Cutaneous Mucormycosis in an Immunocompetent Child following a Minor Skin Trauma.
Cutaneous mucormycosis is a rare infection by the Zygomycetes class of fungi, which carries significant morbidity and mortality. While typically associated in patients with underlying immunocompromise (especially in the current era of COVID-19), it may also be seen in immunocompetent patients. We report a case of a healthy 4-year-old girl with acute right leg cellulitis and abscess formation, who required surgical debridement following poor response to antibiotic therapy and initial incision and drainage. Tissue histopathology returned cutaneous zygomycosis despite negative tissue cultures. At four-week follow-up, her wound was healed well. Clinicians should maintain a high degree of clinical suspicion for cutaneous mucormycosis given its potential for rapidly progressive and disseminated disease. Currently, the mainstay of diagnostic investigations is tissue histopathology, with a growing role for tissue fungal PCR. Treatment involves multidisciplinary management between surgeons and Infectious Diseases team to guide the role for surgical debridement and antifungal therapy.


Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM), which govern the delicate balance between HSC quiescence, self-renewal, and differentiation. Previous reports have proposed that HSCs localize to the vascular niche, comprised of endothelium and tightly associated perivascular cells. Herein, we examine the capacity of BM endothelial cells (BMECs) to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1-activated BMECs (BMEC-Akt1) have a unique transcription factor/cytokine profile that supports functional HSCs in lieu of complex serum and cytokine supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced regenerative hematopoiesis following myeloablative irradiation. These data demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This technical advance may lead to the development of therapies designed to decrease pancytopenias associated with myeloablative regimens used to treat a wide array of disease states.


Comparison of sport-specific and non-specific exercise testing in inline speed skating.
The most effective way to measure exercise performance in inline speed skating (ISS) has yet to be established. Generally most athletes are examined by means of traditional but unspecific cycling (CYC) or running (RUN) testing. The present study investigates whether a sport-specific incremental test in ISS reveals different results. Eight male top level inline speed skaters (age: 30±4 years; 65.4±6.3 mL∙kg-1∙min-1, training: 12-14 h/week) performed three incremental exhaustive tests in a randomized order (ergometer CYC, field RUN, field ISS). During the tests, heart rate (HR), oxygen uptake (V̇O2, energy expenditure (EE) and blood lactate concentration (BLC) were measured. Analysis of variance revealed no significant differences for peak HR (187±9, 191±9, 190±9; P=0.75), BLC (10.9±2.3, 10.8±2.4, 8.5±3.2; P=0.25), V̇O2 (65.4±6.3, 66.8±3.5, 66.4±6.5; P=0.91) and EE (1371±165, 1335±93, 1439±196; P=0.51) between ISS and CYC or RUN test. Similar results appeared for HR and V̇O2 at submaximal intensities (2 and 4 mmol·L-1 BLC; P≥0.05). Small to moderate effect sizes 0.3-0.87 and considerable variability of differences between the exercise modes (mean bias range between 1% and 17% with 95% limits of agreement between 3% and 33%) among submaximal and maximal results limit the comparability of the three tests. Consequently, CYC and RUN tests may be considered as qualified alternatives for a challenging ISS test. However a sport-specific test should be conducted in cases of doubt, or when precision is required (e.g. for elite athletes or scientific studies).


Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and multiprotein complexes.
As the protein sequence and structure databases expand, the relationships between proteins, the notion of protein superfamily, and the driving forces of evolution are better understood. Key steps of the synthesis of the bacterial cell wall peptidoglycan are revisited in light of these advances. The reactions through which the D-alanyl-D-alanine depeptide is formed, utilized, and hydrolyzed and the sites of action of the glycopeptide and beta-lactam antibiotics illustrate the concept according to which new enzyme functions evolve as a result of tinkering of existing proteins. This occurs by the acquisition of local structural changes, the fusion into multimodular polypeptides, and the association into multiprotein complexes.


Positron emission tomography (18FDG-PET) in the detection of medullary thyroid carcinoma metastases.
Medullary thyroid carcinoma (MTC) is usually more advanced at presentation than differentiated thyroid cancers and often has distant metastases. The primary treatment of MTC is total thyroidectomy and regional lymph node dissection. The efficacy of these procedures has been limited by the aggressiveness of the disease and metastatic spread at the time of surgery. Persistently elevated levels of calcitonin (CT) and carcinoembryonic antigen (CEA) or their increase postoperatively are indicative for residual or recurrent disease. Conventional imaging methods such as ultrasonography, computed tomography, magnetic resonance imaging and MIBI scintigraphy usually fail to find the source of calcitonin. Better imaging properties have been shown by DMSA scintigraphy, somatostatin receptor scintigraphy or by positron emission tomography (PET). The aim of the study was to evaluate the diagnostic accuracy of PET for the localisation of occult MTC in patients after surgery with increased concentrations of CT, in whom conventional imaging procedures have not been successful. The PET investigation using (18)F-fluoro- 2-deoxy-D-glucose combined with computed tomography ((18)FDG-PET/CT) was performed at the Department of Nuclear Medicine (Oncology Centre in Bydgoszcz) between January and October 2004. In five patients with postoperative calcitonin ranging from 164 to > 2000 ng/l (normal < 10 ng/l) no tumour lesions were found using other imaging methods. In four of five cases, responsible lesions with a higher metabolism of FDG, indicating MTC tissue (remnants or metastases), were localised. In one patient no focus of FDG accumulation was found despite high CT concentration. PET detected tumour manifestations in the neck and the mediastinum in two patients, in the lung and the left adrenal gland in one case and in the neck and the liver in another patient. As a result of surgery for the removal of a residual tumour or metastases the accuracy of diagnosis was confirmed by histopathology in all four cases and a decrease in CT and CEA levels was observed in 3/4 cases. The metabolic imaging findings by PET/CT ensured that the surgery on these patients was successful. For the detection of occult residual or metastatic MTC lesions, (18)FDG-PET is a valuable procedure in imaging diagnostics.


Isolation and characterization of human and canine gastric mucosal glycoproteins and their degradation by proteases and acid hydrolases.
High molecular weight glycoproteins were isolated and purified from canine antral and fundic mucosal tissue by means of non-degrading techniques. The results disclosed the advantage of urea extraction technique over the culture method in isolating the native glycoproteins. The glycoproteins were susceptible to degradation by protease, thus yielding low molecular weight glycopeptides. Chemical analysis of these glycopeptides and their parent macromolecules revealed that the oligosaccharide residues are attached to threonine, serine and proline residues of the protein chains. Similarly, high molecular weight glycoproteins isolated from human gastric gel mucin showed the same characteristics of canine gastric glycoproteins. Canine fundic glycoprotein or glycopeptide released their prosthetic carbohydrate groups under the lytic effect of fundic acid hydrolases.


The Chloroplast Genome of Euglena mutabilis-Cluster Arrangement, Intron Analysis, and Intrageneric Trends.
A comparative analysis of the chloroplast genome of Euglena mutabilis underlined a high diversity in the evolution of plastids in euglenids. Gene clusters in more derived Euglenales increased in complexity with only a few, but remarkable changes in the genus Euglena. Euglena mutabilis differed from other Euglena species in a mirror-inverted arrangement of 12 from 15 identified clusters, making it very likely that the emergence at the base of the genus Euglena, which has been considered a long branch artifact, is truly a probable position. This was corroborated by many similarities in gene arrangement and orientation with Strombomonas and Monomorphina, rendering the genome organization of E. mutabilis in certain clusters as plesiomorphic feature. By RNA analysis exact exon-intron boundaries and the type of the 77 introns identified were mostly determined unambiguously. A detailed intron study of psbC pointed at two important issues: First, the number of introns varied even between species, and no trend from few to many introns could be observed. Second, mat1 was localized in Eutreptiales exclusively in intron 1, and mat2 was not identified. With the emergence of Euglenaceae in most species, a new intron containing mat2 inserted in front of the previous intron 1 and thereby became intron 2 with mat1.


Probing the kinetic landscape of transient peptide-protein interactions by use of peptide (15)n NMR relaxation dispersion spectroscopy: binding of an antithrombin peptide to human prothrombin.
Protein-ligand interactions may lead to the formation of multiple molecular complexes in dynamic exchange, affecting the kinetic and thermodynamic characteristics of the binding equilibrium. We followed the dissociation kinetics of the transient and specific complex of an antithrombotic peptide N-acetyl-Asp(55)-Phe-Glu-Glu-Ile-Pro(60)-Glu-Glu-Tyr-Leu-Gln(65) with human prothrombin by use of (15)N NMR relaxation dispersion spectroscopy of the peptide. Every one of the five (15)N-labeled adjacent residues of the peptide exhibited apparently different kinetic exchange and relaxation behaviors, which were especially evident at different concentrations of prothrombin. Binding-induced (15)N relaxation dispersion of residues Phe(56), Glu(57), Glu(58), and Ile(59) can be fitted phenomenologically to a two-site on-and-off exchange mechanism with physically feasible relaxation and kinetic parameters obtained for residues Phe(56), Glu(58), and Ile(59), independent of the prothrombin concentration. The apparent kinetic parameters of Glu(57) show some dependence on the concentration of prothrombin and the extracted transverse relaxation rate for Glu(57) in the bound state was severalfold higher than that expected for a protein-peptide complex with a size of approximately 72 kDa. In addition, the equilibrium population of the bound peptide obtained for Glu(57) was inconsistent with those for Phe(56), Glu(58), and Ile(59) and with the prothrombin/peptide ratios used in the experiments. These discrepancies can be explained by the presence of two conformations for the peptide-protein complex exchanging at a rate of approximately 100 s(-)(1). In all, our study shows that fast dissociation of protein-peptide complexes can be studied quantitatively using peptide (15)N NMR relaxation dispersion measurements without a precise knowledge of the peptide and protein concentrations. In addition, protein titration was found to improve the accuracy of quantitative analysis and may make it possible to determine the rate of conformational changes within the protein-peptide complex.


Serum C4 levels in patients with systemic lupus erythematosus in remission.
Abstract Twenty-six patients with systemic lupus erythematosus (SLE) showing systemic lupus activity measure (SLAM) and SLE disease activity index (SLEDAI) scores ≤2, as well as a lower C4 concentration than the mean C4 levels of healthy controls, were selected to evaluate the C4 levels of SLE patients in remission. Serum complement (CH50), complement components (C4, C3, and B), complement split products (C4d, iC3b, and Bb), phenotypic expression of C4 allotype, C4 production by peripheral blood monocytes, peripheral blood lymphocyte subpopulation, and interferon-gamma (IFN-γ) production were examined. In patients with SLE in remission, the C4 consumption (C4d/C4) was found to increase, and this was considered to be the most important factor for determining the serum concentration of C4. However, the relevance of the C4 allotypic expression was minimal. The IFN-γ-stimulated production of C4 by peripheral blood monocytes in SLE patients in remission was also less than that of the healthy controls. The IFN-γ-stimulated production of C4 in SLE patients in remission correlated with the peripheral blood CD4-positive cells. Less IFN-γ was produced by lymphocytes of SLE in remission than by those of healthy adults. We conclude that the serum C4 levels in SLE patients in remission reflect the degree of C4 consumption as well as the disease state, rather than genetic influences such as a C4A defect.


Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome.
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10-5), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2707C>T and CAPN21112C>T variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.


The little-known determinants of virus pathogenicity.
Of the four cardinal facets of microbial pathogenicity: (1) entry to the host usually by penetrating mucous membranes; (2) multiplication in the host tissues; (3) interference with host defence; and (4) damage to the host; only multiplication (replication) has received much attention in studies of virus pathogenicity. This article points out the gaps in our knowledge of the other three areas emphasising that although some observations have been made on the invasive and pathological processes involved, the viral determinants concerned are mostly unknown.


A Unique Perspective on Lead Compounds for Dementia with the Lewy Body.
Dementia with Lewy Bodies is a neurodegenerative disorder characterised by abnormal α-Synuclein aggregate accumulation in Lewy Bodies and Lewy Neurites and the most common form of dementia after Alzheimer's disease. The presynaptic protein alpha-synuclein (α-Syn) regulates synaptic vesicle trafficking and the subsequent release of neurotransmitters in the brain. These aggregates go through a number of crucial stages, such as aggregation, oligomerization, and fibrillation. Treatment of this disorder is generally symptomatic. This necessitates the development of cutting-edge therapeutic approaches that can either stop or change the course of the diseases. Many studies have shown that α-synuclein is a significant therapeutic target and that inhibiting α-synuclein aggregation, oligomerization, and fibrillation is an important disease-modifying strategy. Since α-syn is a defining feature of Parkinson's disease, the current review provides an overview of plant phytochemicals and synthetic heterocyclic compounds that target α-syn in Parkinson's disease in order to develop new drugs for Dementia with Lewy Bodies.


Response of primary human airway epithelial cells to influenza infection: a quantitative proteomic study.
Influenza A virus exerts a large health burden during both yearly epidemics and global pandemics. However, designing effective vaccine and treatment options has proven difficult since the virus evolves rapidly. Therefore, it may be beneficial to identify host proteins associated with viral infection and replication to establish potential new antiviral targets. We have previously measured host protein responses in continuously cultured A549 cells infected with mouse-adapted virus strain A/PR/8/34(H1N1; PR8). We here identify and measure host proteins differentially regulated in more relevant primary human bronchial airway epithelial (HBAE) cells. A total of 3740 cytosolic HBAE proteins were identified by 2D LC-MS/MS, of which 52 were up-regulated ≥2-fold and 41 were down-regulated ≥2-fold after PR8 infection. Up-regulated HBAE proteins clustered primarily into interferon signaling, other host defense processes, and molecular transport, whereas down-regulated proteins were associated with cell death signaling pathways, cell adhesion and motility, and lipid metabolism. Comparison to influenza-infected A549 cells indicated some common influenza-induced host cell alterations, including defense response, molecular transport proteins, and cell adhesion. However, HBAE-specific alterations consisted of interferon and cell death signaling. These data point to important differences between influenza replication in continuous and primary cell lines and/or alveolar and bronchial epithelial cells.


Apelin-13 in blood pressure regulation and cardiovascular disease.
Despite extensive pharmacological treatment, hypertension and heart failure still pose as high health and economic burden. Thus, novel therapeutic approaches are needed to promote more effective treatment of hypertension and cardiovascular disease. In this review we summarized recent evidence supporting the therapeutic potential of apelin-13, a recently discovered endogenous ligand for the G-protein coupled receptor APJ. Systemic administration of apelin-13 or its posttranslationally modified form, pyroglutamate apelin-13, exert vasodilatory and antihypertensive effects. Yet, central application of apelin increases blood pressure and its systemic effects may be compromised in the presence of endothelial dysfunction. In addition, positive inotropic effects by exogenous apelin in the normal and failing heart, as well as cardioprotective effects after myocardial infarction, strongly suggest its therapeutic potential in preventing and treating heart failure and consequences of myocardial ischemia. However, therapeutic use of apelin is limited primarily by its short half-life and parenteral administration, and significant effort has been directed to the development of novel agonists, delivery methods, and improving the efficacy of agonists at APJ. The apelin/APJ axis may represent a new target for the development of novel therapeutic approaches for the treatment of hypertension and cardiovascular disease.


Improvement in colon cancer screening through use of a multilevel intervention: A QI initiative.
Colon cancer is the second leading cause of cancer-related deaths in the United States but is highly treatable when diagnosed early. The purpose of this quality improvement (QI) initiative was to develop, implement, and evaluate a multilevel intervention to raise colon cancer screening rates. A pre- and postintervention design was used with patients who were largely Caucasian and English speaking. Patients were mailed information about the importance of screening, and a phone line was created for patients to select a colonoscopy, fecal immunochemical test, or decline screening. Patients not responding via the phone line received an e-mail or postcard about the importance of screening. Electronic flags were sent to providers on the day of the visit to remind staff to address screening. Uninsured patients received free screening. Across three clinics, colon cancer screening rates increased by 6.3%-6.9% through use of a multilevel intervention. Staff satisfaction was moderately high for ease of use, staff education, and perceived success of the QI initiative. Patient education, decision support tools, outreach to patients by mail, phone, e-mail, electronic flags, and free screening for uninsured patients collectively can increase colon cancer screening rates in an at-risk population.


Effects of hydrogen peroxide on the light reflectance and morphology of bovine enamel.
The purpose of this study was to examine the effects of a bleaching agent (30% hydrogen peroxide) on the surface of bovine enamel using a scanning electron microscope and a UV-VIS-NIR spectrophotometer. Five non-carious bovine incisors were bleached for 0, 1, 2 and 3 days using 30% hydrogen peroxide. The light reflectance spectrum was measured using a spectrophotometer with diffuse reflectance mode. Colour values and colour differences in the teeth were evaluated from the reflectance measurements with the CIE L*a*b* colour coordinate system. Surface alterations in the bleached and unbleached teeth were studied using a scanning electron microscope. The change of reflectance in the teeth was related to the change of colour. Most reflectance change occurred within a 1-day bleaching, and this result was confirmed by a CIE L*a*b* colour coordinate system. The colour differences in the bleached teeth were significant enough to be perceived by the observer's eye. The comparison of bleached to unbleached bovine enamel revealed that the bleached surface showed non-uniform slight morphological alterations, and it developed varying degrees of surface porosity. This study indicates that the bleached bovine teeth showed apparent colour differences as well as slight morphological alterations after bleaching.


How High Pressure Unifies Solvation Processes in Liquid Chromatography.
A series of core-shell-based stationary phases of varying surface chemistry were subjected to solvent adsorption investigation under ultra-HPLC conditions. Acetonitrile and water excess isotherms were measured using a minor disturbance method. It was observed that adsorption of organic solvent is unified under high pressure. Preferential solvation due to specific interactions between the stationary phases and solvent molecules was limited. The obtained results showed that the solvation process is almost independent of surface chemistry, in contrast to HPLC conditions in which specific interactions differentiate solvation processes.


Differential enhancement of early and late components of the cerebral somatosensory evoked potentials during forced-paced cognitive tasks in man.
1. Cerebral potentials evoked by random sequences of electrical stimuli to four fingers were recorded in intact man performing selective attention tasks. Eye movements and other artifacts were excluded from the averaged traces. Different finger stimuli were designated as targets to be mentally counted in alternate runs of each experiment. The high mean random rate of stimuli (150/min) fully involved the processing capacities of the subject. Vigilance changes or differential expectancy effects were excluded by the reciprocal random design with four different sensory channels. Task-related enhancements of somatosensory evoked potentials (s.e.p.) components were estimated by comparison with the s.e.p.s to physically identical finger stimuli recorded in runs when the subject attended signals in the opposite hand. The experimental design avoided subject's fatigue.2. The primary s.e.p. components N(20) and P(45) were not significantly influenced and this excluded centrifugal gating of the corticipetal signals as a mechanism.3. The earliest task-related changes in s.e.p. occurred 55-135 msec (mean 77.7 msec) after the target finger stimuli. In most cases the negative N(140) component was markedly enhanced both for target signals and for non-targets in the adjacent finger of the same hand. However, in several subjects the targets elicited a positive P(100) component instead. Both N(104) and P(100) were larger at the contralateral parietal focus than ipsilaterally. They were definitely smaller at the vertex and frontal scalp locations.4. Enhancements of N(140) were not observed in similar random four-finger experiments carried out at a 4 times slower mean rate, but they occurred in a bisensory paradigm with finger shocks and acoustic clicks at that slower rate.5. A large positive P(400) component was only elicited by target stimuli. Its voltage was maximum over the parietal region and was equal on both sides.6. At least three categories of components can be differentiated in the cortical s.e.p. on the basis of their time domains (roughly 18-70 msec, 70 to 200-250 msec and over 200 msec after the finger stimuli), cerebral hemispheres topography and cognitive parameters. Verbal instructions defining specific perceptual tasks can to a large extent switch on and off the components of the second and third categories when the processing resources of motivated subjects are fully committed in a well designed forced paced paradigm. In certain individuals physiological evidence for a different ;stimulus set' processing of target (P(100)) and non-target (N(140)) signals was documented for the first time.


The role of leukodepletion in limiting ischemia/reperfusion damage in the heart, lung and lower extremity.
This article describes the experimental infrastructure and subsequent clinical application of a comprehensive reperfusion strategy to limit the injury following ischemia, resulting in an improvement in post operative organ function. In particular, it examines the role of luekodepletion in minimizing damage and improving functional outcome in the heart, lung and lower extremity. During cardiothoracic procedures, various organs can be subjected to temporary ischemia, particularly the heart (cardioplegic arrest), lung (transplant), and lower extremity (femoral canulation, IABP). The background of ischemia/reperfusion injury is discussed as it applies to each of these 3 organs, as well as findings that ischemia followed by reperfusion results in a similar injury in each organ. Data are then presented to demonstrate that a comprehensive reperfusion strategy, utilizing a modified substrate-enriched blood reperfusate delivered at a low pressure can limit this injury, and that adding white blood cell filtration significantly improves the efficacy of this approach. These principles have now been used in a series of patients undergoing various surgical procedures with excellent results. Application of these concepts may significantly improve the outcome in patients undergoing procedures which subject these organs to temporary ischemia.


Dye laser spectral purity.
Spectral purity of pulsed dye lasers is discussed with regard to signal, noise, and background radiation. Temporal and spatial measurements of these parameters are presented for an excimer-pumped dye laser.


The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer.
We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility. Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models. ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007). This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.


Incidence of Norwalk-like viruses, rotavirus and adenovirus infection in patients with acute gastroenteritis in Jakarta, Indonesia.
Norwalk-like viruses (NLVs), rotavirus and adenovirus are reportedly responsible from 4 to 42% of non-bacterial acute sporadic gastroenteritis. The incidence of NLVs, adenovirus and rotavirus infections in Indonesia is unclear. A total of 402 symptomatic cases from Indonesian patients with acute gastroenteritis and 102 asymptomatic controls that tested negative for bacteria and parasites were screened for the presence of NLVs, rotavirus and adenovirus using the reverse transcriptase-polymerase chain reaction (RT-PCR), Rotaclone kits and Adenoclone kits. Specific prototype probes were used to ascertain which NLV prototypes were present in the area. NLVs were detected in 45/218 (21%), rotavirus was detected in 170/402 (42%) and adenovirus was detected in 11/273 (4%) samples examined. Genetic analysis of the RT-PCR products using specific prototype probes for NLVs indicated that the prototypes were 42% Taunton agent and 58% Hawaii/Snow Mountain agent. Comparative data on patients showed that the incidence of rotavirus infections was two times greater than the NLVs infections, and that adenovirus infections were the least prevalent. All of the control samples tested were negative for NLVs and adenoviruses, however 8/70 (11%) of the samples were positive for rotaviruses. The high incidence of enteric viral-related infections is a threat among acute diarrheic patients in Jakarta, Indonesia.


Trends in Determinants of Hypercholesterolemia among Chinese Adults between 2002 and 2012: Results from theNational Nutrition Survey.
Hypercholesterolemia is a known risk factor for cardiovascular diseases and affects a high proportion of the population. This study aimed to assess and compare the determinants of hypercholesterolemia among Chinese adults aged 18 years and above, from 2002 to 2012. The study used a stratified multistage cluster sampling method to select participants. Sociodemographic and lifestyle information was collected during face-to-face interviews. Dietary intake was calculated by 3-day, 24-h dietary records in combination with weighted edible oil and condiments. Hypercholesterolemia was defined as total cholesterol above 6.22 mmol/L (240 mg/dL) from fasting blood samples. The study included 47,701 (mean age 43.0 years) and 39,870 (mean age 51.0 years) participants in 2002 and 2010-2012 surveys respectively. The weighted prevalence of hypercholesterolemia increased from 1.6% (2.1% urban, 1.0% rural) in 2002 to 6.0% (6.4% urban, 5.1% rural) in 2012. The intake of plant-based food decreased but the intake of pork increased over the 10 years. A high intake of protein and pork, alcohol drinking and overweight/obesity were positively associated with hypercholesterolemia. Neither education nor fruit and vegetable intake were associated with hypercholesterolemia. In conclusion, the burden of hypercholesterolemia increased substantially between 2002 and 2012 in China. Unhealthy lifestyle factors and change in traditional dietary pattern were positively associated with hypercholesterolemia. Further research on the role of diet in the development and prevention of hypercholesterolemia is needed.


Determination of polybrominated biphenyls in Tasmanian devils (Sarcophilus harrisii) by gas chromatography coupled to electron capture negative ion tandem mass spectrometry or electron ionization high-resolution mass spectrometry.
Two gas chromatography/mass spectrometry (GC/MS) methods for the determination of polybrominated biphenyls (PBBs) by isotope dilution analysis (IDA) using (13)C(12)-PBB 153 in the presence of polybrominated diphenyl ethers (PBDEs) were compared. Recovery of (13)C(12)-PBB 153 which was added to the extracted lipids before sample purification was commenced ranged from 88-117% (mean value 98.2 +/- 8.9%). Nevertheless, IDA analysis of PBBs using (13)C(12)-labelled congeners is limited by the potential co-elution of PBBs with polybrominated diphenyl ethers (PBDEs). The pair PBB 153 and BDE 154 was inspected since M(+) and [M-2Br](+) ions of (13)C(12)-PBB 153 and BDE 154 were only separated by 4 u. Gas chromatography/electron ionization high-resolution mass spectrometry with selected ion monitoring (GC/EI-HRMS-SIM) was suitable when m/z 475.7449 and m/z 477.7429 were used for (13)C(12)-PBB 153 because they are below the monoisotopic peak of the [M-2Br](+) fragment ion of hexaBDEs at m/z 479.7. Gas chromatography/electron capture negative ion tandem mass spectrometry selected reaction monitoring (GC/ECNI-MS/MS-SRM) measurements could be applied because (13)C(12)-PBB 153 and BDE 154 were separated by GC on a 25-m Factor Four CP-Sil 8MS column.Comparative measurements with GC/EI-HRMS-SIM and GC/ECNI-MSMS-SRM were carried out with samples of Tasmanian devils from Tasmania (Australia), an endangered species due to a virus epidemy which has already proved fatal for half of the population. Both techniques verified concentrations of PBB 153 in the range 0.3-11 ng/g lipids with excellent agreement of the levels in all but two samples. The PBB residue pattern demonstrated that PBB pollution originated from the previous discharge with technical hexabromobiphenyl which is dominated by PBB 153. Other congeners such as PBB 132 and PBB 138 were detected in the Tasmanian devils but the proportions relative to PBB 153 were lower than in the technical product. Samples of healthy and affected Tasmanian devils showed no significant difference in the PBB pollution level. The PBB concentrations in the Tasmanian devils were significantly below those causing toxic effects. On the other hand, PBB concentrations were one level or even higher than PBDEs.


In situ Impact of the Antagonistic Fungal Strain, Trichoderma gamsii T30 on the Plant Pathogenic Fungus, Rhizoctonia solani in Soil.
Rhizoctonia solani is a soil-borne fungus causing a wide range of plants diseases. Trichoderma gamsii strain T30 has previously been reported as antagonistic against R. solani. Although there are a few studies about the influence of Trichoderma strains on the R. solani density in a pathosystem in the presence of plant hosts, this report for the first time comprehensively describes in situ effects of a T. gamsii strain on the population density of R. solani in the soil microcosmic conditions. The population dynamics of R. solani were followed in the autoclaved and non-autoclaved soils in artificially prepared microcosms up to day 25 after co-inoculation with T. gamsii in the variable ratios (R1/T1; R1/T0.1; R1/T0.01 of R. solani/T. gamsii). The population density of R. solani was evaluated by qPCR. In the autoclaved soil, target DNA copies of R. solani increased in the control samples from 1 × 105 to 6.5 × 106. At R1/T0.01, the number of target DNA copies were not significantly changed until day 11; however, it decreased by around five times at day 25. At R1/T0.1 and R1/T1, the number of DNA copies was reduced to 2.1 × 106 and 7.6 × 105 at day 11, respectively and the reduction was as much as 17 times at day 25. In the non-autoclaved soil, the number of the fungal cells decreased at day 25 whether inoculated or not with Trichoderma indicating a general suppression by the soil microbiome. In brief, T. gamsii significantly inhibited the growth of R. solani in the soil in situ and there was a general suppressive effect of the natural microbiome. Rhizoctonia solani is a soil-borne fungus causing a wide range of plants diseases. Trichoderma gamsii strain T30 has previously been reported as antagonistic against R. solani. Although there are a few studies about the influence of Trichoderma strains on the R. solani density in a pathosystem in the presence of plant hosts, this report for the first time comprehensively describes in situ effects of a T. gamsii strain on the population density of R. solani in the soil microcosmic conditions. The population dynamics of R. solani were followed in the autoclaved and non-autoclaved soils in artificially prepared microcosms up to day 25 after co-inoculation with T. gamsii in the variable ratios (R1/T1; R1/T0.1; R1/T0.01 of R. solani/T. gamsii). The population density of R. solani was evaluated by qPCR. In the autoclaved soil, target DNA copies of R. solani increased in the control samples from 1 × 105 to 6.5 × 106. At R1/T0.01, the number of target DNA copies were not significantly changed until day 11; however, it decreased by around five times at day 25. At R1/T0.1 and R1/T1, the number of DNA copies was reduced to 2.1 × 106 and 7.6 × 105 at day 11, respectively and the reduction was as much as 17 times at day 25. In the non-autoclaved soil, the number of the fungal cells decreased at day 25 whether inoculated or not with Trichoderma indicating a general suppression by the soil microbiome. In brief, T. gamsii significantly inhibited the growth of R. solani in the soil in situ and there was a general suppressive effect of the natural microbiome.


Infection fatality risk of the pandemic A(H1N1)2009 virus in Hong Kong.
One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60-69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.


A performance test protocol and scoring scale for the evaluation of ankle injuries.
The aim of the study was to introduce and evaluate a standardized test protocol and scoring scale for evaluation of ankle injuries. After evaluation of 11 different functional ankle tests, questionnaire answers, and results of clinical ankle examination, the final test protocol consisted of 3 simple questions describing the subjective assessment of the injured ankle, 2 clinical measurements (range of motion in dorsiflexion, laxity of the ankle joint), 1 ankle test measuring functional stability (walking down a staircase), 2 tests measuring muscle strength (rising on heels and toes), and 1 test measuring balance (balancing on a square beam). Each selected test showed excellent reproducibility when tested with a reference group of 100 uninjured persons. According to the test results of a population of 148 patients with an operatively treated grade III lateral ligament injury of the ankle, each test could significantly differentiate healthy controls and patients with excellent overall healing from those with poor or fair recovery. The final total test score correlated significantly with the isokinetic strength results of the ankle, subjective opinion about the recovery, and subjective-functional assessment. The scale presented is recommended for studies evaluating functional recovery after ankle injury.


Cyclin E and chromosome instability in colorectal cancer cell lines.
The development of colorectal cancer depends on at least two distinct pathways involving genetic instability, namely: chromosome instability (CIN) and microsatellite instability. Cyclin E is involved in aneuploidy and several cancer types show an abnormal number of chromosomes. Cyclin E protein and mRNA values were analysed in human fetal skin fibroblasts and five colorectal cancer cell lines. Cells with an aberrant number of chromosomes had higher cyclin E mRNA values and a significant increase in protein concentrations. These data suggest that cyclin E regulation is altered in aneuploid cells and is an important factor in the CIN pathway.


Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney model.
Accumulation of plasma advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease. However, the biologic consequences of AOPP consumption on progression of renal disease still are unclear. For testing of the hypothesis that AOPP accelerate progression of chronic kidney disease, Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham operation. Rats in each group were randomly assigned in three subgroups (n = 30 in each group) and treated with repeated intravenous injections of AOPP-modified rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period. Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats displayed greater proteinuria, higher serum creatinine, and lower creatinine clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage influx, and greater renal fibrosis in the remnant kidney. Chronic administration of AOPP in sham-operated rats increased urinary protein excretion and renal macrophage infiltration, but histologic renal fibrosis was not observed during the study period. AOPP treatment enhanced AOPP level in renal tissue. This was associated with marked increase of thiobarbituric acid reactive substances, decrease of glutathione peroxidase activity, and upregulated expression of monocyte chemoattractant protein-1 and TGF-beta1 in renal cortex. These data indicate that AOPP might be a new and potentially important mediator of renal fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal fibrosis probably via a redox-sensitive inflammatory pathway.


What are terminally ill cancer patients told about their expected deaths? A study of cancer physicians' self-reports of prognosis disclosure.
Little is known about how physicians discuss prognosis with terminally ill cancer patients. Thus, we sought to obtain cancer physicians' self-reports of their prognosis communication practices. A survey seeking self-reports regarding prognosis communication with their terminally ill cancer patients was mailed to a systematic sample of medical oncologists in the United States. Of 1,137 physicians, 729 completed and returned surveys (64% response rate). Median age of respondents was 51 years (range, 33 to 80 years); 82% were men. Respondents had practiced cancer care for a median of 18 years (range, 1.5 to 50 years) and reported seeing a median of 60 patients per week (range, 0 to 250 patients per week). Although 98% said their usual practice is to tell terminally ill patients that they will die, 48% specifically described communicating terminal prognoses to patients only when specific preferences for prognosis information were expressed. Forty-three percent said they always or usually communicate a medical estimate of time as to when death is likely to occur, and 57% reported sometimes, rarely, or never giving a time frame. Seventy-three percent said prognosis communication education was either absent or inadequate during their training, and 96% believed it should be part of cancer care training. Medical oncologists report routinely informing their terminally ill patients that they will die. However, they are divided in describing themselves as either always discussing a terminal prognosis or doing so if it is consistent with their patients' preferences for prognostic information. Most medical oncologists say they do not routinely communicate an estimated survival time to their patients.


[The correlation between BRAF mutations, RET/PTC rearrangements and platelet-derived growth factor B expression in papillary thyroid carcinomas].
To investigate the prevalence of BRAF T1799A mutation and RET/PTC rearrangement in Qingdao and detect the expression of platelet-derived growth factor B (PDGF-B) in order to investigate the correlation between gene mutation and PDGF-B. Fresh tissue from 48 papillary thyroid carcinomas (PTC) patients was examined for BRAF mutation RET rearrangements (RET/PTC1 and RET/PTC3) by PCR, followed by direct-sequence analysis. The expression of PDGF was analyzed by immunohistochemistry. Among the 48 patients, 14 (29.2%) were micro PTC; 18 (37.5%) had BRAF T1799A mutations and 23(47.9%) had RET/PTC rearrangement. There were 17 (35.4%) cases of RET/PTC1 and 6 (12.5%) of RET/PTC3, with no multiple rearrangements. Both BRAF T1799A mutation and RET/PTC rearrangement were present in 6 (12.5%) cases of non-micro PTC. The level of PDGF-B expression in BRAF T1799A positive was higher than that in the negative, and the level of PDGF-B expression in RET/PTC3 was higher than that in RET/PTC1 (P < 0.05). The more advanced neoplasm stage was, the stranger PDGF-B expression was. The incidence of BRAF T1799A mutation and RET/PTC rearrangement is higher in Qingdao. BRAF T1799A mutation and RET/PTC3 rearrangement in patients suggests a poorer prognosis than the negative one. The BRAF T1799A mutation and RET/PTC3 rearrangement may strengthen the expression of PDGF-B. Both variations suggest a poor prognosis.


Aspherical, Nanostructured Microparticles for Targeted Gene Delivery to Alveolar Macrophages.
Introducing novel shapes to particulate carrier systems adds unique features to modern drug and gene delivery. Depending on the route of administration, particle geometry can influence deposition and fate within biological environments. In this work, a template-assisted engineering technique is applied, providing full control of size and shape in the preparation of aspherical, nanostructured microparticles. Based on the interconnection of nanoparticles, stabilized by a functional layer-by-layer (LbL) coating, the resulting cylindrical micrometer architecture is especially qualified for pulmonary delivery. Designed as gene delivery system, plasmid-DNA (pCMV-luciferase) and branched polyethylenimine are used to reach both structural integrity of the carrier system and delivery of genes into the cells of interest. Due to their size, particles are exclusively taken up by phagocytes, which also adds a targeting effect to the introduced system. The luciferase expression is demonstrated in macrophages showing increasing levels over a time period of at least 7 d. Furthermore, it is shown for the first time that the expression is depending on the LbL design. From in vivo experiments, corresponding luciferase expression is observed in mice alveolar macrophages. Combining site specific transport with the possibility of genetically engineering immunocompetent phagocytes, the presented system offers promising potential to improve applications for cell-based immunotherapy.


Does oestriol add to the beneficial effect of combined hormonal prophylaxis against early postmenopausal osteoporosis?
Sixty-nine healthy women in the early menopause were assessed in terms of calcium metabolism, coronary risk factors, Kupperman index, and various serum hormones before and during replacement therapy with 17 beta-oestradiol plus oestriol and norethisterone acetate. The patients were followed for 1 year, and the daily doses used were: 17 beta-oestradiol: 2 mg from day 1 to day 22, 1 mg from day 23 to day 28; oestriol: 1 mg from day 1 to day 22, 0.5 mg from day 23 to day 28; and norethisterone acetate: 1 mg from day 13 to day 22. Group A (n = 22) received 17 beta-oestradiol and norethisterone acetate; group B (n = 20) received 17 beta-oestradiol plus oestriol and norethisterone acetate and group C (n = 23) received a placebo. The responses in groups A and B were similar with no significant difference between the two therapy regimens. The results suggest that in the dose given, oestriol does not add significantly to the beneficial effect of combined hormonal prophylaxis against early postmenopausal osteoporosis.


Expression of three proteins in endometrioid adenocarcinoma and their significance in clinical nursing, diagnosis and treatment.
This study aimed to investigate the role of NEDD9 (neural precursor cell expressed developmentally down-regulated 9), BCAR1/P130CAS (BCAR1/P130 Crk-associated substrate) and paxillin in predicting the prognosis of endometrioid adenocarcinoma (EA), so as to guild the nursing of EA. A total of 65 patients who visited Affiliated Hongqi Hospital of Mudanjiang Medical University between June 2015 and June 2017 were enrolled. They underwent gynecological surgery and had their EA confirmed by pathology, and they were assigned to the EA group. All EA tissues were sampled and archived in paraffin blocks. In addition, 40 specimens of atypical endometrial hyperplasia (EAH) (the EAH group) and 40 specimens of normal proliferative endometria with benign uterine fibroids (the EN group) were selected as controls. The protein levels of NEDD9, BCAR1/P130CAS, and paxillin in each group were then detected by immunohistochemical staining. The expression of the three proteins in the EA group and EAH group was significantly higher than that in the EN group, and their expression was significantly correlated with the clinical stage, histological grade and lymph node metastasis of EA. In addition, the expression of NEDD9, BCAR1/P130CAS, and paxillin in the EA group was positively correlated with each other. BCAR1/P130CAS and paxillin interact with NEDD9 to participate in the growth and migration of EA cells. Therefore, their proteins can be used as biomarkers for the diagnosis, treatment, and prognosis of EA.


A mouse cerberus/Dan-related gene family.
The Xenopus cerberus gene is able to induce ectopic heads in Xenopus embryos. At the time of its identification, cerberus shared significant homology with only one other protein, the putative rat tumor suppressor protein Dan. Sequence analysis has revealed that cerberus and Dan are members of a family of predicted secreted proteins, here called the can family. The identification of a can-family member in the nematode Caenorhabditis elegans, CeCan1, suggests that this family is of ancient origin. In the mouse, there are at least five family members: Cer1, Drm, PRDC, Dan, and Dte. These genes are expressed in patterns that suggest that they may play important roles in patterning the developing embryo. Cer1 marks the anterior visceral endoderm at E6.5. Dte is expressed asymmetrically in the developing node. Dan is first seen in the head mesoderm of early head fold stage embryos and Drm is expressed in the lateral paraxial mesoderm at E8.5. The region of homology shared by these genes, here called the can domain, closely resembles the cysteine knot motif found in a number of signaling molecules, such as members of the TGFbeta superfamily. Epitope-tagged versions of Cer1 show that, unlike in TGFbeta superfamily members, the cysteine knot motif is not processed away from a proprotein. Recent experiments in Xenopus have suggested that cerberus may act as an inhibitor of BMP signaling. To examine this further, the ability of Dan, Cer1, and human DRM to attenuate Bmp4 signaling has been assessed in P19 cells using pTlx-Lux, a BMP-responsive reporter. All three genes are able to inhibit Bmp4 signaling. These data suggest that the different family members may act to modulate the action of TGFbeta family members during development.


Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial.
Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic. To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer. This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019. Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily). The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction. Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 patients [58.8%]; OR, 0.06; 95% CI, 0.01-0.25; P < .001) and pain associated with taking the medication (4 patients [2.1%] vs 92 patients [49.2%]; OR, 9.20; 95% CI, 2.67-31.82; P < .001). These findings suggest that oral apixaban is a potentially safe, less painful, and easier-to-take alternative to subcutaneous enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The efficacy of apixaban to prevent venous thromboembolic events is hypothesized as being equivalent. ClinicalTrials.gov Identifier: NCT02366871.


Cardiotoxicity of ErbB2-targeted therapies and its impact on drug development, a spotlight on trastuzumab.
Trastuzumab, a therapeutic monoclonal antibody directed against ErbB2, is often noted as a successful example of targeted therapy. Trastuzumab improved outcomes for many patients with ErbB2-positive breast and gastric cancers, however, cardiac side effects [e.g., left ventricular dysfunction and congestive heart failure (CHF)] were reported in the early phase clinical studies. This finding, subsequently corroborated by multiple clinical studies, raised concerns that the observed cardiotoxicity induced by trastuzumab might adversely impact the clinical development of other therapeutics targeting ErbB family members. Areas covered: In this review we summarize both basic research and clinical findings regarding trastuzumab-induced cardiotoxicity and assess if there has been an impact of trastuzumab-induced cardiotoxicity on the development of other agents targeting ErbB family members. Expert opinion: There are a number of scientific gaps that are critically important to address for the continued success of HER2-targeted agents. These include: 1) elucidating the molecular mechanisms contributing to cardiotoxicity; 2) developing relevant preclinical testing systems for predicting cardiotoxicity; 3) developing clinical strategies to identify patients at risk of cardiotoxicity; and 4) enhancing management of clinical symptoms of cardiotoxicity.


A prospective study of adolescents who choose among levonorgestrel implant (Norplant), medroxyprogesterone acetate (Depo-Provera), or the combined oral contraceptive pill as contraception.
Levonorgestrel implants (Norplant) and medroxyprogesterone acetate injections (Depo-Provera) represent additional contraception options for adolescents. The purpose of this study was to examine prospectively clinical profiles among adolescents who chose one of the two long-term contraceptives compared with profiles among those who chose the combined oral contraceptive pill (OCP). Girls who needed contraception and did not require confidentiality were presented with a contraceptive menu consisting of Norplant (n = 58), Depo-Provera (n = 66), or OCP (n = 75). At baseline and follow-up visits over 6 months, patients were interviewed regarding gynecologic history, side effect symptoms, and satisfaction. The average age of subjects was 15.5 years (range 11 to 20 years); 66% were African-American and 34% white. Significantly more teens who chose Depo-Provera (73%) reported having used some method of birth control previously than those selecting either Norplant (30%) or OCP (26%). Adolescents who chose either Norplant (34%) or Depo-Provera (43%) were significantly more likely to have been pregnant previously than those choosing OCP (12%). Those selecting Depo-Provera were significantly more likely to report a history of genital infection with Chlamydia trachomatis (42%) than those in the other two contraceptive groups (22%). Prevalences of reported recent depression and fatigue before initiation of treatment were high, exceeding 35% across the three groups. A total of 105 and 40 adolescents were assessed at 3 and 6 months, respectively. At follow-up, more than 80% of OCP users maintained regular menstrual cycles, whereas over 80% of those choosing Norplant or Depo-Provera had disrupted cycles. Complaints of nausea and dizziness among Norplant users and fatigue among Depo-Provera and OCP users increased significantly between the baseline and follow-up visits. Reports of local reactions to the Norplant device were common but not clinically significant. Blood pressure readings, facial acne, and body mass index did not change over time in any treatment group. Subjects in the Norplant and Depo-Provera groups appreciated freedom from daily compliance to maintain contraceptive effectiveness and the "hidden" nature of the method. Appointment compliance at the end of 6 months was 78% for Depo-Provera, 40% for Norplant, and 46% for OCP. The implant and injection forms of contraception appear to be especially popular among girls with previous pregnancies or birth control use. The common occurrences of medical symptoms and sexually transmitted diseases before initiation of therapy underscore the importance of baseline evaluation. Norplant users may be warned about nausea and dizziness as well as minor local symptoms around the insertion site and unpredictable uterine bleeding patterns. Adolescent patients choosing Depo-Provera may expect amenorrhea by the end of 6 months of therapy along with possible fatigue. Early intervention may be needed with adolescents who choose Norplant or OCP to encourage better compliance with follow-up appointments.


Diagnosis and management of trigemino-cavernous fistulas: case reports and review of the literature.
Although usually asymptomatic, a persistent trigeminal artery (PTA) can rarely be associated with a direct fistula to the cavernous sinus (ie, trigemino-cavernous fistula). We present three patients with trigemino-cavernous fistulas; two were subsequently treated using modern endovascular techniques while the third initially declined therapy. We then review the literature of reported cases of this unusual entity. The aberrant anatomy associated with a PTA presents unique challenges to the management of these lesions, and must be well delineated prior to treatment. Finally, conservative management of trigemino-cavernous fistulas, either de novo or recurrent, may be considered if they demonstrate no evidence of cortical venous reflux and patient symptoms are tolerable.


Facial growth of males and females compared by tensor analysis.
This study compares and contrasts the longitudinal differences in facial development between 18 male and 22 female subjects, employing the technique of tensor analysis. Children were examined in two age ranges: prepubertal (aged 7-10 years) and post-pubertal (15-20 years of age). Both the changes over time and the differences in amount and direction of growth between the sexes were subjected to statistical analysis. A tensor analysis permits the computation of differences in form (that is in size and shape) without specifically measuring either. Mean values for 21 hard and soft tissue landmarks were determined for both males and females at each age. Customized computer software allowed examination of the growth changes between 32 selected groups of points. Results indicated that the tensor analysis reinforced and supplemented the more conventional descriptions of facial growth. Females grew a smaller amount over the period examined than their male peers and development was in a relatively more vertical direction. These differences in growth between the sexes were highly statistically significant.


[Clinical observation on therapeutic effect of myopia in children treated with abdominal acupuncture].
To observe the clinical effects of myopia in children treated with abdominal acupuncture. Ninety children with myopia were randomly divided into an abdominal acupuncture group (45 cases with 90 ill eyes) and an auricular point group(45 cases with 90 ill eyes). In the abdominal acupuncture group, Zhongwan (CV 12), Shangqu(KI 17), Xiawan(CV 10), Tianshu(ST 25), Qihai(CV 6), Guanyuan(CV 4) were treated with tapping method. The needles were not retained and down to the lower in accordance with the order from Zhongwan (CV 12) to Guanyuan(CV 4) for 5 min,and the erubescence skin without blood was proper. In the auricular point group, vaccaria seeds were pasted at gan(CO12), shen(CO10),pi(CO13), wei(CO4), yan(LO5), pingjianqian(TG2i), pingjianhou(ATli) and zhen(AT3); one ear was chosen every time and the other ear the second time with pressing of patient's own for 5 min every day. The treatment was given twice a week and 10 treatments were considered as one course in the two groups. The changes of the visual levels in visual chart before treatment, 20 min after the first treatment, after 5 weeks' and 3 months' treatment were compared between the two groups,and the clinicall efficacy was compared between the two groups as well. (1) The visual levels in visual chart were improved in the abdominal acupuncture group and auricular point group, and the effects 20 min after the first treatment, after 5 weeks' and 3 months' treatment in the abdominal acupuncture group were superior to those in the auricular point group(4. 78±0. 16 vs 4. 69±0. 22, P<0. 01; 4. 85±0. 16 vs 4. 79±0. 21, P<0. 05; 4. 89±0. 13 vs 4. 71±0. 25, P<0. 01). (2)The effective rates 20 min after the first treatment, after 5 weeks' and 3 months' treatment in the abdominal acupuncture group were better than those in the auricular point group[31. 4% (27/86) vs 0% (0/82). 81.4%(70/86) vs 60. 0%(49/82); 88. 4%(76/86) vs 51. 2%(42/82), all P<0. 01]. Abdominal acupuncture for improving the visual levels of myopia in children is superior to auricular point sticking.


Ten-year outcome of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration.
The aim of this study was to report the 10-year visual outcome in eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents for neovascular age-related macular degeneration (nAMD) and to assess the impact of switching treatment as part of routine clinical care. Electronic records of treatment-naïve eyes initiated on intravitreal ranibizumab between January and December 2009 were accessed. The primary outcome measured was the change in visual acuity (VA) in Early Treatment of Diabetic Retinopathy Study letters. The frequency and reasons for treatment discontinuation during each year of follow-up and the impact of switching from ranibizumab to aflibercept were some of the secondary outcomes. Of the 223 eyes (203 patients), 60 eyes completed 10 years of continuous follow-up. After a mean follow-up of 121.4 months, VA declined by 5.6 letters (95% confidence interval [CI] -0.25 to -11.1, P = 0.04). Final VA of ≥70 letters was seen in 20% of eyes and 35% had VA ≤ 35 letters. VA gain of ≥10 letters was seen in 23% and loss of ≥10 letters was seen in 40% of the eyes. Twenty-nine eyes remained on ranibizumab monotherapy and 31 switched to aflibercept. Switched eyes showed a visual decline of 7.1 letters (5.5 letters in monotherapy eyes, P = 0.32) and received a significantly higher number of injections (39.6 ± 9.9 vs. 24.4 ± 13.1, P < 0.0001). Patients discontinuing treatment were older and had lower baseline vision compared to completers. VA declined below the baseline after 10 years of follow-up and switching did not have any effect on the final visual outcome.


Energy Efficient All-Electric-Field-Controlled Multiferroic Magnetic Domain-Wall Logic.
Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.


Superficial and deep sternal wound infection after more than 9000 coronary artery bypass graft (CABG): incidence, risk factors and mortality.
Sternal wound infection (SWI) is an uncommon but potentially life-threatening complication of cardiac surgery. Predisposing factors for SWI are multiple with varied frequencies in different studies. The purpose of this study was to assess the incidence, risk factors, and mortality of SWI after coronary artery bypass grafting (CABG) at Tehran Heart Center. This study prospectively evaluated multiple risk factors for SWI in 9201 patients who underwent CABG at Tehran Heart Center between January 2002 and February 2006. Cases of SWI were confirmed based on the criteria of the Centers for Disease Control and Prevention. Deep SWI (bone and mediastinitis) was categorized according to the Oakley classification. In the study period, 9201 CABGs were performed with a total SWI rate of 0.47 percent (44 cases) and deep SWI of 0.22 percent (21 cases). Perioperative (in-hospital) mortality was 9.1% for total SWI and about 14% for deep SWI versus 1.1% for non-SWI CABG patients. Female gender, preoperative hypertension, high functional class, diabetes mellitus, obesity, prolonged intubation time (more than 48 h), and re-exploration for bleeding were significant risk factors for developing SWI (p = 0.05) in univariate analysis. In multivariate analysis, hypertension (OR = 10.7), re-exploration (OR = 13.4), and female gender (OR = 2.7) were identified as significant predictors of SWI (p < 0.05 for all). The rate of SWI was relatively similar in 3 groups of prophylactic antibiotic regimen (Cefazolin, Cefazolin + Gentamycin and Cefazolin + Amikacin: 0.5%, 0.5%, and 0.34% respectively). Rarely reported previously, the two risk factors of hypertension and the female gender were significant risk factors in our study. Conversely, some other risk factors such as cigarette smoking and age mentioned as significant in other reports were not significant in our study. Further studies are needed for better documentation.


Coordination Chemistry of Homoleptic Actinide(IV)-Thiocyanate Complexes.
The synthesis, X-ray crystal structure, vibrational and optical spectroscopy for the eight-coordinate thiocyanate compounds, [Et4 N]4 [Pu(IV) (NCS)8 ], [Et4 N]4 [Th(IV) (NCS)8 ], and [Et4 N]4 [Ce(III) (NCS)7 (H2 O)] are reported. Thiocyanate was found to rapidly reduce plutonium to Pu(III) in acidic solutions (pH<1) in the presence of NCS(-) . The optical spectrum of [Et4 N][SCN] containing Pu(III) solution was indistinguishable from that of aquated Pu(III) suggesting that inner-sphere complexation with [Et4 N][SCN] does not occur in water. However, upon concentration, the homoleptic thiocyanate complex [Et4 N]4 [Pu(IV) (NCS)8 ] was crystallized when a large excess of [Et4 N][NCS] was present. This compound, along with its U(IV) analogue, maintains inner-sphere thiocyanate coordination in acetonitrile based on the observation of intense ligand-to-metal charge-transfer bands. Spectroscopic and crystallographic data do not support the interaction of the metal orbitals with the ligand π system, but support an enhanced An(IV) -NCS interaction, as the Lewis acidity of the metal ion increases from Th to Pu.


Molecular binding at gold transport interfaces. IV. Thiol chemisorption.
Alkene thiol/coinage metal molecular interfaces are relatively easy to make, and can result in well-ordered self-assembled monolayer films. The energetics of such formation is complex-differing experimental and theoretical accounts have focused on the nature of the binding, the energetics via different pathways (thiol radical, thiol or thiolate) and the geometry of binding. We report density functional theory calculations on a four atom gold cluster interacting with different (alkane, alkene, alkyne) thiolates. We find thiolate addition to be strongly exoergic, thiol radical to be roughly half as favorable, and thiol to be slightly favorable. We also find that the S-H bond can remain when the thiol attaches to the gold cluster, formally resulting in increased coordination on the sulfur atom.


A non-interventional study of the genetic polymorphisms of NOD2 associated with increased mortality in non-alcoholic liver transplant patients.
Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival. During a period of 20-months, 231 patients were recruited in this non-interventional, prospective study. Thirteen different SNPs and their impact on the patients' survival, infection rate, and use of dialysis were assessed. NOD 2 wildtype genes were protective with respect to the survival of non-alcoholic, cirrhotic transplant patients (3 year survival: 66.8% wildtype vs. 42.6% gene mutation, p = 0.026). This effect was not observed in alcoholic transplant recipients.The incidence of dialysis-dependent kidney failure and infection in the liver transplant patients was not influenced by NOD 2 gene polymorphisms. No effect was noted in the remaining 12 SNPs.Patients with early allograft dysfunction experienced significantly more infections, required dialysis and had significantly worse survival.In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival. NOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these data should be validated in a larger cohort.


Met in urological cancers.
Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.


Platelet alpha 2-adrenoceptor binding and function during the menstrual cycle.
Blood platelet receptors are widely used as peripheral models of central nervous system receptors, particularly in attempts to understand the biological basis of a number of neurological and psychiatric disorders. It is important to differentiate factors other than the primary disease process which may influence platelet receptors. One such potential factor is the menstrual cycle. In this study we have determined platelet high-affinity alpha 2-adrenoceptor binding, using the agonist ligand 3H-UK-14,304 and platelet aggregatory responses to adrenaline in 14 healthy young women, sampled on four occasions at weekly intervals. Our results indicate that, within the limits of individual variation, neither the KD or Bmax of high-affinity 3H-UK-14,304 binding or the aggregatory responses to adrenaline differed significantly between various stages of the menstrual cycle.


Partial Correlation-Based Retinotopically Organized Resting-State Functional Connectivity Within and Between Areas of the Visual Cortex Reflects More Than Cortical Distance.
Numerous studies have demonstrated functional magnetic resonance imaging (fMRI)-based resting-state functional connectivity (RSFC) between cortical areas. Recent evidence suggests that synchronous fluctuations in blood oxygenation level-dependent fMRI reflect functional organization at a scale finer than that of visual areas. In this study, we investigated whether RSFCs within and between lower visual areas are retinotopically organized and whether retinotopically organized RSFC merely reflects cortical distance. Subjects underwent retinotopic mapping and separately resting-state fMRI. Visual areas V1, V2, and V3, were subdivided into regions of interest (ROIs) according to quadrants and visual field eccentricity. Functional connectivity (FC) was computed based on Pearson's linear correlation (correlation), and Pearson's linear partial correlation (correlation between two time courses after the time courses from all other regions in the network are regressed out). Within a quadrant, within visual areas, all correlation and nearly all partial correlation FC measures showed statistical significance. Consistently in V1, V2, and to a lesser extent in V3, correlation decreased with increasing eccentricity separation. Consistent with previously reported monkey anatomical connectivity, correlation/partial correlation values between regions from adjacent areas (V1-V2 and V2-V3) were higher than those between nonadjacent areas (V1-V3). Within a quadrant, partial correlation showed consistent significance between regions from two different areas with the same or adjacent eccentricities. Pairs of ROIs with similar eccentricity showed higher correlation/partial correlation than pairs distant in eccentricity. Between dorsal and ventral quadrants, partial correlation between common and adjacent eccentricity regions within a visual area showed statistical significance; this extended to more distant eccentricity regions in V1. Within and between quadrants, correlation decreased approximately linearly with increasing distances separating the tested ROIs. Partial correlation showed a more complex dependence on cortical distance: it decreased exponentially with increasing distance within a quadrant, but was best fit by a quadratic function between quadrants. We conclude that RSFCs within and between lower visual areas are retinotopically organized. Correlation-based FC is nonselectively high across lower visual areas, even between regions that do not share direct anatomical connections. The mechanisms likely involve network effects caused by the dense anatomical connectivity within this network and projections from higher visual areas. FC based on partial correlation, which minimizes network effects, follows expectations based on direct anatomical connections in the monkey visual cortex better than correlation. Last, partial correlation-based retinotopically organized RSFC reflects more than cortical distance effects.


The effects of nicotine administration on the pathophysiology of rat aortic wall.
Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.


DNA agarose gel electrophoresis for antioxidant analysis: Development of a quantitative approach for phenolic extracts.
Most of the fast in vitro assays proposed to determine the antioxidant capacity of a compound/extract lack either biological context or employ complex protocols. Therefore, the present work proposes the improvement of an agarose gel DNA electrophoresis in order to allow for a quantitative estimation of the antioxidant capacity of pure phenolic compounds as well as of a phenolic rich extract, while also considering their possible pro-oxidant effects. The result obtained demonstrated that the proposed method allowed for the evaluation of the protection of DNA oxidation [in the presence of hydrogen peroxide (H2O2) and an H2O2/iron (III) chloride (FeCl3) systems] as well as for the observation of pro-oxidant activities, with the measurements registering interclass correlation coefficients above 0.9. Moreover, this method allowed for the characterization of the antioxidant capacity of a blueberry extract while demonstrating that it had no perceived pro-oxidant effect.


Comparison between minimally invasive, percutaneous osteosynthesis and locking plate osteosynthesis in 3-and 4-part proximal humerus fractures.
The ideal method for the surgical treatment of proximal humeral fractures has not yet been found. We therefore conducted a retrospective matched-pair analysis and compared osteosynthesis with open reduction and internal fixation and that with an angular stable plate with minimally invasive, closed reduction, percutaneous fixation with the Humerusblock. During a study period of 3 years, we matched 30 patients treated with angular stable plates (group 1) for age, gender, fracture type and handedness (dominant or nondominant) to 30 patients treated using the Humerusblock (group 2). At a minimal follow-up of 24 months, clinical evaluation included the Constant-Murley score, the UCLA score and the Simple Shoulder Test. Subjective pain was evaluated using the VAS pain scale. Patients were asked to rate their subjective satisfaction of final outcome as excellent, good, satisfied or dissatisfied. The mean CMS, UCLA score and SST differed significantly between groups 1 and 2 (60.9 vs 71.9, p < 0.01), (25.1 vs 29.5, p < 0.01) and (8.1 vs 9.4, p < 0.05), respectively. The VAS pain score was significantly lower in group 2 than in group 1 (1.2 vs 2.4; p < 0.01). The mean abduction (109.7° vs 133.7°; p < 0.01) and anterior flexion (128.3° vs 145.7°; p < 0.01) were significantly worse in group 1. The mean operation time was significantly shorter in group 2 (117.3 vs 72.1, p < 0.01). Complications occurred in 30 % (group 1) and 23 % (group 2) of patients. In this study, the functional outcome is superior in the Humerusblock group. However, the general outcome after surgical treatment of 3-and 4-part fractures is moderate, and the complication rate has to be considered, even though it can be lowered with the use of minimally invasive implants.


Mycobacterium tuberculosis and Mycobacterium avium modify the composition of the phagosomal membrane in infected macrophages by selective depletion of cell surface-derived glycoconjugates.
The growth of pathogenic mycobacteria in phagosomes of the host cell correlates with their ability to prevent phagosome maturation. The underlying molecular mechanism remains elusive. In a previous study, we have shown that Mycobacterium avium depletes the phagosome membrane of cell surface-derived glycoconjugates (de Chastellier and Thilo, Eur. J. Cell Biol. 81, 17-25, 2002). We now extended these quantitative observations to the major human pathogen, Mycobacterium tuberculosis (H37Rv). At increasing times after infection of mouse bone marrow-derived macrophages, cell-surface glycoconjugates were labelled enzymatically with [3H]galactose. Subsequent endocytic membrane traffic resulted in a redistribution of this label from the cell surface to endocytic membranes, including phagosomes. The steady-state distribution was measured by quantitative autoradiography at the electron microscope level. Relative to early endosomes, with which phagosomes continued to fuse and rapidly exchange membrane constituents, the phagosome membrane was depleted about 3-fold, starting during infection and in the course of 9 days thereafter. These results were in quantitative agreement with our previous observations for Mycobacterium avium. For the latter case, we now showed by cell fractionation that the depletion was selective, mainly involving glycoproteins in the 110-210 kDa range. Together, these results indicated that pathogenic mycobacteria induced and maintained a bulk change in phagosome membrane composition that could be of special relevance for survival of pathogenic mycobacteria within phagosomes.


An examination of the relationship between health information use and health orientation in Korean mothers: focusing on the type of health information.
The present study explores the relationship between mothers' health information use and health orientation regarding their children's health. Given that the online mothering community (i.e., parenting websites) is currently an important source of parenting information for mothers of young children, the present study distinguishes between informal online health information provided by mothering communities and formal online health information provided by health-related websites to test for differences. An online survey of 533 Korean mothers of children between the ages of 0 and 3 years revealed that the frequency of health-related website use (i.e., formal information) was associated with mothers' health consciousness and their health information orientation toward their children's health. The frequency of mothering community use (i.e., informal information) was associated with health information orientation, but not with health consciousness. Mass media use and contact with a health care professional for health information were not related to health consciousness or health information orientation. However, mothers' education level moderated the relationship between interpersonal communication and health consciousness, and between print media use and health information orientation. Results are discussed with an emphasis on the theoretical and practical implications of our findings.


Decontamination of autogenous bone grafts: systematic literature review and evidence-based proposal of a protocol.
There is a lack of consensus guidelines for the decontamination of autogenous bone grafts after exposure to a nonsterile environment during graft contouring, intraoral bone harvesting, or when inadvertently dropped off the sterile field. Transplantation of contaminated bone may cause infectious complications or even augmentation failure. When selecting the antimicrobial agent of choice to treat harvested bone for transplantation purposes, focus should be placed on the safety of the agent towards bone and osteoprogenitor cells, maximum elimination of targeted pathogens that directly affect bone tissue, and a short exposure time. In systematically reviewing study results on the degree of bone graft contamination and the effects of decontamination methods, a protocol for decontamination of autogenous bone grafts is proposed. Among various decontamination agents investigated, 1% chlorhexidine proved highly effective (mean reduction of bacterial colony-forming units compared to saline solution: 99.97%). Minimum contact time required is 15 seconds and cell proliferation can be observed up to 30 seconds of exposure. The proposed decontamination protocol (1% chlorhexidine for 15 seconds) seems to represent a reasonable compromise in reference to sterility and cell viability. Comparative effectiveness research, however, is needed before clinical recommendations may be posed.


Evaluation of the accuracy of Demirjian's method for estimating chronological age from dental age in Shiraz, Iran: Using geometric morphometrics method.
Knowing the growth and developmental stages of a child or an adolescent allows for a comparison between their developmental and chronological age. The purpose of this study was to evaluate the accuracy of dental age estimation by Demirjian's method and to examine the applicability of Demirjian's method to Iranian children and adolescents. To do so, we investigated the relationship between chronological and dental age in a total of 158 children (81 female and 77 male) from Shiraz. The present study, for the first time, employs geometric morphometrics, a relatively new technique, to offer an accurate quantitative assessment of Demirjian's method. The correlation coefficient between chronological and dental age showed a significant relationship between dental age and chronological age. The average of the chronological age difference between girls and boys at the time of reaching the same stages of dental development was 0.77 years, which meant girls reached each stage of dental development 9 months earlier than their male peers. According to the results of this study, although the use of Demirjian's method in estimating the age of children in the city of Shiraz has acceptable accuracy, more precise studies are recommended to calibrate the method and develop a table adjusted to reflect development in the Iranian population.


Medical sociology as a vocation.
This article extends Weber's discussion of science as a vocation by applying it to medical sociology. Having used qualitative methods for nearly 40 years to interpret problems of meaning as they arise in the context of health care, I describe how ethnography, in particular, and qualitative inquiry, more generally, may be used as a tool for understanding fundamental questions close to the heart but far from the mind of medical sociology. Such questions overlap with major policy questions such as how do we achieve a higher standard for quality of care and assure the safety of patients. Using my own research, I show how this engagement takes the form of showing how simple narratives of policy change fail to address the complexities of the problems that they are designed to remedy. I also attempt to explain how I balance objectivity with a commitment to creating a more equitable framework for health care.


Determination of polybrominated biphenyl residues in dairy products.
A method for the determination of polybrominated biphenyls (PBBs) in dairy products is described. Fat is extracted from the products by the official AOAC method. The PBB residues are separated from the fatty material by gel permeation chromatography prior to gas-liquid chromatographic (GLC) quantitation. An additional cleanup using petroleum ether elution through a miniature Florisil column is necessary for thin layer chromatographic (TLC) confirmation. Recoveries of PBBs from samples fortified at levels from 0.1 to 0.5 ppm ranged from 94 to 104% with an average of 99%. GLC sensitivity permits the estimation of PBB residue levels as low as 0.007 ppm. Routine TLC confirmation is limited by sensitivity to greater than or equal to 0.2 ppm.


Medical management of ectopic pregnancy--the role of methotrexate.
Ectopic pregnancy is an increasing health risk for women throughout the world. Recent advances in measurements of serum quantitative beta human chorionic gonadotropin and transvaginal ultrasonography have made it possible to diagnose ectopic pregnancy without laparoscopy. These developments have provided the atmosphere for trials using methotrexate as a nonsurgical treatment for ectopic pregnancy. This article briefly reviews the epidemiology and diagnosis of ectopic pregnancy. The medical management of ectopic pregnancy with methotrexate is then reviewed in more detail.


Comparison of plate-screw systems used in mandibular fracture reduction: finite element analysis.
A finite element model of the human dentate mandible has been developed to provide a comparison of fixation systems used currently for fracture reduction. Volume domains for cortical bone, cancellous bone, and teeth were created and meshed in ANSYS 8.0 based on IGES curves created from computerized tomography data. A unilateral molar clench was loaded on the model with a fracture gap simulated along the symphysis. Results based on Von Mises stress in cortical and cancellous bone surrounding the screws, and on fracture surface spatial fixation, show some relative differences between different screw-plate systems, yet all were judged to be appropriate in their reduction potential.


Pilot postoperative ileus study of escin in cancer patients after colorectal surgery.
Postoperative ileus, a common complication in patients after abdominal surgery, brings no benefit to the recovery of postoperative patients, and treatment targeted at restoring gastrointestinal motility may shorten the hospital stay. Studies have shown that escin accelerates gastrointestinal transit in mice and improves gastrointestinal motility in patients after abdominal surgery. A pilot study of escin's effect on the recovery of gastrointestinal motility was conducted in colorectal cancer patients in anticipation of a multiple-center randomized controlled trial. A total of 72 postoperative colorectal cancer patients were randomly assigned to four parallel groups on the basis of sealed envelopes-escin 5 mg group (E5 mg), escin 15 mg group (E15 mg), escin 25 mg group (E25 mg), and placebo group-with 18 patients in each group. Escin or placebo was diluted in 500 ml 5% dextrose injection, which was given once daily through the subclavian vein. The first injection took place 6 h after completion of the surgery. The treatment continued for 7 days or stopped at the time of the patient's first bowel movement. Time to recovery of passage of gas (TRPG), time to recovery of gastrointestinal sounds (TRGS), and time to recovery of bowel movements (TRBM) were recorded to evaluate the efficacy of escin. The TRPGs of the three escin treatment groups were 76.78 + 28.81 h (E5 mg), 72.06 + 14.65 h (E15 mg), and 65.50 + 26.70 h (E25 mg), respectively, with differences of 6.03 +/- 7.64 h (p = 0.436; E5 mg), 10.75 +/- 4.92 h (p = 0.036; E15 mg), and 17.31 +/- 7.20 h (p = 0.022; E25 mg) compared with the placebo group. The TRGSs of the three escin treatment groups were 45.28 +/- 26.15 h (E5 mg), 41.22 +/- 16.98 h (E15 mg), and 40.33 +/- 14.09 h (E25 mg), respectively, with differences of 4.33 +/- 7.12 h (p = 0.547; E5 mg), 8.39 +/- 5.36 h (p = 0.127; E15 mg), and 9.28 +/- 4.87 h (p = 0.065; E25 mg) compared with the placebo group. The TRBMs of the three escin treatment groups were 89.25 +/- 23.77 h (E5 mg), 84.83 +/- 27.91 h (E15 mg), and 84.44 +/- 19.74 h (E25 mg), respectively, with differences of 19.03 +/- 10.13 h (p = 0.069; E5 mg), 23.44 +/- 10.70 h (p = 0.035; E15 mg), and 23.83 +/- 9.63 h (p = 0.019; E25 mg) compared with the placebo group. The results of this pilot Postoperative Ileus Study of Escin (PISE) showed that escin can shorten the time to recovery of gastrointestinal motility in cancer patients after colorectal surgery.


Protein Disulfide Isomerase Modulates the Activation of Thyroid Hormone Receptors.
Thyroid hormone receptors (TRs) are responsible for mediating thyroid hormone (T3 and T4) actions at a cellular level. They belong to the nuclear receptor (NR) superfamily and execute their main functions inside the cell nuclei as hormone-regulated transcription factors. These receptors also exhibit so-called "non-classic" actions, for which other cellular proteins, apart from coregulators inside nuclei, regulate their activity. Aiming to find alternative pathways of TR modulation, we searched for interacting proteins and found that PDIA1 interacts with TRβ in a yeast two-hybrid screening assay. The functional implications of PDIA1-TR interactions are still unclear; however, our co-immunoprecipitation (co-IP) and fluorescence assay results showed that PDI was able to bind both TR isoforms in vitro. Moreover, T3 appears to have no important role in these interactions in cellular assays, where PDIA1 was able to regulate transcription of TRα and TRβ-mediated genes in different ways depending on the promoter region and on the TR isoform involved. Although PDIA1 appears to act as a coregulator, it binds to a TR surface that does not interfere with coactivator binding. However, the TR:PDIA1 complex affinity and activation are different depending on the TR isoform. Such differences may reflect the structural organization of the PDIA1:TR complex, as shown by models depicting an interaction interface with exposed cysteines from both proteins, suggesting that PDIA1 might modulate TR by its thiol reductase/isomerase activity.


Application of plastic conjugated materials in the repair of sports injury.
For professional athletes or fitness crowd who often participate in sports, sports injury are more common. However, the traditional repair materials for sports injury have many problems, such as long recovery period and poor repair effect. In recent years, many studies have found that conjugated materials have good stability, small side effects and other excellent characteristics, and conjugated materials are used in sports injury repair materials. In order to study the repair effect of conjugated materials on sports injury tissues, this paper prepared nitrogen porphyrin conjugated organic skeleton materials with pyrrole and p-benzaldehyde as substrates, used chemical synthesis and selective laser sintering technology to form plastic conjugated scaffold materials with polyvinyl alcohol, polylactide and conjugated materials, and established mechanical properties and constitutive formula to evaluate the performance characteristics of repair materials. In order to test the effect of plastic conjugated materials on sports injury, experiments were carried out from the aspects of degradability, mechanical properties of repair materials, repair effect of radius defect and new bone formation area. Experimental data: The proportion of newly formed bone area at weeks 3, 6, and 9 using this method was 32%, 52%, and 68%, while the proportion of newly formed bone area at weeks 3, 6, and 9 using traditional methods was 12%, 18%, and 23%, indicating that this method had better bone repair effects than traditional methods. The research in this paper provided a new idea for the application of plastic conjugated materials in the field of sports medicine.