Toward efficient analysis of mutations in single cells from ethanol-fixed, paraffin-embedded, and immunohistochemically stained tissues.
Only a few studies have demonstrated successful molecular analysis after whole genome amplification using single cells dissected from paraffin-embedded tissues. The results in these studies were limited by low-amplification efficiency and high rates of allele dropout. In the present study, the amplification rate using a thoroughly modified primer extension and preamplification-PCR protocol was improved significantly for single cells microdissected from paraffin-embedded and immunohistochemically stained tissues. Tissue fixation with ethanol (85%) and the addition of 0.2 mmol/L EDTA helped to achieve an amplification rate between 67% (segments 200 to 400 bp) and 72% (segments <200 bp). Normal tissue sections were immunohistochemically double stained for overabundance of p53 protein and proliferating cell nuclear antigen. Microdissection of single cells was performed with a manual micromanipulator equipped with a Tungsten needle. Sequence analysis of the TP53 gene was performed after improved primer extension preamplification-PCR and multiplex PCR from single microdissected cells. The rate of allele dropout was at least 68%. These technical advances facilitate routine mutation analysis using a single cell or a few cells microdissected from routinely processed paraffin-embedded normal and tumor tissues. Allele dropout still represents a serious problem in single-cell mutation analysis, especially in samples with limited template DNA and prone to DNA damage.


Variability of the modified Balance Error Scoring System at baseline using objective and subjective balance measures.
To investigate preseason modified Balance Error Scoring System (mBESS) performance in a collegiate football cohort; to compare scores to an objective mobile balance measurement tool. Eighty-two athletes completed simultaneous balance testing using mBESS and the King-Devick Balance Test, an objective balance measurement tool. Errors on mBESS and objective measurements in the double-leg, single-leg (SS) and tandem stances were compared. Mean mBESS error score was 7.23 ± 4.65. The SS accounted for 74% of errors and 21% of athletes demonstrated the maximum error score. There was no significant correlation between mBESS score and objective balance score. The high variability and large number of errors in the SS raises concerns over the utility of the SS in identifying suspected concussion.


Is There an Association between Paw Preference and Emotionality in Pet Dogs?
Research with humans and other animals has suggested that preferential limb use is linked to emotionality. A better understanding of this still under-explored area has the potential to establish limb preference as a marker of emotional vulnerability and risk for affective disorders. This study explored the potential relationship between paw preference and emotionality in pet dogs. We examined which paw the dogs preferentially used to hold a Kong™ and to perform two different locomotion tests. Dogs' emotionality was assessed using a validated psychometric test (the Positive and Negative Activation Scale-PANAS). Significant positive correlations were found for dogs' paw use between the different locomotion tasks, suggesting that dogs may show a more general paw preference that is stable across different types of locomotion. In comparison, the correlations between the Kong™ Test and locomotion tests were only partially significant, likely due to potential limitations of the Kong™ Test and/or test-specific biomechanical requirements. No significant correlations were identified between paw preference tests and PANAS scores. These results are in contrast to previous reports of an association between dog paw preference and emotionality; animal limb preference might be task-specific and have variable task-consistency, which raises methodological questions about the use of paw preference as a marker for emotional functioning.


Curcumin-mediated effects on anti-diabetic drug-induced cardiotoxicity.
The present study was designed to compare the cardiotoxicity of two very commonly used anti-diabetic drugs namely pioglitazone (Pio) and metformin (Met); and to study the effects of curcumin (Curc) against these drug-induced cardiotoxicity. Curc, being an anti-oxidant molecule and having cardio-protective potential, can have promising synergistic effects in reducing the cardiac stress induced by anti-diabetic therapies. Various dose and time-dependent cell viability and oxidative stress assays were conducted to study cardiotoxic side-effects and Curc-mediated effects in cardiomyoblasts. Effects of Curc were also studied in hyperglycaemia induced cardiac stress in the presence of drugs. Quantitative assays for cell growth, reactive oxygen species (ROS) generation, lipid peroxidation and mitochondrial permeability followed by anti-oxidant enzymes and caspases activity assays were done to study the mechanism of action of the induced cardiotoxicity. Significant dose and time mediated deleterious effects of Pio and Met were witnessed. Oxidative stress studies showed a remarkable increase in ROS with increasing dose of anti-diabetic drugs. Increased caspase activity and altered mitochondrial integrity were also witnessed in presence of Met and Pio in cardiomyoblasts. These alterations were found to be significantly reduced when treated with Curc simultaneously. The study confirms that Met and Pio exert toxic effects on cardiac cells by generating oxidative stress. Curc, being an anti-oxidative molecule, can suppress this effect and, therefore, can be used as a supplement with anti-diabetic drugs to suppress the induced cardiac stress.


[Depression and psoriasis].
Psychiatric co-morbidity is very frequently associated with psoriasis and depression is observed in numerous patients with psoriasis. Early detection and treatment are very important. The links between psoriasis and depression are not only psychopathological. Biological factors could also explain this association. There is a vicious circle psoriasis-alteration of quality of life-depression, but psoriasis improvement is not always followed by an improvement of depression. A contrario, it is obvious that a depressive patient has a bad observance of treatment.


Studies of the thymus in mice bearing the Lewis lung carcinoma. I. Thymic natural killer cell activity in 3LL tumor-bearing mice.
Natural killer (NK) cell activity of spleen and thymus was studied in Lewis lung carcinoma (3LL)-bearing mice. A high level of hydrocortisone-sensitive NK cell cytotoxicity was found in the thymus after excision of the primary tumor, but not in nonamputated mice. Conversely, splenic NK cell activity was diminished in nonamputated tumor-bearing mice and remained unmodified in amputated tumor-bearing mice. Excision of the primary tumor prevented tumor-induced thymic atrophy and splenomegaly. Histological study of the thymus revealed the presence of metastatic cells within the cortex. These data suggest that NK cells or their precursors are present in the thymus and can be triggered or unmasked in situ by tumor cells migrating from the primary tumor.


Phylogeny and the patterns of leaf phenolics in gap-and forest-adapted Piper and Miconia understory shrubs.
The types and quantities of defense compounds found in plants occupying ecologically distinct habitats have received much theoretical and little empirical attention. Here we characterize the leaf phenolic chemistry of eight species in two genera of tropical rainforest shrubs; four species in each genus are typical of disturbed sites, and four are typical of mature forest understory. Two Miconia species growing in light gaps had significantly higher leaf tannin and total phenolic contents than congenors growing in the primary forest; this pattern was not found among the gap- and forest-adapted Piper species. Tannin patterns were not mirrored by leaf cinnamic acids. These results indicate that plant phylogeny must be considered when predicting plant defense investment.


[Risk factors for surgical site infections in newborns in a neonatal intensive care unit].
To identify risk factors associated to surgical site infection (SSI) in newborns. Case-control study. Site. Neonatal intensive care unit (NICU), Hospital de Pediatría, Centro Medico Nacional SXXI, IMSS. 279 patients were included (125 cases and 154 controls). Gestational age, birth weight, previous infection, hospital stay, type of surgery, surgical drains, length of surgical procedure, bleeding during surgery, surgical site classification, serum albumin, classification of infection and surgeon performing the procedure. Five independent factors associated to SSI were identified: surgical reinterventions (OR = 13.6, CI 95% = 4.3-42.7); length of surgery > 60 minutes (OR = 3.0, CI 95% = 1.4-6.3); preoperative stay > 5 days (OR = 2.8, CI 95% = 1.3-5.6); consultant surgeon (OR = 2.7, CI 95% = 1.3-5.3), and previous systemic infection (OR = 2.1, CI 95% = 1.1-4.3). Lethality was 8.2% (n = 23), 74% in the group of cases (n = 17). Factors associated to SSI are mainly related to the characteristics of surgery and those of the patient. Lethality was low, but most of deaths were in the group of cases.


Propofol weakens hypoxia-aroused apoptosis and autophagy via elevating microRNA-137 in neurocytes.
Hypoxia was proven to cause brain cell apoptosis and autophagy. Herein, we tested the influences of propofol, a commonly used intravenous sedative hypnotic drug, on apoptosis and autophagy aroused by hypoxia stimulation in PC-12 and HT-22 cells. Followed by hypoxia and/or propofol treatment, cell viability of PC-12 and HT-22 cells, apoptosis and autophagy, along with microRNA-137 (miR-137) expression were measured, respectively. Then, miR-137 inhibitor was transfected to silence miR-137. Whether miR-137 took part in the impacts of propofol on hypoxia-exposed cells was explored. Finally, the activities of PI3K/AKT/mTOR and ERK pathways were measured. Hypoxia stimulation aroused cell apoptosis and elevated cell autophagy in PC-12 and HT-22 cells. Propofol weakened the apoptosis and autophagy of PC-12 and HT-22 cells aroused by hypoxia. Moreover, propofol elevated the miR-137 level in PC-12 and HT-22 cells. Silencing miR-137 declined the influences of propofol on hypoxia-induced injuries. Besides, propofol promoted PI3K/AKT/mTOR and ERK pathways activation in hypoxia-exposed cells through raising miR-137. Propofol weakened hypoxia-aroused apoptosis and autophagy of PC-12 and HT-22 cells might be through raising miR-137 level and thereby promoting PI3K/AKT/mTOR and ERK pathways activation.


Participation in leisure activities from the perception of children with disabilities and their families in Brazil.
To understand the perception of children with disabilities and their families regarding factors that interfere with participation in leisure activities in Brazil. This qualitative study included 14 focus groups, involving a total of 80 participants (40 children with disabilities and 40 family members). Discus-sions were recorded and transcribed. Coding was based on the International Classification of Functioning Disability and Health, following linking rules. A total of 80 individuals participated in the study. For parents and children the most-cited barriers to participation in leisure activities were relat-ed to environmental factors. For children, the main barriers were the attitudes of their nuclear family, acquaintances, and friends. Access to products and technology for personal mobility were also important obstacles. For them, support from immediate family was both a facilitator and barrier. Other barriers identified by family members were open-space planning services and assets. As facilitators, the atti-tudes and support of people in positions of authority also were reported by this group. For parents and children, most disabling barriers were related to environmental factors, such as access to products and technology, support, and attitudes. Some differences in perception were observed between comments from children and parents; for example, regarding barriers due to immediate family. Parents showed greater awareness of barriers and facilitators to participation in leisure activities.


Assessing locomotor-stimulating effects of cocaine in rodents.
Locomotor activity procedures are useful for characterizing the behavioral effects of a drug, the influence of pharmacological, neurobiological, and environmental manipulations on drug sensitivity, and changes in activity following repeated administration (e.g., tolerance or sensitization) are thought to be related to the development of an addiction-like behavioral phenotype. The effects of cocaine on locomotor activity have been relatively extensively characterized. Many of the published studies use between-subject experimental designs, even though changes in sensitivity within a particular individual due to experimental manipulations, or behavioral and pharmacological histories is potentially the most important outcome as these changes may relate to differential development of an addiction-like phenotype in some, but not all, animals (including humans). The two behavioral protocols described herein allow extensive within-subject analyses. The first protocol uses daily locomotor activity levels as a stable baseline to assess the effects of experimental manipulations, and the second uses a pre- versus post-session experimental design to demonstrate the importance of drug-environment interactions in determining the behavioral effects of cocaine.


Digitalization of the Logistics Process in Short Food Supply Chains. An online Viable System Model application during the COVID-19 pandemic.
This paper reports an ongoing exercise concerning the design of a logistics App to support operations within Farmers' Markets in Mexico. This exercise is part of a wider research agenda focused on 'Supporting Alternative Food Networks' (SAFeNET). This is a research agenda to conceive, build, implement, and develop better-informing decision-making processes that support effective and efficient AFNs (also known as Short Food Supply Chains) logistics operations in a digital environment, through smooth flows of goods and information among producers, AFNs coordinators, and consumers. This view calls for taking a systemic approach to help collectives of people to improve their autonomy and viability. Initial plans were to conduct this collaborative design exercise, using the Viable System Model (VSM) as a conversational tool. Accordingly, a series of face-to-face interviews and a focus group were planned. However, the lockdown due to COVID-19 forced researchers to abandon the face-to-face option and conduct the primary data collection online. The VSM intervention had to be adapted for its use on an online platform, in such a way that the platform would support knowledge building interactively, with a series of participants. This paper describes the format and visual appearance of the online VSM framework, its application, and the lessons learned through this exercise. Two points deserve to be highlighted: First, although the exercise outcome was very valuable for the next stage of the design, the participants' capacity for collective and individual reflection during the workshop was limited. Second, participants continued adding comments via the adopted online visual collaboration platform after the workshop ended, showing an understanding of the process and commitment beyond the researchers' expectations. The outcomes from this experiment are promissory, suggesting that online Systems Thinking interventions deserve further development.


Cardiac radiology.
Cardiac imaging is a relatively new and developing field. This article is aimed at radiology trainees, radiographers, and non-specialist radiologists who would like to learn more about this exciting subspecialty. What follows is a list of carefully selected web resources that may also be of interest to specialists for use in training. Hyperlinks are available in the electronic version of this article.


Dual role of NER in mutagenesis in Pseudomonas putida.
Nucleotide excision repair (NER) is one of the most important repair systems which counteracts different forms of DNA damage either induced by various chemicals or irradiation. At the same time, less is known about the functions of NER in repair of DNA that is not exposed to exogenous DNA-damaging agents. We have investigated the role of NER in mutagenesis in Pseudomonas putida. The genome of this organism contains two uvrA genes, uvrA and uvrA2. Genetic studies on the effects of uvrA, uvrA2, uvrB and UvrC in mutagenic processes revealed that all of these genes are responsible for the repair of UV-induced DNA damage in P. putida. However, uvrA plays more important role in this process than uvrA2 since the deletion of uvrA2 gene had an effect on the UV-tolerance of bacteria only in the case when uvrA was also inactivated. Interestingly, the lack of functional uvrB, uvrC or uvrA2 gene reduced the frequency of stationary-phase mutations. The contribution of uvrA2, uvrB and uvrC to the mutagenesis appeared to be most significant in the case of 1-bp deletions whose emergence is dependent on error-prone DNA polymerase Pol IV. These data imply that NER has a dual role in mutagenesis in P. putida-besides functioning in repair of damaged DNA, NER is also important in generation of mutations. We hypothesize that NER enzymes may initiate gratuitous DNA repair and the following DNA repair synthesis might be mutagenic.


Risk factors for biochemical recurrence following radical perineal prostatectomy in a large contemporary series: a detailed assessment of margin extent and location.
The implications of positive surgical margin (PSM) extent and location during radical perineal prostatectomy (RPP) have not been assessed in a contemporary series. We aimed to examine the incidence, location, and extent of PSM as well as their impact on biochemical recurrence (BCR) following RPP. A total of 794 patients underwent RPP by a single surgeon between June 1993 and August 2010. Covariates included age, pathologic T stage, pathologic Gleason sum, preoperative PSA, prostate volume, PSM extent, and location. Life table, Kaplan-Meier, and Cox regression analyses assessed predictors of BCR following RPP. PSM were recorded in 162 patients (20.4%); of these, 83 (51.2%) were focal (≤ 1 mm) whereas 79 (48.8%) were broad (>1 mm). Location of PSM was anterior 10.5%, posterior or lateral 14.8%, bladder neck 23.5%, apical 32.1%, and multifocal 19.1%. At a median follow-up of 54 months, the 5-year BCR-free probability was 90.8% in patients with negative margins, 77.5% in patients with focal PSM, and 47.5% in patients with broad PSM. On multivariable analyses adjusted for age, pathologic T stage, pathologic Gleason sum, preoperative PSA, and prostate volume, broad PSM, (HR = 3.49, P < 0.001) as well as anterior (HR = 3.77, P = 0.003), bladder neck (HR = 2.25, P = 0.01) and multifocal (HR = 3.55, P < 0.001) PSM were independent predictors of BCR. In this study, we present oncologic outcomes following RPP in a large contemporary cohort of patients undergoing RPP. In adjusted analyses, broad and anterior PSM carried the highest risk of recurrence after RPP.


Effect of iron deficiency on the digestive utilization of iron, phosphorus, calcium and magnesium in rats.
The influence of the source of dietary Fe (ferric citrate alone or mixed with bovine blood at a proportion of 1:1 (v/v)) on the digestive utilization of Fe, P, Ca and Mg, and on haemoglobin regeneration efficiency (HRE) was investigated in control and Fe-deficient rats. Diet A contained (by analysis) 43.5 mg Fe/kg diet (as ferric citrate), and diet B contained 44.3 mg Fe/kg diet (ferric citrate-bovine blood). In Fe-deficient rats fed on diet A or B the apparent digestibility coefficient (ADC) of Fe increased by 42.3 and 45.7% respectively. The ADC of Ca and Mg decreased significantly in Fe-deficient rats regardless of the source of dietary Fe. The HRE increased by 72.9% in Fe-deficient rats fed on diet A, and by 91.1% in Fe-deficient animals fed on diet B. In Fe-deficient rats fed on Fe for 10 d the values of haematological variables approached normality. However, serum Fe remained low, indicating that Fe reserves were still depleted. A deficient dietary supply of Fe for 30 d did not significantly modify the numbers of circulating leucocytes.


Mapping and Sustaining Leadership Development: An Innovation Academic Service Partnership.
To improve leadership competency, academic and clinical partners planned and implemented a 2-day facilitated workshop that actively engaged nurse leaders in preparing for their current and future careers by focusing on "The Leader Within." We anticipated that an emphasis on this particular dimension of leadership, that is, knowing oneself, would lead to improvements in the science and the art of leadership among nurse managers (NMs) and assistant NMs (ANMs). Using the Nurse Manager Skills Inventory (NMSI), we conducted precompetency and 8-month postcompetency surveys and interviews. Although 41 nurses completed the pretest, only 17 completed the posttest. The sample of 50% NMs and 50% ANMs had an average age of 38.4 (SD, 8.2) years' and 8.2 (SD, 6.3) years' experience. Self-rated leadership competency scores were improved at the 8-month posttest period on all NMSI sections: the Science, the Art, and the Leader Within. Actively cultivating "The Leader Within" facilitates reflective practice that may lead to more deliberate leadership competency attainment and career planning.


Radio-fluorogenic nanoclay gel dosimeters with reduced linear energy transfer dependence for carbon-ion beam radiotherapy.
The precise assessment of the dose distribution of high linear energy transfer (LET) radiation remains a challenge, because the signal of most dosimeters will be saturated due to the high ionization density. Such measurements are particularly important for heavy-ion beam cancer therapy. On this basis, the present work examined the high LET effect associated with three-dimensional gel dosimetry based on radiation-induced chemical reactions. The purpose of this study was to create an ion beam radio-fluorogenic gel dosimeter with a reduced effect of LET. Nanoclay radio-fluorogenic gel (NC-RFG) dosimeters were prepared, typically containing 100 μM dihydrorhodamine 123 (DHR123) and 2.0 wt% nanoclay together with catalytic additives promoting Fenton or Fenton-like reactions. The radiological properties of NC-RFG dosimeters having different compositions in response to a carbon-ion beam were investigated using a fluorescence gel scanner. An NC-RFG dosimeter capable of generating a fluorescence intensity distribution reflecting the carbon-ion beam dose profile was obtained. It was clarified that the reduction of the unfavorable LET dependence results from an acceleration of the reactions between DHR123 and H2 O2 , which is a molecular radiolysis product. The effects of varying the preparation conditions on the radiological properties of these gels were also examined. The optimum H2 O2 catalyst was determined to include 1 mM Fe3+ ions, and the addition of 100 mM pyridine was also found to increase the sensitivity. This technique allows the first-ever evaluation of the depth-dose profile of a carbon-ion beam at typical therapeutic levels of several Gy without LET effect.


Identification and assessment of virulence of a natural reassortant of infectious bursal disease virus.
Infectious bursal disease virus (IBDV) is one of the most important immunosuppressive viral agents in poultry production. Prophylactic vaccinations of chicken flocks are the primary tool for disease control. Widely used immunoprophylaxis can, however, provide high pressure which contributes to the genetic diversification of circulating viruses, e.g. through reassortment of genome segments. We report the genetic and phenotypic characterization of a field reassortant IBDV (designated as Bpop/03) that acquired segment A from very virulent IBDV and segment B from classical attenuated D78-like IBDV. Despite the mosaic genetic make-up, the virus caused high mortality (80%) in experimentally infected SPF chickens and induced lesions typical of the acute form of IBD. The in vivo study results are in contrast with the foregoing experimental investigations in which the natural reassortants exhibited an intermediate pathotype, and underline the complex nature of IBDV virulence.


Discover binding pathways using the sliding binding-box docking approach: application to binding pathways of oseltamivir to avian influenza H5N1 neuraminidase.
Drug binding and unbinding are transient processes which are hardly observed by experiment and difficult to analyze by computational techniques. In this paper, we employed a cost-effective method called "pathway docking" in which molecular docking was used to screen ligand-receptor binding free energy surface to reveal possible paths of ligand approaching protein binding pocket. A case study was applied on oseltamivir, the key drug against influenza a virus. The equilibrium pathways identified by this method are found to be similar to those identified in prior studies using highly expensive computational approaches.


Preoperative nomogram to predict risk of bowel injury during adhesiolysis.
Inadvertent bowel injury during adhesiolysis is a major cause of increased morbidity and mortality following abdominal surgery. Identification of risk factors predicting this complication would guide preoperative counselling and surgical decision-making. The aim of this study was to identify predictive preoperative factors for inadvertent bowel injury occurring during adhesiolysis. All patients undergoing elective abdominal surgery between June 2008 and June 2010 were evaluated prospectively as part of the LAPAD study. Data on adhesiolysis and inadvertent organ injury were gathered by direct observation during operation. Univariable logistic regression was used to investigate factors that increased the risk of inadvertent bowel injury. Independent predictors of bowel injury were identified using multivariable logistic regression and used to create a clinical nomogram. Of 715 patients eligible for analysis, 48 (6.7 per cent) had inadvertent bowel injuries. In 42 patients the defect was detected during operation and in nine at a later time (3 patients had both). Bowel resection was required for almost two-thirds of the enterotomies. The number of previous laparotomies, anatomical site of the operation, presence of bowel fistula and laparotomy via a pre-existing median scar were independent predictors of bowel injury. A clinical scoring system was constructed using a nomogram incorporating these risk factors; this had a predictive discrimination, measured as the area under the receiver operating characteristic curve, of 0.85. A nomogram based on four independent factors predicted the risk of inadvertent bowel injury. NCT01236625 (http://www.clinicaltrials.gov).


Presentation and course of asymptomatic primary biliary cirrhosis.
Twenty patients without symptoms of hepatobiliary disease were diagnosed as having asymptomatic primary biliary cirrhosis. In every patient liver histology was diagnostic of, suggestive of, or compatible with the diagnosis. Eighteen had a positive serum mitochondrial antibody, 18 had raised serum immunoglobulin M, and 17 had markedly raised serum alkaline phosphatase values. A mean of 4.5 years after diagnosis, 10 of the patients had not developed hepatobiliary symtoms; 4 of these 10 patients have survived 6 to 10 years. Ten patients developed symptoms after a mean of 2.2 years from initial diagnosis; 7 are still alive but 3 have died of liver failure. The development of symptoms could not be predicted by either serum biochemical tests or hepatic histology. It is concluded that the diagnosis of asymptomatic primary biliary cirrhosis is compatible with 10 or more asymptomatic years.


Assay and properties of N-acetylglucosamine-6-phosphate deacetylase from rat liver.
A single-vial assay has been developed for N-acetylglucosamine-6-phosphate deacetylase, in which [3H]acetate released from 3H-acetyl-labeled substrate is measured in a biphasic liquid scintillation counting system after acidification of the reaction mixture. The deacetylase was partially purified from rat liver, and some of its properties were determined. Chromatography on a calibrated Sepharose CL-6B column indicated a molecular weight of 345,000. The Km for the substrate at pH 8.0 was 0.3 mM. Glucosamine 6-phosphate and glucose 6-phosphate inhibited the enzyme, whereas N-acetylgalactosamine, N-acetylglucosamine, N-acetylglucosamine 1-phosphate, and glucosamine 1-phosphate were without effect. The effects of several divalent cations were also examined. Under the conditions tested, Ca2+, Mg2+, and Ba2+ had essentially no effect, whereas Mn2+, Ni2+, and Cu2+ were inhibitory and Co2+ stimulated activity at low concentrations but inhibited above 5 mM. An increase in the ionic strength of the reaction mixture to 0.3 M decreased the activity by 40%.


4,4'-Methylenedianiline in hydrolysed serum and urine from a worker exposed to thermal degradation products of methylene diphenyl diisocyanate elastomers.
A 45-year-old mechanic employed in blowing hot air (350 degrees-600 degrees C) onto the surface of a polyurethane methylene diphenyl diisocyanate (MDI) conveyer belt developed dyspnoea, rhinoconjunctivitis and fever. The illness was suggestive of an MDI-associated illness, compatible with both immediate hypersensitivity and a complement-mediated immune-complex reaction. In his serum there were specific IgG and IgE antibodies against MDI and other isocyanates, and high values of circulating immune complexes. The patient's blood and urine samples were analysed for the presence of 4,4'-methylenedianiline (MDA) in hydrolysed urine and plasma. MDA was derivatized to amides using pentafluoropropionic acid anhydride (PFPA). Gas chromatography-mass spectrometry determinations were made monitoring the (M-20; M = molecular mass) fragments from the MDA-PFPA and the [2H2]MDA-PFPA derivative. The first urine sample was obtained 22 h and the last sample 114 h after start of exposure. The urine concentrations of MDA were corrected for creatinine. The half-time of MDA was 70-80 h. The first serum sample was obtained 19 h and the last sample 1967 days after the start of exposure. The half-time was 21 days, which suggests the presence of MDI/MDA plasma protein adducts in the exposed worker.


Risk stratification based on nutritional screening on admission: Three-year clinical outcomes in hospitalized patients with acute heart failure syndrome.
Several blood tests are commonly used to assess nutritional status, including serum albumin levels (SAL) and lymphocyte counts (LC). The aim of this study is to investigate whether nutritional screening on admission can be used to determine risk levels for adverse clinical events in acute heart failure syndrome (AHFS) patients. In 432 consecutive AHFS patients, we measured SAL and LC and prospectively followed the patients for their combined clinical events (all-cause death and re-hospitalization for heart failure) for three years from admission. The classification and regression tree (CART) tool identified the cut-off criteria for SAL and LC to differentiate among patients with different risks of clinical events as 3.5g/dl and 963/mm3, respectively. The CART tool classified 15.5% patients as high risk, 15.7% as intermediate risk, and 68.8% as low risk. The CART for nutritional status (CART-NS) values were strongly correlated with combined clinical events [hazard ratio of 2.13 (low vs high risk), 95% confidence interval of 1.42-3.16, p<0.001], even after adjusting for plasma brain natriuretic peptide levels. The CART-NS analysis improved the specificity (89.5%) of predictions of clinical outcomes with the comparable sensitivity (36.3%) compared with the use of a single criterion (SAL <3.5g/dl: 70.2, 42.4% or LC <963/mm3: 73.4, 41.7%, respectively). A substantial proportion of AHFS patients are at risk of malnutrition, and this risk is associated with poor clinical outcomes. We demonstrate that this algorithm for nutritional screening, even in emergency clinical settings, can determine risk levels for further adverse events in AHFS patients.


Inhibition of cholesterol synthesis and cell growth by 24(R,S),25-iminolanosterol and triparanol in cultured rat hepatoma cells.
24(R,S),25-Iminolanosterol (IL) and triparanol added to cultures of rat hepatoma cells, H4-II-C3 (H4), interrupt the conversion of lanosterol to cholesterol and, depending on their concentrations, cause the accumulation in the cells of intermediates in the lanosterol to cholesterol conversion. At 45 microM, both substances cause the accumulation of 5 alpha-cholesta-8(9),24-dien-3 beta-ol (zymosterol), and at the low concentration of 4.5 microM, they cause the accumulation of cholesta-5.24-dien-3 beta-ol (desmosterol). The effect of intermediate concentrations of 9 or 22.5 microM of either substance is to cause the accumulation in the cells of three sterols: cholesta-5,7,24-trien-3 beta-ol, zymosterol, and desmosterol. The synthesis of these intermediary sterols, not found normally in H4 cells, is particularly pronounced in cultures kept in lipid-depleted media that contain the inhibitors and proceeds by the use of endogenous substrates at the expense of cholesterol. The synthesis of cholesterol from [14C]acetate or [2-14C]mevalonate is completely blocked by either inhibitor even at 4.5 microM. IL or triparanol inhibits the growth of H4 cells. Cells seeded into either full growth or lipid-depleted medium containing 22.5 microM IL will not grow unless the media are supplemented with low density lipoproteins (60 micrograms/ml). Supplementation of the media with 4.6 mM mevalonate does not counteract the inhibitory effect of IL on cell growth.


Association between Negative Life Events on Mental Health and College Student Adjustment: A Mediated Moderating Effect.
Objective: To explore the association between negative life events and college student adjustment and to explore the mediating and moderating effects of social support and grade level in the relationship between the two. Methods. The research was conducted with 1717 college students using the Adolescent Self-Rating Life Events Checklist (ASLEC), China College Student Adjustment Scale (CCSAS), and the Social Support Rating Scale (SSRS). Results. (1) Negative life events were significantly negative in correlation with adjustment and social support (r = -0.373, -0.174, Ps < 0.001), while social support was significantly positive in correlation with adjustment (r = 0.359, P < 0.001). (2) The main effects of negative life events, social support, and grade on adjustment were significant (effect = -0.190, P < 0.001, 95% CI [-0.288∼-0.092]; effect = 0.307, P < 0.001, 95% CI [0.265∼0.348]; effect = 0.163, P < 0.001, 95% CI [0.126∼0.200]). (3) In the relationship between negative life events and adjustment, social support played a mediating role (effect = -0.054, 95% CI [-0.071∼-0.037]) and grade level played a moderating role (effect = -0.049, P=0.009, 95% CI [-0.085∼-0.012]). Conclusion. Negative life events, social support, and grade level affected college student adjustment, and social support networks for college students should be actively constructed and targeted education should be conducted according to different grade levels, which can promote college student adjustment.


Progressive and degenerative journals: on the growth and appraisal of knowledge in scholarly publishing.
Despite continued attention, finding adequate criteria for distinguishing "good" from "bad" scholarly journals remains an elusive goal. In this essay, I propose a solution informed by the work of Imre Lakatos and his methodology of scientific research programmes (MSRP). I begin by reviewing several notable attempts at appraising journal quality - focusing primarily on the impact factor and development of journal blacklists and whitelists. In doing so, I note their limitations and link their overarching goals to those found within the philosophy of science. I argue that Lakatos's MSRP and specifically his classifications of "progressive" and "degenerative" research programmes can be analogized and repurposed for the evaluation of scholarly journals. I argue that this alternative framework resolves some of the limitations discussed above and offers a more considered evaluation of journal quality - one that helps account for the historical evolution of journal-level publication practices and attendant contributions to the growth (or stunting) of scholarly knowledge. By doing so, the seeming problem of journal demarcation is diminished. In the process I utilize two novel tools (the mistake index and scite index) to further illustrate and operationalize aspects of the MSRP.


Brazilin inhibits activities of protein kinase C and insulin receptor serine kinase in rat liver.
Hypoglycemic action of brazilin was found to be based on the improvement of peripheral glucose utility, and this action might be correlated with the insulin action pathway. In the present study we investigated the effect of brazilin on the insulin receptor autophosphorylation, protein kinase C (PKC), protein phosphatase and insulin receptor serine kinase in order to confirm whether the hypoglycemic mechanism is concerned with insulin action pathway. Brazilin was found to inhibit PKC and insulin receptor serine kinase, which are involved in the regulation of insulin signal pathway. But any significant effect was not shown on insulin receptor tyrosine kinase activity, autophosphorylation and phosphatase activity. These findings suggest that brazilin might enhance insulin receptor function by decreasing serine phosphorylation, which might mediate hypoglycemic effect of brazilin.


Diagnostic techniques for hair disorders. Part II: Microscopic examination of hair bulbs, tips, and casts.
For the patient who presents with a hair disorder, a host of diagnostic techniques are available in addition to history, physical examination, and laboratory assessment. Microscopic hair bulb, tip, and cast examination is presented as a technique for establishing a definitive diagnosis.


Development of new bioabsorbable implants with de novo adipogenesis.
Poly-L-lactic acid (PLLA) mesh implants containing collagen sponge (CS) were replaced with autologous adipose tissue regeneration in vivo. Herein, we investigated the optimal external frames and internal fillings using poly (lactic-co-ε-caprolactone) (P (LA/CL)), PLLA, and low-molecular-weight PLLA (LMW-PLLA) as the external frame and polyglycolic acid (PGA) nanosheets and CS as the internal filling. We prepared six implants: P (LA/CL) with PGA nano, PLLA with PGA nano, PLLA with CS, PLLA with 1/2 CS, PLLA with 1/4 CS, and LMW-PLLA with CS, and evaluated adipogenesis at 6 and 12 months using a rat inguinal model. The internal spaces in the P (LA/CL) and LMW-PLLA implants collapsed at 6 months, whereas those in the other four implants collapsed at 12 months. Adipose tissue regeneration was not significantly different between the PLLA-implanted groups at 6 and 12 months and was greater than that in the P (LA/CL) with PGA nano and LMW-PLLA with CS groups. The PGA nanosheet inside PLLA was comparable to the CS inside PLLA in the regeneration of adipose tissue and macrophage infiltration. In summary, PLLA is a promising external frame material in which the internal space can be replaced with adipose tissue. Thus, PGA nanosheets are an alternative internal filling material for adipose tissue regeneration.


Trendelenburg position and passive leg raising do not significantly improve cardiopulmonary performance in the anesthetized patient with coronary artery disease.
The effects of the Trendelenburg (TREND) position and passive straight leg raising (PLR) on cardiopulmonary performance in 18 anesthetized patients undergoing myocardial revascularization were studied with a two-dimensional transesophageal echocardiography probe and a thermodilution right ventricular ejection fraction (RVEF) pulmonary artery catheter. The TREND position (at 20 degrees) and PLR (at 60 degrees) were studied in relation to the level-supine position in random order. At 3 min, the TREND caused significant (p less than .05) decreases in heart rate (62 +/- 9 to 58 +/- 10 [SD] beat/min) and RVEF (0.48 +/- 0.11 to 0.44 +/- 0.10), and significant increases in mean arterial pressure (77 +/- 11 to 82 +/- 11 mm Hg), mean pulmonary artery pressure (16 +/- 4.3 to 19 +/- 5.5 mm Hg), wedge pressure (11 +/- 4 to 13 +/- 4 mm Hg), cardiac index (CI) (2.36 +/- 0.79 to 2.52 +/- 0.93 L/min.m2), right ventricular end-systolic volume index (44 +/- 21 to 58 +/- 21 ml/m2), right ventricular end-diastolic volume index (83 +/- 24 to 102 +/- 22 ml/m2), and shunt fraction (0.16 +/- 0.06 to 0.19 +/- 0.06). CVP and left ventricular areas did not change significantly. PLR had similar effects as the TREND position, except CI did not change significantly. Thus, the TREND and PLR resulted in minor hemodynamic improvement with right ventricular dilation, decreased RVEF, and impaired oxygenation in the anesthetized cardiac surgical patient.


Plasmodium fragile: detection of a ring-infected erythrocyte surface antigen (RESA).
A ring-infected erythrocyte surface antigen (RESA) has been detected by modified immunofluorescence assay in erythrocytes infected with the simian malaria parasite, Plasmodium fragile. This RESA, of Mr 95,000, shares many characteristics with the RESA initially found in the human malaria parasite P. falciparum. Both antigens are found in the membrane of erythrocytes infected with young asexual parasite stages, in merozoite-enriched preparations, and in parasite culture supernatant. Since the RESA of P. falciparum has been shown to confer protective immunity and since P. fragile infection of rhesus monkeys mimics P. falciparum infection in humans, the finding of a RESA in P. fragile underlines the importance of this species as an animal model for antimalarial vaccines.


Ultralarge Stokes Shift Phosphorescence Artificial Harvesting Supramolecular System with Near-Infrared Emission.
A two-step sequential phosphorescence harvesting system with ultralarge Stokes shift and near-infrared (NIR) emission at 825 nm is successfully constructed by racemic 1,2-diaminocyclohexan-derived 6-bromoisoquinoline (BQ), cucurbit[8]uril (CB[8]), and amphipathic sulfonatocalix[4]arene (SC4AD) via cascaded assembly strategy in aqueous solution. In virtue of the confinement effect of CB[8] with rigid cavity, BQ can generate an emerging phosphorescent emission at 555 nm. Subsequently, the binary BQ⊂CB[8] further assemblies with SC4AD to form close-packed spherical aggregate, which contributes to the dramatic enhancement of phosphorescence emission intensity ≈30 times with prolonged lifetime from 21.3 µs to 0.364 ms. Notably, the BQ⊂CB[8]@SC4AD assembly can serve as an energy donor to conduct stepwise phosphorescence harvesting process through successive introduction of primary acceptors, cyanine 5 (Cy5) or nile blue (NiB), and secondary acceptor, heptamethine cyanine (IR780). The final aggregate with remarkable ultralarge Stokes shift (≈525 nm) and long-lived NIR photoluminescence (PL) emission at 825 nm is further employed as imaging agent for NIR cell labeling.


Engineering of galectin-3 for glycan-binding optical imaging.
Galectin-3 (Gal-3) is a multifunctional glycan-binding protein that participates in many pathophysiological events and has been described as a biomarker and potential therapeutic target for severe disorders, such as cancer. Several probes for Gal-3 or its ligands have been developed, however both the pathophysiological mechanisms and potential biomedical applications of Gal-3 remain not fully assessed. Molecular imaging using bioluminescent probes provides great sensitivity for in vivo and in vitro analysis for both cellular and whole multicellular organism tracking and target detection. Here, we engineered a chimeric molecule consisting of Renilla luciferase fused with mouse Gal-3 (RLuc-mGal-3). RLuc-mGal-3 preparation was highly homogenous, soluble, active, and has molecular mass of 65,870.95 Da. This molecule was able to bind to MKN45 cell surface, property which was inhibited by the reduction of Gal-3 ligands on the cell surface by the overexpression of ST6GalNAc-I. In order to obtain an efficient and stable delivery system, RLuc-mGal-3 was adsorbed to poly-lactic acid nanoparticles, which increased binding to MKN45 cells in vitro. Furthermore, bioluminescence imaging showed that RLuc-mGal-3 was able to indicate the presence of implanted tumor in mice, event drastically inhibited by the presence of lactose. This novel bioluminescent chimeric molecule offers a safe and highly sensitive alternative to fluorescent and radiolabeled probes with potential application in biomedical research for a better understanding of the distribution and fate of Gal-3 and its ligands in vitro and in vivo.


Squamous cell carcinoma arising in chronic osteomyelitis.
Squamous cell carcinoma (SCC) is a rare but well-documented complication of chronic osteomyelitis. Between February 1991 and March 1999, 13 cases (12 men and one woman) of SCC arising in chronic osteomyelitis were diagnosed and treated in our clinic. Mean age was 56.5 (38-70) years. Twelve patients underwent amputation and one underwent limb salvage. Average follow-up was 56 (24-121) months. Among the 13 patients two died of the disease. Treatment of choice for these tumours has been amputation.


Intracellular distribution of beta-galactosidases in mucosal cells from hog small intestine.
1. Intracellular distribution of three types of beta-galactosidases (beta-D-galactoside galactohydrolase EC 126.96.36.199) i.e. hetero beta-galactosidase, lactase and acid beta-galactosidase, was studied by examining the properties of subcellular fractions isolated by a systematic fractionation of mucosal cells of the small intestine of the hog. Localization of hetero beta-galactosidase in cytosol could be shown. 2. Localization of lactase in the brush borders was shown by analyzing the purified brush borders prepared separately. 3. To domonstrate the lysosomal localization of acid belta-galactosidase, lysosomes were purified separately and their extract was chromatographed on a hydroxylapatite column. The activities of various enzymes in the purified lysosomes as well as in the intermediary fractions obtained during lysosome purification and the pattern of the hydroxylapatite chromatography led us to conclude that acid beta-galactosidase is a lysosomal enzyme.


Target-catalyzed hairpin assembly and intramolecular/intermolecular co-reaction for signal amplified electrochemiluminescent detection of microRNA.
Herein, a new electrochemiluminescence (ECL) strategy for enzyme-free microRNA-21 (miR-21) amplified detection was designed based on target-catalyzed hairpin assembly by combining the signal-amplification capability of both intramolecular and intermolecular ECL co-reaction. In this strategy, two hairpin DNA probes of H1 and H2 were designed as capture probes and detection probes, respectively. To be specific, the capture probes of H1 were immobilized on the multilayer interface of AuNPs and thiosemicarbazide (TSC) assembly on the single-walled carbon nanohorns decorated electrode, while the detection probes of H2 was anchored on the nanocarriers of gold nanoparticals functionalized reduced graphene oxide (Au-rGO) which were tagged with the self-enhanced ruthenium complex (PEI-Ru(ΙΙ)) in advance. Based on the target-catalyzed hairpin assembly, target miR-21 could trigger the hybridization of H1 and H2 to further be released for initiating the next hybridization process to capture a large number of H2 bioconjugates on the sensing surface. Herein, the TSC was used not only as a coupling reagent to attach the AuNPs via Au-S and Au-N bonds but also as a novel intermolecular coreactant to enhance the ECL intensity, and the PEI-Ru(ΙΙ) as emitters exhibited enhanced ECL efficiency. Therefore, a strong ECL signal was achieved by the dual amplification strategies of target recycle and the intramolecular/intermolecular co-reaction of PEI-Ru(ΙΙ) and TSC. The designed protocol provided an ultrasensitive ECL detection of miR-21 down to the sub-femtomolar level with a linear response about 6 orders of magnitude (from 1.0 × 10(-16)M to 1.0 × 10(-11)M) with a relatively low detection limit of 0.03 fM (S/N=3).


Unemployment and reproductive outcome. An Australian study.
The Mater-University of Queensland Study involves the follow-up of 8556 pregnant women who were enrolled at their first clinic visit. This analysis compares four groups of women categorized according to their own and their partners' employment status. Group 1 comprised women unemployed, partners not unemployed. Group 2 comprised women not unemployed with unemployed partners. Group 3 comprised women and partners who were both unemployed. In group 4 neither partner was unemployed. Initial analysis showed that there was a significant association between birthweight and birthweight for gestational age, and unemployment as reported by mothers. After adjustment for lifestyle variables (principally smoking) there were no remaining statistically significant associations.


A procedure to detect general association based on concentration of ranks.
In modern high-throughput applications, it is important to identify pairwise associations between variables, and desirable to use methods that are powerful and sensitive to a variety of association relationships. We describe RankCover, a new non-parametric association test of association between two variables that measures the concentration of paired ranked points. Here 'concentration' is quantified using a disk-covering statistic similar to those employed in spatial data analysis. Considerations from the theory of Boolean coverage processes provide motivation, as well as an R2-like quantity to summarize strength of association. Analysis of simulated and real datasets demonstrate that the method is robust and often powerful in comparison to competing general association tests.


[Influence of adaptation of hypoxia on the relationship between tissue respiration, temperature and oxygen tension in vitro].
The effect of adaptation to hypoxia on rat tissue respiration at different pO2 and temperature in vitro was studied. The temperature coefficient Q10 and the Michaelis constant Km for oxygen were estimated. The tissue sensitivity to low pO2 and low temperature obviously decreased while the tissue affinity for oxygen and the direct temperature dependence on Km increased in animals adapted to hypoxia. A functional interrelationship between adaptational changes of Q10 and Km of tissue respiration in different organs was revealed. The data obtained suggest participation of cellular oxidation changes in adaptive increase of oxygen affinity.


Reflex contractions of the ischiocavernosus muscles following electrical and pressure stimulations.
In a previous study, we have demonstrated that voluntary muscular contractions of the ischiocavernosus muscles (IC) correlate with changes in intracavernous pressure and, therefore, with penile rigidity. The purpose of our current research project was to verify whether reflex contractions of the IC muscles exist and under what conditions. Our results confirm that reflex contractions occur following electrical or pressure stimulations. Following electrical stimulation, the mean latency of the reflex contractions was 67.5 ms for the IC muscles and 34.9 ms for the bulbocavernosus muscles (BC). Following pressure stimulation, the pressure threshold necessary to elicit contractions of the IC muscles varied between 18.2 mm. Hg and 34.8 mm. Hg. We also observed that pressure variation (increase and decrease) rather than a relatively constant pressure is necessary to produce this reflex response. We interpret these results to suggest that pressure stimulations on the glans penis during coitus contribute to the erectile process and, specifically, to the increase in intracavernous pressure. These findings suggest the possibility of a physiotherapeutic management for patients with penile rigidity problems.


Endoscopic visualization of angiotensin-converting enzyme inhibitor-induced small bowel angioedema as a cause of relapsing abdominal pain using double-balloon enteroscopy.
A 40-year-old woman presented with 3 episodes of abdominal pain. Abdominal ultrasound demonstrated edema of the small bowel. Double-balloon enteroscopy (DBE) showed diffuse swelling of the small intestine, petechial bleeding in the jejunum, and focal inflammation of the ileum. Pain and small bowel edema resolved spontaneously within 48 h during each episode. Review of the patient's history revealed that she had been started on enalapril for arterial hypertension two weeks before her first episode. Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the small bowel was suspected and enalapril was discontinued. The patient remained symptom-free after discontinuing the ACE inhibitor. Review of the literature reveals only 11 similar cases with this case being the first to apply DBE to visualize macroscopic alterations to the small intestine. Angioedema of the intestine is a diagnostic pitfall frequently leading to prolonged diagnostic procedures and is a potential cause for abdominal pain in patients taking ACE inhibitors.


Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.
The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.


Surgical complications of skin sparing mastectomy and immediate prosthetic reconstruction after neoadjuvant chemotherapy for invasive breast cancer.
Neoadjuvant chemotherapy is gaining acceptance as an option for breast cancer treatment, particularly in young women. These women may seek immediate breast reconstruction after mastectomy even though it is not known whether such preoperative chemotherapy may be detrimental to post-reconstruction wound healing. Therefore, we set out to assess the influence of neoadjuvant chemotherapy for invasive breast cancer on the short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction. The short-term surgical outcome of 48 immediate breast reconstructions in 37 women treated with neoadjuvant chemotherapy from 2006 through 2009 was prospectively compared to that of 215 immediate reconstructions in 176 women who were operated in the same period without neoadjuvant chemotherapy. The overall rate of short-term postoperative complications was significantly less among neoadjuvantly treated women (15% vs. 29%; p = 0.042) but this did not result in a reduction of loss of prostheses (8% vs. 11%; p = 0.566). Because neoadjuvant chemotherapy is not associated with an increase in short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction in patients with invasive breast cancer, such combined surgical therapy may be offered as treatment option for this particular group of patients also.


Effect of compressive loading and incubation with clodronate on the RANKL/OPG system of human osteoblasts.
In vivo studies have shown that bisphosphonates result in slow rates of orthodontic tooth movement. This study investigated whether clodronate modifies the impact of mechanical loading on the RANKL/OPG system of human osteoblasts. Osteoblasts were cultured in vitro with 0.5 or 5.0 µM clodronate for 48 h and/or subjected to 3 h of compressive loading at 34.9 g/cm(2). Cell viability was determined by MTT assay. Real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and immunocytochemical staining were used to analyze the cells for their production of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) at the transcriptional and protein levels. Compressive loading did not affect osteoblast viability in a significant way. Clodronate (5.0 µM) mildly reduced the viability of both compressed and uncompressed cells. Compressive loading induced a 4.2-fold increase in RANKL gene expression, while clodronate led to a concentration-dependent inhibition of this effect (1.8-fold increase at 5.0 µM). OPG gene expression was decreased by compressive loading both in the presence of 0.5 µM clodronate and in the absence of clodronate, and OPG protein synthesis in the compressed cells was significantly decreased in the presence of clodronate. Immunocytochemical staining revealed an increase of RANKL protein synthesis in compressed cells, while clodronate and cell compression reduced this increase. This study demonstrates that clodronate decreases the compression-induced RANKL/OPG ratio expressed by human osteoblasts. Reported in vivo findings of reduced osteoclast numbers on the compression side of orthodontic tooth movement under the action of clodronate-and the associated slow rate of tooth movement-might be attributable not only to a direct impact on osteoclasts but also to changes in osteoblast-osteoclast interaction resulting from the presence of clodronate.


Immunohistochemically detected p53 and P-glycoprotein predict the response to chemotherapy in lung cancer.
While resistance to chemotherapy is a major problem in lung cancer treatment, there is no useful predictor of treatment response. We thus designed this study to determine the utility of p53 and P-glycoprotein expression in predicting the response to chemotherapy in patients with primary lung cancer, retrospectively. We evaluated transbronchial biopsy (TBB) specimens from 60 patients with lung cancer, who were previously untreated. Formalin-fixed, paraffin-embedded TBB specimens were immunostained using anti-p53 antibody (DO-1) and anti-P-glycoprotein antibody (JSB-1). The positivity of p53 was 63%, and that of P-glycoprotein was 17%. No correlation was observed between p53 and P-glycoprotein immunostaining. Positivity of p53 correlated significantly (P = 0.004) with a lack of response to chemotherapy in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC). In contrast, positivity of P-glycoprotein was correlated with chemotherapy resistance in SCLC (P = 0.003), but not in NSCLC. Multiple logistic regression analysis revealed that positive immunostaining for p53 was a significant risk factor for chemotherapy resistance in NSCLC. These results suggest that immunostaining of p53 and P-glycoprotein for TBB specimens may help to predict response to chemotherapy in NSCLC and SCLC, although the results should be confirmed in a larger, more homogeneous series.


Contribution of NIPD-CTDR to the parasitic diseases control and elimination in China: Memory of the 70th anniversary for NIPD-CTDR.
China has achieved a great success in control and elimination of key parasitic diseases. In 2007, the elimination of lymphatic filariasis was verified by WHO. The schistosomiasis incidence and snail-distributed areas have reduced to the lowest level in the history. The transmission and disease burden of echinococcosis have been contained largely, and the populations infected with soil-transmitted trematode and food-borne parasites have also shown a significantly declining trend. Because of rapid globalization and climate changes, however, many new challenges have arisen. In his paper, the 2020-2030 roadmaps towards the control and elimination of these key parasitic diseases are described. Moreover, China is actively implementing its global health strategy, and will be more and more engaged into global health affairs, in which a series of China-Africa health cooperation projects have been in planning with a wish of making a greater contribution to the SDGs.


Lymph node evaluation for endometrial hyperplasia: a nationwide analysis of minimally invasive hysterectomy in the ambulatory setting.
Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation. Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P < 0.05). Among those independent factors, presence of atypia exhibited the largest association for lymph node evaluation (adjusted odds ratio 3.75, 95% confidence interval 3.39-4.16). There were 20 unique patterns of lymph node evaluation based on histology, hysterectomy type, patient age, year of surgery, and hospital bed capacity, ranging from 0 to 20.3% (absolute rate difference, 20.3%). Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines.


Effects of optogenetic stimulation of vasopressinergic retinal afferents on suprachiasmatic neurones.
Physiological circadian rhythms are orchestrated by the hypothalamic suprachiasmatic nucleus (SCN). The activity of SCN cells is synchronised by environmental signals, including light information from retinal ganglion cells (RGCs). We recently described a population of vasopressin-expressing RGCs (VP-RGC) that send axonal projections to the SCN. To determine how these VP-RGCs influence the activity of cells in the SCN, we used optogenetic tools to specifically activate their axon terminals within the SCN. Rats were intravitreally injected with a recombinant adeno-associated virus to express the channelrhodopsin-2 and the red fluorescent protein mCherry under the vasopressin promoter (VP-ChR2mCherry). In vitro recordings in acute brain slices showed that approximately 30% of ventrolateral SCN cells responded to optogenetic stimulation with an increase in firing rate that progressively increased during the first 200 seconds of stimulation and which persisted after the end of stimulation. Finally, application of a vasopressin V1A receptor antagonist dampened the response to optogenetic stimulation. Our data suggest that optogenetic stimulation of VP-RGC axons within the SCN influences the activity of SCN cells in a vasopressin-dependent manner.


Bartonella henselae prosthetic valve endocarditis in an adult patient with congenital heart disease: favorable outcome after combined medical and surgical management.
Bartonella spp. are a known cause of culture-negative endocarditis. We report a 42-year-old male with underlying surgically corrected congenital heart disease who was diagnosed with Bartonella henselae endocarditis involving the right-ventricle-to-pulmonary-artery conduit.


Therapeutic potential of human minor salivary gland epithelial progenitor cells in liver regeneration.
Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs). hMSG-EpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET-1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liver-associated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a two-thirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSG-EpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.


Reconstructing pedigrees: some identifiability questions for a recombination-mutation model.
Pedigrees are directed acyclic graphs that represent ancestral relationships between individuals in a population. Based on a schematic recombination process, we describe two simple Markov models for sequences evolving on pedigrees--Model R (recombinations without mutations) and Model RM (recombinations with mutations). For these models, we ask an identifiability question: is it possible to construct a pedigree from the joint probability distribution of extant sequences? We present partial identifiability results for general pedigrees: we show that when the crossover probabilities are sufficiently small, certain spanning subgraph sequences can be counted from the joint distribution of extant sequences. We demonstrate how pedigrees that earlier seemed difficult to distinguish are distinguished by counting their spanning subgraph sequences.


Radiosurgery of cerebral arteriovenous malformations in children: a series of 57 cases.
To evaluate the efficacy and outcome of Linac radiosurgery (RS) as treatment of cerebral arteriovenous malformations (cAVM) in a series of 57 children. Between 1984 and 2000, we used Linac radiosurgery to treat 792 patients with cAVM. This series included 57 children (7.2%) under the age of 15 years at the time of RS (range = 7-15 years, median = 12 years). We were able to evaluate 49 of the children (86%) by angiography, 21 boys and 28 girls (sex ratio = 0.75). First symptoms were: hemorrhage, 34 patients (69.4%); seizures, 6 patients (12.5%); headache, 6 patients (12.5%); and progressive neurologic deficit, 1 patient (2.1%). Nidus size ranged from 5 to 50 mm (median = 20 mm). Nidus volume ranged from 0.6 to 16 cc (median = 3.5 cc). Patient distribution according to Spetzler-Martin grade was as follows: Grade 1, n = 5 (11%); Grade 2, n = 18 (35%); Grade 3, n = 21 (40%,); Grade 4, n = 5 (14%); and Grade 5, n = 0%. Twenty-seven patients (55.1%) had other treatment before RS: embolization, n = 14 (31.1%); neurosurgery, n = 9 (20.5%); embolization and neurosurgery, n = 3 (6.1%). RS was performed with the system used for adults. Patients were seated in a Betti armchair. Circular 15 MV X-ray minibeams (6 to 20 mm) were delivered in coronal arcs by a GECGR Saturne 43 Linac. Planification and dosimetry were carried out using the Associated Target Methodology and Dosigray TPS dosimetric systems. The dose at the peripheral isodose (50-70%) ranged from 18 to 28 Gy. Median and mean doses were 25 Gy and 23.8 Gy. Mono-isocentric planification was used in 25 patients (53.2%) and multi-isocentric in 24 patients (2 to 5 isocenters). The overall follow-up ranged from 7 to 172 months (mean 40 months, median 34 months). The overall rate of obliteration (OR) was 30/49 (61.2%). Mean time to obliteration was 34 months (range = 7 to 172 months). OR varied according to nidus size and volume: OR was 80% for nidus <15 mm, 67% for nidus between 15 and 25 mm, and 42% for nidus >25 mm (p = 0.058). OR was 100% for nidus <1 cc, 73% for nidus between 1 and 4 cc, and 40% for nidus of 4 to 10 cc (p = 0.019). OR according to patient gender was 84.2% for boys and 40% for girls. OR according to minimum dose (Dmin) was 44% for Dmin < 15 Gy (p = 0.01), 89% for D min from 15 to 20 Gy, and 100% for Dmin > 20 Gy (p = 0.01). OR was 62% in nonembolized AVM and 58% in previously embolized AVM (NS). OR according to the number of isocenters was 68.2%, 55.6%, 80%, 50%, and 0% for 1, 2, 3, 4, and 5 isocenters, respectively. After multivariate analysis, only Dmin closely correlated with OR (beta = 0.462; SE = 0.244, p = 0.057). Of the 6 patients with seizures before RS, 5 (80%) were seizure-free without medication after RS. One patient died of pneumonia. Four patients (8.2%) had bleeding after RS at 39, 45, 51, and 59 months. No new neurologic deficit was found during the follow-up period. Twenty-nine patients underwent magnetic resonance imaging. Thirteen patients (44.8%) showed no parenchymal changes. Thirteen patients (44.8%) had Grade 2 changes, that is, T2 hypersignals. Two patients (6.9%) had Grade 3 changes, and 1 patient (3.4%) had Grade 4 "necrosis-like" changes. In our experience, Linac RS has proven to be a safe and effective method to treat cerebral AVM in children <15 years, whether used alone or in association with embolization and/or neurosurgery.


Monohydroxy fatty acids esterified to phospholipids are decreased in lesional psoriatic skin.
Because of the increasing number of reports of the important roles of monohydroxy derivatives of poly-unsaturated fatty acids in the regulation of cell function, we determined the pools of unesterified and esterified monohydroxy fatty acids (MHFAs) in keratomed epidermal slices, taken from lesional and non-lesional psoriatic skin. Extracted phospholipids were separated by thin-layer chromatography. The isolated fractions of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidyl-ethanolamine (PE) were treated with phospholipase A2 to release fatty acids in the sn-2 position. Released MHFAs were separated by reversed-phase and straight-phase high-performance liquid chromatography and identified as the linoleic acid derivatives 9-hydroxy-octadecadienoic acid (9-HODE) and 13-hydroxy-octadecadienoic acid (13-HODE) and as the arachidonic acid derivative 15-hydroxy-eicosatetraenoic acid (15-HETE). These findings are consistent with the presence of unesterified 9-HODE, 13-HODE and 15-HETE. In contrast, 12-hydroxy-eicosatetraenoic acid (12-HETE), although found to be present in high amounts as unesterified 12-HETE, was not detectable in the phospholipids. When compared with non-lesional psoriatic skin, the levels of 9-HODE, 13-HODE and 15-HETE esterified to the sn-2 position of PC, PI and PE in lesional psoriatic skin were significantly decreased (to 28-78% of those in non-lesional skin). This depletion of MHFAs in specific phospholipids may be due to an imbalance between phospholipase and acyltransferase activities. Because the levels of esterified MHFAs may influence signal transduction and eicosanoid metabolism the described changes may be relevant for the inflammatory processes occurring in psoriasis.


Educational Intervention on Undergraduate Cancer Awareness and Self-Directed Learning.
Traditional lecture-based learning (LBL) can increase cancer awareness in undergraduates. However, because of the rapidly changing knowledge base in medicine, undergraduates must develop skills required for lifelong self-directed learning (SDL). Problem-based learning (PBL) has been suggested as an SDL approach. This study used a nonequivalent control group with a pretest-posttest design for comparing PBL and LBL for their effectiveness in increasing cancer awareness and SDL among nonmedicine or nonnursing major undergraduates in a health-related general education course. Experimental groups 1 and 2 were instructed using PBL while the control group was instructed using LBL. Cancer educational programs were offered to experimental group 1 and the control group but not to experimental group 2. Among the 325 undergraduates who completed a questionnaire regarding cancer awareness and SDL in the pretest, 223 completed the 12-week follow-up survey of the posttest. Cancer awareness significantly improved between the pretest and posttest in the control group (P < 0.001). No significant difference in cancer awareness improvement was observed between experimental group 1 and the control group (P = 0.934). Cancer awareness improvement in experimental group 2 was significantly less than in the control group (P = 0.010). No statistically significant change in SDL was observed in the control group during the study (P = 0.897). However, the SDL of experimental groups 1 and 2 improved more significantly than that of the control group (P = 0.049 and 0.023, respectively). Therefore, PBL is an effective method of increasing cancer awareness and SDL in undergraduates.


Ca2(+)-independent stimulation of adenylate cyclase activity by muscarinic receptors in rat olfactory bulb.
In rat olfactory bulb homogenate, carbachol stimulated adenylate cyclase activity in a concentration-dependent manner (EC50 = 1.1 microM). The carbachol stimulation occurred fully in membranes that had been prepared in the presence of 1 mM EGTA and incubated in a Ca2(+)-free enzyme reaction medium. Under these conditions, exogenous calmodulin (1 microM) failed to stimulate adenylate cyclase activity. In miniprisms of olfactory bulb, carbachol (1 mM) increased accumulation of inositol phosphates, but this response was markedly reduced in a Ca2(+)-free medium. Moreover, the carbachol stimulation of adenylate cyclase activity was not affected by staurosporine at a concentration (1 microM) that completely blocked the stimulatory effect of phorbol 12-myristate 13-acetate, an activator of Ca2+/phospholipid-dependent protein kinase. Quinacrine, a nonselective phospholipase A2 inhibitor, reduced the carbachol stimulation of adenylate cyclase activity, but this inhibition appeared to be competitive with a Ki of 0.2 microM. Nordihydroguaiaretic acid and indomethacin, two inhibitors of arachidonic acid metabolism, failed to affect the carbachol response. These results indicate that in rat olfactory bulb, muscarinic receptors stimulate adenylate cyclase activity through a mechanism that is independent of Ca2+ and phospholipid hydrolysis.


Prostaglandin production and lipolysis in isolated rat adipocytes as affected by dietary fat.
The influence of dietary fat on prostaglandin production and lipolysis was tested in basal and norepinephrine stimulated adipocytes isolated from the epididymal fat pads of fasted rats. Seven diets varying in fat calories and polyunsaturation were utilized. No basal differences were noted for prostaglandin E2 production or lipolysis. Norepinephrine stimulated prostaglandin E2 and F2alpha production was significantly (P less than 0.01) increased with greater polyunsaturation of fat, but not by increased fat calories. Norepinephrine stimulated lipolysis was depressed by an increase in fat calories but was unaffected by the degree of polyunsaturation of fat. This is in vitro evidence against the concept that prostaglandins play a feedback regulator role in fat cell lipolysis since no correlation could be made between the two parameters.


Investigating chronic symptoms in HIV: an opportunity for collaborative nursing research.
Because of improved life expectancy for people with HIV infection, today's clinician needs to understand and manage chronic symptoms that limit function and quality of life. The authors describe two collaborative HIV symptom-management studies conducted by the Division of Intramural Research of the National Institute of Nursing Research. Studies such as these are necessary to provide nurses and other healthcare personnel with the knowledge essential for appropriate, comprehensive, and quality patient care.


Cytotoxic Activity of Some Lupeol Derivatives.
The synthesis of 3-0-acyl derivatives of lupeol is presented, as well as lupenone and the oxime of lupenone. The obtained derivatives were subjected to the MTT test in order to evaluate their cytotoxic activity toward HeLa, KB, MCF-7 and A-549 cell lines in comparison with lupeol (1). The IC₅₀ values for lupeol (1) and all of the tested derivatives (2-6) were from about 7-10 μM for lupenone (5) to about 81 μM for o-phthaloyl-lupeol (4). Acylation of the C-3 hydroxy function of compound 1 decreased the cytotoxic activity of compounds 2-4. The most active anticancer agent was lupenone (5), with IC₅₀ values 7.1-9.1 μM in comparison with 37.7-51.9 μM for lupeol (1).


Respiration-induced movement of the upper abdominal organs: a pitfall for the three-dimensional conformal radiation treatment of pancreatic cancer.
Respiration-induced movement of the upper abdominal organs (pancreas, liver and kidneys) was assessed in 12 subjects using dynamic magnetic resonance imaging. The movement of each organ in the cranio-caudal, the lateral and the anterior-posterior direction was deduced from the movement of the center of gravity on two-dimensional images. This center of gravity was computed from the volume delineated on sequential 8-mm slices of both sagittal and coronal dynamic series. The largest movements were noticed in the cranio-caudal direction for pancreas and liver (23.7+/-15.9 mm and 24.4+/-16.4 mm). The kidneys showed smaller movements in the cranio-caudal direction (left kidney 16.9+/-6.7 mm and right kidney 16.1+/-7.9 mm). The movements of the different organs in the anterior-posterior and lateral directions were less pronounced. It is of the greatest importance to be aware of these movements in the planning of a conformal radiation treatment for pancreatic cancer.


Continuous wave amplified spontaneous emission in phase-stable lead halide perovskites.
Sustained stimulated emission under continuous-wave (CW) excitation is a prerequisite for new semiconductor materials being developed for laser gain media. Although hybrid organic-inorganic lead-halide perovskites have attracted much attention as optical gain media, the demonstration of room-temperature CW lasing has still not been realized. Here, we present a critical step towards this goal by demonstrating CW amplified spontaneous emission (ASE) in a phase-stable perovskite at temperatures up to 120 K. The phase-stable perovskite maintains its room-temperature phase while undergoing cryogenic cooling and can potentially support CW lasing also at higher temperatures. We find the threshold level for CW ASE to be 387 W cm-2 at 80 K. These results indicate that easily-fabricated single-phase perovskite thin films can sustain CW stimulated emission, potential at higher temperatures as well, by further optimization of the material quality in order to extend the carrier lifetimes.


Assessing likelihood of using the Bruininks-Oseretsky test of motor proficiency to predict preclinical performance of dental students.
The acquisition of motor skills is a key competency for the practice of dentistry, and innate abilities have been shown to influence motor performance. Thus, finding the most efficient manual dexterity tests may predict performance of dental students. The current study used the Bruininks-Oseretsky Test of Motor Proficiency, to assess motor skills of first year (D1) and second year (D2) dental students. Three fine motor subsets of the BOT-2-fine motor precision, fine motor integration, and manual dexterity-were administered to D1 and D2 dental students in 2017 and 2018. The BOT-2 subset scores of D1 students were compared with those of D2 students, who had preclinical dental experiences. For D2 students, we tested for correlations between BOT-2 subset scores and performance scores in a preclinical operative dentistry course. No differences were found between D1 and D2 students for any BOT-2 subtest scores (all Ps > .09). No correlations were found between total scores of each BOT-2 subtest and the operative dentistry course for D2 students (all Ps > .20). Our results suggested the BOT-2 was not predictive of manual skills of dental applicants or preclinical dental students. Although we assumed students would perform well with instruction, practice, and feedback, we were unable to determine whether innate abilities influenced acquisition of manual dexterity skills. More research about the acquisition of technical clinical skills in dentistry is required.


A connection between the mitochondrial permeability transition pore, autophagy, and cerebral amyloidogenesis.
In a drug reprofiling attempt, we explored novel neuroprotective properties of 4-azasteroids by synthesizing chemical affinity tags capturing adenine nucleotide translocator-1, as a potential target. Dutasteride inhibits the mitochondrial transition pore and induces an increase of autophagosomal structures in human cell lines. In vivo, a surprising reduction of the beta-amyloid plaque load in a model for cerebral amyloidosis appears to connect release of neurotoxic peptides, mitochondrial apoptosis and autophagy.


CPEB1 orchestrates a fine-tuning of miR-145-5p tumor-suppressive activity on TWIST1 translation in prostate cancer cells.
TWIST1 is a basic helix-loop-helix transcription factor, and one of the master Epithelial-to-Mesenchymal Transition (EMT) regulators. We show that tumor suppressor miR-145-5p controls TWIST1 expression in an immortalized prostate epithelial cell line and in a tumorigenic prostate cancer-derived cell line. Indeed, shRNA-mediated miR-145-5p silencing enhanced TWIST1 expression and induced EMT-associated malignant properties in these cells. However, we discovered that the translational inhibitory effect of miR-145-5p on TWIST1 is lost in 22Rv1, another prostate cancer cell line that intrinsically expresses high levels of the CPEB1 cytoplasmic polyadenylation element binding protein. This translational regulator typically reduces TWIST1 translation efficiency by shortening the TWIST1 mRNA polyA tail. However, our results indicate that the presence of CPEB1 also interferes with the binding of miR-145-5p to the TWIST1 mRNA 3'UTR. Mechanistically, CPEB1 binding to its first cognate site either directly hampers the access to the miR-145-5p response element or redirects the cleavage/polyadenylation machinery to an intermediate polyadenylation site, resulting in the elimination of the miR-145-5p binding site. Taken together, our data support the notion that the tumor suppressive activity of miR-145-5p on TWIST1 translation, consequently on EMT, self-renewal, and migration, depends on the CPEB1 expression status of the cancer cell. A preliminary prospective study using clinical samples suggests that reconsidering the relative status of miR-145-5p/TWIST1 and CPEB1 in the tumors of prostate cancer patients may bear prognostic value.


Vaginal Hysterectomy in a Large Health Maintenance Organization: Retrospective Application of a Clinical Algorithm.
The primary objective was to describe practice patterns of benign hysterectomy within a large community health maintenance organization (HMO) and evaluate clinical and surgeon characteristics associated with the performance of vaginal hysterectomy (VH). Secondary objectives were to retrospectively apply a VH algorithm to determine how our practice patterns conform, and compare rates of perioperative complications among patients who did and did not meet the algorithm. Patient and surgeon characteristics, and perioperative complications, were compared between patients who underwent VH and did or did not meet the VH algorithm. Retrospective cohort study. Large community HMO. Women undergoing benign hysterectomy. None. Route of hysterectomy, patient and surgeon characteristics, perioperative complications. One hundred and thirty-one of 984 (13.3%) benign hysterectomies from January 1, 2013 to June 30, 2015 were vaginal. Patients who were vaginally parous, Hispanic, had normal preoperative uterine size and documentation of uterine descent were more likely to have VH (all p <.05). High-volume surgeons performed 18.8% of their hysterectomies vaginally, as compared to low-volume surgeons who performed 11.4% of their hysterectomies vaginally (p <.01). VH were more likely to be performed by surgeons with longer practice durations than non-vaginal hysterectomies (16.3 vs 12.2 years, p <.01). Seventy-five percent of patients who met the VH algorithm underwent non-vaginal hysterectomy and they had longer operative durations and higher rates of postoperative complications compared to patients who underwent VH. Conversely, patients who underwent VH despite not meeting the VH algorithm did not have significantly different rates of perioperative complications or blood loss than patients who met the VH algorithm. Seventy-five percent of patients deemed appropriate for VH by our algorithm underwent non-vaginal hysterectomy and had more postoperative complications and longer operative durations. Our data suggest that surgeon characteristics, including surgical volume and duration of practice, may explain some of this performance gap. These findings contribute additional insight into current practice patterns and describe clinical factors that should be included in VH algorithms.


Spectroscopic Study of Plasma Polymerized a-C:H Films Deposited by a Dielectric Barrier Discharge.
Plasma polymerized a-C:H thin films have been deposited on Si (100) and aluminum coated glass substrates by a dielectric barrier discharge (DBD) operated at medium pressure using C₂Hm/Ar (m = 2, 4, 6) gas mixtures. The deposited films were characterized by Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS), Raman spectroscopy, and ellipsometry. FT-IRRAS revealed the presence of sp³ and sp² C-H stretching and C-H bending vibrations of bonds in the films. The presence of D and G bands was confirmed by Raman spectroscopy. Thin films obtained from C₂H₄/Ar and C₂H₆/Ar gas mixtures have ID/IG ratios of 0.45 and 0.3, respectively. The refractive indices were 2.8 and 3.1 for C₂H₄/Ar and C₂H₆/Ar films, respectively, at a photon energy of 2 eV.


Effects of amphetamine, dexfenfluramine, diazepam, and dietary manipulations on responding reinforced by stimuli paired with food in nonhuman primates.
The purpose of this study was to determine how stimuli paired with food alters the effects of pharmacological and dietary manipulations on food intake. Responding of baboons was studied using a schedule of reinforcement that simulated food 'seeking' and food 'taking'. Under one condition, responding during the initial seeking component was reinforced by flashing lights that were paired with food delivery during the latter-taking component. Under another condition, responding during seeking components was reinforced by a 1-s time out that was paired with food delivery during the latter-taking component. Dexfenfluramine (DFEN) decreased responding within seeking and taking components under both conditions. Diazepam (DZP) increased responding within seeking and taking components under both conditions. Amphetamine (AMPH) increased responding within seeking components under the flashing-light condition, but did not alter responding within seeking components under the 1-s time-out condition. AMPH decreased responding within taking components under both conditions. As observed with AMPH, caloric prefeeding also increased responding within seeking components only under the flashing-light condition. As observed with DZP, acute deprivation also increased responding within seeking and taking components under both conditions. The effects of AMPH and caloric prefeeding on food seeking are dependent upon the type of stimuli, paired with primary reinforcement.


TLR4 Activation Promotes the Secretion of IL-8 Which Enhances the Invasion and Proliferation of Endometrial Stromal Cells in an Autocrine Manner via the FAK Signal Pathway.
Chronic inflammation is important for the occurrence of endometriosis, but the molecular mechanisms are still poorly understood. TLR4 is not only expressed on immune cells but is also present in the human endometrium, and its regulation might be crucial for the pathogenesis of endometriosis. In this study, the expression of TLR4 in normal, eutopic endometrium, and ectopic tissues was analyzed by immunohistochemistry. The expression of the key molecules in endometrial stromal cells (ESCs) was assessed by in-cell Western assays. The invasion of eutopic ESCs from patients with endometriosis was evaluated by Matrigel invasion assay. The effects of CXCL8 on the proliferation of ESCs in vitro were assessed using BrdU assays. We found that the expression of TLR4 is higher in the eutopic endometrium than the normal endometrium and that ectopic tissue had the highest level of expression. TLR4 activation stimulated IL-8 secretion and the expression of its receptor CXCR1 in ESCs by activating p38/ERK, but not JNK and NK-κB signal pathways. IL-8 could enhance the invasion and proliferation of ESCs through the FAK signal pathway, and these effects could be abolished by an anti-CXCL8 neutralizing antibody or by a FAK inhibitor.


Longitudinal associations between preschool psychopathology and school-age peer functioning.
The current study examined the effects of preschool psychopathology on peer functioning around school entry. Children (N = 211) were assessed at ages 3 and 6. A semi-structured diagnostic interview, the Preschool Age Psychiatric Assessment, was administered to a parent at both time points to assess psychopathology. The peer functioning constructs examined at age 6 included child popularity, socially inappropriate behavior, and conflicted shyness. Simultaneous multiple regressions revealed that age 3 anxiety disorder diagnosis was the only unique diagnostic predictor of age 6 socially inappropriate behavior and conflicted shyness, with age 3 anxiety dimensional scores uniquely predicting all three peer constructs. Age 3 anxiety disorder had direct effects on both socially inappropriate behavior and conflicted shyness, which were not mediated by concurrent anxiety disorder at age 6. Thus, preschool anxiety disorders may have enduring effects on child peer relationships in the early school-age years. Possible explanations and implications are explored.


Heteroleptic copper(II) complexes of prenylated flavonoid osajin behave as selective and effective antiproliferative and anti-inflammatory agents.
Heteroleptic copper(II) complexes, containing prenylated flavonoid osajin isolated from the fruits of Maclura pomifera Schneid., were prepared and thoroughly characterized, including single crystal X-ray analysis. Some of the following complexes of the general composition [Cu(L)(bpy)]NO3 (1), [Cu(L)(dimebpy)]NO3·2MeOH (2) [Cu(L)(phen)]NO3·H2O (3), [Cu(L)(bphen)]NO3 (4) and [Cu(L)(dppz)]NO3 (5), where HL stands for 3-(4-hydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one (osajin), bpy = 2,2'-bipyridine, dimebpy = 4,4'-dimethyl-2,2'-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline and dppz = dipyrido[3,2-a:2',3'-c]phenazine, were also monitored for their solution stability and interactions with cysteine and glutathione by mass spectrometry. The in vitro cytotoxicity of the complexes was evaluated against a panel of eight human cancer cell lines: (MCF-7, HOS, A549, PC-3, A2780, A2780R, Caco-2, and THP-1). The results revealed high antiproliferative activity of the complexes with the best IC50 values of 0.5-3.4 μM for complexes (4) and (5), containing the bulkier N,N'-donor ligands (bphen, and dppz, respectively). The complexes also revealed a relatively low toxicity towards human hepatocytes (IC50 values are higher than 100 μM in some cases), and thus proved to be highly selective towards the cancer cells. On the other hand, the complexes showed a strong in vitro nuclease effect using the model pUC-19 plasmid. In the model of lipopolysaccharide-stimulated (LPS) THP-1 monocytes, the complexes revealed ability to lower the activity of nuclear factor kappa-B/activator protein 1 (NF-κB /AP-1) system and decrease the secretion of tumor necrosis factor alpha (TNF-α). Thus, the complexes have been identified as strong antiproliferative and anti-inflammatory compounds.


Anticlastogenic and antigenotoxic effects of selenomethionine on doxorubicin-induced damage in vitro in human lymphocytes.
The use of antioxidants during chemotherapy has been shown to reduce or prevent the undesirable effects experienced by healthy cells. Micronutrient selenium is well known for its antioxidant properties; however, selenium exhibits a bimodal nature in that both its beneficial and toxic properties lie within a limited and narrow dose range. The present study investigated the possible protective effects of selenomethionine (SM) on the cytotoxicity, genotoxicity and clastogenicity of the chemotherapic doxorubicin (DXR), a key chemotherapic used in cancer treatment. Human peripheral lymphocytes were treated in vitro with varying concentrations of SM (0.25 microM, 0.5 microM, 1.0 microM and 2.0 microM), tested in combination with DXR (0.15 microg/mL). SM alone was not cytotoxic and when combined with DXR treatment, reduced the DNA damage index significantly, the frequency of chromosomal aberrations, the number of aberrant metaphases and the frequency of apoptotic cells. The mechanism of chemoprotection of SM may be related to its antioxidant properties as well as its ability to interfere with DNA repair pathways. Therefore this study showed that SM is effective in reducing the genetic damage induced by the antitumoral agent DXR.


Evaluation of seven DNA barcodes for differentiating closely related medicinal Gentiana species and their adulterants.
Species identification of living organisms by standard DNA sequences has been well-accepted. Consortium for the Barcode of Life (CBOL) recommends chloroplast regions rbcL and matK as the DNA barcodes for the land plants. This study aims to evaluate the feasibility and limitations of rbcL, matK, and 5 other commonly used regions as the DNA barcodes for the medicinal Gentiana and their adulterants, Gentiana. rhodantha and Podophyllum hexandrum. The species differentiation power of rbcL, matK, nuclear internal transcribed spacer (ITS) and 5S rRNA intergenic spacer, and chloroplast trnH-psbA, trnL-F and rpl36-rps8 intergenic spacers were tested in different medicinal Gentiana, including Gentiana scabra, Gentiana triflora, Gentiana manshurica and Gentiana rigescens, from common adulterants such as Gentiana rhodantha and Podophyllum hexandrum (a toxic herb producing podophyllotoxin). All seven tested loci could be used to differentiate medicinal Gentiana species from their adulterants, and to distinguish Guanlongdan from Jianlongdan. In terms of general differentiation powers, rbcL and matK had no significant advantages over the other five loci. Only the 5S rRNA and trnL-F intergenic spacers were able to discriminate the closely related species G. triflora, G. scabra and G. manshurica. The DNA barcodes rbcL and matK are useful in differentiation of closely related medicinal species of Gentiana, but had no significant advantages over the other five tested loci.


[Rheumatology in private practice: yesterday-today-tomorrow].
Rheumatologic practices were still rare in the early 1990s and rheumatologic treatment took place mainly in the rheumatology clinics and university rheumatology clinics. In the following decades, the number of the rheumatologists in private practices increased and in the year 2004 about two thirds of the outpatient care were already carried out in private practices. In 2020 a total of 597 rheumatologists out of 1106 nationwide worked in private practices, including 203 who were employed. Since 2008, the number of rheumatologists in medical care centers increased more than the number of rheumatologists in private practice. In 2020 only 75% of panel rheumatologists in private practice were in full-time employment. This development to an altered work mentality of the incoming generation and an age structure in which approximately 30% of panel rheumatologists are older than 60 years, threatens a further deterioration of the anyway insufficient outpatient care. In contrast, there are developments that strengthen the outpatient care especially in practices, such as the outpatient specialist medical care and quality-oriented selective contracts as well as rheumatological and immunological laboratory diagnostics. These cornerstones give rheumatology a special position in the panel medical care within the group of specialties in internal medicine and an attractive economic basis. In addition to the medically and scientifically interesting discipline, this could be a further incentive for young trainees to choose rheumatology as a specialty and working in a private practice.