Effects of cigarette smoke on nitric oxide synthase expression in the rat lung.
To examine the effects of cigarette smoke on nitric oxide synthase (NOS) gene expression and protein production, groups of rats were exposed to smoke once only or daily and were sacrificed after 1, 2, 7, or 28 days of exposure. NOS-1, NOS-2, and NOS-3 mRNAs in whole lung were quantified using reverse transcription polymerase chain reaction (RT-PCR), and NOS protein levels were determined by Western blots. Neither NOS-1 gene expression nor protein levels changed with smoke exposure. Levels of NOS-2 expression were more than doubled in smokers at Day 1 and decreased to control values during 1 month with daily smoke exposure, while protein levels did not change. NOS-3 expression was increased approximately 35% after 2 days of smoke exposure and remained increased to 28 days, whereas protein levels were increased by approximately 60% at Day 7 and remained elevated. In situ hybridization showed that NOS-2 was diffusely expressed in the lung parenchyma, airways, and vessels, and that NOS-3 was strongly expressed in vascular endothelium. Protein distribution, as determined by immunohistochemical staining, was identical to mRNA tissue distribution, and these distributions were not changed by smoke. We conclude that smoke exposure induces a rapid but transient increase in transcription of NOS-2, and a sustained increase in transcription and translation of NOS-3; up-regulation of NOS occurs within the anatomic compartment where these genes are normally expressed. These findings indicate that cigarette smoke can directly and rapidly affect NOS expression, and thus potentially affect the function of the pulmonary vasculature.


Histidine availability alters glucagon gene expression in murine alphaTC6 cells.
Because individual amino acids (AA) stimulate glucagon release from pancreatic alpha-cells, the purpose of this study was to determine if individual AA could influence glucagon gene expression. Preproglucagon mRNA levels were 67% lower (P < 0.05) in mouse alphaTC6 cells incubated for 12 h in amino acid-free medium compared with cells incubated in complete medium containing all 20 AA. A time-course study indicated that alphaTC6 cells incubated in amino acid-free medium +/-1 micromol/L puromycin or amino acid-containing medium plus puromycin exhibited similar preproglucagon mRNA decreases over 12 h. When 1 micromol/L actinomycin was added to medium with or without AA, ppG mRNA concentrations decreased (P < 0.05) for 3h; however, values at 12 h were not different than those at 3 h. Deletions of single AA from complete medium demonstrated that only histidine removal or depletion reproduced the decrease in ppG mRNA observed in amino acid-free medium. We conclude that histidine is involved in the regulation of preproglucagon mRNA levels in alphaTC6 cells and that this regulation may be operative during both transcriptional and post-transcriptional events.


Performance tests of newly developed adsorption/plasma combined system for decomposition of volatile organic compounds under continuous flow condition.
The adsorption/plasma decomposition with the combination of adsorption honeycomb-sheets and a plasma element is a new technology for small-sized apparatuses to decompose volatile organic compounds (VOCs) at concentrations lower than about 100 ppm. The feasibility of the prototype adsorption/plasma decomposition apparatus was evaluated with the simulated exhausts containing one VOC component and with real exhausts from a painting booth and an adhesion factory. The apparatus decomposed VOCs effectively at the painting booth exhaust but not always satisfactorily at the adhesion factory exhaust. The performance test results with real exhausts were discussed with respect to the concentration and discharge pattern of the exhausts and the basic properties of the system such as cooperation of adsorption and plasma reaction and the concentration dependence of the performance.


A rapid method for determination of 22 selected drugs in human urine by UHPLC/MS/MS for clinical application.
A rapid and sensitive ultra-HPLC/MSIMS (UHPLC/MSIMS) assay method for the simultaneous determination in human urine of 22 drugs belonging to different pharmaceutical groups was developed. The drugs were extracted from urine samples and then separated on a Zorbax Rapid Resolution High Definition SB-C18 column. The mobile phase consisted of methanol and water containing formic acid with gradient elution. The chromatographic separation time was 7 min. The MSIMS detector, equipped with an electrospray ionization source, was set up in both positive and negative modes. The lower LOQs for the drugs in this method were between 0.05 and 0.60 ng/mL. Calibration curves in human urine were generated in the range of 0.05-600 ng/mL. Method validation parameters such as intraday and interday precision, accuracy, extraction recovery, stability, selectivity, dilution integrity, and carryover effect for all the compounds were within the acceptable ranges. This simple and fast method was applied successfully to study the pharmacokinetics of four selected drugs in human urine collected from patients. This UHPLC/MS/MS method offers an attractive way forward for the development of a routine rapid analysis for selected substances, particularly given the growing amount of new information about drug properties.


Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach, over 8 years, in 11 cities of Turkey.
To evaluate the effectiveness of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach in Turkey and analyse predictors of poor hand hygiene compliance. An observational, prospective, interventional, before-and-after study was conducted from August 2003 to August 2011 in 12 intensive care units (ICU) of 12 hospitals in 11 cities. The study was divided into a baseline and a follow-up period and included random 30-minute observations for hand hygiene compliance in ICU. The hand hygiene approach included administrative support, supplies availability, education and training, reminders in the workplace, process surveillance, and performance feedback. We observed 21,145 opportunities for hand hygiene. Overall hand hygiene compliance increased from 28.8% to 91% (95% CI 87.6-93.0, p 0.0001). Multivariate and univariate analyses showed that several variables were significantly associated with poor hand hygiene compliance: males vs. females (39% vs. 48%; 95% CI 0.79-0.84, p 0.0001), ancillary staff vs. physicians (35% vs. 46%, 95% CI 0.73-0.78, p 0.0001), and adult vs. pediatric ICUs (42% vs. 74%, 95% CI 0.54-0.60, p 0.0001). Adherence to hand hygiene was significantly increased with the INICC Hand Hygiene Approach. Specific programmes should be directed to improve hand hygiene in variables found to be predictors of poor hand hygiene compliance.


Current problems and future opportunities of abdominal magnetic resonance imaging at higher field strengths.
Introduction of high-field-strength whole-body MR scanners to clinical routine made abdominal magnetic resonance (MR) imaging widely available. Higher field strength provides improved signal yield, but other issues such as shorter wavelength and increased power deposition of radiofrequency in tissue must also be taken into account. This review describes current problems and future opportunities of abdominal MR imaging at 3.0 T under special consideration of relevant physical properties and technical challenges: impact of higher field strength on signal-to-noise ratio, Larmor frequency, and chemical shift effects are elucidated in detail. Furthermore, changes in longitudinal and transverse relaxation times as well as increased susceptibility effects at 3.0 T are reported. General safety issues and limitations in radiofrequency power deposition are discussed. Subsequently, implications of the previously mentioned changed MR properties at 3.0 T on clinical abdominal examinations applying different sequence types are described.


Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in premature infants.
To identify the patent ductus arteriosus (PDA) shunt flow pattern using Doppler echocardiography; and to assess whether it could be used to predict the development of clinically significant PDA. Premature infants weighing under 1500 g, who required mechanical ventilation, and in whom daily echocardiography could be performed from day 1 until the ductus closed, and on day 7 to confirm closure, were studied. The PDA shunt flow was identified from four Doppler patterns, and the closed pattern of a closed duct was also presented. Clinically significant PDA was diagnosed when there was colour Doppler echocardiographic evidence of left to right ductal shunt associated with at least two of the following clinical signs: heart murmur (systolic or continuous); persistent tachycardia (heart rate > 160/min); hyperactive precordial pulsation; bounding pulses; and radiographic evidence of cardiomegaly or pulmonary congestion. Of 68 infants enrolled into this study, clinically significant PDA developed in 31. The most recordable sequence of transition change of shunt flow pattern for clinically significant PDA was: pulmonary hypertension pattern, to growing pattern, to pulsatile pattern, to closing pattern, to closed pattern. And that for non-clinically significant PDA was: pulmonary hypertension pattern, to closing pattern, to closed pattern. The growing and the pulsatile patterns were mostly documented in infants with clinically significant PDA. The first documented growing pattern to predict clinically significant PDA gave a sensitivity of 64.5% and a specificity of 81.1%; the first documented pulsatile pattern gave a sensitivity of 93.5% and a specificity of 100%. Doppler echocardiographic assessment of PDA shunt flow pattern during the first 4 days of life is useful for predicting the development of clinically significant PDA in premature infants. At that stage, the closing or closed Doppler pattern indicates that infants are not at risk of developing clinically significant PDA; the growing or pulsatile Doppler pattern indicates a continuing risk of developing clinically significant PDA.


Models and mechanisms of energy balance regulation in the young.
The proportion of the child and adolescent population that is in appropriate energy balance is declining throughout the developed world, and childhood obesity is a particular problem in the UK relative to other northern European countries. Assessment of the underlying causes of obesity, and the different routes to its development, may assist in the definition of successful intervention strategies. The network of peripheral and central (brain) regulatory systems that underlie energy balance and body weight and composition can, for the most part, only be approached experimentally through the study of appropriate laboratory animal models. This problem is particularly acute when the target is overweight and obesity in the young. Some of the mechanisms underlying the development of energy imbalance and specifically the onset of overweight and obesity in the young, and the metabolic health consequences of obesity, can be addressed by examination of experimental rodent models in which mutation of a single gene causes early-onset extreme obesity, genetic susceptibility to obesity is revealed in an obesogenic environment or early-life nutritional experience programmes susceptibility to obesity or metabolic problems in later life. These studies highlight genes that are essential to normal body-weight regulation in rodents and man, the impact of diet and diet-induced obesity on regulatory systems in the young and the potential sensitivity of developing regulatory systems to nutritional experiences in utero and during early life.


[Umbilical fibrous hamartoma of infancy: A case report].
Fibrous hamartoma of infancy (FHI) is a benign, soft tissue tumor that usually oc curs in children and has a characteristic histological morphology. To describe a case of congenital FHI with atypical histological and clinical characteristics. Full-term male newborn, with no perinatal morbid history was referred to dermatology due to a congenital erythe matous plaque in the umbilical region. The histological study showed a fusocelullar proliferation in dermis and hypodermis of biphasic distribution, with an infiltrative, swirling pattern and bundles of spindle fibroblast-like and myofibroblast-like cells, associated in depth with a mature adipose tissue component. The immunohistochemical study revealed diffuse positivity for CD34, and focal posi tivity for FXIIIa, without immunoreactivity for actin, desmin, MyoD1, S100, HMB45, Melan-A, or EMA. Fluorescent in situ hybridization (FISH) was negative for platelet-derived growth factor recep tor beta (PDGFR-beta) and for ETV6 gene. PDGFR-beta and ETV6 gene are present in congenital dermatofibrosarcoma protuberans and infantile fibrosarcoma, respectively. This history, in addition to previous histological findings, supported the diagnosis of FHI. Surgical resection was performed, without signs of recurrence during clinical follow-up. It is important to consider the FHI within the differential diagnosis of subcutaneous tumors in children, especially in those under two years of age. Although its behavior is benign, it is similar to multiple benign and malignant le sions, which makes it imperative to perform a histological study in front of suspicious clinical lesions.


Advances in the design of combination therapies for the treatment of tuberculosis.
Tuberculosis requires lengthy multi-drug therapy. Mycobacterium tuberculosis occupies different tissue compartments during infection, making drug access and susceptibility patterns variable. Antibiotic combinations are needed to ensure each compartment of infection is reached with effective drug treatment. Despite drug combinations' role in treating tuberculosis, the design of such combinations has been tackled relatively late in the drug development process, limiting the number of drug combinations tested. In recent years, there has been significant progress using in vitro, in vivo, and computational methodologies to interrogate combination drug effects. This review discusses the advances in these methodologies and how they may be used in conjunction with new successful clinical trials of novel drug combinations to design optimized combination therapies for tuberculosis. Literature searches for approaches and experimental models used to evaluate drug combination effects were undertaken. We are entering an era richer in combination drug effect and pharmacokinetic/pharmacodynamic data, genetic tools, and outcome measurement types. Application of computational modeling approaches that integrate these data and produce predictive models of clinical outcomes may enable the field to generate novel, effective multidrug therapies using existing and new drug combination backbones.


Time-action analysis (TAA) of the surgical technique implanting the collum femoris preserving (CFP) hip arthroplasty. TAASTIC trial identifying pitfalls during the learning curve of surgeons participating in a subsequent randomized controlled trial (an observational study).
Two types of methods are used to assess learning curves: outcome assessment and process assessment. Outcome measures are usually dichotomous rare events like complication rates and survival or require an extensive follow-up and are therefore often inadequate to monitor individual learning curves. Time-action analysis (TAA) is a tool to objectively determine the level of efficiency of individual steps of a surgical procedure. We are currently using TAA to determine the number of cases needed for surgeons to reach proficiency with a new innovative hip implant prior to initiating a multicentre RCT. By analysing the unedited video recordings of the first 20 procedures of each surgeon the number and duration of the actions needed for a surgeon to achieve his goal and the efficiency of these actions is measured. We constructed a taxonomy or list of actions which together describe the complete surgical procedure. In the taxonomy we categorised the procedure in 5 different Goal Oriented Phases (GOP): 1. the incision phase. 2. the femoral phase. 3. the acetabulum phase. 4. the stem phase. 5. the closure pase. Each GOP was subdivided in Goal Oriented Actions (GOA) and each GOA is subdivided in Separate Actions (SA) thereby defining all the necessary actions to complete the procedure. We grouped the SAs into GOAs since it would not be feasible to measure each SA. Using the video recordings, the duration of each GOA was recorded as well as the amount of delay. Delay consists of repetitions, waiting and additional actions. The nett GOA time is the total GOA time - delay and is a representation of the level of difficulty of each procedure. Efficiency is the percentage of nett GOA time during each procedure. This allows the construction of individual learning curves, assessment of the final skill level for each surgeon and comparison of different surgeons prior to participation in an RCT. We believe an objective and comparable assessment of skill level by process assessment can improve the value of a surgical RCT in situations where a learning curve is expected.


A comparison of the anticipated benefits and received outcomes of pediatric cochlear implantation: parental perspectives.
Findings of a study that investigated parents' expectations and experiences of their children's outcomes with cochlear implants are presented. A survey completed by 247 parents whose children had received implants in eastern Australia compared parents' reports of their preimplant expectations with their experiences of postimplant outcomes on several items related to communication, academic, and psychosocial domains. Quantitative findings derived from the survey data were extended and elaborated on by qualitative findings from interviews with 27 of the parents. The findings indicated that parents' relatively high expectations of their children's outcomes largely had been met, although a tenth of survey respondents reported that their expectations had not been met. It appeared that professionals generally provided parents with realistic expectations. The qualitative findings revealed a complex interaction among parents' expectations, hopes, and determination that their children would do well with the implant. Implications for professionals are discussed.


A low-frequency variant in MAPK14 provides mechanistic evidence of a link with myeloperoxidase: a prognostic cardiovascular risk marker.
Genetics can be used to predict drug effects and generate hypotheses around alternative indications. To support Losmapimod, a p38 mitogen-activated protein kinase inhibitor in development for acute coronary syndrome, we characterized gene variation in MAPK11/14 genes by exome sequencing and follow-up genotyping or imputation in participants well-phenotyped for cardiovascular and metabolic traits. Investigation of genetic variation in MAPK11 and MAPK14 genes using additive genetic models in linear or logistic regression with cardiovascular, metabolic, and biomarker phenotypes highlighted an association of RS2859144 in MAPK14 with myeloperoxidase in a dyslipidemic population (Genetic Epidemiology of Metabolic Syndrome Study), P=2.3×10(-6)). This variant (or proxy) was consistently associated with myeloperoxidase in the Framingham Heart Study and Cardiovascular Health Study studies (replication meta-P=0.003), leading to a meta-P value of 9.96×10(-7) in the 3 dyslipidemic groups. The variant or its proxy was then profiled in additional population-based cohorts (up to a total of 58 930 subjects) including Cohorte Lausannoise, Ely, Fenland, European Prospective Investigation of Cancer, London Life Sciences Prospective Population Study, and the Genetics of Obesity Associations study obesity case-control for up to 40 cardiovascular and metabolic traits. Overall analysis identified the same single nucleotide polymorphisms to be nominally associated consistently with glomerular filtration rate (P=0.002) and risk of obesity (body mass index ≥30 kg/m(2), P=0.004). As myeloperoxidase is a prognostic marker of coronary events, the MAPK14 variant may provide a mechanistic link between p38 map kinase and these events, providing information consistent with current indication of Losmapimod for acute coronary syndrome. If replicated, the association with glomerular filtration rate, along with previous biological findings, also provides support for kidney diseases as alternative indications.


The oncolytic adenovirus VCN-01 promotes anti-tumor effect in primitive neuroectodermal tumor models.
Last advances in the treatment of pediatric tumors has led to an increase of survival rates of children affected by primitive neuroectodermal tumors, however, still a significant amount of the patients do not overcome the disease. In addition, the survivors might suffer from severe side effects caused by the current standard treatments. Oncolytic virotherapy has emerged in the last years as a promising alternative for the treatment of solid tumors. In this work, we study the anti-tumor effect mediated by the oncolytic adenovirus VCN-01 in CNS-PNET models. VCN-01 is able to infect and replicate in PNET cell cultures, leading to a cytotoxicity and immunogenic cell death. In vivo, VCN-01 increased significantly the median survival of mice and led to long-term survivors in two orthotopic models of PNETs. In summary, these results underscore the therapeutic effect of VCN-01 for rare pediatric cancers such as PNETs, and warrants further exploration on the use of this virus to treat them.


Oscillations and patterns in a model of simultaneous CO and C2H2 oxidation and NO(x) reduction in a cross-flow reactor.
A model describing simultaneous catalytic oxidation of CO and C2H2 and reduction of NOx in a cross-flow tubular reactor is explored with the aim of relating spatiotemporal patterns to specific pathways in the mechanism. For that purpose, a detailed mechanism proposed for three-way catalytic converters is split into two subsystems, (i) simultaneous oxidation of CO and C2H2, and (ii) oxidation of CO combined with NOx reduction. The ability of these two subsystems to display mechanism-specific dynamical effects is studied initially by neglecting transport phenomena and applying stoichiometric network and bifurcation analyses. We obtain inlet temperature - inlet oxygen concentration bifurcation diagrams, where each region possessing specific dynamics - oscillatory, bistable and excitable - is associated with a dominant reaction pathway. Next, the spatiotemporal behaviour due to reaction kinetics combined with transport processes is studied. The observed spatiotemporal patterns include phase waves, travelling fronts, pulse waves and spatiotemporal chaos. Although these types of pattern occur generally when the kinetic scheme possesses autocatalysis, we find that some of their properties depend on the underlying dominant reaction pathway. The relation of patterns to specific reaction pathways is discussed.


[Necessity of neurophysiological monitoring in the operating room].
Inadequate anesthesiological appliance that manifests itself as either intraanesthestic awakening or excessively deep anesthesia remains one of the unsolved problems of current anesthesiology. In our opinion, the absence of necessary monitoring and clear criteria for the sufficient depth of anesthesia is a principal cause of inadequate anesthesia. Our experience and the data available in the literature show that only monitoring of the functional activity of the central nervous system (CNS) most fully meets the requirements presented. The inclusion of monitoring of the intraoperative state of CNS provides each patient adequate anesthesiological protection irrespective of the body's individual traits.


Removal efficiency of calcium hydroxide dressing from the root canal without chemically active adjuvant.
Compare the efficiency in removing two calcium hydroxide [Ca(OH)2] preparations from root canal and apical third using single use syringe, ultrasonics and RinsEndo((®)) with saline solution. One hundred and eighty human singlerooted teeth were instrumented using ProTaper((®)) rotary system, divided into two groups according to Ca(OH)2 filling. A: Powder mixed with water, B: Pulpdent((®)). Each group was divided into three subgroups for the irrigation: A1, B1: Single use syringe; A2, B2: Ultrasonics; A3, B3: RinsEndo((®)). Teeth were split longitudinally, photographed and imported into Adobe Photoshop. The percentage ratios of Ca(OH)2 remaining in the canal and in the apical third were calculated. Data were statistically analyzed using 'ANOVA two-way' and 'univariate tests'. (a) Remnants of medicament were found in all teeth, (b) no statistically significant difference in the elimination of both Ca(OH)2 from the entire canal (p = 0.436), however, mixed powder was better eliminated from the apical third (p = 0.005), (c) no statistically significant difference among the irrigation techniques in the whole canal (p = 0.608), though, RinsEndo((®)) and ultrasonics were the most effective in cleaning the apical third (p = 0.032) when mixed powder was used. None of the techniques removed completely Ca(OH)2 from the canal. In the apical third, RinsEndo((®)) and ultrasonics were the most effective when mixed powder was used. Ca(OH)2, the most commonly used intracanal dressing, should be completely eliminated before the obturation to assure a good endodontic sealing. Based on the results of this study, RinsEndo((®)) and ultrasonics were the most effective in removal of Ca(OH)2 especially the powder mixed with water presentation.


Dispersive white-light spectral interferometry with absolute phase retrieval to measure thin film.
We present a white-light spectral interferometric technique for measuring the absolute spectral optical path difference (OPD) between the beams in a slightly dispersive Michelson interferometer with a thin-film structure as a mirror. We record two spectral interferograms to obtain the spectral interference signal and retrieve from it the spectral phase, which includes the effect of a cube beam splitter and the phase change on reflection from the thin-film structure. Knowing the effective thickness and dispersion of the beam splitter made of BK7 optical glass, we use a simple procedure to determine both the absolute spectral phase difference and OPD. The spectral OPD is measured for a uniform SiO(2) thin film on a silicon wafer and is fitted to the theoretical spectral OPD to obtain the thin-film thickness. The theoretical spectral OPD is determined provided that the optical constants of the thin-film structure are known. We measure also the nonlinear-like spectral phase and fit it to the theoretical values in order to obtain the thin-film thickness.


Laryngeal trauma. Diagnosis and management.
Acute laryngeal trauma caused by either blunt or penetrating injuries is a difficult airway management problem. Patients may be aphonic or intubated due to the injury, and important historical facts may not be available. Because of this, the recognition and initial proper management of this injury is essential to a successful outcome. Flexible endoscopy provides an easy and accurate examination of the injured larynx without risk of injury to the patient. Assessment of vascular and esophageal injuries is also the key in management of this patient group. The use of CT imaging helps delineate injuries that are not well defined by physical examination. Immediate operative intervention with repair of mucosal injuries and stabilization of cartilaginous framework usually results in good airway and voice quality.


Enhancement of polyphenol recovery from rosemary (Rosmarinus officinalis) and sage (Salvia officinalis) by enzyme-assisted ensiling (ENLAC).
The efficacy of enzyme-assisted ensiling (ENLAC) in the recovery of polyphenols from rosemary and sage was tested. Fresh rosemary and sage were chopped and ensiled in 0.5-L anaerobic jars. Treatments comprised control (no additives), 0.5% glucose and lactic acid bacteria, and 1% cellulase plus 1% hemicellulase plus pectinase. Following storage at room temperature for 45 days (experiment 1) and 26 days (experiment 2), polyphenols were extracted from the silages in ethanol either by direct blending or by cold extraction. The enzyme treatment resulted in silages with the lowest pH values, lowest fiber content, highest water-soluble sugar content, and highest polyphenol recovery; this treatment resulted in increased polyphenol recovery from rosemary and sage, by 100 and 20%, respectively. Comparison between direct blending and cold extraction revealed similar efficiency of polyphenol recovery.


Imaging pediatric bone sarcomas. Diagnosis and treatment-related issues.
The treatment of pediatric bone malignancies has undergone dramatic change in the past two decades. With the use of adjuvant chemotherapy, survival of patients with osteosarcoma and Ewing's sarcoma has greatly increased and most extremity lesions are now managed with an initial course of chemotherapy followed by limb-sparing surgery rather than amputation. Radiologists are called on not only to help diagnose and stage these tumors, but also to assess their extent, to determine response to preoperative chemotherapy, and to monitor patients for postoperative complications and recurrent disease. This article discusses imaging solutions to clinical issues that arise during the care of these children.


Performance of nutritional screening tools in predicting poor six-month outcome in hospitalised older patients.
Malnutrition is a major problem in hospitalised older people. Many nutrition screening tools are available for malnutrition identification, however little is known about their prognostic ability. This prospective, observational study investigated the prognostic value of three nutritional screening tools in a Geriatric Evaluation and Management Unit: the Geriatric Nutritional Risk Index (GNRI), the Mini Nutritional Assessment (MNA) and the Mini Nutritional Assessment short form (MNA-SF), incorporating either body mass index or calf circumference. Poor six- month outcome was defined as new admission to higher level residential care or mortality at six months post-discharge. Predictive ability of poor outcome was assessed by logistic regression models, adjusting for age, gender, cognition and co-morbidity. Predictive accuracy was determined by area under Receiver Operator Characteristic curves, sensitivity, specificity, predictive values and Youden Index. One hundred and seventy-two consecutive patients with a mean (SD) age=85.2 (6.4) years were included in the study. Malnutrition was identified in 31% of patients using the MNA and was associated with a higher risk of poor six-month outcome when identified by the MNA (OR, 95% CI=3.29, 1.17-9.23) and the GNRI (OR, 95% CI=2.84, 1.31-6.19), but not by the MNA-SF. All screening tools lacked discriminative power for outcome prediction. The MNA and GNRI were useful clinical predictors of poor six-month outcome, although their accuracy of prediction was low. Nutritional screening remains a priority in the routine assessment of hospitalised older people.


Spatiotemporal variation and socioeconomic factors of financial hardships of out-of-pocket health expenditure in Pakistan.
Financial hardships of out-of-pocket health expenditure (OPHE) is a growing concern for health policy makers in many low and middle-income countries. Spatiotemporal variation between Pakistan's four provinces over 2001-2015 is discussed, which would help comparing existing health services delivery and financial risk protection plans. In this paper, we estimate financial hardship of OPHE in Pakistan. We use the data sets of the household integrated economic surveys 2001-02, 2005-06, 2010-11 and 2015-16. We estimate OPHE share in household total and non-subsistence expenditure, catastrophic headcount at the threshold of OPHE ≥ 10% of total expenditure or OPHE ≥ 25% of non-subsistence expenditure. We estimate impoverishment of OPHE using national poverty lines. Finally, we explore socioeconomic factors of financial hardships of OPHE. Over the years, catastrophic headcount and impoverishment of OPHE had decreased at national level (-1.3% points) and in the provinces of Sindh (-7.8% points) and Khyber Pukhtoonkhawa (KPK), (-2.8% points). The province of KPK and the year 2005-06 witnessed the highest incidence of financial catastrophe (26.89% points) and impoverishment (4.8% points) of OPHE. Households in rural areas, in the middle and rich quintiles and those headed by a male were more likely to encounter financial catastrophe and impoverishment due to OPHE. Inter-provincial variation in financial hardships of OPHE provide aide to provincial level priority setting. The high impact of OPHE in the non-poor, in rural areas, and in KPK calls for enhanced targeting of financial risk protection plans.


Comparison of the toxicity of aluminum oxide nanorods with different aspect ratio.
Aluminum oxide nanoparticles are listed among 14 high-priority nanomaterials published by the Organization for Economic Co-operation and Development, but limited information is available on their potential hazards. In this study, we compared the toxicity of two different aluminum oxide nanorods (AlNRs) commercially available in vivo and in vitro. Considering aspect ratio, one was 6.2 ± 0.6 (long-AlNRs) and the other was 2.1 ± 0.4 (short-AlNRs). In mice, long-AlNRs induced longer and stronger inflammatory responses than short-AlNRs, and the degree reached the maximum on day 7 for both types and decreased with time. In addition, in vitro tests were performed on six cell lines derived from potential target organs for AlNPs, HEK-293 (kidney), HACAT (skin), Chang (liver), BEAS-2B (lung), T98G (brain), and H9C2 (heart), using MTT assay, ATP assay, LDH release, and xCELLigence system. Long-AlNRs generally produced stronger toxicity than short-AlNRs, and HEK-293 cells were the most sensitive for both AlNRs, followed by BEAS-2B cells, although results from 4 kinds of toxicity tests conflicted among the cell lines. Based on these results, we suggest that toxicity of AlNRs may be related to aspect ratio (and resultant surface area). Furthermore, novel in vitro toxicity testing methods are needed to resolve questionable results caused by the unique properties of nanoparticles.


Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.
We are coming to appreciate that at fertilization human spermatozoa deliver the paternal genome alongside a suite of structures, proteins and RNAs. Although the role of some of the structures and proteins as requisite elements for early human development has been established, the function of the sperm-delivered RNAs remains a point for discussion. The presence of RNAs in transcriptionally quiescent spermatozoa can only be derived from transcription that precedes late spermiogenesis. A cross-platform microarray strategy was used to assess the profile of human spermatozoal transcripts from fertile males who had fathered at least one child compared to teratozoospermic individuals. Unsupervised clustering of the data followed by pathway and ontological analysis revealed the transcriptional perturbation common to the affected individuals. Transcripts encoding components of various cellular remodeling pathways, such as the ubiquitin-proteosome pathway, were severely disrupted. The origin of the perturbation could be traced as far back as the pachytene stage of spermatogenesis. It is anticipated that this diagnostic strategy will prove valuable for understanding male factor infertility.


Study on insulin resistance in TCM treatment of noninsulin-dependent diabetes mellitus.
In the present paper, it is advanced that in TCM treatment of noninsulin-dependent diabetes mellitus (NIDDM), insulin resistance must be studied; and it is held that reversing or relieving of insulin resistance is the ultimate aim for treating NIDDM, and looking for the prescriptions of reversing the insulin resistance is an urgent task. Therefore, establishing the indexes of comprehensive assessment for the insulin resistance and the related models of the disease is the basis and prerequisite for the study.


Maggots as a wound debridement agent for chronic venous leg ulcers under graduated compression bandages: A randomised controlled trial.
Slough in chronic venous leg ulcers may be associated with delayed healing. The purpose of this study was to assess larval debridement in chronic venous leg ulcers and to assess subsequent effect on healing. All patients with chronic leg ulcers presenting to the leg ulcer service were evaluated for the study. Exclusion criteria were: ankle brachial pressure indices <0.85 or >1.25, no venous reflux on duplex and <20% of ulcer surface covered with slough. Participants were randomly allocated to either 4-layer compression bandaging alone or 4-layer compression bandaging + larvae. Surface areas of ulcer and slough were assessed on day 4; 4-layer compression bandaging was then continued and ulcer size was measured every 2 weeks for up to 12 weeks. A total of 601 patients with chronic leg ulcers were screened between November 2008 and July 2012. Of these, 20 were randomised to 4-layer compression bandaging and 20 to 4-layer compression bandaging + larvae. Median (range) ulcer size was 10.8 (3-21.3) cm(2) and 8.1 (4.3-13.5) cm(2) in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Mann-Whitney U test, P = 0.184). On day 4, median reduction in slough area was 3.7 cm(2) in the 4-layer compression bandaging group (P < 0.05) and 4.2 cm(2) (P < 0.001) in the 4-layer compression bandaging + larvae group. Median percentage area reduction of slough was 50% in the 4-layer compression bandaging group and 84% in the 4-layer compression bandaging + larvae group (Mann-Whitney U test, P < 0.05). The 12-week healing rate was 73% and 68% in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Kaplan-Meier analysis, P = 0.664). Larval debridement therapy improves wound debridement in chronic venous leg ulcers treated with multilayer compression bandages. However, no subsequent improvement in ulcer healing was demonstrated.


A novel method for rapid detection of Streptococcus pneumoniae antigen in sputum and its application in adult respiratory tract infections.
A highly sensitive immunochromatography test kit, ODK0501, was developed using specific polyclonal antibodies against the C-polysaccharide moiety of Streptococcus pneumoniae for the rapid detection of S. pneumoniae antigen in sputum samples. The clinical utility of ODK0501 for this detection was evaluated prospectively in 52 adult patients with respiratory infections and compared with that of a urinary antigen detection kit. Overall, 21 patients (40.4 %) showed positive results with ODK0501, compared with 16 patients (30.8 %) using the urinary antigen detection kit, and S. pneumoniae was cultured from 18 patients. ODK0501 and the urinary antigen detection kit exhibited a sensitivity of 94.4 and 55.6 % (P<0.01), respectively, and a specificity of 88.2 and 82.4 %, respectively. Eleven of thirteen patients with conflicting results between the two test kits exhibited consistent results for sputum cultures. Moreover, eight out of nine patients positive for ODK0501 and negative for the urinary antigen detection kit were S. pneumoniae culture-positive, including five who exhibited phagocytosis, indicating S. pneumoniae as a causative agent of infection, in Gram staining of sputum samples. These results suggest that the ODK0501 direct sputum detection kit is more clinically useful than the urinary antigen detection kit in adult patients with respiratory infections.


Local control and distant metastases in primary canine malignant melanomas treated with hyperthermia and/or radiotherapy.
Forty-three dogs with primary malignant melanoma were randomized to receive radiotherapy alone (XRT) or hyperthermia plus radiotherapy (delta + XRT). Tumour responses were analysed in terms of complete response rates, rate of one year disease free survival and the incidence and time to develop distant metastasis. The frequency of complete responses (CR) was greater with adjuvant heat (76 per cent vs 21 per cent for XRT; P = 0.001). A trend towards an improvement in one year disease free survival was observed with delta + XRT (23.8 per cent) as compared with XRT (7.7 per cent), but the difference was not statistically significant. The frequency of distant metastases was not different between the two treatments. Descriptors of intratumoural temperatures achieved during therapy indicated that higher CR rates could be achieved with higher minima. When minima were less than and greater than 20 Equivalent minutes at 43 degrees C (Eq43) the CR rates were 64 and 90 per cent, respectively. One year disease free survival rates and frequencies of distant metastases seemed to be correlated with the intratumoural temperatures as well. This was reflected in analyses examining temperature minima and maxima. Examination of patterns of failure suggested that the most plausible explanation for the correlation between intratumoural temperature and metastases was the high local failure rate (70 per in the heated group). The results of this study emphasize the need for further investigation of the influence of local hyperthermia as a part of curative therapy on the frequency of distant metastases.


Enhancement of polymer endurance to UV light by incorporation of semiconductor nanoparticles.
Improvement of polyvinyl alcohol stability against ultraviolet (UV) illumination is achieved by introducing cadmium sulfide (CdS) nanoparticles into the polymeric matrix. Enhancement of stability is analyzed by optical characterization methods. UV protection is achieved by diminishing the probability of photo-activated formation of defects in polymer. The sources of polymer protection are the lowering of the efficiency of polymer excitation via partial absorption of incident light by the embedded nanoparticles as well as the de-excitation of the macromolecules that have already absorbed UV quanta via energy drain to nanoparticles. Within the nanoparticles, the energy is either dissipated by conversion to the thermal energy or reemitted as visible-range photoluminescence quanta.


Where Are the Women in Orthopaedic Surgery?
Although women account for approximately half of the medical students in the United States, they represent only 13% of orthopaedic surgery residents and 4% of members of the American Academy of Orthopaedic Surgeons (AAOS). Furthermore, a smaller relative percentage of women pursue careers in orthopaedic surgery than in any other subspecialty. Formal investigations regarding the gender discrepancy in choice of orthopaedic surgery are lacking. (1) What reasons do women orthopaedic surgeons cite for why they chose this specialty? (2) What perceptions do women orthopaedic surgeons think might deter other women from pursuing this field? (3) What role does early exposure to orthopaedics and mentorship play in this choice? (4) What professional and personal choices do women in orthopaedics make, and how might this inform students who are choosing a career path? A 21-question survey was emailed to all active, candidate, and resident members of the Ruth Jackson Orthopaedic Society (RJOS, n = 556). RJOS is the oldest surgical women's organization incorporated in the United States. An independent orthopaedic specialty society, RJOS supports leadership training, mentorship, grant opportunities, and advocacy for its members and promotes sex-related musculoskeletal research. Although not all women in orthopaedic practice or training belong to RJOS, it is estimated that 42% of women AAOS fellows are RJOS members. Questions were formulated to determine demographics, practice patterns, and lifestyle choices of women who chose orthopaedic surgery as a specialty. Specifically, we evaluated the respondents' decisions about their careers and their opinions of why more women do not choose this field. For the purpose of this analysis, the influences and dissuaders were divided into three major categories: personal attributes, experience/exposure, and work/life considerations. The most common reasons cited for having chosen orthopaedic surgery were enjoyment of manual tasks (165 of 232 [71%]), professional satisfaction (125 of 232 [54%]), and intellectual stimulation (123 of 232 [53%]). The most common reasons indicated for why women might not choose orthopaedics included perceived inability to have a good work/life balance (182 of 232 [78%]), perception that too much physical strength is required (171 of 232 [74%]), and lack of strong mentorship in medical school or earlier (161 of 232 [69%]). Respondents frequently (29 of 45 [64%]) commented that their role models, mentors, and early exposure to musculoskeletal medicine were influential, but far fewer (62 of 231 [27%]) acknowledged these in their top five influences than they did the more "internal" motivators. To our knowledge, this is the largest study of women orthopaedic surgeons regarding factors influencing their professional and personal choices. Our data suggest that the relatively few women currently practicing orthopaedics were attracted to the field because of their individual personal affinity for its nature despite the lack of role models and exposure. The latter factors may impact the continued paucity of women pursuing this field. Programs designed to improve mentorship and increase early exposure to orthopaedics and orthopaedic surgeons may increase personal interest in the field and will be important to attract a diverse group of trainees to our specialty in the future.


The effect of decalcified bone matrix on the osteogenic potential of bone marrow.
Rabbit bone marrow cells were cultured in diffusion chambers with or without decalcified bone matrix. The chambers were assayed after 28 days for alkaline phosphatase activity, deoxyribonucleic acid (DNA), calcium, and phosphorus contents. Morphologically, marrow cells incubated with or without matrix differentiated to form bone and cartilage. With bone matrix, the calcium and phosphorus contents of chambers were significantly higher than control chambers. Alkaline phosphatase activity and DNA content were not influenced by inclusion of bone matrix. These results indicate that bone matrix constituents exert a stimulatory effect on bone formation from marrow cells. This osteogenic stimulation could be due to the influence of an osteoinductive factor and/or to stimulation of osteoprogenitor cells known to be present in the marrow.


A comparative study on the shaping ability of k3, profile and protaper instruments in simulated curved root canals.
The objective of this study was to compare the shaping ability of three rotary filing systems; constant taper K3 instruments, constant taper ProFile instruments and progressive taper ProTaper rotary instruments in clear resin blocks with simulated curved root canals. Forty five resin blocks were divided into three groups. Group A preparation was conducted with K3, Group B with ProFile and Group C with ProTaper instruments. Pre and post instrumentation images were superimposed and assessment of the canal shape was completed with a computer image analysis program at 14 levels of the root canal system. Group A inner and outer curvature pre and post instrumentation values were significantly different (P<0.05) at levels 3; at level 13 only the outer curvature and levels 6, 7, 8 the inner curvature had significantly different values between pre and post instrumentation. Group C had significant P values (P<0.05) at levels 2, 3, 4, 12, 13 in the outer curvature and at levels 6, 7, 8 of the inner curvature. Overall, all three rotary instruments maintained root canal curvatures well. ProTaper instruments significantly removed more resin material from outer canal curvature in the apical third when compared to the other two groups.


[Viscosity of free and protein-bound lipids in membranes].
Structural transitions induced by temperature in the lipid bilayer of rabbit sarcoplasmic reticulum membranes have been detected by means of the hydrophobic fluorescent probe pyren. Using the phenomenon of energy migration from membrane protein tryptophan residues to pyren a correct estimate of lipid viscosity near protein molecules was made by an empirical formula. The structural transitions of free and protein-bound lipids proceeded at the same temperature intervals. It was found that viscosity of protein-bound lipids was higher than that of free lipids, but they became equal at 36--39 degrees C.


[Effect of indomethacin on the development of cardiac and hemodynamic disorders in shock of immune origin].
Blockade of biosynthesis of prostaglandins (indomethacin) was shown to decrease significantly disorders of cardio- and hemodynamics after immune heart damages (intracoronary anticardiac serum injections) in experimental anesthetized dogs. A positive effect of indomethacin was produced by blockade of the first part (0-15 min) of capacity vessels dilation reaction (blood deposition), subsequent decrease of venous return limit and fall of heart output. Indomethacin potentiated constriction of coronary vessels.


[Asperger syndrome with highly exceptional calendar memory: a case report].
Some patients with pervasive developmental disorders develop unusual talents, which are characterized as savant syndrome. Herein we present neuropsychological examination and brain imaging (fMRI and brain SPECT) findings of an 18-year-old male with Asperger syndrome and highly unusual calendar memory. Neuropsychological evaluation of the case indicated mild attention, memory, and problem solving deficits, and severe executive function deficits that included conceptualization, category formation, and abstraction. Functional MRI findings showed activation above the baseline level (P<0.05) in the bilateral inferior parietal lobule, precuneus, superior and middle frontal gyri, and medial frontal cortex. Brain SPECT findings, in comparison to rest-SPECT findings, showed that there was hypoperfusion in some brain regions, including the right frontal cortex and right parietal cortex. Baseline blood perfusion in the left frontal cortex was also observed, as well as hypoperfusion in the right parietal-occipital cortex and in the right basal ganglion (compared to the left side). The results of the present study and further research will contribute to our understanding of calendar memory and savant syndrome.


Ethical challenges in global health-related stigma research.
It is critically important to conduct research on stigmatized conditions, to include marginalized groups that experience stigma, and to develop interventions to reduce stigma. However, such research is ethically challenging. Though superficial reference is frequently made to these widely acknowledged challenges, few publications have focused on ethical issues in research on stigmatized groups or conditions. In fact, a brief literature review found only two such publications. At a recent Science of Stigma Reduction workshop comprising 60 stigma researchers from the USA and low and middle-income countries, the need for more robust and critical discussion of the ethics of the research was highlighted. In this paper we describe, illustrate through cases, and critically examine key ethical challenges that are more likely to arise because a research study focuses on health-related stigma or involves stigmatized groups or conditions. We examine the ethics of this research from two perspectives. First, through the lens of overprotection, where we discuss how the perception of stigma can impede ethical research, disrespect research participants, and narrow the research questions. Second, through the lens of research risks, where we consider how research with stigmatized populations can unintentionally result in harms. Research-related harms to participants include potential breaches of confidentiality and the exacerbation of stigma. Potential harms also extend to third parties, including families and populations who may be affected by the dissemination of research results. Research with stigmatized populations and on stigmatized conditions should not be impeded by unnecessary or inappropriate protective measures. Nevertheless, it may entail different and greater risks than other health research. Investigators and research ethics committees must be particularly attentive to these risks and how to manage them.


Perinatal depression screening in a Women, Infants, and Children (WIC) program: perception of feasibility and acceptability among a multidisciplinary staff.
Best practices for addressing women's mental health and screening for depression in public health clinics are not available. Clinic staff are often responsible for screening for depression; however, few studies examine staff perceptions on feasibility and acceptability of using perinatal screening for mood disorders in ethnically diverse public health clinics. During December 2012, we conducted four focus groups using a semistructured interview guide with public health clinic staff of varying disciplines (n=25) in a Special Supplemental Nutrition Program for Women, Infants, and Children. All interviews were audio recorded and analyzed using thematic analysis. We found five descriptive themes related to acceptability and feasibility of screening for perinatal depression in a public health clinic. The main themes include (1) literacy barriers, (2) need for referrals and follow-up with outside services, (3) training and capacity needs, (4) stigma of depression, and (5) location and privacy of screening. Although multiple barriers to universal depression screening in a public health clinic were identified, participants found value in practice of screening low-income women for depression. Factors for facilitating implementation of systematic depression screening in a public health clinic have been identified. Implications discuss how policy makers and public health clinic administrators can improve the universal depression screening process.


Clinical depressive symptoms and diabetes in a binational border population.
Depression affects more Hispanics with type 2 diabetes than other ethnic groups. This exploratory, binational study examined the prevalence and correlates of clinical depressive symptoms in Hispanics of Mexican origin with type 2 diabetes living on both sides of the Texas Mexico border. Two binational samples, consisting of 172 adult patients of Mexican origin with type 2 diabetes in South Texas and 200 from the Northeastern region of Mexico, were compared. Logistic regression analyses were used to test personal and social correlates to clinical depressive symptoms. The rate of clinical depressive symptoms was similar in both South Texas and Northeastern Mexico patients (39% and 40.5%, respectively). Gender, education, emergency department visits, and burden of diabetes symptoms were predictors of clinical depressive symptoms in the South Texas sample. Among respondents in the Northeastern Mexico sample, the only statistically significant correlate to clinical depressive symptoms was the burden of diabetes symptoms. Diabetes and depression must be addressed as priorities in diabetes initiatives at the US Mexico border region. Further research is warranted to examine the extent and impact of involving family practice physicians from both sides of the border in depression screenings among patients with type 2 diabetes.


Disparate SPF Testing Methodologies Generate Similar SPFs. II. Analysis of P2 Standard Control SPF Data.
In the original scientific publication evaluating sunscreen methodologies, Garzarella and Caswell showed there to be no clinically significant or statistically significant difference in the average Sun Protection Factor (SPF) of a sunscreen formulation between any of three methodologies, Food and Drug Administration (FDA) Final Monograph, Australia/New Zealand, and European Cosmetics Association (COLIPA) International, suggesting that any differences in methodology were insignificant in the resulting SPF determined. These three major older methodologies have coalesced into two methodologies, 2011 FDA-Final Rule and ISO 24444, so that current sunscreen SPF testing is mostly 2011 FDA-Final Rule and ISO 24444. Another approach to evaluating the impact of methodological differences in sunscreen testing is to compare data on a control standard or reference sunscreen. If the difference between the two SPF values of P2 is statistically significant for the two different methodologies, then this would present evidence for a clinically significant difference in the SPF value between the two methodologies. For 2011 FDA-Final Rule, the expected SPF of P2 is 16.3 ± 3.43; for ISO 24444, the expected SPF of P2 is 16.1 ± 2.42. Using least squares average and standard error on 952 observations, the 2011 FDA-Final Rule SPF of P2 is 15.4 ± 0.12; using least squares average and standard error on 1,551 observations, the ISO 24444 SPF of P2 is 15.6 ± 0.10. The data described herein indicate no clinically significant nor statistically significant difference between the SPF average of P2 using the 2011 FDA-Final Rule methodology versus that using ISO 24444 methodology. Further statistical analysis indicates that the average SPF of P2 is independent of solar simulator type, time of year (month), age of subject, gender of subject, or Fitzpatrick Skin Phototype of subject. A statistically significant negative correlation was found between a subject's SPF of P2 and the subject's unprotected minimal erythemal dose. The implications of this relationship on SPF testing are explored.


Binding of thyroid hormone receptors to the rat thyrotropin-beta gene.
Negative regulation of rat TSH beta gene expression by thyroid hormone is mediated largely by decreased transcription of the gene. This is apparently mediated by a cis-acting element which has been localized to a 57-basepair fragment spanning the second transcriptional start site of the rat TSH beta gene. We have investigated whether thyroid hormone receptors bind specifically to DNA sequences in this region of the gene. We compared binding of native T3 receptor to the TSH beta gene sequences and to the rat GH (rGH) gene T3 response element (TRE), and examined the ability of two different forms of in vitro synthesized T3 receptor to bind to the TSH beta gene. The avidin-biotin complex DNA binding assay was used to examine sequence-specific binding of the receptor. [125I]T3-labeled receptor in GH3 cell nuclear extracts bound to a site within the first exon of TSH beta and also to a region immediately upstream of the second transcriptional start site of the gene. In addition, the Hc-erbA beta and r-erbA alpha-1 forms of the T3 receptor each bound to TSH beta and rGH sequences, demonstrating that both alpha- and beta-forms of T3 receptor can bind to TREs exerting either positive or negative transcriptional regulation. Competition experiments showed that both native and in vitro synthesized T3 receptor bound to the first exon of TSH beta with an affinity slightly less than that for the rGH TRE. The two receptor-binding sites of the rTSH beta gene show sequence similarity to adjacent regions of the rGH TRE. These data indicate that negative regulation of rat TSH beta gene transcription may be effected by direct binding of the T3-receptor complex to one or both of the binding sites flanking the second transcriptional start site.


Obstructive mechanical mitral valve thrombosis and gastric adenocarcinoma: A therapeutic dilemma.
Fibrinolysis is an option for the management of mechanical prosthetic valve thrombosis when surgery has prohibitive risks. Current guidelines suggest recombinant tissue plasminogen activator (not to exceed 100 mg) with unfractionated heparin. A low-dose (25 mg) alteplase regimen as treatment in patients with a high risk of bleeding warrants further research. This report describes the case of a 65-year-old woman with a history of mechanical prosthetic mitral valve replacement who was diagnosed with signet ring cell adenocarcinoma of the stomach and obstructive mechanical prosthetic thrombosis on echocardiogram. Details of challenging aspects of this case and the use of modified fibrinolytic therapy are provided.


Humiliation: its nature and consequences.
In this article, we present a new analysis of what is involved when individuals undergo significant public humiliation. We describe the structure of humiliation-that is, the factors that, taken collectively, render certain life events and circumstances humiliating; the most common destructive consequences of being subjected to them; and several personality factors that, when present, can serve to amplify the damaging effects of humiliating experiences. The analysis is intended to enable forensic clinicians, lawyers, judges, and other relevant parties to understand better what happens when individuals are humiliated and to identify more precisely the damage that such persons sustain. It is also intended to have heuristic value for the discussion, confrontation, and alleviation of humiliation in correctional, jurisprudential, clinical, and general societal contexts.


Initial clinical experience evaluating Yttrium-90-chimeric T84.66 anticarcinoembryonic antigen antibody and autologous hematopoietic stem cell support in patients with carcinoembryonic antigen-producing metastatic breast cancer.
cT84.66 is a human/murine IgG1 with high affinity and specificity for carcinoembryonic antigen (CEA). An earlier Phase I trial defined the maximum tolerated dose for 90Y-diethylenetriaminepentaacetic acid (DTPA)-cT84.66 at 22 mCi/m2. Dose-limiting toxicities were reversible leukopenia and thrombocytopenia. The purpose of this Phase I trial was to evaluate the feasibility and toxicities of administering higher activities of 90Y-DTPA-cT84.66 with stem cell support in patients with CEA-producing breast cancer. Patients with CEA-producing breast cancer refractory to standard therapies underwent peripheral stem cell collection followed by infusion of 111indium-DTPA-cT84.66. Those patients demonstrating tumor targeting received a single therapy dose of 90Y-DTPA-cT84.66, followed by Ca-DTPA infusion for 72 h posttherapy. Stem cells were reinfused following a divided schedule. To date, seven patients have been accrued to this trial. Each patient received an imaging dose of (111)In-cT84.66. Six patients demonstrated tumor imaging and received a single cycle of 90Y-cT84.66 at 15 mCi/m2 (three patients) and 22.5 mCi/m2 (three patients). One patient did not demonstrate tumor imaging and was not treated. At these administered activities, 90Y-cT84.66 was well tolerated. No dose-limiting toxicities have been observed. All patients demonstrated hematopoietic recovery after stem cell infusion. One patient demonstrated stable disease for 4 months; one patient had stable disease and reduction of bone pain for 3 months; and a third patient experienced >50% reduction of an ovarian metastasis, resolution of malignant pleural effusion, stable pleural metastases, and stable bone scan for 14 months. Preliminary results from this ongoing Phase I trial are promising and demonstrate the feasibility and potential for antitumor effects of stem cell supported 90Y-cT84.66 therapy in patients with CEA-producing breast cancers.


Isoflurane improves the tolerance to pacing-induced myocardial ischemia.
Fourteen patients with normal, global, left ventricular function scheduled for elective myocardial revascularization were studied at rest and during atrial pacing before and during isoflurane anesthesia (0.5% end-tidal) plus 50% nitrous oxide. Rapid atrial pacing was performed in a stepwise fashion until the onset of angina pectoris in the awake patients. The same step increase in pacing rate was applied in the anesthetized patients. Compared with prepacing baseline values, isoflurane significantly decreased systemic blood pressure, coronary perfusion pressure, the rate-pressure product, and cardiac index. No patient had ST-segment depression while awake or during isoflurane anesthesia before pacing was started. Prepacing left and right ventricular filling pressures and wave forms were normal, both while awake and during isoflurane anesthesia. The mean pacing rate at which first signs of myocardial ischemia appeared (V5 ST-segment depression greater than or equal to 0.1 mV, increase in pulmonary capillary wedge pressure (PCWP) to greater than or equal to 15 mmHg, and prominent PCWP v-waves greater than or equal to 20 mmHg) was significantly higher during isoflurane anesthesia than in the awake patients (128 +/- 4 vs. 115 +/- 5 beats/min). With the exception of one patient, the individual pacing rates inducing first signs of ischemia in the awake patients were below the anginal threshold. None of the patients had a reduced ischemic threshold during anesthesia. Eleven anesthetized patients tolerated a higher pacing rate until initial signs of ischemia appeared. In four of these patients, the pacing rate required to induce first signs of ischemia was above the heart rate at which chest pain had been induced while they were awake. At a peak atrial pacing rate of 129 +/- 5 beats/min, which had induced angina pectoris in the awake patients, the increase in PCWP was significantly smaller during pacing with isoflurane than during control pacing. Prominent PCWP v-waves (greater than or equal to 20 mmHg) appeared in 12 of the 14 patients during initial pacing to angina and in eight patients paced during isoflurane anesthesia. In six of these eight patients, the abnormal v-waves were less prominent than those observed during control pacing. Ischemic ST-segment changes developed in 13 of 14 patients during initial pacing and in nine patients during pacing with isoflurane. Mean V5 ST-segment depression during the two pacing periods was significantly different, averaging 0.19 and 0.11 mV, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


Near infrared fluorescence-guided real-time endoscopic detection of peritoneal ovarian cancer nodules using intravenously injected indocyanine green.
Near infrared fluorescence-guidance can be used for the detection of small cancer metastases and can aid in the endoscopic management of cancer. Indocyanine green (ICG) is a Food and Drug Administration (FDA)-approved fluorescence agent. Through non-specific interactions with serum proteins, ICG achieves enhanced permeability and retention (EPR) effects. Yet, ICG demonstrates rapid clearance from the circulation. Therefore, ICG may be an ideal contrast agent for real-time fluorescence imaging of tumors. To evaluate the usefulness of real-time dual fluorescence and white light endoscopic optical imaging to detect tumor implants using the contrast agent ICG, fluorescence-guided laparoscopic procedures were performed in mouse models of peritoneally disseminated ovarian cancers. Animals were administered intravenous ICG or a control contrast agent, IR800-conjugated to albumin. The ability to detect small ovarian cancer implants was then compared. Using the dual view microendoscope, ICG clearly enabled visualization of peritoneal ovarian cancer metastatic nodules derived from SHIN3 and OVCAR5 cells at 6 and 24 hr after injection with significantly higher tumor-to-background ratio than the control agent, IR800-albumin (p < 0.001). In conclusion, ICG has the desirable properties of having both EPR effects and rapid clearance for the real-time endoscopic detection of tiny ovarian cancer peritoneal implants compared to a control macromolecular agent with theoretically better EPR effects but longer circulatory retention. Given that ICG is already FDA-approved and has a long track record of human use, this method could be easily translated to the clinic as a robust tool for fluorescence-guided endoscopic procedures for the management and treatment of cancer.


A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions.
The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions (MPE). In this multi-institutional study conducted between March 1994 and February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 distribution to either an indwelling pleural catheter or doxycycline pleurodesis. Patients receiving the indwelling catheter drained their effusions via vacuum bottles every other day or as needed for relief of dyspnea. The median hospitalization time was 1.0 day for the catheter group and 6.5 days for the doxycycline group. The degree of symptomatic improvement in dyspnea and the quality of life was comparable in each group. Six of 28 patients who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of their effusions or a blockage of their catheter after the initially successful treatment (P = 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) achieved spontaneous pleurodesis at a median of 26.5 days. A chronic indwelling pleural catheter is an effective treatment for the management of patients with symptomatic, recurrent, malignant pleural effusions. When compared with doxycycline pleurodesis via tube thoracostomy, the pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis.


The lived experiences of midwives with spirituality in childbirth: mana from heaven.
The purpose of this study was to describe the lived experiences of midwives who experienced the phenomenon of spirituality when they attended births. The research design was descriptive, using a transcendental phenomenological approach reflected in Moustakas' model. Purposive and snowball sampling were used to recruit the sample of 10 certified nurse-midwives. The major findings of this study consisted of 5 theme categories that revealed the essential structure of the midwives' lived experiences of spirituality during childbirth: belief in the existence of a higher power, the essence of spirituality, birth is spiritual, the essence of midwifery, and relationships. The midwives in the study experienced spirituality as an integral and essential component of childbirth. The midwives reported using elements of spirituality as instruments that helped them assist their clients through the process of pregnancy and birth. The midwives also revealed their dependence on spirituality and belief in a higher being who guided their lives and their calling to midwifery.


[A case with apraxia of tool use: selective inability to form a hand posture for a tool].
Impaired tool use is recognized as a symptom of ideational apraxia. While many studies have focused on difficulties in producing gestures as a whole, using tools involves several steps; these include forming hand postures appropriate for the use of certain tool, selecting objects or body parts to act on, and producing gestures. In previously reported cases, both producing and recognizing hand postures were impaired. Here we report the first case showing a selective impairment of forming hand postures appropriate for tools with preserved recognition of the required hand postures. A 24-year-old, right-handed man was admitted to hospital because of sensory impairment of the right side of the body, mild aphasia, and impaired tool use due to left parietal subcortical hemorrhage. His ability to make symbolic gestures, copy finger postures, and orient his hand to pass a slit was well preserved. Semantic knowledge for tools and hand postures was also intact. He could flawlessly select the correct hand postures in recognition tasks. He only demonstrated difficulties in forming a hand posture appropriate for a tool. Once he properly grasped a tool by trial and error, he could use it without hesitation. These observations suggest that each step of tool use should be thoroughly examined in patients with ideational apraxia.


Changes in peripheral blood and bone marrow specimens following therapy with recombinant alpha 2 interferon for hairy cell leukemia.
The authors studied peripheral blood (PB) and bone marrow (BM) biopsy specimens from 12 patients treated with recombinant alpha 2 interferon (raIFN) for hairy cell leukemia (HCL), to assess changes caused by raIFN therapy. Specimens were obtained immediately before therapy and during follow-up periods for 6 months to 12 months. Before raIFN, 11 patients had hairy cells (HC) in the PB; 11 were granulocytopenic; 12, monocytopenic; and 6, thrombocytopenic. The median bone marrow hairy cell index (HCI = %HC X %BM cellularity/10,000), an indicator of HC packing in the BM, was 0.56 (range, 0.12-0.83). The myeloid:erythroid (M:E) ratio was below 1:1 in all patients. By the end of the study, HC in the PB had disappeared or decreased in numbers. Granulocytopenia, monocytopenia, and thrombocytopenia had resolved in 10 of the 11, 10 of the 12, and 5 of the 6 patients, respectively, in whom they were present before raIFN. The numbers of large granular lymphocytes (LGL) increased in 11 patients after raIFN, but often fluctuated, and in 3 patients fell to pre-raIFN values. In the BM, improvement was noted with median HCI of 0.12 (range, 0.03-0.4). In no case were HC completely absent from the BM. The BM showed increased percentages of granulocytic elements in 11 patients, of erythroid precursors in 12, and of megakaryocytes in 10. However, the M:E ratio was 1:1 or higher in only six patients at any time during the study. Marrow reticulin fibers remained increased. This study morphologically confirms the clinical improvement reported in patients with HCL who are treated with recombinant alpha 2 interferon.


Basement membrane biosynthesis as a target to tumor therapy.
Tricyclodecan-9-yl-xanthate (D609) was identified as an agent that caused selective killing of tumor cells by an unknown mechanism of action. We report an inhibition by D609 of basement membrane collagen biosynthesis in the chick chorioallantoic membrane system in vitro. In the same system in vivo D609 inhibits angiogenesis. Also treatment of rats bearing Walker 256 carcinoma with D609 results in a dose-dependent antitumor effect. These results indicate that basement membrane synthesis may be a target for developing anti-angiogenic compounds with antitumor properties.


Peri-operative third party red blood cell transfusion in renal transplantation and the risk of antibody-mediated rejection and graft loss.
Historic red blood cell transfusion (RBCT) may induce anti-HLA antibody which, if donor specific (DSA), is associated with increased antibody-mediated rejection (AMR). Whether post-operative RBCT influences this risk is unknown. We examined the RBCT history in 258 renal transplant recipients stratified according to prevalent recipient HLA antibody (DSA, Non-DSA or No Antibody). AMR occurred more frequently in patients who received RBCT both pre and post transplant compared with all other groups (Pre+Post-RBCT 21%, Pre-RBCT 4%, Post-RBCT 6%, No-RBCT 6%, HR 4.1 p=0.004). In the 63 patients who received Pre+Post-RBCT, 65% (13/20) with DSA developed AMR compared with 0/6 in the Non-DSA group and 2/37 (5%) in the No-Antibody group (HR 13.9 p<0.001). In patients who received No-RBCT, Pre-RBCT or Post-RBCT there was no difference in AMR between patients with DSA, Non-DSA or No-Antibody. Graft loss was independently associated with Pre+Post-RBCT (HR 6.5, p=0.001) AMR (HR 23.9 p<0.001) and Non-AMR (6.0 p=0.003) after adjusting for DSA and delayed graft function. Re-exposure to RBCT at the time of transplant is associated with increased AMR only in patients with preformed DSA, suggesting that RBCT provides additional allostimulation. Patients receiving Pre+Post-RBCT also had an increased risk of graft loss independently of AMR or DSA. Both pre and post procedural RBCT in renal transplantation is associated with modification of immunological risk and warrants additional study.


Tracing the molecular dynamics of living mitochondria under phototherapy via surface-enhanced Raman scattering spectroscopy.
Subcellular mitochondrion has become a target for improving the therapeutic efficiency and reducing side damage to normal cells via a combination of many therapeutic strategies. However, the underlying molecular mechanisms associated with cell death induced by subcellular dysfunction remain unknown or disputed. In this study, we investigated the dynamic molecular changes of living mitochondria upon phototherapy (photothermal therapy plus photodynamic therapy, PTT & PDT) by surface-enhanced Raman scattering spectroscopy (SERS) and intended to disclose the photo-induced cell death route in breast cancer cells (MCF-7) taking into account the mitochondrion. Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved clinic blood-injection near-infrared angiographic contrast agent and a PTT & PDT drug, was used for the evaluation of the phototherapy effect. The results revealed that the content of phenylalanine (Phe) in mitochondria evidently increased during the phototherapy-induced cell death process. Moreover, the phototherapy-induced cell apoptosis was mainly regulated through the DNA structures. We expect that the understanding of mitochondrial molecular stress responses will be helpful for the diagnosis and therapy of cellular processes associated with mitochondria and provide valuable guidance for the further design and development of more effective therapeutic platforms and methods at the sub-cellular level.


Characterization of fossilized relatives of the White Spot Syndrome Virus in genomes of decapod crustaceans.
The White Spot Syndrome Virus (WSSV) is an important pathogen that infects a variety of decapod species and causes a highly contagious disease in penaeid shrimps. Mass mortalities caused by WSSV have pronounced commercial impact on shrimp aquaculture. Until now WSSV is the only known member of the virus family Nimaviridae, a group with obscure phylogenetic affinities. Its isolated position makes WSSV studies challenging due to large number of genes without homology in other viruses or cellular organisms. Here we report the discovery of an unusually large amount of sequences with high similarity to WSSV in a genomic library from the Jamaican bromeliad crab Metopaulias depressus. De novo assembly of these sequences allowed for the partial reconstruction of the genome of this endogenized virus with total length of 200 kbp encompassed in three scaffolds. The genome includes at least 68 putative open reading frames with homology in WSSV, most of which are intact. Among these, twelve orthologs of WSSV genes coding for non-structural proteins and nine genes known to code for the major components of the WSSV virion were discovered. Together with reanalysis of two similar cases of WSSV-like sequences in penaeid shrimp genomic libraries, our data allowed comparison of gene composition and gene order between different lineages related to WSSV. Furthermore, screening of published sequence databases revealed sequences with highest similarity to WSSV and the newly described virus in genomic libraries of at least three further decapod species. Analysis of the viral sequences detected in decapods suggests that they are less a result of contemporary WSSV infection, but rather originate from ancestral infection events. Phylogenetic analyses suggest that genes were acquired repeatedly by divergent viruses or viral strains of the Nimaviridae. Our results shed new light on the evolution of the Nimaviridae and point to a long association of this viral group with decapod crustaceans.


Molecular simulation of water and hydration effects in different environments: challenges and developments for DFTB based models.
We discuss the description of water and hydration effects that employs an approximate density functional theory, DFTB3, in either a full QM or QM/MM framework. The goal is to explore, with the current formulation of DFTB3, the performance of this method for treating water in different chemical environments, the magnitude and nature of changes required to improve its performance, and factors that dictate its applicability to reactions in the condensed phase in a QM/MM framework. A relatively minor change (on the scale of kBT) in the O-H repulsive potential is observed to substantially improve the structural properties of bulk water under ambient conditions; modest improvements are also seen in dynamic properties of bulk water. This simple change also improves the description of protonated water clusters, a solvated proton, and to a more limited degree, a solvated hydroxide. By comparing results from DFTB3 models that differ in the description of water, we confirm that proton transfer energetics are adequately described by the standard DFTB3/3OB model for meaningful mechanistic analyses. For QM/MM applications, a robust parametrization of QM-MM interactions requires an explicit consideration of condensed phase properties, for which an efficient sampling technique was developed recently and is reviewed here. The discussions help make clear the value and limitations of DFTB3 based simulations, as well as the developments needed to further improve the accuracy and transferability of the methodology.


Experimental characterization of a silicon photonic biosensor consisting of two cascaded ring resonators based on the Vernier-effect and introduction of a curve fitting method for an improved detection limit.
We studied a refractive index sensor that consists of two cascaded ring resonators and that works analogously to a Vernier-scale. We implemented it in silicon-on-insulator and experimentally determined its sensitivity to be as high as 2169 nm/RIU in aqueous environment. We derived formulas describing the sensor's operation, and introduced a fitting procedure that allows to accurately detect changes in the sensor response. We determined the detection limit of this first prototype to be 8.310(-6)RIU.


[Molecular and cellular aspects of radiation hormesis in Drosophila melanogaster].
The long-term effects of the R-irradiation of D. melanogaster at the 1-hour egg stage with the dosages of 0.25, 0.50, 0.75, 1.0, 2.0 and 4.0 Gy were investigated. DNA samples were isolated from whole 5-6-days adult males. The aliquots of DNA were digested by S1-nuclease. Preimaginal stage lethality increased with irradiation dose increasing. At the same time, decrease in imaginal LS (life span) was observed after irradiation with the greatest dose (4 Gy) only. Moreover, hormesis by LS has revealed: in males irradiation with 0.25, 0.75 and 1 Gy increased the mean LS, and with 0.25 and 0.5 Gy caused the maximum LS; in females exposures with 0.25, 0.75 and 2 Gy increased the maximum LS. The densitometric assay of DNA electrophoregrams showed decrease by 39.2% of the part of high-molecular-weight DNA in control as a result of S1-nuclease action. Samples of DNA from the irradiated flies were more stable to enzyme action. The higher stability of DNA originated from the irradiated flies could be the result of reparation system activation. Ultrastructural changes induced at the egg stage by irradiation at the dose of 0.75 Gy testify the increased transcriptional activity of the brain cells.


Store-operated Ca2+ channel signaling: Novel mechanism for podocyte injury in kidney disease.
Studies over the last decade have markedly broadened our understanding of store-operated Ca2+ channels (SOCs) and their roles in kidney diseases and podocyte dysfunction. Podocytes are terminally differentiated glomerular visceral epithelial cells which are tightly attached to the glomerular capillary basement membrane. Podocytes and their unique foot processes (pedicels) constitute the outer layer of the glomerular filtration membrane and the final barrier preventing filtration of albumin and other plasma proteins. Diabetic nephropathy and other renal diseases are associated with podocyte injury and proteinuria. Recent evidence demonstrates a pivotal role of store-operated Ca2+ entry (SOCE) in maintaining structural and functional integrity of podocytes. This article reviews the current knowledge of SOCE and its contributions to podocyte physiology. Recent studies of the contributions of SOC dysfunction to podocyte injury in both cell culture and animal models are discussed, including work in our laboratory. Several downstream signaling pathways mediating SOC function in podocytes also are examined. Understanding the pivotal roles of SOC in podocyte health and disease is essential, as SOCE-activated signaling pathways are potential treatment targets for podocyte injury-related kidney diseases.


The auto-inhibitory domain and ATP-independent microtubule-binding region of Kinesin heavy chain are major functional domains for transport in the Drosophila germline.
The major motor Kinesin-1 provides a key pathway for cell polarization through intracellular transport. Little is known about how Kinesin works in complex cellular surroundings. Several cargos associate with Kinesin via Kinesin light chain (KLC). However, KLC is not required for all Kinesin transport. A putative cargo-binding domain was identified in the C-terminal tail of fungal Kinesin heavy chain (KHC). The tail is conserved in animal KHCs and might therefore represent an alternative KLC-independent cargo-interacting region. By comprehensive functional analysis of the tail during Drosophila oogenesis we have gained an understanding of how KHC achieves specificity in its transport and how it is regulated. This is, to our knowledge, the first in vivo structural/functional analysis of the tail in animal Kinesins. We show that the tail is essential for all functions of KHC except Dynein transport, which is KLC dependent. These tail-dependent KHC activities can be functionally separated from one another by further characterizing domains within the tail. In particular, our data show the following. First, KHC is temporally regulated during oogenesis. Second, the IAK domain has an essential role distinct from its auto-inhibitory function. Third, lack of auto-inhibition in itself is not necessarily detrimental to KHC function. Finally, the ATP-independent microtubule-binding motif is required for cargo localization. These results stress that two unexpected highly conserved domains, namely the auto-inhibitory IAK and the auxiliary microtubule-binding motifs, are crucial for transport by Kinesin-1 and that, although not all cargos are conserved, their transport involves the most conserved domains of animal KHCs.


The role of weathering on fly ash charge distribution during triboelectrostatic beneficiation.
Triboelectrostatic beneficiation of coal combustion fly ashes with high-unburned carbon contents can produce low-carbon ash products having value as mineral admixtures and meeting technical requirements for replacing cement in concrete. This capability is a result of establishing bipolar charge on mineral ash versus carbon particles where, typically, unburned carbon attains positive surface charge and ash attains negative surface charge under the tribocharging conditions employed in triboelectrostatic technologies. However, long-term exposure of fly ash to weathering conditions, such as moisture or high humidity, before beneficiation is known to dramatically diminish carbon-ash separation efficiencies. Although experimentation has shown that water soluble surface species can be redistributed on fly ash particles after exposure to moisture, which could affect the extent of charging and polarities, measurement of the actual amount of charge and polarity on particles after weathering exposure versus after removal of surface moisture has not been accomplished. Hence, a new experimental methodology was developed and applied to measure charge distributions on tribocharged ash and carbon particles in a fly ash that had been exposed to weathering conditions for 6 months before and after removal of the surface moisture. Weathered ash particles were found to have an average zero charge, whereas carbon particles attained an average negative charge, opposite of the normal polarity for carbon. Although the extent of uncharged particles decreased and ash particles attained an average negative charge after drying, carbon particles attained only an average zero charge. These changes were reflected in very small increases in carbon-ash separation efficiency, in contrast to previous beneficiation tests in which fly ash drying led to significant increases in carbon-ash separation efficiency. It is suggested that removal of surface moisture in the absence of other processes like surface ion redistribution would beneficially impact carbon-ash triboelectrostatic beneficiation.


Papillary intralymphatic angioendothelioma of the thigh: A case report and review of the literature.
The term angiosarcoma, encompasses several neoplasms, all of which exhibit a malignant process derived from endothelial cells of the vessels. The most common form of angiosarcoma is highly aggressive, often fatal, and usually affects the head and neck region of elderly white men. Other low-grade forms of angiosarcoma, including papillary intralymphatic angioendothelioma, also known as Dabska tumor, are less invasive, affect a wider age range, and offer a better prognosis. There are several predisposing factors that increase the risk of angiosarcoma and include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies. We report an unusual case of a very small, low-grade angiosarcoma on the thigh of an adult female with no known predisposing risk factors.


Surgical Treatment of an Infected Nonunion of the Middle Third of the Femur Associated with Femoral Shortening in a Hemophilia Patient.
The management of nonunion and limb length discrepancy has remained a constant challenge in hemophilic patients. In this study, we aimed to present the treatment of femur infected nonunion and limb length discrepancy in a twenty-seven-year-old patient with hemophilia type A. A 27-year-old male patient with hemophilia type A referred to our institution for the treatment of right femur infected nonunion and 10 cm shortness of the femur. Resection of the nonunion site and bone-to-bone fixation with autologous bone grafting were performed. Compression to the pseudoarthrosis site and distraction from new osteotomy site were applied with the unilateral external fixator. Union was achieved, and 6 cm lengthening was obtained according to the initial length. Patient was followed up for 7 years. After this treatment, the patient is able to walk with full weight bearing on the affected extremity with 4 cm shortening which is compensated by the heel lift. The results of this case indicate that limb lengthening and treatment of nonunion with the external fixation could be reliable and effective method for hemophilic patients.


Comparative chemical analysis of volatile compounds of Echinops ilicifolius using hydrodistillation and headspace solid-phase microextraction and the antibacterial activities of its essential oil.
The volatile compounds from various parts of Echinops ilicifolius (Compositae) such as flowers, leaves and roots obtained by hydrodistillation (HD) and headspace solid-phase microextraction (HS-SPME) methods were subsequently analysed by GC and GC/MS and compared. Thirty-seven and 20 components of the flower of E. ilicifolius were characterized, representing 99.7% and 100.0% of the total compositions using the HD and HS-SPME methods, respectively. The major constituents of the hydrodistilled oil were identified as linalool (58.6%), geraniol (17.4%), n-dodecane (10.9%) and nerol (5.4%), whereas HS-SPME extract was rich in n-octane (34.0%), n-decane (25.1%), p-cymene (11.1%), γ-terpinene (5.3%) and 1,8-cineole (5.1%). n-Hexadecanoic acid (32.3%), linalool (16.4%) and geraniol (8.3%) were the main components among 43 constituents identified in hydrodistilled extract of the leaf, representing 99.5% of the total components detected, whereas 16 compounds representing 99.9% of the HS-SPME method were identified, among which n-decane (32.6%), p-cymene (14.0%), n-octane (10.3%), limonene (9.2%), γ-terpinene (9.1%), 1,8-cineole (7.9%) and α-pinene (5.9%) were the major ones. Among 23 components comprising 91.2% of the total hydrodistilled oil detected, n-decane (23.1%), n-dodecane (14.5%), silphiperfol-4,7(14)-diene (11.1%), selin-11-en-4-a-ol (9.5%), n-hexadecanoic acid (7.8%) and n-tetradecane (5.3%) were the main constituents in the root of E. ilicifolius, whereas 1,8-cineole (29.0%), n-decane (12.6%), n-octane (12.6%), camphor (12.0%), p-cymene (9.6%) and γ-terpinene (5.9%) were the main components among the 20 constituents characterized in HS-SPME extract, representing 99.9% of the total components detected. The antibacterial activity of the flower, leaf and root oils of E. ilicifolius against six Gram-positive and Gram-negative bacteria was determined using the MIC method. The growth inhibitory zone (mm) was also measured.


6-(1-Oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone inhibits lewis lung cancer by antiangiogenesis and apoptosis.
Lung cancer is a leading cause of cancer mortality worldwide. Novel and nontoxic agents targeting angiogenesis and tumor cell proliferation and survival are desirable for lung cancer chemoprevention and treatment. Previously we have reported that 6-(1-oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone (OXO) exhibits anti-tumor activity against S-180 sarcoma in vitro and in vivo. Here we studied the anti-angiogenic and apoptogenic attributes of OXO in vitro and in vivo targeting lung cancer. In human umbilical vein endothelial cells (HUVECs), we show that OXO more potently inhibited VEGF-stimulated than basic bFGF-stimulated HUVEC proliferation and capillary differentiation. In Lewis lung carcinoma (LLC) cells, OXO not only induces S-phase arrest and mitochondria/caspase-9 pathway mediated apoptosis, but also effectively down-regulated the hypoxia-induced expression of HIF-1alpha and VEGF at mRNA and protein levels in LLC and decreased VEGF secretion into conditioned culture media. OXO significantly reduced in vivo functional angiogenesis in the mouse Matrigel plug assay. Furthermore, OXO potently inhibited the growth of LLC cells inoculated on the flank of syngenic mice at dosages that did not affect their body weight. The in vivo anti-cancer effect was associated with decreased HIF-1alpha and VEGF expression, decreased microvessel density as well as a reduction of tumor cell proliferation and increased tumor cell apoptosis. Taken together, these results demonstrate that OXO exerts anti-cancer activity through anti-angiogenesis and tumor cell cycle arrest and apoptosis. These findings warrant additional studies of OXO as a novel agent for the chemoprevention and treatment of lung cancer.


Serum ferritin level is inversely related to number of previous pregnancy losses in women with recurrent pregnancy loss.
To study whether low serum ferritin (s-ferritin) levels are associated with recurrent pregnancy loss (RPL), and whether low s-ferritin predicts the risk of another pregnancy loss or the ability to conceive. Cohort study. Fertility clinic at a university hospital. Eighty-four women referred to the RPL Unit and 153 women of reproductive age with no known fertility problem. s-Ferritin levels were measured in serum samples taken before pregnancy attempt. None. s-Ferritin levels were correlated to pregnancy history, ability to conceive, and time to conception during the first 2 years after sampling. Furthermore, s-ferritin levels were correlated to outcome of the first pregnancy after referral for RPL. Women with RPL had lower s-ferritin than the comparison group, 39.9 μg/L versus 62.2 μg/L, and had a higher prevalence of low iron stores (s-ferritin <30 μg/L), 35.7% versus 13.7%. We found an inverse relationship between s-ferritin level and number of pregnancy losses before referral. We did not find s-ferritin level to be associated with ability to conceive or time to pregnancy in either group. Nor did s-ferritin level predict the risk of losing the first pregnancy after referral for RPL. The inverse relationship between s-ferritin levels and previous pregnancy losses suggests that low s-ferritin is associated with a more severe reproductive disturbance in women with RPL. Whether low s-ferritin is causally related to RPL and if such women could benefit from iron supplementation to achieve a live birth warrants further investigation.


Theoretical limitations in the immunodiagnostic imaging of cancer with computed tomography and nuclear scanning.
In order to help assess the feasibility of using immunologically tagged agents to render tumors detectable with current computed tomographic and nuclear scanners, mathematical formulations were developed to determine the theoretical limits of tumor detection relative to size and depth of the lesions. The results of our analysis suggest that visualization with computed tomography of a tiny tumor (1 sq mm, cross-sectional area) would require binding in the order of 2 x 10(5) iodine atoms/antigenic site, while imaging of a very large (900-sq mm) tumor would require approximately 10(4) atoms/site. Very low energy scanners might reduce these discouraging estimates by an order of 10(2). The immunological imaging of tumors with nuclear scanning appears quite feasible from our formulations, as has been demonstrated by others clinically. Small (1-sq cm) and deep (greater than or equal to 5-cm) tumors appear detectable with uptake ratios of the order of 5 or higher, which seem to be attainable currently. Smaller and deeper tumors require much higher uptake ratios to be detected.