Adaptive Comparative Judgment: A Tool to Support Students' Assessment Literacy.
Comparative judgment in assessment is a process whereby repeated comparison of two items (e.g., assessment answers) can allow an accurate ranking of all the submissions to be achieved. In adaptive comparative judgment (ACJ), technology is used to automate the process and present pairs of pieces of work over iterative cycles. An online ACJ system was used to present students with work prepared by a previous cohort at the same stage of their studies. Objective marks given to the work by experienced faculty were compared to the rankings given to the work by a cohort of veterinary students (n=154). Each student was required to review and judge 20 answers provided by the previous cohort to a free-text short answer question. The time that students spent on the judgment tasks was recorded, and students were asked to reflect on their experiences after engaging with the task. There was a strong positive correlation between student ranking and faculty marking. A weak positive correlation was found between the time students spent on the judgments and their performance on the part of their own examination that contained questions in the same format. Slightly less than half of the students agreed that the exercise was a good use of their time, but 78% agreed that they had learned from the process. Qualitative data highlighted different levels of benefit from the simplest aspect of learning more about the topic to an appreciation of the more generic lessons to be learned.


Indicators of Marine Pollution in the North Pacific Ocean.
The complex nature of ocean pollution underscores the utility in identifying and characterizing a limited number of "indicators" that enables scientists and managers to track trends over space and time. This paper introduces a special issue on indicators of marine pollution in the North Pacific Ocean and builds on a scientific session that was held at the North Pacific Marine Science Organization. The special issue highlights studies using a variety of indicators to provide insight into the identification of legacy and emerging contaminants, the ranking of priority pollutants from various sources, and the effects of contaminants on ecosystem health in the North Pacific Ocean. Examples include the use of mussels to illustrate spatial and temporal trends of a number of contaminants following the 2011 tsunami in Japan, the use of molecular marker (linear alkylbenzenes, hopanes, and polycyclic aromatic hydrocarbons) profiles to identify pollution sources, and the use of plastic resin pellets to illustrate spatial trends of petroleum pollution around the world. Stable isotopes were used to strengthen the utility of the Glaucous-winged gull (Larus glaucescens) as an indicator of marine pollution. Examples also demonstrate the development and application of biomarker approaches, including gene transcripts, oxidative stress, estradiol, hatchability, and respiration and swimming behavior abnormalities, as a function of exposure to polychlorinated biphenyls, sulfur-diesel, Pinghu crude oil, galaxolide and antifouling biocides. We provide a brief review of indicators of marine pollution, identify research gaps, and summarize key findings from the articles published within the issue. This special issue represents the first compilation of research pertaining to marine pollution indicators in the North Pacific Ocean and provides guidance to inform mitigation and monitoring efforts of contaminants in the region.


Lipid phase transition in planar bilayer membrane and its effect on carrier- and pore-mediated ion transport.
Using mixed-chain lipids, we have recorded cooling and heating curves of planar bilayer membranes while they passed the lipid phase transition range. With unmodified planar bilayers, spontaneous current fluctuations are observed near the lipid phase transition temperature (tc approximately 29 degrees C). This effect coincides with the expected and measured decrease in membrane capacitance. Carrier (valinomycin)-modified planar bilayers exhibit near tc an abrupt change from a high-conducting state above tc to the state of bare membrane conductance below tc. In contrast to this behavior, planar bilayers modified by pore-forming antibiotics (gramicidin A, alamethicin) do not show any peculiar effect at tc. However, at 22--23 degrees C a pronounced maximum in pore-induced conductance is seen. Whereas the gramicidin A pore abruptly stops stepwise fluctuations below approximately 16 degrees C, with alamethicin a few long-lasting pore and pore state fluctuations persist down to 10 degrees C. It is suggested that the carrier may freeze out into the membrane/water interface. The effects observed with pore-forming substances, on the other hand, are interpreted in terms of lateral phase separation into pure lipid and lipid/antibiotic domains.


Differences in health care quality for children and adults under managed care: justification for separate quality assessments?
To assess reported results of health care quality for children and adults in managed systems of care and to determine if variations exist between reported quality results for adults and children within the same plan. We utilized Consumer Assessment of Health Plan Survey results reported from 424 managed care plans to the National Committee for Quality Assurance in 1999. Responses from 218 530 adults (515 per plan, 424 plans) and 55 081 parents of children 0-12 years of age (304 per plan, 181 plans) were available. Restricting analyses to the 178 plans reporting both adult and child results, we performed matched-pairs analyses to test the hypothesis that child results would be the same as their adult counterparts within the same plan. Regression methods were employed to test for potential demographic differences explaining observed differences. Within the same plan, reported results for care provided by specialists and primary care physicians to adults and children in the same plan revealed marked variation, including rating of doctor (Spearman correlation coefficient, r(S) =.504) and rating of specialist (r(S) =.326). Conversely, assessments of activities related directly to health plan activities showed little variation, including rating of health plan (r(S) =.850) and claims processing (r(S) =.857). Differences in demographic characteristics between adults and child survey respondents do not appear to explain observed variations. Separate quality of care assessments for adults and children within the same managed care system identify significant differences in reported quality. Having health plan quality information about adult care does not serve as a proxy for needed information on children, particularly the care related to primary care and specialist providers. Areas of health plan assessment common to both adults and children (eg, claims processing) could be replaced with more targeted assessments of importance to parents and purchasers (eg, children with chronic conditions).


Bone mineral density in patients with end-stage renal failure.
Renal osteodystrophy is a well-recognized complication of chronic renal failure (CRF) and is associated with a marked morbidity. Bone mineral density (BMD) has been shown to be the best predictor of fracture risk in different circumstances. In this cross-sectional study, we measured BMD using dual photon absorptiometry at three skeletal sites of functional importance such as the lumbar spine (LS), the femoral shaft (FS) and the femoral neck (FN) in 106 patients with end-stage renal failure (11 predialysis patients and 95 patients on maintenance dialysis). These skeletal sites are characterized by various relative amounts of trabecular and cortical bone. The results indicate that decreased bone mass was detectable in all skeletal sites before the beginning of dialysis and that BMD was negatively related to dialysis duration in LS and FS. Nevertheless, the deleterious effects of renal osteodystrophy were more pronounced at the FS level, where cortical bone is predominant. A separate analysis of BMD in both sexes revealed that females presented a more important bone loss in both cortical and trabecular bone than males. We did not find any significant difference in BMD at the three measured sites between patients on continuous ambulatory peritoneal dialysis and on regular hemodialysis. This study emphasizes the need to pay more attention to the prevention of bone loss in patients on CRF before the start of dialysis therapy, and to the fact that the female population might display a more pronounced susceptibility to bone loss.


Reversible physical absorption of SO2 by ionic liquids.
Ionic liquids can reversibly absorb large amounts of molecular SO(2) gas under ambient conditions with the gas captured in a restricted configuration, possibly allowing SO(2) to probe the internal cavity structures in ionic liquids besides being useful for SO(2) removal in pollution control.


A new, simple test for thrombogenicity.
A simple technique is described to test thrombogenicity in dogs. Materials to be tested are introduced percutaneously into the femoral arteries of dogs in the form of a No. 5 catheter which is advanced to the aortic bifurcation. Another catheter can be introduced into the contralateral femoral artery in order to test two different materials in the same animal at the same time. After the catheter has been exposed to arterial blood for one hour, it is removed with a large-bore retrieval system, and all fibrin deposits are collected in a plastic basket. Significant thrombus formation was almost uniformly present in over 100 control studies. The technique has the advantage of being relatively noninvasive, allowing the testing of several materials in the same animal and yielding consistent results.


Do schools provide an opportunity for meeting The Health of the Nation targets?
The development of school health education has been uneven over the past 20 years. Major surveys conducted during this period indicate that the considerable growth observed in the late 1970s to mid-1980s was followed by a period of stagnation and erosion which has persisted to the present day. This paper traces the contents and influences of key national policies with the greatest influence on these trends. It is concluded that the most recently formulated policies on both health education and general education are having a detrimental effect and are limiting provision within this field. Recommendations are made for purchasers of health promotion services to assist schools at the local level in maintaining and developing programmes reflecting good practice in the teaching of the subject.


Changes and clinical significance of serum vaspin levels in patients with type 2 diabetes.
We investigated serum visceral adipose tissue-derived serpin (vaspin) levels in patients with normal glucose regulation and recently diagnosed type 2 diabetes (T2DM) and explored the association between vaspin and body mass index, age, gender, glucose, lipid metabolism, and insulin sensitivity. Fasting serum vaspin levels in 66 patients with T2DM and 48 normal subjects were detected using enzyme-linked immunosorbent assay. We found that serum vaspin levels in the DM group were 0.65 ± 0.13 mg/L in non-obese patients and 1.13 ± 0.25 mg/L in obese patients. Serum vaspin levels in the control group were 0.38 ± 0.18 mg/L in non-obese patients and 0.95 ± 0.11 mg/L in obese patients. Average serum vaspin levels were significantly higher in obese patients than in non-obese patients in both the DM group and control group. In the DM group, the serum vaspin level was 0.76 ± 0.22 mg/L in males and 0.92 ± 0.35 mg/L in females. In the control group, the serum vaspin level was 0.48 ± 0.14 mg/L in males and 1.05 ± 0.21 mg/L in females. Association analysis showed that serum vaspin levels were significantly associated with body mass index, waist-to-rip ratio (WHR), fat percentage, triglyceride, fasting plasma insulin, and insulin sensitivity index. Stepwise multiple regression analysis showed that gender, insulin sensitivity index, and WHR were the most significant independent factors affecting vaspin. Therefore, serum vaspin levels were significantly elevated in obese people and were independently associated with WHR, gender, and index sensitivity index.


Community-based randomized double-blind study of gastrointestinal effects and copper exposure in drinking water.
We assessed gastrointestinal effects in 1,365 adults exposed to either < 0.01 (controls), 2, 4, or 6 mg copper/L of drinking water for 2 months in a randomized, double-blind community-based study. The risk of symptoms increased with increasing Cu exposure and decreased with time. The best model by counting-process analysis included Cu concentration and sex. The risk of symptoms remained significantly higher in women than in men during weeks 1-4 for all concentrations tested; at week 1 comparison with the < 0.01-mg/L group showed that differences became significant in women at 4 mg/L [relative risk (RR) = 1.53; 95% confidence interval (CI), 1.02-2.05), and in men at 6 mg/L (RR = 1.9; 95% CI, 1.02-2.79). At week 2 for men and week 4 in women, the Cu concentration required to obtain significant differences on symptom report was > 6 mg Cu/L. We conclude that exposure to Cu in drinking water results in gastrointestinal symptoms, which are modulated by Cu concentration, time, and sex.


Resonant Raman spectra and first molecular hyperpolarizabilities of strongly charge-transfer molecules.
The effect of vibrational structure on the frequency dependence of the first molecular hyperpolarizability of two thiophene-based charge-transfer chromophores is investigated. A time domain formulation is used to express the polarizability. The new expression includes the solvent-induced inhomogeneous distribution of electronic transition frequencies as well as the effect of the motion of solvent molecules that modulates the vibrational and electronic transition frequencies of the nonlinear optical molecule on which the first molecular hyperpolarizability depends. Resonance Raman scattering and one-photon absorption spectra of the chromophores are measured. By simultaneously fitting the experimental one-photon absorption spectrum and Raman cross sections of vibrational lines derived from resonance Raman scattering to a theoretical model, important parameters needed for the calculation of the first molecular hyperpolarizability are obtained. The first molecular hyperpolarizability is calculated as a function of frequency covering both nonresonance and two-photon resonance regions. The calculated result is compared with the measured hyperpolarizability as a function of frequency of the excitation laser. The resonance Raman-based analysis is shown to account reasonably well for the dispersion of the hyperpolarizability of the two charge transfer chromophores.


The Ethical Implications of the Reclassification of Noninvasive Follicular Variant Papillary Thyroid Carcinoma.
Several studies have highlighted the lack of consensus in the diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC). An international multidisciplinary panel to address the controversy was assembled at the annual meeting of the Endocrine Pathology Society in March of 2015, leading to the recent publication reclassifying encapsulated (or noninvasive) FVPTC (EFVPTC) as a benign neoplasm. Does this change in histologic taxonomy warrant a change in clinical practice, and how should it affect those who have been given this diagnosis in the past? We consider the financial and psychological impact of this reclassification and discuss the ethical, legal, and practical issues involved with sharing this information with the patients who are affected. The total direct and indirect cost of thyroid cancer surveillance in patients is significant. High levels of clinically relevant distress affect up to 43% of patients with papillary thyroid carcinoma, as estimated by the Distress Thermometer developed by the National Comprehensive Cancer Network for detecting distress in cancer patients. Although there are currently no legal opinions that establish a precedent for recontacting patients whose clinical status is altered by a change in nomenclature, the prudent course would be to attend to the requirements of medical ethics. Informing patients with a previous diagnosis of EFVPTC that the disease has been reclassified as benign is expected to have a dramatic effect on their surveillance needs and to alleviate the psychological impact of living with a diagnosis of cancer. It is important to re-evaluate the pathologic slides of those patients at risk to ensure that the invasive nature of the tumor is comprehensively evaluated before notifying a patient of a change in diagnosis. The availability of the entire tumor for evaluation of the capsule may prove to be a challenge for a portion of the population at risk. We believe that it is the clinician's professional duty to make a sincere and reasonable effort to convey the information to the affected patients. We also believe that the cost savings with respect to the need for additional surgery, radioactive iodine, and rigorous surveillance associated with a misinterpretation of the biology of the diagnosis of EFVPTC in less experienced hands will likely more than offset the cost incurred in histologic review and patient notification.


New trends in the field of coagulation diagnosis--new possibilities to improve monitoring of antithrombotic therapy.
Two specific and sensitive enzyme immunoassays have been developed for the measurement of TAT and PTF, respectively. The TAT-ELISA uses two different antibodies binding selectively to the corresponding antigen moieties of TAT; anti-PTF antibodies were obtained from rabbits using a synthetic peptide from the COOH-terminus of PTF. Concentration in plasma samples of healthy individuals was found to be 1.45 +/- 0.4 micrograms/l for TAT, and 0.65 +/- 0.2 nMol/l for PTF. Patients with coagulation disorders showed markedly increased concentrations of both TAT and PTF. It can be assumed that these parameters might be suitable indicators for monitoring of both anticoagulant and thrombolytic therapy.


Enhancing assessment and treatment of hepatitis C in the custodial setting.
Acute and chronic hepatitis C (HCV) infections are prevalent in custodial settings worldwide, yet provision of antiviral therapies is uncommon. This disparity between the burden of disease and hepatitis service delivery reflects the marginalized patient population, which features high rates of injection drug use and poor mental health. In addition, the prison environment is intended for deprivation of liberty and not healthcare. Screening for HCV infections is provided in most jurisdictions, but uptake rates remain low. Assessment and treatment of inmates is often provided only by community-based services. Despite these challenges, assessment and treatment of inmates with chronic HCV via prison-based services has been shown to be feasible and effective. These services offer the potential to substantively increase HCV treatment uptake and reduce the burden of disease for the community at large. Improvements in the efficacy of HCV therapies via direct-acting antivirals, which also offer reduced treatment duration and decreased toxicities, mean that prison health services will be well placed for the treatment of large numbers of people with HCV who do not access health services in the community.


Loss of mouse cardiomyocyte talin-1 and talin-2 leads to β-1 integrin reduction, costameric instability, and dilated cardiomyopathy.
Continuous contraction-relaxation cycles of the heart require strong and stable connections of cardiac myocytes (CMs) with the extracellular matrix (ECM) to preserve sarcolemmal integrity. CM attachment to the ECM is mediated by integrin complexes localized at the muscle adhesion sites termed costameres. The ubiquitously expressed cytoskeletal protein talin (Tln) is a component of muscle costameres that links integrins ultimately to the sarcomere. There are two talin genes, Tln1 and Tln2. Here, we tested the function of these two Tln forms in myocardium where Tln2 is the dominant isoform in postnatal CMs. Surprisingly, global deletion of Tln2 in mice caused no structural or functional changes in heart, presumably because CM Tln1 became up-regulated. Tln2 loss increased integrin activation, although levels of the muscle-specific β1D-integrin isoform were reduced by 50%. With this result, we produced mice that had simultaneous loss of both CM Tln1 and Tln2 and found that cardiac dysfunction occurred by 4 wk with 100% mortality by 6 mo. β1D integrin and other costameric proteins were lost from the CMs, and membrane integrity was compromised. Given that integrin protein reduction occurred with Tln loss, rescue of the phenotype was attempted through transgenic integrin overexpression, but this could not restore WT CM integrin levels nor improve heart function. Our results show that CM Tln2 is essential for proper β1D-integrin expression and that Tln1 can substitute for Tln2 in preserving heart function, but that loss of all Tln forms from the heart-muscle cell leads to myocyte instability and a dilated cardiomyopathy.


Quantitative early decision making metric for identifying irregular breathing in 4DCT.
To develop a quantitative early decision making metric for prediction of breathing pattern and irregular breathing and validate the metric in a large patient population receiving clinical phase-sorted four-dimensional computed tomography (4DCT). This study employed three patient cohorts. The first cohort contained 47 patients, imaged with a nonclinical tidal volume metric. The second cohort contained a sample of 256 patients who received a clinical 4DCT. The third cohort contained 86 patients who received three 4DCT scans at 1-week increment during the course of radiotherapy. The second and third cohorts did not have tidal volume measurements, as per standard radiation oncology clinical practice. Based on a previously published technique that used a single abdominal surrogate, the ratio of extreme inhalation tidal volume to normal inhalation tidal volume (κ) metric was calculated and the patient breathing pattern was characterized. The use of a single surrogate precluded the use of a κ determined by tidal volume, so a κ(rel) was defined based on the amplitude of the surrogate. Patients were classified as either Type 1 or Type 2, based on a previously published technique, where Type 1 patients were apneic at end of exhalation and Type 2 patients exhibited forced respiration. The Ansari-Bradley test was used to determine the statistical similarity between the Type 1 and Type 2 distributions. A Kruskal-Wallis one way analysis of variance was used to determine the statistical similarities among the classified breathing types, κ(rel), and the qualified medical physicist denoted breathing classification (regular or irregular). Receiver operator characteristic curves were used to quantitatively determine optimal cutoff value j(κ) and efficiency cutoff value (τ(κ)) κ(rel) to provide a quantitative early warning of irregular breathing during 4DCT procedures. The statistical tests show a significant consistency for the breathing pattern classifications between the physiologically measured cohort #1 and the remaining cohorts. The classification types were statistically different between Type 1 and Type 2 patients over all cohorts. Values of κ(rel) in excess of 1.72 indicated a substantial presence of irregular breathing that could negatively affect the quality of a 4DCT image dataset. Values of κ(rel) in lower than 1.45 indicated minimal presence of irregular breathing. For values of κ(rel) such that j(κ) ≤ κ(rel) ≤ τ(κ), the decision to reacquire the 4DCT would be at the discretion of the physician. This accounted for only 11.9% of the patients in this study. The magnitude of κ(rel) held consistent over three weeks of treatment for 73% of the patients in cohort #3. The decision making metric based on κ was shown to be an accurate classifier of regular and irregular breathing patterns in a large patient population. Breathing type, as defined in a previous published work, was accurately classified by κ(rel) with the use of a single respiratory surrogate compared to the physiological use of multiple respiratory surrogates. This work provided a quantitative early decision making metric to quickly and accurately assess breathing patterns as well as the presence and magnitude of irregular breathing during 4DCT.


Overcorrecting minus lens therapy in patients with intermittent exotropia: Should it be the first therapeutic choice?
To evaluate medium-term outcomes of overminus lens treatment in patients with intermittent exotropia [X(T)]. A retrospective analysis was performed of the outcomes of 19 children with X(T) who were prescribed overminus lens (-2.00 to -4.00 D) for a median period of 18 months (6-33). The success was evaluated using two assessment methods: 1. Newcastle Control System (NCS), and 2. Jampolsky's assessment. The mean age of the patients was 6.8 ± 3.3 years (range 3-14 years). After the therapy, the median NCS score significantly improved from 5 to 1 (p < 0.001). Sixteen children (84 %) showed a NCS score of 2 or less after overminus lens treatment. According to Jampolsky's assessment, 84 % of the patients showed marked improvement from the baseline (47 % had qualitative improvement, 37 % quantitative decrease in the angle of deviation in addition to a qualitative improvement). The median pre-treatment distant angle decreased from 25 prism diopters (PD) to 18 PD after the treatment (p = 0.002). Overcorrecting minus lens treatment has a reasonable rate of success in the medium term and may be advised as primary therapeutic alternative for X(T). Both NCS and Jampolsky's scoring system appear to be useful and comparable for follow-up of patients with X(T).


SpoIIQ, a forespore-expressed gene required for engulfment in Bacillus subtilis.
A crucial step in converting an actively growing Bacillus subtilis cell into a dormant spore is the formation of a cell within a cell. This unusual structure is created by a phagocytosis-like process in which the larger mother cell progressively engulfs the adjacent smaller forespore. Only mutations blocking engulfment at an early stage and affecting genes expressed in the mother cell have been identified. Here we describe a new locus, spoIIQ, which is transcribed in the forespore and which encodes a membrane-bound protein required at a late stage of engulfment. Immunofluorescence microscopy analysis have shown that SpoIIQ is initially targeted to the septum at the boundary between the two cells and then spreads around the entire membrane of the forespore. Septum targeting requires only the first 52 residues of SpoIIQ as well as unidentified forespore-specific components. Electron-microscopy studies of cells engineered to activate the mother-cell program of gene expression independently of the forespore indicate that other as yet uncharacterized genes are involved in engulfment and that this morphological process is driven from both sides of the forespore envelope.


Confronting physiology: how do infected flies die?
Fruit fly immunology is on the verge of an exciting new path. The fruit fly has served as a strong model for innate immune responses; the field is now expanding to use the fruit fly to study pathogenesis. We argue here that, to understand pathogenesis in the fly, we need to understand pathology - and to understand pathology, we need to confront physiology with molecular tools. When flies are infected with a pathogen, they get sick. We group the events following infection into three categories: innate immune responses (defence mechanisms by which the fly attempts to kill or neutralize the microbe, some of which can themselves cause harm to the fly); microbial virulence (mechanisms by which the microbe evades the immune response); and host pathology (physiologies adversely affected by either the immune response or microbial virulence). We divide this review into sections mirroring these categories. The molecular study of infection in the fruit fly has focused on the first category, has begun to explore the second, and has yet to tap the full potential of the fly regarding the third.


Nucleosides for the treatment of respiratory RNA virus infections.
Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.


[Topography of small, intensely fluorescing cells in rat lumbar sympathetic ganglia].
The localization of small intensely fluorescent (SIF cells on serial cryostat slices and total preparations of the L2 and L4 rat lumbar sympathetic ganglia was studied after treatment by the modified Falck method. In the ganglia, the SIF cells occur both as clusters and singly. The cells are round in shape, frequently forming processes. The clusters of the SIF cells are usually localized beneath the ganglionic capsule in the proximity to the blood vessels. Large sympathetic ganglia contain from 35 to 51 cells, whereas small ganglia 5 to 9 cells. The regions of preferable SIF cells localization in L3 and L4 ganglia were found.


Three-dimensional co-culture microfluidic model and its application for research on cancer stem-like cells inducing migration of endothelial cells.
To build a three-dimensional co-culture model in a microfluidic device for cancer research and evaluate its feasibility by investigating cancer stem-like cells (SCs) induced migration of human umbilical vein endothelial cells (ECs). The microfluidic device provided two-dimensional and three-dimensional (2D/3D) culture and co-culture environments without affecting cell viability. The device also provided an effective concentration for the chemiotaxis of cells, and to support real-time monitoring of cell behavior. In this model, SCs significantly increased the migration area of ECs with a hepatocarcinoma cell line (MHCC97H; MCs). The presence of ECs also induced both MCs and SCs invasion into Matrigel. The migration area of MCs and SCs significantly increased when co-cultured with ECs. This 3D co-culture microfluidic model is a suitable model in cancer research. Compared with MCs, SCs had greater potential in inducing EC migration and interacting with ECs.


The fabrication and evaluation of inline coupling of microdialysis with capillary electrophoresis and its application in the determination of blood glucose.
A novel method of inline coupling of microdialysis (MD) with CE has been investigated. A polysulfone MD membrane was in situ prepared at the inlet end of the separation capillary, which endued the capillary with an additional function of clean-up sampling and made the pretreatment of complex matrices simple. The properties of the membrane and its influence on electrophoresis were evaluated. The membrane cut off macromolecules and particles efficiently and persistently, and changing the components of membrane-casting solution could control the molecular weight cutoff of the membrane. Using the capillary having the MD membrane in electrophoresis, column efficiency with little reduction was achieved. The mixture of chlorpheniramine (CPA) and BSA was used to verify the analytical characteristics. Only the peak of CPA appears in the electropherograms and the RSDs of migration times and peak areas of CPA were 0.8 and 4.6%, respectively. The method was applied for the determination of glucose in human blood using an electrochemical detector. Whole blood containing glucose and macromolecules was electrokinetically injected directly into the capillary without pretreatment, and the concentration of glucose in human blood was 5.5 mmol/L. Equilibrium dialysis injection is also investigated in this paper. The results show that the method may be further used for in vivo sampling to monitor the endogenous or exogenous small molecules and their metabolites.


Histological comparison of different compressive forces on particulate grafts during alveolar ridge preservation: a prospective proof-of-concept study.
The aim of this study was to determine the impact of different compressive forces on deproteinized bovine bone mineral (DBBM) particles covered by native bilayer collagen membrane (NBCM) during alveolar ridge preservation (ARP) in the molar area, and to identify any histomorphometric and clinical differences according to the compressive force applied. Sockets were filled with DBBM after tooth extraction, and different compressive forces (30 N and 5 N, respectively) were applied to the graft material in the test (30 N) and control (5 N) groups. The DBBM in both groups was covered with NBCM in a double-layered fashion. A crossed horizontal mattress suture (hidden X) was then made. A core biopsy was performed using a trephine bur without flap elevation at the implant placement site for histomorphometric evaluations after 4 months. The change of the marginal bone level was measured using radiography. Twelve patients completed the study. The histomorphometric analysis demonstrated that the mean ratios of the areas of new bone, residual graft material, and soft tissue and the implant stability quotient did not differ significantly between the groups (P>0.05). However, the mean size of the residual graft material showed a significant intergroup difference (P<0.05). The application of 2 compressive forces (5 N, 30 N) on particulate DBBM grafts during open-healing ARP in the posterior area led to comparable new bone formation, implant feasibility and peri-implant bone level.


A comparative study of a preservative-free latanoprost cationic emulsion (Catioprost) and a BAK-preserved latanoprost solution in animal models.
Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free latanoprost 0.005% cationic emulsion (Catioprost(®)), and a BAK-preserved latanoprost 0.005% solution (Xalatan(®)), were compared. The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed. Both the preservative-free and BAK-preserved latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free latanoprost cationic emulsion. In animal models, a preservative-free latanoprost cationic emulsion was as effective as Xalatan(®) for lowering IOP with an improved ocular tolerance profile.


Serum granulocyte colony-stimulating factor levels in chronic neutropenia of infancy.
Eight infants with chronic neutropenia ranging in age from 1 to 13 months were studied for serum granulocyte colony-stimulating factor (G-CSF) levels. Serum G-CSF levels were elevated, especially when peripheral blood absolute neutrophil counts (ANC) were under 500/microliter in seven patients with autoimmune neutropenia. On the other hand, in a patient with congenital agranulocytosis (Kostmann type), G-CSF levels were below the sensitivity of the assay (less than 50 pg/ml) despite severe neutropenia (less than 100/microliter).


Undergraduate health care informatics education: a needs analysis and proposed curriculum.
This paper describes a needs analysis and resulting curriculum in Health Care Informatics. It is implemented as a track for the BS degree within the Department of Information Systems at the University of Maryland, Baltimore County. The track in Health Care Informatics is an interdisciplinary specialty within the broader field of Information Systems which is itself an interdisciplinary field. The needs analysis shows current thinking by practitioners and educators in the new field of Health Care Informatics. It also presents a survey of undergraduate students to monitor interest in and knowledge of this field. A curriculum design is presented that addresses these needs.


Dihydro-Si-rhodamine for live-cell localization microscopy.
Fluorophores with photo-modulatory fluorescence properties are valuable for cutting-edge localization microscopy. The existing probes are either photo-activatable, or photo-switchable, but not both. We report a probe (DH-SiR), a leuco-dye obtained by reduction of Si-rhodamine, with both photo-activatable and photo-switchable fluorescence. The potential for super-resolution microscopy was showcased.


Growth of Mycobacterium leprae in nude mice.
Athymic nude mice were introduced in our laboratories in 1982. In this paper results over one year period of nude mice inoculated with small numbers of M. leprae are described. In this study we showed that 1 X 10(4) M. leprae with low numbers of viable bacilli inoculated into hind foot pads of nude mice housed both in vinyl plastic isolators and "clean room" conditions had the ability to grow and reach remarkable levels. There was dissemination of the infection to other uninoculated foot pads by six months.


Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.
This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.


Lectin histochemistry and ultrastructure of medullary carcinoma of the thyroid gland.
Lectin histochemistry and electron microscopy were used to study a series of 13 solid or microacinar medullary carcinomas of the thyroid (MCTs) and compare them with four follicular MCTs and other forms of thyroid cancer. Lectin histochemistry was not found to be of diagnostic value, since the MCT did not display any distinct lectin-binding pattern. This approach demonstrated that all MCTs, irrespective of their histologic appearance, consist of polarized cells, arranged into microfollicles that can be demonstrated readily by electron microscopy. We conclude that all MCTs form follicles, some visible by light microscopy, while others are submicroscopic and apparent only on histochemical staining. Because of the histochemical and ultrastructural similarities between solid MCTs and tumors with a follicular pattern, the latter should not be considered a distinct variant of C-cell neoplasia.


PVP versus HoLEP current outcomes and future strategies.
Photoselective vaporization of the prostate (PVP) with a potassium titanyl phosphate (KTP) laser and Holmium laser enucleation of the prostate (HoLEP) currently represent the most promising new technologies applied to the treatment of benign prostatic hyperplasia (BPH) associated with benign prostatic obstruction (BPO). The specific laser-light characteristics and the optimal interactions between lasers and prostatic tissue result in an even and efficient ablation of the prostate resulting in the formation of a clearly de-obstructed prostate cavity. PVP and HoLEP can be considered day-case procedures, as they require only a few hours of catheterization and are associated with minimal postoperative discomfort, while at the same time they offer results at least equivalent to the reference standards transurethral resection of the prostate and open prostatectomy. There is no doubt that larger studies with longer follow up are necessary to further define the durability of results of PVP and HoLEP in the management of BPH, this review will address current issues regarding how both techniques are performed, their results and limitations as well as their role in the future management of BPH.


Revisiting the role of the insula and smoking cue-reactivity in relapse: A replication and extension of neuroimaging findings.
The ability to direct smoking cessation treatment based on neuroscientific findings holds incredible promise. However, there is a strong need for consistency across studies to confirm neurobiological targets. While our prior work implicated enhanced insula reactivity to smoking cues in tobacco smoking relapse vulnerability, this finding has not been confirmed. Using functional magnetic resonance imaging (fMRI), we evaluated the pre-cessation brain reactivity to smoking vs. neutral cues in nicotine dependent smokers who were and were not able to maintain subsequent abstinence. Of the 23 (7 women) individuals assessed, 13 relapsed and there were no demographic differences between those who did and did not relapse. However, smokers who relapsed showed enhanced reactivity to smoking cues in the right insula and dorsal striatum, showing significant overlap between our current and prior work despite methodological differences, including the fact that our previous work only included women. The current work supports our prior results and builds on the concept that the insula and dorsal striatum work in concert to maintain nicotine dependence. Specifically, dorsal striatal-mediated habitual responding may be triggered both by the external drug-associated cues, and the insula-mediated internal states that provide additional context motivating drug use. This replicated finding also mirrors preclinical work that finds the same individualized distinction, as only some rodents attribute incentive salience to drug cues and are more likely to reinstate drug seeking after extinction. To effectively treat addiction, these individual characteristics and their underlying neurobiological foundations must be considered.


[Management of the impalpable testis in children].
To explore the management of the impalpable testis in children. From April 2003 to August 2005, 36 children aged 20 months to 8 years with impalpable testes underwent inguinal and laparoscopy explorations. The clinical data were reviewed, including the indications of laparoscopy and inguinal explorations and the correspondence between the ultrasonic and surgical Of the 36 cases (36 / 361 ) of impalpable testis (41 testes), laparoscopy and inguinal explorations revealed 18 results. testes to be vanishing ones, 21 located intra-abdominally and 2 scrotal nubbins. Manifestations were divided into 4 types according to the laparoscopic findings, and 9 testes fell into Type I, 9 Type II, 13 Type III and 10 Type IV. Orchidopexies were performed by traditional and laparoscopic techniques. The positive diagnoses by ultrasound accounted for 75% (27/36). The volumes of the contralateral testes of the cryptorchid children were larger than those with intra-abdominal testes and testicular nubbins. One case of testicular atrophy was detected by ultrasound in the follow-up period. Laparoscopy should be performed as a routine in children with impalpable testes. Children with Type II testes need not undergo inguinal exploration. Inguinal and scrotal explorations are necessary for children with Type I testes. Preoperative ultrasonic examination of the contralateral testis helps to evaluate vanishing testes or testicular nubbins.


Effects of pre-exhausting the biceps brachii muscle on the performance of the front lat pull-down exercise using different handgrip positions.
The aim of the present study was to investigate the effects of pre-exhaustion (PE) of the biceps brachii muscle (BB) on the number of repetitions and the rate of perceived exertion (RPE) in the front lat pull-down (FLPD) using different handgrip positions. Additionally, the effect of sex and its interaction with performance and the RPE were also examined. The participants were 19 healthy subjects: 8 men (age: 27.13±2.85 years; body height: 180.63±6.65 cm; body mass: 82.05±8.92 kg; and body fat: 14.67±6.09%); and 11 women (age: 28.81±3.68 years; body height: 162.91±6.51 cm; body mass 59.63±6.47 kg; and body fat: 24.11±4.33%). The number of repetitions and the RPE in the FLPD exercise with different handgrip positions, with and without PE of the BB, was documented. The following main significant effects were seen: i) PE of the BB decreased the number of repetitions (p<0.001) and increased the RPE (p<0.001); ii) the narrow handgrip width elicited a higher RPE (p<0.001) and iii) women performed fewer repetitions than men in all FLPD exercise variations (p=0.023). Significant interactions were also observed between: i) PE or sex and the RPE (p=0.024); and ii) PE or handgrip width and the number of repetitions (p<0.001). In conclusion, PE of the BB promotes a decreased performance in the FLPD exercise along with a greater RPE, especially when using a narrow handgrip position.


CONGENITAL HYPOTHYROIDISM IN A BORNEAN ORANGUTAN (PONGO PYGMAEUS) AND A SUMATRAN ORANGUTAN (PONGO ABELII).
Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.


Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs.
The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.


Primary obstructive megaureter: the role of high pressure balloon dilation.
There is a growing interest in minimally invasive treatment of primary obstructive megaureter (POM) in children. The absence of long-term follow-up data, however, makes it difficult to establish the indication for an endoscopic approach. The aim of our study is to determine the long-term efficacy of endourologic high-pressure balloon dilation of the vesicoureteral junction (VUJ) in children with POM that necessitates surgical treatment. We retrospectively reviewed the clinical records from children with POM who were treated with endourologic high-pressure balloon dilation of the VUJ from March 2003 to April 2010. To determine the long-term, a cohort study was conducted in November 2011. Endourologic dilation of the VUJ was performed with a semicompliant high-pressure balloon (2.7 FG) with a minimum balloon size of 3 mm, followed by placement of a Double-J stent. We have treated 29 (32 renal units, left [n=16], right [n=10] and bilateral [n=3]) children with a diagnosis of POM within this period. The median age at the time of the endourologic treatment was 4.04 months (range 1.6-39 months). In three cases, an open ureteral reimplantation was needed, in two cases because of intraoperative technical failure and postoperative Double-J stent migration in one patient. The 26 children (29 renal units) who had a successful endourologic dilation of the VUJ were followed with ultrasonography and MAG-3-Lasix (furosemide) studies that showed a progressive improvement of both the ureterohydronephrosis and drainage in the first 18 months in 20 patients (23 renal units) (69%). In two patients who were treated with a 3 mm balloon, a further dilation was needed, with an excellent outcome. The cohort study (at a median follow-up of 47 months) showed that in all patients who had a good outcome at the 18-month follow-up after endourologic balloon dilation remained asymptomatic with resolution of ureterohydronephrosis on the US and good drainage on the renogram, in the children with some persistent hydronephrosis. Our study shows that children with POM who were treated with high-pressure ballon dilation of the VUJ who have satisfactory appearance at 18 months maintain these results over time.


GDP-l-fucose synthase is a CD4+ T cell-specific autoantigen in DRB3*02:02 patients with multiple sclerosis.
Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)-l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid-infiltrating CD4+ T cells from HLA-DRB3*-positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.


Effects of acute sublethal exposure to coumaphos or diazinon on acquisition and discrimination of odor stimuli in the honey bee (Hymenoptera: Apidae).
Two organophosphate compounds, coumaphos and diazinon, were examined for effects of sublethal exposure on odor learning and generalization in honey bees, Apis mellifera L. Using proboscis extension response training as a measure of odor learning and discrimination, a series of two experiments tested whether these compounds would inhibit bees from learning a new odor or discriminating between different odors. Bees were exposed to coumaphos or diazinon in acetone applied to the thorax, or to coumaphos or diazinon in hexane injected intracranially. At no dose tested or exposure method used was coumaphos shown to inhibit acquisition of a novel odor stimulus, although it was shown to slightly reduce discriminatory ability when given by intracranial injection. Diazinon had effects on odor learning at several small doses, and a small injected dose was shown to significantly inhibit learning of an odor stimulus paired with a sucrose reward. When bee head acetylcholineasterase activity was measured after dermal applications of both pesticides, only the higher doses of diazinon showed reduced activity, indicating that externally-applied coumaphos shows no significant effect on bee brain acetylcholinesterase activity. These data suggest that acute application of coumaphos has only slight nonlethal effects upon the behavior of honey bees and should have little effect upon bee tasks that involve odor learning.


Determining the enzymatic activities of iodothyronine 5'-deiodinases in renal medulla and cortex.
Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones conversion is not fully understood. The activities of different types of iodothyronine deiodinases in the kidney structures have not been determined yet. The aim of this study was to determine the activity of deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal cancer patients. Samples of renal cortex and medulla (ten patients) or renal cortex alone (13 patients) were taken from kidneys resected because of malignant cancer, from a site opposite to the cancer. Resections were performed in the 23 patients (seven female and 16 male) who were 52-82 years old. The material was stored at -72 oC. Activity of D1 in renal cortex was 3.785 ± 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 ± 0.125 fmol 125I/mg protein/minute. There was a strong positive correlation between D1 and D2 activities in renal cortex (r = 0.890, p 〈 0.001). Activity of D1 in renal medulla was 2.157 ± 2.176 fmol 125I/mg protein/minute, and activity of D2 was 0.168 ± 0.095 fmol 125I/mg protein/minute. A positive correlation between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well. Activities of D1 in cortex and medulla were strongly and positively associated (r = 0.794, p = 0.006), whereas there was no correlation between the activities of D2 in cortex and medulla (r = 0.224, p = 0.553). Results presented in this study suggest that both cortical and medullary D1 and D2 may be involved in thyroid hormone metabolism. This finding could be of clinical relevance in patients with impaired renal function.


Vibrational Bands of the 2-Butyn-1-yl Radical.
The 2-butyn-1-yl radical is an isomer of C4H5 and is structurally similar to the propargyl radical, which is the simplest resonance-stabilized hydrocarbon radical. The C4H5 radical is likely to be important to astrochemistry and combustion, similar to propargyl, yet little research has been done on its spectroscopic properties. In this work, seven vibrational bands of the 2-butyn-1-yl radical are reported. The radical was formed by pyrolysis of 1-bromo-2-butyne at 800 K and isolated in a low-temperature argon matrix. The experimentally observed frequencies and intensities of the seven vibrational bands were found to be consistent with QCISD predictions from the literature and with new B3LYP calculations in this work.


The relationship between chitotriosidase activity and tuberculosis.
Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future.


Peripheral skin necrosis in the recipient of monochorionic twins complicated by twin-twin transfusion syndrome.
Twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic, diamniotic twin pregnancies and if untreated carries a high perinatal loss rate of between 80% and 100%, depending on the stage. The underlying pathology in TTTS appears to be an imbalanced intertwin perfusion difference, secondary to functional unidirectional arteriovenous anastomoses within a monochorionic placenta. We report two cases of monochorionic twin pregnancy complicated by TTTS, in which the pregnancies were treated by serial aggressive amnioreduction. However, the recipient twin in each pregnancy developed 'ischemic damage' to a lower limb.


Ecklonia cava extracts inhibit lipopolysaccharide induced inflammatory responses in human endothelial cells.
Ecklonia cava (EC) is a brown alga that evidences radical scavenging, bactericidal, tyrosinase inhibitory and protease inhibitory activities. However, the antiinflammatory effects in human endothelial cells and its molecular mechanism remain poorly understood. In this study, we attempted to determine whether pretreatment with EC extracts induce a significant inhibition of antiinflammatory activities in lipopolysaccharide (LPS) induced human endothelial cells. We found that each EC extract inhibits LPS induced barrier permeability, expression of cell adhesion molecules, monocytes adhesion, and transendothelial migration to human endothelial cells. Further studies revealed that EC extracts suppress the production of tumor necrosis factor-alpha (TNF-alpha) and activation of nuclear factor-kappa B (NF-kappaB). Particularly, the antiinflammatory effects of ethyl acetate (EtOAc) and butanol (n-BuOH) extracts were better than those of other extracts. Collectively, these results suggest that EC extracts possess barrier integrity activity, inhibitory activity on cell adhesion and migration to endothelial cells by blocking the activation of NF-kappaB expression and production of TNF-alpha, thereby endorsing its usefulness as therapy for vascular inflammatory diseases.


Spinal deformity in patients who have fibrodysplasia ossificans progressiva.
We reviewed roentgenograms and clinical records in order to characterize the spinal deformity in forty patients who had an established diagnosis of fibrodysplasia ossificans progressiva. Twenty-six (65 per cent) of the patients had scoliosis, which, according to the clinical records and the recollection of the patients, had been present during childhood. Twenty-three (88 per cent) of the twenty-six curves were unbalanced c-shaped curves, while the remaining three (12 per cent) were balanced s-shaped curves. Twenty-one (91 per cent) of the twenty-three c-shaped curves involved the thoraco-lumbar or lumbar spine. The c-shaped curves ranged in magnitude from 15 to more than 80 degrees. Curves became rigid by early adulthood and many resulted in severe pelvic obliquity with impaired sitting or standing balance. An osseous bridge developed between the posterolateral aspect of the iliac crest and the posterolateral aspect of the rib cage in twenty-two (55 per cent) of the forty patients. Nineteen (86 per cent) of these twenty-two patients had scoliosis; there was a significant association between the development of scoliosis and the presence of the osseous bridge (p < 0.005). Ossification of the paravertebral muscles and fascia during the first decade of life limited the development of a normal thoracic kyphosis in ten (42 per cent) of twenty-four patients for whom lateral roentgenograms of the spine were available. A spinal orthosis was used to treat the scoliosis in two patients, but this method resulted in breakdown of the skin and failed to halt progression of the curve.(ABSTRACT TRUNCATED AT 250 WORDS)


Sampling design for an integrated socioeconomic and ecological survey by using satellite remote sensing and ordination.
Environmental variability is an important risk factor in rural agricultural communities. Testing models requires empirical sampling that generates data that are representative in both economic and ecological domains. Detrended correspondence analysis of satellite remote sensing data were used to design an effective low-cost sampling protocol for a field study to create an integrated socioeconomic and ecological database when no prior information on ecology of the survey area existed. We stratified the sample for the selection of tambons from various preselected provinces in Thailand based on factor analysis of spectral land-cover classes derived from satellite data. We conducted the survey for the sampled villages in the chosen tambons. The resulting data capture interesting variations in soil productivity and in the timing of good and bad years, which a purely random sample would likely have missed. Thus, this database will allow tests of hypotheses concerning the effect of credit on productivity, the sharing of idiosyncratic risks, and the economic influence of environmental variability.


Ongoing epidemic of cutaneous leishmaniasis among Syrian refugees, Lebanon.
In September 2012, a cutaneous leishmaniasis outbreak began among Syrian refugees in Lebanon. For 948 patients in whom leishmaniasis was not confirmed, we obtained samples for microscopic confirmation and molecular speciation. We identified Leishmania tropica in 85% and L. major in 15% of patients. After 3 months of megulamine antimonite therapy, patients initial cure rate was 82%.


Phospholipid barrier to fibrinolysis: role for the anionic polar head charge and the gel phase crystalline structure.
The massive presence of phospholipids is demonstrated in frozen sections of human arterial thrombi. Purified platelet phospholipids and synthetic phospholipids retard in vitro tissue-type plasminogen activator (tPA)-induced fibrinolysis through effects on plasminogen activation and plasmin function. The inhibition of plasminogen activation on the surface of fibrin correlates with the fraction of anionic phospholipid. The phospholipids decrease the amount of tPA penetrating into the clot by 75% and the depth of the reactive surface layer occupied by the activator by up to 30%, whereas for plasmin both of these parameters decrease by approximately 50%. The phospholipids are not only a diffusion barrier, they also bind the components of the fibrinolytic system. Isothermal titration calorimetry shows binding characterized with dissociation constants in the range 0.35-7.64 microm for plasmin and tPA (lower values with more negative phospholipids). The interactions are endothermic and thermodynamically driven by an increase in entropy, probably caused by the rearrangements in the ordered gel structure of the phospholipids (in line with the stronger inhibition at gel phase temperatures compared with liquid crystalline phase temperatures). These findings show a phospholipid barrier, which should be overcome during lysis of arterial thrombi.


Topical treatment with sacran, a sulfated polysaccharide from Aphanothece sacrum, improves corneocyte-derived parameters.
Sacran, a polysaccharide isolated from Aphanothece sacrum (Suizenji-nori) alga, has unique characteristics in terms of its physiological properties and effects on the skin, and has recently become a focus of attention as a novel biomaterial. In a previous study, we reported the unique physical characteristics of sacran, which forms a gel-like film containing water in the presence of polyols. This film resists penetration by water and chemicals. We expected this unique physical characteristic to act as an artificial barrier upon the application of sacran to the skin. In the present study, we tested the efficacy of sacran application in healthy individuals who reported previous symptoms of dry or inflamed skin, to evaluate the potential benefits of sacran for skin care in patients with mild atopic dermatitis. Compared with placebo, sacran-containing serum did not significantly alter either the water content of the skin surface or transepidermal water loss. However, subjects using the serum showed improvements in corneocyte parameters including size, percentage of thick abrasion, ratio of SH to SS groups, ratio of interleukin (IL)-1 receptor antagonist to IL-1α, and carbonylated protein level. These results indicate that the sulfated polysaccharide sacran is an effective agent for improving or maintaining the skin conditions.


Effects of serum on hepatocyte growth factor secretion and activation by periodontal ligament and gingival fibroblasts.
Hepatocyte growth factor (HGF)/scatter factor is a paracrine growth factor secreted by mesenchymal cells, which exerts an effect on a variety of epithelial cell types. Our recent study revealed that periodontal ligament fibroblasts (PLF) and gingival fibroblasts (GF) cultured in the presence of serum which contains various stimulants produced HGF or HGF-like factor, a predominant chemoattractant for gingival epithelial cells, and suggested that it could be involved in epithelial down-growth in periodontitis. To clarify whether serum in medium stimulates PLF and GF to synthesize or activate HGF, the effect of fetal bovine serum (FBS) on HGF production was determined by enzyme-linked immunoabsorbent assay (ELISA), and its chemotactic activity for gingival epithelial cells was examined by modified Boyden chamber assay. One to 10% FBS in the culture medium stimulated HGF secretion in a dose-dependent manner and the chemotactic activity was decreased by treatment with anti-hHGF neutralizing antibody. Furthermore, fibroblast-conditioned medium incubated with FBS and aprotinin reduced its chemotactic activity. Interestingly, serum-free culture of PLF and GF produced potent chemoattractants for gingival epithelial cells other than HGF. These results show that FBS stimulates both HGF secretion and activation by PLF and GF.


Diversity and antibiotic resistance of Acinetobacter spp. in water from the source to the tap.
Acinetobacter spp. are ubiquitous bacteria in the environment. Acinetobacter spp. isolated from a municipal drinking water treatment plant and from connected tap water were identified to the species level on the basis of rpoB gene partial sequence analysis. Intraspecies variation was assessed based on the analysis of partial sequences of housekeeping genes (rpoB, gyrB, and recA). Antibiotic resistance was characterized using the disk diffusion method and isolates were classified as wild or non-wild type (non-WT), according to the observed phenotype. The strains of Acinetobacter spp. were related to 11 different validly published species, although three groups of isolates, presenting low rpoB sequence similarities with previously described species, may represent new species. Most of the isolates were related to the species A. johnsonii and A. lwoffii. These two groups, as well as others related to the species A. parvus and A. tjernbergiae, were detected in the water treatment plant and in tap water. Other strains, related to the species A. pittii and A. beijerinckii, were isolated only from tap water. Most of the isolates (80 %) demonstrated wild type (WT) to all of the 12 antibiotics tested. Non-WT for tetracycline, meropenem, and ceftazidime, among others, were observed in water treatment plant or in tap water samples. Although, in general, this study suggests a low prevalence of acquired antibiotic resistance in water Acinetobacter spp., the potential of some species to acquire and disseminate resistance via drinking water is suggested.


A functional glycogen biosynthesis pathway in Lactobacillus acidophilus: expression and analysis of the glg operon.
Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of Lactobacillus acidophilus, a probiotic microbe, in the human gastrointestinal environment. L. acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and growth phase-dependent, and were repressed by glucose. The highest intracellular glycogen content was observed in early log-phase cells grown on trehalose, which was followed by a drastic decrease of glycogen content prior to entering stationary phase. In raffinose-grown cells, however, glycogen accumulation gradually declined following early log phase and was maintained at stable levels throughout stationary phase. Raffinose also induced an overall higher temporal glg expression throughout growth compared with trehalose. Isogenic ΔglgA (glycogen synthase) and ΔglgB (glycogen-branching enzyme) mutants are glycogen-deficient and exhibited growth defects on raffinose. The latter observation suggests a reciprocal relationship between glycogen synthesis and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase) resulted in defective growth and increased bile sensitivity. The data indicate that glycogen metabolism is involved in growth maintenance, bile tolerance and complex carbohydrate utilization in L. acidophilus.


Overview: psychiatric sequelae to multiple trauma.
The authors discuss the setting, patients, and staff, and the role of psychiatric consultants in intensive care units and trauma centers. They point out the similarities and differences between patients with multiple trauma and those who have had open-heart surgery and head or spinal cord injuries. They also deal with the question of an element of self-destructive behavior in accidents and offer suggestions for the psychiatric management of severely traumatized patients. The authors conclude that the role and obligation of the psychiatrist of the the future will lie in crisis intervention within the medical-biological model.


[Laryngeal and pharyngolaryngeal cancers: evaluation of the laryngectomy's quality of life].
The concept of life quality plays a more and more significant role in the caring of cancer patients, because the illness and the therapies used have a strong influence at the physical, psychological and relational level. The laryngeal and pharyngolaryngeal cancers have two characteristics: they challenge the life prognosis by affecting three essential functions: breathing, phonation and feeding and they disrupt the relation life. The locoregional treatments are mainly based on surgery and radiotherapy. In surgery, there are two tendencies: the saving techniques and the necessity of carrying out strong mutilations, such as laryngectomy or total pharyngolaryngectomy. To adapt to the illness and the after-effects of therapeutic caring, the patient must cope with multiple difficulties. Measuring life quality will allow the caretakers to evaluate the needs of the patient in the prospect of contributing to his reintegration in his family, society and professional life. This procedure must prove useful in the eyes of the patients, their environment and the caring teams.


Fatty marrow in the vertebrae. A parameter for hematopoietic activity in the aged.
Fatty alteration of bone marrow was analyzed in upper lumbar vertebrae obtained from 94 autopsies. Of these, 85 were from individuals over 60 years of age. Fatty marrows were classified grossly into three groups: Group I, a massive type, Group II, a moderate or less significant type; Group III, a nonfatty type. Fatty marrows of Groups I and II were found most frequently in the older subjects. They were not observed (0/9) below 60 years of age, but were present in 42% (5/12) in the 6th decade, 61% (23/38) in the 7th decade, 76% (25/33) in the 8th decade, and 100% (2/2) in the 9th decade. This may relate to a decreasing volume of a reservoir stem cell compartment for blood cell generation. Since the vertebral marrow is the last reserve site for hematopoietic activity, the volume of fatty marrow in the vertebrae may be used as a parameter for the estimation of hematopoietic activity in the entire skeletal system in the aged.


[Measurement of the mitral area with three-dimensional cardiac echography].
Two dimensional planimetry of mitral stenosis is sometimes difficult due to the complex morphology of the mitral valve. Three dimensional cardiac echography images the projected area of the mitral valve allowing precise planimetry of the orifice. Thirty patients with mitral stenosis were included in this study in order to obtain planimetry of the mitral orifice with two dimensional and three dimensional "freehand" mode transthoracic echocardiography. In 10 patients, the measurements were taken before and after percutaneous commissurotomy. The mitral area measured with three dimensional echography was 1.36+/-0.45 cm2 and 1.39+/-0.43 cm2 in two dimensional mode. The correlation between the 2 methods was good (y=1.01x - 0.08, r=0.92, p<0.001) but three dimensional echocardiography significantly underestimated the two dimensional planimetry by 0.05+/-0.27 cm2 (4+/-20%, p<0.05). The intra- and inter-observer reproducibility of the three dimensional measurements were 0.95 and 0.91 respectively. Three dimensional free-hand mode cardiac echography allows precise measurement of the mitral orifice area in patients with mitral stenosis.


Nitric oxide inhibits FTO demethylase activity to regulate N6-methyladenosine mRNA methylation.
N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. Demethylation of m6A on mRNA is catalyzed by the enzyme fat mass and obesity-associated protein (FTO), a member of the nonheme Fe(II) and 2-oxoglutarate (2-OG)-dependent family of dioxygenases. FTO activity and m6A-mRNA are dysregulated in multiple diseases including cancers, yet endogenous signaling molecules that modulate FTO activity have not been identified. Here we show that nitric oxide (NO) is a potent inhibitor of FTO demethylase activity by directly binding to the catalytic iron center, which causes global m6A hypermethylation of mRNA in cells and results in gene-specific enrichment of m6A on mRNA of NO-regulated transcripts. Both cell culture and tumor xenograft models demonstrated that endogenous NO synthesis can regulate m6A-mRNA levels and transcriptional changes of m6A-associated genes. These results build a direct link between NO and m6A-mRNA regulation and reveal a novel signaling mechanism of NO as an endogenous regulator of the epitranscriptome.


Putrefactive rigor: apparent rigor mortis due to gas distension.
Artifacts due to decomposition may cause confusion for the initial death investigator, leading to an incorrect suspicion of foul play. Putrefaction is a microorganism-driven process that results in foul odor, skin discoloration, purge, and bloating. Various decompositional gases including methane, hydrogen sulfide, carbon dioxide, and hydrogen will cause the body to bloat. We describe 3 instances of putrefactive gas distension (bloating) that produced the appearance of inappropriate rigor, so-called putrefactive rigor. These gases may distend the body to an extent that the extremities extend and lose contact with their underlying support surface. The medicolegal investigator must recognize that this is not true rigor mortis and the body was not necessarily moved after death for this gravity-defying position to occur.


Oral Health Care Practice and Circumstances during Covid-19 among Dental Patients in Tertiary Care Hospital in Nepal.
Background Patients are hesitant to enter a dental hospital because of the significant danger of cross infection and illness transmission due to rapid spread of corona virus. Objective To assess knowledge regarding Covid-19, oral health practices and circumstances on dental treatment during a pandemic. Method Cross sectional study was conducted among patients visiting dental department of Dhulikhel hospital from September to October 2020. Questionnaires were interviewed following safety protocols regarding the pandemic and descriptive analysis was performed. Both verbal and written consent as well as ethical approval was taken before the study. Result A total 411 patients aged 14 to 75 years old from 14 different districts across Nepal participated in the study. All of the patient were free of Covid-19 symptoms and had strong knowledge and awareness about disease transmission. During the crisis 96% of the people maintain good oral hygiene while 25.8% acquire new dental problems where majority experienced oral discomfort and swelling, 93.2% of them did not attend a dental clinic or hospital in the interim owing to fear and inaccessibility. Majority of the participants were impressed by the safety precautions and preparations during treatment and 99.3% strongly suggest or pledge to visit dental department if necessary during the pandemic. Conclusion Dental patient visiting Dhulikhel hospital is highly aware of current health crisis, possible transmission and preventive measures. Proper safe hospital setup can encourage them to seek dental treatment during crisis. Dental pain and swelling in Endodontic department recorded most common dental emergency during this pandemic.


ABI3- and PIF1-mediated regulation of GIG1 enhances seed germination by detoxification of methylglyoxal in Arabidopsis.
Methylglyoxal (MG) is a toxic by-product of the glycolysis pathway in most living organisms and was previously shown to inhibit seed germination. MG is detoxified by glyoxalase I and II family proteins in plants. MG is abundantly produced during early embryogenesis in Arabidopsis seeds. However, the mechanism that alleviates the toxic effect of MG in maturing seeds is poorly understood. In this study, by T-DNA mutant population screening, we found that mutations in a glyoxalase I gene (named GERMINATION-IMPAIRED GLYOXALASE 1, GIG1) led to significantly impaired germination compared with wild-type seeds. Transformation of full-length GIG1 cDNA under the constitutively active cauliflower mosaic virus 35S promoter in the gig1 background completely recovered the seed germination phenotype. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses revealed that GIG1 is uniquely expressed in seeds and is upregulated by abscisic acid (ABA) and downregulated by gibberellic acid (GA) during seed germination. An ABA signaling component, ABI3, directly activated GIG1 in maturing seeds. In addition, PHYTOCHROME INTERACTING FACTOR 1 (PIF1) also plays cooperatively with ABI3 in the regulation of GIG1 expression in the early stage of imbibed seeds. Furthermore, GIG1 expression is stably silenced by epigenetic repressors such as polycomb repressor complexes. Altogether, our results indicate that light and ABA signaling cooperate to enhance seed germination by the upregulation of GIG1 to detoxify MG in maturing seeds.


Microscopic versus macroscopic biomass models in activated sludge systems.
Today's models of activated sludge systems are based on average composition of biomass (macroscopic models). With the introduction of cell internal storage compounds (structured biomass) in ASM2 and ASM3 cell composition influences the kinetic behavior of activated sludge. Since the kinetics of most processes is not linear, adding up the behavior of individual cells (microscopic models) does not result in the same model prediction as obtained when predictions are made with average cell composition. Based on first simple computations with microscopic models which consider up to 100,000 individual bacteria, differences in model prediction are identified. It becomes clear that kinetic parameters for lumped, macroscopic models are system specific: whereas biomass from SBR systems yields kinetic parameters suited for application in microscopic models--biomass from continuous flow systems can only be used for the calibration of macroscopic models. Application of SBR models to continuous flow systems requires the use of microscopic models.


Co-creative development of an eHealth nursing intervention: Self-management support for outpatients with cancer pain.
Co-creative methods, having an iterative character and including different perspectives, allow for the development of complex nursing interventions. Information about the development process is essential in providing justification for the ultimate intervention and crucial in interpreting the outcomes of subsequent evaluations. This paper describes a co-creative method directed towards the development of an eHealth intervention delivered by registered nurses to support self-management in outpatients with cancer pain. Intervention development was divided into three consecutive phases (exploration of context, specification of content, organisation of care). In each phase, researchers and technicians addressed five iterative steps: research, ideas, prototyping, evaluation, and documentation. Health professionals and patients were consulted during research and evaluation steps. Collaboration of researchers, health professionals, patients and technicians was positive and valuable in optimising outcomes. The intervention includes a mobile application for patients and a web application for nurses. Patients are requested to monitor pain, adverse effects and medication intake, while being provided with graphical feedback, education and contact possibilities. Nurses monitor data, advise patients, and collaborate with the treating physician. Integration of patient self-management and professional care by means of eHealth key into well-known barriers and seem promising in improving cancer pain follow-up. Nurses are able to make substantial contributions because of their expertise, focus on daily living, and their bridging function between patients and health professionals in different care settings. Insights from the intervention development as well as the intervention content give thought for applications in different patients and care settings.


Frontiers of stochastic electronic structure calculations.
In recent years there has been a rapid growth in the development and application of new stochastic methods in electronic structure. These methods are quite diverse, from many-body wave function techniques in real space or determinant space to being used to sum perturbative expansions. This growth has been spurred by the more favorable scaling with the number of electrons and often better parallelization over large numbers of central processing unit (CPU) cores or graphical processing units (GPUs) than for high-end non-stochastic wave function based methods. This special issue of the Journal of Chemical Physics includes 33 papers that describe recent developments and applications in this area. As seen from the articles in the issue, stochastic electronic structure methods are applicable to both molecules and solids and can accurately describe systems with strong electron correlation. This issue was motivated, in part, by the 2019 Telluride Science Research Center workshop on Stochastic Electronic Structure Methods that we organized. Below we briefly describe each of the papers in the special issue, dividing the papers into six subtopics.


Instrumental measurements of skin color and skin ultraviolet light sensitivity and risk of cutaneous malignant melanoma: a case-control study in an Italian population.
The authors evaluated objective measurements of constitutive skin color and ultraviolet light sensitivity in relation to risk of cutaneous malignant melanoma (CMM). Incident CMM cases (n = 183) were diagnosed between December 1994 and January 1999 at the Maurizio Bufalini Hospital in Cesena, Italy. Controls (n = 179) were mostly spouses/partners of cases and were frequency-matched by age and sex. In addition to interviews, constitutive skin color and skin ultraviolet light sensitivity were assessed by colorimetry and minimal erythema dose (MED), respectively. Odds ratios were estimated using unconditional logistic regression. The odds of CMM increased by a factor of 1.20 (95 percent confidence interval: 1.12, 1.30) for each unit of skin brightness and by a factor of 1.24 (95 percent confidence interval: 1.07, 1.43) per 10 mJ/cm(2) of MED. These associations were largely independent of phenotypic or sun-related characteristics and were modified by sun exposure. Increased risk of CMM was observed only among subjects with the highest levels of sun exposure. Epidemiologic studies of CMM may benefit from the inclusion of colorimetric and MED measurements along with traditional risk factors to obtain more accurate, quantitative, and objective information.


Immunomodulation by Corynebacterium parvum in normal humans.
Four normal human donors were immunized with 2 mg of heat-killed Corynebacterium parvum by subcutaneous and intracutaneous injections, and lymphocyte surface markers, antibody-dependent (ADCC), and spontaneous cell-mediated (SCMC) cytotoxicities followed for a 28-day period. Although no changes were observed in the relative proportions of B, T, and Fc receptor-carrying lymphocytes, two T cell subpopulations, namely, the autologous rosette-forming cells and active rosette-forming cells, both exhibited significant increases. Significant increases were also demonstrated in the proportion of monocytes carrying Fc receptors and in the proportion of monocytes phagocytizing Latex beads. Although no consistent changes could be found in ADCC against the P 815 mastocytoma cell line, the SCMC against both the myeloid leukaemia line K 562 and the lymphoma line RAJI was found to be elevated as early as 6 hr post-vaccination. The possibility that the enhanced SCMC activity was induced in vivo by interferon was supported thus: 1) Enhancement of SCMC in vitro by interferon was abrogated by the vaccination. 2) Serum interferon determinations showed significant increases in parallel with the lack of in vitro SCMC enhancement.


The effect of movement on the holding power of screws in bone.
Movement between screw threads and bone inhibits bone formation, revascularization and remodeling of dead bone. Movement causes the screw to become enveloped by fibrous tissue in response to necrosis and resorption of adjacent dead cortical bone. This results in a radiologically discernible radiolucent "halo" about the screw, a certain sign of screw loosening.


Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts.
Advanced ovarian cancer is very responsive to first line platinum therapy, however almost invariably it relapses with a resistant disease. We have reported that patient derived ovarian xenografts (PDXs), independently from the degree of the initial response to cisplatin (DDP), show a significantly lower response to a second DDP cycle. We here report the effect of new combination regimens containing a MEK inhibitor (MEK), bevacizumab (BEV) and paclitaxel (PTX) as second line therapy in platinum-relapsing PDXs.We selected three DDP-relapsing PDX models based on the presence of activation of the RAS/RAF/MEK/ERK axis, mutated p53, lack of PTEN expression and activation of the PI3K pathway. In all the selected xenograft models, the antitumor efficacy of the doublets can be summarized as PTX/BEV > BEV/MEK > PTX/MEK and the antitumor activity of the triple combination was higher than any double combination. All the different combinations were well tolerated. The present data corroborate the activity of bevacizumab in combination with chemotherapy for the treatment of relapsing ovarian tumors and suggest that the addition of another targeted agents (MEK inhibitor) can further increase the antitumor activity without any increase in toxicity. PDX models represent a useful model to test second line therapy after failure of DDP first line.


Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study.
Recent studies in rodents indicate that a combination of exercise training and supplementation with nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials analyzing this. This study investigates the effects of a combination of exercise training and supplementation with nicotinamide mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness in healthy amateur runners. A six-week randomized, double-blind, placebo-controlled, four-arm clinical trial including 48 young and middle-aged recreationally trained runners of the Guangzhou Pearl River running team was conducted. The participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo). Each group consisted of ten male participants and two female participants. Each training session was 40-60 min, and the runners trained 5-6 times each week. Cardiopulmonary exercise testing was performed at baseline and after the intervention, at 6 weeks, to assess the aerobic capacity of the runners. Analysis of covariance of the change from baseline over the 6 week treatment showed that the oxygen uptake (VO2), percentages of maximum oxygen uptake (VO2max), power at first ventilatory threshold, and power at second ventilatory threshold increased to a higher degree in the medium and high dosage groups compared with the control group. However, there was no difference in VO2max, O2-pulse, VO2 related to work rate, and peak power after the 6 week treatment from baseline in any of these groups. NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle. ChiCTR2000035138 .


Management of Wounds with Exposed Bones or Tendons in Children by Vacuum-Assisted Closure Therapy: A Prospective Study.
Background The management of complex soft tissue defects with exposed bones/tendons is always a challenging task for the surgeon and the problem becomes more pronounced when it comes to the management of these wounds in children. Though flap procedures are considered the standard for managing the complex soft tissue defects with exposed bones/tendons yet small blood vessels for anastomosis, long operative period, increased chances of perioperative thrombosis, and difficult perioperative management in children add to the difficulty in performing flap procedures in children. The vacuum-assisted closure (VAC) therapy has emerged as a novel modality for the management of the difficult wounds with added advantages, especially in children. Objective To evaluate the efficacy of VAC in the management of wounds with exposed bones/tendons in children. Patients and Method Forty-six children of complex wounds with exposed bones/tendons were included in the study from July 2016 to June 2018. Results Out of 46 patients, 31 were male; the patients had a mean age of 8.4 years. Road traffic accident was the most common mode of injury (54%), with most of the wounds located over extremities. The mean duration of VAC therapy was 12 days. More than 90% coverage of the exposed structure was seen in 89% of patients. The wounds were definitively managed by split-thickness skin graft in 89% of patients and flap cover in 6.5% of patients. The mean cost of the VAC therapy at our government run hospital was 187 Indian rupees per day. No significant major complications were seen during the treatment. Conclusion VAC therapy is an efficient, safe, and cost-effective modality of treatment for the management of complex wounds in the pediatric population.


Hemostatic spray as a therapy for pancreatic stump bleeding after cephalic duodenopancreatectomy.
A 70-year-old man with a cholangiocarcinoma underwent a cephalic duodenopancreatectomy. On the 2nd postoperative day, he had hematemesis without hemodynamic instability. Upper endoscopy (EGD) revealed a massive clot at the pancreatic stump, suspected as the source of hemorrhage. After partial clot removal, no active bleeding was found and no therapy was performed. Pancreaticogastric and gastrojejunal anastomoses, as well as the efferent-limb, showed no suspicious lesions. Octreotide was initiated and heparin prophylaxis was temporarily stopped. Bleeding from pancreatic stump following pancreatoduodenectomy is a rare but a life-threatening condition. Conventional endoscopic therapies, including clip placement and cautery, are mostly ineffective and with high risk of pancreatitis. We report the second case of hemostatic powder as a safe and successful therapy in this scenario.


[Action of various disinfectants on 7 envelope-free viruses].
The activity of 15 disinfectants on seven nude viruses belonging to groups significant in human and veterinary medicine and in the bio-industry was investigated by a dilution technique. These trials, performed organic matters being either present or not revealed that current products such as 0.8% sodium hydroxyde and 1 degree chlorine water were the most active. According to their compositions, the chemicals varied greatly in their efficacy.


Current perspectives in the management of soft-tissue sarcoma. The role of chemotherapy in multimodality therapy.
The role of chemotherapy in adult soft-tissue sarcomas is controversial. In this review, the author examines the effectiveness of single-agent and combination chemotherapy to manage advanced disease and the role of adjuvant combination chemotherapy to control primary tumours and prevent the spread of the disease. Doxorubicin (Adriamycin) is still considered the most effective single agent for advanced soft-tissue sarcoma. Ifosfamide has given similar results and may have greater potential in combination therapy than cyclophosphamide. A current study using trimetrexate shows early positive results. Doxorubicin, cyclophosphamide, vincristine and dacarbazine is currently the most efficacious combination. The efficacy of adjuvant chemotherapy remains to be established. The majority of studies indicate some benefit with chemotherapy, particularly in the relapse-free survival rate, but no consistent improvement in overall survival has been noted.


Late congenital syphilis of the larynx and pharynx presenting at endotracheal intubation.
The case of a 73-year-old lady with late congenital pharyngo-laryngeal syphilis is presented. Its finding was at a potentially difficult intubation during the induction of general anaesthesia. She was asymptomatic; there was no evidence of active disease on either clinical examination or serology and no treatment was required. However, it is important to differentiate this condition from others which may require treatment.