Delivery of doxorubicin-loaded PLGA nanoparticles into U87 human glioblastoma cells.
The paramount problem in the therapy of brain tumors is the inability of most drugs to cross the blood-brain barrier. PLGA nanoparticles overcoated with poloxamer 188 could overcome this problem and enabled a high anti-tumoral effect against the very aggressive intracranial 101.8 glioblastoma in rats that closely resembles human grade IV glioblastomas. The basis for the transport of these particles across the blood-brain barrier appears to be adsorption of blood apolipoproteins (ApoE or ApoA-I) on the nanoparticle surface caused by the poloxamer 188-coating, followed by receptor-mediated transcytosis of the nanoparticles. The objective of the present study is the elucidation of the mechanism by which the poloxamer 188-coated nanoparticles then enter the brain tumor cells. Their intracellular fate, therefore, was investigated using the U87 human glioma cell line. The main mechanism of the PLGA nanoparticle internalization by U87 cells was clathrin-mediated endocytosis. Within 1h free doxorubicin was released from late endosomes and could reach its target site, i.e. the DNA in the nuclei without degradation, whereas the PLGA nanoparticles, which were labeled with Cy5.5, still were observed in the endo-lysosomal compartment. These results demonstrate that the underlying mechanism of action in the brain cells is by diffusive doxorubicin release from the nanoparticles rather than by their intracellular degradation.


Natural maternal transmission of H. pylori in Mongolian gerbils.
To investigate maternal H. pylori infection status to determine the potential of maternal transmission. In the present study, we examined these issues in an experimental murine model, which is a Mongolian gerbil model that has been reported as an optimal laboratory animal model to study H. pylori. Pregnant Mongolian gerbils, infected experimentally with H. pylori, were divided into as four groups. Following the experimental design, the stomachs of the mother and litters were isolated and assessed for transmission of H. pylori at the prenatal period, parturition day, 1-wk old and 3-wk old respectively. Bacterial culture and polymerase chain reaction (PCR) were used to examine the presence of transmitted H. pylori. All litters showed no transmission of H. pylori during pregnancy and at parturition day. However, they revealed 33.3% and 69.6% at 1-wk and 3-wk of age respectively by PCR. These results suggested that vertical infection during the prenatal period or delivery procedure is unlikely as a route of mother-to-child H pylori infection. It may be that H. pylori is acquired through breast-feeding, contaminated saliva and fecal-oral transmission during co-habitation.


2-Methoxyestradiol causes matrix metalloproteinase 9-mediated transactivation of epidermal growth factor receptor and angiotensin type 1 receptor downregulation in rat aortic smooth muscle cells.
Studies have demonstrated the therapeutic potential of estrogen metabolite 2-methoxyestradiol (2ME2) in several cardiovascular disorders, including hypertension. However, the exact mechanism(s) remains unknown. In this study, primary rat aortic smooth muscle cells (RASMCs) were exposed to 2ME2, and angiotensin type 1 receptor (AT1R) expression, function, and associated signaling pathways were evaluated. In RASMCs, 2ME2 downregulated AT1R expression in a concentration- and time-dependent manner, which was correlated with reduced mRNA expression. The 2ME2 effect was through G protein-coupled receptor 30 (GPR30) that inhibits second messenger cAMP. Moreover, 2ME2 exposure phosphorylated ERK1/2 that was sensitive to MEK inhibitor PD98059. Selective epidermal growth factor receptor (EGFR) inhibitor AG1478 blocked 2ME2-induced EGFR transactivation and attenuated subsequent phosphorylation of ERK1/2 preventing AT1R downregulation. The transactivation was dependent on 2ME2-induced release of matrix metalloproteinase 9 (MMP9) and epidermal growth factor demonstrated by ELISA. Furthermore, transfection with small interfering (si) RNA targeting MMP9 impeded ERK1/2 activation and AT1R downregulation in response to 2ME2 and G1 stimulation. Interestingly, under similar conditions, stimulation of GPR30 with the selective agonist G1 elicited similar signaling pathways and downregulated the AT1R expression that was reversed by GPR30 antagonist G15. Furthermore, 2ME2 and G1 inhibited angiotensin II (ANG II) induced Ca2+ release, a response consistent with AT1R downregulation. Collectively, our study demonstrates for the first time that 2ME2 binding to GPR30 induces MMP9 specific transactivation of EGFR that mediates ERK1/2-dependent downregulation of AT1R in RASMCs. The study provides critical insights into the newly discovered role and signaling pathways of 2ME2 in the regulation of AT1R in vascular cells and its potential to be developed as a therapeutic agent that ameliorates hypertension.


An integrated approach for a knowledge-based clinical workstation: architecture and experience.
Today, the demand for medical decision support to improve the quality of patient care and to reduce costs in health services is generally recognized. Nevertheless, decision support is not yet established in daily routine within hospital information systems which often show a heterogeneous architecture but offer possibilities of interoperability. Currently, the integration of decision support functions into clinical workstations is the most promising way. Therefore, we first discuss aspects of integrating decision support into clinical workstations including clinical needs, integration of database and knowledge base, knowledge sharing and reuse and the role of standardized terminology. In addition, we draw up functional requirements to support the physician dealing with patient care, medical research and administrative tasks. As a consequence, we propose a general architecture of an integrated knowledge-based clinical workstation. Based on an example application we discuss our experiences concerning clinical applicability and relevance. We show that, although our approach promotes the integration of decision support into hospital information systems, the success of decision support depends above all on an adequate transformation of clinical needs.


Hierarchical Self-Assembly of Perylene Diimide (PDI) Crystals.
Controlling molecular self-assembly of organic semiconductors is a key factor in enhancing the performance of organic electronics and optoelectronics. However, unlike various p-type organic semiconductors, it has proven elusive to control molecular self-assembly with about tens of nm dimensions using n-type organic semiconductors including perylene diimide (PDI), which is the most promising alternative to fullerene derivatives, without using an additional synthetic method or additives, thus far. Here, we developed a simple self-assembling method for the hierarchical self-assembly of PDI crystals with nanometer-to-micrometer scale features using pristine PDI-C8 without using an additional synthetic method or additive. Interestingly, we observed crystalline and optical properties of self-assembled PDI crystals depending on their size and structural features. In addition, we fabricated p-n junctions composed of PDI and poly(3-hexylthiophene) (P3HT), where the p-n junctions had coassembled and blended nanomorphologies, and confirmed that coassembled nanomorphologies enabled more effective energy transfer than the blended nanomorphologies.


Effects of supplementary composts on microbial communities and rice productivity in cold water paddy fields.
Cold water paddy field soils are relatively unproductive, but can be ameliorated by supplementing with inorganic fertilizer from animal waste-based composts. The yield of two rice cultivars was significantly raised by providing either chicken manure or cow dung-based compost. The application of these composts raised the soil pH as well as both the total nitrogen and ammonium nitrogen content, which improved the soil's fertility and raised its nitrification potential. The composts had a measurable effect on the abundance of nitrogencycling- related soil microbes, as measured by estimating the copy number of various bacterial and archaeal genes using quantitative real-time PCR. The abundance of ammonia oxidizing archaea and bacteria was markedly encouraged by the application of chicken manure-based compost. Supplementation with the composts helped promote the availability of soil nitrogen in the cold water paddy field, thereby improving the soil's productivity and increasing the yield of the rice crop.


Understanding prebiotics in infant and childhood nutrition.
Prebiotics and probiotics are ingredients in the diet that strengthen beneficial microbes in the gut, especially bifidobacteria. This article discusses their effects on health and their use in infant formula and foods for children and adults. They may also have benefits for the elderly population, since bifidobacteria are known to decrease with old age.


A new HLA-A*31 null allele, A*3114N.
A new HLA-A*31 null allele results from addition of an extra C near the beginning of exon 4 after a string of seven Cs.


Hydralazine is a Suitable Mimetic Agent of Hypoxia to Study the Impact of Hypoxic Stress on In Vitro Blood-Brain Barrier Model.
Understanding cellular mechanisms induced by hypoxia is fundamental to reduce blood-brain barrier (BBB) disruption. Nevertheless, the investigation of hypoxia on cellular pathways is complex with true hypoxia because HIF-1α has a short lifetime and rapidly reverts back to a normoxic state. To overcome this difficulty, mimetic agents of the hypoxia pathway have been developed, including the gold standard CoCl2. In this study, we proposed to compare CoCl2 and hydralazine in order to determine a suitable mimetic agent of hypoxia for the study on the BBB. We studied the cytotoxicity and the impact of these molecules on the integrity of an in vitro BBB model by comparing them to hypoxia controls. We showed that the impact of hypoxic stress in our in vitro BBB model is rather similar between hydralazine and CoCl2. Chemical hypoxic stress led to an increase of BBB permeability either with CoCl2 or hydralazine. Tight junction protein expressions showed that this chemical hypoxic stress decreased ZO-1 but not occluding expressions, and cells had set up a defence mechanism by increasing expression and activity of their efflux transporters. Our results demonstrated that hydralazine is a better mimetic agent and more suitable than CoCl2 because it had the same effect but without the cytotoxic effect on in vitro BBB cells.


Categorical Perception for Emotional Faces.
Categorical perception (CP) refers to how similar things look different depending on whether they are classified as the same category. Many studies demonstrate that adult humans show CP for human emotional faces. It is widely debated whether the effect can be accounted for solely by perceptual differences (structural differences among emotional faces) or whether additional perceiver-based conceptual knowledge is required. In this review, I discuss the phenomenon of CP and key studies showing CP for emotional faces. I then discuss a new model of emotion which highlights how perceptual and conceptual knowledge interact to explain how people see discrete emotions in others' faces. In doing so, I discuss how language (emotion words included in the paradigm) contribute to CP.


Paradoxical inotropic effects of clonidine and labetalol in the conscious rabbit.
Both clonidine and labetalol when given by bolus intravenous injection into conscious rabbits produce an initial rise in left ventricular pressure associated with a decrease in myocardial contractility as assessed by left ventricular dP/dt. While clonidine also produces a marked bradycardiac effect, labetalol causes no change in heart rate. Acute beta-adrenoceptor blockade with propranolol, 1 mg/kg, i.v., does not significantly modify the response produced by either clonidine or labetalol. Following cardiac cholinergic blockade with scopolamine methylbromide, 50 microgram/kg, the negative inotropic effect produced by clonidine is abolished and is replaced by a positive inotropic effect, while the negative inotropic response produced by labetalol is attenuated. Following cardiac autonomic blockade with propranolol and scopolamine methyl-bromide, both clonidine and labetalol produce a positive inotropic response. These positive inotropic responses may be due to the partial alpha-adrenoceptor-agonist properties which both drugs possess and which could be unmasked by cardiac autonomic blockade.


Long-term positive and negative psychosocial outcomes in young childhood cancer survivors, type 1 diabetics and their healthy peers.
This study examined posttraumatic growth (PTG) in young childhood cancer survivors (CCS) and type 1 diabetics (DM), with physically healthy peers as the control group (CG). Anxiety and depression as negative mental outcomes in the three groups, as well as fear of progression in DM and CCS were examined. A total of 107 participants with ages ranging from 18 to 35 years were examined: CCS (n=33), type 1 diabetics (n=39) and peers without a history of chronic disease (n=35). PTG and negative psychosocial outcomes were assessed with self-report questionnaires. There was a significant difference between the groups regarding PTG. On a subscale level DM reported higher appreciation of life (p=0.024), higher personal strength (p=0.010), and more new possibilities (p=0.010) compared to CG. CCS experienced higher spiritual changes than DM (p=0.050). DM reported higher levels of anxiety compared to CCS (p=0.026) and CG (p=0.049). Depression was higher in DM compared to CG (p=0.003). Fear of progression was higher in DM compared to CCS (p<0.001). These findings show that psychological growth was experienced by young CCS and participants with DM. Furthermore, these findings highlight that adolescents with a significant health diagnosis in childhood or youth can undergo a similar or even more positive psychosocial development as peers without a history of chronic disease. However, young type 1 diabetics seem to be a more vulnerable group in terms of anxiety, depression and fear of progression.


Prognostic relevance of epilepsy at presentation in glioblastoma patients.
Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due to early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in glioblastoma patients. Multivariable Cox regression was applied to survival data of 647 consecutive patients diagnosed with de novo glioblastoma between 2005 and 2013 in order to investigate the association between epilepsy and survival in glioblastoma patients. In addition, we quantified the association between survival and valproic acid (VPA) treatment. Epilepsy correlated positively with survival (HR: 0.75 (95% CI: 0.61-0.92), P < .01). This effect is independent of age, sex, performance status, type of surgery, adjuvant therapy, tumor location, and tumor volume, suggesting that this positive correlation cannot be attributed solely to early diagnosis. For patients who presented with epilepsy, the use of the antiepileptic drug VPA did not associate with survival when compared with patients who did not receive VPA treatment. Epilepsy is an independent prognostic factor for longer survival in glioblastoma patients. This prognostic effect is not solely explained by early diagnosis, and survival is not associated with VPA treatment.


Analysis of the effect of particle size on polymorphic quantitation by Raman spectroscopy.
Raman spectroscopy has been widely used to monitor various aspects of the crystallization process. Although it has long been known that particle size can influence Raman signal, relatively little research has been conducted in this area, in particular for mixtures of organic materials. The aim of this study was to investigate the effect of particle size on quantification of polymorphic mixtures. Several sets of calibration samples containing different particle size fractions were prepared and Raman spectra were collected with different probes. Calibration models were built using both univariate and multivariate analysis. It was found that, for a single component system, Raman intensity decreased with increasing particle size. For mixtures, calibration models generated from the same particle size distribution as the sample yielded relatively good predictions of the actual sample composition. However, if the particle sizes of the calibration and unknown samples were different, prediction errors resulted. For extreme differences in particle sizes, prediction errors of up to 20% were observed. Prediction errors could be minimized by changing the sampling optics employed.


Neuroprotective effect of Hydrocotyle sibthorpioides against monosodium glutamate-induced excitotoxicity.
We aimed to evaluate the neuroprotective effect of H. sibthorpioides against monosodium-glutamate (MSG) induced excitoneurotoxicity in rats. We randomly divided the animals into 11 groups (n = 8) and subjected them to high doses of MSG (2 g/kg body weight) and the test dose (1 week). The test chemicals were H. sibthorpioides extracts of petroleum ether, chloroform, methanol, and water. We used Dizocilpine-hydrogen-maleate as a standard and assessed the cognitive property using Morris-water-maze and elevated-plus-maze. After the experimental period, we evaluated the biochemical parameters. We found chloroform and methanolic extracts significantly enhanced the cognitive behaviour of rats compared to control. Biochemical analysis suggested that there was a high level of antioxidants and lower levels of glutamate and proinflammatory cytokines in the cortex and hippocampus. We concluded that chloroform and methanolic extracts of H. sibthorpioides enhanced the level of antioxidants, decreased proinflammatory-cytokines and glutamate in the brain, and thus prevented the monosodium-glutamate-induced-excite-neurotoxicity.


Granulomatosis with Polyangiitis in Adolescence: Two Distinct Presentations.
Introduction. Granulomatosis with polyangiitis (GPA) is a rare disease in pediatric age. We report two cases with distinct presentations. Case Reports. A seventeen-year-old male with prolonged febrile syndrome, cough, and constitutional symptoms. CT-scan showed cavitated lesions of the lung and bronchial biopsy a necrotizing inflammatory process. The remaining investigation revealed hematoproteinuria and positive C-ANCA and anti-PR3. Complications: Bilateral acute pulmonary thromboembolism, splenic infarction, and extensive popliteal and superficial femoral deep vein thrombosis. He was treated with corticosteroids, immunoglobulin, rituximab, and anticoagulation. Rituximab was maintained every six months during the first two years. Control angio-CT was performed with almost complete resolution of previous findings. In a twelve-year-old female with inflammatory signs of the limbs, investigation showed myositis of the thigh and tenosynovitis of the wrist, normocytic normochromic anemia (Hg 9.4 g/dL), mild elevation of inflammatory markers, and high creatine kinase. During hospitalization, she presented an extensive alveolar hemorrhage associated with severe anemia and positive C-ANCA and anti-PR3. Clinical deterioration prompted intravenous methylprednisolone pulses and plasmapheresis. Induction therapy with rituximab and prednisolone showed good results. Rituximab was maintained every six months, for 18 months, with gradual tapering of corticoids. Discussion. GPA is a systemic disease with variable clinical presentation and severity. Pediatric patients have similar clinical manifestations to adults but different frequencies of organ involvement; constitutional symptoms are also more common. We highlight the different presentation of these two cases, as well as the need for an individualized approach. Rituximab has been used for both induction-remission and maintenance therapy, with good results, particularly in young patients.


The Value of Food Allergy Prevention in Clinical Practice in Pediatrics: Targeting Early Life.
Food allergies are common and increasing in prevalence, representing a major health concern in many countries around the world. In an effort to diminish the burden of food allergy, many research studies have focused on prevention, and recent findings have revolutionized the way we introduce allergenic foods in early life. We discuss the role of early allergenic food introduction and the value of food allergy prevention in this manuscript.


Inverse relationship of protein concentration and aggregation.
To determine the effect of protein concentration on aggregation induced through quiescent shelf-life incubation or shipping-related agitation. All aggregation was measured by size-exclusion high-performance liquid chromatography. Aggregation was induced by time-dependent incubation under stationary conditions or by agitation caused by shaking, vortexing, or vibration using simulated shipping conditions. Protein aggregation is commonly a second- or higher-order process that is expected to increase with higher protein concentration. As expected, for three proteins (PEG-GCSF, PEG-MGDF, and OPG-Fc) that were examined, the aggregation increased with higher protein concentration if incubated in a quiescent shelf-life setting. However, aggregation decreased with higher protein concentration if induced by an air/water interface as a result of agitation. This unexpected result may be explained by the rate-limiting effect on aggregation of the air/water interface and the critical nature of the air/ water interface to protein ratio that is greatest with decreased protein concentration. The non-ionic detergent polysorbate 20 enhanced the aggregation observed in the quiescently incubated sample but abrogated the aggregation induced by the air/water interface. The effect of protein concentration was opposite for aggregation that resulted from quiescent shelf-life treatment compared to induction by agitation. For motionless shelf-life incubation, increased concentration of protein resulted in more aggregation. However, exposure to agitation resulted in more aggregation with decreased protein concentration. These results highlight an unexpected complexity of protein aggregation reactions.


Reporting and ideal testosterone levels in men undergoing androgen deprivation for prostate cancer-time for a rethink?
This study aims to review current laboratory reporting strategies across Australia and New Zealand with a view to propose a more useful template for reporting serum testosterone in the context of prostate cancer. Registered pathology laboratories in Australia and New Zealand were enrolled into the current study. An electronic or a phone survey was utilized to collect data from each participating laboratory. Obtained information included assay utilized, units reported, reference intervals, lowest reported value, and lowest detectable value. To identify recommendations for testosterone testing, a systematic search was performed across Web of Science (including MEDLINE), EMBASE, and Cochrane libraries. Assessment of national pathology laboratories identified significant heterogeneity in the reporting methods. Reports typically used a "normal healthy male of 35 years of age" as a comparator but did not refer to optimal castrate levels, the lowest level that their assay was able to detect, nor did they include appended clinical guidelines relating to the prostate cancer patient cohort. Across Australia and New Zealand, various methods for testing and reporting serum testosterone exist, while international guidelines remain vague. The fashion in which serum testosterone levels are displayed should be re-evaluated to address the relevant clinical population and reflect an agreed-upon castrate threshold in patients undergoing androgen deprivation therapy.


Risk Factors for Revision Surgery After Superior Labral Anterior-Posterior Repair: A National Perspective.
Data regarding risk factors for revision surgery after superior labral anterior-posterior (SLAP) repair are limited to institutional series. To define risk factors for revision surgery after SLAP repair among patients in a large national database. Case-control study; Level of evidence, 3. A national insurance database was queried for patients undergoing arthroscopic SLAP repair (Current Procedural Terminology [CPT] code 29807) for the diagnosis of a SLAP tear. Patients without a CPT modifier for laterality were excluded. Revision surgery was defined as (1) subsequent ipsilateral SLAP repair (CPT 29807), (2) ipsilateral arthroscopic debridement for the diagnosis of a SLAP tear (CPT 29822 or 29823, with diagnosis code 840.7), (3) subsequent ipsilateral arthroscopic biceps tenodesis (CPT 29828), (4) subsequent ipsilateral open biceps tenodesis (CPT 23430), and (5) subsequent biceps tenotomy (CPT 23405). Multivariable binomial logistic regression analysis was performed to identify risk factors for revision surgery after SLAP repair, including patient demographics/comorbidities, concomitant diagnoses, and concomitant procedures performed. Odds ratios (ORs), 95% CIs, and P values were calculated. The estimated financial impact of revision surgery was also calculated. There were 4751 patients who met inclusion and exclusion criteria. Overall, 121 patients (2.5%) required revision surgery after SLAP repair. Regression analysis identified numerous risk factors for revision surgery, including age >40 years (OR, 1.5; 95% CI, 1.2-1.8; P = .045), female sex (OR, 1.5; 95% CI, 1.3-1.8; P = .010), obesity (OR, 1.8; 95% CI, 1.5-2.2; P = .001), smoking (OR, 2.0; 95% CI, 1.6-2.4; P < .0001), and diagnosis of biceps tendinitis (OR, 3.5; 95% CI, 3.0-4.2; P < .0001) or long head of the biceps tearing (OR, 5.1; 95% CI, 4.1-6.3; P < .0001) at or before the time of surgery. Concomitant rotator cuff repair and distal clavicle excision were not significant risk factors for revision surgery. The cost of revision surgery averaged almost $9000. Risk factors for revision surgery after SLAP repair include age >40 years, female sex, obesity, smoking, and diagnosis of biceps tendinitis or long head of the biceps tearing. The diagnosis of biceps tendinitis (OR, 3.5) or long head of the biceps tearing (OR, 5.1) at or before the time of surgery was an especially significant risk factor for revision surgery. The high cost of revision surgery highlights the importance of appropriate indications to avoid the need for subsequent procedures.


Characterizing the relationship between systemic inflammatory response syndrome and early cardiac dysfunction in traumatic brain injury.
Systolic dysfunction was recently described following traumatic brain injury (TBI), and systemic inflammation may be a contributing mechanism. Our aims were to 1) examine the association between the early systemic inflammatory response syndrome (SIRS) and systolic cardiac dysfunction following TBI, and 2) describe the longitudinal change in SIRS criteria, cardiac function, and hemodynamic parameters during the first week of hospitalization. We used a secondary analysis of a prospective cohort study examining cardiac function (with transthoracic echocardiography on the first day and serially over the first week of hospitalization) in 32 moderate-severe isolated TBI patients, and quantified the admission and daily SIRS response to injury. We determined the association of admission SIRS and systolic dysfunction following TBI. Admission SIRS was present in 7 (21%) patients and was associated with systolic dysfunction on multivariable analysis (relative risk 4.01; 95% 1.16-13.79, p = .028). Both SIRS criteria and systolic cardiac function improved over the first week of hospitalization. In conclusion, early SIRS is common among patients with moderate-severe TBI, and the presence of SIRS criteria on admission is associated with systolic cardiac dysfunction following TBI.


Ureteric profilometry. A study of the ureteric pressure profile in the normal and pathologic ureter.
The ureteric pressure profile in the normal and pathologic ureter was studied. A 3F ureteric catheter was introduced through the ureteric orifice up to the mid-renal pelvis, and was connected to a pressure transducer. The catheter was pulled down to the urinary bladder and during withdrawal the pressures in the renal pelvis, uretero-pelvic junction (UPJ), ureter, ureterovesical junction (UVJ) and urinary bladder were recorded. The normal ureteric pressure profile started with a peak rise at the UPJ followed by a drop and fluctuations representing the peristaltic waves, and ended with a peak rise at the UVJ. The strictured moderately dilated ureter showed peristaltic waves with irregular rhythm and pressure amplitude, a condition we call "ureteroarryhthmia". The hugely dilated ureter exhibited no waves, i.e. a "silent" profile. The refluxing ureter with normal caliber showed an ureteroarrhythmic pressure profile, while the dilated ureter exhibited either a ureteroarrhythmic or a silent pattern. The study could define a characteristic profilometric pattern for the normal ureter. Two pathologic patterns could be identified: ureteroarrhythmic and silent. Ureteric pressure profilometry is suggested acts as a diagnostic tool in the various pathologic conditions of the ureter.


Development and validation of an ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method for the simultaneous determination of selected flavonoids in Ginkgo biloba.
A rapid and sensitive ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous determination of 13 flavonoids in leaf, stem, and fruit extracts of male and female trees of Ginkgo biloba to investigate gender- and age-related variations of flavonoids content. Chromatographic separation was accomplished on an Acquity UPLC BEH C18 column (50 mm × 2.1 mm id, 1.7 μm) in 5 min. Quantitation was performed using negative electrospray ionization mass spectrometry in multiple reaction monitoring mode. The calibration curves of all analytes showed a good linear relationship (r(2) ≥ 0.9977) over the concentration range of 1-1000 ng/mL. The precision evaluated by an intra- and interday study showed RSD ≤ 1.98% and good accuracy with overall recovery in the range from 97.90 to 101.09% (RSD ≤ 1.67%) for all analytes. The method sensitivity expressed as the limit of quantitation was typically 0.25-3.57 ng/mL. The results showed that the total content of 13 flavonoids was higher in the leaf extract of an old male Ginkgo tree compared to young female Ginkgo trees.


Embedded tags triumph in project.
The first decontamination processing experience of utilising radio frequency identification tags hermetically sealed in metal cases is described by Graham Cox, decontamination and sterile services manager, Leeds Teaching Hospitals NHS Trust.


Weight Gain in Psychiatric Inpatients: Are Interventions Making a Positive Impact?
The negative impact of weight gain is a common problem facing all patients, but it is especially concerning in the seriously mentally ill population. The literature is replete with interventions to mitigate weight gain in this population; however, most focus on outpatient settings. This study was undertaken to quantify weight gain in an inpatient setting and to assess whether instituted interventions to reduce weight gain were effective. This retrospective study analyzed weight changes in adult psychiatric inpatients with length of stay of 30 days or more. Data regarding weight changes were collected from records before (July 2005 to June 2006) a hospital-wide policy change to combat weight gain and after (July 2013 to June 2014) the changes were instituted. A total of 537 charts were reviewed. Male inpatients gained a mean of 7.61 lb and females gained 6.02 lb. The mean weight change increased for the pre and post policy change periods: 6.08 lb and 7.85 lb, respectively, a 29% increase in mean weight. This study demonstrates that weight in psychiatric inpatients hospitalized for 30 days or longer increased despite widespread changes in the hospital setting implemented to limit weight gain.


The number of analyzed lymph nodes - a prognostic factor in colorectal cancer.
The prognostic significance of the number of lymph nodes examined in surgical specimen of colorectal cancer was determined. One thousand and twenty five patients with colorectal cancer stage II and III were included in the study. These patients underwent surgery from 1991 to 1997 and were enrolled in clinical trials to evaluate the efficacy of adjuvant 5-fluorouracil (5FU) based chemotherapy. The median number of examined lymph nodes was five. Only 13% of the patients had > or = 12 lymph nodes analyzed. The number of examined lymph nodes was an independent prognostic factor for overall survival in the entire group of patients with stage II and III colorectal cancer (p=0.009). Patients with a higher number of lymph nodes examined had a longer overall survival. In stage III colorectal cancer the ratio of the number of metastatic lymph nodes to the number of examined lymph nodes (lymph node ratio, LNR) was an independent prognostic factor for overall survival. A decreasing LNR was correlated with a longer overall survival (p<0.0001). Increasing age was associated with a reduction of lymph node harvest (p=0.04). Patients with rectal cancer treated with preoperative radiotherapy had a lower number of lymph nodes analyzed compared with non-radiated (p<0.001). The number of examined lymph nodes in the surgical specimen is an independent prognostic factor for overall survival in colorectal cancer. The LNR is an independent prognostic factor in stage III colorectal cancer.


Composition and In Vitro Effects of Cultivars of Humulus lupulus L. Hops on Cholinesterase Activity and Microbial Growth.
Common hop (Humulus lupulus L.) has significant health-promoting properties. Hop cones contain resins, essential oils, proteins, polyphenols, lipids, waxes, and cellulose. Hop extracts include bioactive compounds such as polyphenolic compounds (phenolic acids, and flavonols), and chlorophylls. The aim of this study was to compare the pro-health potential of hop cone extracts obtained from three cultivars (Magnum, Lubelski, and Marynka). The results showed that the cones of Magnum cultivar demonstrated the highest biological activity. The sum of phenolic acids and flavonols in ethanol extract was the highest for this variety and was equal 4903.5 µg/g dw. Ethanol extracts of Magnum cultivars showed the highest degree of iron ion chelation (55.43-88.76%) as well as the activity against 1,1-diphenyl-2-picrylhydrazyl radical (4.75 mmol Tx/g dw). Hop cone extracts as cholinesterase inhibitors showed high potential for aqueous variants. In terms of antimicrobial activity, all investigated extracts demonstrated strong inhibition against Staphylococcus aureus and Staphylococcus epidermidis, with the Magnum cultivar showing the strongest inhibition. Owing to the biofunctional features of hop cone, it can be concluded that it is an attractive raw material with pro-health potential that can be used much more widely in food technology. However, it should be noted that toxicological tests and in vitro tests must be carried out before the raw material is used in food production.


Simultaneous multi-parametric acquisition and reconstruction techniques in cardiac magnetic resonance imaging: Basic concepts and status of clinical development.
Simultaneous multi-parametric acquisition and reconstruction techniques (SMART) are gaining attention for their potential to overcome some of cardiovascular magnetic resonance imaging's (CMR) clinical limitations. The major advantages of SMART lie within their ability to simultaneously capture multiple "features" such as cardiac motion, respiratory motion, T1/T2 relaxation. This review aims to summarize the overarching theory of SMART, describing key concepts that many of these techniques share to produce co-registered, high quality CMR images in less time and with less requirements for specialized personnel. Further, this review provides an overview of the recent developments in the field of SMART by describing how they work, the parameters they can acquire, their status of clinical testing and validation, and by providing examples for how their use can improve the current state of clinical CMR workflows. Many of the SMART are in early phases of development and testing, thus larger scale, controlled trials are needed to evaluate their use in clinical setting and with different cardiac pathologies.


Rapid dipstick test for diagnosis of urinary tract infection.
The rapid dipstick test of urine leukocyte esterase (LE) activity and nitrite has not been studied fully in pediatric clinical situations. We investigated the usefulness of the dipstick LE and nitrite test in the screening of urinary tract infection (UTI) in pediatric patients. Ninety-two fresh urine samples were obtained from children suspected of having UTI. Leukocyte esterase activity and nitrite were measured in the urine specimens read by a photometer. Leukocytes were also counted on a disposable slide. Urine samples were examined for bacteriuria by the standard culture method. The results of the urine dipstick test of LE showed a close relationship with leukocyte counts on a counting chamber. Leukocyte esterase (-) indicated leukocyte counts of less than 10/uL with a probability of 97% (58/60). Of the 22 urine samples with significant bacteriuria diagnosed by standard urine culture, the nitrite test did not detect bacteriuria in 10. While the sensitivities of the dipstick tests of nitrite (+) and LE +/- or more for the diagnosis of significant bacteriuria were 55% (12/22) and 86% (19/22), respectively, the sensitivity and negative predictive value of the combined test were 100%. These results suggest that use of the dipstick test of LE and nitrite can avoid a large part of the cost incurred by urine culture and is useful for screening UTI in children.


Confocal microscopy and molecular-specific optical contrast agents for the detection of oral neoplasia.
Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium.


Reduction of polyspermic penetration using biomimetic microfluidic technology during in vitro fertilization.
Efforts to improve the in vitro embryo production process in pigs have included modifying culture medium and number of spermatozoa inseminated in order to reduce the incidence of polyspermy. Polyspermy is a pathological condition which results in aberrant embryonic development. The microchannels are designed to more closely mimic the function of the oviduct and create a flow pattern of spermatozoa past the oocytes similar to the pattern in the oviduct. In vitro fertilization of porcine oocytes in the microchannels has produced a higher incidence of monospermic penetration (p<0.05) as compared to the oocytes fertilized in the traditional microdrop system with comparable penetration and male pronucleus formation rates. Additionally, cleavage rates of the embryos as well as development to the blastocyst stage are similar. Here we demonstrate that the biomimetic microchannel in vitro fertilization system can reduce polyspermy and, therefore, increase the number of potentially viable embryos without reducing the overall in vitro production efficiency.


MALDI-TOF MS for Rapid Analysis of Bacterial Pathogens Causing Urinary Tract Infections in the Riyadh Region.
The successful treatment of bacterial disease is relied on selecting a suitable drug based on the type of bacteria and antimicrobial susceptibility testing. The study's objective was to identify bacterial isolates from urine samples of patients from the community, followed by antimicrobial susceptibility testing of the isolated bacteria. A total of seventy urine samples were received in the clinical microbiology laboratory; out of which 18 culture-positive cultures and by direct identification using MALDI-TOF MS (Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry) were identified. Of 18 identified bacteria, 17 (94%) were pathogenic. The culture demonstrated that the major species detected in urine samples were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Aeromonas caviae. E. coli (72.2%) was the most common bacterium retrieved from urine samples followed by K. pneumoniae (16.6%). Interestingly, all the isolates, except Enterococcus faecalis, were resistant to erythromycin. The isolates 8 of 13 (61.5%) were resistant to both of the cotrimoxazole and tetracycline. We performed MLST (Multi-locus Sequence Typing) typing of 13 E. coli isolates to study their genetic relatedness and diversity. MLST typing of E. coli showed a total of nine different STs (Sequence Types), which showed the diversity among them. ST 129 was the most common ST found in three E. coli isolates. In our study, two isolates with ST 1126 and ST 1432 represented the global clonal complex 155. MALDI-TOF MS provided dependable results for identifying the bacteria up to species level from urine samples by indirect culture methods. Such local surveillances are highly recommended for empirical therapy awareness and determining isolates' level of resistance.


An antifungal coating for dental silicones composed of chlorhexidine nanoparticles.
The aims of this study were to synthesise a range of chlorhexidine-containing nanoparticles (CHX-NPs), and investigate the feasibility of using these as an antifungal coating for dental silicones. CHX-NPs were precipitated in aqueous reaction by mixing solutions of CHX digluconate with solutions of sodium triphosphate (TP), trimetaphosphate (TMP) or hexametaphosphate (HMP). CHX-NPs were deposited on commercial dental silicones by immersion coating, and these were characterised for hydrophilicity (contact angle) and water uptake (mass change). Soluble CHX elution into artificial saliva was measured using ultraviolet spectrophotometry. Antifungal efficacy against Candida albicans was investigated using a cell proliferation assay. Coating silicones with CHX-NPs did not significantly affect hydrophilicity, as assessed using water contact angle, or water uptake as assessed by mass change following 16 weeks' immersion in artificial saliva. CHX-NP-coated silicone specimens released soluble CHX into artificial saliva. The salt of CHX and the immersion time affected the rate, concentration and duration of CHX release, with CHX-HMP exhibiting a slow, sustained release and CHX-TP and CHX-TMP exhibiting a faster, more concentrated release. C. albicans metabolic activity was inhibited by presence of CHX-HMP-NPs in suspension. CHX-NPs provided a localised, controlled dose of soluble CHX at the surface of dental silicones without adversely affecting hydrophilicity or water uptake. CHX-HMP NPs provided effective antifungal control of C. albicans in a cell proliferation assay. Coating materials with these nanoparticles could be an effective way of delivering low, but clinically relevant, concentrations of chlorhexidine in the oral environment. Denture stomatitis is a common oral infection and is associated with fungal infestation of denture soft lining and obturator materials, which are often silicones such as those used here. Our study suggests that CHX-NPs may be a useful strategy in design of antifungal coatings for these materials.


Integrative spatial analysis of cell morphologies and transcriptional states with MUSE.
Spatial transcriptomics enables the simultaneous measurement of morphological features and transcriptional profiles of the same cells or regions in tissues. Here we present multi-modal structured embedding (MUSE), an approach to characterize cells and tissue regions by integrating morphological and spatially resolved transcriptional data. We demonstrate that MUSE can discover tissue subpopulations missed by either modality as well as compensate for modality-specific noise. We apply MUSE to diverse datasets containing spatial transcriptomics (seqFISH+, STARmap or Visium) and imaging (hematoxylin and eosin or fluorescence microscopy) modalities. MUSE identified biologically meaningful tissue subpopulations and stereotyped spatial patterning in healthy brain cortex and intestinal tissues. In diseased tissues, MUSE revealed gene biomarkers for proximity to tumor region and heterogeneity of amyloid precursor protein processing across Alzheimer brain regions. MUSE enables the integration of multi-modal data to provide insights into the states, functions and organization of cells in complex biological tissues.


Pulmonary arterial wedge and left atrial pressures and the site of hypoxic pulmonary vasoconstriction.
The pulmonary vascular response to breathing 5% oxygen in nitrogen was studied in anesthetized, artificially ventilated dogs. The pulmonary arterial (Pa), pulmonary arterial wedge (PW), left atrial (LAP) pressures and pulmonary blood flow (Q) were monitored. The pulmonary arterial catheter was wedged at the mid-lung level. At 10 min of hypoxia, Pa-PW pressure gradient increased while the PW-LAP gradient did not change significantly. The PW and LAP were significantly correlated during room air breathing (r=0.832) and during hypoxia (r=0.980). The calculated resistance from the pulmonary artery to the wedged catheter (Pa-Pa/Q) increased and the calculated resistance from the wedged catheter (Pa-Pw/Q) did not change significantly. These findings indicate that the mean LAP and PW pressures are not significantly different during severe hypoxia, and that the increase in pulmonary vascular resistance during hypoxia is due to constriction of the large precapillary vessels.


A novel approach to investigate recursion and iteration in visual hierarchical processing.
We describe a new method to explore recursive cognition in the visual domain. We define recursion as the ability to represent multiple hierarchical levels using the same rule, entailing the ability to generate new levels beyond those previously encountered. With this definition recursion can be distinguished from general hierarchical embedding. To investigate this recursion/hierarchy distinction in the visual domain, we developed two novel methods: The Visual Recursion Task (VRT), in which an inferred rule is used to represent new hierarchical levels, and the Embedded Iteration Task (EIT), in which additional elements are added to an existing hierarchical level. We found that adult humans can represent recursion in the visuo-spatial domain, and that this ability is distinct from both general intelligence and the ability to represent iterative processes embedded within hierarchical structures. Compared with embedded iteration, visual recursion correlated positively with other recursive planning tasks (Tower of Hanoi), but not with specific visuo-spatial resources (spatial short-term memory and working memory). We conclude that humans are able to use recursive representations to process complex visuo-spatial hierarchies and that our visual recursion task taps into specific cognitive resources. This method opens exciting opportunities to explore the relationship between visual recursion and language.


Nonlinear analyte concentration gradients for one-step kinetic analysis employing optical microring resonators.
Conventional methods to probe the binding kinetics of macromolecules at biosensor surfaces employ a stepwise titration of analyte concentrations and measure the association and dissociation to the immobilized ligand at each concentration level. It has previously been shown that kinetic rates can be measured in a single step by monitoring binding as the analyte concentration increases over time in a linear gradient. We report here the application of nonlinear analyte concentration gradients for determining kinetic rates and equilibrium binding affinities in a single experiment. A versatile nonlinear gradient maker is presented, which is easily applied to microfluidic systems. Simulations validate that accurate kinetic rates can be extracted for a wide range of association and dissociation rates, gradient slopes, and curvatures, and with models for mass transport. The nonlinear analyte gradient method is demonstrated with a silicon photonic microring resonator platform to measure prostate specific antigen-antibody binding kinetics.


Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter baumannii.
We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A. baumannii isolates that had developed polymyxin B resistance in vivo compared to isolates that had developed polymyxin B resistance in vitro.


Electrophysiologic evaluation of lumbosacral single nerve roots using compound muscle action potentials.
Transcutaneous electrical stimulation applied to the vertebral column produces compound muscle action potentials (CMAPs) from the leg muscles. Using this method, we evaluated the efferent pathways of the lumbosacral nerve roots. The subjects were 26 healthy volunteers and 31 patients with lumbar disc herniation (LDH). CMAP recordings were obtained from the bilateral vastus medialis, tibialis anterior, extensor digitorum brevis, and abductor hallucis muscles using low-output-impedance stimulation. In normal subjects, the CMAP latency increased linearly with the distance between the stimulating electrode and the recording electrode, with little difference in latency between the left and the right sides in each subject. The CMAP amplitude was significantly lower in the patients with LDH, and the latency was also prolonged when the stimulating electrode was placed above the lesion. This technique may thus be a useful noninvasive method for assessing lumbosacral nerve root function in patients with LDH.


Implementing CDS Hooks Communication in an Arden-Syntax-Based Clinical Decision Support Platform.
Arden Syntax is a Health Level Seven International standard for the development of clinical decision support (CDS) solutions. CDS Hooks is a specification for an interface to call CDS services from an electronic health record. Implementing the CDS Hooks interface into ArdenSuite, an Arden-Syntax-based CDS platform, will further enhance its interoperability with external systems. The development of this interface consisted of three parts: (1) The RESTful interface defined by CDS Hooks had to be implemented; this included the support of specifically formatted data for the input and output of the CDS functions. (2) The existing FHIR connector had to be adjusted. In CDS Hooks, a FHIR server can be defined for each CDS service call individually. In the current version of the connector, a FHIR server has to be configured in advance to call the CDS service. (3) Additional data points that did not exist previously, such as a description or hook for each CDS service, had to be collected and saved. Basic support of the CDS Hooks API was established in the ArdenSuite and tested. The FHIR connector was adapted. The missing parts for full CDS Hooks support were implemented. As a use case, we employed Hepaxpert, an interpretive system for hepatitis serology tests. CDS Hooks defines FHIR as the only data source. ArdenSuite, in contrast, offers the option of various data sources with connectors and extensions.


The sacral networks and neural pathways used to elicit lumbar motor rhythm in the rodent spinal cord.
Identification of neural networks and pathways involved in activation and modulation of spinal central pattern generators (CPGs) in the absence of the descending control from the brain is important for further understanding of neural control of movement and for developing innovative therapeutic approaches to improve the mobility of spinal cord injury patients. Activation of the hindlimb innervating segments by sacrocaudal (SC) afferent input and by specific application of neurochemicals to the sacral networks is feasible in the isolated spinal cord preparation of the newborn rat. Here we review our recent studies of sacral relay neurons with lumbar projections and evaluate their role in linking the sacral and thoracolumbar (TL) networks during different motor behaviors. Our major findings show that: (1) heterogeneous groups of dorsal, intermediate and ventral sacral-neurons with ventral and lateral ascending funicular projections mediate the activation of the locomotor CPGs through sacral sensory input; and (2) rhythmic excitation of lumbar flexor motoneurons, produced by bath application of alpha-1 adrenoceptor agonists to the sacral segments is mediated exclusively by ventral clusters of sacral-neurons with lumbar projections through the ventral funiculus.


Iatrogenic Direct Carotid-cavernous Fistula Following Mechanical Thrombectomy: A Case Report and Review of the Literature.
A carotid-cavernous fistula (CCF) is an abnormal connection between the arteries and veins of the cavernous sinus. Iatrogenic CCFs have been described as potential complications following aneurysm coiling, balloon angioplasty, and transsphenoidal surgery. In this case report, we describe a rare case of an iatrogenic direct CCF following mechanical thrombectomy (MT) for acute ischemic stroke. A 78-year-old female presented to an outside hospital with a new onset of right-sided weakness and aphasia and underwent emergency MT for a left middle cerebral artery (MCA) occlusion. The procedure was complicated by iatrogenic injury to the left cavernous internal carotid artery (ICA), which resulted in a direct high-flow CCF. The patient was transferred to our hospital and the fistula was closed with transarterial coils. Ten days later, she returned with diplopia and cranial nerve VI palsy due to residual pseudoaneurysm and was treated with a flow-diverting stent. On follow-up, the patient was neurologically intact and imaging showed no residual fistula. As the frequency of MTs performed for acute ischemic stroke continues to rise, neurointerventionalists should be aware of this potential rare complication and be prepared to manage patients who develop symptomatic CCF.


Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats.
High-altitude hypoxia causes polycythaemia and a hypercoagulable state in humans and animals. This study examines the effects of a hypobaric, hypoxic environment (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m in altitude for 1-12 weeks. After 2 weeks of exposure to HHE, platelet counts decreased significantly; after 4 weeks, the prothrombin and activated partial thromboplastin times were significantly prolonged, compared with those of control rats. In addition, individual coagulation factors (VII, IX, X, XI, and XII) were significantly decreased at 8 weeks (P < 0.05). Levels of anti-thrombin III and alpha 2-plasmin inhibitor also decreased (between 4 and 8 weeks). After 4-12 weeks of exposure to HHE, 30 of 56 rats (54 per cent) developed (i) non-bacterial thrombotic endocarditis (NBTE) or (ii) infarction of the myocardium or kidney, or both (i) and (ii). The incidence of NBTE increased from 33 per cent (5/15 rats) at 4 weeks to 100 per cent (7/7 rats) at 12 weeks. Electron microscopy showed detached endothelial cells in the mitral valves at 1 week; platelets adhered to the subendocardial matrix and platelet aggregation with thrombus formation was seen at 2 weeks of exposure. The results suggest that exposure to HHE induces a hypercoagulable state and causes an NBTE in rats that may result in consumption coagulopathy.


[Sexual traumatic events and neurotic disorders picture--sexuality-related and sexuality-unrelated symptoms].
There is an ample evidence of the impact of severe traumatic events, such as sexual abuse in childhood, on the formation of disorders--especially the non-psychotic ones: sexual, neurotic and personality. So far, an increase of the risk with the accumulation of traumatic factors has been indicated, but less attention has been paid to adverse events such as lack of sexual education, negative attitudes of the caregivers towards sexuality, etc. Assessment of the risk of such adverse events in childhood and adolescence, concerning the symptoms from the area of sexuality as well as other neurotic disorders areas. The coexistence of the earlier life circumstances and currently present symptoms was examined on the basis of KO "0" Symptom Checklist and Life Inventory, completed prior to treatment in a day hospital for neurotic disorders. In the group of 2582 females and 1347 males, there was a significant prevalence of symptoms related to sexuality, as well as of other neurotic symptoms. Patients reported traumatic events of varying frequency (from a relatively rare incest, to much more frequent sense of lack of sex education). Regression analyses showed a significant relationship between the analyzed events and symptoms, for instance, lack of sexual satisfaction in adulthood co-occurred in women with punishing for childhood sexual plays or masturbation. The other analyzed symptoms--'non-sexual', such as panic attacks, were not so clearly related to the burdensome circumstances. The presence of adverse life events concerning sexuality, not necessarily the most serious ones e.g. abuses, but such as inadequate sex education, child punishing for masturbation or sexual plays, unwanted sexual initiation, are associated with a higher occurrence of most of the analyzed symptoms in the sphere of sexuality. Weaker connection for other than sexual neurotic symptoms suggests that the impact of childhood sexual trauma is mainly focused on the area of sexual dysfunctions.


Impact of female genital mutilation on maternal and neonatal outcomes during parturition.
To evaluate the impact of female genital mutilation on parturition and to create awareness of its implication on women and neonatal health. A cross-sectional study. Tikur Anbessa, St. Paul's and Ghandhi Memorial hospitals between January and December 1997. One thousand two hundred and twenty five mothers with and 256 without FGM who have had spontaneous, term, singleton and vertex vaginal delivery. Of these, 762 (51.5%) were primipara and 719 (48.5%) of them multipara. The parameters focussed upon included age, ethnicity, parity, type of circumcision, episiotomy, stages of labour, Apgar scores and related complications. The study revealed that 82.7% of the subjects had one form of FGM. The mean ages for the circumcised and non-circumcised were 25.9 +/- 5.9 and 21.8 +/- 4.5 years, respectively. The frequently performed genital mutilation was type II (85.5%). The mothers who required an episiotomy incision for foetal and maternal indications among the circumcised accounted for 43.0% whereas it was only 24.6% for the referent group. The mean duration of labour by conventional standards is prolonged in primiparae and multiparae both in the circumcised and non-circumcised groups, though the second stage is delayed more so for the circumcised category (p<0.05). The first and tenth minute mean Apgar scores seem to be more favourable for the non-circumcised (p<0.05) but the perinatal mortality rates are quite similar. More complications in terms of perineal tears, bleeding, incontinence and febrile illnesses are registered for the FGM. The study demonstrates the negative impact of FGM more on maternal than neonatal outcomes during parturition.


Development of a Computer Adaptive Test for Depression Based on the Dutch-Flemish Version of the PROMIS Item Bank.
We developed a Dutch-Flemish version of the patient-reported outcomes measurement information system (PROMIS) adult V1.0 item bank for depression as input for computerized adaptive testing (CAT). As item bank, we used the Dutch-Flemish translation of the original PROMIS item bank (28 items) and additionally translated 28 U.S. depression items that failed to make the final U.S. item bank. Through psychometric analysis of a combined clinical and general population sample ( N = 2,010), 8 added items were removed. With the final item bank, we performed several CAT simulations to assess the efficiency of the extended (48 items) and the original item bank (28 items), using various stopping rules. Both item banks resulted in highly efficient and precise measurement of depression and showed high similarity between the CAT simulation scores and the full item bank scores. We discuss the implications of using each item bank and stopping rule for further CAT development.


Alternating versus sequential chemotherapy in small cell lung cancer. A randomized German multicenter trial.
A total of 306 patients with small cell lung cancer (SCLC) were randomized to receive chemotherapy in a sequential or alternating mode. Sequential chemotherapy consisted of eight cycles of cyclophosphamide, Adriamycin (doxorubicin), and vincristine (CAV) and alternating chemotherapy consisted of three cycles (1, 3, 5) of etoposide, vindesine, and ifosfamide (EVI); three cycles (2, 4, 6) of cisplatin, Adriamycin, and vincristine (PAV); and two cycles (7, 8) of cyclophosphamide, methotrexate, and CCNU (CMC). Responsive patients received prophylactic cranial irradiation after three cycles and chest irradiation after eight cycles of chemotherapy. No maintenance therapy was applied to patients achieving complete remission. Minimum follow-up was 2 years. Of the 302 patients evaluable, overall response rate was 59% in the sequential arm and 70% in the alternating arm. Patients treated with CAV had a complete response rate of 21% in contrast to 36% for those receiving alternating therapy. The median survival for all patients was 9.8 versus 11.3 months, for limited disease 11.1 versus 13.4 months, and for extensive disease 8.9 versus 9.9 months, all in favor of the alternating treatment. Two-year survival rate for all patients was 6% versus 9%, for limited disease 11% versus 14%, and for extensive disease 3% versus 6%, all preferring the alternating treatment mode. Progression-free survival demonstrated a strong correlation to the extent of response irrespective of the treatment regimen applied. Toxicity included 11 lethal and 8 life-threatening complications with a higher frequency in the alternating treatment arm. These results suggest that alternating treatment of SCLC with different drug combinations is more effective than sequential application of CAV.


Influence of two vehicles for zinc oxide on zinc absorption through intact skin and wounds.
The zinc absorption from zinc oxide applied on intact and on wounded skin were compared using two vehicles: one containing gum rosin and the other containing hydrocolloids. After treatment of intact human forearm skin for 48 h, the zinc concentration was more than two-fold higher in the epidermis and interstitial fluid beneath the rosin vehicle than beneath the hydrocolloid vehicle. Systemic absorption of zinc through full-thickness rat skin wounds treated with zinc oxide increased significantly, however, with the use of the hydrocolloid vehicle. In vitro experiment indicated that the solubility of zinc oxide in buffered saline (pH 7.4) increased in the presence of hydrocolloids. The study, thus, indicates that rosin in combination with zinc oxide enhances the transport of zinc through intact human skin, and that hydrocolloids promote the zinc absorption through wounds.


Clinical experience with theophylline. Relarionships between dosage, serum concentration, and toxicity.
Relationships between theophylline dosage, serum theophylline concentration, and theophylline toxicity were evaluated retrospectively in 47 hospitalized adults. The amount of theophylline administered daily varied more than sixfold, from 6 to 38 mg/kg. The serum theophylline concentrations, however, varied 24-fold from 2 to 49 mug/ml. The relationship between daily dosage and serum concentration was unpredictable in an individual patient. Fourteen patients (30%) had a toxic reaction to theophylline. Toxic symptoms, which were not always gastrointestinal, occurred commonly with serum concentrations over 25 mug/ml but were not noted with concentrations below 15 mug/ml. High serum theophylline concentrations and a toxic reaction developed just as often with the oral route as when the drug was given intravenously. In six patients, measurement of serum theophylline concentration disclosed subtherapeutic concentrations. Serum theophylline determination appears to be important clinically in guiding effective and safe usage of theophylline.


Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism.
Human CD4 T cells are constantly exposed to IL-12 during infections and certain autoimmune disorders. The current paradigm is that IL-12 promotes the differentiation of naïve CD4 T cells into Th1 cells, but recent studies suggest IL-12 may play a more complex role in T cell biology. We examined if exposure to IL-12 alters human CD4 T cell responses to subsequent TCR stimulation. We found that IL-12 pretreatment increased TCR-induced IFN-γ, TNF-α, IL-13, IL-4 and IL-10 production. This suggests that prior exposure to IL-12 potentiates the TCR-induced release of a range of cytokines. We observed that IL-12 mediated its effects through both transcriptional and post-transcriptional mechanisms. IL-12 pretreatment increased the phosphorylation of AKT, p38 and LCK following TCR stimulation without altering other TCR signaling molecules, potentially mediating the increase in transcription of cytokines. In addition, the IL-12-mediated enhancement of cytokines that are not transcriptionally regulated was partially driven by increased oxidative metabolism. Our data uncover a novel function of IL-12 in human CD4 T cells; specifically, it enhances the release of a range of cytokines potentially by altering TCR signaling pathways and by enhancing oxidative metabolism.


Preliminary validation of the Klenico diagnostic software self-report module through comparison with the diagnostic gold standard in an outpatient routine clinical sample.
Inaccuracy in current diagnostic procedures for mental disorders can lead to misdiagnosis and increase the burden on the healthcare system. Therefore, Klenico, a diagnostic software designed to support comprehensive and efficient clinical diagnostic procedures that is easy to apply in everyday clinical practice, was developed. This study aimed to take the first step toward validating the Klenico self-report module. Data of 115 patients from a German psychotherapeutic outpatient clinic were included in this study. Criterion validity was tested by comparing Klenico with the diagnoses based on the structured clinical interview for DSM-IV (SCID). Construct validity was investigated by comparing Klenico with commonly used self-reporting questionnaires. The results showed that most of the Klenico disorder domains were able to differentiate between corresponding diagnoses and other diagnoses, confirming criterion validity. Construct validity was demonstrated by high correlations with the compared convergent questionnaire scales and non-significant or low correlations with most of the divergent scales. These preliminary results demonstrate the psychometric properties of the Klenico self-report module and imply that the Klenico system has high potential to improve the accuracy of diagnostic procedures in everyday clinical practice.


Patient participation in EHR benefits.
Patient participation in EHR creation can significantly broaden the range of healthcare information in the record and, ultimately, improve clinical decision support. The care with which patient-authored information is handled, however, must equal the care devoted to clinician data entry and review. Web-based access, self-service management, consent delegation and agent permissions management are just a few of the features that will encourage active and positive patient involvement with their healthcare records and with their own health management.


B cell development in the chicken.
A central feature of the vertebrate humoral immune system is that an organism must have a vast repertoire of antibodies to protect it against foreign pathogens. Chickens create a diverse immunological repertoire by intrachromosomal gene conversion of the single variable gene segments of the Ig heavy and light chain genes. This diversification process has been shown to require the bursa of Fabricius. Immature cells commit to the B cell lineage by rearranging their Ig genes prior to migration to the bursa. Recent work has suggested that the ability of a developing B cell to migrate to the bursa may depend on the expression of the carbohydrate structure sialyl Lewis x. Developing B cells in the spleen with the ability to migrate to the bursa have been shown to express sialyl Lewis x. Cells expressing sialyl Lewis x begin appearing in the bursa anlage between embryonic Days 10 and 12. These sialyl Lewis x-positive cells appear to form the nascent bursal follicles and are induced to proliferate. Coincident with the time that B cells initiate the gene conversion process, cells cease expressing sialyl Lewis x and begin expressing the related surface epitope Lewis x. As cells mature further, they undergo another phenotypic change and switch from expressing high levels of Lewis x to become Lewis x-low. At the same time that Lewis x-low cells accumulate in the bursa, cells with this phenotype begin to appear in the spleen. These phenotypic markers may be useful in identifying chicken B cells at different developmental stages.


RNA-directed DNA polymerase and virus-induced leukemia in mice.
Rifamycin antibiotics, which inhibit RNA-directed DNA polymerase of Rauscher leuckemia virus, prevent the leukemogenic activity of the virus, and the effect of leukemogenesis correlates with the magnitude of inhibition of the purified enzyme. This inhibition of enzyme activity by rifamycin SV derivatives is due to a relatively tight binding between the enzymes and the inhibitors, yet the binding can be reversed by nonionic detergent. The results of this study suggest that RNA-directed DNA polymerase is essential for induction of leukemia by exogenous virus and correlate with the previous observation that the same derivatives block viral transformation in vitro.


Low oxidation state iron(0), iron(I), and ruthenium(0) dinitrogen complexes with a very bulky neutral phosphine ligand.
The synthesis of a series of iron and ruthenium complexes with the ligand P(2)P3(Cy), P(CH2CH2PCy2)3 is described. The iron(0) and ruthenium(0) complexes Fe(N2)(P(2)P3(Cy)) (1) and Ru(N2)(P(2)P3(Cy)) (2) were synthesized by treatment of [FeCl(P(2)P3(Cy))](+) and [RuCl(P(2)P3(Cy))](+) with an excess of potassium graphite under a nitrogen atmosphere. The Fe(I) and Ru(I) species [Fe(N2)(P(2)P3(Cy))](+) (3) and RuCl(P(2)P3(Cy)) (4) were synthesized by treatment of [FeCl(P(2)P3(Cy))](+) and [RuCl(P(2)P3(Cy))](+) with 1 equiv of potassium graphite under a nitrogen atmosphere. The cationic dinitrogen species [Fe(N2)H(P(2)P3(Cy))](+) (6) and [Ru(N2)H(P(2)P3(Cy))](+) (7) were formed by treatment of 1 and 3, respectively, with 1 equiv of a weak organic acid. The iron(II) complex Fe(H)2(P(2)P3(Cy)) (5) was also synthesized and characterized. Complexes [RuCl(P(2)P3(Cy))][BPh4], 1, 2, 3[BPh4], 4, 5, 6[BF4], and 7[BF4] were characterized by X-ray crystallography. The Fe(I) and Ru(I) complexes 3 and 4 were characterized by electron paramagnetic resonance (EPR) spectroscopy, and the Fe(I) complex has an EPR spectrum typical of a metal-centered radical.


Ease of use, safety, and efficacy of integra bilayer wound matrix in the treatment of diabetic foot ulcers in an outpatient clinical setting: a prospective pilot study.
Integra bilayer wound matrix (IBWM) is a bilayer skin replacement system composed of a dermal regeneration layer and a temporary epidermal layer. It is used to treat various types of deep, large wounds via an inpatient procedure in an operating room. We sought to determine ease of use and effectiveness of IBWM in an outpatient clinical setting when treating diabetic foot ulcers. In addition, no epidermal autografting was performed in conjunction with the IBWM after silicone release, as is common in the inpatient setting. This 12-week, single-arm, prospective pilot study was conducted in three outpatient clinics. Weekly evaluations included monitoring the wound for signs of infection during the 12-week follow-up phase. Eleven patients with diabetic foot ulcers who met the inclusion and exclusion criteria were enrolled. One patient was discontinued from the study owing to noncompliance leading to a serious adverse event. Therefore, ten patients who received the study intervention were included in the per-protocol population reported herein. The mean patient age was 60.6 years, with an average 11-year history of diabetes mellitus. Each ulcer was located on the plantar aspect of the foot. No infection was reported during the study. Patients treated with IBWM showed progressive wound healing over time: the greatest mean wound reduction was approximately 95% in week 12. Seven of ten patients (70%) achieved complete wound closure by week 12. No recurrent ulcers were reported during follow-up. These results are consistent with the hypothesis that IBWM is easy to use, safe, and effective when used on diabetic foot ulcers in an outpatient clinical setting without the secondary procedure of autografting for closure.


Bacterial contamination of the pressure receiver of a vitrectomy machine.
On a routine sterility check, the authors found bacteria in their vitrectomy machine. Serratia marcescens was detected in the pressure receiver of a roller pump vitrectomy machine. The authors improved the machine by installing a millipore filter in front of the receiver that prevents bacteria from entering it without interfering with the pressure measurements. The origin of Serratia was probably a patient with endophthalmitis who was operated on long before the routine check. Although this appears to be the first report of a bacterial contamination of a vitrectomy machine, the results of testing show that this situation is indeed possible. The authors strongly recommend routine checks of the equipment and suggest mounting an antibacterial filter.


Optimal blood pressure in patients with peripheral artery disease following endovascular therapy.
This study examined the associations between blood pressure (BP) and event incidence to define optimal BP after endovascular therapy (EVT) in patients who underwent EVT. BP was monitored every 6 months for 5 years, and the patients were divided into two groups by average BP: ≥ 140/90 mmHg and < 140/90 mmHg. The association of BP with several events was examined. Although no significant differences in total mortality were observed between the groups, restenosis rates were significantly higher among patients who did not achieve target BP (36.2%) than among those who did (18.2%) (p < 0.01). The percentage of patients with glycosylated haemoglobin > 7.0% was significantly higher among those who did not achieve target BP in the restenosis group (42.9%) than in the other group (10.8%) (p < 0.01). In the restenosis group, there was a significantly higher percentage of patients taking metformin (p < 0.01) than in the other group. Metformin seemed to be administered to patients with more severe diabetes mellitus. In conclusion, it is important to manage hypertension and diabetes to prevent restenosis after EVT.


The effect of maternal nutritional variables on birthweight outcomes of infants born to Sherpa women at low and high altitudes in Nepal.
A prospective, longitudinal study was conducted in Nepal to investigate the effects of maternal nutrition on the pregnancy outcome of Sherpa women living at low and high altitudes. It was hypothesized that variation in nutrition and energy expenditure of pregnant women would correlate with variation in infant birthweight. Anthropometric dimensions, energy consumption and expenditure, and demographic and migration information were collected on a large sample of women living in two regions of Nepal: the Khumbu region (3480-3930 m) and Kathmandu (1330 m). This paper reports findings for a subset of the sample; 17 women at low altitude and 21 women at high altitude who became pregnant and were followed during pregnancy. The results showed no significant differences for mean birthweights between the low (X = 3069 ± 341 grams) and high (X = 3099 ± 483 grams) altitude samples. Furthermore, larger birthweights were associated with larger weight gains during pregnancy for the high altitude sample. A stepwise regression analysis found a negative association between high energy expenditures during the second trimester and infant birthweight, but positive associations were found between third trimester calcium and second trimester protein intakes and birthweight. Prepregnancy BMI and stature were associated positively with infant birthweight, suggesting that good nutritional status prior to pregnancy may play an important role in pregnancy outcome for this population. Am. J. Hum. Biol. 9:751-763, 1997. © 1997 Wiley-Liss, Inc.


Orbital cysts lined with both stratified squamous and columnar epithelia: a late complication of silicone implants.
Two patients presented with orbital cysts 5 and 7 years after orbital blowout fracture repair with silicone plate implants. The orbital cysts caused significant exophthalmos and restriction in ocular motility. Surgical excision revealed thick-walled cysts that were displacing the globe and encapsulating the silicone implant. On histopathologic examination, the cysts were lined with both stratified squamous and ciliated columnar (respiratory) epithelia. We propose that squamous and respiratory epithelial cells may have been deposited during surgery from the conjunctival and sinus epithelia, respectively. This case series illustrates that although an uncommon complication, epithelium-lined inclusion cysts may develop several years after orbital fracture repair with a silicone implant. A transconjunctival surgical approach is a possible risk factor.


Chromatin subunits elicit species-specific antibodies against nucleoprotein antigenic determinants.
Nucleosomes composed of 195 base pairs of DNA associated with histones H2A, H2B, H3, and H4 purified from chicken erythrocyte nuclei were used to elicit antibodies in rabbits. Specific serological reaction between the antisera and the nucleosomes is demonstrated by immunodiffusion, immunofluorescence, microcomplement fixation, solid-phase radioimmunoassay, immunosedimentation, and polyacrylamide gel electrophoresis of 5'-32P end-labeled nucleosomes. The antisera did not react with DNA extracted from these nucleosomes, core histones, or the cross-linked histone octamer from chicken erythocytes, calf thymus total histones, or chromosomal proteins HMG-1 or HMG-17. Nucleosome antigenicity was not affected by redigestion with micrococcal nuclease. Digestion with DNase I brought about 50% loss of reactivity while digestion with trypsin or proteinase K resulted in total loss of activity. The antisera reacted strongly with trimer, dimer, and monomer nucleosomes as well as with the core particle (145 base pairs of DNA) and subnucleosome (greater than 145 base pairs) obtained from chicken. It reacted less well with nucleosomes obtained from HeLa cells and was almost totally devoid of activity against chromatin particles obtained from rat liver or wheat germ. Experiments employing the technique of transferring proteins from a polyacrylamide gel to diazobenzyloxymethyl paper and visualization of antigens by autoradiography excluded the possibility that the serum contains antibodies against tissue-specific antigens which are found in small amounts but are very immunogenic. It is concluded that most of the anitbodies in the sera are directed against nucleoprotein antigenic determinants composed of the N-terminal portion of the histones and segments of DNA. Antibody binding is dependent on contact between the histone and DNA segments and is independent of the integrity of the entire nucleosome. Thus, certain histone DNA contacts remain intact even though the structure of the nucleosome has been disrupted.


Kernel-based geographically and temporally weighted autoregressive model for house price estimation.
Spatiotemporal nonstationarity and autocorrelation are two crucial points in modeling geographical data. Previous studies have demonstrated that geographically and temporally weighted autoregressive (GTWAR) model accounts for both spatiotemporal nonstationarity and autocorrelation simultaneously to estimate house prices. Therefore, this paper proposes a kernel-based GTWAR (KBGTWAR) model by incorporating the basic principle of support vector machine regression into spatially and temporally varying coefficients model. The efficacy of KBGTWAR model is demonstrated through a case study on housing prices in the city of Shenzhen, China, from year 2004 to 2008. Comparing the existing models, KBGTWAR model obtains the lowest value for the residual sum of squares (RSS) and the highest value for the coefficient of determination R2. Moreover, KBGTWAR model improves the goodness of fit of the existing GTWAR model from 12.0 to 4.5 in terms of RSS, from 0.914 to 0.968 in terms of R2 and from 3.84 to 4.45 in terms of F-statistic. The results show that KBGTWAR model provides a comparatively high goodness of fit and sufficient explanatory power for both spatiotemporal nonstationarity and autocorrelation. The results of this study demonstrate that the proposed KBGTWAR model can be used to effectively formulate polices for real estate management.


Evaluation of antioxidant capacity of cereal brans.
Several oat brans (crunchy oat bran, oat bran alone, and oat breakfast cereal) and wheat brans (wheat bran alone, wheat bran powder, wheat bran with malt flavor, bran breakfast cereal, tablet of bran, and tablet of bran with cellulose) used as dietary fiber supplements by consumers were evaluated as alternative antioxidant sources (i) in the normal human consumer, preventing disease and promoting health, and (ii) in food processing, preserving oxidative alterations. Products containing wheat bran exhibited higher peroxyl radical scavenging effectiveness than those with oat bran. Wheat bran powder was the best hydroxyl radical (OH*) scavenger. In terms of hydrogen peroxide (H2O2) scavenging, wheat bran alone was the most effective, while crunchy oat bran, oat bran alone, and oat breakfast cereal did not scavenge H2O2. The shelf life of fats (obtained by the Rancimat method for butter) increased most in the presence of crunchy oat bran. When the antioxidant activity during 28 days of storage was measured by the linoleic acid assay, all of the oat and wheat bran samples analyzed showed very good antioxidant activities. The Trolox equivalent antioxidant capacity (TEAC) assay was used to provide a ranking order of antioxidant activity. The wheat bran results for TEAC (6 min), in decreasing order, were wheat bran powder > wheat bran with malt flavor > or = wheat bran alone > or = bran breakfast cereal > tablet of bran > tablet of bran with cellulose. The products made with oat bran showed lower TEAC values. In general, avenanthramide showed a higher antioxidant level than each of the following typical cereal components: ferulic acid, gentisic acid, p-hydroxybenzoic acid, protocatechuic acid, syringic acid, vanillic acid, vanillin, and phytic acid.


Identification of QTLs for 14 Agronomically Important Traits in Setaria italica Based on SNPs Generated from High-Throughput Sequencing.
Foxtail millet (Setaria italica) is an important crop possessing C4 photosynthesis capability. The S. italica genome was de novo sequenced in 2012, but the sequence lacked high-density genetic maps with agronomic and yield trait linkages. In the present study, we resequenced a foxtail millet population of 439 recombinant inbred lines (RILs) and developed high-resolution bin map and high-density SNP markers, which could provide an effective approach for gene identification. A total of 59 QTL for 14 agronomic traits in plants grown under long- and short-day photoperiods were identified. The phenotypic variation explained ranged from 4.9 to 43.94%. In addition, we suggested that there may be segregation distortion on chromosome 6 that is significantly distorted toward Zhang gu. The newly identified QTL will provide a platform for sequence-based research on the S. italica genome, and for molecular marker-assisted breeding.


Fundamental frequency during couple conflict: an analysis of physiological, behavioral, and sex-linked information encoded in vocal expression.
The human voice is one of the sounds most frequently experienced by human beings. During couple conflict, higher fundamental frequency (f0), a physical property of human speech, has been linked to an increased risk of divorce, less beneficial response to couple therapy, and higher levels of dysfunctional communication behavior. F0 is generally considered to be a measure of emotional arousal, but it is not currently clear whether this interpretation is appropriate for understanding spouses' f0 during couple interaction. The goal of the current article is to clarify what forms of information are encoded in f0 during couple conflict by examining the relations between f0 range, physiological variables, and communication behavior during the conflict discussions of 67 German couples. In line with evolutionary models of speech production, associations emerged in the expected directions between f0 and: (a) physiological variables (e.g., heart rate, blood pressure, and cortisol); (b) self-reported communication behavior; and (c) observationally coded communication behavior. Additionally, simultaneous examination of physiological variables and observationally coded communication behaviors revealed that associations between both sets of variables and f0 range were largely independent of one another. Furthermore, women's range of f0 was significantly greater than men's range of f0. With regard to social signaling theories, f0 range can be understood as a nonverbal transmission of distress. Implications for future research on and use of f0 are discussed.


Advancing genetic and genomic technologies deepen the pool for discovery in Xenopus tropicalis.
Xenopus laevis and Xenopus tropicalis have long been used to drive discovery in developmental, cell, and molecular biology. These dual frog species boast experimental strengths for embryology including large egg sizes that develop externally, well-defined fate maps, and cell-intrinsic sources of nutrients that allow explanted tissues to grow in culture. Development of the Xenopus cell extract system has been used to study cell cycle and DNA replication. Xenopus tadpole tail and limb regeneration have provided fundamental insights into the underlying mechanisms of this processes, and the loss of regenerative competency in adults adds a complexity to the system that can be more directly compared to humans. Moreover, Xenopus genetics and especially disease-causing mutations are highly conserved with humans, making them a tractable system to model human disease. In the last several years, genome editing, expanding genomic resources, and intersectional approaches leveraging the distinct characteristics of each species have generated new frontiers in cell biology. While Xenopus have enduringly represented a leading embryological model, new technologies are generating exciting diversity in the range of discoveries being made in areas from genomics and proteomics to regenerative biology, neurobiology, cell scaling, and human disease modeling.


Branching pattern in CT scans of mucin producing carcinoma metastases to the liver.
Intrahepatic calcification occurring in a branching pattern with a periportal distribution has not previously been described in hepatic metastases. We report a patient with a unique branching pattern of calcified hepatic metastases. There were no low density masses associated with the calcifications as is usually seen in calcified metastases to the liver demonstrated by computed tomography.


Controlling malignant melanoma. A focus on pediatricians.
There is evidence that the mortality rate associated with malignant melanoma can be decreased by early identification of the risk factors for melanoma and precursor lesions and by reducing sun exposure in young patients at higher risk. Many of the risk factors for malignant melanoma are seen in the pediatric age group. To determine pediatricians' awareness of risk factors for melanoma and their ability to recognize the precursors of melanoma, we studied three departments of pediatrics--at an urban and a suburban medical center and a medical college. Ninety-six members of the audience, which included full-time faculty, practicing pediatricians, and pediatrics residents, responded to questionnaires before and after a presentation on the risk factors for melanoma. Based on the results of the questionnaires, this group of pediatricians believed that they were not sufficiently knowledgeable about the risk factors for melanoma and did not routinely examine their patients for these risk factors or counsel them on proper sunlight protection. These findings indicate a need for making pediatricians aware of the risk factors for melanoma and of the critical role they play in decreasing the incidence and mortality rate associated with this disease.


Management of chloroquine-resistant Plasmodium falciparum malaria in a pregnant Ethiopian immigrant--a case report.
Plasmodium falciparum malaria is infrequently recognized in Israel as a cause of infection during pregnancy. We expect that with increasing frequency physicians in Israel will confront patients with malaria. Special concern should be given to malaria in pregnancy because of its serious complications. Thus, prompt diagnosis and treatment are essential. While chloroquine is safe for use in pregnancy, drug resistance is common, especially with Plasmodium falciparum. There is concern about the safety of other antimalarial agents during pregnancy. We recently observed a case of chloroquine-resistant Plasmodium falciparum malaria during pregnancy in a new immigrant primigravida from Ethiopia. Malaria in patients from endemic regions is less severe than in nonimmune hosts. Therefore, we elected to follow the patient's parasitemia periodically without additional antimalarial treatment until after delivery.


Visual saliency and semantic incongruency influence eye movements when inspecting pictures.
Models of low-level saliency predict that when we first look at a photograph our first few eye movements should be made towards visually conspicuous objects. Two experiments investigated this prediction by recording eye fixations while viewers inspected pictures of room interiors that contained objects with known saliency characteristics. Highly salient objects did attract fixations earlier than less conspicuous objects, but only in a task requiring general encoding of the whole picture. When participants were required to detect the presence of a small target, then the visual saliency of nontarget objects did not influence fixations. These results support modifications of the model that take the cognitive override of saliency into account by allowing task demands to reduce the saliency weights of task-irrelevant objects. The pictures sometimes contained incongruent objects that were taken from other rooms. These objects were used to test the hypothesis that previous reports of the early fixation of congruent objects have not been consistent because the effect depends upon the visual conspicuity of the incongruent object. There was an effect of incongruency in both experiments, with earlier fixation of objects that violated the gist of the scene, but the effect was only apparent for inconspicuous objects, which argues against the hypothesis.


Comparison of lower limb lifting and squeeze exsanguination before tourniquet inflation during total knee arthroplasty.
During total knee arthroplasty(TKA), tourniquet is widely used by most surgeons whereas the optimal application is still controversial. With this prospective randomized controlled study, we intend to investigate the effect of lower limb lifting and squeeze exsanguination methods on clinical outcomes in a series of TKAs. Prospectively enrolled a total of 236 TKA patients from March, 2012 to November, 2016. Of which 118 patients randomly constitute Group A with lower limb lifting exsanguination technique; and the other 118 patients comprise Group B with squeeze exsanguination method. A year's follow-up measurements were recorded in detail for analysis. The pre-tourniquet time of Group A was significantly shorter than that in Group B (P < 0.001). Significant difference was found on skin tension blister, 3 happened in Group A and 11 happened in Group B (P = 0.031), which resulted in a difference in total complications (P = 0.039). The VAS score was significantly lower in Group A at one and seven days postoperatively, P < 0.001 and P = 0.011, respectively. No significant differences were found regarding all other clinical outcome measurements. The lower limb lifting exsanguination is a safe and effective technique. Compared with squeeze exsanguination method, it could decrease the incidence of skin tension blister and alleviate early postoperative pain reaction, no additional risks occurred regarding other clinical outcomes. Thus, it might have the potentiality to be commonly utilized in TKA procedure. ClinicalTrials.gov Identifier: ChiCTR1800020471. Registered on 31 December 2018 Retrospectively registered.


Analysis of nitrogen-fixing members of the epsilon subclass of Proteobacteria in salt marsh sediments.
Based on phylogenetic analysis of clones retrieved from two nifH gene clone libraries that were created using cDNA from suboxic sediment samples obtained from areas densely vegetated with the high-salt marsh plant Spartina patens, a primer set was designed to target nitrogen-fixing bacteria with sequence similarities to members of the epsilon subclass of Proteobacteria. Nested PCR, denaturing gel electrophoresis, and subsequent sequence analysis of reamplified fragments confirmed the specificity of the primer set by retrieving nifH sequences of only putative members of the epsilon subclass of Proteobacteria, all of which were characterized by a highly divergent 27- or 36-bp insertion in both DNA and cDNA.


Both saturated and n-6 polyunsaturated fat diets reduce phosphorylation of insulin receptor substrate-1 and protein kinase B in muscle during the initial stages of in vivo insulin stimulation.
Our aim was to determine the importance of changes in phosphorylation of key insulin signaling intermediates in the insulin resistance observed in skeletal muscle of rats fed diets high in saturated or n-6 polyunsaturated fat. We used phospho-specific antibodies to measure the time course of phosphorylation of key components of the insulin signaling pathway by immunoblotting during the initial stages of a physiological elevation in the circulating insulin concentration. The phosphorylation of insulin receptor at Tyr1162/1163 (IR Tyr1162/1163) increased over 20 min of insulin infusion, whereas the downstream phosphorylation of insulin receptor substrate-1 Tyr612 (IRS-1 Tyr612) peaked at 5 min and declined thereafter. Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the insulin signal despite a constant level of insulin stimulation. In muscle from rats fed high n-6 polyunsaturated or saturated fat diets, however, there was no insulin-stimulated increase in IRS-1 Tyr612 phosphorylation and a temporal difference in PKB Ser473 phosphorylation despite no difference in IR Tyr1162/1163 phosphorylation, IRS-1 Tyr895 phosphorylation, and ERK phosphorylation. These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet.