A class experiment in clinical pharmacology using beta-adrenoceptor antagonist drugs.
Cardiac beta-adrenoceptor blocking activity was evaluated in a between-subject study carried out as a class experiment with pre-clinical medical students participating in a practical pharmacology course. From each of 10 groups of students, three healthy male volunteers, took oral propranolol 80 mg, pindolol 10 mg or placebo, according to a double-blind randomised protocol. Pre-treatment, and 45-60 min (1 h) and 105-120 min (2 h) post-treatment heart rate (HR) was determined electrocardiographically in the last 15 s during periods of rest (sitting for 5 min), isometric exercise (applying a standardized hand grip to a rolled sphygmomanometer cuff to elevate pressure from 50 to 150 mm Hg; 2 min) and dynamic exercise (bicycle ergometry with a load of 150 W for 3 min). Reductions from pre-treatment HR yielded statistically significant differences during exercise (isometric and dynamic) between all corresponding changes on placebo and active drugs (P less than 0.05-0.01), except with the 1 h post-propranolol hand grip HR. At rest, only the difference between 2 h HR changes on placebo and propranolol achieved statistical significance (P = 0.05); presumably, the partial agonist activity of pindolol overcame any minimal HR slowing liable to occur at rest. Cardiac beta-adrenoceptor blocking activity as judged by reductions in HR from pretreatment values, was more evident during cycling than during hand grip; and during hand grip than at rest.


Twenty-five years.
Having returned to Australia from the United Kingdom in late 1979, it has been my privilege to witness first-hand the quite dramatic changes in Sexual Health Medicine which have taken place during the final 25 years of my professional life. In this article I give a snapshot of my early experiences at the Melbourne Communicable Diseases Centre, highlighting some of the deficiencies that needed urgent attention. I wish I could say that this picture was an exaggeration to make the article more interesting but unfortunately that is not the case. I also attempt to examine some of the factors that brought about the much-needed improvements, especially the effect human immunodeficiency virus had on sexual health practice. It is impossible to mention all the individuals most involved in initiating change, but I have mentioned a couple of names, only because of close personal knowledge about their contribution.


A domino enyne/IMDA approach to the core structure of (-) vinigrol.
We report here an enantioselective formal synthesis of vinigrol involving a 1-2-3 strategy: one pot and two reactions with the formation of three rings leading to the core structure of vinigrol from its stereochemically well-defined acyclic precursor.


Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2.
Increased activity of the lysine methyltransferase NSD2 driven by translocation and activating mutations is associated with multiple myeloma and acute lymphoblastic leukemia, but no NSD2-targeting chemical probe has been reported to date. Here, we present the first antagonists that block the protein-protein interaction between the N-terminal PWWP domain of NSD2 and H3K36me2. Using virtual screening and experimental validation, we identified the small-molecule antagonist 3f, which binds to the NSD2-PWWP1 domain with a Kd of 3.4 μM and abrogates histone H3K36me2 binding to the PWWP1 domain in cells. This study establishes an alternative approach to targeting NSD2 and provides a small-molecule antagonist that can be further optimized into a chemical probe to better understand the cellular function of this protein.


Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study.
Laboratories worldwide carry out MIC/disc diffusion (DD) tests using various national methods, often published by local organizations. Potentially different results may complicate drug development or registration between the US methods and those used in the European Union (EU). This study uses a new des-F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized antimicrobial susceptibility testing methods. Investigators in France, Germany, Spain, Sweden and the UK tested two bacterial collections designated, challenge (CC; n = 330) containing quinolone-resistant strains and national (NC; n = 540) that were recent clinical isolates (2000-2001). Results were compared with values derived from the National Committee for Clinical Laboratory Standards (NCCLS) methods, carried out by the US coordinating site. Discords (greater than four-fold) between MIC method results were repeated. Results were analysed for variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by regression statistics. Ciprofloxacin was used as the control quinolone agent. CC and NC testing compliance averaged 98.4% and 86.4% among participating centres, respectively, and correlation (r) of the national method to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96) and UK (0.95). CC produced MIC results that were identical to the NCCLS (Spain) to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK). Similar patterns were observed for the NC (r = 0.93-0.98), and all nations had >99% of results within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values. MIC results from four national methods were slightly elevated compared to the NCCLS result (average 0.2 x log(2)). Control ciprofloxacin MIC and DD test results showed similar patterns. Inter-method garenoxacin susceptibility test results indicate that MIC and zone diameter endpoints derived from five EU methods compare favourably to the NCCLS method results, and generally were identical or a fraction of a log(2) dilution step higher. In contrast, zone diameters for garenoxacin and ciprofloxacin were routinely larger for the EU methods. This unique inter-method 'bridging' experiment allows regulatory agencies to better correlate in vitro testing results derived from procedures that use different national methodologies.


Amorphous Cr2WO6-Modified WO3 Nanowires with a Large Specific Surface Area and Rich Lewis Acid Sites: A Highly Efficient Catalyst for Oxidative Desulfurization.
The oxidative desulfurization (ODS) of fuel oils is of great significance for environmental protection, and the development of efficient ODS heterogeneous catalysts is highly desired. Herein, we have designed and synthesized a novel material of amorphous Cr2WO6-modified WO3 (a-Cr2WO6/WO3) nanowires (3-6 nm) with a large specific surface area of 289.5 m2·g-1 and rich Lewis acid sites. The formation of such a unique nanowire is attributed to the adsorption of Cr3+ cations on non-(001) planes of WO3. In the ODS process, the a-Cr2WO6/WO3 nanowires can efficiently oxidize benzothiophene (BT), dibenzothiophene (DBT), and 4,6-dimethyldibenzothiophene (4,6-DMDBT) to their corresponding sulfones in a quasi-microemulsion reaction system and possess the highest activity (Ea = 55.4 kJ/mol) for DBT: 99.0% of 15,000 ppm DBT with 2600 ppm S can be removed (70 °C, H2O2 as the oxidant). The improvement in ODS activity from most of WO3 catalysts is owing to the sufficient active sites and enhanced adsorption of DBT on the basis of structural features of a-Cr2WO6/WO3 nanowires. Combined with free radical capture experiments, a possible ODS mechanism of W(O2) peroxotungstate route based on surface -OH groups is reasonably proposed. Moreover, the a-Cr2WO6/WO3 nanowires have good stability and can be synthesized on a large scale, suggesting its potential applications as an efficient heterogeneous catalyst.


[Prostatic urethral lift: A novel minimally invasive treatment for benign prostatic hyperplasia].
Benign prostatic hyperplasia (BPH) and BPH-induced lower urinary tract symptoms (LUTS) are common factors influencing the quality of life (QOL) of elderly males. In case of undesirable or adverse effects of medication, many BPH patients seek surgical treatment. Transurethral resection of the prostate (TURP), though evidently effective for BPH, fails to preserve the sexual function and therefore reduces the QOL of the patients. Moreover, some elderly patients with comorbidities may be unfit for TURP. Prostatic urethral lift (PUL) is a newly developed surgical procedure for the treatment of LUTS secondary to BPH. With the advantages of minimal invasiveness, low rate of peri- and post-operative complications, and maximal preservation of patients' erectile and ejaculatory functions, PUL is winning more and more attention from the clinicians and patients.


Variational, geometric, and statistical methods for modeling brain anatomy and function.
We survey the recent activities of the Odyssée Laboratory in the area of the application of mathematics to the design of models for studying brain anatomy and function. We start with the problem of reconstructing sources in MEG and EEG, and discuss the variational approach we have developed for solving these inverse problems. This motivates the need for geometric models of the head. We present a method for automatically and accurately extracting surface meshes of several tissues of the head from anatomical magnetic resonance (MR) images. Anatomical connectivity can be extracted from diffusion tensor magnetic resonance images but, in the current state of the technology, it must be preceded by a robust estimation and regularization stage. We discuss our work based on variational principles and show how the results can be used to track fibers in the white matter (WM) as geodesics in some Riemannian space. We then go to the statistical modeling of functional magnetic resonance imaging (fMRI) signals from the viewpoint of their decomposition in a pseudo-deterministic and stochastic part that we then use to perform clustering of voxels in a way that is inspired by the theory of support vector machines and in a way that is grounded in information theory. Multimodal image matching is discussed next in the framework of image statistics and partial differential equations (PDEs) with an eye on registering fMRI to the anatomy. The paper ends with a discussion of a new theory of random shapes that may prove useful in building anatomical and functional atlases.


[Anti-proliferation and chemo-sensitization effects of apigenin on human lung cancer cells].
To investigate the antitumor effect of apigenin on human lung cancer cells. The anti-proliferation and sensitization effects of apigenin on human lung cancer cells was accessed by counting cells after Trypan blue staining and MTS assay. (1) Apigenin significantly suppressed the proliferation of four types of human lung cancer cells (A549:P=0.041, H460:P=0.050, LTEP-a2:P=0.039, H292:P=0.016); (2) Apigenin significantly increased the susceptibility of human lung cancer cells to antitumor drugs (P<0.05 or P<0.01) in a synergistic way (almost all of the combination index values are less than 1). Apigenin widely inhibits cell proliferation of various lung cancer cell lines in a dose-dependent manner and the combination treatment of apigenin and antitumor drugs is very effective in human lung cancer cells, and Nrf2-ARE pathway may contribute to the mechanism.


Cerebral Venous Thrombosis Mimicking Acute Ischemic Stroke in the Emergency Assessment of Thrombolysis Eligibility: Learning from a Misdiagnosed Case.
Cerebral venous thrombosis (CVT) occasionally presents with acute focal neurologic signs, mimicking arterial stroke syndrome. Diagnosing CVT in the setting of thrombolysis eligibility evaluation is challenging. We reported this case to discuss the promptly recognizing CVT in the setting of thrombolysis eligibility evaluation, and review the literature of thrombolytic therapy in CVT patients. A 57-year-old man presented with acute-onset right upper extremity monoparesis, right facial palsy, and aphasia. He underwent emergent thrombolysis with recombinant tissue plasminogen activator according to American Stroke Association guidelines. Subsequently, CVT was identified on multiphase computed tomography (CT) angiography. His symptoms initially improved but subsequently deteriorated because of intracranial hemorrhage. Cryoprecipitate and tranexamic acid were immediately administered. Anticoagulation was started 24 hours after the onset of hemorrhage. His modified Rankin Scale score was 4 at 120 days after the hemorrhage. Patients with CVT have a higher risk of thrombolysis-related intracranial hemorrhage than other stroke mimics. A greater focus on noncontrast brain CT and the venous phase of CT angiography help identifying this stroke mimic before thrombolysis.


Iron and infection in infancy--report on field studies in Papua New Guinea: 1. Demographic description and pilot surveys.
Madang district was selected for a longitudinal study of the effects of iron prophylaxis on infectious morbidity in infancy and the topography, climate, domicile, ethnology, demography, disease patterns, nutrition and health services of the district are described. The area has a tropical, humid climate and a mixed economy. Pneumonia was the main killing disease at all ages, and malaria was endemic. A base hospital and well organized maternal and child health services ensured that morbidity surveillance would be optimal. Pilot haematological surveys confirmed a high incidence of anaemia in infancy. Mean haemoglobin between nine and 52 weeks of age was 8.6 g/dl. Results suggested that malaria and iron deficiency were important causes of this anaemia.


Artificial neural network-based method of screening heart murmurs in children.
Early recognition of heart disease is an important goal in pediatrics. Efforts in developing an inexpensive screening device that can assist in the differentiation between innocent and pathological heart murmurs have met with limited success. Artificial neural networks (ANNs) are valuable tools used in complex pattern recognition and classification tasks. The aim of the present study was to train an ANN to distinguish between innocent and pathological murmurs effectively. Using an electronic stethoscope, heart sounds were recorded from 69 patients (37 pathological and 32 innocent murmurs). Sound samples were processed using digital signal analysis and fed into a custom ANN. With optimal settings, sensitivities and specificities of 100% were obtained on the data collected with the ANN classification system developed. For future unknowns, our results suggest the generalization would improve with better representation of all classes in the training data. We demonstrated that ANNs show significant potential in their use as an accurate diagnostic tool for the classification of heart sound data into innocent and pathological classes. This technology offers great promise for the development of a device for high-volume screening of children for heart disease.


[The clinical and pathogenetic types of gastroesophageal reflux disease: risk factors and predictors].
To study the clinical and pathogenetic types of gastroesophageal reflux disease (GERD) in terms of different types of reflux into the esophagus, their risk factors and predictors. The clinical, morphological, motor tonic characteristics of the esophagogastroduodenal area, the phenotypic and visceral signs of existing undifferentiated connective tissue dysplasias (UDCTD), and the suprasegmental and segmental autonomic apparatus were studied in detail in 124 patients with GERD. Two clinical and pathogenetic types of GERD associated with the predominance of gastroesophageal or duodenogastroesophageal refluxes (GER and DGER) are identified. The type of the disease running in the predominance of GER develops in subjects with the high rate of visceral stigmas of UDCTD--cardiac failure and hiatal hernias, sympathetic autonomic tone in the digestive system. The feeding preference of piquant and spicy dishes and spices serves to realize the predictors of this type. The DGER-associated type develops in subjects with a concurrence of sympathetic and parasympathetic total autonomic tones in the digestive system in the presence of preexisting biliary tract diseases, including abnormalities in the structure of the gallbladder as visceral signs of UDCTD and it is realized in the feeding preference of high-calorie dishes. It is promising to study the autonomic status and the signs of UDCTD as structural and functional predictors of GERD and its types for the prediction of the disease, professional orientation, and the acquisition of eating behavior primarily in young people.


Effects of morphactin and other auxin transport inhibitors on soybean senescence and pod development.
Because triiodobenzoic acid increases pod number, albeit variably, in soybean (Glycine max), we tested other auxin-transport inhibitors. Morphactins, especially methylchlorflurenol (MCF), were found to be very active (optimal concentration 10 micromolar) when sprayed onto the foliage. Applications at 1 week after the start of flowering were most effective, producing a 40% increase in pod number with little inhibition (12%) of stem elongation. MCF increased the number of pods initiated (reaching 1 cm length) at least partially by prolonging the initiation period, while pod abortion (failure of pods > 1 cm long) remained low. Generally, MCF did not increase seed yield (dry weight/plant); more, but smaller seeds, were formed by the treated plants. The promotive effect of MCF on pod initiation seems to be independent of its inhibition of stem elongation, which is insignificant at 10 micromolar. MCF delayed pod maturation by 3 to 4 days, while foliar yellowing, blade abscission, and petiole abscission were retarded by 2, 4, and 2 days, respectively. MCF has only a small effect on senescence and that could be indirect, due to a delay in pod development. Other auxin-transport inhibitors tested, including N-1-naphthylphthalamic acid, produced little or no increase in pod number; however, 0.1 millimolar 5-[2'-carboxyphenyl]-3-phenylpyrazole caused a 27% increase. These results implicate auxin as a potential regulator of pod development, and they show that soybean seed yield is not simply sink limited.


Local Nordic tobacco interests collaborated with multinational companies to maintain a united front and undermine tobacco control policies.
To analyse how local tobacco companies in the Nordic countries, individually and through National Manufacturers' Associations, cooperated with British American Tobacco and Philip Morris in denying the health hazards of smoking and undermining tobacco control. Analysis of tobacco control policies in the Nordic countries and tobacco industry documents. Nordic countries were early adopters of tobacco control policies. The multinational tobacco companies recognised this fact and mobilised to oppose these policies, in part because of fear that they would set unfavourable precedents. Since at least 1972, the Nordic tobacco companies were well informed about and willing to participate in the multinational companies activities to obscure the health dangers of smoking and secondhand smoke and to oppose tobacco control policies. Cooperation between multinational companies, Nordic national manufacturer associations and local companies ensured a united front on smoking and health issues in the Nordic area that was consistent with the positions that the multinational companies were taking. This cooperation delayed smoke-free laws and undermined other tobacco control measures. Local tobacco companies worked with multinational companies to undermine tobacco control in distant and small Nordic markets because of concern that pioneering policies initiated in Nordic countries would spread to bigger market areas. Claims by the local Nordic companies that they were not actively involved with the multinationals are not supported by the facts. These results also demonstrate that the industry appreciates the global importance of both positive and negative public health precedents in tobacco control.


Pleuropulmonary blastoma. A rare childhood malignancy.
Pleuropulmonary blastoma PPB is an extremely rare, intrathoracic neoplasm of early childhood with unfavorable outcome. We present a case of a 4-year-old boy with progressive dyspnea due to tension pneumothorax. After chest tube insertion, the CT scan showed large multilocular cystic lesions containing air and solid areas involving the right lower lobe, and its related pleura. Thoracotomy was carried out, and the cyst was removed with the pleural solid areas. Histopathological examination confirmed the diagnosis of PPB type II. Postoperatively, the patient was scheduled to start chemotherapy in a specialized pediatric oncology center to complete the treatment.


Fermentation of rice-bengal gram dhal blends with whey: changes in phytic acid content and in vitro digestibility of starch and protein.
Whey fermentation of various rice and bengal gram dhal blends prepared by mixing them in different proportions at 35 degrees C for 18 h brought about a significant decline in phytic acid content. Phytic acid content in various blends decreased to the extent of 23 to 36 per cent over the control values. Whey incorporation as well as fermentation improved the starch and protein digestibility (in vitro) of all the rice-bengal gram dhal mixtures. Improvement in starch and protein digestibility is related to the reduction in phytic acid content, as this antinutrient is known to inhibit amylolysis and proteolysis. A significant negative correlation found between phytic acid and digestibility of starch and protein strengthens our findings.


Small pH gradients inhibit cytochrome c oxidase: implications for H+ entry to the binuclear center.
Respiring cytochrome c oxidase proteoliposomes generate internal alkalinity (delta pH) and a membrane potential (delta psi). Valinomycin collapses delta psi, increases delta pH, and slows steady state respiration. If delta pH is heterogeneously expressed trapped probes will underestimate it. Internal pH changes were therefore followed in COV containing two buffer systems of differing pKs. The alkalinization rate at pH 7 was unaffected by adding AMPSO (pK 9.0) to the usual internal HEPES (pK 7.5). At higher pH, AMPSO slowed the approach to steady state. delta pH inhibition is therefore not due to a large alkalinization in a small COV fraction. The O2-reducing center may move protons via a local aqueous phase that is near electrical and pH equilibrium with the phase inside the COV. The dielectric in this membrane region can put the center electrically 'inside' even though it is physically 'outside'.


The Texas collaborative center for hepatocellular cancer: Reducing liver cancer mortality in Texas through coordination, collaboration and advocacy.
Texas has the highest age-adjusted incidence rate of hepatocellular carcinoma (HCC) in the United States. To address cancer prevention and early detection through research, Cancer Prevention and Research Institute of Texas (CPRIT) has funded the Texas Collaborative Center for Hepatocellular Cancer (TeCH) to facilitate liver cancer research, education and advocacy activities. This paper describes the organizational structure, program measures, the actions completed and future plans of TeCH. This center is comprised of several cores and committees including the Administrative Core, Steering Committee, Data and Biospecimen Core, Scientific Committee, Clinical Network Committee, and the Community Outreach Committee. Each core and committee provide its own level of connectivity and necessary research support. We have developed and published a TeCH Framework, a conceptual model designed for improving primary and secondary prevention of HCC. TeCH and its committees facilitate connections and collaborations among HCC researchers and clinicians, healthcare leaders, biotechnology companies and the public to reduce liver cancer mortality in Texas by 2030.


Sensing glucose concentrations at GHz frequencies with a fully embedded Biomicro-electromechanical system (BioMEMS).
The progressive scaling in semiconductor technology allows for advanced miniaturization of intelligent systems like implantable biosensors for low-molecular weight analytes. A most relevant application would be the monitoring of glucose in diabetic patients, since no commercial solution is available yet for the continuous and drift-free monitoring of blood sugar levels. We report on a biosensor chip that operates via the binding competition of glucose and dextran to concanavalin A. The sensor is prepared as a fully embedded micro-electromechanical system and operates at GHz frequencies. Glucose concentrations derive from the assay viscosity as determined by the deflection of a 50 nm TiN actuator beam excited by quasi-electrostatic attraction. The GHz detection scheme does not rely on the resonant oscillation of the actuator and safely operates in fluidic environments. This property favorably combines with additional characteristics-(i) measurement times of less than a second, (ii) usage of biocompatible TiN for bio-milieu exposed parts, and (iii) small volume of less than 1 mm3-to qualify the sensor chip as key component in a continuous glucose monitor for the interstitial tissue.


[Perioperative antibiotic prophylaxis in cancer surgery].
The effectiveness of perioperative antibiotic prophylaxis in reducing surgical site infections has been demonstrated. Its utility is recognized for clean-contaminated procedures and some clean surgeries. Prophylactic antibiotics are used as intended to cover the most common germs in the surgical site; first and second generation cephalosporins are the most used. For optimal prophylaxis, an antibiotic with a targeted spectrum should be administered at sufficiently high concentrations in serum, tissue, and the surgical wound during the time that the incision is open and risk of bacterial contamination. The infusion of the first dose of antimicrobial should begin within 60 min before surgical incision and should be discontinued within 24 h after the end of surgery The prolonged use of antibiotic prophylaxis leads to emergence of bacterial resistance and high costs. The principles of antimicrobial prophylaxis in cancer surgery are the same as those described for general surgery; it is recommended to follow and comply with the standard criteria. In mastectomies and clean head and neck surgery there are specific recommendations that differ from non-cancer surgery. In the case of very extensive surgeries, such as pelvic surgery or bone surgery with reconstruction, extension of antibiotics for 48-72 h should be considered.


Ketamine injection used orally.
Ketamine has been used parenterally for pain unresponsive to opioids, including neuropathic pain, and has also been used as an alternative analgesic agent after surgery. Although oral administration of ketamine has been used for some time as a single dose, it has not been given by this route on a regular basis. The use of ketamine administered orally is described for two patients with severe neuropathic pain who were intolerant of, or whose pain was unrelieved by, more commonly used agents. Pain relief was achieved without significant side effects.


Constitutive activation of MAP kinase kinase (MEK1) is critical and sufficient for the activation of MMP-2.
We investigated the role of MEK1 signaling in MMP-2 activation by use of constitutive active/dominant negative forms of MEK1 and MEK1-specific inhibitor. We found that cell transformation with active forms of MEK1 dramatically increased secretion and proteolytic activation of MMP-2 and subsequently stimulated invasiveness of cells. Contrary, expression of dominant negative form of MEK1 in v-src-transformed cells or in Con A-activated cells resulted in the suppression of the augmented secretion and proteolytic activation of MMP-2. In addition, treatment of v-src-transformed cells with PD98059, a MEK1-specific inhibitor, strongly suppressed the secretion and activation of MMP-2, whereas treatment with wortmannin, a PI3 kinase inhibitor, showed no clear effect on MMP-2 secretion. Taken together, these results strongly suggest that MEK-MAP kinase signaling, but not PI3 kinase signaling, plays a critical role in the activation of MMP-2 secretion and, subsequently, in the invasiveness of v-src-transformed cells.


Assessment of psychological aspects during systemic provocation tests in patients with pseudoallergic drug reactions.
Basic mechanisms of pseudoallergic drug reactions as well as a possible role of the psyche are currently unknown. Examination of psychological status and reactions during diagnostic provocation tests in patients with previous pseudoallergic reactions to drugs. Ten inpatients, admitted for provocation tests, were studied in a double-blind, placebo-controlled setting, with inventories of anxiety and depression being measured at baseline and psychological reactions and symptoms being recorded daily by patients and the attending physician. Patients reported more than twice as many symptoms as the physician, independent of the type of exposure. While the basic psychological profile of the patients was normal, anxiety trait and state values were high during testing, with a significant increase depending on whether the patients thought they had received a drug or a placebo. Similarly, frequency of symptoms was dependent on the patients' perception of the type of exposure. These findings demonstrate a high level of anxiety during systemic provocation tests in patients with previous pseudoallergic drug reactions, raising serious questions as to the diagnostic validity of the routine application of this testing.


[Biologic factors hazardous to health: classification and criteria of exposure assessment].
Occupational biohazards include not only factors that have long been known (viruses, bacteria, fungi, parasites), but also agents exerting allergic and toxic effects, which are directly responsible for the development of various diseases in many occupational groups. Numerous agents of this group (allergens, microbial toxins, pollen allergens and allergens of animal origin) are components of bioacrosols--potential hazards inducing occupational respiratory diseases among farmers and people involved in other occupations. Contrary to the majority of chemical and physical factors, neither commonly approved criteria for assessing exposure to biological factors, nor threshold values and methodological recommendations are as yet available. The lack of these criteria renders it difficult to implement in Poland and in other countries Directive 2000/54/EC on the protection of workers against the risk of occupational exposure to biohazards, issued by the European Community. The Institute of Rural Medicine in Lublin has drafted the proposals for threshold limit values of occupational exposure to bioaerosols associated with plant and animal dusts, including: mesophilic bacteria, Gram-negative bacteria, thermophilic actinomycetes, fungi and bacterial endotoxins. These proposals could be considered as a starting point for developing appropriate facultative standards that would facilitate the practical implementation of the aforesaid Directive. Meantime it is essential to be strict in following the binding concentration limits of the plant and animal dusts in the air.


Spontaneous rupture of a giant hepatic hemangioma. Sequential treatment with preoperative transcatheter arterial embolization and conservative hepatectomy.
Hemangioma is the most common benign tumor of the liver and it is often asymptomatic. Spontaneous rupture of liver hemangiomas is a rare but potentially lethal complication. Emergent hepatic resection has been the treatment of choice but carries high operative morbidity and mortality. Recently, preoperative transcatheter arterial embolization (TAE) has been used successfully for the management of bleeding ruptured liver tumors and non-operative treatment of symptomatic giant liver hemangiomas. We report a case of spontaneous rupture of a giant hepatic hemangioma that presented with thoracic and abdominal pain and shock due to hemoperitoneum. Once proper diagnosis was made the patient was successfully managed by TAE, followed by conservative hepatic resection.


Treatment of Attention-Deficit/Hyperactivity Disorder in Preschool-Age Children: Child and Adolescent Psychiatrists' Adherence to Clinical Practice Guidelines.
To compare child and adolescent psychiatrists' (CAPs) practices in the treatment of preschool children with attention-deficit/hyperactivity disorder (P-ADHD) with published guidelines, and to determine which clinical factors most influence physicians' decisions to initiate pharmacotherapy for P-ADHD. We developed and mailed the Preschool ADHD Treatment Questionnaire (PATQ) to a randomly selected national sample of ∼2200 CAPs trained in the management of ADHD. The PATQ asked CAPs about their approach to clinical management of children ages 4-5 years with ADHD-specifically, how often they recommend parent training in behavior management, medication as a first- or second-line treatment, and which medication they typically choose first. CAPs also rated the perceived importance of 19 different clinical factors in their decision to initiate pharmacotherapy. These 19 factors reflected five child-centered areas of concern: ADHD risk factors, education concerns, social issues (SI), emotional stress, and physical safety (PS). The physicians were asked to rate each factor on a 4-point Likert scale from "not important" to "very important." The final sample consisted of 339 board-certified CAPs. When adherence to the Academy of Child and Adolescent Psychiatry (AACAP) guidelines was defined as initial treatment with behavior management (not medication) and pharmacotherapy specifically with methylphenidate as second-line treatment, only 7.4% of CAPs followed clinical guidelines. Most physicians identified PS as an important or very important factor when initiating pharmacotherapy for P-ADHD (93.4%), followed by educational concerns (EC) (79.9%), emotional stress (69.6%), SI (52.8%), and the presence of risk factors for ADHD (32.7%). The overwhelming majority of CAPs do not follow current AACAP guidelines for treatment of P-ADHD, especially regarding medication initiation and selection. When deciding whether to prescribe medication for P-ADHD, safety and EC were the most important and historical risk factors for ADHD were the least important clinical factors.


Organic osmolytes in methanogenic archaebacteria.
Methanogenic archaebacteria have developed unique ways of dealing with osmotic stress. While several of them have transport systems capable of internalizing betaine, an osmolyte in many eubacteria, in general they have developed de novo synthesis of a novel series of beta-amino acids as compatible solutes. 13C-NMR spectroscopy has been the key tool in elucidating both the identity of these organic osmolytes and in investigating their dynamics.


Integrating themes, evidence gaps, and research needs identified by workshop on iron screening and supplementation in iron-replete pregnant women and young children.
This report addresses the evidence and the uncertainties, knowledge gaps, and research needs identified by participants at the NIH workshop related to iron screening and routine iron supplementation of largely iron-replete pregnant women and young children (6-24 mo) in developed countries. The workshop presentations and panel discussions focused on current understanding and knowledge gaps related to iron homeostasis, measurement of and evidence for iron status, and emerging concerns about supplementing iron-replete members of these vulnerable populations. Four integrating themes emerged across workshop presentations and discussion and centered on 1) physiologic or developmental adaptations of iron homeostasis to pregnancy and early infancy, respectively, and their implications, 2) improvement of the assessment of iron status across the full continuum from iron deficiency anemia to iron deficiency to iron replete to iron excess, 3) the linkage of iron status with health outcomes beyond hematologic outcomes, and 4) the balance of benefit and harm of iron supplementation of iron-replete pregnant women and young children. Research that addresses these themes in the context of the full continuum of iron status is needed to inform approaches to the balancing of benefits and harms of screening and routine supplementation.


Optimizing Pharmacotherapy for Direct Oral Anticoagulants in Older Adults: Strategies for Managing Drug Interactions.
Direct oral anticoagulants (DOACs) have been increasingly used by older adults. Although these medications offer several therapeutic advantages over traditional anticoagulants, such as warfarin, they have limitations. One significant concern associated with DOACs is their potential for drug-drug interactions. These interactions may compromise the safe and effective use of DOACs and can potentially lead to serious adverse events and complications, particularly major bleeding. Polypharmacy is common among older adults with chronic diseases, which can increase the risk of drug-drug interactions with DOACs. The current article discusses the impact and risks of drug-drug interactions with DOACs in the context of older adults and explores ways to improve and manage these interactions through the collaboration of an interprofessional team. [Journal of Gerontological Nursing, 49(9), 7-13.].


Realization of an Optical Thermometer via Structural Confinement and Energy Transfer.
The influence of temperature on a variety of physiological or chemical processes has generated considerable interest, and recently noninvasive lanthanide-incorporated optical thermometers have been considered as promising candidates for monitoring its changes at different scales. Herein, a novel Bi3+-activated Sr3-xGdxGaO4+xF1-x phosphor with tunable color has been constructed by a cooperative cation-anion substitution strategy with to the replacement of [Sr2+-F-] by [Gd3+-O2-]. When x = 0, the sample Sr3GaO4F/Bi3+ possesses a peak wavelength at 438 nm, and this value will shift to 470 nm if x is equal to 1 (Sr2GdGaO5/Bi3+). In addition, photoluminescence tuning from blue to red has been realized successfully by an efficient Bi3+ → Eu3+ energy migration model in Sr2.6Gd0.4GaO4.4F0.6 samples. The specific Bi3+ → Eu3+ energy transfer has been explained by dipole-dipole interactions derived from a model of the Dexter pathway. Intriguingly, the two dopants (a blue signal from Bi3+ and a red signal from Eu3+) possess different thermal responses to increasing temperature. Accordingly, the intensity ratio values are sensitive to the temperature changes. The energy level cross relaxation causes the quenching effect of Bi3+, and the multi-phonon de-excitation mode leads to the thermal quenching of Eu3+. At room temperature (298 K), the determined maximum relative sensitivity (Sr) is 1.27% K-1. Moreover, the absolute sensitivity (Sa) is 0.067 K-1 since the temperature is elevated to 523 K. The collected results are superior to most of the reported optical thermometry materials.


[Long-term follow-up report of multicenter clinical study on childhood renal tumor].
Objective: To find the possibility of establishing multicenter cooperative group in China and to analyze the data and provide evidences for further revision of the protocol for improving the studies on renal tumor. Method: The multicenter renal tumor cooperative group was established under the Chinese Children Cancer Group. The diagnosis and staging criteria, the regulation for surgery, chemotherapy and radiation therapy were included in the protocol for renal tumor studies. Uniform data collection form was sent out to all the centers and collected data back by e-mail. All the cases have to meet the data collection criteria including pathological diagnosis, staging and follow-up. Result: This protocol was administered in 21 pediatric centers, 11 of them sent back on date as requested. Totally 361 cases were recruited and another 19 cases were excluded of the analysis because they did not fit or not registered fully as requested. The age was between 1 to 163 months, median 28 months. A percent of 65.9%(238/361)the patients was diagnosed at the age of younger than 3 years. Male and female ratio was 1.4∶1. After followingup for 24-204 months (medium 57 months), 5 year event-free survival (EFS) was 80.0% for all group, 81.2% (300 cases) for FH, 71.7% (32 cases) for UFH, 68.8% (17 cases) for clear cell, and 60.0% (5 cases) for rhabdoid tumor( χ2=7.795, P=0.099). In FH group, 5 year EFS was 91.7% for stage Ⅰ (93 cases), 78.0% (87 cases) for stage Ⅱ, 78.3% (81 cases) for stage Ⅲ, 77.2% and 50.4% for stage Ⅳ (31 cases) and V (8 cases) (χ2=11.787, P=0.019 ). Totally 177 cases needed radiation therapy based on protocol guideline, but only 97 of them were radiated because of different reasons. Five year EFS for 97 cases radiated and 80 cases not radiated were 83.1% and 64.5% (χ2=9.419, P=0.002 ). Sixty-four cases (17.7%) died of disease progression, relapse and abandonment of treatment. Conclusion: Multi-center cooperative group model for childhood renal tumor is feasible in China. The result is reasonable, but can be improved further. The result is the same between FH stage Ⅱ and Ⅲ. And it may be related to down-staging Ⅲ to Ⅱ or under-therapy for stage Ⅱ. Radiation therapy is important for stage Ⅲ and Ⅳ patients, and to which more attention should be paid. The reliability of data collection should be improved further.


Vasodilatation, not hypotension, improves resistance vessel design during treatment of essential hypertension: a literature survey.
Correction of structural abnormalities in resistance arteries of patients with essential hypertension is a potential treatment goal, in addition to blood pressure reduction. However, available evidence from human as well as from animal studies indicates that antihypertensive therapy is not always accompanied by normalization of resistance vessel structure, despite normalization of blood pressure. Thus, blood pressure is not the only factor determining resistance vessel structure, and experimental studies show that several factors could play a role, including shear stress and hormonal stimulation. To date, there has been no systematic review of the many published papers which have studied the structural effects of antihypertensive therapy, and it is not known which conditions are best able to normalize resistance vessel structure. We have therefore made a survey of the available literature. The survey shows that change in blood pressure in indeed a poor indicator of change in resistance vessel structure. However, it is a remarkably consistent finding that normalization of resistance vessel structure is obtained with therapeutic regimens which reduce blood pressure by vasodilation rather than by lowering cardiac output Thus, to the extent that normalization of resistance vessel structure is deemed a goal of antihypertensive treatment, the survey points towards the importance of considering not only the treatment effect on blood pressure, but also the haemodynamic effects within patients with essential hypertension.


Gene therapy with viral vectors.
A key factor in the success of gene therapy is the development of gene delivery systems that are capable of efficient gene transfer in a broad variety of tissues, without causing any pathogenic effect. Currently, viral vectors based on many different viruses have been developed, and their performance and pathogenicity has been evaluated in animal models. The results of these studies form the basis for the first clinical trials for correcting genetic disorders using retroviral, adenoviral, and adeno-associated viral vectors. Even though the results of these trials are encouraging, vector development is still required to improve and refine future treatment of hereditary disorders.


Complications of free flap transfers for head and neck reconstruction following cancer resection.
The reported success rate of microvascular free flap reconstruction ranges between 95% and 97%. However when complications occur, they must be identified early and managed efficiently because there is a narrow window of opportunity to salvage potential flap failure. While technical advances in instrumentation and magnification have improved overall success rates, the rare complication may prove devastating for the patient, his/her hospital stay, and the optimum rehabilitation. Complications of microvascular free tissue transfer may occur at the recipient site or at the donor site. Complications occurring at the recipient site are largely a result of vessel thrombosis while complications occurring at the donor site may result from many causes, ranging from infection to those related to the harvesting of the flap. Irrespective of the site of the complication, it is essential that complications be recognized and addressed early in their course to prevent or minimize devastating consequences.


Electron microscopic characteristics of beta2-microglobulin amyloid deposits in long-term haemodialysis.
The electron microscopic features of beta2-microglobulin amyloid, deposited in the synovial membrane, are presented and discussed. The patient, a 69-year-old woman underwent chronic hemodialysis for 3 years. Because of constant pain and destructive arthropathy, endoprosthesis of the hip joints were implanted. Extra- and intracellular filamentous-fibrillar amyloid deposits have been demonstrated in ultrathin sections. The extracellular amyloid deposits showed a loose, filamentous or fibrillar structure at the periphery and a dense central core. The loose, filamentous structure may represent an early stage of fresh, newly deposited beta2-microglobulin amyloid, while the condensed and fragmented amyloid filaments may be an advanced "mature" stage of amyloid deposition.


CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up.
Cytomegalovirus (CMV) hepatitis is described as the most frequent manifestation of CMV tissue invasive disease after liver transplantation. Its correlation with HLA-matching, hepatic artery thrombosis, and chronic rejection is still controversial. Risk factors, incidence, clinical course, and complications of CMV hepatitis were retrospectively analyzed in a 12-year series of 1,146 consecutive liver transplantations in 1,054 patients. All patients received only low-dose acyclovir but no gancyclovir prophylaxis. CMV infection was diagnosed by viral culture, pp65 antigenemia, or by polymerase chain reaction (PCR). CMV hepatitis was proven by liver biopsy. Treatment of CMV disease consisted of intravenous ganciclovir for a minimum of 14 days. Long-term follow-up of patients included monthly routine laboratory values and routine liver biopsies 1, 3 and 5 years after transplantation. CMV hepatitis was a rare event after liver transplantation, with a total incidence of 2.1% (24 cases). It was significantly more frequent in CMV seronegative (5.2%) than in seropositive recipients (0.7%). The leading indication in patients with CMV hepatitis was HCV cirrhosis (n = 8). The maximum number of pp65 positive white blood cells was 82 +/- 23 per 10,000 cells. Most courses manifested as isolated hepatitis; only 2 patients had disseminated disease. Nine of 24 patients had received OKT3 monoclonal antibodies because of steroid-resistant rejection before CMV hepatitis. In seronegative patients with CMV hepatitis, 71% revealed 1 or 2 HLA DR matches, in contrast to 32% in patients without CMV hepatitis. One-, 3-, and 5-year graft survival was 78%, 65%, and 59% in patients with CMV hepatitis compared with 88%, 81%, and 79% in patients without. Chronic rejection was observed in one patient, but already before onset of CMV hepatitis. Beneath D+R-constellation and OKT3 treatment as risk factors, HLA DR-matched grafts and HCV seem to favor manifestation of CMV hepatitis after liver transplantation. Long-term complications of CMV hepatitis were not observed, and especially no correlation with chronic rejection was found.


Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies.
Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound's relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents.


Growth and modelling of spherical crystalline morphologies of molecular materials.
Crystalline, yet smooth, sphere-like morphologies of small molecular compounds are desirable in a wide range of applications but are very challenging to obtain using common growth techniques, where either amorphous films or faceted crystallites are the norm. Here we show solvent-free, guard flow-assisted organic vapour jet printing of non-faceted, crystalline microspheroids of archetypal small molecular materials used in organic electronic applications. We demonstrate how process parameters control the size distribution of the spheroids and propose an analytical model and a phase diagram predicting the surface morphology evolution of different molecules based on processing conditions, coupled with the thermophysical and mechanical properties of the molecules. This experimental approach opens a path for exciting applications of small molecular organic compounds in optical coatings, textured surfaces with controlled wettability, pharmaceutical and food substance printing and others, where thick organic films and particles with high surface area are needed.


[Effects of rikkunshito on postoperative anorexia].
Rikkunshito is a traditional Japanese medicine used to treat a variety of gastrointestinal symptoms. In several previous studies, it was demonstrated that rikkunshito stimulates gastrointestinal movement, accelerates gastric emptying, and promotes gastric adaptive relaxation. Clinically, it is known that rikkunshito attenuates dyspeptic symptoms, appetite loss, and gastroesophageal reflux after gastrointestinal surgery and in chemotherapy-induced nausea and anorexia. A recent study has demonstrated that rikkunshito affects the appetite-enhancing hormone ghrelin. Rikkunshito was also reported to increase plasma ghrelin levels and to enhance the action of ghrelin. Rikkunshito may alleviate dyspeptic symptoms after gastrointestinal surgery through its prokinetic effects and ghrelin.


Golgi quality control and autophagy.
Organelles can easily be disrupted by intracellular and extracellular factors. Studies on ER and mitochondria indicate that a wide range of responses are elicited upon organelle disruption. One response thought to be of particular importance is autophagy. Cells can target entire organelles into autophagosomes for removal. This wholesale nature makes autophagy a robust means for eliminating compromised organelles. Recently, it was demonstrated that the Golgi apparatus is a substrate of autophagy. On the other hand, various reports have shown that components traffic away from the Golgi for elimination in an autophagosome-independent manner when the Golgi apparatus is stressed. Future studies will reveal how these different pieces of machinery coordinate to drive Golgi degradation. Quantitative measurements will be needed to determine how much autophagy contributes to the maintenance of the Golgi apparatus.


A Method for Recovery of Poliovirus 1 from a Variety of Foods.
A method was developed for the recovery of low numbers of plaque-forming units (PFU) of inoculated poliovirus type 1 from seven different foods. Viruses were eluted at pH 9.0 from 25-g food test portions, concentrated at pH 4.5, and eluted at pH 7.5. The final eluates were assayed for PFU in African green monkey kidney (BGM) cell monolayers. The average virus input ranged from 55 to 79 PFU per unit portion. The average percent recoveries were as follows: potato salad, 61; radishes, 54; celery, 45; mushrooms, 44; carrots, 42; clams, 38; and oysters, 35. Three control products were negative for each food.


Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis.
The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE) is the delay between hospital admission and initiation of acyclovir. In this study, factors associated with late initiation of acyclovir were identified. The study included adults from northern France whose cerebrospinal fluid (CSF) was positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of >1 day from hospital admission. In total, 184 patients were retrospectively enrolled from January 1991 to December 2002. The median age was 60 years (range: 17-91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital admission in 68 patients (37.0%). According to multivariate analysis, independent risk factors for late initiation of acyclovir were severe underlying disease (Knaus score >or=C) (OR 4.1; 95% CI 1.5-11.7); alcohol abuse (OR 3.4; 95% CI 1.3-8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI 3.9-18.0). In addition, univariate analysis suggested an association between a finding of <10 leukocytes/mm(3) in CSF at admission (OR 2.5; 95% CI 0.7-5.8). These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27 (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%) patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often present with severe underlying disease, chronic alcohol abuse, or atypical CSF findings, and such factors should not be allowed to delay diagnosis and administration of acyclovir.


Inhibitory effects of citrus essential oils and their components on the formation of N-nitrosodimethylamine.
Twenty-eight kinds of citrus essential oils and their components were studied for inhibitory effects on the formation of N-nitrosodimethylamine (NDMA). The reaction mixture consisted of dimethylamine and sodium nitrite adjusted at pH 3.6, in addition to essential oils and an emulsifying agent. The quantification was determined by high-performance liquid chromatography monitored at 220 nm. All of the essential oils inhibited the formation of NDMA in the range of 20-85%. The oils of ujukitsu (Citrus ujukitsu Hort. ex Shirai), yuzu (C. junos Tanaka), mochiyu (C. inflata Hort. ex Tanaka), and ponkan (C. reticulata Blanco cv. F-2426) inhibited the formation of NDMA much more effectively than other citrus oils. The inhibitory proportions of components of citrus essential oils such as myrcene, alpha-terpinene, and terpinolene were as high as 80%.


Evaluating the Effects of a Medication Adherence Packaging Program on Outcomes in Older People.
Objective To determine the impact of an adherence packaging and medication synchronization program on hospital visits for older people living independently in the community. Design A retrospective pre-post study that evaluated patient outcomes over a 24-month period was conducted. Patient-specific socio-demographic, medical, and hospital visit-related data were collected for 12 months before and after patient enrollment in the adherence packaging program. Setting The study was conducted at Rx Partners LTC, LLC, a University of Pittsburgh Medical Center (UPMC) pharmacy in Pittsburgh, Pennsylvania. Participants Patients 65 years of age or older, of any gender, with UPMC Health Plan insurance coverage, who enrolled in the adherence packaging program between July 2019 and December 2019. Intervention Enrollment in the adherence packaging program included medication synchronization and packaging in prefilled medication sets delivered to the patient's home monthly. Monthly medication reconciliation and review by clinical pharmacists was an included value-added service. Results Of the 92 patients included in the analysis, 60 had hospital visits during their pre-enrollment period for a total of 146 visits, compared with 54 patients in the postenrollment period totaling 126 visits; however, the mean rate of hospital visits was not statistically significant (1.59 versus 1.37; P = 0.48). Pharmacists prevented 1.87 medication errors/patient in the postenrollment setting. Conclusion Enrollment in the program was associated with fewer hospital visits, though not statistically significant, and pharmacists had abundant opportunity to prevent medication errors and optimize regimens. Further evaluation is warranted in a larger cohort.


History of breastfeeding and Helicobacter pylori infection in pre-school children: results of a population-based study from Germany.
Helicobacter pylori infection is predominantly acquired in early childhood. Therefore, childhood nutrition may be related to acquisition of infection. However, there are few current data from developed countries to elucidate this association. We investigated the relation between history of breastfeeding and H. pylori infection in a large population-based sample. Study subjects were all pre-school children in the city of Ulm, located in southern Germany and two nearby communities who were screened for school fitness between January and July 1997. The infection status of the children and of the accompanying mother was determined by the 13C-urea breath test. The parents provided additional information through a standardized questionnaire. In all, 946 children (mean age 5.9 years) and their mothers were included in the final analysis (response in study population 80.2%). Overall, H. pylori prevalence was 9.8% in children and 34.7% in their mothers; there was a strong association between children's and mother's infection. Of the children, 82.5% had ever been breastfed. Prevalence of H. pylori infection was higher in children breastfed compared to never breastfed children (10.1% versus 8.4%) and showed a positive relationship with duration of breastfeeding. After controlling for covariates, including mother's H. pylori status, by means of multivariable analysis, the odds ratio (OR) for children's H. pylori infection was 1.56 (95% CI: 0.79-3.11) for any versus never breastfeeding and 2.57 (95% CI: 1.19-5.55) given the child was breastfed > or =6 months. These data suggest that breastfeeding in infancy does not protect against H. pylori infection among pre-school children in industrialized countries.


Skeletal muscle changes after short term vibration.
Six female Wistar rats were anaesthetised and attached to a vibrating table, (80 Hz/32 m/s2) five hours daily for two days. Histological, enzyme and immunohistochemical, and morphometric analyses of the directly exposed and opposite control plantar muscles were made. Neither fibre necrosis nor regenerative activity were seen. The mean (SD) area (micron2) of vibration-exposed muscle fibres was significantly increased compared with controls (682 (274) and 642 (230), p < 0.05). Both type 1 and 2C fibres were significantly larger after vibration (773 (293) and 650 (223) compared with 683 (209) and 579 (149), p < 0.05) while type 2A and 2AB fibres were not significantly enlarged. The percentage of centrally located nuclei was significantly increased after vibration. This study shows that short term vibration can induce changes in size in muscle fibres. We postulate that this is the first indication of a vibration-induced muscle injury that may develop into chronic impairment of muscle function if the exposure continues for an extended period of time.


Cellular organization of an antennal mechanosensory pathway in the cockroach, Periplaneta americana.
Escape responses of cockroaches, Periplaneta americana, can be triggered by wind and mediated by a group of "giant interneurons" that ascend from cercal mechanoreceptors to motor centers. Recently it has been observed that escape also can be triggered by tactile stimulation of the antennae, and it is then independent of the giant interneurons. Here we identify a descending antennal mechanosensory pathway that may account for escape. Cobalt backfills demonstrated that a limited number of cells in the head ganglia have axons that project through all three thoracic ganglia. Comparison with known wind-sensory pathways indicated that wind is not a reliable stimulus for activating descending antennal pathways. However, direct touch stimulation of an antenna reliably evoked short-latency responses in cells with axons in the cervical connectives. Intracellular recording and dye injection revealed members of this pathway, referred to as descending mechanosensory interneurons (DMIs). The two axons of largest diameter in the cervical connectives were found to belong to DMIs, and these large-caliber interneurons were studied in detail. One had a soma in the supraesophageal ganglion, and the other in the subesophageal ganglion. Both had extensive neuritic arborizations at the same level as the soma and axonal arbors in all three thoracic ganglia. Each of these DMIs exhibited short-latency responses to small antennal movements, demonstrated a degree of directional sensitivity, and rapidly conducted impulses to thoracic levels. These cells have properties suggesting that they play a role in a short-latency behavior such as touch-evoked escape.


Extraction and reliable determination of acrylamide from thermally processed foods using ionic liquid-based ultrasound-assisted selective microextraction combined with spectrophotometry.
Acrylamide (AAm) is a carcinogenic chemical that can form in thermally processed foods by the Maillard reaction of glucose with asparagine. AAm can easily be formed especially in frequently consumed chips and cereal-based foods depending on processing conditions. Considering these properties of AAm, a new, simple and green method is proposed for the extraction of AAm from thermally processed food samples. In this study, an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, [Bmim][BF4]) as extractant was used in the presence of a cationic phenazine group dye, 3,7-diamino-5-phenylphenazinium chloride (PSH+, phenosafranine) at pH 7.5 for the extraction of AAm as an ion-pair complex from selected samples. Under optimum conditions, the analytical features obtained for the proposed method were as follows; linear working range, the limits of detection (LOD, 3Sb/m) and quantification (LOQ, 10Sb/m), preconcentration factor, sensitivity enhancement factor, sample volume and recovery% were 2.2-350 µg kg-1, 0.7 µg kg-1, 2.3 µg kg-1, 120, 95, 60 mL and 94.1-102.7%, respectively. The validity of the method was tested by analysis of two certified reference materials (CRMs) and intra-day and inter-day precision studies. Finally, the method was successfully applied to the determination of AAm levels in thermally processed foods using the standard addition method.


Data quality improvement of a multicenter clinical trial dataset.
Medical datasets are usually affected by several problems, such as missing values, inconsistencies, redundancies, that can influence the data mining process and the extraction of useful knowledge. For these reasons, a preprocessing phase should be performed for improving the overall quality of data and, consequently, of the information that may be discovered from them. In this study we applied five steps of data preprocessing to improve the quality of a large dataset derived from a multicenter clinical trial. Our dataset included 298 patients enrolled in a prospective, multicenter, clinical trial, characterized by 22 input variables and one class variable (MIPI value). In particular, data coming from different medical centers were firstly integrated to obtain a homogeneous dataset. The latter was normalized to scale all variables into smaller and similar intervals. Then, all missing values were estimated by means of an imputation step. The complete dataset was finally discretized and reduced to remove redundant variables and decrease the amount of data to be managed. The improvement of data quality after each step was evaluated by means of the patients' classification accuracy using the KNN classifier. Our results showed that the proposed pipeline produced an increment of more than 20% of the classification performances. Moreover, the highest growth of accuracy was obtained after missing value imputation, whereas the discretization and feature selection steps allowed for a significant reduction of variables to be managed, without any deterioration of the information contained in data.


Quisqualate and L-glutamate inhibit retinal horizontal-cell responses to kainate.
Currents elicited by L-glutamate and the related agonists quisqualate and kainate were analyzed under voltage clamp in isolated goldfish horizontal cells, using the whole-cell recording configuration of the patch-clamp method [Hamill, O.P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. (1981) Pflügers Arch. 391, 85-100]. These currents resulted from an increase in cationic conductance and were indistinguishable from one another in terms of reversal potential (approximately equal to 0 mV) and apparent elementary conductance (2-3 pS). The power-density spectra of the noise increases produced by each agonist were fit by the sum of two Lorentzian curves having similar cutoff frequencies (tau 1 approximately equal to 5 msec, tau 2 approximately equal to 1 msec), but the relative power of these components were different for quisqualate and glutamate than for kainate. Moreover, the responses to high doses of either quisqualate or glutamate rapidly faded, whereas the responses to kainate did not. Finally, quisqualate and glutamate produced an inhibition of responses to kainate which appeared to be uncompetitive. Kainate, quisqualate, and in our preparation, glutamate appear to activate channels different than those activated by N-methyl-D-aspartate in other preparations. At least some of the effects of quisqualate and glutamate appear to be mediated by receptors bound by kainate.


Diagnosis and treatment of cancer of the mouth.
Oral cancer, which includes the lips, buccal mucosa, hard palate and the anterior two-thirds of the tongue, is particularly difficult for patients to cope with, as the cancer and its treatment are highly visible. This article covers the aetiology, classification and treatment of these cancers and presents a case study which highlights the care needed.


Insulin resistance syndrome.
Insulin resistance syndrome, also referred to as the metabolic syndrome, affects 1 in 3 to 4 adults older than 20 years. This syndrome consists of a clustering of metabolic abnormalities that put people at risk for type 2 diabetes and cardiovascular disease. These clinical abnormalities include dyslipidemia, specifically elevated triglycerides and low high-density lipoprotein cholesterol, elevated glucose, and hypertension. The incidence of this morbid syndrome is expected to continue to grow both in the United States and worldwide, and thus is of tremendous interest to nurses seeking to measure their impact on patient outcomes. The key lifestyle interventions essential to treating this syndrome are weight loss and physical activity. The purpose of this article is to (1) describe the insulin resistance syndrome and discuss the current focuses for inquiry in major outcome areas (eg, mortality, morbidity, costs); (2) describe the status of specific lifestyle interventions (weight loss, diet, and exercise); (3) identify outcomes that nurses could measure to assess their impact on patient care; and (4) identify areas for future nursing research.


Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein.
Mice transgenic for human P301S tau protein exhibit many characteristics of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and neurodegeneration leading to nerve cell loss. At 5 months of age, the pathological changes are most marked in brainstem and spinal cord. Here we show that these changes are accompanied by marked neuroinflammation. Many tau-positive nerve cells in brainstem and spinal cord were strongly immunoreactive for interleukin-1beta and cyclooxygenase-2, indicating induction and overproduction of proinflammatory cytokines and enzymes. In parallel, numerous activated microglial cells were present throughout brain and spinal cord of transgenic mice, where they concentrated around tau-positive nerve cells. These findings suggest that inflammation may play a significant role in the events leading to neurodegeneration in the tauopathies and that anti-inflammatory compounds may have therapeutic potential.


Entanglement of Square Nets in Covalent Organic Frameworks.
Two entangled 2D square covalent organic frameworks (COFs) have been synthesized from 4,4',4″,4‴-(9,9'-spirobi[fluorene]-2,2',7,7'-tetrayl)-tetrabenzaldehhyde (SFTB) and p-phenylenediamine (PPA) and benzidine (BZD) to form COF-38, [(SFTB)(PPA)2]imine, and its isoreticular form COF-39, [(SFTB)(BZD)2]imine. We also report the single-crystal electron diffraction structure of COF-39 and find that it is composed of mutually entangled 2D square nets (sql). These COFs represent the first examples of entangled 2D COF structures, which, as we illustrate, were made possible by our strategy of using the distorted tetrahedral SFTB building unit. SFTB overcomes the propensity of 2D COFs to stack through π-π stacking and allows entanglements to form. This work significantly adds to the design principles of COFs.


Desperate times, desperate measures: rotablating dissections in acute myocardial infarction.
The concomitant existence of an acute ST elevation myocardial infarction (STEMI) and a truly undilatable lesion is not a common occurrence, although STEMI lesions can be calcified and sometimes difficult to fracture. The manufacturer lists the presence of a dissection as a contraindication to use for rotational atherectomy. There are no previously reported cases in the literature of rotablation of significant macro dissections in the setting of acute myocardial infarction (MI). Noncompliant balloons, the Cutting Balloon Ultra (Boston Scientific), the Fx miniRAIL™ (Abbott Vascular), and the "cutting wire" technique have all been previously described for calcific lesion modification.1 Heavily calcific lesions especially in the setting of a thrombotic infarction may predispose to under expansion, restenosis, and stent thrombosis. Rotational atherectomy (RA) through plaque ablation and altering arterial wall compliance may be helpful in negotiating heavily calcific lesions.2 Previously, a single case report of the use of RA in the setting of a STEMI has been reported.3 Two previous RA reports have been de- scribed in the setting of acute and delayed healing of dissections; however neither were in the setting of acute STEMI.4,5 We describe the first report to our knowledge of RA for a truly undilatable lesion with accompanying NHLBI type C iatrogenic dissection post balloon dilation during an acute STEMI to allow lesion fracture and subsequent stent deployment.


Augmentation of various immune reactivities of tumor-bearing hosts with an extract of Cordyceps sinensis.
In order to enhance general reactivity of immune system in the tumor-bearing host, we employed extract of Cordyceps sinensis (CSE) as a biological response modifier. Cordyceps sinensis is an interesting material produced by a kind of mushroom parasitic to larval moths and was used to hasten recovery from exhaustion in ancient China. In this experiment, C57BL/6 mice implanted subcutaneously with syngeneic EL-4 lymphoma cells were employed as the host. Oral administration of the extract leads to a reduction of tumor size and prolongation of the host survival time. As judged by plaque-forming cells against T-dependent (sheep erythrocytes) and T-independent (bacterial lipopolysaccharide) antigens, CSE showed to augment the antibody responses. As for the activities of peritoneal macrophages, chemotaxis was dramatically depressed within a few days after EL-4 transplantation up to the end of life, but treatment with CSE at -14, -7, -4, +4, +7 and +10 days after the tumor transplantation augmented the activity about four times stronger than that of control. Phagocytic activity of macrophages was also decreased in tumor-bearing mice treated with cyclophosphamide (100 mg/kg) 3 and 5 days after tumor transplantation. But administration of CSE restored the activity to more than the normal level. The overall efficacy of CSE was tested with protective activity against systemic infection by Salmonella enteritides. The tumor-bearing mice receiving this medicine lived significantly longer than any other groups without CSE.


An evaluation of pulsus alternans in closed-chest dogs.
Pulsus alternans is a condition in which the arterial pressure generated by the heart oscillates between two levels on a beat-to-beat basis. We evaluated the onset of pulsus alternans in chronically instrumented dogs subjected to tachycardia and inferior vena caval occlusion. During pulsus alternans, the left ventricular (LV) end-diastolic volume (EDV) was larger before the strong beats (28.7 +/- 5.3 vs. 25.9 +/- 4.5 ml, P less than 0.001 by paired t test), suggesting that the Frank-Starling mechanism participates in the alternating difference in end-systolic pressure. In addition, however, the ratio of pressure to volume at end systole was greater in the strong beats (2.01 +/- 0.36 vs. 1.46 +/- 0.45, P less than 0.005 by paired t test), a difference that cannot be explained by the Frank-Starling mechanism alone. This indicates that there is also a difference in end-systolic inotropic states between strong and weak beats. These changes occurred without significant alterations in beat-to-beat levels of coronary flow. The time constant of isovolumic pressure fall (T) was faster for the strong beats (37.5 +/- 4.2 vs 61.1 +/- 12.7 ms, P less than 0.002 by paired t test). The onset of oscillation in T preceded the onset of changes in LVEDV and LV systolic pressure in every case by an average of seven beats (range 3-11), suggesting that abnormalities of intracellular calcium handling led to the occurrence of pulsus alternans.(ABSTRACT TRUNCATED AT 250 WORDS)


A pilot study of the use of biocide-impregnated gauze as an adjunct to wound care in a burn population.
The aim of this study was to evaluate the use of a polyhexamethylene biguanide biocide-impregnated gauze (Kerlix™ AMD gauze dressing, Covidien d/b/a Tyco Healthcare Group LP) as an adjuvant to routine burn care and its impact on the incidence of hospital-associated infections in burn population. One hundred eight burn patients admitted to the Burn Treatment Center were prospectively enrolled from August 2008 to June 2009 and matched 1:2 with historic controls who were admitted from March 2006 to July 2008. Clinical care remained otherwise unchanged; however, several hospital initiatives (the national surgical improvement project, the surgical care improvement project, and a central venous line bundle) were initiated before and during the study. There were significantly less infections in the study population (18.52% of case patients vs 28.70% of control patients had infections, P = .047). Although there was a decrease in each infection subtype analyzed, a statistically significant reduction was only reached for pneumonias (1.85% in cases vs 5.86 in controls, P = .042). Implementation of polyhexamethylene biguanide biocide-impregnated gauze was temporally correlated with a significant decrease in healthcare-associated infections in burn population. As there was no corresponding decrease in wound infections, the impact of the gauze on healthcare-associated infections, if any, cannot be conclusively determined by this study. A larger prospective study powered to detect a decrease in wound-related infections is warranted.


How much convergence exists between registered process measures and patient reported experience measures? A study on Catalan primary healthcare.
The use of quality measures is important for transparency and the continuous improvement of performance. However, we do not know enough about the relationship between registered process measures and patient reported experience measures (PREMs) in primary healthcare. Recent studies point to areas of convergence that run contrary anticipated trends. This is a relevant question for healthcare management and governments as their position is stronger when system's guidelines and targets also matter to patients or, vice versa, when patient-centered measures are used to develop new process measures. Our aim is to study both type of measures, their logic and their level of convergence. We also assess the relationship between PREMs, patients' demographic characteristics and area socioeconomic level. We estimated pairwise correlations with patient experience aggregated at the health-center level and a series of multilevel regression models to assess the adjusted effect of four registered process measures on ratings of patient experience at the patient level. We use patient experience as measured by survey data, two composite quality indices and two single indicators regularly computed by the Catalan Health Service. Continuity of care with the same doctor and accessibility are positively associated with patient experience. No relationship was observed in the index created to measure quality of assistance. The index measuring the quality of prescriptions was positively associated with patient experience but only when analyzed separately. We conclude that registered process measures and PREMs are not entirely independent, hence improvements of the management side have the potential to impact patient experience.


Trends in cleft palate incidence in the era of obstetric sonography and early detection.
The effect of improvement in prenatal identification of cleft lip or palate (CL/P) on termination of pregnancy (TOP) worldwide is scarcely reported. Our aim was to assess changes in the prevalence of cleft palate attributed to the high access and availability of prenatal advanced screening and pregnancy termination in Israel. A retrospective study was conducted on CL/P patients which were treated in our institute and born between January 2000 and December 2018. Clinical and demographic data were extracted from medical records. Data on TOP were collected based on accessible information from the Ministry of Health. Cleft palate severity was evaluated using the Veau Classification. The study was conducted on 258 patients. Higher incidence of Veau II and III was evident throughout the examined period (2000-2018). However, when evaluating the incidence per year, we found that the incidence of severe cases (Veau III and IV) decreased every year showing a major decline of 60% in the last decade, whereas mild cases (Veau type I and II) demonstrated a marked increase of 90%. Regarding the incidence of abortions in Israel, a decrease of 30% was observed in the last two decades, meanwhile a substantial increase was detected in the rate of abortions related to physical malformations of the fetus. Additionally, the number of late terminations due to physical malformations significantly increased in the last decade. Significant decrease was observed in the incidence of severe cleft palate cases in the last decade. Concurrently, we found a substantial increase in percentage of abortions performed due to physical malformations. We suggest that these changes might be attributed to the accessibility of advanced prenatal screening and pregnancy termination in Israel under the social healthcare system.


[Atrial fibrillation in patients with heart failure: treatment and management].
Atrial fibrillation (AF) is common in patients with heart failure (HF). It is recognized that AF leads to clinical deterioration and results in worsening HE AF also increases the risk of mortality and morbidity in HF patients. For the management of AF in HF patients, (1) background HF treatment should be optimized, (2) oral anticoagulant is generally indicated when AF is present, (3) ventricular rate control is required and beta-blockers are preferred over digitalis, (4) rhythm control strategy has not been shown to be superior to rate control in HF patients with AF. Amiodarone can be safely used in HF patients. Catheter ablation may be considered in selected HF patients with AF. The therapeutic goal is improvement in survival and quality of life in HF patients with AF.


Circulating immune complexes with pulmonary hemorrhage during pregnancy in idiopathic pulmonary hemosiderosis.
Circulating immune complexes occurred during pulmonary hemorrhage in a pregnant patient with idiopathic pulmonary hemosiderosis, an association not previously reported. The patient required mechanical ventilation, but recovered; after a prolonged hospitalization, she was delivered of a healthy infant without further complications.


The CLAVATA and SHOOT MERISTEMLESS loci competitively regulate meristem activity in Arabidopsis.
The CLAVATA (CLV1 and CLV3) and SHOOT MERISTEMLESS (STM) genes specifically regulate shoot meristem development in Arabidopsis. CLV and STH appear to have opposite functions: c1v1 and Clv3 mutants accumulate excess undifferentiated cells in the shoot and floral meristem, while stm mutants fail to form the undifferentiated cells of the shoot meristem during embryonic development. We have identified a weak allele of stm (stm-2) that reveals STM is not only required for the establish- ment of the shoot meristem, but is also required for the continued maintenance of undifferentiated cells in the shoot meristem and for proper proliferation of cells in the floral meristem. We have found evidence of genetic interactions between the CLV and STM loci. clv1 and c1v3 mutations partially suppressed the stm-1 and stm-2 phenotypes, and were capable of suppression in a dominant fashion. clv stm double mutants and plants homozygous for stm but heterozygous for clv, while still lacking an embryonic shoot meristem, exhibited greatly enhanced postembryonic shoot and floral meristem development. Although stm phenotypes are recessive, stm mutations dominantly suppressed clv homozygous and heterozygous phenotypes. These results indicate that the stm phenotype is sensitive to the levels of CLV activity, while the clv phenotype is sensitive to the level of STM activity. We propose that these genes play related but opposing roles in the regulation of cell division and/or cell differentiation in shoot and floral meristems.


How to diagnose cardiac tamponade.
Malignant pericardial effusion is a potentially fatal complication of malignancy unless recognised and treated promptly. Patients with this condition are often difficult to diagnose. Physical examination, chest radiography and electrocardiography have poor diagnostic values in identification of patients with pericardial effusion. Echocardiography, which allows rapid confirmation of the presence of an effusion and precise assessment of its haemodynamic impact, is the gold standard for diagnosis.


Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging.
Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme. Because of the high resemblance between haptoglobin and haptoglobin-related protein, the receptor also takes up the complex of hemoglobin and the HDL-bound haptoglobin-related protein. This tricks the parasite into internalizing another HDL-associated protein and toxin, apolipoprotein L-I, that kills the parasite. In conclusion, variant human homologous hemoglobin-binding proteins that collectively may be designated the haptoglobins have diverted from the haptoglobin gene. On hemoglobin and receptor interaction, these haptoglobins contribute to different biologic events that go beyond simple removal from plasma of the toxic hemoglobin.


Linker Deprotonation and Structural Evolution on the Pathway to MOF-74.
The synthesis of MOF-74 (MOF = metal-organic framework) proceeds first through the generation of chemically and topologically distinct materials, referred to as phases, displaying exclusively carboxylate coordination, followed by further deprotonation to enable oxo coordination and MOF-74 formation. The synthesis of Mg-MOF-74 at high concentrations of linker and metal enables the stabilization and characterization of the previously unobserved, exclusively carboxylate coordinating phases. Ex situ and in situ approaches are leveraged to provide the time-resolved observation of Mg-MOF-74 synthesis and the formation of phases that precede Mg-MOF-74 formation as well as metastable phase dissolution. These data support dissolution and redeposition as the mechanism of MOF-74 formation and provide insight into the formation mechanism of MOFs with multiple linker coordination types.


The Bonding Nature and Adhesion of Polyacrylic Acid Coating on Li-Metal for Li Dendrite Prevention.
The success of polyacrylic acid (PAA) to suppress Li dendrite growth suggests that the mechanical properties of polymer-based coatings, including the modulus, toughness, and interfacial adhesion are important design criteria. However, the measurement of the adhesion of thin PAA, as well as other polymer coatings to the reactive Li-metal anode surface is limited experimentally and challenging computationally. In this paper, a strategy was proposed to estimate the adhesion and delamination of the PAA(polymer)/Li interface, based on the bonding nature at the simpler PAA (oligomer)/Li interfaces using density functional theory calculations. It has been shown that the carboxylic acid groups in PAA reacted strongly with metallic Li, which significantly enhances the interfacial adhesion through the Li-O bonds formation, Li ionization and its incorporation into PAA, and -H or -OH termination of Li after decomposition of the COOH functional group. During delamination, it was found that the most likely PAA delamination route involved breaking partial Li-O bonds and lifting some ionized Li atoms from the Li-metal, especially for the Li atoms that showed a charge closer to +1 or are bonded with two O atoms from PAA. Based on the average bonding energies from PAA(oligomer)/Li interface delamination calculations, the work of separation, Wsep, of the PAA(polymer)/Li interface was estimated to be ∼1.0 (J/m2). The high Wsep of PAA (polymer)/Li was comparable with the Li2O/Li interface and higher than Li2CO3/Li and LiF/Li interfaces. This order correlated well with the areal density of Li-O bonds, which can serve as a descriptor for the interfacial adhesion. This computational approach can be applied to other interfaces with polymer-based coatings.


Characterization of a two-component regulatory system that regulates succinate-mediated catabolite repression in Sinorhizobium meliloti.
When they are available, Sinorhizobium meliloti utilizes C(4)-dicarboxylic acids as preferred carbon sources for growth while suppressing the utilization of some secondary carbon sources such as α- and β-galactosides. The phenomenon of using succinate as the sole carbon source in the presence of secondary carbon sources is termed succinate-mediated catabolite repression (SMCR). Genetic screening identified the gene sma0113 as needed for strong SMCR when S. meliloti was grown in succinate plus lactose, maltose, or raffinose. sma0113 and the gene immediately downstream, sma0114, encode the proteins Sma0113, an HWE histidine kinase with five PAS domains, and Sma0114, a CheY-like response regulator lacking a DNA-binding domain. sma0113 in-frame deletion mutants show a relief of catabolite repression compared to the wild type. sma0114 in-frame deletion mutants overproduce polyhydroxybutyrate (PHB), and this overproduction requires sma0113. Sma0113 may use its five PAS domains for redox level or energy state monitoring and use that information to regulate catabolite repression and related responses.


[Preliminary effects of closing surgical incision with needleless incision and non-suturing subcutaneous tissue in abdominal oncological surgery].
To observe the preliminary effects of closing surgery incision with needleless incision and leaving subcutaneous tissue non-sutured in the operations of abdominal tumor. There were 52 patients (33 males and 19 females) undergoing abdominal tumor operations between April 2012 and September 2012. Abdominal incision was sutured by a new method of leaving subcutaneous tissue non-sutured closing with a needleless incision close. As a control, the clinical data of 68 patients (47 male and 21 females) received similar operations between April 2011 and September 2011. Abdominal incision was sutured by a traditional method of suturing subcutaneous tissue and skin layer-by-layer. The intergroup incidence of poor healing incident was analyzed by χ(2) test. Risk factors of poor healing were analyzed by Logistic regression analysis. No significant difference existed between the new method group and the traditional group as to poor healing of incision (11.54% (6/52) vs 5.88% (4/68), P = 0.2666). Age (OR = 0.918,95% CI:0.224-3.764), gender(OR = 1.371,95% CI:0.364-5.163), wound length(OR = 2.567,95% CI:0.52-12.665), preoperative diabetes(OR = 1.469,95% CI:0.286-7.554), postoperative serum albumin(OR = 0.536,95% CI:0.108-2.655), laparoscopic surgery(OR = 0.390,95%CI:0.079-1.922)and suturing method(OR = 0.479,95% CI:0.128-1.795) were not risk factors of poor healing. The mean operation duration was 15 min shorter in the new method group than that in the traditional method group. There was no occurrence of scar at either side of incision. The new abdominal incision closing method does not increase the incidence of poor healing. And this time-saving procedure shows potential cosmetic outcomes.


Percutaneous revascularization of chronic total occlusions.
Many patients with severe intermittent claudication (IC) or critical limb ischemia (CLI) have chronic total occlusions (CTO) in their lower extremity vascular bed. The successful treatment of these lesions is becoming increasingly more important as the population ages and the prevalence of diseases such as diabetes mellitus and its consequences increases. Many of these patients have significant comorbidities and may benefit from less invasive treatment options. Several endovascular techniques have now become well established in the treatment of these lesions. Additionally, several new adjunctive tools have been developed to enhance the technical success of CTO revascularization. These tools and techniques offer a minimally invasive alternative for limb salvage in this compromised patient population and have become an established practice in many centers. Although some concerns about procedure durability and lower rates of primary patency exist, particularly when compared to surgical bypass, the limb salvage and amputation-free survival rates are much more encouraging. Advantages of these techniques compared to surgical bypass are reduced morbidity and mortality, reduced anesthesia requirements, and potential reductions in length of hospital stay and cost. In addition, bypass options are typically preserved after endovascular treatment. The more conventional and some newer endovascular treatment approaches, some of the adjunctive tools and techniques used in CTO revascularization as well as their clinical results will be discussed in this review.


Effect of Graded Facetectomy on Lumbar Biomechanics.
Facetectomy is an important intervention for spinal stenosis but may lead to spinal instability. Biomechanical knowledge for facetectomy can be beneficial when deciding whether fusion is necessary. Therefore, the aim of this study was to investigate the biomechanical effect of different grades of facetectomy. A three-dimensional nonlinear finite element model of L3-L5 was constructed. The mobility of the model and the intradiscal pressure (IDP) of L4-L5 for standing were inside the data from the literature. The effect of graded facetectomy on intervertebral rotation, IDP, facet joint forces, and maximum von Mises equivalent stresses in the annuli was analyzed under flexion, extension, left/right lateral bending, and left/right axial rotation. Compared with the intact model, under extension, unilateral facetectomy increased the range of intervertebral rotation (IVR) by 11.7% and IDP by 10.7%, while the bilateral facetectomy increased IVR by 40.7% and IDP by 23.6%. Under axial rotation, the unilateral facetectomy and the bilateral facetectomy increased the IVR by 101.3% and 354.3%, respectively, when turned to the right and by 1.1% and 265.3%, respectively, when turned to the left. The results conclude that, after unilateral and bilateral facetectomy, care must be taken when placing the spine into extension and axial rotation posture from the biomechanical point of view.


Definition of agonists and design of antagonists for alloreactive T cell clones using synthetic peptide libraries.
Alloreactive T cells form an important barrier for organ transplantation. To reduce the risk of rejection patients are given immunosuppressive drugs, which increase the chance of infection and the incidence of malignancies. It has been shown that a large proportion of alloreactive T cells specifically recognize peptides present in the groove of the allogeneic MHC molecule. This implies that it might be possible to modulate the alloresponse by peptides with antagonistic properties, thus preventing rejection without the side effects of general immunosuppression. Peptide antagonists can be designed on the basis of the original agonist, yet for alloreactive T cells these agonists are usually unknown. In this study we have used a dedicated synthetic peptide library to identify agonists for HLA-DR3-specific alloreactive T cell clones. Based on these agonists, altered peptide ligands (APL) were designed. Three APL could antagonize an alloreactive T cell clone in its response against the library-derived agonist as well as in its response against the original allodeterminant, HLA-DR3. This demonstrates that peptide libraries can be used to design antagonists for alloreactive T cells without knowledge about the nature of the actual allostimulatory peptide. Since the most potent agonists are selected, this strategy permits detection of potent antagonists. The results, however, also suggest that the degree of peptide dependency of alloreactive T cell clones may dictate whether a peptide antagonist can be found for such clones. Whether peptide antagonists will be valuable in the development of donor-patient-specific immunosuppression may therefore depend on the specificity of the in vivo-generated alloreactive T cells.


The immunohistochemical evidence of amyloid diffuse deposits as a pathological hallmark in Alzheimer's disease.
We performed an immunocytochemical study of cerebral cortex from cases of Alzheimer's disease and from aged nondemented controls, using periodic acid pretreatment and polyclonal beta-protein antibodies. In addition to senile plaques (SP) and amyloid angiopathy (AA), the beta-protein antibodies detected band-like deposits present throughout the cortical layers. Moreover, large plaque-like infiltrations with diffuse and amorphous characteristics were observed in the cortical gray and white matter, and these deposits were often associated with capillaries. Our results suggest that an abundance of these lesions, which were detected only with this immunostaining procedure in Alzheimer cortex, may be characteristic of Alzheimer's disease.


Structural basis of von Willebrand factor multimerization and tubular storage.
The von Willebrand factor (VWF) propeptide (domains D1D2) is essential for the assembly of VWF multimers and its tubular storage in Weibel-Palade bodies. However, detailed molecular mechanism underlying this propeptide dependence is unclear. Here, we prepared Weibel-Palade body-like tubules using the N-terminal fragment of VWF and solved the cryo-electron microscopy structures of the tubule at atomic resolution. Detailed structural and biochemical analysis indicate that the propeptide forms a homodimer at acidic pH through the D2:D2 binding interface and then recruits 2 D'D3 domains, forming an intertwined D1D2D'D3 homodimer in essence. Stacking of these homodimers by the intermolecular D1:D2 interfaces brings 2 D3 domains face-to-face and facilitates their disulfide linkages and multimerization of VWF. Sequential stacking of these homodimers leads to a right-hand helical tubule for VWF storage. The clinically identified VWF mutations in the propeptide disrupted different steps of the assembling process, leading to diminished VWF multimers in von Willebrand diseases (VWD). Overall, these results indicate that the propeptide serves as a pH-sensing template for VWF multimerization and tubular storage. This sheds light on delivering normal propeptide as a template to rectify the defects in multimerization of VWD mutants.