volume in outpatient clinics (95.5%) and elective operations (95.8%) compared to reports for emergency operations (50.2%). They also noted a decrease in academic training [Bedside teaching (92.1%), seminar presentation (91.1%) and journal presentation (91.8%)] and research (80.5%). Except in bedside teaching, those who had other virtual academic programmes were thrice the number of those who used in-person mode for the events. COVID-19 pandemic has caused a significant change in pattern and a decrease in the volume of patients seen by surgeons in their practice as well as a decrease in the frequency of academic programs and research activities in Nigeria.


Knowledge-informed behavior and the nursing culture: a preliminary study.
The pilot study reported in this article was undertaken to identify roles that nurses perform in actual practice and factors and behaviors that enable or prevent them from resolving practice problems in a knowledge-informed way. It was theorized that if nursing roles based on actual practice can be described and if behaviors which enhance knowledge-utilization can be identified, nurses can learn to implement the specific activities needed to ensure the full application of professional knowledge in the practice setting. This preliminary study uncovered six intersecting roles assumed by nurses in the practice of their profession and identified nine categories of behavior and their influence on the ability to use knowledge in carrying out each role. The findings provide additional insight into the nursing culture and suggest the need for changes for education and service.


Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.
Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.


Concurrent chemoradiotherapy with weekly docetaxel versus cisplatin in the treatment of locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis.
Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy (CCRT) were reported in head and neck cancer. In addition, the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma (NPC) was verified. However, CCRT with docetaxel for locoregionally advanced NPC are not well studied. This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC. Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel (15 mg/m2) or tri-weekly cisplatin (80-100 mg/m2) were reviewed. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics. Adverse events and survival were compared between the two groups. A total of 962 patients were included as the whole cohort, and 448 patients were matched and were regarded as the matched cohort. The median follow-up duration was 48 months for the whole cohort. The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole (hazard ratio [HR] = 0.37, 95% confidence interval [CI] 0.19-0.72, P = 0.030) and matched cohorts (HR = 0.33, 95% CI 0.14-0.79, P = 0.023). However, no significant differences were observed in overall survival, local recurrence-free survival, and distant metastasis-free survival between the two groups in both cohorts. Significantly higher rates of grade 3 radiodermatitis (6.7% vs. 1.8%, P = 0.001), mucositis (74.5% vs. 37.9%, P < 0.001), and leucopenia (2.2% vs. 11.6%, P < 0.001) were observed in the docetaxel group, but any grade of renal injury (1.8% vs. 15.1%, P < 0.001), vomiting (18.8% vs. 88.3%, P < 0.001), and ALT elevation (19.2% vs. 31.3%, P = 0.027) were more common in the cisplatin group. CCRT with weekly low-dose docetaxel is an effective and tolerable therapeutic regimen for locally advanced NPC. It provides a survival benefit mainly by improving the control of regional lymph node metastases, especially for patients with low pretreatment EBV DNA levels.


Cochlear nerve action potentials during cerebellopontine angle surgery: relationship of latency, amplitude, and threshold measurements to hearing.
The cochlear nerve action potential (AP) was monitored during two types of hearing preservation surgery: (1) removal of small cerebellopontine angle tumors and (2) retrolabyrinthine vestibular nerve section. The purpose of this investigation was to study the relationship between changes in intraoperative AP latency, amplitude, and threshold, and changes in audiometric hearing subsequent to surgery. The presence or absence of a cochlear nerve AP toward the end of surgery accurately predicted the presence or absence of postoperative hearing (93%). Regression analyses were performed to explore the relationship between audiometric pre- and postoperative thresholds and intraoperative AP threshold changes. Statistically significant relationships were found for (1) pre-operative audiometric thresholds and initial AP click thresholds (p = 0.0068); (2) final AP click thresholds and postoperative audiometric thresholds (p = 0.0003); (3) AP click (p = 0.0001) and 1 kHz (p = 0.0006) threshold shifts and pre- to postoperative audiometric threshold shifts. No relationship was found between either AP latency or amplitude values and postoperative hearing. Intraoperative threshold measurements can be used as an indicator of hearing change. If amplitude or latency indices are also monitored it may be better to use stimulus levels close to the evoked potential threshold.


Total joint replacement in digits of the foot.
Digital deformities present one of the most common entities seen by the podiatric physician today. Surgical correction of these deformities has historically centered upon the "arthroplasty" or phalangeal head resection, but the advent of Silastic implants that replace the interphalangeal joints of the lesser digits may improve the results of revision arthroplasties or severely arthritic joints. This paper will present two types of lesser digital implants that have successfully been used when the proper indications are met.


Cholestasis in patients with acquired immunodeficiency syndrome: a surgeon's perspective.
Cholestasis is a common finding in patients with acquired immunodeficiency syndrome. The underlying causes may be related to intrahepatic processes, cholecystitis, papillary stenosis, or sclerosing cholangitis. Published reports of hepatobiliary diseases in patients with acquired immunodeficiency syndrome are reviewed. The etiological factors are considered, and available therapeutic approaches are discussed. Hepatic causes of cholestasis indicate poor prognosis, and effective treatments are not yet available. Cholecystitis, often acalculous in origin, remains a surgical disease. Endoscopic sphincterotomy appears to give good results in the treatment of papillary stenosis. Although a standard approach to sclerosing cholangitis has not been established, a trial of appropriate antibiotics may be beneficial. Frequently, the cause of cholestasis is multifactorial in these patients; thus, a coherent therapeutic approach is essential for optimal clinical results.


Glass Fiber Reinforced Epoxy-Amine Thermosets and Solvate IL: Towards New Composite Polymer Electrolytes for Lithium Battery Applications.
To effectively use (Li) lithium metal anodes, it is becoming increasingly necessary to create membranes with high lithium conductivity, electrochemical and thermal stabilities, as well as adequate mechanical properties. Composite gel polymer electrolytes (CGPE) have emerged as a promising strategy, offering improved ionic conductivity and structural performance compared to polymer electrolytes. In this study, a simple and scalable approach was developed to fabricate a crosslinked polyethylene oxide (PEO)-based membrane, comprising two different glass fiber reinforcements, in terms of morphology and thickness. The incorporation of a solvated ionic liquid into the developed membrane enhances the ionic conductivity and reduces flammability in the resulting CGPE. Galvanostatic cycling experiments demonstrate favorable performance of the composite membrane in symmetric Li cells. Furthermore, the CGPE demonstrated electrochemical stability, enabling the cell to cycle continuously for more than 700 h at a temperature of 40 °C without short circuits. When applied in a half-cell configuration with lithium iron phosphate (LFP) cathodes, the composite membrane enabled cycling at different current densities, achieving a discharge capacity of 144 mAh·g-1. Overall, the findings obtained in this work highlight the potential of crosslinked PEO-based composite membranes for high-performance Li metal anodes, with enhanced near room temperature conductivity, electrochemical stability, and cycling capability.


Spatiotemporal coordinated hierarchical properties of cellular protrusion revealed by multiscale analysis.
We present a methodology for integrative multiscale analysis to highlight hierarchical properties of cellular protrusion and mechanochemical interactions in cellular protrusion based on live cell imaging data with high spatiotemporal resolution. As an appropriate experimental system, we selected non-polarized full-moon-shaped keratocytes that present balanced protrusion around the entire cell periphery at the cellular scale simultaneously with active protrusion and retraction at the subcellular scale. We achieved the observation of a whole cell with sub-micrometer spatial precision and sub-second time resolution for three minutes or more. The multiscale characteristics of cell peripheral activity and those of the cell peripheral shape were extracted from an identical image sequence by estimating the cell protrusion rates and the cell peripheral curvatures at various differential intervals. The spatiotemporal maps of the cell protrusion rates demonstrated a spatiotemporally nested structure of travelling waves of active protruding regions at the cellular and subcellular scales. Moreover, correlation analysis demonstrated the relationship between the cell protrusion rate and peripheral curvature at the subcellular scale. The novel integrative methodology presented here well highlighted the hierarchical properties of organized cellular protrusion, and further provided insight about the underlying mechanochemical interactions between the cell membrane and the actin filaments under the membrane.


The temperature-mortality relationship: an analysis from 31 Chinese provincial capital cities.
We aim to explore the Minimum Mortality Temperature (MMT) of different cities and regions, and that provides evidence for developing reasonable heat wave definition in China. The death data of 31 Chinese provincial capital cities from seven geographical regions during 2008-2013 was included in this study. In the first stage, a DLNM (Distributed Lag Non-linear Model) was used to estimate the association between mean temperature and mortality in a single city, then we pooled them with a multivariate meta-analysis to estimate the region-specific effects. The range of MMT was from 17.4 °C (Shijiazhuang) to 28.4 °C (Haikou), and the regional MMT increased as the original latitude decreased. Different cities and regions have their own specialized MMT due to geography and demographic characteristics. These findings indicate that the government deserves to adjust measures to local conditions to develop public health policies.


Predictors and risk factors for recurrent scleroderma renal crisis in the kidney allograft: case report and review of the literature.
Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1-2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987-July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.


[Metastatic spread of renal cell carcinoma in the area of the ethmoid and frontal sinuses].
Metastatic lesions represent 1-8% of all malignant tumors of the mouth and jaws, with rare sites of metastasis originating from different primary tumors, especially the lung and breast. The vast majority of these lesions (up to 90%) have been observed in the mandible and maxilla (5-20%). Another rare type of cancer that usually metastasizes to the lungs, lymph nodes, bones, liver or brain may occasionally also show spread to the paranasal sinuses. In the present paper we report our management of a 50-year-old male with renal cell carcinoma who developed metastases to the frontal and ethmoid sinuses.


Structure refinement and superspace description of the system Bi(2(n + 2))Mo(n)O(6(n + 1)) (n = 3, 4, 5 and 6).
The system Bi(2(n + 2))Mo(n)O(6(n + 1)) is described within the superspace formalism. Two superspace models are proposed for the different members of this family, depending on the parity of the parameter n. The superspace model for the odd members is constructed through the embedding of the cationic distribution of the member with n = 3, and the modification of a superspace model previously proposed for the compound Bi(2)MoO(6). However, this model cannot be applied to the even members of the family. Performing the appropriate transformations, a suitable superspace model for the even members is obtained. The atomic structure of the different compounds of the family have been refined through the Rietveld method combining synchrotron X-ray and neutron powder diffraction data.


How Pulse Width Affects Laser Ablation of Organic Liquids.
Laser synthesis in liquids is often carried out in organic solvents to prevent oxidation of metals during nanoparticle generation and to produce tailored carbon-based nanomaterials. This work investigates laser ablation of neat organic liquids acetone, ethanol, n-hexane, and toluene with pulse widths ranging from 30 fs to 4 ps through measurements of reaction kinetics and characterization of the ablation products with optical spectroscopy and mass spectrometry. Increasing the pulse width from 30 fs to 4 ps impacts both the reaction kinetics and product distributions, suppressing the formation of solvent molecule dimers and oxidized molecules while enhancing the yields of gaseous molecules, sp-hybridized carbons, and fluorescent carbon dots. The observed trends are explained in the context of established ionization mechanisms and cavitation bubble dynamical processes that occur during ultrashort pulsed laser ablation of liquid media. The results of this work have important implications both for controlling the formation of carbon shells around metal nanoparticles during the ablation of solid targets in liquid and producing carbon nanomaterials directly from the ablation of organic liquids without a solid target.


Herbal medicines: balancing benefits and risks.
Herbal medicines are preparations containing exclusively plant material. Their efficacy can be tested in clinical trials much like synthetic drugs but numerous methodological and logistical problems exist. For several herbal medicines, efficacy has been established; for many others, this is not the case mostly because the research has not been done. Many consumers believe that herbal medicines are natural and therefore safe. This is a dangerous simplification. Some herbal medicines are associated with toxicity others interact with synthetic drugs. The often under-regulated quality of herbal medicines amounts to another safety issue. Contamination or adulteration of herbal medicines are possible and can cause harm. In order to conduct a risk-benefit analysis of a specific herbal medicine for a specific indication, we require definitive efficacy and safety data. This is currently the case for only very few such preparations. It follows that, in order to advise consumers responsibly, the gaps in our present knowledge require filling.


Endemic malagasy Dalbergia species inhibit quorum sensing in Pseudomonas aeruginosa PAO1.
Various species of the plant genus Dalbergia are traditionally used as medicine for sundry ailments and some of them have been shown recently to quench the virulence of Gram-positive and Gram-negative bacteria. Cell-to-cell communication mechanisms, quorum sensing (QS) in particular, are key regulators of virulence in many pathogenic bacteria. Screening n-hexane extracts of leaves, roots and bark of endemic Malagasy Dalbergia species for their capacity to antagonize QS mechanisms in Pseudomonas aeruginosa PAO1 showed that many reduced the expression of the QS-regulated genes lasB and rhlA. However, only the extract of Dalbergia trichocarpa bark (DTB) showed a significant reduction of QS gene expression without any effect on the aceA gene encoding a QS-independent isocitrate lyase. Further characterization of DTB impact on QS revealed that the QS systems las and rhl are inhibited and that swarming, twitching, biofilm formation and the production of pyocyanin, elastase and proteases are also hampered in the presence of the DTB extract. Importantly, compared with the known QS inhibitor naringenin, the DTB extract showed a stronger negative effect on twitching, biofilm formation and tobramycin resistance. Preliminary structural characterization of these potent biofilm disrupters suggests that they belong to the phytosterols. The strong inhibition of motility and biofilm formation suggests that the DTB extract contains agents disrupting biofilm architecture, which is an important observation in the context of the design of new drugs targeting biofilm-encapsulated pathogens.


Low expression of LACTB promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a major life-threatening malignancy worldwide. HCC has an unfavorable prognosis, mainly due to late diagnosis, early metastasis, and post-surgical recurrence. Recent studies have demonstrated that beta-lactamases (LACTB) plays a pivotal role in the pathogenesis and progression of several malignant tumors, but its expression and functional role in HCC has not been reported. In this study, we explored the expression of LACTB using The Cancer Genome Atlas datasets and two independent tissues microarrays. We then analyzed the correlation between LACTB expression and clinical outcomes in HCC. We demonstrated that LACTB mRNA and protein levels were both down-regulated in HCC, and decreased LACTB expression was associated with TNM stage, histologic grade, and overall survival of patients. Additionally, through Gene Set Enrichment Analysis, we found that the genes negatively related to the survival of HCC patients were enriched in the low LACTB expression group. Furthermore, we confirmed that overexpression of LACTB inhibited HCC cell proliferation, invasion, and migration in vitro, as well as decreased tumor growth in vivo. Online prediction results suggested that the LACTB gene was markedly correlated with genes involved in the lipid metabolism pathway. In conclusion, these findings suggest that down-regulated LACTB could function as a novel biomarker for diagnosis and prognosis prediction, and LACTB could serve as a promising target in HCC therapy.


Method for quantification of porcine type I interferon activity using luminescence, by direct and indirect means.
Type I interferons are widely used in research applications and as biotherapeutics. Current assays used to measure interferon concentrations, such as plaque reduction assays and ELISA, are expensive, technically challenging, and may take days to provide results. We sought to develop a robust and rapid assay to determine interferon concentrations produced from transiently transfected cell cultures. Indirect quantification of recombinant interferon was evaluated using a novel bi-cistronic construct encoding the Foot-and-mouth disease virus 2A translational interrupter sequence to yield equimolar expression of Gaussia princeps luciferase and porcine interferon α. Direct quantification was evaluated by expression of a novel fusion protein comprised of Gaussia princeps luciferase and porcine type I interferon. Plasmids encoding constructs are transiently transfected into cell cultures and supernatant harvested for testing of luminescence, ELISA determined concentration, and anti-viral activity against vesicular stomatitis virus. Bi-cistronic constructs, utilized for indirect quantification, demonstrate both luciferase activity and anti-viral activity. Fusion proteins, utilized for direct quantification, retained secretion and luminescence however only the interferon α fusion protein had antiviral activity comparable to wildtype porcine interferon α. A strong linear correlation was observed between dilution and luminescence for all compounds over a dynamic range of concentrations. The correlation of antiviral and luciferase activities demonstrated the utility of this approach, both direct and indirect, to rapidly determine recombinant interferon concentrations. Concentration can be determined over a more dynamic concentration range than available ELISA based assays using this methodology.


Podcasts--an emerging form of digital publishing.
Podcasting has recently emerged as an important information technology tool for health professionals and consumers around the world. Prestigious journals, international conferences, universities and government agencies among other entities are starting to publish digital informotion via audio and video podcasts. Podcosting is distinguished from other forms of digital audio-video content because it can be subscribed to (using Real Simple Syndication or RSS) and easily accessed from a personal computer. Further, it can be downloaded to a mobile device, such as an iPod where the user is able to listen to or watch it anywhere, anytime. Podcosting is used in new and evolving ways to publish information for healthcare education, patient care, professional continuing education, and in support of healthcare research. In addition to a description of what podcasting is, how podcasts are created, and how they are used, this paper addresses four critical issues that are emerging concerning podcasts. These issues are intellectual property and copyright, podcast preservation, podcast location, and podcast standards. As podcasting matures and new uses are discovered, we will see podcasting incorporated into our education, research and patient care publication paradigm.


A case of acute tuberculous pleuropneumonia in a patient with acute lymphoblastic leukemia.
Respiratory system infections are the most common complications in immunocompromised cancer patients. We here report a 14-year-old male who was admitted to the hospital because of acute pneumonia, who had been diagnosed with acute lymphoblastic leukemia (ALL) when he was 12 years old. A diagnosis of acute tuberculous pleuropneumonia was made based on clinical and radiographical findings, and Mycobacterium tuberculosis was identified by Ziehl-Neelson acid-fast stain and culture on Löwenstein-Jensen medium. Twenty months before pneumonia onset, the patient had been treated with immunosupressive therapy (ALL IC-BFM 2002 protocol).


Optic Nerve Crush in Mice to Study Retinal Ganglion Cell Survival and Regeneration.
In diseases such as glaucoma, the failure of retinal ganglion cell (RGC) neurons to survive or regenerate their optic nerve axons underlies partial and, in some cases, complete vision loss. Optic nerve crush (ONC) serves as a useful model not only of traumatic optic neuropathy but also of glaucomatous injury, as it similarly induces RGC cell death and degeneration. Intravitreal injection of adeno-associated virus serotype 2 (AAV2) has been shown to specifically and efficiently transduce RGCs in vivo and has thus been proposed as an effective means of gene delivery for the treatment of glaucoma. Indeed, we and others routinely use AAV2 to study the mechanisms that promote neuroprotection and axon regeneration in RGCs following ONC. Herein, we describe a step-by-step protocol to assay RGC survival and regeneration in mice following AAV2-mediated transduction and ONC injury including 1) intravitreal injection of AAV2 viral vectors, 2) optic nerve crush, 3) cholera-toxin B (CTB) labeling of regenerating axons, 4) optic nerve clearing, 5) flat mount retina immunostaining, and 6) quantification of RGC survival and regeneration. In addition to providing all the materials and procedural details necessary to execute this protocol, we highlight its advantages over other similar published approaches and include useful tips to ensure its faithful reproduction in any modern laboratory.


Citizens and Health Data - Untapped Resource for Telehealth?
In this paper I will engage with the discussion on Citizen and Health Data, and look specifically at challenges in citizen-centered digital health information management, if the goal is to stimulate self-management, support holistic trajectories of health and wellbeing, and implement new practice models with efficient use of health care services. A focus will be citizens' opportunities to engage in activities to a) collect, b) curate, c) control access to personal Health Data and relate these activities to telehealth locally and globally.


Prevalence of micronutrient malnutrition worldwide.
Recent estimates indicate that globally over two billion people are at risk for vitamin A, iodine, and/or iron deficiency, in spite of recent efforts in the prevention and control of these deficiencies. The prevalence is especially high in Southeast Asia and sub-Saharan Africa, and pregnant women and young children are at greatest risk. Other micronutrient deficiencies of public health concern include zinc, folate, and the B vitamins. However, there is limited data on the actual prevalence of these deficiencies. Finally, in many settings, more than one micronutrient deficiency exists, suggesting the need for simple approaches that evaluate and address multiple micronutrient malnutrition.


The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas.
The present study was aimed at localizing gamma-aminobutyric acid (GABA) and its enzyme of synthesis, glutamic acid decarboxylase (GAD), in the mouse pancreas by immunocytochemical methods. The influence of GABA on hormone release was also studied with normal mouse and rat islets and the isolated perfused rat pancreas. Particular attention was paid to glucagon release to test a recent hypothesis suggesting that GABA mediates the still unexplained glucose-induced inhibition of glucagon release. GABA and GAD were identified only in islet cells and never in the exocrine tissue. Exogenous GABA, baclofen (agonist of GABAB receptors), muscimol (agonist of GABAA receptors), or bicuculline (antagonist of GABAA receptors) did not affect insulin and somatostatin release by isolated mouse or rat islets. GABA was also without effect on glucose-induced electrical activity in mouse B-cells. Glucagon secretion by mouse islets was only slightly inhibited (approximately 20%) by GABA. Since muscimol had a similar effect, and baclofen was ineffective, the inhibition by GABA probably involves GABAA receptor activation. Bicuculline, however, did not antagonize the inhibitory effects of GABA and muscimol, probably because the antagonist alone also decreased glucagon secretion. In contrast to GABA, low (3 mM) and high (20 mM) concentrations of glucose strongly inhibited (approximately 50-65%) glucagon release; this inhibition was not prevented by bicuculline. Similar results were obtained with the perfused rat pancreas; muscimol slightly inhibited glucagon release under various conditions, and bicuculline did not reverse the strong inhibition produced by 16.7 mM glucose. In conclusion, GABA does not affect insulin and somatostatin secretion, but inhibits A-cells, probably by acting on GABAA receptors. It is unlikely, however, that this small inhibitory effect can account for the inhibition of glucagon release produced by glucose.


Mortality and adverse events after protamine administration in patients undergoing cardiopulmonary bypass.
We designed this study to determine whether adverse hemodynamic events after a protamine administration increase the risk of in-hospital mortality. Using a retrospective cohort study design, medical and anesthesia records of patients undergoing cardiopulmonary bypass (CPB) at the Hospital of the University of Pennsylvania, Philadelphia, between 1990 and 1994 were reviewed. Adverse events after a protamine administration were determined using strict, predefined criteria, and in-hospital mortality was assessed without knowledge of exposure status. Mortality was more frequent among the 53 patients with adverse events (13.2%) than the 223 patients without events (2.7%; crude odds ratio 5.50; 95% confidence interval, 1.49-20.6). After adjusting for confounders, the odds ratio was 6.98 (95% confidence interval, 1.36-35.9; P = 0.017). Those suffering severe events had the highest mortality (23.5% compared with 8.3% among those with less severe events versus 2.7% among those without any event, P = 0.001 for trend). In addition, the odds ratio was largest when using the strictest definition for protamine-related events. In conclusion, patients undergoing CPB who experience adverse events after a protamine administration have an increased risk of in-hospital mortality. Further studies to confirm these findings and development and testing of protamine alternatives or prophylactic therapies are required to determine if mortality can be reduced. A retrospective cohort study demonstrated an association between adverse events after a protamine administration and increased in-hospital mortality.


Integrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria.
Heterogeneity and high plasticity are common features of cells from the mononuclear phagocyte system: monocytes (MOs), macrophages, and dendritic cells (DCs). Upon activation by microbial agents, MO can differentiate into MO-derived DCs (MODCs). In previous work, we have shown that during acute infection with Plasmodium berghei ANKA (PbA), MODCs become, transiently, the main CD11b+ myeloid population in the spleen (SP) and once recruited to the brain play an important role in the development of experimental cerebral malaria (ECM). Here, we isolated 4 cell populations: bone marrow (BM) MOs (BM-MOs) and SP-MOs from uninfected mice; BM inflammatory MOs (BM-iMOs) and SP-MODCs from PbA-infected mice and used a system biology approach to a holistic transcriptomic comparison and provide an interactome analysis by integrating differentially expressed miRNAs (DEMs) and their differentially expressed gene targets (DEGs) data. The Jaccard index (JI) was used for gauging the similarity and diversity among these cell populations. Whereas BM-MOs, BM-iMOs, and SP-MOs presented high similarity of DEGs, SP-MODCs distinguished by showing a greater number of DEGs. Moreover, functional analysis identified an enrichment in canonical pathways, such as DC maturation, neuroinflammation, and IFN signaling. Upstream regulator analysis identified IFNγ as the potential upstream molecule that can explain the observed DEMs-Target DEGs intersections in SP-MODCs. Finally, directed target analysis and in vivo/ex vivo assays indicate that SP-MODCs differentiate in the SP and IFNγ is a main driver of this process.


Maintenance of hemostasis in transoral robotic surgery.
The last decade has seen a tremendous growth in the field of robotic surgery with an increasing number of cardiac and urologic procedures performed each year. Several attributes of this technology may offer advantages to laryngeal and pharyngeal surgery in that it allows for exceptional visualization of the operative field, precise handling of soft tissues, and multiplanar transection of tissues. One potential limitation is the management of bleeding in transoral pharyngeal and laryngeal surgery, which is critical to prevent both intravascular volume loss and aspiration. To demonstrate methods for management of bleeding in the surgical field during transoral robotic surgery (TORS). We developed a canine robotic surgery model for the evaluation of the ability to control bleeding in laryngeal and pharyngeal procedures using the daVinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, Calif., USA). Both large- and small-vessel hemostasis was obtained with both robotically controlled monopolar and bipolar cautery and with robotically controlled small hemoclips. Additionally, manually controlled large hemoclips were applied by an assistant surgeon viewing on a video monitor for management of large arterial vessels. Suction was performed with both flexible suction catheters controlled by the robotic arms and with manually controlled conventional suction catheters. Data were collected with still and video photography. The lingual artery as well as small arteries and veins were easily controlled and there were no difficulties with maintenance of hemostasis. Effective hemostasis with control of both large and small vessels can be obtained using both surgical hemoclips and electrocautery during TORS in a canine model.


Th1/Th2 differentiation and cross-regulation.
The T helper (Th) phenotypes, Thl/Th2, are acquired upon interaction of a naive T helper cell and an antigen presenting cell (APC). Naive T helper cells may differentiate into either phenotype, and the actual outcome is determined by the density and avidity of the antigenic determinants presented by the APC, and the APCs inherent costimulatory properties. Until recently it was thought that differentiation is further affected by cytokines. However, Murphy et al. have demonstrated that the experimental results, formerly interpreted as Th1/Th2 differentiation, in effect comprise an observation of two consecutive processes. (i) An interaction between naive T cells and APC creates a mixture of mature cells irreversibly committed to Th1 or Th2 phenotype. (ii) Subsequent addition of regulatory cytokines, promotes expansion of one phenotype while suppressing the other. The consequent shift in the per culture production of marker cytokines mimics the appearance of a cellular phenotype switch. We present and analyse a mathematical model that extrapolates these experimental facts into systemic behavior during an immune response. Despite the fact that differentiation produces cells of Th1 and Th2 phenotypes with the same receptor specificity, our results indicate that competition for antigenic stimulation, mediated by the APCs, combines with cytokine mediated cross-suppression between phenotypes to yield a response that is eventually dominated by T helper cells that are uniform in both receptor specificity (clonotype) and in cytokine secretion phenotype.


Infantile lumbosacral spinal subdural abscess with sacral dermal sinus tract.
Clinical case report of a spinal subdural abscess in an infant presenting with sacral dermal sinus tract (DST). To suggest that sacral DST with caudal direction may require surgical resection as early as possible. DST may induce the formation of a spinal abscess. However, it is sometimes difficult to decide on early surgical resection for DST, especially in cases that are located at a lower level than the lumbar spine and directed caudally that is not accompanied by cerebrospinal fluid leakage. A 9-month-old girl was transferred due to intermittent fever and vomiting, with the midline sinus of the lower back at the second sacral spinal level. She showed mild tenderness of the lower back and slight weakness of both lower extremities with increased residual urine volume of the bladder. Magnetic resonance imaging (MRI) showed that the low-lying sacral DST traced into the subdural space with caudal orientation, and the presence of extensive subdural spinal abscess from the first lumbar spine to the fourth sacrum. Emergency resection of the sacral DST was performed after laminotomy from the first lumbar spine to the second sacrum, and the subdural spinal abscess was also surgically removed. After 8 weeks of intravenous antibiotic treatment, she showed no neurologic deficit and no evidence of residual abscess on MRI. We suggest that even low-lying sacral DST may require surgical resection as early as possible because it may result in indolent and extensive spinal abscesses.


Intraperitoneal chemotherapy: standard of care for patients with minimal residual stage III ovarian cancer?
Epithelial ovarian cancer is the leading cause of death from gynecological cancer in most of the Western world, and long-term survival remains poor despite good initial response to systemic therapy after debulking surgery. Even after complete pathological response, the risk of recurrence in the first few years is substantial. The peritoneum is the predominant site of failure and the disease remains confined to the peritoneal cavity for much of its course. Efforts to improve clinical outcomes in this group of patients included investigation of intraperitoneal administration of active agents to expose the low-volume postoperative residual disease in the peritoneum to high concentrations of these drugs. In spite of three National Cancer Institute-sponsored randomized trials demonstrating clinical benefit with intraperitoneal therapy in patients with advanced ovarian cancer, the fact remains that it is not uniformly accepted by the gynecologic oncology community in the USA and is rarely used by clinicians in Europe. Intraperitoneal regimens are perceived to be too toxic for administration, although most of the toxicity is reversible. In this article we discuss the available evidence for intraperitoneal chemotherapy, challenges facing the gynecologic oncology community to make this modality more widely acceptable, the selection of patients most likely to tolerate intraperitoneal therapy and ongoing research in this field.


[Coronary reoperations: recurrence of angina and clinical outcome].
To evaluate the features of coronary artery bypass reoperations and to reduce the influence of the factors affecting postoperative morbidity and mortality. The records of 53 consecutive patients (88.7% of men, 11.3% of women; mean age 67.1+/-7.5 years) who underwent coronary artery bypass reoperations were reviewed retrospectively. Coronary artery bypass reoperations comprised 2.98% of all coronary artery bypass grafting operations during that period. Coronary artery bypass reoperations performed within 4-week period after the last operation and complex procedures were excluded. Postoperative mortality after 53 reoperations and 1775 primary coronary artery bypass grafting operations was 7.5 and 2.52%, respectively, and the results are comparable with the results from other clinics of cardiac surgery. Mean time interval between primary coronary artery bypass grafting and reoperation was 90.7+/-49.9 months. Angiography at that period showed patency of venous and arterial conduits--34.6 and 76.5%, respectively. Twenty-nine patients (54.7%) received only venous conduits during reoperation. There were 2.4+/-1.1 anastomoses constructed during reoperation comparing to 3.5+/-0.9 anastomoses per patient during primary coronary artery bypass grafting. According to our data mortality after coronary reoperations remains higher comparing to primary coronary artery bypass grafting, however, it does not differ significantly. We observed an increasing number of elderly patients in coronary reoperations. We think that it is related to the demographical changes within our country and increased use of arterial conduits during primary coronary artery bypass grafting operations. Arterial conduits are patent at least 10 years; it means that the time period until recurrent angina and reoperation is delayed. However, progression of arterial atherosclerosis remains the main reason for coronary artery bypass grafting reoperation.


Measures of Financial Capacity: A Review.
Capacity to manage finances and make financial decisions can affect risk for financial exploitation and is often the basis for legal determinations of conservatorship/guardianship. Several structured assessments of financial capacity have been developed, but have not been compared regarding their focus, validity, or reliability. Therefore, we conducted a review of financial capacity measures to examine these factors. We searched electronic databases, reference lists in identified articles, conference proceedings and other grey literature for measures of financial capacity. We then extracted data on the length and domains of each measure, the population for which they were intended, and their validity and reliability. We identified 10 structured measures of financial capacity. Most measures could be completed in 25-30 min, and were designed to be administered to older adults with some level of cognitive impairment. Reliability and validity were high for most. Measurement of financial capacity is complex and multidimensional. When selecting a measure of financial capacity, consideration should be made of the population of focus and the domains of capacity to be assessed. More work is needed on the cultural sensitivity of financial capacity measures, their acceptability, and their use in clinical work. Better understanding of when, and to whom, to administer different financial capacity measures could enhance the ability to accurately detect those suffering from impaired financial capacity, and prevent related negative outcomes like financial exploitation.


TGFβ (transforming growth factor β) superfamily members and their receptors in the fetal porcine ovaries: effect of prenatal flutamide treatment.
We have recently demonstrated that antiandrogen treatment during fetal life resulted in delayed folliculogenesis. The aim of the present study was to investigate the effect of androgen deficiency induced by flutamide on the expression of TGFβ superfamily members and their receptors which are involved in follicle formation and its transition to the primary stage. Pregnant gilts were injected with flutamide (for seven days, 50 mg/day/kg b.w.) or corn oil (controls) starting at 43 (GD50), 83 (GD90) or 101 (GD108) gestational day. The expression in fetal ovaries of selected TGFβ superfamily members (AMH, BMP4, GDF9), their receptors (AMHR-II, BMPR-IB, BMPR-II), and Smad1 and Smad3 proteins involved in signal transduction were investigated by real-time PCR and/or immunohistochemistry. Flutamide treatment increased the expression of BMP4 mRNA on GD50 and GD108 and BMPR-IB mRNA on GD50. The expression of BMPR-II was decreased at mRNA level and lower immunostaining intensity was observed after flutamide administration only on GD50. GDF9 and AMHR-II mRNA expression levels were significantly downregulated in both GD90 and GD108 groups. However, AMHR-II was immunolocalized only on GD108 and less positively stained oocytes were found after flutamide treatment. AMH mRNA level was diminished in the GD90 group, while it was elevated in the GD108 group. Moreover, the higher amounts of positively stained oocytes for phosphorylated form of Smad1 were observed following flutamide administration on GD108. Experimentally-induced androgen deficiency during fetal development deregulates the expression level of some of TGFβ superfamily members and their receptors which may affect primordial follicle assembly. Our findings further underline the role of androgens in the early stages of follicle development.


Peritonitis secondary to spontaneous perforation of a primary gastrointestinal stromal tumour of the small intestine: A case report and a literature review.
A few cases of acute abdomen caused by perforation of small-intestinal gastrointestinal stromal tumours (GISTs) have been reported in the literature. Together with a review of the published cases, here we report a case of an elderly patient with peritonitis due to spontaneous perforation of a GIST of the jejunum. An 82-year-old man was admitted to the emergency unit of our hospital with fever and severe abdominal pain. An abdominal enhanced computed tomography scan detected a 6cm solid mass in the left upper quadrant adherent to a jejunal loop and surrounded by free fluid and free air. Due to the radiological features of the mass, the diagnosis of a perforation of a GIST arising from the jejunum wall was suspected. The patient underwent emergency laparotomy. Intraoperative findings confirmed diffuse peritonitis secondary to jejunal tumour perforation. A segmental resection of the jejunum containing the mass was performed followed by a mechanical end-to-side anastomosis. The histopathologic examination of the mass confirmed the diagnosis of a perforated GIST of the small intestine (high-risk category). The post-operative course was uneventful and the patient was treated with adjuvant imatinib therapy. Twenty-one other cases of spontaneous perforation of small intestine GISTs are reported in the literature and are summarized in the present review. The described case is the tip of the iceberg and spontaneous rupture or perforation of GISTs are a far more frequent first presentation of this rare tumour.


Redox signaling in plants.
Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment.


Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization.
Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barré syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5' end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis.


External fixation versus ORIF for distal intra-articular tibia fractures.
Tibia plafond fractures have historically demonstrated high complication rates. The purpose of this study was to assess the outcomes of tibia plafond fractures following treatment with definitive external fixation vs delayed open reduction and internal fixation (ORIF). Sixty patients were enrolled in a prospective cohort trial at 1 Level I trauma center. No differences were noted between the 2 treatment groups in terms of age, smoking history, presence of comorbidities, mechanism of injury, incidence of open fractures, or Orthopaedic Trauma Association fracture classification. Complete 12-month follow-up was available for 18 patients in the definitive external fixation group and 27 patients in the ORIF group. No difference was noted in articular reduction between the groups at 6 and 12 months postoperatively. Delayed union or non-union occurred in 4 (22.2%) of 18 patients in the external fixation group and 1 (3.7%) of 27 patients in the ORIF group (P=.05). Deep infection was equally likely in either group (P=.33). The ORIF group had improved Iowa Ankle Scores at 6 (23.6 ± 12.1 vs 11.1 ± 7.7; P<.05) and 12 months (5.5 ± 2.2 vs 3.1 ± 1.7; P<.05) postopertively and improved Short Form-36 Physical Function scores at 6 months (49.7 ± 30.1 vs 25.5 ± 8.0; P<.05) postoperatively compared with the external fixation group.External fixation and ORIF can attain bony union with adequate articular reduction and similar infection rates. Patients treated with ORIF appeared to have improved union rates and early outcomes with ankle function and Short Form-36 Physical Function scores.


Plant Sterols and Plant Stanols in Cholesterol Management and Cardiovascular Prevention.
Atherosclerotic cardiovascular disease (ASCVD) remains the major mortality cause in developed countries with hypercholesterolaemia being one of the primary modifiable causes. Lifestyle intervention constitutes the first step in cholesterol management and includes dietary modifications along with the use of functional foods and supplements. Functional foods enriched with plant sterols/stanols have become the most widely used nonprescription cholesterol-lowering approach, despite the lack of randomized trials investigating their long-term safety and cardiovascular efficacy. The cholesterol-lowering effect of plant-sterol supplementation is well-established and a potential beneficial impact on other lipoproteins and glucose homeostasis has been described. Nevertheless, experimental and human observational studies investigating the association of phytosterol supplementation or circulating plant sterols with various markers of atherosclerosis and ASCVD events have demonstrated controversial results. Compelling evidence from recent genetic studies have also linked elevated plasma concentrations of circulating plant sterols with ASCVD presence, thus raising concerns about the safety of phytosterol supplementation. Thus, the aim of this review is to provide up-to-date data on the effect of plant sterols/stanols on lipid-modification and cardiovascular outcomes, as well as to discuss any safety issues and practical concerns.


Developing an evening clinical experience for baccalaureate community health nursing students.
With the ever-changing directions in health care delivery, baccalaureate nursing instructors are being challenged with the task of seeking out innovative approaches to community health nursing clinical experiences. With the focus on "community as client," an evening clinical program was designed and piloted for nontraditional nursing students who, because of daytime employment, were in need of evening courses to further their nursing education. The pilot project incorporated family nursing care, community-centered practice, and observational experiences. The evening community health nursing clinical experience was found to be mutually beneficial to clients and students and served to fill a gap in health teaching within the community.


Overview of Paediatric Dental Sedation: 1. current UK guidelines.
The use of conscious sedation in paediatric dentistry is very beneficial for the management of anxious children. It is essential that it is provided according to national guidelines in a safe and effective manner. Dentists carrying out conscious sedation in children must be aware of current national guidance and the most appropriate techniques to use.


RBFOX2 alters splicing outcome in distinct binding modes with multiple protein partners.
RBFOX2 controls the splicing of a large number of transcripts implicated in cell differentiation and development. Parsing RNA-binding protein datasets, we uncover that RBFOX2 can interact with hnRNPC, hnRNPM and SRSF1 to regulate splicing of a broad range of splicing events using different sequence motifs and binding modes. Using immunoprecipitation, specific RBP knockdown, RNA-seq and splice-sensitive PCR, we show that RBFOX2 can target splice sites using three binding configurations: single, multiple or secondary modes. In the single binding mode RBFOX2 is recruited to its target splice sites through a single canonical binding motif, while in the multiple binding mode RBFOX2 binding sites include the adjacent binding of at least one other RNA binding protein partner. Finally, in the secondary binding mode RBFOX2 likely does not bind the RNA directly but is recruited to splice sites lacking its canonical binding motif through the binding of one of its protein partners. These dynamic modes bind distinct sets of transcripts at different positions and distances relative to alternative splice sites explaining the heterogeneity of RBFOX2 targets and splicing outcomes.


Age, sex, and type of medication predict the effect of anti-VEGF treatment on central retinal thickness in wet age-related macular degeneration.
Randomized clinical trials studying the effects of VEGF inhibition on wet age-related macular degeneration (wAMD) are designed so that the effects of individually varying risk factors on the treatment response are eliminated. The influence of these risk factors can be studied in large data sets from real-life experience. All 2,255 patients diagnosed with wAMD requiring anti-VEGF treatment in at least one eye over more than 9 years in a defined Danish population with 0.9 million inhabitants were studied. The predictive value of eye laterality, sex, current smoking status, type of anti-VEGF compound, membrane position, membrane type, leakage area, number of injections, number of visits, age, time to follow-up, visual acuity, and central retinal thickness (CRT) at baseline on change in CRT after three monthly injections with anti-VEGF compound followed by treatment pro re nata for up to 12 months was assessed. After 12 months, 67 patients had died, 903 had had stable CRT for at least 6 months, and 1,285 patients had not achieved stable CRT. The reduction in CRT was -84.8±118.3 μm, whereas the increase in visual acuity was 2.2±14.7 Early Treatment Diabetic Retinopathy Study letters. The risk factors included contributed to 64% of the variation in CRT reduction. High age and high CRT at baseline predicted high CRT reduction, whereas more injections, treatment with ranibizumab, and male sex predicted a low CRT reduction. Age, sex, and type of anti-VEGF medication can be used to plan treatment and inform patients about the expected response of anti-VEGF treatment in wAMD.


Technical note: Effects of pegylation and route of administration on leptin kinetics in newborn lambs1.
Chronic energy insufficiency resulting from inadequate feed intake or increased nutrient demand reduces plasma leptin in ruminants. Treatment of energy-deficient ruminants with exogenous leptin has identified some physiological consequences of reduced plasma leptin, but their full complement remains unknown. Additional leptin-dependent responses could be identified by using strategies that interfere with leptin signaling such as administration of leptin mutants that act as competitive antagonists. The effectiveness of these antagonists depends on their fold excess over endogenous leptin, and this condition can be achieved under in vivo conditions by extending the half-life (t1/2) of the antagonist by addition of a polyethylene glycol (PEG) molecule (pegylation). Use of this approach in ruminants, however, is limited by the lack of information on the t1/2 of native and pegylated leptin and on the most effective route of administration. To answer these questions, newborn lambs (n = 3) were injected with an intravenous (i.v.) bolus of 150 µg of human leptin followed by blood sampling over the next 12 h. Analysis of the semilog plasma leptin concentration over time yielded a t1/2 of 43 ± 4.9 min; an i.v. bolus of 276 µg of bovine leptin yielded a comparable t1/2 (P > 0.05). Next, newborn lambs (n = 4) received a single dose of 229 μg/kg of metabolic body weight (BW0.75) of pegylated super human leptin antagonist (PEG-SHLA) via the i.v. or subcutaneous (s.c.) route. Plasma PEG-SHLA concentration reached a peak of 1,528 ± 78 ng/mL after 1 min and a nadir of 71 ± 9 ng/mL after 24 h with the i.v. route versus a peak of 423 ± 43 ng/mL after 300 min and a nadir of 146 ± 22 ng/mL after 24 h for the s.c. route; the t1/2 of PEG-SHLA was 394 ± 29 min for the i.v. route and 433 ± 58 min for the s.c. route. Finally, plasma concentration of PEG-SHLA was modeled when given either i.v. or s.c. at a dose of 229 μg/kg BW0.75 every 12 h. Once a steady state was reached, peak and lowest concentrations PEG-SHLA over the 12-h windows were 2,269 and 403 ng/mL for the i.v. route and 814 and 555 ng/mL for the s.c. route. Weighted PEG-SHLA concentrations over the 12-h period were 1,455 and 713 ng/mL for the i.v. and s.c. route, translating into 364- and 178-fold excess over endogenous plasma leptin. These data confirm the effectiveness of pegylation in extending the t1/2 of leptin antagonists in newborn lambs and in increasing their circulation in fold excess over endogenous leptin.


[An electroencephalographic study of the foetus during labour. Technique and interpretation (author's transl)].
The authors report their experiences in recording foetal E.E.Gs at the time of labour, based on 140 studies. They studied normal E.E.Gs and emphasise the existence of a sleep-waking pattern during dilatation. They consider the E.E.G. changes during the different stages of labour and assess the results against other techniques used to assess foetal well-being. They record the effects on the E.E.G. of various anaesthetics and analgesics given to the mother. The difficulty of the technique is stressed and they conclude that despite the obvious interest of the technique it is not currently suitable for routine obstetric practice.


In vitro evaluation of CAD/CAM composite materials.
The purpose of this in vitro study was to evaluate the microstructural, elemental and mechanical properties of contemporary computer-aided-design/computer-aided manufacturing (CAD/CAM) resin based composite (RBC) materials. Six CAD/CAM RBC materials [Brilliant CRIOS (Coltene Whaledent AG), Cerasmart (GC), Lava Ultimate (3M ESPE), Tetric CAD (Ivoclar Vivadent), Shofu Block HC (Shofu), Grandio Blocs (VOCO GmbH)] were tested. Ten rectangular blocks (14 Χ 12 Χ 18 mm) for each material, after metallographic grinding and polishing, were subjected to Instrumented Indentation Testing (ΙIT). Martens Hardness (HM), Indentation Elastic Modulus (EIT), Elastic (ηIT) and Creep indices (CIT) were determined according to formulas provided by ISO 14577. The diagonal length of each indentation was measured and HV was determined. The results of HM, EIT, ηΙΤ, HV, and CIT were statistically analyzed by one-way ANOVA and Tukey post hoc test employing the material as a discriminating variable (a = 0.05), while the possible correlations were determined by Spearman's correlation test. One specimen from each group was examined by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Backscattered Electron images and EDX analysis demonstrated differences in size, shape and type of fillers along with elemental composition among materials tested. Statistical significant differences were identified for all mechanical properties tested. Grandio Blocs had the significantly higher HM (953±7 N/mm2), HV (136±1) and EIT (23±1 GPa) followed by Lava Ultimate (ΗM=674±25 N/mm2, HV=105±2, EIT=15±1 GPa). Elastic index ranged from 41% to 52%, with Shofu Block demonstrating the significantly highest ηIT (52 ± 1%) values. Cerasmart had significantly higher CIT value (8.4 ± 0.1%) than all other materials tested, while Grandio Blocs and Lava Ultimate had the lowest ones. Spearman's correlation revealed that all mechanical properties tested exhibited correlations with each other, apart from ηΙΤ. The results showed that the CAD/CAM materials tested have differences in their microstructure, elemental composition and mechanical properties. The RBCs tested showed significant differences in mechanical properties and thus differences in clinical performance are anticipated. RBCs with increased filler loading had the most favorable combination of hardness, elastic modulus and creep index indicating that these materials may have better clinical performance under intraoral loading conditions.


[Correlations between folic acid, human papilloma virus (HPV) and cervix neoplasms].
The study aimed to verify the probable correlation between the incidence of cervical cancer and the presence of human papilloma virus (HPV) in relation to a state of folic acid hypovitaminosis. In this context, however, it is important not to overlook the important protective role played by vitamins A and C in cancer prevention, as mentioned in the paper. Numerous authors agree that this is a real finding in cervical pathology, as shown in our research, even if folic acid therapy does not alter the course and prognosis of disease. On the contrary, low blood levels of folic acid appear to increase the risk of contracting the disease. Extensive and radical surgery therefore appears to be even more justified in order to increase the probability of recovery on the operating table in view of the irrational and inexorable progress of this pathology, especially if metastases are already present.


[The duration of the outpatient nonstress test (NST) and the diagnosis of fetal reactivity with noncomputerized cardiotocography, A critical review of 1160 tracings].
Our purpose was to verify the times of appearance and the relative percentage of fetal reactivity during a nonstress test. The minimum time for each control has been fixed at 30 minutes. To identify fetal reactivity we have observed the conventional patterns of fetal heart rate. We have examined 1160 cardiotocograms of 483 patients with obstetric low risk controlled by ambulatory NST in the morning and by appointment. We have divided the tracings according to three different periods of pregnancy (< 37, between 37 and 40 and over 40 weeks) and each tracing in three periods of 10 minutes. In each period we have checked the mean values and standard deviations of accelerations, decelerations, uterine contractions and fetal movements. For each patient the total numbers of NST and the type of birth (spontaneous or caesarean section for fetal distress) has been considered. At statistic analysis we have employed "t"-Student test. We have observed a significative difference (p < 0.001) between the presence of fetal reactivity after 20 and 30 minutes and the number of doubtful cases after 30 minutes for the different periods of pregnancy. With minimum time of 30 minutes of NST, an incidence of doubtful cases of 4.48% and an incidence of caesarean section for fetal distress for the same group of 19.27% has been observed, while for all the cases with reactive NST this incidence intrapartum has been of 9.73%. Our experience confirms that the optimal duration of NST has been of 30 minutes. We think that this time must be suggested also from prudence, since the noncomputerized cardiotocography is often characterized by false positiveness and low predictability.


A probabilistic Poisson-based model accounts for an extensive set of absolute auditory threshold measurements.
Thresholds for detecting sounds in quiet decrease with increasing sound duration in every species studied. The neural mechanisms underlying this trade-off, often referred to as temporal integration, are not fully understood. Here, we probe the human auditory system with a large set of tone stimuli differing in duration, shape of the temporal amplitude envelope, duration of silent gaps between bursts, and frequency. Duration was varied by varying the plateau duration of plateau-burst (PB) stimuli, the duration of the onsets and offsets of onset-offset (OO) stimuli, and the number of identical bursts of multiple-burst (MB) stimuli. Absolute thresholds for a large number of ears (>230) were measured using a 3-interval-3-alternative forced choice (3I-3AFC) procedure. Thresholds decreased with increasing sound duration in a manner that depended on the temporal envelope. Most commonly, thresholds for MB stimuli were highest followed by thresholds for OO and PB stimuli of corresponding durations. Differences in the thresholds for MB and OO stimuli and in the thresholds for MB and PB stimuli, however, varied widely across ears, were negative in some ears, and were tightly correlated. We show that the variation and correlation of MB-OO and MB-PB threshold differences are linked to threshold microstructure, which affects the relative detectability of the sidebands of the MB stimuli and affects estimates of the bandwidth of auditory filters. We also found that thresholds for MB stimuli increased with increasing duration of the silent gaps between bursts. We propose a new model and show that it accurately accounts for our results and does so considerably better than a leaky-integrator-of-intensity model and a probabilistic model proposed by others. Our model is based on the assumption that sensory events are generated by a Poisson point process with a low rate in the absence of stimulation and higher, time-varying rates in the presence of stimulation. A subject in a 3I-3AFC task is assumed to choose the interval in which the greatest number of events occurred or randomly chooses among intervals which are tied for the greatest number of events. The subject is further assumed to count events over the duration of an evaluation interval that has the same timing and duration as the expected stimulus. The increase in the rate of the events caused by stimulation is proportional to the time-varying amplitude envelope of the bandpass-filtered signal raised to an exponent. We find the exponent to be about 3, consistent with our previous studies. This challenges models that are based on the assumption of the integration of a neural response that is directly proportional to the stimulus amplitude or proportional to its square (i.e., proportional to the stimulus intensity or power).


Autophagic death induced by thermo‑chemotherapy in gastric cancer cells results from the reactive oxygen species pathway.
Gastric cancer is the third leading type of cancer and has the third leading cancer‑associated mortality in China. The mechanism of thermo‑chemotherapy in gastric cancer cells remains to be elucidated. The present study aimed to investigate the role of autophagic cell death in the thermo‑chemotherapy of gastric cancer. The current study included four groups: An empty control group, a hyperthermia group, a chemotherapy (oxaliplatin) group, and a thermo‑chemotherapy group. Cell viability was analyzed by the MTS assay. Production of intracellular reactive oxygen species (ROS) was quantified by flow cytometry. Autophagy‑associated proteins, Beclin 1, microtubule‑associated protein 1A/1B‑light chain (LC3B) and mammalian target of rapamycin (mTOR), were determined by western blot analysis. The results indicated that thermo‑chemotherapy markedly increased intracellular ROS production, and decreased mitochondrial membrane potential. The transmission electron microscopy results indicated that thermo‑chemotherapy induced production of autophagic bodies. In addition, thermo‑chemotherapy‑induced cell damage at the cellular and animal levels indicated a notable increase in the expression of the autophagy‑associated genes, LC3B and Beclin 1. A negative correlation between mTOR expression and autophagy was also identified, which demonstrates that thermo‑chemotherapy induces autophagic cell death by activating the autophagy‑associated signaling pathways. The results of the present study demonstrated that the ROS level is important in autophagic death of the gastric carcinoma cells, and the increased ROS level, induced by thermo‑chemotherapy treatment, induced autophagy in gastric carcinoma cells.