The effect of Nd:YAG laser resection on symptom control, time to progression and survival in lung cancer patients.
The aim of this study was to determine the effect of Nd:YAG laser resection of centrally located tumors on the control of various symptoms and signs, time to progression and survival in lung cancer patients. We evaluated the effects of Nd: YAG laser resection in combination with high-dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT) vs. combination of HDR brachytherapy and EBRT alone on lung cancer symptoms and signs, ECOG performance status, time to progression and overall survival in lung cancer patients. Patients in group I (n=81) were treated with combination of HDR brachytherapy and EBRT, while patients in group II (n=97) were treated with Nd:YAG laser in combination with HDR brachytherapy and EBRT. Patients were evaluated before and after treatment, and were followed-up regularly every 3 months until the end of life. After RT +/- laser treatment all patients received standard chemotherapy (cisplatin plus etoposide) during the course of disease. After treatment in both groups significant improvement in all investigated parameters was seen. Improvement in dyspnoea, thoracic pain, body weight loss and ECOG performance status was significantly better in group II (p <0.05), as were time to progression and overall survival (p <0.05). Laser resection improves symptom control in lung cancer patients with central airway obstruction (CAO). Longer time to progression and survival of lung cancer patients could be the result of imminent airway desobstruction accomplished with Nd:YAG laser.


Characterization of protein extracts from different types of human teeth and insight in biomineralization.
The present study describes an efficient method for isolation and purification of protein extracts from four types of human teeth i.e. molar, premolar, canine, and incisor. Detailed structural characterization of these protein extracts was done by Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) which showed that a major fraction of the proteins present are unstructured in nature including primarily random coils in addition to the other structures like extended beta (β) structure, poly-l-proline-type II (PPII) helix, turns, with only a small fraction constituting of ordered structures like alpha (α) helix and β sheets. These resultant labile structures give the proteins the necessary flexibility that they require to interact with a variety of substrates including different ions like calcium and phosphates and for other protein-protein interactions. We also did initial studies on the mineralization of calcium phosphate with the protein extracts. Nanoparticle tracking analysis (NTA) show an increase in the size of calcium phosphate accumulation in the presence of protein extracts. We propose that protein extracts elevate the crystallization process of calcium phosphate. Our current biophysical study provides novel insights into the structural characterization of proteins from human teeth and their implications in understanding the tooth biomineralization. As per our knowledge, this is the first report which focuses on the whole protein extraction from different types of human teeth as these extracts imitate the in vivo tooth mineralization.


[The hospital in Lund during the 1850's].
At the Hospital in Lund a new central building was opened in 1850 bringing the total number of beds up to 150. In the same year the hospital was divided into one "External" department including surgery and the maternity ward and one "Internal" including medicine and the ward for venereal diseases. We reviewed the patient charts and the yearly reports from 1851 to 1860 including 40 autopsy reports from this period. During these years, 8,785 patients were admitted, 2,292 of these for syphilis. Mean hospitalization time in the surgical department was 55-60 years, average 35-45 days, in the medical department a mean of around 45 days. The longest hospital stay was 350-900 days, mostly for patients with joint diseases, probably mainly tuberculosis. The number of patients admitted each year, the number of hospital days, age distribution of the patients and costs are presented in diagrams. The mean age of the patients was around 28 years, and the largest 5-year group was 16-20 years. Syphilis, various manifestations of tuberculosis and different kinds of diffuse gastric trouble were dominating diagnoses. Infectious diseases were common and serious during these years, but only very few patients, apart from the diagnoses mentioned above, were admitted to the hospital. Chlorosis, anaemia and rheumatic disorders were common. Hirudines, cupping, in some cases venesection or cauterization, locally irritating cataplasms, laxatives and enemas were dominating parts of the therapeutic resources. The operative activity was very moderate, only a total of 275 operations were performed for incarcerated hernia, stone, cataract, external tumour and injuries. Medical drugs were collected mostly from plants but various preparations of iron, mercury and lead and their salts were also frequently used. Quinine was the only drug for fevers, not only for malaria,. Several lay "bonesetters" were active in the area, the best known of whom, belonging to a family active for 200 years, were mentioned with some criticism in a few patient charts. Clinical education for the medical students was conducted by A.S. Bruzelius, director of the "Institutum Clinicum", and the professors of surgery and medicine had only limited access to inpatients for their teaching. In 1850, Bruzelius was relieved from the teaching of internal medicine, and this became the reason to divide the hospital into the two departments. The organization of medical education in Sweden was much discussed during most of last century after the Karolinska Institute in Stockholm was opened in 1812 as an addition to the universities in Uppsala and Lund. In 1859 a committee suggested that, since the number of patients available for the medical students in Uppsala and Lund (which we can verify for Lund) were very modest compared to the hospitals in Stockholm, all medical education should be concentrated to one medical school in Stockholm. Fortunately, it all ended with a compromise. Otherwise, the two universities might have been closed completely, since the faculties of medicine were very important parts of the universities of this time.


Lipidomic profiling of patient-specific iPSC-derived hepatocyte-like cells.
Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model to primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a three-step protocol through the definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid-metabolism-related genes were performed during the entire differentiation process from iPSCs to HLCs. Additionally, fatty acid (FA) composition of the cell culture media at different stages was determined. Our results show that major alterations in the molecular species of lipids occurring during DE and early hepatic differentiation stages mainly mirror the quality and quantity of the FAs supplied in culture medium at each stage. Polyunsaturated phospholipids and sphingolipids with a very long FA were produced in the cells at a later stage of differentiation. This work uncovers the previously unknown lipid composition of iPSC-HLCs and its alterations during the differentiation in conjunction with the expression of key lipid-associated genes. Together with biochemical, functional and gene expression measurements, the lipidomic analyses allowed us to improve our understanding of the concerted influence of the exogenous metabolite supply and cellular biosynthesis essential for iPSC-HLC differentiation and function. Importantly, the study describes in detail a cell model that can be applied in exploring, for example, the lipid metabolism involved in the development of fatty liver disease or atherosclerosis.


Spanning maternal, newborn and child health (MNCH) and health systems research boundaries: conducive and limiting health systems factors to improving MNCH outcomes in West Africa.
Despite improvements over time, West Africa lags behind global as well as sub-Saharan averages in its maternal, newborn and child health (MNCH) outcomes. This is despite the availability of an increasing body of knowledge on interventions that improve such outcomes. Beyond our knowledge of what interventions work, insights are needed on others factors that facilitate or inhibit MNCH outcome improvement. This study aimed to explore health system factors conducive or limiting to MNCH policy and programme implementation and outcomes in West Africa, and how and why they work in context. We conducted a mixed methods multi-country case study focusing predominantly, but not exclusively, on the six West African countries (Burkina Faso, Benin, Mali, Senegal, Nigeria and Ghana) of the Innovating for Maternal and Child Health in Africa initiative. Data collection involved non-exhaustive review of grey and published literature, and 48 key informant interviews. We validated our findings and conclusions at two separate multi-stakeholder meetings organised by the West African Health Organization. To guide our data collection and analysis, we developed a unique theoretical framework of the link between health systems and MNCH, in which we conceptualised health systems as the foundations, pillars and roofing of a shelter for MNCH, and context as the ground on which the foundation is laid. A multitude of MNCH policies and interventions were being piloted, researched or implemented at scale in the sub-region, most of which faced multiple interacting conducive and limiting health system factors to effective implementation, as well as contextual challenges. Context acted through its effect on health system factors as well as on the social determinants of health. To accelerate and sustain improvements in MNCH outcomes in West Africa, an integrated approach to research and practice of simultaneously addressing health systems and contextual factors alongside MNCH service delivery interventions is needed. This requires multi-level, multi-sectoral and multi-stakeholder engagement approaches that span current geographical, language, research and practice community boundaries in West Africa, and effectively link the efforts of actors interested in health systems strengthening with those of actors interested in MNCH outcome improvement.


The pharmacodynamics of the p53-Mdm2 targeting drug Nutlin: the role of gene-switching noise.
In this work we investigate, by means of a computational stochastic model, how tumor cells with wild-type p53 gene respond to the drug Nutlin, an agent that interferes with the Mdm2-mediated p53 regulation. In particular, we show how the stochastic gene-switching controlled by p53 can explain experimental dose-response curves, i.e., the observed inter-cell variability of the cell viability under Nutlin action. The proposed model describes in some detail the regulation network of p53, including the negative feedback loop mediated by Mdm2 and the positive loop mediated by PTEN, as well as the reversible inhibition of Mdm2 caused by Nutlin binding. The fate of the individual cell is assumed to be decided by the rising of nuclear-phosphorylated p53 over a certain threshold. We also performed in silico experiments to evaluate the dose-response curve after a single drug dose delivered in mice, or after its fractionated administration. Our results suggest that dose-splitting may be ineffective at low doses and effective at high doses. This complex behavior can be due to the interplay among the existence of a threshold on the p53 level for its cell activity, the nonlinearity of the relationship between the bolus dose and the peak of active p53, and the relatively fast elimination of the drug.


The Effects of Long-term Storage on Commonly Measured Serum Analyte Levels.
Cohort studies typically bank biospecimens for many years before assay and investigators do not know whether levels of analytes have degraded. We collected control samples from 22 nonstudy participants using the same enrollment criteria and specimen collection, processing, and storage protocols as The Sister Study. Serum samples were assayed for 21 analytes at collection and 6 years later. For each sample, the difference between the result at baseline and at 6 years was calculated for each analyte. Some of the analytes experienced a marked decrease in concentration after 6 years of frozen storage in liquid nitrogen vapor, compared with their baseline value. The confidence interval for the mean paired difference excluded 0 for 8 of the 21 analytes tested (aspartate transaminase, total cholesterol, estradiol, glucose, high-density lipoprotein [HDL] cholesterol, luteinizing hormone, protein, and triglycerides). Two analytes, lactate dehydrogenase and sex hormone binding globulin, increased substantially in concentration over time (confidence interval excluded 0). For compounds substantially affected by storage time, the internal laboratory control variance was greater than the estimated mean percent change for HDL cholesterol and luteinizing hormone, indicating that extent of degradation for these analytes did not exceed technical variation. Despite evidence for systematic changes over long-term storage, correlations between baseline and later measures were high with little relation between size of the correlation and estimated mean difference across time points. QC experiments to assess the impact of long-term storage on anticipated analytes of interest are important in planning cohort studies with banked samples.


A screening test for heroin based on sequential injection analysis with dual-reagent chemiluminescence detection.
A sequential injection analysis procedure with dual-reagent chemiluminescence detection was applied to the screening of street drug seizure samples for the presence of heroin. The chemiluminescence reagents (acidic potassium permanganate and tris(2,2'-bipyridine)ruthenium(III)) were aspirated from either side of a sample aliquot that was sufficiently large to prevent interdispersion of the reagent zones, and therefore two different chemical reactions could be performed simultaneously at either end of the sample zone. The presence of heroin in seizure samples was indicated by a strong response with the tris(2,2'-bipyridine)ruthenium(III) reagent and confirmed by a significant increase in the response with the permanganate reagent when the sample was treated with sodium hydroxide to hydrolyse the heroin to morphine. Nicomorphine (a morphine-derived pharmaceutical) was synthesised and tested under the same conditions. The responses with the permanganate reagent were similar to those for heroin, which supports the proposed chemical basis for the test. However, the responses with tris(2,2'-bipyridine)ruthenium(III) were far lower for nicomorphine than heroin (approximately 5-fold for the samples that had not been hydrolysed).


Intentional partnering: a grounded theory study on developing effective partnerships among nurse and physician managers as they co-lead in an evolving healthcare system.
The aim of this study was to describe the process of how nurse and physician managers in formalized dyads work together to address clinical management issues in the surgical division of one hospital setting. Nurse and physician managers are uniquely positioned to co-lead and transform healthcare delivery. However, little is known about how this management dyad functions in the healthcare setting. A constructivist grounded theory approach was used to investigate the process of how nurse and physician managers work together in formalized dyads in an urban Canadian university affiliated teaching hospital. Data collection occurred from September 2013-August 2014. Data included participant observation (n = 142 hours) and intensive interviews (n = 36) with nurse-physician manager dyads (12 nurses, 9 physicians) collected in a surgical department. Theoretical sampling was used to elaborate on properties of emerging concepts and categories. A substantive theory on 'intentional partnering' was generated. Nurses' and physicians' professional agendas, which included their interests and purposes for working with each other served as the starting point of 'intentional partnering'. The theory explains how nurse and physician managers align their professional agendas through the processes of 'accepting mutual necessity', 'daring to risk (together)' and 'constructing a shared responsibility'. Being credible, earning trust and safeguarding respect were fundamental to communicating effectively. Intentional partnering elucidates the relational components of working together and the strategizing that occurs as each partner deliberates on what he or she is willing to accept, risk and put into place to reap the benefits of collaborating.


A 12-day-old male newborn with extensive vesicles and fever.
Neonatal varicella infection is a rare condition since vaccine introduction. The authors report the case of a 12-day-old male who presented with a fever and generalised vesicular eruption. The patient's mother had varicella infection 1 day before delivery without treatment. The neonate initially did not receive prophylaxis or treatment. He subsequently was started on intravenous acyclovir and recovered without further complications or sequelae. Prompt diagnosis and treatment for maternal prenatal varicella infection is necessary to prevent infection in the newborn, and healthcare provider awareness to avoid nosocomial transmission.


Single-particle electron microscopy in the study of membrane protein structure.
Single-particle electron microscopy (EM) provides the great advantage that protein structure can be studied without the need to grow crystals. However, due to technical limitations, this approach played only a minor role in the study of membrane protein structure. This situation has recently changed dramatically with the introduction of direct electron detection device cameras, which allow images of unprecedented quality to be recorded, also making software algorithms, such as three-dimensional classification and structure refinement, much more powerful. The enhanced potential of single-particle EM was impressively demonstrated by delivering the first long-sought atomic model of a member of the biomedically important transient receptor potential channel family. Structures of several more membrane proteins followed in short order. This review recounts the history of single-particle EM in the study of membrane proteins, describes the technical advances that now allow this approach to generate atomic models of membrane proteins and provides a brief overview of some of the membrane protein structures that have been studied by single-particle EM to date.


Probing Protein Secondary Structure using EPR: Investigating a Dynamic Region of Visual Arrestin.
One key application of site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is the determination of sequence-specific secondary structure in proteins. Regular secondary structure leads to a periodic variation in both side chain motion and solvent accessibility, two properties easily monitored by EPR techniques. Specifically, saturation recovery (SR) EPR spectroscopy has proven to be useful for making accessibility measurements for multiple protein structure populations by determining individual accessibilities and is therefore well suited to study the structure of proteins exhibiting multiple conformations in equilibrium. Here we employ both continuous wave and SR EPR spectroscopy in combination to examine the secondary structure of a short sequence showing conformational heterogeneity in visual rod arrestin. The EPR data presented here clearly distinguish between the unstructured loop and the helical structure formed in the crystallographic tetramer of visual arrestin and show that this region is unstructured in solution.


Activation of the fifth and sixth component of the complement system: similarities between C5b6 and C(56)a with respect to lytic enhancement by cell-bound C3b or A2C, and species preferences of target cell.
Brief shift of purified C5 and C6 at 0 degrees C to pH 6.4, followed by immediate neutralization, results in the generation of a factor, designated C(56)a, that lyses erythrocytes together with C7, C8, and C9. We compared C(56)a and C5b6 generated by an alternative-pathway convertase, with regard to their action on different target cells. We found tht C(56)a is similar to C5b6 in the following properties: 1) Together with C7, C(56)a forms a stable intermediate on either sheep or guinea pig erythrocytes. 2) Membrane-bound C3b, or A2C incorporated in the membrane, enhances lysis by C(56)a-9, as well as lysis by C5b6-9. We also found that the lysis of EC(56)a7 or EC5b67 intermediates by C8 and C9 depends on the species of the erythrocytes and the species of C8 and C9. Thus, lysis of sheep erythrocytes is more efficient with guinea pig C8 and C9 than with human C8 and C9. In the case of guinea pig erythrocytes, this relationship is reversed, i.e., these cells lyse more efficiently when human C8 and C9 are used. Enhancement of lysis by membrane-bound C3b or A2C does not abrogate this species incompatibility pattern.


[Academician S. N. Fyodorov's contribution to Russian and world ophthalmology].
The article is dedicated to academician S. N. Fyodorov, an outstanding surgeon, scientist, and a public figure. The paper covers the milestones of S. N. Fyodorov's creative way. His motto was uncompromisingness, diligence, and innovation. The main result of academician Fyodorov's many-year work, his brainchild, was Eye Microsurgery Complex, an inter-branch scientific and technical establishment, which became the material base for his most daring projects. S. N. Fyodorov made a real revolution in ophthalmology by changing it from a modest surgeless science into a bright and stormily progressing field of medicine. Thanks to his achievement, Russia is still one of the world's leaders in ophthalmology. Today, Eye Microsurgery is the flag of Russian ophthalmology. It provides more than 50% of all high-technology ophthalmologic aid in the country.


Interfacial reactions of nano-structured Cu-doped indium oxide/indium tin oxide ohmic contacts to p-GaN.
Interfacial microstructure and elemental diffusion of Cu-doped indium oxide (CIO)/indium tin oxide (ITO) ohmic contacts to p-type GaN for light-emitting diodes (LEDs) were investigated using cross-sectional transmission electron microscopy (XTEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction. The CIO/ITO contacts gave specific contact resistances of approximately 10(-4) omegacm2 and transmittance greater than 95% at a wavelength of 405 nm when annealed at 630 degrees C for 1 min in air. After annealing at 630 degrees C, multi-component oxides composed of Ga2O3-In2O3, Ga2O3-CuO, and In2O3-CuO formed at the interface between p-GaN and ITO. Formation of multi-component oxides reduced the barrier height between p-GaN and ITO due to their higher work functions than that of ITO, and caused Ga in the GaN to diffuse into the CIO/ITO layer, followed by generation of acceptor-like Ga vacancies near the GaN surface, which lowered contact resistivity of the CIO/ITO contacts to p-GaN after the annealing.


Regulatory Information and Guidance on Biosimilars and Their Use Across Europe: A Call for Strengthened One Voice Messaging.
Beyond evaluation and approval, European and national regulators have a key role in providing reliable information on biosimilars and the science underpinning their development, approval, and use. This study aims to (i) review biosimilar information and guidance provided by EMA and national medicines agencies and (ii) explore stakeholder perspectives on the role of regulators in enabling acceptance and use of biosimilars. This study consists of (i) a comparative review of regulatory information and position statements across medicine agencies (n = 32) and (ii) qualitative interviews with stakeholders in Europe (n = 14). The comparative analysis showed that regulatory information and guidance about biosimilars offered by national medicines agencies in Europe varies, and is limited or absent in multiple instances. Approximately 40% (13/31) of the national medicines agencies' websites did not offer any information regarding biosimilars, and for about half (15/31) no educational materials were provided. Only less than half of national medicines agencies provided guidance on biosimilar interchangeability and switching (8/31 and 12/31, respectively). Among the national medicines agencies that did offer guidance, the extent (e.g., elaborate position vs. brief statement) and content (e.g., full endorsement vs. more cautious) of the guidance differed substantially. Countries that have a strong involvement in EU level biosimilar regulatory activities generally had more elaborate information nationally. Interviewees underwrote the need for (national) regulators to intensify biosimilar stakeholder guidance, especially in terms of providing clear positions regarding biosimilar interchangeability and switching, which in turn can be disseminated by the relevant professional societies more locally. This study revealed that, despite strong EU-level regulatory biosimilar guidance, guidance about biosimilars, and their use differs considerably across Member States. This heterogeneity, together with the absence of a clear EU-wide position on interchangeability, may instill uncertainty among stakeholders about the appropriate use of biosimilars in practice. Regulators should strive for a clear and common EU scientific position on biosimilar interchangeability to bridge this gap and unambiguously inform policy makers, healthcare professionals, and patients. Furthermore, there is a clear opportunity to expand information at the national level, and leverage EU-developed information materials more actively in this regard.


Adenoma of the islets of Langerhans.
An adenoma of the islets of Langerhans may be found anywhere in the pancreas but is more common in the body and tail, and more than one tumor may be present. When such a tumor produces insulin the symptoms observed are those of hyperinsulinism, varying from pallor, sweating, weakness and amnesia in mild cases to coma and convulsions in the more severe. The diagnosis rests largely on Whipple's triad, namely, the onset of symptoms during the fasting period or after exertion, sugar content in the blood of less than 50 mg. per 100 cc. during an attack, and immediate relief of symptoms upon the administration of glucose in one form or another. Surgical removal of an adenoma is the only known cure, and unless it is done the patient will eventually die of the effects of prolonged hyperinsulinism. The procedure entailed may be relatively simple, or fraught with great difficulties and postoperative complications of a major nature. The literature indicates that there has been a mortality rate of 8 or 9 per cent associated with the surgical treatment of this condition.


A study of the relationship between self-care, compassion satisfaction, compassion fatigue, and burnout among hospice professionals.
Hospice care professionals (HCPs) experience a large number of stressors in their work settings. The purpose of this study was to investigate the relationship between self-care, compassion fatigue, burnout, and compassion satisfaction among HCPs. Thirty-seven HCPs were surveyed regarding their levels of compassion satisfaction, compassion fatigue, and burnout. Respondents also reported the types of self-care activities in which they took part. Results indicated a relationship between self-care strategies and lower levels of burnout and compassion fatigue, and higher levels of compassion satisfaction. Several suggestions are offered for continued research and practice in the hospice care field.


Proceedings of the physical and occupational therapy special interest group meeting.
At the 1997 American Burn Association meeting in New York City the Physical Therapy/ Occupational Therapy (PT/OT) Special Interest Group met and discussed five pertinent topics that affect therapists. A summary of the information was received from the five discussion groups. This information is presented so that the entire PT/OT membership can be kept informed and updated about the information presented at this meeting. Moderators can be resources for more in-depth information regarding these topics.


Metal-dependent SpoIIE oligomerization stabilizes FtsZ during asymmetric division in Bacillus subtilis.
SpoIIE is a bifunctional protein involved in asymmetric septum formation and in activation of the forespore compartment-specific transcription factor σF through dephosphorylation of SpoIIAA-P. The phosphatase activity of SpoIIE requires Mn2+ as a metal cofactor. Here, we show that the presence of a metal cofactor also influences SpoIIE oligomerization and asymmetric septum formation. Absence of Mn2+ from sporulation medium results in a delay of the formation of polar FtsZ-rings, similar to a spoIIE null mutant. We purified the entire cytoplasmic part of the SpoIIE protein, and show that the protein copurifies with bound metals. Metal binding both stimulates SpoIIE oligomerization, and results in the formation of larger oligomeric structures. The presence of SpoIIE oligomers reduces FtsZ GTP hydrolysis activity and stabilizes FtsZ polymers in a light scattering assay. Combined, these results indicate that metal binding is not just required for SpoIIE phosphatase activity but also is important for SpoIIE's role in asymmetric septum formation.


Intracranial stent placement for recanalization of acute cerebrovascular occlusion in 32 patients.
Stents have been reported as an option for improvement of the recanalization rate in AIS. The authors have also used intracranial stents in failed cases of IAT with pharmacologic and mechanical methods since 2004. We retrospectively reviewed our cases of intracranial stent use for IAT of AIS for recanalization and as a rescue procedure for iatrogenic intracranial vascular dissection during IAT. Thirty-two patients, who were diagnosed with AIS, were treated with intracranial stents (28 balloon-mounted and 7 self-expandable stents) at our neurovascular center between April 2004 and December 2008. The stent use for all 32 patients was the final attempt to recanalize occluded vessels after various trials of pharmacologic or mechanical thrombolysis or to treat iatrogenic vascular dissection. Among the 32 patients, immediate poststenting angiographic recanalization was achieved in 100% with TIMI/TICI 2 (15 of 32 lesions, 46.9%) or TIMI/TICI 3 (17 of 32 lesions, 53.1%). However, complication rates were also high. Major symptomatic intracerebral hemorrhage (1 case of procedural symptomatic hemorrhage and 3 cases of delayed symptomatic hemorrhage) occurred in 4 (12.5%); intracranial vascular dissection, in 4 (12.5%); extracranial vascular dissection, in 3 (9.4%); immediate IST, in 4 (12.5%); subacute (within 1 week) IST, in 2; late (>1 week) IST, in 1, and 1 case of in-stent restenosis occurred twice (at 5 and 17 months). Intracranial stent placement for AIS management has an excellent recanalization rate. However, it is associated with high complication risks as our series showed. We believe that the decision to treat AIS with intracranial stent placement should be made after careful consideration of potential benefits and risks.


Lactobacillus plantarum GX17 benefits growth performance and improves functions of intestinal barrier/intestinal flora among yellow-feathered broilers.
Lactobacillus plantarum has recently been found to be a natural source feed additive bacteria with great advantages in food safety and animal welfare. Discovering novel strains with commercial application potentiation could benefit the local poultry industry, and in particular support Chinese farmers. In this study, we tested a recently isolated novel strain of Lactobacillus plantarum GX17 as a feed additive on the growth performance and intestinal barrier functions of 1-day-old Chinese yellow-feather chicks. As good as other commercial probiotics, feeding with Lactobacillus plantarum GX17 showed significant improvements in humoral immune responses and enhanced the immune effect after vaccination for either the Newcastle disease vaccine or the avian influenza vaccine. This study also found that feeding with Lactobacillus plantarum GX17 improved the feed-to-weight ratio and caused a significant increase of the villus length to crypt depth ratio. Furthermore, Lactobacillus plantarum GX17 significantly up-regulated the mRNA expression of CLDN, MUC2, and TLR2, all of which are jejunum-associated barrier genes, indicating an improvement of the intestinal barrier functions by enhancing the tight junction between epithelia cells. These results are comparable to the effects of feeding the commercial complex probiotics that improve the expression levels of CLDN, ocludin, MUC2, TLR2, and TLR4. In terms of maintaining intestinal health, commercial complex probiotics increased the relative abundance of Parabacteroides and Romboutsia, while Lactobacillus plantarum GX17 increased the relative abundance of Pseudoflavonifractor. Our data suggest that Lactobacillus plantarum GX17 could enhance the intestinal absorption of nutrients and therefore improve the growth performance of Chinese yellow-feather chicks. In conclusion, compared with the commercial complex probiotics, Lactobacillus plantarum GX17 has more positive effects on the growth performance and intestinal barrier function of yellow-feather chickens, and can be used as a feed additive.


Identification and characterization of human KIAA1391 and mouse Kiaa1391 genes encoding novel RhoGAP family proteins with RA domain and ANXL repeats.
The commonly deleted region of breast cancer at human chromosome 11q23.1 is located between microsatellite markers D11S927 and D11S1347. We have previously identified and characterized the KIAA1735 gene, encoding MTH and DIX domain protein, within the 11q23.1 commonly deleted region. The BTG4 gene, encoding BTG/TOB family protein, as well as the SIK2 gene, encoding salt-inducible serine/threonine kinase 2, were also located within the 11q23.1 region. We identified and characterized the KIAA1391 gene within the 11q23.1 commonly deleted region by using bioinformatics. The nucleotide position 11-3586 of human KIAA1391 cDNA was predicted as the coding region of human KIAA1391 gene. Mouse Kiaa1391 gene was located within mouse genome sequences RP23-95E13 (AC102770.4), RP23-212M11 (AC140363.1), and mouse chromosome 9 genomic contig NT_039473.1. Exon-intron structure was well conserved between human KIAA1391 gene and mouse Kiaa1391 gene. Nucleotide sequence of mouse Kiaa1391 cDNA was determined in silico by assembling nucleotide sequences of exon 1-15 of mouse Kiaa1391 gene. Human KIAA1391 protein (1191 aa) and mouse Kiaa1391 protein (1182 aa) showed 79.1% total-amino-acid identity. RA domain (codon 198-274), RhoGAP domain (codon 363-546), and two Annexin-like (ANXL) repeats (codon 657-767 and 796-909) of human KIAA1391 protein were conserved in mouse Kiaa1391 protein. This is the first report on the comprehensive characterization of human KIAA1391 gene and mouse Kiaa1391 gene, encoding RhoGAP proteins with RA domain and two ANXL repeats.


Design and Fabrication of an Instrumented Handrim to Measure the Kinetic and Kinematic Information by the Hand of User for 3D Analysis of Manual Wheelchair Propulsion Dynamics.
The repetitious nature of propelling a wheelchair has been associated with the high incidence of injury among manual wheelchair users (MWUs), mainly in the shoulder, elbow and wrist. Recent literature has found a link between handrim biomechanics and risk of injury to the upper extremity. The valid measurement of three-dimensional net joint forces and torques, however, can lead to a better understanding of the mechanisms of injury, the development of prevention techniques, and the reduction of serious injuries to the joints. In this project, an instrumented wheel system was developed to measure the applied loads dynamically by the hand of the user and the angular position of the wheelchair user's hand on the handrim during the propulsion phase. The system is composed of an experimental six-axis load cell, and a wireless eight channel data logger mounted on a wheel hub. The angular position of the wheel is measured by an absolute magnetic encoder. The angular position of the wheelchair user's hand on the handrim during the propulsion phase (ɸ) or point of force application (PFA) is calculated by means of a new-experimental method using 36 pairs of infrared emitter/receiver diodes mounted around the handrim. In this regard, the observed data extracted from an inexperienced able-bodied subject pushed a wheelchair with the instrumented handrim are presented to show the output behavior of the instrumented handrim. The recorded forces and torques were in agreement with previously reported magnitudes. However, this paper can provide readers with some technical insights into possible solutions for measuring the manual wheelchair propulsion biomechanical data.


Impact of a Patient Support Program on Patient Adherence to Adalimumab and Direct Medical Costs in Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis, and Ankylosing Spondylitis.
AbbVie provides a free-to-patient patient support program (PSP) to assist adalimumab-treated patients with medication costs, nurse support, injection training, pen disposal, and medication reminders. The impact of these services on patient adherence to adalimumab and direct medical costs associated with autoimmune disease has not been assessed. To quantify the relationship between participation in a PSP and outcomes (adalimumab adherence, persistence, and direct medical costs) in patients initiating adalimumab treatment. A longitudinal, retrospective, cohort study was conducted using patient-level data from the PSP combined with Symphony Health Solutions administrative claims data for patients initiating adalimumab between January 2008 and June 2014. The sample included patients aged ≥ 18 years with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who were biologic-naïve before initiation of adalimumab. Patients who enrolled in the PSP (PSP cohort) were matched to those who did not enroll (non-PSP cohort) based on age, sex, year of treatment initiation, comorbidities, diagnosis, and initiation at a specialty pharmacy. For the PSP cohort, the index date was assigned as the earliest date of PSP enrollment, and time to enrollment following adalimumab initiation was used to assign index dates for the non-PSP cohort. All patients were required to have evidence of medical and pharmacy coverage for at least 6 months before and after their first adalimumab claim and at least 12 months after their index date. Adherence (proportion of days covered during the 12 months following PSP opt-in [index date]) was compared between cohorts using t-tests. Persistence was assessed using survival analysis of discontinuation rates. Medical costs for emergency department, inpatient, physician, and outpatient visits (all-cause and disease-related) and total costs (medical plus drug costs) were compared at 12 months following the index date using t-tests. A total of 2,386 patients were included in the study and were allocated to the PSP (n = 1,199) and non-PSP (n = 1,187) cohorts. Baseline characteristics were similar between cohorts. During the follow-up period, adalimumab adherence was 14% greater in the PSP cohort than for the non-PSP cohort (67.0% vs. 58.8%; P < 0.001). The discontinuation rate for adalimumab was 14% lower in the PSP cohort compared with the non-PSP cohort (39.7% vs. 46.2%; P = 0.001). Univariate analyses showed that PSP patients had 23% lower 12-month medical costs (excluding costs for biologic treatment) than did non-PSP patients ($18,322 vs. $23,679; P = 0.003). Disease-related medical costs were 22% lower for PSP than for non-PSP patients ($8,001 vs. $10,202; P = 0.045). Total costs were 10% lower for PSP than for non-PSP patients ($35,741 vs. $39,713; P = 0.030). Patient enrollment in the PSP was associated with greater adherence, improved persistence, and reduced medical (all-cause and disease-related) and total health care costs for patients receiving adalimumab therapy. Design, study conduct, and financial support for this study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Rubin has received consulting fees or research support from AbbVie, Amgen, Emmi, Genentech, Ironwood, Janssen, Pfizer, Prometheus, Shire, and Takeda. Skup and Mittal are employees and stockholders of AbbVie. Chao was an employee of AbbVie at the time of the study and may hold AbbVie stock. Johnson and Davis are employees of Medicus Economics, which received payment from AbbVie to participate in this research. Study concept and design were contributed by Rubin, Mittal, Chao, and Skup, along with Davis and Johnson. Davis and Johnson took the lead in data collection, with assistance from the other authors, and data interpretation was performed by Rubin, Mittal, Chao, and Skup, with assistance from Davis and Johnson. All authors contributed to the writing and revision of the manuscript. The abstract for this study was published as Rubin DT, Skup M, Davis M, Johnson S, Chao J. Impact of AbbVie's patient support program on resource costs in Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. J Manag Care Spec Pharm. 2015;21(Suppl 4a):S74-75 (poster presentation at Academy of Managed Care, 27th Annual Meeting and Expo; April 7-10, 2015; San Diego, CA) and as abstract 2339 in Arthritis Rheumatol. 2015;67(Suppl 10; poster presentation at American College of Rheumatology 2015 ACR/AHRP Annual Meeting; November 7-11, 2015; San Francisco, CA).


Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility.
Nanobiointerfaces were prepared based on an electrically conductive polyethylenedioxythiophene (PEDOT). Thin (<100 nm), ultrasmooth (roughness ( R(rms)) < 5 nm), and functionalized PEDOT films have been successfully electropolymerized using aqueous microemulsion. The microemulsion polymerization is found to be catalyzed in the presence of a low concentration of acid and allows for film formation from various functionalized ethylenedioxythiophenes (EDOTs) (e.g., EDOT-OH, C(2)-EDOT-COOH, C(4)-EDOT-COOH, C(2)-EDOT-NHS, EDOT-N(3)) and their mixtures. The nanobiointerfaces are compositionally tunable and controlled to deposit on selected electrode surfaces. They prefer orthogonal growth on patterned surfaces and are synthesized within seconds. These thin PEDOT films exhibit very low intrinsic cytotoxicity and display no inflammatory response upon implantation, making them ideal for biosensing and bioengineering applications.


Load-bearing capacity of corticocancellous bone grafts in the spine.
We investigated the relationship between the densities and areas of commonly used autogenous tricortical bone grafts from the iliac crest and the fibula and their mechanical load-bearing abilities. Intact corticocancellous grafts, seven millimeters thick, were obtained during elective spinal arthrodeses from fifty-six patients: from the anterior part of the pelvis in twenty-four patients, the posterior part of the pelvis in twenty-nine patients, and the fibula in three patients. The apparent densities and cross-sectional areas of the cortical and cancellous bone were measured with use of a specific computed-tomographic technique before the specimens were mechanically tested to failure in uniaxial compression. Specimens from the anterior superior iliac spine were able to bear significantly higher axial loads (average, 3230 newtons; range, 430 to 8112 newtons) than were those from the posterior superior iliac spine (average, 1458 newtons; range, 350 to 4639 newtons) (p < 0.001). The cancellous density was the most significant single factor in the prediction of the load to failure of the grafts from the iliac crest (adjusted r2 = 0.58; p < 0.0001). When all of the physical variables (the cancellous and cortical densities and areas) were entered into a multiple-regression model, the combination of the cortical and cancellous densities and the cortical area was a good predictor (adjusted r2 = 0.68; p < 0.001) of the load to failure. The fibular grafts were stronger than those from the other two sites, but they had the least over-all cross-sectional area and cancellous bone.(ABSTRACT TRUNCATED AT 250 WORDS)


Ethylene glycol poisoning.
Ethylene glycol (EG) can be found in many agents, such as antifreeze. Ingestion of EG may cause serious poisoning. Adults are typically exposed when EG is ingested as a cheap substitute for ethanol or in suicide-attempts. Children may be exposed by accidental ingestion caused by decantation of EG to unlabeled bottles. EG has in itself a low toxicity, but is in vivo broken down to four organic acids: glycoaldehyde, glycolic acid, glyoxylic acid and oxalic acid. The metabolites are cell toxins that cause central nervous system depression, and cardio-pulmonary and renal failure. Glycolic acid causes severe acidosis, and oxalate is precipitated as calcium oxalate in the kidneys and other tissues. We present five case reports of fatal EG-poisoning, and review the literature concerning clinical presentation and diagnosis, pathological findings, treatment and prevention.


Low Serum Vascular Endothelial Growth Factor Level Predicts Adverse Outcomes in Neonates with Respiratory Distress Syndrome.
Objective: Preterm neonates are susceptible to neonatal respiratory distress syndrome (NRDS). Lower levels of cord blood vascular endothelial growth factor (VEGF) are implicated in NRDS. This study aims to explore whether the serum VEGF level has prognostic values on neonates with respiratory distress syndrome (RDS). Methods: A total of 80 infants diagnosed with NRDS were enrolled, with 70 preterm neonates without NRDS as controls. Cord blood samples before treatment and venous blood samples after treatment were collected and clinical information was recorded. The serum VEGF level was measured using enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curve was used to evaluate whether serum VEGF is a biomarker of NRDS. Newborns were followed up for 1 month to collect survival information. The influence of VEGF levels on overall survival was analyzed using the Kaplan-Meier method. The univariate and multivariate Cox regression models were adopted to assess the prognostic factor of NRDS. Results: VEGF level was decreased in sera of neonates with RDS. The area under the ROC curve of VEGF level in distinguishing neonates with RDS from neonates without RDS was 0.949, with a cutoff value of 39.72 (87.50% sensitivity, 87.14% specificity). Serum VEGF was a biomarker of NRDS. Neonates with RDS with high VEGF levels had longer periods of survival than those with low VEGF levels. NRDS grade and VEGF level were independent prognostic factors affecting the overall survival of neonates with RDS. Conclusion: Decreased serum VEGF level in RDS neonates can predict the poor prognosis of NRDS, and VEGF level might be an independent prognostic factor for the overall survival of RDS neonates. Clinical Trial Registration No. 201901A.


Using ovitraps to assess the quantity of mosquito larval habitat during local eradication with source reduction and ovitraps.
The quantity of mosquito larval habitat in a specified area was assessed by placing a known number of ovitraps in the same area. The ovitraps competed for oviposition with the unknown quantity of larval habitat, and that quantity was deduced by comparing the number of eggs laid in the ovitraps when the number of ovitraps was changed from one time to another. This method can be used to assess the effectiveness of source reduction. It also provides key information for using ovitraps to eradicate local mosquito populations by competing with existing breeding sites for oviposition. The same ovitraps that are used for control can provide information on how many ovitraps are necessary to ensure eradication.


Role of Nudt2 in Anchorage-Independent Growth and Cell Migration of Human Melanoma.
Nudt2 encodes a diadenosine tetraphosphate (Ap4A) hydrolase that catalyzes the hydrolysis of Ap4A and is involved in the lysyl tRNA synthetase-Ap4A-Nudt2 (LysRS-Ap4A-Nudt2) signaling pathway. We have previously demonstrated that this pathway is active in non-small cell lung cancer. Nudt2 was shown to be involved in cell proliferation in breast cancer, making it an important target in cancer therapy. Currently, the function of Nudt2 in malignant melanoma has not been demonstrated. Therefore, we investigated the role played by Nudt2 in the growth of human melanoma. Our study showed that Nudt2 knockdown suppressed anchorage-independent growth of human melanoma cells in vitro. The in vivo effect of Nudt2 was determined by investigating the role played by Nudt2 knockdown on the ability of the cells to form tumors in a mice xenograft model. Nudt2 knockdown significantly suppressed tumor growth in this model. Moreover, overexpression of Nudt2 resulted in an increase in anchorage-independent growth of these cells, whereas Nudt2 knockdown decreased their migration. In addition, Nudt2 knockdown reduced vimentin expression. Vimentin is one of the mesenchymal markers that are involved in the epithelial mesenchymal transition (EMT) process. Thus, Nudt2 plays an important role in promoting anchorage-independent growth and cell migration in melanoma.


[Retracted] NCTD elicits proapoptotic and antiglycolytic effects on colorectal cancer cells via modulation of Fam46c expression and inhibition of ERK1/2 signaling.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 2C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Moreover, certain of the western blotting data shown internally within Fig. 4E and F appeared to be strikingly similar, even though the experiments portrayed in these Figure parts were intended to show the results obtained from different cell lines. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, prior to its submission to Molecular Medicine Reports, and based on an overall lack in the confidence in the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 774‑782, 2020; DOI: 10.3892/mmr.2020.11151].


Facilitating influence of procainamide on conversion of atrial flutter by rapid atrial pacing.
In a prospective, double-blind, randomized, placebocontrolled study we investigated the facilitating influence of intravenous procainamide on conversion of atrial flutter by rapid atrial pacing. Fifty consecutive patients with spontaneous sustained atrial flutter were 1:1 randomized into two homogenous groups: group A received 10 mg.kg-1 procainamide intravenously, group B placebo. After infusion there was a significant (P < 0.01) lengthening of the flutter cycle with respect to baseline in group A, exceeding the flutter cycle length of the control group (P < 0.05). The overall success rate of rapid atrial pacing in restoring sinus rhythm was significantly higher after pre-treatment with procainamide compared to placebo (100% vs 76%; P < 0.05): 20 patients of group A reverted immediately after pacing to sinus rhythm, the remaining five after a brief episode of atrial fibrillation. In the placebo group, 16 patients showed a prompt conversion to sinus rhythm and three after transient atrial fibrillation. In the remaining six patients, due to sustained pacing-induced atrial fibrillation, direct current cardioversion was necessary. After administration of procainamide a less aggressive stimulation protocol with significantly (P < 0.01) longer paced cycles to interrupt atrial flutter was achievable. In conclusion, intravenous procainamide augments the efficacy of atrial pacing to convert atrial flutter to sinus rhythm.


Cadmium and zinc in human liver and kidney.
Liver and kidney samples obtained from 76 autopsies were analyzed for cadmium and zinc content. The patients had died of various internal diseases. None of them had any known occupational exposure to cadmium. A record was made of age, sex, place of residence, diagnosis, and smoking habits of each patient. The results showed no significant correlation between cadmium accumulation and hypertension or cardiovascular disease. There was, however, a significantly higher kidney cadmium level in smokers than in nonsmokers.


Effect of zeta-globin substitution on the O2-transport properties of Hb S in vitro and in vivo.
Hemoglobin zeta(2)beta(2)(S) is generated by substituting embryonic zeta-globin subunits for the normal alpha-globin components of Hb S (alpha(2)beta(2)(S)). This novel hemoglobin has recently been shown to inhibit polymerization of Hb S in vitro and to normalize the pathological phenotype of mouse models of sickle cell disease in vivo. Despite its promise as a therapeutic tool in human disease, however, the basic O(2)-transport properties of Hb zeta(2)beta(2)(S) have not yet been described. Using human hemoglobins purified from complex transgenic-knockout mice, we show that Hb zeta(2)beta(2)(S) exhibits an O(2) affinity as well as a Hill coefficient, Bohr response, and allosteric properties in vitro that are suboptimally suited for physiological O(2) transport in vivo. These data are substantiated by in situ analyses demonstrating an increase in the O(2) affinity of intact erythrocytes from mice that express Hb zeta(2)beta(2)(S). Surprisingly, though, co-expression of Hb zeta(2)beta(2)(S) leads to a substantial improvement in the tissue oxygenation of mice that model sickle cell disease. These analyses suggest that, in the context of sickle cell disease, the beneficial antisickling effects of Hb zeta(2)beta(2)(S) outweigh its O(2)-transport liabilities. The potential structural bases for the antisickling properties of Hb zeta(2)beta(2)(S) are discussed in the context of these new observations.


Rapid detection of -alpha 4.2 deletion of alpha-thalassemia-2 by polymerase chain reaction.
We sequenced part of the X boxes of alpha-thalassemia-1 of Southeast Asia type (- -SEA) with -alpha 4.2, -alpha 3.7, -alpha G-Taichung, and alpha CS alpha. We found the X box of -alpha 3.7 belonged to the X box of alpha 2 globin gene and the X box of alpha CS alpha contained X boxes of both alpha 1 and alpha 2 globin gene, whereas the X box of -alpha 4.2 and -alpha G-Taichung was a hybrid of X boxes of alpha 2 and alpha 1 globin gene. We also found there are two types of -alpha 4.2 deletion; type 1 is a common type of -alpha 4.2 deletion and type 2 is linkage to -alpha G-Taichung. We used a combination of two methods, the amplification refractory mutation system (ARMS) and the amplified created restriction sites (ACRS), to amplify the hybrids of X boxes specifically. The upstream primer for X box of alpha 2 globin gene was designed following the standard ARMS procedure to amplify the X segment of the alpha-globin gene. The downstream primer was designed according to the ACRS method to check the specificity of PCR products. Using this approach, we can diagnose the different types of -alpha 4.2 deletion. This kind of approach can also be used to amplify the specific region from the cluster of highly homologous genes.


The impact of COVID-19 national restrictions on dental antibiotic dispensing trends and treatment activity in England: January 2016 to July 2021.
Reducing inappropriate antibiotic prescribing tempers the growing threat of antimicrobial resistance. We aimed to quantify the associated impact of COVID-19-related national restrictions in England on dental antibiotic dispensing and describe changes in appointments and modes of delivery of care. Interrupted time series analyses were completed using NHS Business Service Authority (NHSBSA) ePACT2 data to measure the associated change in antibiotic dispensing in England following COVID-19-related restrictions (which began March 2020). For face-to-face dental consultations, NHS dental treatment plan (FP17) data were used. For remote consultations during the COVID-19 period, NHSBSA Compass system remote management data were used. Between January 2016 and February 2020, there was a decreasing trend in antibiotic dispensing (-0.02 per 1000 population per month, P < 0.05). In contrast, there was an increase of 0.98 per 1000 population (P < 0.05) in March. The peak in antibiotic use occurred between June 2020 and July 2020, once the restrictions were eased. At the end of the study period (July 2021), the elevated prescribing trend had not returned to pre-pandemic counterfactual levels, although exhibiting a declining trend. A stable trend in dental treatment plans was seen pre-COVID-19, with a sharp decline coinciding with the restrictions. Dental treatment plans had not yet returned to the higher pre-pandemic levels. Dental antibiotic prescribing significantly increased with the national COVID-19 restrictions when service delivery was altered with the closure of dental practices and introduction of remote consultations. Teledentistry was likely associated with inappropriate antibiotic prescribing. Continued antimicrobial stewardship and prudent use of antibiotics in dentistry is important.


Efficacy of synergistic activity of seed oils from Carthamus tinctorius (Safflower) and Nasturtium officinale (Watercress) on the lethality of the cattle tick Hyalomma scupense (Acari: Ixodidae).
Ticks and tick-borne diseases are a severe economic and public-health problem for cattle producers. The emergence of acaricide resistance to synthetic chemical treatments has prompted interest in developing alternative tick control methods. The main objective of the current research was to identify the chemical structure of Carthamus tinctorius and Nasturtium officinale seed oils and to assess their anti-tick properties against Hyalomma scupense ticks both alone and in combination (1:1). Analytical methods were used to analyze the chemical components. For in vitro assays, adults of H. scupense were immersed in C. tinctorius and N. officinale seed oils at 100, 125, 200, and 300 mg/ml concentrations; for 5 minutes. Larvae of H. scupense were dipped in 25, 50, 100, 125, 200, and 300 mg/ml doses of seed oils; the mortality percentage was determined after 24 hours. The seed oil safflower was mainly composed of linoleic acid (84.48%), followed by palmitic acid (6.54%) and stearic acid (3.77%). Meanwhile, watercress seed oil was mainly composed of linolenic acid (50.78%), gondoic acid (13.57%), linoleic acid (10.58%), palmitic acid (8.02%), and erucidic acid (6.62%). The Adults Immersion Test showed the sensitivity of ticks to C. tinctorius and N. officinale seed oil: C. tinctorius seed oil caused (95%) mortality of H. scupense at 300 mg/ml, while N. officinale seed oil induced (88.68%) mortality at the same concentration. At a 200 mg/ml concentration, C. tinctorius and N. officinale oil combined caused 100% mortality. Tested oils showed larvicidal efficacy. LC50 values for C. tinctorius and N. officinale seed oils were 84.16 and 61.78 mg/ml, respectively, in 24 hours. LC50 value of oils association (50% C. tinctorius: 50% N. officinale) was 47.96 mg/ml.The mixture of seed oils from two plants tested against H. scupense larvae and adult females at a 1:1 ratio showed synergistic interaction. Seed oils tested alone, and the mixture could be used as an alternative solution in the fight against ticks.


Resolution of cross-type optical particle separation.
A real-time, continuous optical particle separation method, termed cross-type optical particle separation, is investigated theoretically and experimentally. The trajectory of a particle subject to cross-type optical particle separation is predicted by solving the particle dynamic equation and compared with experimental data. For various flow velocities and particle sizes, the retention distances are measured where the displacement perpendicular to the fluid flow direction is referred to as the retention distance. The measured retention distances are in good agreement with theoretical predictions. The retention distance increases as the particle size increases due to the radiation force, but decreases as the flow velocity increases since the residence time of a particle in the laser beam decreases with increasing flow velocity. To evaluate the performance of the cross-type optical particle separation method, size-based separation resolution is derived theoretically in terms of the refractive index of the particle and instrumental fluctuations. Furthermore, an expression for the maximum resolution is derived.


Air toxics and the risk of autism spectrum disorder: the results of a population based case-control study in southwestern Pennsylvania.
Autism spectrum disorders (ASD) constitute a major public health problem affecting one in 68 children. There is little understanding of the causes of ASD despite its serious social impact. Air pollution contains many toxicants known to have adverse effects on the fetus. We conducted a population based case-control study in southwestern Pennsylvania to estimate the association between ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30 neurotoxicants. A total of 217 ASD cases born between 2005 and 2009 were recruited from local ASD diagnostic and treatment centers. There were two different control groups: 1) interviewed controls (N = 224) frequency matched by child's year of birth, sex and race with complete residential histories from prior to pregnancy through the child's second birthday, and 2) 5,007 controls generated from a random sample of birth certificates (BC controls) using residence at birth. We used logistic regression analysis comparing higher to first quartile of exposure to estimate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for mother's age, education, race, smoking status, child's year of birth and sex. Comparing fourth to first quartile exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17-3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI = 1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66). There were borderline significant ORs for the BC comparison for methylene chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI = 0.98-2.11, p = 0.064). Living in areas with higher levels of styrene and chromium during pregnancy was associated with increased risk of ASD, with borderline effects for PAHs and methylene chloride. These results are consistent with other studies. It is unclear, however, whether these chemicals are risk factors themselves or if they reflect the effect of a mixture of pollutants. Future work should include improved spatiotemporal estimates of exposure to air toxics, taking into account the dynamic movement of individuals during daily life.


Structural and functional similarities between mitochondrial malate dehydrogenase and L-3-hydroxyacyl CoA dehydrogenase.
Pig heart mitochondrial malate dehydrogenase (EC 220.127.116.11), which has been obtained free of electrophoretic subforms, has been shown to have a molecular weight of 67,000 and to be composed of two polypeptide chains. Comparison of these and other properties, such as amino-acid composition, isoelectric point, and keto-substrate inhibition, with those of (L)-3-hydroxyaeyl CoA dehydrogenase (EC 220.127.116.11), another NAD(+)-dependent dehydrogenase of mitochondrial origin, suggests structural similarities of the type associated with proteins possessing common evolutionary origins. This conclusion is supported by immunological crossreactivity. In view of these observations, the dissimilarity in the stereospecificity of hydrogen transfer from cofactor to substrate catalyzed by the two enzymes is attributed to 180 degrees rotation in the binding orientation of the nicotinamide moiety of the NAD(+), rather than to gross differences in the geometry of the active site of the two enzymes.


Bioactive 6S-styryllactone constituents of Polyalthia parviflora.
Parvistones A-E (1-5), five new styryllactones possessing a rare α,β-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parviflora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure-activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained.


A nucleosome assembly protein-like polypeptide binds to chloroplast group II intron RNA in Chlamydomonas reinhardtii.
In the unicellular green alga Chlamydomonas reinhardtii, the chloroplast-encoded tscA RNA is part of a tripartite group IIB intron, which is involved in trans-splicing of precursor mRNAs. We have used the yeast three-hybrid system to identify chloroplast group II intron RNA-binding proteins, capable of interacting with the tscA RNA. Of 14 candidate cDNAs, 13 encode identical polypeptides with significant homology to members of the nuclear nucleosome assembly protein (NAP) family. The RNA-binding property of the identified polypeptide was demonstrated by electrophoretic mobility shift assays using different domains of the tripartite group II intron as well as further chloroplast transcripts. Because of its binding to chloroplast RNA it was designated as NAP-like (cNAPL). In silico analysis revealed that the derived polypeptide carries a 46 amino acid chloroplast leader peptide, in contrast to nuclear NAPs. The chloroplast localization of cNAPL was demonstrated by laser scanning confocal fluorescence microscopy using different chimeric cGFP fusion proteins. Phylogenetic analysis shows that no homologues of cNAPL and its related nuclear counterparts are present in prokaryotic genomes. These data indicate that the chloroplast protein described here is a novel member of the NAP family and most probably has not been acquired from a prokaryotic endosymbiont.


Minimally Invasive Surgery in Periodontal Regeneration: A Review of the Literature.
New techniques have emerged to achieve periodontal regeneration without the drawbacks associated with conventional flap surgery. Minimally invasive surgery (MIS) is a method of surgical access that minimizes flap reflection and tissue trauma, resulting in maintenance of critical blood supply, stability of the blood clot within the wound site, and less postoperative recession over time. As advancements in materials and techniques are made, MIS in periodontal regeneration continues to evolve. The emergence of a videoscope for use during MIS (VMIS) has improved visual access to surgical sites, facilitating improved defect debridement and root planing. As demonstrated, VMIS has resulted in an actual gain in soft-tissue height up to 3 years postoperatively.


Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α.
Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice. DEX inhibited the neuronal autophagy in the peri-ischemic brain, and increased viability and decreased apoptosis of primary cultured neurons in oxygen-glucose deprivation (OGD) model. DEX induced expression of Bcl-1 and p62, while reduced the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in primary cultured neurons through inhibition of apoptosis and autophagy. Meanwhile, DEX promoted the expression of hypoxia-inducible factor-1α (HIF-1α) both in vivo and in vitro, and 2-Methoxyestradiol (2ME2), an inhibitor of HIF-1α, could reverse DEX-induced autophagic inhibition. In conclusion, our study suggests that post-conditioning with DEX at the beginning of reperfusion protects mouse brain from ischemia-reperfusion injury via inhibition of neuronal autophagy by upregulation of HIF-1α, which provides a potential therapeutic treatment for acute ischemic injury.


The association between oxidative stress-induced galectins and differentiation of human promyelocytic HL-60 cells.
Galectins are multifunctional β-galactoside-binding proteins that are involved in the regulation of cellular stress responses and differentiation. The relationship between these processes is unclear and we report here that galectins display oxidative-stress specific expression patterns in neutrophil-like differentiated HL-60 cells. Three galectins (-1, -3, and -10) are upregulated in response to either menadione or DMSO exposure whereas galectins -9 and -12 exhibited a stimulus-dependent downregulation. Changes in galectin expression are oxidant dependent based on the observations that 1) oxidative stress biomarkers HMOX1 (heme oxygenase-1) and NCF1 (neutrophil cytosolic factor 1, which is also a biomarker of neutrophil differentiation) are elevated in both cases, and 2) the antioxidant N-acetyl-L-cysteine restores basal expression of galectin-3 following oxidant exposure. In addition, our results suggest that the regulation of oxidative stress-sensitive galectins involves DNA hypomethylation mechanisms. Expression of galectin-3 and galectin-12 exhibits an opposite relationship to the expression of HMOX1/NCF1, suggesting a stimulatory and inhibitory role of these galectins in neutrophil-like differentiation of HL-60 cells. We also show that the inhibition of galectins reduces the growth rate of HL-60 cells, and facilitates their neutrophil-like differentiation. Collectively, our findings indicate that the process of cellular differentiation implicates, in part, oxidative stress-sensitive galectins, which further highlights a biological significance of galectin network remodeling in cells.


Hepatitis E Virus-Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing.
Hepatitis E virus (HEV) infection uncommonly causes chronic hepatitis and neurologic disease. We describe a case of genotype 3a HEV meningoencephalitis diagnosed by metagenomic next-generation sequencing, illustrating the power of an unbiased molecular approach to microbial testing and the first reported case of HEV infection presumably acquired through lung transplantation.


Pericardiocentesis adverse event risk factors: a nationwide population-based cohort study.
Echocardiography-guided pericardiocentesis has been the leading procedure for diagnosis and therapy of pericardial effusion. We aimed to identify risk factors for recurrence, complications, and mortality in pericardial effusion patients treated with pericardiocentesis. We identified and collected data from 8,101 patients receiving pericardiocentesis between 1997 and 2010 from the Taiwan National Health Insurance Research Database. A multivariate regression model was used to investigate risk factors for recurrence, complications, and death. There were 8,565 admissions among 8,101 patients. The most common underlying condition was malignancy (41%), especially lung cancer (23%), tuberculosis (9.0%), and acute pericarditis (8.2%). Surgical drainage was required in 12.7% of cases. Recurrence was more likely in patients with malignancy (HR 2.20, p < 0.001), but complications were less likely (OR 0.52, p = 0.003). In-hospital death numbers and complication risks (OR 2.38, p < 0.001; OR 1.27, p = 0.01) were greater in the catheter-related cardiac procedure group than in the other groups. Malignant neoplasms and catheter-based cardiac procedures have become major risk factors for adverse events in patients receiving pericardiocentesis in Taiwan. Malignancy leads to an increase in recurrence and in-hospital mortality but is associated with a lower rate of acute complications. Cardiac catheterization procedures and surgery increase both complications and in-hospital mortality.


Constructive and Destructive Interference in Nonadiabatic Tunneling via Conical Intersections.
As a manifestation of the molecular Aharonov-Bohm effect, tunneling-facilitated dissociation under a conical intersection (CI) requires the inclusion of the geometric phase (GP) to ensure a single-valued adiabatic wave function encircling the CI. In this work, we demonstrate using a simple two-dimensional model that the GP induces destructive interference for vibrational states with even quanta in the coupling mode, but it leads to constructive interference for those with odd quanta. The interference patterns are manifested in tunneling wave functions and clearly affect the tunneling lifetime. It is further shown that the inclusion of the diagonal Born-Oppenheimer correction is necessary for agreement with exact results.


Single Center Experience on Anatomy-and Histopathology-Based Gastric Cancer Molecular Classification.
We analyzed the clinical utility of molecular classification based on anatomical and histological background. The study was conducted on 457 patients treated for gastric cancer with additional information about microsatellite instability status. We divided the patients in three groups of molecular classification based on anatomical and histological background: proximal non-diffused, diffused, and distal non-diffused groups. These groups varied in terms of clinical and pathological factors as well as survival rates. The molecular classification based on anatomical and histological data seems to be a useful tool in a simple classification of gastric cancer.


Depletion of Arabidopsis SC35 and SC35-like serine/arginine-rich proteins affects the transcription and splicing of a subset of genes.
Serine/arginine-rich (SR) proteins are important splicing factors which play significant roles in spliceosome assembly and splicing regulation. However, little is known regarding their biological functions in plants. Here, we analyzed the phenotypes of mutants upon depleting different subfamilies of Arabidopsis SR proteins. We found that loss of the functions of SC35 and SC35-like (SCL) proteins cause pleiotropic changes in plant morphology and development, including serrated leaves, late flowering, shorter roots and abnormal silique phyllotaxy. Using RNA-seq, we found that SC35 and SCL proteins play roles in the pre-mRNA splicing. Motif analysis revealed that SC35 and SCL proteins preferentially bind to a specific RNA sequence containing the AGAAGA motif. In addition, the transcriptions of a subset of genes are affected by the deletion of SC35 and SCL proteins which interact with NRPB4, a specific subunit of RNA polymerase II. The splicing of FLOWERING LOCUS C (FLC) intron1 and transcription of FLC were significantly regulated by SC35 and SCL proteins to control Arabidopsis flowering. Therefore, our findings provide mechanistic insight into the functions of plant SC35 and SCL proteins in the regulation of splicing and transcription in a direct or indirect manner to maintain the proper expression of genes and development.


Timing of tracheotomy in mechanically ventilated critically ill morbidly obese patients.
Background. The optimal timing of tracheotomy and its impact on weaning from mechanical ventilation in critically ill morbidly obese patients remain controversial. Methods. We conducted a retrospective chart review of morbidly obese subjects (BMI ≥ 40 kg/m(2) or BMI ≥ 35 kg/m(2) and one or more comorbid conditions) who underwent a tracheotomy between July 2008 and June 2013 at a medical intensive care unit (ICU). Clinical characteristics, rates of nosocomial pneumonia (NP), weaning from mechanical ventilation (MV), and mortality rates were analyzed. Results. A total of 102 subjects (42 men and 60 women) were included; their mean age and BMI were 56.3 ± 15.1 years and 53.3 ± 13.6 kg/m(2), respectively. There was no difference in the rate of NP between groups stratified by successful weaning from MV (P = 0.43). Mortality was significantly higher in those who failed to wean (P = 0.02). A cutoff value of 9 days for the time to tracheotomy provided the best balanced sensitivity (72%) and specificity (59.8%) for predicting NP onset. Rates of NP and total duration of MV were significantly higher in those who had tracheostomy ≥ 9 days (P = 0.004 and P = 0.002, resp.). Conclusions. The study suggests that tracheotomy in morbidly obese subjects performed within the first 9 days may reduce MV and decrease NP but may not affect hospital mortality.


Clostridium septicum Sepsis and Colon Carcinoma: Report of 4 Cases.
An association exists between colon carcinoma and Clostridium septicum infection, especially bacteremia. We reviewed retrospectively all positive blood cultures for this organism at a 300-bed general hospital over 4 years. Four of 15 cases were associated with concurrent colon carcinoma. C. septicum infection was the presenting feature of previously undiagnosed large bowel malignancy in three patients. We report this small case series to alert clinicians to the diverse spectrum and diagnostic difficulties of this rare, potentially catastrophic association. Although commonly associated with necrotizing skin or soft tissue infections, this bacterium can present with nonspecific or atypical symptoms. All patients with positive blood cultures for C. septicum, even without clinical suspicion of large bowel malignancy, should undergo colonoscopy to evaluate for colon carcinoma.


Mutational analysis of the terminal protein Tpg of Streptomyces chromosomes: identification of the deoxynucleotidylation site.
The linear chromosomes and linear plasmids of Streptomyces are capped by terminal proteins (TPs) covalently bound to the 5' ends of the DNA. The TPs serve as primers for DNA synthesis that patches in the single-stranded gaps at the telomeres resulting from the bi-directional replication ('end patching'). Typical Streptomyces TPs, designated Tpgs, are conserved in sequence and size (about 185 amino acids), and contain a predicted helix-turn-helix domain and a functional nuclear localization signal. The Tpg-encoding gene (tpg) is often accompanied by an upstream gene tap that encodes an essential telomere-associating protein. Five lone tpg variants (not accompanied by tap) from various Streptomyces species were tested, and three were found to be pseudogenes. The lone tpg variant on the SLP2 plasmid, although functional, still requires the presence of tap on the chromosome for end patching. Using a combination of in vitro deoxynucleotidylation, physical localization, and genetic analysis, we identified the threonine at position 114 (T114) in Tpg of Streptomyces lividans chromosome as the deoxynucleotidylated site. Interestingly, T114 could be substituted by a serine without destroying the priming activity of Tpg in vitro and in vivo. Such T114S substitution is seen in and a number of pseudogenes as well as functional Tpgs. T114 lies in a predicted coil flanked by two short helixes in a highly hydrophilic region. The location and structural arrangement of the deoxynucleotidylated site in Tpg is similar to those in the TPs of phage ø 29 and adenoviruses. However, these TPs are distinct in their sequences and sizes, indicating that they have evolved independently during evolution. Using naturally occurring and artificially created tpg variants, we further identified several amino acid residues in the N-terminus and the helix-turn-helix domain that were important for functionality.


Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype.
We have shown earlier that low concentrations of ouabain that do not perturb the ionic milieu can initiate proliferation of vascular smooth muscle cells (VSMCs) in the synthetic phenotype from three different species: canine, rodent, and human. This effect occurs by activation of Src and the epidermal growth factor receptor (EGFR), and thus supports the concept of an additional, nonionic, transducing function of the Na pump. The present study presents data suggesting that such activation occurs through specific Na pump sites localized to the caveolae, and subsequent interactions with selected signaling proteins resident within the same membrane microdomain. Our data show that at rest, 30% of the total number of Na pumps are concentrated within the caveolae. When the various VSMCs were treated with proliferating concentrations of ouabain, the key protein content in isolated caveolae was increased. However, the recruited proteins were different between the different tissues. Thus ouabain activated the recruitment of both the Na pump alpha1-subunit and EGFR in the caveolae from rat A7r5 cells, whereas in both human and canine cells, ouabain activated the recruitment of Src, with the caveolar content of the other proteins remaining constant. These data demonstrate that ouabain interacts with the alpha1-subunit of the Na pump that resides within the caveolar domain, and such interaction selectively recruits signal transducing proteins to this microdomain resulting in their activation, which is necessary for the initiation of the proliferative cascade.


Genetic status determines 18 F-FDG uptake in pheochromocytoma/paraganglioma.
Although few studies have demonstrated utility of 18 F- fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomography (18 F-FDG PET/CT) in benign pheochromocytoma/paragangliomas (PCC/PGLs), there limited data on factors predicting the FDG uptake in PCC/PGL. The study was conducted at a tertiary health care centre. In addition to the routine investigations, all patients (n = 96) with PCC/PGL were evaluated with 18 F-FDGPET/CT and majority (n = 78) underwent 131 I-metaiodobenzyl guanidine (131 I-MIBG) scintigraphy. Forty-three patients also underwent testing for germline mutations in five PCC/PGL susceptibility genes (VHL, RET, SDHB, SDHC and SDHD) and all patients were evaluated clinically for neurofibromatosis-1. The study included 96 patients with PCC/PGL(82 benign and 14 malignant). FDGSUVmax was significantly higher for malignant than benign PCC/PGL(P = 0.009) and for extra-adrenal PGL than adrenal PCC (P = 0.017). In subgroup analysis, metanephrine-secreting PCC and non-secretory PCC had significantly lower FDG SUVmax than normetanephrine-secreting PCC (P = 0.017, P = 0.038 respectively), normetanephrine-secreting-sympathetic PGL (P = 0.008, P = 0.019 respectively) and non-secretory sympathetic PGL (P = 0.003, P = 0.009 respectively). Patients with mutations in cluster 1 genes (n = 14) had significantly higher FDG SUVmax than those with mutations in cluster 2 genes (n = 4) (P = 0.04). Sensitivities of 131 I-MIBG and 18 F-FDG PET/CTwere 77.78% and 100% for cluster 1 genes-related PCC/PGL whereas they were 100% and 50% for cluster 2 genes-related PCC/PGL, respectively. Multivariate regression analysis of mutation positive patients identified genetic status as the only independent predictor of FDG SUVmax. The study suggests that the underlying genetic status determines FDG uptake in PCC/PGL and not location, secretory status or malignancy.


AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3/NF-κB axis.
Multiple studies have shown that protein kinase Bβ (AKT2) is involved in the development and progression of ovarian cancer, however, its precise role remains unclear. Here we explored the underlying molecular mechanisms how AKT2 promotes ovarian cancer progression. We examined the effects of AKT2 in vitro in two ovarian cancer cell lines (SKOV3 and HEY), and in vivo by metastasis assay in nude mice. The migration and invasion ability of SKOV3 and HEY cells was determined by transwell assay. Overexpression and knockdown (with shRNA) experiments were carried out to unravel the underlying signaling mechanisms induced by AKT2. Overexpression of AKT2 led to increased expression of pyruvate kinase (PKM2) in ovarian cancer cells and in lung metastatic foci from nude mice. Elevated AKT2/PKM2 expression induced cell migration and invasion in vitro, as well as lung metastasis in vivo; silencing AKT2 blocked these effects. Meanwhile, PKM2 overexpression was unable to increase AKT2 expression. The expressions of p-PI3K, p-AKT2, and PKM2 were increased when stimulated by epidermal growth factor (EGF); however, these expressions were blocked when inhibited the PI3K by LY294002. STAT3 expression was elevated and NF-κB p65 nuclear translocation was activated both in vitro and in vivo when either AKT2 or PKM2 was overexpressed; and these effects were inhibited when silencing AKT2 expression. Taken together, AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated elevation of STAT3 expression and NF-κB activation. In conclusion, we highlight a novel mechanism of the AKT2-PKM2-STAT3/NF-κB axis in the regulation of ovarian cancer progression, and our work suggested that both AKT2 and PKM2 may be potential targets for the treatment of ovarian cancer.


Joint sounds in complete denture wearers. Literature review.
Long-term denture wearers can present with prosthesis instability, reduced occlusal vertical dimension and incorrect positioning of the jaw. This can lead to muscular changes and joint vibration. This study presents the main considerations related to joint vibrations in partially or totally edentulous patients. Occlusal treatment improves the disc-condyle relationship in the mandibular fossa. Furthermore, a detailed clinical exam and anamnesis must be performed to identify the dysfunction and its etiology, so that appropriate treatment can be provided.


Exogenous purines induce differential responses in the proximal and distal regions of the possum sphincter of Oddi.
1. The aim of this study was to compare the effect of exogenous ATP and adenosine on spontaneous motility of the proximal and distal regions of the possum sphincter of Oddi (SO). 2. ATP or adenosine (1 microm-1 mm) was applied to distal-SO or proximal-SO muscle rings in organ baths in the absence or presence of tetrodotoxin (TTX) or P1/P2 antagonists. 3. Both ATP and adenosine altered spontaneous activity, predominantly in proximal-SO rings. 4. Exogenous ATP induced a bi-phasic response consisting of a brief TTX-sensitive excitatory component, and a longer-lasting TTX-insensitive inhibitory component. 5. The excitatory ATP response likely involves P2X receptors, whereas the late inhibitory response likely involves P2Y receptors. 6. Exogenous adenosine decreased spontaneous SO activity, via a TTX-insensitive mechanism. 7. Exogenous purines modulate SO motility, acting primarily in the proximal region of the SO, via neural and non-neural mechanisms and multiple purine receptor subtypes.


[Bayesian and RFLP linkage analysis on a DMD family].
Three methods were applied to estimate the carrier risk of the daughter of an obligate carrier of the Duchenne gene in a pedigree of Duchenne muscular dystrophy (DMD). According to Mendel's law of segregation, the daughter (III-3) of the obligate carrier (II-2) has a 50% chance of being a carrier. III-3 is also found to have a normal value in a carrier test, creatine phosphate kinase (CPK), and so the Bayesian analysis in risk estimation shows that the posterior probability that she is a carrier (25%). The restriction fragment length polymorphism (RFLP) linkage analysis indicates that the probability that III-3 is a carrier less than 5%. This result can be included in the Bayesian analysis to give an even lower risk of less than 2%. Our study demonstrates that the best result of carrier risk estimation can be obtained by a simultaneous application of Mendel's law, RFLP linkage analysis and the Bayesian analysis.


No differences in cycling efficiency between world-class and recreational cyclists.
The aim of this experiment was to compare the efficiency of elite cyclists with that of trained and recreational cyclists. Male subjects (N = 69) performed an incremental exercise test to exhaustion on an electrically braked cycle ergometer. Cadence was maintained between 80 - 90 rpm. Energy expenditure was estimated from measures of oxygen uptake (VO (2)) and carbon dioxide production (VCO(2)) using stoichiometric equations. Subjects (age 26 +/- 7 yr, body mass 74.0 +/- 6.3 kg, Wpeak 359 +/- 40 W and VO(2)peak 62.3 +/- 7.0 mL/kg/min) were divided into 3 groups on the basis of their VO (2)peak (< 60.0 (Low, N = 26), 60 - 70 (Med, N = 27) and > 70 (High, N = 16) mL/kg/min). All data are mean +/- SE. Despite the wide range in aerobic capacities gross efficiency (GE) at 165 W (GE (165)), GE at the same relative intensity (GE (final)), delta efficiency (DE) and economy (EC) were similar between all groups. Mean GE (165) was 18.6 +/- 0.3 %, 18.8 +/- 0.4 % and 17.9 +/- 0.3 % while mean DE was 22.4 +/- 0.4 %, 21.6 +/- 0.4 % and 21.2 +/- 0.5 % (for Low, Medium and High, respectively). There was no correlation between GE (165), GE (final), DE or EC and VO(2)peak. Based on these data, we conclude that there are no differences in efficiency and economy between elite cyclists and recreational level cyclists.


The Frequency of Staphylococcus aureus Isolated from Endocervix of Infertile Women in Northwest Iran.
Infertility is one of the major social issues. Due to the asymptomatic cervical infection associated with Staphylococcus aureus (S. aureus), the majority of patients remain undiagnosed. The present study intended to assess the frequency of S. aureus isolated from infertile women's endocervix in northwest Iran. In a descriptive cross sectional study, specimens were randomly collected during vagina examination using a sterile speculum and swabbing. After performance of antibiotic susceptibility testing, polymerase chain reaction (PCR) was used to identify methicillin-resistance S. aureus (MRSA) and toxic shock syndrome toxin-1 (TSST-1). About 26 (26%) and 9 (9%) women's urogenital tracts were colonized by S. aureus and Candida spp., respectively, of which three (11.5%) patients were infected with fungi and S. aureus, simultaneously. Antibiotic susceptibility results showed high activity of vancomycin and co-trimoxazole on isolates. Regarding PCR results, mecA sequences were detected in 7 (26.9%) strains, whilst the tst gene encoding TSST-1 was not detected in any of clinical strains. The prevalence of S. aureus was very high in infertile women. Therefore, it demands all patients undergoing infertility treatment to be investigated thoroughly for this type of infection.


[Canavan disease or N-acetyl aspartic aciduria: a case report].
Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive leukodystrophy characterized by spongy degeneration of brain. The disease is an inborn error of metabolism caused by aspartoacylase deficiency resulting from accumulation of N-acetyl aspartic acid in the brain. The authors report a case in a 10-month-old boy who presented with developmental delay and megalencephaly noticeable after 4 months of age. Magnetic resonance imaging of the brain showed diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed by nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry.


Separation of Short Single- and Double-Stranded DNA Based on Their Adsorption Kinetics Difference on Graphene Oxide.
Separation of short single- and double-stranded DNA typically requires gel electrophoresis followed by DNA extraction, which is a time consuming process. Graphene oxide adsorbs single-stranded DNA more quickly than double-stranded ones, allowing for selective removal of the former with a simple mixing and centrifugation operation. The effect of DNA length and salt on adsorption selectivity has been characterized and its application in DNA melting curve measurement has been demonstrated.


[Expression and function of laminin receptor in laryngeal squamous cell carcinoma].
To investigate the role of 67 000 laminin receptor (LN-R) in the processes of invasion and metastasis of laryngeal squamous cell carcinoma. Expression of 67 000 LN-R mRNA in 20 cases with laryngeal squamous cell carcinomas and corresponding normal tissues was determined by RT-PCR, and the relationship between its expression level and patients' clinicopathological features was analyzed. Expression of 67 000 LN-R on the surface of AMC-HN-8 laryngeal carcinoma cells was examined by flow cytometry. The effect of 67 000 LN-R monoclonal antibody (MLuC5) on the adhesive and invasive abilities was observed by adhesion test and Boyden chamber invasiveness test in vitro. The expression level of 67 000 LN-R mRNA in human laryngeal squamous cell carcinoma was significantly higher than that in normal tissues (P < 0.05). The expression level of 67 000 LN-R mRNA in laryngeal squamous cell carcinomas with cervical lymph node metastases was higher than in those without cervical lymph node metastases (P < 0.05). There was a significant negative correlation between the expression level of 67 000 LN-R mRNA and the degree of tumor differentiation, the level being higher in poorly differentiated tumors (P < 0.05). Flow cytometry showed that (80.9 +/- 0.9)% of AMC-HN-8 cells expressed 67 000 LN-R. MLuC5 inhibited the adhesion of AMC-HN-8 cells on LN, and after treated with MLuC5 for 60 and 120 minutes, the adhesion inhibition rate was 57.1% and 63.2%, respectively. The invasive ability to artificial basement membrane was reduced by MLuC5. Laryngeal carcinoma overexpressing 67 000 LN-R has stronger invasiveness, and 67 000 LN-R monoclonal antibody may contribute to prevent metastasis of laryngeal carcinoma.


Pharmacokinetic interaction between modified Atkins diet and antiepileptic drugs in adults with drug-resistant epilepsy.
The aim was to examine the influence of modified Atkins diet on serum concentration of antiepileptic drugs (AEDs). Prospective data from 63 adult patients with either focal or generalized drug-resistant epilepsy recruited to 12-week dietary treatment as add-on to AEDs are analyzed. AED serum concentrations, ketones, glucose, and hemoglobin A1c were measured before and after the dietary intervention. Paired t test was used and Spearman correlation coefficient, r, was estimated. Mean age was 37 years (range 16-65 years). Mean serum concentrations of carbamazepine, clobazam, and valproate were significantly reduced after 4 and 12 weeks of the diet period (<.001 ≤ P ≤ .02). Levels of lacosamide, lamotrigine, and topiramate were less reduced (.02 ≤ P ≤ .08), whereas the serum concentrations of oxcarbazepine, zonisamide, and levetiracetam were unchanged (.06 ≤ P ≤ .90). The largest reduction in serum concentration was found for clobazam: mean reduction after 12 weeks was 1.5 μmol/L (34%). Percent change in serum concentration after 4 and 12 weeks of all drugs analyzed was -10.5% (95% confidence interval [CI] -14.1 to -6.8; n = 60; P < .001) and -13.5% (95% CI -18.8 to -8.3; n = 56; P < .001), respectively. Percent change in serum concentration of AEDs was not significantly correlated to percent change in seizure frequency after 12 weeks of dietary treatment (r = .14, P = .33, n = 53) but negatively correlated to urine ketosis (r = -.43; P = .003; n = 46). A reduction in AED serum concentrations may counteract a seizure-reducing effect of the diet, and in patients without such an effect, it may cause seizure aggravation. Thus, we recommend that clinicians who are treating patients with ketogenic diets monitor serum concentrations of the concomitant AEDs.


In vitro dissociation of self-assembly of three chaperonin 60s: the role of ATP.
A comparative study has investigated the in vitro dissociation and self-assembly of chaperonin 60 14-mers isolated from E. coli (GroEL), yeast mitochondria and pea chloroplasts. In all cases Mg2+ inhibits, and low temperature stimulates, the urea-induced dissociation. ATP or ADP in the presence of Mg2+ enhance the dissociation of the chaperonins. Re-assembly of the 14-mers from their monomers shows different efficiencies between the three proteins. In all cases, however, self-assembly is stimulated by Mg-adenine nucleotides. Surprisingly, effective self-assembly of GroEL is promoted by 20% glycerol in the absence of ATP. The role of Mg-adenine nucleotides in the dissociation and assembly of the chaperonins is discussed.