A long-term comparison between enalapril and captopril on insulin sensitivity in normotensive non-insulin dependent diabetic volunteers.
There are conflicting reports about the effects of angiotensin converting enzyme inhibitors on insulin sensitivity and glycaemic control. In addition, the chronic effects of ACEI on insulin sensitivity in normotensive but insulin resistant individuals have been controversial. To determine the long-term effects of low-dose captopril or enalapril on insulin sensitivity and lipid parameters in normotensive non-insulin dependent diabetic volunteers. Twenty-eight normotensive non-insulin dependent diabetes mellitus subjects on diet alone or diet plus oral hypoglycaemic agents were randomized in a single-blind cross-over study to receive either captopril (12.5 mg daily) or enalapril (5 mg daily). Initially, captopril was compared with enalapril for 28 days with a 28-day washout period between drug regimens. For the long-term study, the subjects then remained on the second ACEI for a further 11 months. Insulin sensitivity was measured using the isoglycaemic hyperinsulinaemic clamp (insulin infusion rate 20 mIU/kg/min) at the start and completion of each part of the cross-over study and then at 3, 6 and 12 months of drug therapy. Fasting glucose, insulin, HbA1, lipids and lipoproteins were measured at the start of each clamp. No first or second order carry-over effects were demonstrated between the ACEIs. No differences were detected between enalapril and captopril on insulin sensitivity at any of the time points. Statistically significant hypotension was avoided, and at doses used the ACEIs did not modify any parameters of glycaemic control over the 12-month study period. There were no significant alterations in plasma cholesterol, triglycerides, HDL cholesterol or Apo A1 levels during the study. Long-term low-dose ACEIs (captopril/enalapril) do not modify insulin sensitivity, glycaemic control or lipids in normotensive non-insulin dependent diabetic subjects.


Anaphylaxis to trimethoprim: an under-appreciated risk in acute medical care.
Anaphylaxis is a severe, systemic allergic reaction, which is frequently unexpected and carries a high mortality risk as a medical emergency. Anaphylaxis to trimethoprim is not a well recognized event. Since trimethoprim represents the leading antibiotic for the treatment of urinary tract infections, its potential to cause anaphylaxis needs to be recognized, whether alone or as the 'active' ingredient in cotrimoxazole (trimethoprim-sulphamethoxazole combination), by those prescribing it and those providing acute care. A case of probable anaphylaxis following trimethoprim ingestion is presented with discussion supporting its potency including evidence at an immunological level highlighting its under-appreciated risk in acute medical care.


Urethral pressure changes during voiding.
Intraurethral pressure changes in the external sphincter zone during voiding were recorded using a specially constructed double lumen urethral catheter in 3 normal subjects. It was noted in all the 3 subjects that the urethral pressure in this zone dropped simultaneously with decrease of electromyographic activities of the external urethral sphincter when the subjects strained to void. It was ascertained for the catheter position to remain unchanged irrespective of voiding action during urethrometrography.


Pulmonary hyalinizing granuloma mimicking multiple lung metastases: report of fluorodeoxyglucose positron emission findings.
Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search.


Cognitive deficits and health-related quality of life in chronic heart failure.
Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. This study was part of a larger explanatory study; 249 patients with HF completed face-to-face interviews. Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care.


Measurements of WW and WZ production in W + jets final states in pp collisions.
We study WW and WZ production with ℓνqq (ℓ=e,μ) final states using data collected by the D0 detector at the Fermilab Tevatron Collider corresponding to 4.3 fb(-1) of integrated luminosity from pp collisions at sqrt[s]=1.96 TeV. Assuming the ratio between the production cross sections σ(WW) and σ(WZ) as predicted by the standard model, we measure the total WV (V=W,Z) cross section to be σ(WV)=19.6(-3.0)(+3.2) pb and reject the background-only hypothesis at a level of 7.9 standard deviations. We also use b-jet discrimination to separate the WZ component from the dominant WW component. Simultaneously fitting WW and WZ contributions, we measure σ(WW)=15.9(-3.2)(+3.7) pb and σ(WZ)=3.3(-3.3)(+4.1) pb, which is consistent with the standard model predictions.


Symmetrical reversed plantar calcaneal spurs in children. A normal variant?
Three cases of unrelated children who have symmetrical posteriorly directed plantar calcaneal spurs are presented. Only one reference to this appearance could be found in the English literature. These spurs are asymptomatic and probably represent variations in the normal development of the calcaneus.


Hydroxylation and carboxylation--two crucial steps of anaerobic benzene degradation by Dechloromonas strain RCB.
Benzene is a highly toxic industrial compound that is essential to the production of various chemicals, drugs, and fuel oils. Due to its toxicity and carcinogenicity, much recent attention has been focused on benzene biodegradation, especially in the absence of molecular oxygen. However, the mechanism by which anaerobic benzene biodegradation occurs is still unclear. This is because until the recent isolation of Dechloromonas strains JJ and RCB no organism that anaerobically degraded benzene was available with which to elucidate the pathway. Although many microorganisms use an initial fumarate addition reaction for hydrocarbon biodegradation, the large activation energy required argues against this mechanism for benzene. Other possible mechanisms include hydroxylation, carboxylation, biomethylation, or reduction of the benzene ring, but previous studies performed with undefined benzene-degrading cultures were unable to clearly distinguish which, if any, of these alternatives is used. Here we demonstrate that anaerobic nitrate-dependent benzene degradation by Dechloromonas strain RCB involves an initial hydroxylation, subsequent carboxylation, and loss of the hydroxyl group to form benzoate. These studies provide the first pure-culture evidence of the pathway of anaerobic benzene degradation. The outcome of these studies also suggests that all anaerobic benzene-degrading microorganisms, regardless of their terminal electron acceptor, may use this pathway.


Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).
Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated the potential utility of genomic endpoints to enhance the LLNA and support further exploration of this approach through examination of a more diverse array of chemicals.


The results of major clinical trials: critical assessment, the circulation of information and media coverage.
The round table elected to focus its discussion on trials that, in terms of their importance, are likely to modify medical practices and behaviour. Such trials may be pre- or postmarketing studies. For the findings of a trial to result in a change in practice, they must be credible and fulfil the basic methodological criteria. It is nonetheless appropriate to complete that binary assessment by the use of an assessment checklist appropriate to each category of users, i.e. the Regulatory Agency, prescribing physicians and patients, who are sometimes informed directly by the media. The members of the round table proposed the 'Giens 2003 checklist'. It consists of an interpretative semi-quantitative assessment checklist based on simple messages relevant to practice. Critical assessment is a necessary prelude to the circulation of the results to the various parties involved (healthcare professionals, patients, patient associations, the media and the general public) and the process of informing those parties in readily understandable but accurate terms. The practical implementation of the results, with a change in behaviour and/or the issuing of guidelines, are subsequent stages for which a certain lag time is inevitable. The assessment of implementation programmes, together with an accurate analysis of the obstacles to changing medical practice, should, in the future, improve and accelerate the implementation of important results in order to optimise patient management.


Sustained improvement of clinical outcome with risperidone long-acting injectable in psychotic patients previously treated with olanzapine.
The efficacy and tolerability of risperidone long-acting injectable were investigated in patients with schizophrenia or other psychotic disorders who had previously been symptomatically stable on olanzapine treatment. Patients received risperidone long-acting injectable, 25 mg, by intramuscular injection every 2 weeks; the dose could be increased to 37.5 or 50 mg if necessary. Patients were transferred directly from their previous medication to risperidone long-acting injectable without a run-in period of oral risperidone treatment. Of 192 patients recruited, 134 patients (70%) completed the study. The principal reasons for discontinuation were withdrawal of consent (8%), adverse events (6%), insufficient response (5%) and non-compliance (4%). Risperidone long-acting injectable produced a significant improvement (p = 0.0001) in Positive and Negative Syndrome Scale (PANSS) total scores, from 74.2+/-21.3 at baseline to 65.8+/-21.4 at endpoint. There were also significant reductions in PANSS subscales (positive symptoms, negative symptoms, general psycho-pharmacology) and Marder factor scores. The Clinical Global Impression increased significantly from baseline to endpoint (p = 0.0001), as reflected by the increase in the proportion of patients rated as 'not ill' or 'borderline ill' from 10% at baseline to 21% at endpoint. Risperidone long-acting injectable was also associated with significant improvements in Global Assessment of Function, patient satisfaction with treatment, and quality of life, measured on the SF-36 scale. Movement disorders, measured on the Extrapyramidal Symptom Rating Scale, were significantly reduced following the change to risperidone long-acting injectable. Treatment with risperidone long-acting injectable was well tolerated, and no significant weight gain occurred during the study. This open study suggests that risperidone long-acting injectable produces symptomatic improvement in schizophrenia patients previously considered symptomatically stable with olanzapine, along with improvement in movement disorders. The combination of improved efficacy and good tolerability may have important implications for patient adherence to therapy and subsequent long-term outcomes.


Effects of static and cyclic compressive loading on articular cartilage plugs in vitro.
The influence of static and intermittent stress on articular cartilage metabolism was examined in vitro. Full-thickness plugs of cartilage from femoral condyles of normal adult dogs were cultured while static or cyclic stresses were applied for 2 hours. The plugs were then incubated under atmospheric pressure for 2 hours in medium containing radioactive label, to provide measurements of net synthesis of glycosaminoglycan (GAG) or protein. As a control, cartilage from the same knee was cultured in the apparatus at atmospheric pressure. When cartilage plugs were exposed to static stress, or to cyclic stresses at a duty cycle of 60 seconds on/60 seconds off, net GAG synthesis was suppressed to 30-60% of that in controls. In contrast, when a duty cycle of 4 seconds on/11 seconds off was used, GAG synthesis was increased by 34%. The duty cycle which increased GAG synthesis did not affect protein synthesis or tissue contents of DNA, uronic acid, or water. At the cycle which suppressed GAG synthesis, protein synthesis and uronic acid content were decreased, and water content was increased. As judged by uptake of 14C-aminoisobutyric acid and 14C-xylose, the above changes in GAG synthesis do not appear to have been due to changes in diffusion of nutrient molecules through the cartilage during loading.


Polyplex exposure inhibits cell cycle, increases inflammatory response, and can cause protein expression without cell division.
We sought to evaluate the relationship between cell division and protein expression when using commercial poly(ethylenimine) (PEI)-based polyplexes. The membrane dye PKH26 was used to assess cell division, and cyan fluorescent protein (CFP) was used to monitor protein expression. When analyzed at the whole population level, a greater number of cells divided than expressed protein, regardless of the level of protein expression observed, giving apparent consistency with the hypothesis that protein expression requires cells to pass through mitosis in order for the transgene to overcome the nuclear membrane. However, when the polyplex-exposed population was evaluated for the amount of division in the protein-expressing subpopulation, it was observed that substantial amounts of expression had occurred in the absence of division. Indeed, in HeLa S3 cells, this represented the majority of expressing cells. Of interest, the doubling time for both cell lines was slowed by ~2-fold upon exposure to polyplexes. This change was not altered by the origin of the plasmid DNA (pDNA) transgene promoter (cytomegalovirus (CMV) or elongation factor-1 alpha (EF1α)). Gene expression arrays in polyplex-exposed HeLa S3 cells showed upregulation of cell cycle arrest genes and downregulation of genes related to mitosis. Chemokine, interleukin, and toll-like receptor genes were also upregulated, suggesting activation of proinflammatory pathways. In summary, we find evidence that a cell division-independent expression pathway exists, and that polyplex exposure slows cell division and increases inflammatory response.


HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb.
In the present study, we report the synthesis and human growth factor receptor-2 (HER2) specific tumor targeting properties of a dendrimer conjugated to anti-HER2 mAb (monoclonal antibody) conjugate. The polyamidoamine (PAMAM) dendrimer generation five (G5) was labeled with alexaFluor 488 and conjugated to anti-HER2 mAb. The binding and internalization of the antibody-conjugated dendrimer to HER2-expressing cells was evaluated by flow cytometry and confocal microscopy. Uniquely, the conjugate demonstrated cellular uptake and internalization in HER2-expressing cells as compared to free antibody. The time course of internalization and blocking experiments with free antibody suggest that the rapid and efficient cellular internalization of the dendrimer-antibody conjugate was achieved without alterations in specificity of targeting. Animal studies demonstrated that the conjugate targets HER2-expressing tumors.


Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction.
Hypercholesterolemia characterized by elevation of low-density lipoprotein (LDL) cholesterol is a major risk factor for atherosclerotic vascular disease. p66shc mediates hypercholesterolemia-induced endothelial dysfunction and atheromatous plaque formation. We asked if LDL upregulates endothelial p66shc via changes in the epigenome and examined the role of p66shc in LDL-stimulated endothelial cell dysfunction. Human LDL stimulates human p66shc promoter activity and p66shc expression in human endothelial cells. LDL leads to hypomethylation of two CpG dinucleotides and acetylation of histone 3 in the human p66shc promoter. These two CpG dinucleotides mediate LDL-stimulated p66shc promoter activity. Inhibition or knock down of DNA methyltransferases negates LDL-induced endothelial p66shc expression. p66shc mediates LDL-stimulated increase in expression of endothelial intercellular adhesion molecule-1 (ICAM1) and decrease in expression of thrombomodulin (TM). Mirroring these changes in ICAM1 and TM expression, p66shc mediates LDL-stimulated adhesion of monocytes to endothelial cells and plasma coagulation on endothelial cells. These findings indicate that LDL cholesterol upregulates human endothelial p66shc expression via hypomethylation of CpG dinucleotides in the p66shc promoter. Moreover, they show that LDL-stimulated p66shc expression mediates a dysfunctional endothelial cell surface, with proadhesive and procoagulant features.


Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.
Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.


[Halothane hepatitis].
The greatest disadvantage of the halothane, widely used in the anaesthesiology is its ability to cause liver damage. After halothane anaesthesia mild liver enzyme elevation in the one fifth of the patients was detected. The incidence of fatal halothane hepatitis is rare. It depends on several risk factors: on the genetic predisposition, repeated halothane anaesthetics, female sex, age of patient, obesity, intrahepatic hypoxia and enzyme induction. In the pathophysiology of liver toxicity the metabolism of halothane and immune functions play an important role. In this review the last results of researches concerning to the hepatotoxicity of halothane are summarised and the authors call the attention on the opportunity of its effective prevention.


mTORC1 senses stresses: Coupling stress to proteostasis.
Beyond protein synthesis and autophagy, emerging evidence has implicated mTORC1 in regulating protein folding and proteasomal degradation as well, highlighting its prominent role in cellular proteome homeostasis or proteostasis. In addition to growth signals, mTORC1 senses and responds to a wide array of stresses, including energetic/metabolic stress, genotoxic stress, oxidative stress, osmotic stress, ER stress, proteotoxic stress, and psychological stress. Whereas growth signals unanimously stimulate mTORC1, stresses exert complex impacts on mTORC1, most of which are repressive. mTORC1 suppression, as a generic adaptive strategy, empowers cell survival under various stressful conditions. In this essay, we provide an overview of the emerging role of mTORC1 in proteostasis, the distinct molecular mechanisms through which mTORC1 reacts to diverse stresses, and the schemes exploited by cancer cells to circumvent stress-induced mTORC1 suppression. Hence, acting as a stress sensor, mTORC1 intimately couples stresses to cellular proteostasis.


Debulking of skin cancers with radio frequency before cryosurgery.
The purpose of prior debulking of skin cancers, by curettage, is to prepare the lesion for cryosurgical treatment. The main inconveniences of that procedure are the nearly always inevitable hemorrhage and the time necessary to control it. We performed a study consisting of debulking skin tumors with radiosurgery, prior to cryosurgery, on a series of 38 patients (31 basal cell carcinomas, six squamous cell carcinomas, and one Bowen's disease), meeting the classical indications for cryotherapy. The advantages of the latter procedure over the traditional debulking by curettage are: the time needed to perform a biopsy, with easy and fast control of the bleeding, is considerably shortened; the whole procedure can be easily performed in one single session; the required surgical material also is greatly reduced; and the treatment can be performed on an out-patient regimen.


A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials.
We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.


IFNgamma induces functional chemokine receptor expression in human mesangial cells.
Infiltration of leucocyte populations into sites of inflammation is a common feature in renal diseases. Glomerular mesangial cells are potent producers of a variety of chemokines, leading to specific attraction of distinct types of inflammatory leucocytes into the glomerulus, but so far there is limited knowledge about the responsiveness of mesangial cells to chemokines. We investigated the expression of chemokine receptors and the responsiveness of primary human mesangial cells (HMC) to the chemokines which they produce, namely monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-8. We found that mRNAs of the chemokine receptors CCR1, which has been shown before, CCR2 and CXCR2 were induced by T-helper cytokine interferon-gamma (IFNgamma). In IFNgamma-stimulated cells, CCR2 and CXCR2 were detectable by flow cytometry. Following treatment with IFNgamma, HMC responded to MCP-1 and IL-8 with an increase of IL-6 mRNA and protein expression, which was in part blocked by pertussis toxin. Moreover, chemokine stimulation of transfected HMC led to an activation of the immunoregulatory transcription factors NFkappaB and AP-1. Additionally, we found that MCP-1 enhanced the expression of its own mRNA in cells activated to express CCR2, suggesting autocrine feedback mechanisms in MCP-1 regulation. Finally, IFNgamma-activated cells migrated towards an MCP-1 gradient in a chemotaxis assay. These results strengthen the assumption that chemokines are not only involved in the recruitment of immune cells to inflamed tissues, but also seem to play a central role in the autocrine regulation of local tissue cells, leading to proceeding inflammation and possibly contributing to healing by mediating cell growth and migration.


Artistic quality of drawings and judges' evaluations of the DAP.
When art quality varied for a set of figure drawings, judges were unable to differentiate hospitalized schizophrenic females from a matched nonpatient group. Both trained and naive judges erroneously tended to see drawings of low are quality as a patient origin, and drawings of high overall quality as of nonpatient origin. When art quality was held constant judges did slightly 0etter than chance in differentiating the patient vs nonpatient drawings. Psychologists were no more accurate than untrained judges. Results support the position that art quality of drawings influences judges' evaluations, and, in terms of the present investigation, represents a major source of error in drawing interpretation. Even when art quality was controlled, however, judges' rate of success was low, casting doubt on the status validity of the Draw-A-Person test (DAP).


Observation of Phase-Filling Singularities in the Optical Dielectric Function of Highly Doped n-Type Ge.
Phase-filling singularities in the optical response function of highly doped (>10^{19} cm^{-3}) germanium are theoretically predicted and experimentally confirmed using spectroscopic ellipsometry. Contrary to direct-gap semiconductors, which display the well-known Burstein-Moss phenomenology upon doping, the critical point in the joint density of electronic states associated with the partially filled conduction band in n-Ge corresponds to the so-called E_{1} and E_{1}+Δ_{1} transitions, which are two-dimensional in character. As a result of this reduced dimensionality, there is no edge shift induced by Pauli blocking. Instead, one observes the "original" critical point (shifted only by band gap renormalization) and an additional feature associated with the level occupation discontinuity at the Fermi level. The experimental observation of this feature is made possible by the recent development of low-temperature, in situ doping techniques that allow the fabrication of highly doped films with exceptionally flat doping profiles.


Neuro-ophthalmic complications of intracranial catheters.
We report four patients who sustained direct injury to the brain after insertion of intraventricular shunts and pressure monitoring lines, which resulted in permanent neuro-ophthalmic deficits. These included hemianopsia from an optic tract lesion, esotropia and residual bilateral facial paresis from dorsal pontine injury, unilateral blindness from damage to the optic nerve, and dorsal midbrain syndrome from catheter compression in the region of the posterior commissure. Although presumably rare, such injuries should be considered in diagnosing patients with neuro-ophthalmic complaints after insertion of such devices.


A rare occurrence of hairy cell leukemia in the Thai population: a case report.
Hairy cell leukemia (HCL) has been mainly reported from the Western countries. Herein we describe a case of HCL diagnosed in a Thai patient. A 36-year-old man presented with abdominal discomfort, frequent gum bleeding and significant weight loss for 2 months. Physical examination revealed moderate anemia, petechial hemorrhage on the extremities and an enlarged spleen down to the umbilicus. No hepatomegaly or lymphadenopathy was detected. Complete blood counts revealed a hemoglobin (Hb) of 6.6 g/dL, a white blood cell (WBC) count of 1.6 x 10(9)/L (neutrophil 16%, lymphocyte 71%, monocyte 11%, atypical lymphocyte 1%), and a platelet (PLT) count of 17 x 10(9)/L. Abnormal large mononuclear cells with villous projections were seen in the blood smear. Although bone marrow (BM) aspiration resulted in a dry tap, abnormal lymphocytes with villous projections could again be identified in the touch preparation. Flow cytometric analysis showed a distinct population above the normal lymphocyte region on CD45/SSC gates with a strong expression of CD19, CD20, CD22, CD25, CD11c, and kappa. CD5, CD23, CD10, CD4, and CD8 were all negative. BM biopsy was consistent with HCL. The patient was treated with splenectomy followed by 8 cycles of fludarabine and cyclophosphamide chemotherapy. At 21 months after diagnosis, the patient was doing well with a Hb of 16.9 g/dl, a WBC count of 6.8 x 10(9)/L, neutrophil 49.9%, lymphocyte 39.6%, monocyte 8.6%, and a PLT count of 329 x 10(9)/L). No abnormal lymphoid cells were detected in the blood smear. This present report represents the first Thai HCL case that was immunophenotypically confirmed by flow cytometry and successfully treated at Siriraj Hospital.


Does intermittent pneumatic compression increase the risk of pulmonary embolism in deep venous thrombosis after joint surgery?
The present study aimed to identify the incidence and risk factors of symptomatic pulmonary embolism and evaluate the safety of early intermittent pneumatic compression application in patients with deep venous thrombosis (DVT) after joint surgery. A total of 144 patients with DVT undergoing joint surgery were divided into two groups according to the appearance of symptomatic pulmonary embolism. Venography and computed tomographic pulmonary angiography were utilized as the assessment methods. The total incidence of symptomatic pulmonary embolism was 0.39% after joint surgery. However, the prevalence increased to 3.5% when computed in patients with DVT. Patients with symptomatic pulmonary embolism were older than those without symptomatic pulmonary embolism (69 ± 4 versus 61 ± 15 years, P = 0.04). The occurrence rate of symptomatic pulmonary embolism in patients with diabetes mellitus was much higher than that in the patients without diabetes mellitus (40.0% versus 8.6%, respectively, P = 0.02). The prevalence of symptomatic pulmonary embolism after joint surgery in patients with DVT was not distinctive. Increased age and diabetes mellitus put patients with DVT at risk of suffering symptomatic pulmonary embolism after joint surgery. In addition, early postoperative application of intermittent pneumatic compression was safe in these patients.


Do water-limiting conditions predispose Norway spruce to bark beetle attack?
Drought is considered to enhance susceptibility of Norway spruce (Picea abies) to infestations by the Eurasian spruce bark beetle (Ips typographus, Coleoptera: Curculionidae), although empirical evidence is scarce. We studied the impact of experimentally induced drought on tree water status and constitutive resin flow, and how physiological stress affects host acceptance and resistance. We established rain-out shelters to induce both severe (two full-cover plots) and moderate (two semi-cover plots) drought stress. In total, 18 sample trees, which were divided equally between the above treatment plots and two control plots, were investigated. Infestation was controlled experimentally using a novel 'attack box' method. Treatments influenced the ratios of successful and defended attacks, but predisposition of trees to infestation appeared to be mainly driven by variations in stress status of the individual trees over time. With increasingly negative twig water potentials and decreasing resin exudation, the defence capability of the spruce trees decreased. We provide empirical evidence that water-limiting conditions impair Norway spruce resistance to bark beetle attack. Yet, at the same time our data point to reduced host acceptance by I. typographus with more extreme drought stress, indicated by strongly negative pre-dawn twig water potentials.


Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses.
A role for type II interferon (IFN-gamma) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-gamma-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-gamma1b and a potent, consensus type I IFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-gamma1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-gamma1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (Th1) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.


[Neurosurgical therapy of transorbital intracranial foreign bodies: review of 28 cases].
To discuss the benefits and complications of the neurosurgical therapy in transorbital intracranial foreign bodies. The clinical data of 28 cases of transorbital intracranial foreign bodies, metallic in 13 cases, vegetal 5 cases, and vitreous, plastic and other kinds in 10 cases, were analyzed retrospectively. Optic nerve injury was found in 13 cases, orbital apex syndrome in 11 cases; CSF rhinorrhea in 13 cases, CSF orbital leak in 3 cases, and hemiplegia in 2 cases. All the patients underwent head CT scan, and orbital horizontal and coronal CT scan. The patients with metallic foreign bodies had DSA exams, and the non-metallic cases had MRA scans. 22 cases had orbital-frontal craniotomy and foreign body resection, and 6 cases had direct foreign body extraction. All the cases received antibiotic and nerve nutritional therapy postoperatively. The cases in which the foreign bodies came from the orbital roof into the skull recovered well postoperatively; and the cases in which the foreign bodies came from the superior orbital fissure into the skull showed hemiplegia (n = 2) or orbital apex syndrome (n = 6) postoperatively. Transorbital intracranial foreign body should be diagnosed in early stage to avoid missed diagnosis. Omission should be avoided during resection of the foreign body. The relationship between the foreign body and internal carotid artery should be examined carefully before the extraction. Direct extraction of foreign body causes less injury, and patients' condition should be followed up.


Selective Enrichment of Clostridium Spp. by Nutrition Control from Sihe Coal Geological Microbial Communities.
In the coal biogasification, butyric acid is an important intermediate product. The enrichment of butyric acid-producing bacteria in coal geological methanogens is critical to confirm this assertion. Therefore, to study a method for enrichment of butyric acid-producing bacteria and to explore characteristic factors for evaluating the enrichment effect would be the basis for further strain isolation and metabolomics research. In this study, the nutrition control method was used for the butyric acid-producing bacteria enrichment from concentrated bacteria solution in Sihe coal seam. The characteristic factors' changes in gas production, gas composition, butyric acid concentration, and pH were observed and analyzed in the experiment. High-throughput sequencing was used as a verification method to validate the medium and genera enrichment effect that can be used for the butyric acid-producing bacteria. Through experimental research and analysis, it was identified that the glucose-sucrose-maltose medium was the beneficial medium to the enrichment of butyric acid-producing bacteria, and the high-throughput sequencing determined that the enriched genera were Clostridium spp. Glucose-sucrose-maltose medium experimental data confirmed that the decrease of CO2 and H2 daily yield, the increase of butyric acid concentration, and the decrease of pH value had a significant positive correlation with the enrichment of Clostridium spp.


Perioperative myocardial ischemia reperfusion injury.
Myocardial I-R injury contributes to adverse cardiovascular outcomes after cardiac surgery. The pathogenesis of I-R injury is complex and involves the activation, coordination, and amplification of several systemic and local proinflammatory pathways (Fig. 4). Treatment and prevention of perioperative morbidity associated with myocardial I-R will ultimately require a multifocal approach. Combining preoperative risk stratification (co-morbidity and surgical complexity), minimizing initiating factors predisposing to SIRS, limiting ischemia duration, and administering appropriate immunotherapy directed toward systemic and local proinflammatory mediators of I-R injury, should all be considered. In addition, the role of the genetic-environmental interactions in the pathogenesis of cardiovascular disease is also being examined. Thus, in the near future, preoperative screening for polymorphisms of certain inflammatory and coagulation genes should inevitably help reduce morbidity by permitting the identification of high-risk cardiac surgical patients and introducing the opportunity for gene therapy or pharmacogenetic intervention [42,64].


On passage through resonances in volume-preserving systems.
Resonance processes are common phenomena in multiscale (slow-fast) systems. In the present paper we consider capture into resonance and scattering on resonance in 3D volume-preserving multiscale systems. We propose a general theory of those processes and apply it to a class of kinematic models inspired by viscous Taylor-Couette flows between two counter-rotating cylinders. We describe the phenomena during a single passage through resonance and show that multiple passages lead to the chaotic advection and mixing. We calculate the width of the mixing domain and estimate a characteristic time of mixing. We show that the resultant mixing can be described using a diffusion equation with a diffusion coefficient depending on the averaged effect of the passages through resonances.


Expression of IRAK‑3 is associated with colitis‑associated tumorigenesis in mice.
Interleukin‑1 receptor‑associated kinase‑3 (IRAK‑3) is a negative regulator in Toll‑like receptor (TLR) pathways. The present study investigated the importance of IRAK‑3 in a mouse model of chemically‑induced colitis‑associated tumorigenesis. The colitis‑associated tumorigenesis was induced in ICR mice by the administration of 1,2‑dimethyl hydrazine (DMH) and dextran sodium sulfate (DSS), termed the DMH + DSS group. In the DSS group, mice were administered with DSS; in the DMH group, mice were injected with DMH; in the control group, mice were injected with physiological saline. The clinical signs were examined for 20 weeks; tissue samples were analyzed at week 4, 9, 13 and 20. At week 20, the levels of IRAK‑3 were analyzed using immunohistochemistry, western blot analysis, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis, and methylation‑specific PCR. At week 20, the DMH + DSS group mice exhibited a decrease in total body weight and had developed canalicular adenoma or adenocarcinoma. The mice in the DSS group and DMH group presented with significant colitis at week 20. The mice with colitis‑associated tumorigenesis were found to have decreased levels of IRAK‑3, compared with the mice in the other groups, as evidenced by the results of the immunohistochemistry (P=0.002), RT‑qPCR analysis (P<0.001) and western blot analysis (P<0.001). IRAK‑3 methylation was observed in all experimental groups. Taken together, DMH + DSS induction in colitis led to increased inflammation and risk of tumorigenesis. IRAK‑3 methylation may be a predictive factor in the transition from colitis to cancer.


Persistent global power fluctuations near a dynamic transition in electroconvection.
This is a study of the global fluctuations in power injection and light transmission through a liquid crystal just above the onset of electroconvection. The source of the fluctuations is identified as the creation and annihilation of defects. They are spatially uncorrelated and yet temporally correlated. The temporal correlation is seen to persist for extremely long times. There seems to be an especially close relation between defect creation or annihilation in electroconvection and thermal plumes in Rayleigh-Bénard convection.


Regulation of necrosis of H9c2 myogenic cells upon transient energy deprivation. Rapid deenergization of mitochondria precedes necrosis and is controlled by reactive oxygen species, stress kinase JNK, HSP72 and ARC.
Subjecting myogenic H9c2 cells to transient energy deprivation leads to a caspase-independent death with typical features of necrosis. Here we show that the rupture of cytoplasmic membrane, the terminal event in necrosis, is shortly preceded by rapid depolarization of mitochondrial membranes. The rapid deenergization of mitochondria critically depended upon prior generation of reactive oxygen species (ROS) during ATP depletion stage. Accordingly, expression of catalase prevented mitochondrial depolarization and averted subsequent necrosis. Interestingly, trifluoperazine, a compound that protects cells from ischemic insults, prevented necrosis of H9c2 cells through inhibition of ROS production. Other factors that regulated the mitochondrial membrane depolarization and subsequent loss of plasma membrane integrity include a stress kinase JNK activated at early steps of recovery from ATP depletion, as well as an apoptotic inhibitory protein ARC. Accordingly, inhibition of JNK or overexpression of ARC prevented mitochondrial depolarization and rescued H9c2 cells from necrosis. ROS and JNK affected mitochondrial deenergization and necrosis independently of each other since inhibition of ROS production did not prevent activation of JNK, whereas inhibition of JNK did not suppress ROS accumulation. Therefore, JNK activation and ROS production represent two independent pathways that control mitochondrial depolarization and subsequent necrosis of cells subjected to transient energy deprivation. Overexpression of ARC, although preventing mitochondrial depolarization, did not affect either JNK activation or production of ROS. The major heat shock protein Hsp72 inhibited JNK-related steps of necrotic pathway but did not affect ROS accumulation. Interestingly, mitochondrial depolarization and subsequent necrosis can be suppressed by an Hsp72 mutant Hsp72DeltaEEVD, which lacks chaperone function but can efficiently suppress JNK activation. Thus, Hsp72 is directly implicated in a signaling pathway, which leads to necrotic death.


Fulvestrant in postmenopausal women with advanced breast cancer.
Patients with hormone-sensitive breast cancer who have responded to tamoxifen (TAM) may receive additional benefit from a second endocrine agent after progression or relapse after TAM therapy. Fulvestrant (FVT; Faslodex; i.m. injection, ICI 182,780; AstraZeneca Pharmaceuticals, Wilmington, DE) was developed as a selective antagonist of estrogen. In postmenopausal women, FVT is reported to inhibit the proliferative effects of estrogen on sensitive tissues and has no apparent measurable estrogenic activity. In this report, we describe the data and analyses supporting marketing approval for FVT by the United States Food and Drug Administration (FDA). The FDA review of 16 clinical trials and 6 pharmacokinetic trials, as well as preclinical pharmacology and chemistry data, are described. The bases for marketing approval are summarized. Toxicology studies in the mouse, rat, and dog showed minimal toxicity except for antiestrogenic effects. Because of FVT aqueous insolubility, an i.m. formulation, given at monthly intervals, was selected for clinical studies. Pharmacokinetic studies demonstrated sustained concentrations with monthly injection. In in vitro studies FVT was extensively metabolized, primarily by hepatic cytochrome P450 3A4. Phase I studies showed minimal toxicity, and the maximal dose (250 mg) was limited by FVT solubility. In two Phase III trials, 851 patients were randomized to either 250 mg FVT i.m. monthly or to anastrozole (ANZ) 1 mg p.o. daily. Ninety-six percent of patients had received TAM previously for early (adjuvant treatment) or advanced breast cancer. Response rates (RR) were 17% for both FVT and ANZ study arms in the North American trial, and were 20% versus 15% for FVT versus ANZ, respectively, in the European trial. There were no observed differences between study arms with respect to time to progression or survival. The most common FVT adverse events reported as potentially treatment-related were injection site reactions and hot flashes. FVT was approved on April 25, 2002 by the FDA for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression after antiestrogen therapy. The recommended dose is 250 mg i.m. monthly as a single 5 ml injection or as two concurrent 2.5 ml injections into the buttocks. Approval was based on results of two randomized trials comparing response rates and time to progression of FVT- and ANZ-treated patients. Complete prescribing information is available on the FDA website.


Life events, familial stress, and coping in the developmental course of schizophrenia.
Recent studies have isolated some socioenvironmental factors that seem to predict the onset of schizophrenic episodes in vulnerable persons. In particular, stressful life events have been found to cluster in the 3- to 4- week period preceding a schizophrenic episode in some patients. Many persons with a schizophrenic disorder also seem to contribute to additional stressful life change events--for example, by high geographic mobility--thereby playing an active role in precipitating the onset of illness episodes. Within the family environment, hostile, critical, and emotionally overinvolved attitudes toward the patient by relatives have been found to be related to relapses. Irregularities in the communication style of parents also predict the subsequent development of schizophrenia spectrum disorders among disturbed adolescents. Many schizophrenic patients also seem to be deficient in the coping skills required to remediate the losses brought on by life events or to deal effectively with stressful relatives. Thus, they may experience greater and more prolonged stress than most others due partially to inadequate social and problem-solving skills and less supportive social networks. These findings have important implications for the design of clinical interventions as well as the development of a comprehensive vulnerability/stress model for the course of schizophrenic disorders.


The respiratory microbiome and innate immunity in asthma.
The purpose of this study is to summarize recent studies of the lower respiratory microbiome in asthma, the role of innate immunity in asthma and strategies to understand complex microbiome-immune interactions in asthma. Recent evidence indicates that the composition of lower respiratory microbiota in asthmatic individuals, across a spectrum of disease severity, is altered compared with healthy individuals. Attributes of this altered airway microbiome have been linked to clinical and inflammatory features of asthma. The importance of innate immune cells and mucosal defense systems in asthma is increasingly appreciated and may be dysregulated in the disease. Interactions between the respiratory microbiome and innate mucosal immunity in asthma are complex and a challenge to dissect. Multiple avenues of investigation, leveraging a variety of methodologies, will need to be pursued to understand functional relationships to clinical and inflammatory phenotypes seen in asthma.


Effects of aerosols from nontoxic Stachybotrys chartarum on murine airways.
Acute effects on the upper and lower respiratory tract due to inhalation exposure to Stachybotrys chartarum (Sc) extract were investigated in mice. In addition, the capacity of the Sc exposure to activate immune system and cause inflammation in the respiratory tract was studied. The inhalation of Sc extract aerosols was observed to provoke sensory irritation in the airways of both naive and Sc-immunized mice. In contrast, exposure to aerosolized ovalbumin or phosphate buffered saline did not cause this effect. Exposure to Sc twice a week for 3 wk increased significantly the serum total immunoglobulin E (IgE) levels in BALB/c mice immunized with Sc as well as in nonimmunized mice. A slight presence of inflammatory cells was observed in the alveoli 3 days after the last exposure to Sc. In conclusion, Sc extract has the capacity to provoke sensory irritation in the murine airways and to activate the murine immune system.


IP-Se-06, a Selenylated Imidazo[1,2-a]pyridine, Modulates Intracellular Redox State and Causes Akt/mTOR/HIF-1α and MAPK Signaling Inhibition, Promoting Antiproliferative Effect and Apoptosis in Glioblastoma Cells.
Glioblastoma multiforme (GBM) is a notably lethal brain tumor associated with high proliferation rate and therapeutic resistance, while currently effective treatment options are still lacking. Imidazo[1,2-a]pyridine derivatives and organoselenium compounds are largely used in medicinal chemistry and drug development. This study is aimed at further investigating the antitumor mechanism of IP-Se-06 (3-((2-methoxyphenyl)selanyl)-7-methyl-2-phenylimidazol[1,2-a]pyridine), a selenylated imidazo[1,2-a]pyridine derivative in glioblastoma cells. IP-Se-06 exhibited high cytotoxicity against A172 cells (IC50 = 1.8 μM) and selectivity for this glioblastoma cell. The IP-Se-06 compound has pharmacological properties verified in its ADMET profile, especially related to blood-brain barrier (BBB) permeability. At low concentration (1 μM), IP-Se-06 induced intracellular redox state modulation with depletion of TrxR and GSH levels as well as inhibition of NRF2 protein. IP-Se-06 also decreased mitochondrial membrane potential, induced cytochrome c release, and chromatin condensation. Furthermore, IP-Se-06 induced apoptosis by decreasing levels of Bcl-xL while increasing levels of γ-H2AX and p53 proteins. Treatment with IP-Se-06 induced cell cycle arrest and showed antiproliferative effect by inhibition of Akt/mTOR/HIF-1α and ERK 1/2 signaling pathways. In addition, IP-Se-06 displayed significant inhibition of p38 MAPK and p-p38, leading to inhibition of inflammasome complex proteins (NLRP3 and caspase-1) in glioblastoma cells. These collective findings demonstrated that IP-Se-06 is a bioactive molecule that can be considered a candidate for the development of a novel drug for glioblastoma treatment.


Toxoplasma gondii causes changes in the host's expression of cancer-associated miRNAs.
Throughout the world, numerous individuals are infected with Toxoplasma gondii, which may improve immunity against cancer. Furthermore, microRNAs (miRs) may be differentially expressed in the host upon infection with T. gondii. In the present study, RNA-sequencing analysis and reverse transcription-quantitative PCR revealed that miR-429-3p, miR-145a-5p, miR-211-5p, miR-31-3p and miR-135a-5p were determined to be downregulated, while miR-21a-3p, miR-135b-5p, miR-210-5p and miR-146-3p were upregulated in mice post-infection with T. gondii. Antitumor genes [TNF receptor superfamily member 11b, large tumor suppressor kinase (Lats)2 and Lats1] were identified as targets of miR-429-3p, miR-145a-5p, miR-211-5p, miR-31-3p and miR-135a-5p with a luciferase reporter assay. In addition, the protein levels of Lats2 and Lats1 were detected to be higher in T. gondii-infected mice than in the control group. Therefore, these results provide favorable evidence for the suppression of cancer upon T. gondii infection and may give novel ideas for the treatment of tumors.


Erythrocyte sedimentation rate and C-reactive protein: how best to use them in clinical practice.
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are markers of inflammatory conditions and have been used extensively by clinicians both in outpatient and inpatient settings. It is important to understand the physiologic principles behind these two tests so clinicians may use them appropriately. For example, fibrinogen (for which ESR is an indirect measure) has a much longer half-life than CRP, making ESR helpful in monitoring chronic inflammatory conditions, whereas CRP is more useful in diagnosis as well as in monitoring responses to therapy in acute inflammatory conditions, such as acute infections. Many factors can result in falsely high or low ESR and CRP levels, and it is important to take note of these. Therefore, if used wisely, ESR and CRP can be complementary to good history taking and physical examination in the diagnosis and monitoring of inflammatory conditions.


The Impact of Three Commonly Used Fungicides on Typhlodromus pyri (Acari: Phytoseiidae) in European Vineyards.
The impact of the fungicides mancozeb, myclobutanil, and meptyldinocap on populations of Typhlodromus pyri Scheuten was evaluated under field conditions, when applied following the good agricultural practices recommended for their use. Two complementary statistical models were used to analyze the population reduction compared to the control: a linear mixed model to estimate the mean effect of the fungicide, and a generalized linear mixed model (proportional odds mixed model) to estimate the cumulative probability for those effects being equal or less than a specific IOBC class (International Organization for Biological and Integrated Control of Noxious Animal and Plants). Findings from 27 field experiments in a range of different vine-growing regions in Europe indicated that the use of mancozeb, myclobutanil, and meptyldinocap caused minimal impact on naturally occurring populations of T. pyri. Both statistical models confirmed that although adverse effects on T. pyri can occur under certain conditions after several applications of any of the three fungicides studied, the probability of the effects occurring is low and they will not persist. These methods demonstrated how data from a series of trials could be used to evaluate the variability of the effects caused by the chemical rather than relying on the worst-case findings from a single trial.


BRCA mutation screening and patterns among high-risk Lebanese subjects.
Previous studies have suggested that the prevalence of BRCA1 and 2 mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of BRCA1/2 mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools. We retrospectively reviewed the cases of all individuals undergoing BRCA mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region. Two-hundred eighty one individuals were referred for testing. The prevalence of mutated BRCA1 or 2 genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The BRCA1 c.131G > T mutation was found among 5/17 (29%) unrelated subjects with BRCA1 mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for BRCA mutation screening. The Manchester Score failed to predict pathogenic mutations. The BRCA1 c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in BRCA1 and among 7/269 families in this cohort. On review of recently published data regarding the landscape of BRCA mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations.


Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer.
The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups. A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group. Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM. NCT02314819.


Effect of childhood sexual abuse on gynecologic care as an adult.
The study sought to evaluate whether childhood sexual abuse (CSA) experiences significantly affect the gynecologic care received as an adult. A self-administered questionnaire including eight questions on CSA was completed by 85 women exposed to CSA and 170 matched-control women. Women exposed to CSA experienced gynecologic examinations as anxiety-provoking significantly more often and sought more treatment for acute gynecologic problems; 43.5% of these women experienced memories of the original abuse situation during gynecologic consultations. Gynecologic care is particularly distressing for women exposed to CSA.


Tilted implants and prototyping: a security option for improving the anchorage in atrophic maxilla.
Rehabilitating atrophic maxilla poses many challenges. Reconstructive techniques that require sinus grafting are viable and acceptable; however, these techniques also are considered to be expensive, invasive, and time-consuming. Tilted implants anchored in distal areas using available bone have been reported as a less invasive and highly predictable treatment option. This article presents a case involving implant anchorage via tilted implants as an alternative technique to bone grafting procedures.


Osmium-zinc iodide reacts with interdigitating cells in the mouse lymph nodes and spleen.
It is known that epidermal Langerhans cells react with osmium-zinc iodide (ZIO) mixtures; therefore they can be visualized by this histochemical method. In the last few years it has been shown that Langerhans cells are closely related to the class of interdigitating cells (IDC) which are antigen presenting cells located in the T-dependent areas of lymph nodes and spleen. In this study the reactivity of murine IDC to ZIO has been assessed. Results demonstrate that ZIO procedure yields to a brilliant and selective staining of IDC. The reactivity pattern is quite similar to that previously observed in epidermal Langerhans cells. This finding gives further support to the concept that Langerhans cells and IDC are closely interrelated cell types.


Molecular epidemiology of Mycobacterium leprae as determined by structure-neighbor clustering.
It has proven challenging to investigate the molecular epidemiology of Mycobacterium leprae, the causative agent of leprosy, due to difficulties with culturing of the organism and a lack of genetic heterogeneity between strains. Recently, a cost-effective panel of variable-number tandem-repeat (VNTR) markers has been developed. Use of this panel allows some of those limitations to be overcome and has allowed the genotyping of 475 M. leprae strains from six different countries. In the present report, we provide a comprehensive analysis of the relationships among the strains in order to investigate the patterns of transmission and migration of M. leprae. We find phylogenetic analysis to be inadequate and have developed an alternative method, structure-neighbor clustering, which assigns isolates with the most similar genotypes to the same groups and, subsequently, subgroups, without inferring how the strains descended from a common ancestor. We validate the approach by using simulated data and detecting expected epidemiological relationships from experimental data. Our results suggest that most M. leprae strains from a given country cluster together and that the occasional isolates assigned to different clusters are a consequence of migration. We found three genetically distinguishable populations among isolates from the Philippines, as well as evidence for the significant influx of strains to that nation from India. We also report that reference strain TN originated from the Philippines and not from India, as was previously believed. Lastly, analysis of isolates from the same families and villages suggests that most community infections originate from a common source or person-to-person transmission but that infection from independent sources does occur with measurable frequency.


Reactivity of monoclonal antibodies to Pseudomonas aeruginosa isolates from hospitalized adults and patients with cystic fibrosis.
To assess the potential therapeutic use of three human monoclonal antibodies (MAbs) and one murine MAb, we tested the reactivity of these MAbs toward 100 clinical isolates of Pseudomonas aeruginosa. Seventy-five isolates were from hospitalized patients, while 25 were recovered from patients with documented cystic fibrosis. Nine isolates showed autoagglutination. The three human MAbs and one murine MAb exhibited agglutination with 81% of the P. aeruginosa isolates obtained from hospitalized patients and with 72% of the isolates from patients with cystic fibrosis. Eight of the autoagglutinating isolates were reactive in whole-cell ELISAs with the MAbs. The isolates recovered from patients with cystic fibrosis were reactive mainly with a MAb that is directed to the outer core of lipopolysaccharide (LPS); they showed hardly any reaction with O antigen-specific MAbs or typing sera, a finding indicating that these isolates lacked the O antigen and that the outer core of the LPS was still present. The reactivity of the MAb specific for the outer core of LPS toward P. aeruginosa isolates from patients with cystic fibrosis has potential value in eradicating P. aeruginosa from these patients.


Defining the Indications of PATIO Technique for Urethrocutaneous Fistula Repair.
Despite the advancements in technique and technology, urethrocutaneous fistula (UCF) formation continues to be the most common complication after hypospadias repair. The objective of the current synthesis is to define the indications of PATIO technique for UCF repair. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Ovid, Embase, Web of Science, and Google Scholar were interrogated for studies presenting primary data upon UCF repair by the PATIO technique. Data analysis was performed on MedCalc and R software. Eighteen studies were identified relevant to the current context: inversion of UCF tract has been described in 13 and ligation in 5. There were 2 duplications (abstract and manuscript). The overall success for PATIO is 88.2% (314/356). The success rate was variable between classic PATIO (inversion at 87.2%), ligation-inversion at 86.9%, and ligation alone at 88.9%. The success rate was not improvised upon by supplementing inversion of UCF tract with ligation (p = 0.957) or addition of a waterproofing layer (p = 0.622). PATIO has been used for single or multiple UCFs post hypospadias repair, genital piercing, and genitoplasty in cis- or transgender population for UCF up to 5 mm in size. The success rates were best for UCF <2 mm and worst for those approaching 5 mm. The results were, however, unaffected by the location of UCF along the penile shaft. Besides, the use of urethral catheter is optional and may be eliminated with shorter hospitalization. PATIO repair may be considered for repair of UCFs (a) with diverse etiologies, (b) located anywhere along the penile shaft included coronal UCF, (c) preferably <4 mm in size, (d) single or multiple in number; multiple PATIOs may be done in the same setting, (e) in patients unwilling for prolonged hospitalization, (f) in patients unwilling for a urethral catheter, and (g) in hypospadias cripples wherein mobilization of distant tissues such as tunica vaginalis flap or a buccal mucosal graft may be required for supplementing the UCF repair.


Regional features of the microbial landscape of urine and comparative evaluation of antimicrobial therapy in children with cystitis.
Growing resistance of pathogens to antibiotics, including cross-resistance to other antimicrobial classes that are used in the treatment of recurrent infections of the lower urinary system in children demands constant control of issues of regional antibiotic resistance. In the present days, in the empirical treatment of such patients physicians still choose medications with preserved activity in relation to E. coli. The aim of our study was to investigate the regional features of microbial landscape of urine in children with cystitis and study the efficacy of 7-day administration of Furamag medicinal drug for the treatment of recurrent episodes of this disease in children. 65 children aged 5 to 16 years underwent clinical and laboratory examinations. The patients in Group I (33 children) received Furamag as an antimicrobial therapy; the comparison group consisted of patients (32 children) who received cefuroxime axetil. The both therapies course duration was 7 days. Bacteriological examination results were indicative of prevalence of gram-negative opportunistic microflora; in particular, E. coli prevailed in the structure of isolated causative agents (61.9%). Analysis of detected pathogens susceptibility to antimicrobial agents showed a high level of E.coli resistance to ampicillin, amoxicillin/clavulanate and gentamicin (in 97.4% of cases), and in 50% of cases the E.coli were resistant to cefotaxime, ceftriaxone and cefuroxime. High rates of resistance of Enterococcus spp. (100%) and Enterobacter spp. (96.7%) to cefuroxime, cefotaxime and ceftriaxone were recorded. Furamag demonstrated significantly higher bacteriological efficacy vs. cefuroxime axetil as for eradication of the most clinically significant causative agents of cystitis identified in the Poltava region (93.9% and 68.8%, respectively, p <0.05). During the follow-up study, anti-relapse efficacy of Furamag appeared to be 1.5 times higher as compared to the reference drug in the children examined (p <0.05).


Circulating exosomal miRNAs as potential biomarkers for Barrett's esophagus and esophageal adenocarcinoma.
Exosomes, a class of extracellular vesicles, are small membrane-bound vesicles derived from almost all cell types that can play important roles in intercellular communication. Exosomes contain proteins, lipids, and nucleic acids that are obtained from the parental cells and participate in various pathophysiological processes, including cell growth, migration, inflammation, immune regulation, and tumor pathogenesis. Moreover, exosomes might be applied in clinical settings, such as diagnosis, treatment, and outcome prediction of diseases, including various cancers. The incidence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have increased in recent decades, and studies have proposed specific factors that may contribute to the development and progression of these diseases. However, how exosomes play a role in this pathological process needs to be clarified. Studies have identified candidate microRNAs (miRNAs) that might be related to BE/EAC. Further studies are needed to ascertain whether circulating exosomal miRNAs are altered before or after disease onset, which could also help understand the pathophysiology of and find potential targets for prevention, diagnosis, and therapy in BE/EAC. This review summarizes recent findings on the features of circulating exosomal miRNAs in BE/EAC, which could be valuable for the early diagnosis, therapeutic approaches, and outcome prediction of BE/EAC.


Bioactive Compounds and Sensory Quality in Chips of Native Potato Clones (Solanum tuberosum spp. andigena) Grown in the High Andean Region of PERU.
Native potatoes (Solanum tuberosum spp. andigena) have diverse pigments and are cultivated in Peru's high Andean regions; they are characterized by containing bioactive compounds that prevent various degenerative diseases. The study aimed to evaluate the physicochemical and sensory quality in chips of native potato clones grown at 3496 m altitude, for which the potatoes were cut into slices and fried in extra virgin olive oil at 180 °C for 200 s. This was determined by proximal analysis, reducing sugars, minerals, color, antioxidant capacity (AC), total phenolic compounds (TPC), and anthocyanins in fresh and chips; an instrumental characterization by FTIR and SEM and sensory tests were also performed. The native potatoes presented low moisture and reduced sugar contents; when frying, their bioactive properties improved, increasing AC, TPC, and trace elements, such as K, Mg, Ca, P, Fe, and Zn. To conclude, fresh clones have high yields in the field and are an essential source of nutrients and bioactive; the salt-free chips of clone B presented better physicochemical properties and greater sensory acceptance, closely followed by clone A. Both clones could be used as raw material by food companies that produce snacks to benefit high Andean agricultural producers.


On the switching mechanism and optimisation of ion irradiation enabled 2D MoS2 memristors.
Memristors are prominent passive circuit elements with promising futures for energy-efficient in-memory processing and revolutionary neuromorphic computation. State-of-the-art memristors based on two-dimensional (2D) materials exhibit enhanced tunability, scalability and electrical reliability. However, the fundamental of the switching is yet to be clarified before they can meet industrial standards in terms of endurance, variability, resistance ratio, and scalability. This new physical simulator based on the kinetic Monte Carlo (kMC) algorithm reproduces the defect migration process in 2D materials and sheds light on the operation of 2D memristors. The present work employs the simulator to study a two-dimensional 2H-MoS2 planar resistive switching (RS) device with an asymmetric defect concentration introduced by ion irradiation. The simulations unveil the non-filamentary RS process and propose routes to optimize the device's performance. For instance, the resistance ratio can be increased by 53% by controlling the concentration and distribution of defects, while the variability can be reduced by 55% by increasing 5-fold the device size from 10 to 50 nm. Our simulator also explains the trade-offs between the resistance ratio and variability, resistance ratio and scalability, and variability and scalability. Overall, the simulator may enable an understanding and optimization of devices to expedite cutting-edge applications.


Nurse perceptions of safety climate in Australian acute hospitals: a cross-sectional survey.
Objectives The aim of the present study was to explore nurse perceptions of safety climate in acute Australian hospitals. Methods Participants included 420 nurses who have worked on 24 acute wards from six Australian hospitals. The Safety Attitudes Questionnaire (SAQ) Short Form was used to quantify nurse perceptions of safety climate and benchmarked against international data. Generalised linear mixed models were used to explore factors that may influence safety climate. Results On average, 53.5% of nurses held positive attitudes towards job satisfaction followed by teamwork climate (50.5%). There was variability in SAQ domain scores across hospitals. The safety climate and perceptions of hospital management domains also varied across wards within a hospital. Nurses who had worked longer at a hospital were more likely to have poorer perceptions of hospital management (β=-5.2; P=0.014). Overall, nurse perceptions of safety climate appeared higher than international data. Conclusions The perceptions of nurses working in acute Victorian and New South Wales hospitals varied between hospitals as well as across wards within each hospital. This highlights the importance of surveying all hospital wards and examining the results at the ward level when implementing strategies to improve patient safety and the culture of safety in organisations. What is known about the topic? Prior studies in American nursing samples have shown that hospitals with higher levels of safety climate have a lower relative incidence of preventable patient complications and adverse events. Developing a culture of safety in hospitals may be useful in targeting efforts to improve patient safety. What does this paper add? This paper has shown that the perceptions of safety climate among nurses working in acute Australian hospitals varied between hospitals and across wards within a hospital. Only half the nurses also reported positive attitudes towards job satisfaction and teamwork climate. What are the implications for practitioners? Programs or strategies that aim to enhance teamwork performance and skills may be beneficial to improving the culture of safety in hospitals. Wards may also have their own safety 'subculture' that is distinct from the overall hospital safety culture. This highlights the importance of tailoring and targeting quality improvement initiatives at the ward level.


The prognosis and risk factors for patients with complex karyotype myelodysplastic syndrome undergoing allogeneic haematopoietic stem cell transplantation.
Allogeneic haematopoietic stem cell transplantation (HCT) is the curative treatment for myelodysplastic syndrome with a complex karyotype (CK-MDS). However, only a few studies have been limited to patients with CK-MDS undergoing allogeneic HCT. This study aimed to identify the risk factors for patients with CK-MDS undergoing allogeneic HCT. We included 691 patients with CK-MDS who received their first allogeneic HCT. The overall survival (OS) was the primary end-point, estimated using the Kaplan-Meier method. Prognostic factors were identified using a Cox proportional hazards model. The 3-year OS was 29.8% (95% confidence interval [CI]: 26.3-33.3). In the multivariable analysis, older age (hazard ratio [HR]: 1.44, 95% CI: 1.11-1.88), male sex (HR: 1.38, 95% CI: 1.11-1.71), poor haematopoietic cell transplant comorbidity index (HR: 1.47, 95% CI: 1.20-1.81), red blood cell transfusion requirement (HR: 1.58, 95% CI: 1.13-2.20), platelet transfusion requirement (HR: 1.85, 95% CI: 1.46-2.35), not-complete remission (HR: 1.55, 95% CI: 1.16-2.06), a high number of karyotype abnormality (HR: 1.63, 95% CI: 1.18-2.25) and monosomal karyotype (HR: 1.49, 95% CI: 1.05-2.12) were significantly associated with OS. Thus, the 3-year OS of allogeneic HCT was 29.8% in patients with CK-MDS, and we identified risk factors associated with poor OS.


The Construct Validity of the German Academic Self-regulation Questionnaire (SRQ-A) within Primary and Secondary School Children.
The assessment of students' motivation can be a powerful tool in enhancing and understanding students' learning. One valid and often applied self-report measure is the Academic Self-Regulation Questionnaire (SRQ-A) which is grounded in the self-determination theory. However, to date, there is still no German equivalent to the English version of this questionnaire. Therefore, the aim of the present study was to adapt and validate the SRQ-A on a representative German student sample, consisting of 672 children (327 girls), ages 8-14 from one primary and two secondary German schools. First, the translation-back-translation method was used to ensure the linguistic equivalence of the German questionnaire. Second, item analysis of the generated scores of the German SRQ-A were conducted. Third, the multidimensional factorial structure of the original measure was tested with confirmatory factor analysis (CFA) using maximum likelihood estimation. Last, additional construct validity of the German SRQ-A was tested using correlational analyses with convergent and divergent measures. After conducting CFA, four items were excluded from the original questionnaire, due to loadings lower than 0.40, resulting in 28 items. The German SRQ-A showed good internal consistency for all subscales, with Chronbach's α ranging between 0.75 and 0.88. The simplex-structure of the original measurement could also be confirmed, however, the four-factorial model could not be replicated. The measurement showed good convergent and discriminant validity with other related questionnaires. In summary, the German SRQ-A is a reliable and valid self-report instrument for the assessment of self-determined motivational styles within the school context.


Improved epitope resolution of the prefusion trimer-specific antibody AM14 bound to the RSV F glycoprotein.
Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infections resulting in medical intervention and hospitalizations during infancy and early childhood, and vaccination against RSV remains a public health priority. The RSV F glycoprotein is a major target of neutralizing antibodies, and the prefusion stabilized form of F (DS-Cav1) is under investigation as a vaccine antigen. AM14 is a human monoclonal antibody with the exclusive capacity of binding an epitope on prefusion F (PreF), which spans two F protomers. The quality of recognizing a trimer-specific epitope makes AM14 valuable for probing PreF-based immunogen conformation and functionality during vaccine production. Currently, only a low-resolution (5.5 Å) X-ray structure is available of the PreF-AM14 complex, revealing few reliable details of the interface. Here, we perform complementary structural studies using X-ray crystallography and cryo-electron microscopy (cryo-EM) to provide improved resolution structures at 3.6 Å and 3.4 Å resolutions, respectively. Both X-ray and cryo-EM structures provide clear side-chain densities, which allow for accurate mapping of the AM14 epitope on DS-Cav1. The structures help rationalize the molecular basis for AM14 loss of binding to RSV F monoclonal antibody-resistant mutants and reveal flexibility for the side chain of a key antigenic residue on PreF. This work provides the basis for a comprehensive understanding of RSV F trimer specificity with implications in vaccine design and quality assessment of PreF-based immunogens.


Effect of age and diet on renal cadmium retention in rats.
The results of our previous and recent work on cadmium metabolism in relation to age and diet are presented. Experiments were performed on albino rats aged 1-26 weeks. In some experiments rats were given different foods (milk, meat, bread) instead of standard rat diet. Some animals received trisodium calcium salt of diethylenetriaminepentaacetate (DTPA) intraperitoneally to decrease cadmium retention. Radioactive cadmium (115mCd) was administered orally and intraperitoneally. Whole body (WB), carcass (C) and organ (kidney, liver and brain) retentions were determined 1 and 2 weeks after a single radioisotope administration. The results are expressed as percentages of the administered dose (% D) and as percentages of whole body (% WB) and carcass (% C) radioactivities. After oral administration whole-body cadmium retention was higher in sucklings than in weaned animals, primarily due to increased gut retention. The kidney retention of orally administered cadmium was about 5-7 times higher in sucklings than in older rats. Cadmium distribution (% C) was similar after oral and intraperitoneal administration. In sucklings, kidney retention made a lower fraction of the carcass radioactivity one week after 115mCd administration but reached adult values a week later. Liver retention in sucklings was a slightly lower fraction of the carcass radioactivity than in older rats at both time intervals. Brain retention (% C) was about 10 times higher in sucklings than in older rats throughout the experiment. Preliminary data on the influence of dietary treatments and treatment with DTPA indicate that some treatments which influence cadmium retention also influence cadmium distribution.(ABSTRACT TRUNCATED AT 250 WORDS)


European Phaseolus coccineus L. landraces: population structure and adaptation, as revealed by cpSSRs and phenotypic analyses.
Relatively few studies have extensively analysed the genetic diversity of the runner bean through molecular markers. Here, we used six chloroplast microsatellites (cpSSRs) to investigate the cytoplasmic diversity of 331 European domesticated accessions of the scarlet runner bean (Phaseolus coccineus L.), including the botanical varieties albiflorus, bicolor and coccineus, and a sample of 49 domesticated and wild accessions from Mesoamerica. We further explored the pattern of diversity of the European landraces using 12 phenotypic traits on 262 individuals. For 158 European accessions, we studied the relationships between cpSSR polymorphisms and phenotypic traits. Additionally, to gain insights into the role of gene flow and migration, for a subset of 115 accessions, we compared and contrasted the results obtained by cpSSRs and phenotypic traits with those obtained in a previous study with 12 nuclear microsatellites (nuSSRs). Our results suggest that both demographic and selective factors have roles in the shaping of the population genetic structure of the European runner bean. In particular, we infer the existence of a moderate-to-strong cytoplasmic bottleneck that followed the expansion of the crop into Europe, and we deduce multiple domestication events for this species. We also observe an adaptive population differentiation in the phenology across a latitudinal gradient, which suggests that selection led to the diversification of the runner bean in Europe. The botanical varieties albiflorus, bicolor and coccineus, which are based solely on flower colour, cannot be distinguished based on these cpSSRs and nuSSRs, nor according to the 12 quantitative traits.


Intermediate and advanced hepatocellular carcinoma treated with the antiangiogenic agent sorafenib. Evaluation with unenhanced and contrast-enhanced ultrasonography.
To evaluate the sonographic changes observed in hepatocellular carcinoma (HCC) post antiangiogenic treatment with sorafenib. Twenty one intermediate or advanced HCC patients (19 men, 2 women; mean age: 66.8 years; 32 target tumors-TTs) received sorafenib as monotherapy and were studied with unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) with a second generation echo-enhancer (SonoVue) at bimonthly intervals. Changes in lesional size, echotexture and enhancement were evaluated. Response was classified according to RECIST (Response Evaluation Criteria In Solid Tumors) and modified (m) RECIST. Cystic changes were detected on US in 4 patients (7 lesions); CEUS showed a significant (51-100%) decrease of viable, enhancing TTs in the aforementioned patients. Four additional patients (5 lesions) showed a 73-87% decrease of their viable TTs on CEUS, but no changes on US. 13/21 patients showed less than 30% decrease, no change, or increase of their viable TTs. Based on the last sonographic evaluation, response was as follows: RECIST- Complete Response, CR (n=0), Partial Response, PR (n=1), Stable Disease, SD (n=16), Progressive Disease, PD (n=4); mRECIST- CR (n=2), PR (n=6), SD (n=11), PD (n=2). The 8 responders (CR+PR) according to mRECIST had significantly longer mean overall survival (OS) compared to the 13 non-responders (21.5 vs 12.2 months, p=0.018, Kaplan-Meier method). However, statistical significance was reduced (p=0.065) after adjustment for BCLC and Child's class. US may occasionally detect changes indicative of the effect of sorafenib on HCC, but CEUS is required to evaluate and grade post-therapeutic reduction of tumoral enhancement. The latter is likely to correlate with OS.


The reliability and validity of lung cancer and melanoma clinical quality survival measures.
To develop a risk adjustment approach and test reliability and validity for oncology survival measures. We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2010 to 2013, with mortality data through 2015. We developed 2-year risk-standardized survival rates (RSSR) for melanoma, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC). Patients were attributed to group practices based on the plurality of visits. We identified the risk-adjustment variables via bootstrap and calculated the RSSRs. Reliability was tested via three approaches: (1) signal-to-noise ratio (SNR) reliability, (2) split-half, and (3) test-retest using bootstrap. We tested known group validity by stage at diagnosis using Cohen's d. We selected all patients enrolled in Medicare and linked to SEER during the measurement period with an incident first primary diagnosis of stage I-IV melanoma, NSCLC, or SCLC. We excluded patients with missing data on month and/or stage of diagnosis. Results are based on patients with melanoma (n = 4344); NSCLC (n = 16,080); and SCLC (n = 2807) diagnosed between 2012 and 2013. The median (interquartile range) for the RSSRs at the group practice-level were 0.89 (0.83-0.87) for melanoma, 0.37 (0.30-0.43) for NSCLC, and 0.19 (0.11-0.25) for SCLC. C-statistics for the models ranged from 0.725 to 0.825. The reliability varied by approach with median SNR 0.20, 0.25, and 0.13; median test-retest 0.59, 0.57, and 0.56; median split-half reliability 0.21, 0.29, and 0.29 for melanoma, NSCLC, and SCLC, respectively. Cohen's d for stage I-IIIa and IIIb+ was 1.27, 0.86, 0.60 for melanoma, NSCLC, and SCLC, respectively. Our results suggest that these cancer survival measures demonstrated adequate test-retest reliability and expected findings for the known-group validity analysis. If data limitations and feasibility challenges can be addressed, implementation of these quality measures may provide a survival metric used for oncology quality improvement efforts.


[EFFECTIVENESS OF OPEN REDUCTION AND INTERNAL FIXATION WITH LOCKING ANATOMICAL PLATE FOR TREATING VALGUS IMPACTED PROXIMAL HUMERUS FRACTURE].
To investigate the effectiveness of open reduction and internal fixation with locking anatomical plate for treating valgus impacted proximal humerus fracture. A retrospective analysis was made on the clinical data of 38 patients with valgus impacted proximal humerus fracture who underwent open reduction and internal fixation with locking anatomical plate between January 2009 and January 2014. There were 25 males and 13 females, aged from 47 to 63 years (mean, 52.3 years); the left and the right sides were involved in 18 and 20 cases, respectively. The causes of fracture included high falling injury in 10 cases, traffic accident injury in 15 cases, and falling injury in 13 cases. The time between injury and operation was 5-10 days (mean, 7.5 days). The collodiaphyseal angle was 160-200 degrees (mean, 176 degrees) on X-ray films. All incisions healed by first intention, and there was no early complication related to operation. All these patients were followed up 12-30 months (mean, 18 months). X-ray film showed that clinical healing time of fracture was 10-16 weeks after operation (mean, 12 weeks); at 12 months after operation, the collodiaphyseal angle recovered to 120-145 degrees (mean, 135 degrees). During follow-up, no loss of fracture reduction and no loosening of internal fixation were observed. At 10-12 months, osteonecrosis of the humeral head occurred in 3 cases (7.9%), including 2 cases of Cruess stage III and 1 case of Cruess stage IV. At last follow-up, the Constant shoulder joint scores were 56-95 (mean, 82.6); the results were excellent in 10 cases, good in 15 cases, fair in 9 cases, and poor in 4 cases, with an excellent and good rate of 66%. Visual analogue scale (VAS) scores were 0-6 (mean, 0.9). It can achieve a comparatively satisfactory clinical result to use open reduction and internal fixation with locking anatomical plate for treating valgus impacted proximal humerus fracture.


Scandiatransplant Exchange Program (STEP): Development and Results From an International Kidney Exchange Program.
Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019. This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in ≥3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility.Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023. The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.


Notation of allergies and body weight on patient profiles.
The purpose of this study was to increase the documentation of allergy and body weight information on pharmacy medication profile cards for pediatric patients. The intent was to facilitate pharmacist evaluation of medication dosages ordered for these patients. A plastic allergy/weight imprinting card was supplied to each nursing unit and was used to imprint all admitting physician's order sheets. Allergy and weight information was to be filled in by the physician and/or nurse before routing a copy of these orders to the satellite pharmacy. Inservice education was presented and follow-up phone calls were made. During an 18-day control period, baseline data on documentation of allergies and weight were collected. During an 18-day study period, the allergy/weight card was used and follow-up phone calls were made. During an 18-day post-study period, the card and phone calls were removed. Percent of profiles having allergies and weight were, respectively: control period, 33 percent and 28 percent; study period, 80 percent and 76 percent; post-study period, 47 percent and 46 percent. Imprinting "allergy/weight" with space for filling in this information can result in an increased number of pharmacy patient profiles having these data so that medications can be checked prior to dispensing the first dosages of medication.


Timing the excitotoxic induction of heat shock protein 70 transcription.
The time course of heat-shock protein 70 (HSP70) transcriptional induction was compared with neuronal- and non-neuronal-specific mRNAs following intrastriatal quinolinate (QA) injection. Within one hour of QA exposure, immediate-early gene (IEG; c-fos) activation preceded slight increases in glutamic acid decaroxylase (GAD) mRNA levels. However, glial fibrillary acid protein (GFAP) and HSP70 mRNA levels remained constant. After one hour, HSP70 mRNA levels surged 6 fold during a delayed transcriptional phase that was induced between 4-12 hours. This phase was characterized by massive increases in c-fos and GFAP mRNAs while GAD transcripts fell drastically suggestive of neuronal death. Therefore HSP70 genes may play an important role in glial/immune activation following rapid excitotoxic damage by direct injections of quinolinate.