The prediction of virus mutation using neural networks and rough set techniques.
Viral evolution remains to be a main obstacle in the effectiveness of antiviral treatments. The ability to predict this evolution will help in the early detection of drug-resistant strains and will potentially facilitate the design of more efficient antiviral treatments. Various tools has been utilized in genome studies to achieve this goal. One of these tools is machine learning, which facilitates the study of structure-activity relationships, secondary and tertiary structure evolution prediction, and sequence error correction. This work proposes a novel machine learning technique for the prediction of the possible point mutations that appear on alignments of primary RNA sequence structure. It predicts the genotype of each nucleotide in the RNA sequence, and proves that a nucleotide in an RNA sequence changes based on the other nucleotides in the sequence. Neural networks technique is utilized in order to predict new strains, then a rough set theory based algorithm is introduced to extract these point mutation patterns. This algorithm is applied on a number of aligned RNA isolates time-series species of the Newcastle virus. Two different data sets from two sources are used in the validation of these techniques. The results show that the accuracy of this technique in predicting the nucleotides in the new generation is as high as 75 %. The mutation rules are visualized for the analysis of the correlation between different nucleotides in the same RNA sequence.


The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis.
Urinary tract infections are among the most common types of infections and give rise to inflammation with pain as one of the main symptoms. The herbal medicinal product Canephron® N contains BNO 2103, a defined mixture of pulverized rosemary leaves, centaury herb, and lovage root, and has been used in the treatment of urinary tract infections for more than 25 years. To test the hypothesis that BNO 2103 reduces pain in cystitis and prostatitis by virtue of anti-inflammatory properties, and to reveal potential mechanisms underlying the anti-inflammatory features. BNO 2103 was studied for anti-inflammatory and analgesic properties in three animal models in vivo, and the mode of action underlying the anti-inflammatory features was investigated in human leukocytes and cell-free assays in vitro. To assess the anti-inflammatory and analgesic efficacy of BNO 2103 we employed cyclophosphamide-induced cystitis and carrageenan-induced prostatitis in rats, and zymosan-induced peritonitis in mice. Human neutrophils and monocytes as well as isolated human 5-lipoxygenase and microsomal prostaglandin E2 synthase-1-containing microsomes were utilized to assess inhibition of leukotriene and/or prostaglandin E2 production by HPLC and/or ELISA. When given orally, BNO 2103 reduced inflammation and hyperalgesia in experimental cystitis in rats, while individual components of BNO 2103 also reduced hyperalgesia. Furthermore, BNO 2103 reduced hyperalgesia in rats with carrageenan-induced prostatitis. Cell-based and cell-free studies implicate inhibition of prostaglandin E2 and leukotriene B4 biosynthesis as potential mechanisms underlying the analgesic and anti-inflammatory effects. Our data support the hypothesis that BNO 2103 reduces pain by virtue of its anti-inflammatory properties, possibly related to suppression of prostaglandin E2 and leukotriene B4 formation, and suggest that this combination has the potential to treat clinical symptoms such as inflammatory pain. Thus BNO 2103 may represent an alternative to reduce the use of antibiotics in urinary tract infections.


Asthma in the elderly and late-onset adult asthma.
Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis, and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be underdiagnosed and undertreated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (ie, corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population.


Modeling third-harmonic generation from layered materials using nonlinear optical matrices.
A matrix approach is formulated to describe third-harmonic (TH) generation in stacked materials in the small signal limit, in both transmission and reflection geometries. The model takes into account the contribution from the substrate to the total generated TH, interference of fundamental and nonlinear fields inside the stack, the nonlinear signal generation in forward and backward direction, the beam profile of the focused incident beam in the substrate, and the finite spectrum associated with short laser pulses. The model is applied to design stacks of thin films for efficient TH generation.


Interaction of a Mycobacterium tuberculosis repetitive DNA sequence with eukaryotic proteins.
Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. Its intracellular residence raises the possibility that bacterial nucleic acids might interact with key host proteins and contribute to the pathophysiology of infection. To test this hypothesis, we searched for motifs closely resembling eukaryotic transcription factor binding sites in the M. tuberculosis H37Rv genome and found activator protein-2 and zinc finger protein-5 binding motifs in a 36-nucleotide repetitive mycobacterial DNA sequence (RPT1). RPT1 bound specifically to nuclear extract proteins from U937, A549, and HeLa cells in electrophoretic mobility shift assays but not to activator protein-2. Several nuclear and cytosolic proteins showing at least partial binding specificity for RPT1 were isolated from U937 and A549 cells by pull-down assays, including Ku70 (DNA-dependent protein kinase subunit) and poly(ADP-ribose) polymerase-1. RPT1 also specifically activated DNA-dependent protein phosphorylation. These results suggest that mycobacterial nucleic acid fragments may interact specifically with eukaryotic regulatory proteins which might contribute to bacterial life-cycle maintenance.


Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers.
The expanding and established literature that correlates tumor infiltrating lymphocytes (TILs) with outcomes of patients with solid tumors has contributed greatly to the appreciation of the interaction between the host immune system with neoplastic growth. This analysis has been limited to specific tumors, such as melanoma and ovarian cancer, and our understanding of TILs in relation to many other malignancies has yet to be explored. We review one less well studied malignancy, head and neck squamous cell carcinoma (HNSCC), and the initial attempts to examine the impact of TILs on outcomes of these patients. To provide a context for the discussion of TILs and HNSCC, we first review the epidemiology, relevant head and neck anatomy, immune responses and discuss the historical data regarding the unique immunobiology of these tumors. Finally, with this perspective, we describe our current understanding of tumor infiltrating lymphocyte data for head and neck cancers.


Gm and Km allotypes and typhoid fever.
Gm and Km allotypes of immunoglobulins were determined in children with typhoid fever (Cases), in children without infectious diseases (Con-1), and in children with fever but no Salmonella in their blood or bone marrow (Con-2). Children were sampled from the urban population of Santiago; and they belonged to the low and low-middle socioeconomic strata. Cases had a higher frequency of [f;(-);b1,b3 or 3;(-);5,13] G1m, G2m, G3m haplotype than Con-1 and Con-2. Con-1 and Con-2 did not differ in their Gm haplotype or Km allele frequencies, but they differed in phenotype distribution. Con-1 deviated from Hardy-Weinberg equilibrium for Km due to a lack of Km 1-1 homozygotes. The relationship among these results, the ethnic origin of Chileans, and the differential susceptibility to typhoid fever are discussed.


c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP.
Genetic knock out of the transcriptional co-repressor carboxyl-terminal-binding protein (CtBP) in mouse embryonic fibroblasts results in up-regulation of several genes involved in apoptosis. We predicted, therefore, that a propensity toward apoptosis might be regulated through changes in cellular CtBP levels. Previously, we have identified the homeodomain-interacting protein kinase 2 as such a regulator and demonstrated that HIPK2 activation causes Ser-422 phosphorylation and degradation of CtBP. In this study, we found that c-Jun NH2-terminal kinase 1 activation triggered CtBP phosphorylation on Ser-422 and subsequent degradation, inducing p53-independent apoptosis in human lung cancer cells. JNK1 has previously been linked to UV-directed apoptosis. Expression of MKK7-JNK1 or exposure to UV irradiation reduced cellular levels of CtBP via a proteasome-mediated pathway. This effect was prevented by JNK1 deficiency. In addition, sustained activation of the JNK1 pathway by cisplatin similarly triggered CtBP degradation. These findings provide a novel target for chemotherapy in cancers lacking p53.


Effect of selective posterior rhizotomy on transverse myelitis in a patient with systemic lupus erythematosus.
This report describes the case of a 26-yr-old man experiencing transverse myelitis, a rare but serious complication of systemic lupus erythematosus occurring in less than 1% of patients with systemic lupus erythematosus, 4 yr after the onset of systemic lupus erythematosus. Significant neurologic deficits, including spastic paraplegia, dysthetic pain, and impaired bladder control, which made him completely bedridden and dependent in activities of daily living, continued, despite his immediate diagnosis and treatment. The patient received bilateral L1 to S1 selective posterior rhizotomy 1 yr after the onset of transverse myelitis, and 10 mo after selective posterior rhizotomy, he was completely independent in ambulation and self-care, demonstrating that selective posterior rhizotomy can be safely performed and its goals achieved under different medical conditions, as long as thorough preoperative evaluation and every possible precaution have been taken.


[Genetic identification of rickettsiae of the tick-borne spotted fever group, isolated in the foci of tick-borne rickettsiosis].
A total of 25 rickettsial cultures of the tick-borne spotted fever (TBSF) group from the collection of the Research Institute of Infections in Omsk, isolated from different sources in the territory of the Russian Federation (from the Urals to the Far East) during the period of 1954-2001) were studied by the methods of genetic analysis. The fragments of the gene coding the outer-membrane protein of 190 kD (ompA) and synthetase citrate (gltA) of the rickettsiae under the study were sequenced. 23 isolates were identified as R. sibirica, among them 3 isolates obtained from patients, 16 isolates obtained from Dermacentor ticks, 2 isolates from Haemaphysalis concinna and 2--from Ixodes persulcatus. The strain Primorye 32/84, isolated from D. silvarum ticks in the Far East and earlier identified as S. sibirica by the results of the PCR-RFLP analysis proved to be a genovariant Rickettsia spBJ-90, i.e. close to this species. Strain Karpunino 19/69, isolated in the Kurgan region, was identified as R. slovaca. The results obtained extended our notions of the spectrum of rickettsiae group TBSF in Russia as well as their vectors.


PrEP awareness, willingness, and likelihood to use future HIV prevention methods among undergraduate college students in an ending the HIV epidemic jurisdiction.
Identify factors associated with PrEP awareness, willingness, and future prevention modalities among undergraduate college students. Undergraduates (N = 701) were recruited from a private university, a public research university, and a private historically Black college and university for an online survey. Upon multiple imputations, a multivariate logistic model, a multivariate multinomial model, and independent multivariate ordinal logistic models were used to calculate Rubin's rules-pooled adjusted odds ratios for PrEP awareness, willingness, and future HIV prevention methods. Only 33.4% of students had heard of and 32.4% were willing to take PrEP. PrEP willingness was higher among sexual minority students compared to heterosexual/straight students (OR = 1.65; 95% CI: 1.03-2.63); p = .036). The likelihood to take a future vaccine or antibody prophylaxis treatment was higher than the likelihood to take injectable PrEP or implants. Interventions to increase PrEP uptake and willingness among undergraduates should emphasize equity in HIV education and include future prevention modalities.


Response of Artemisia herba alba to hexavalent chromium pollution under arid and semi-arid conditions.
The aim of this work is to study and evaluate in situ, the Artemisia herba alba responses to hexavalent chromium stress in the arid and semi-arid steppe Algerian soil. This metallic pollutant was selected to its high toxicity and to its great release from several industrial and agricultural activities emissions in the area of the study region. Artemisia herba alba is a medicinal plant but also a forage species widely used in pasture. It has dominated then adapted to the arid and semi-arid climate of Algerian steppe region, due principally to their morphological and physiological characteristics. To establish this work, A. herba alba species were selected in the Algerian steppe region, and their soils were treated weekly with K2CrO4 solution for about three months. Chromium concentrations were determined in the soil and in the different plants' parts to verify its absorption and translocation with and without pollution simulation. This study demonstrated that A. herba alba has a strong resistance to high concentrations of hexavalent chromium. An increase in chromium concentrations at the different parts of plant's has been noticed, without affecting its growth and vegetative development. The results of physiological and elementary analysis indicated that chromium was absorbed by A. herba alba. Cr (VI) accumulation in plant increase when they are increasing in soil. Translocation factor results indicated that Cr (VI) was mainly accumulated by A. herba alba roots. Particle size analysis showed that the soil is poor in organic substances and mostly sandy loams with 79.77% of sand and 9.76% of clay minerals.


[Screening for sleep apnea syndrome].
Sleep apnea syndrome (SAS) consists of nocturnal snoring interrupted by obstructive apnea and of diurnal symptoms like hypersomnolence as a consequence of sleep fragmentation. Cardiovascular morbidity and mortality associated with this syndrome justify early detection and appropriate treatment. Polysomnography is still a frequently used method for early detection; however, several disadvantages like duration, discomfort and expense led to a search for alternatives. Since the beginning of the eighties, oximetry allows recording of nocturnal oxygen saturation of hemoglobin even at home. Nocturnal oximetry reveals O2-desaturation associated with apnea and thus permits often to diagnose or exclude SAS. Diagnosis of SAS is made when at least 20 desaturations per hour with an amplitude of at least 4% are recorded. On the other hand, normal nocturnal oximetry nearly excludes SAS. In those cases where nocturnal oximetry is not diagnostic, polysomnography remains the method of choice. Departing from published work, a model for SAS detection, based mainly on nocturnal oximetry, is proposed.


Evaluation of glucocorticoid-induced TNF receptor (GITR) expression in breast cancer and across multiple tumor types.
Glucocorticoid-induced TNF receptor (GITR) is an emerging immunotherapy target that is expressed at high levels on regulatory T cells. Agonistic anti-GITR antibodies have anti-tumor activity in cancer mouse models, and recent phase 1 trials have demonstrated their safe pharmacological profile. However, there is limited knowledge on the relationship between GITR expression and the tumor microenvironment. GITR protein expression was assayed by immunohistochemistry on 3992 breast cancer surgical excision specimens assembled into tissue microarrays and scored visually by a pathologist for GITR expression on tumor-infiltrating lymphocytes and on carcinoma cells. GITR expression by the malignant cells was further surveyed in gastrointestinal stromal tumor (N = 713), lung carcinoma (N = 705), pancreatic cancer (N = 486), ovarian cancer (N = 445), bladder cancer (N = 88), prostate cancer (N = 88), testicular cancer (N = 76), melanoma (N = 75), renal cell carcinoma (N = 68), epithelioid sarcoma (N = 53), and neuroendocrine tumors (N = 41). In breast cancer, GITR expression on tumor-infiltrating lymphocytes (12.4%) correlated with other immune response biomarkers (PD-L1+ on tumor cells, and PD-1+, LAG-3+, TIM-3+ lymphocytes; p < 0.001), and T-cell markers (CD8+, FOXP3+; p < 0.001). GITR+ carcinoma cells were observed in 6.0% of breast cancer cases and correlated with worse relapse-free survival (p = 0.015). Among the additional tumor types examined, cancers with GITR+ malignant cells included bladder cancer (5.7%), primary (but not metastatic) melanoma (4.5%), and ovarian cancer (3.2%); no expression was identified among examined sarcomas. To our knowledge, this is the first immunohistochemistry study to report the frequency and pattern of GITR expression in a large breast cancer cohort, or to report membranous GITR expression on malignant cells. The co-infiltration of GITR with other immune biomarkers and T-cell markers supports a potential role for anti-GITR agents in combination immunotherapies. In addition, GITR expression on carcinoma cells could imply the existence of a novel cancer immune evasion strategy worthy of further investigation.


Septic arthritis caused by Salmonella enterica serotype Rubislaw: A case report.
An eleven-year-old boy presented with fever and hip pain, with limited mobility of the right side of the hip. Computed tomography scan revealed an increased volume of the right coxo-femoral joint, requiring surgical drainage of purulent secretion, from which Salmonella enterica was isolated. After four weeks of treatment with third-generation cephalosporin, he was discharged with a favorable evolution. Invasive disease caused by Salmonella spp represents a small proportion of salmonellosis cases, although it is responsible for greater rates of hospitalization, morbidity and mortality. Children under 5 years, elders over 60 years and immunodeficient patients have greater risk for invasive salmonellosis.


Psychological, neuropsychological, and electrocortical effects of mixed mold exposure.
The authors assessed the psychological, neuropsychological, and electrocortical effects of human exposure to mixed colonies of toxigenic molds. Patients (N = 182) with confirmed mold-exposure history completed clinical interviews, a symptom checklist (SCL-90-R), limited neuropsychological testing, quantitative electroencephalogram (QEEG) with neurometric analysis, and measures of mold exposure. Patients reported high levels of physical, cognitive, and emotional symptoms. Ratings on the SCL-90-R were "moderate" to "severe," with a factor reflecting situational depression accounting for most of the variance. Most of the patients were found to suffer from acute stress, adjustment disorder, or post-traumatic stress. Differential diagnosis confirmed an etiology of a combination of external stressors, along with organic metabolically based dysregulation of emotions and decreased cognitive functioning as a result of toxic or metabolic encephalopathy. Measures of toxic mold exposure predicted QEEG measures and neuropsychological test performance. QEEG results included narrowed frequency bands and increased power in the alpha and theta bands in the frontal areas of the cortex. These findings indicated a hypoactivation of the frontal cortex, possibly due to brainstem involvement and insufficient excitatory input from the reticular activating system. Neuropsychological testing revealed impairments similar to mild traumatic brain injury. In comparison with premorbid estimates of intelligence, findings of impaired functioning on multiple cognitive tasks predominated. A dose-response relationship between measures of mold exposure and abnormal neuropsychological test results and QEEG measures suggested that toxic mold causes significant problems in exposed individuals. Study limitations included lack of a comparison group, patient selection bias, and incomplete data sets that did not allow for comparisons among variables.


On the renal basis for essential hypertension: nephron heterogeneity with discordant renin secretion and sodium excretion causing a hypertensive vasoconstriction-volume relationship.
We propose herein that there are two functionally abnormal nephron populations in essential hypertension: (1) a group of ischemic nephrons with impaired sodium excretion which chronically hypersecrete renin. Numerically, these ischemic nephrons comprise a minor subgroup since most patients with essential hypertension exhibit no overt evidence of renal insufficiency. (2) In reaction to this, a more numerous group of normal nephrons appears in adaptive hypernatriuresis. They have an increased distal sodium supply and consequently, a chronically suppressed renin secretion. One difference between patients with renovascular hypertension and those with essential hypertension is the intermingling of these two populations of nephrons. In our hypothesis, the adapting hyperfiltering normal nephrons accomplish the hypernatriuresis in response to saline infusion, that is characteristic of all essential hypertension. However, the unsuppressed secretion of renin, that arises from the ischemic nephron population attenuates this compensatory natriuresis in the following ways: (1) by inappropriately acting on the hyperfiltering nephrons to enhance proximal tubular sodium reabsorption; (2) by activating TGF-mediated afferent constriction in these nephrons, and (3) simultaneously, the reactive secretion of renin from ischemic nephrons is diluted by non-participation of the adapting hypernatriuretic nephrons so that plasma renin settles at a level which is insufficient to fully compensate GFR in the ischemic nephrons. These adaptive responses provide a basis for the observation that the inhibition of renin activity with converting enzyme inhibitors in essential hypertension increases renal blood flow and sodium excretion. They also explain why converting enzyme inhibitors can effectively reduce blood pressure, even when renin levels are not absolutely elevated, since any circulating renin imposed upon the adapting hypernatriuretic nephrons inappropriately impairs their sodium excretion. In addition, the theory explains why basal renin secretion is either not suppressed or inadequately suppressed in patients with essential hypertension. As a result, whole kidney homeostatic function is compromised because individual nephrons are responding to their individual stimuli to fulfil their individual need, rather than acting in concert with other nephrons. The net effect of this uncoordinated response is to shift total renal function so that systemic arterial hypertension is sustained by abnormal sodium retention for the inappropriately high plasma renin level, or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-Term Benefits of Adding a Pedometer to Pulmonary Rehabilitation for COPD: The Randomized Controlled STAR Trial.
This Stay Active after Rehabilitation (STAR) study examined the effects of a pedometer-based behavioral intervention for individuals with COPD during three weeks of inpatient pulmonary rehabilitation (PR) on patients' physical activity levels six weeks and six months after PR, including steps (primary outcome), moderate-intensity physical activity, and sedentary time as well as patient quality of life, symptoms, and other psychological and clinical variables. Rehabilitation patients with COPD wore a triaxial accelerometer (ActiGraph wGT3X) for seven days two weeks before (T0) as well as six weeks (T3) and six months (T4) after PR. In addition to the three-week inpatient PR (control group, CG), the randomly allocated intervention group (IG) received a brief pedometer-based behavioral intervention with the application of the following behavior-change techniques: performing the behavior, individual goal-setting, self-monitoring, and feedback. The effects were analyzed using analysis of covariance with an intention-to-treat approach. A total of 327 patients (69% male, age: 58 years, FEV1 (%): 53.5, six-minute walk distance: 447.8 m) were randomly allocated to either the IG (n = 167) or CG (n = 160). Although both groups increased their daily steps after PR (IG: MT3-T0 = 1152, CG: MT3-T0 = 745; IG: MT4-T0 = 795, CG: MT4-T0 = 300), the slightly higher increases in daily steps in the IG compared to the CG at T3 (Δ388 steps, d = 0.16) and T4 (Δ458 steps, d = 0.15) were not statistically significant (p > 0.05 for all). Patients in both groups showed moderate to high pre-post-changes in terms of secondary outcomes, but no advantage favoring the IG was found. The results show that adding a pedometer-based behavioral intervention to standard German three-week inpatient PR for COPD patients did not result in more physical activity in terms of steps and moderate-intensity physical activity or less sedentary time. However, both groups (IG and CG) showed remarkably enhanced physical activity levels six weeks and six months after PR, as well as improvements in other secondary outcomes (eg, quality of life).


[Usefulness of Edoxaban for Deep Cerebral Venous Sinus Thrombosis with Hemorrhagic Infarction:A Case Report].
We describe a case of deep cerebral venous sinus thrombosis(DCVST)that was successfully treated by oral administration of the Xa inhibitor edoxaban. A 53-year-old man was admitted to our hospital because of a headache and undifferentiated dizziness. Computed tomography(CT)demonstrated a low-density area in the bilateral thalamus and high-density lesions in the internal cerebral veins(ICVs)and vein of Galen. Magnetic resonance imaging with diffusion-weighted images detected areas of hyperintensity in the bilateral thalamus. Additionally, the inferior sagittal sinus, ICV, and vein of Galen were not detected by CT venography or cerebral angiography. We therefore diagnosed DCVST and started anticoagulation therapy with heparin(IV)and warfarin. A week after admission, lesions that showed hypointensity on T2* images and high density on CT scans were detected in the bilateral thalamus. We thought that hemorrhagic infarction had occurred in association with DCVST, and changed the anticoagulation therapy to oral administration of edoxaban on day 9. The patient's symptoms gradually diminished, and CT venography indicated partial recanalization of the DCV from the ICV to the vein of Galen on day 72. We report our experience, and discuss the safety and usefulness of the Xa inhibitor for treating DCVST with hemorrhagic infarction.


Serum CYFRA 21-1 in patients with invasive bladder cancer and its relevance as a tumor marker during chemotherapy.
Previous studies have shown that serum levels of the degradation products of cytokeratins could be used as surrogate markers in the diagnosis and followup of patients with solid tumors, including tumors of the bladder. The soluble cytokeratin 19 fragment CYFRA 21-1 was measured by solid phase radioimmunoassay in the serum of 142 patients with invasive transitional cell cancer of the bladder. Of the patients 56 had clinical stage I to III locally confined disease (T1-4aN0M0) and 86 had stage IV metastatic disease with lymph node and/or distant metastases. A control group consisted of 33 healthy volunteers. In a subgroup of 49 patients with metastatic disease receiving combined platinum based chemotherapy serum CYFRA 21-1 was determined prior to the initiation of therapy and after the documentation of response. Abnormal CYFRA 21-1 was observed in 7% of patients with locally invasive disease and in 66% of those with metastatic disease (p < 0.0001). There was no correlation of CYFRA 21-1 with tumor differentiation. Patients with abnormal CYFRA 21-1 showed statistically significant worse median overall survival. Moreover, in the subgroup of patients with metastatic disease receiving chemotherapy CYFRA 21-1 levels correlated with the response to treatment. Patients with transitional cell cancer of the bladder with evidence of distant metastases showed a significant increase in serum CYFRA 21-1. During chemotherapy CYFRA 21-1 appears to be a potentially sensitive and useful indicator for monitoring treatment response.


Asymbiotic in vitro seed germination, in vitro seedling development, and ex vitro acclimatization of Spiranthes.
Reproducible seed propagation and production protocols were developed for Spiranthes and related taxa to facilitate ex situ conservation practices. Spiranthes seeds were scarified for 3- and 10-min intervals in 10% sodium hypochlorite solution, then cultured on three seed germination media. After germination, seedlings were given one of the three photoperiod treatments, and then planted in one of four greenhouse substrates. Seed germination ranged from 0% to 90% and occurred on all three media only after the 3-min scarification. Seedlings in the 24/0-h light/dark and 16/8-h light/dark photoperiods on P723 medium had significantly higher fresh weight than those in the dark treatment group. Ex vitro survival ranged from 55% to 95% across substrates. Results show that Spiranthes seeds are damaged by extended chemical scarification, are adaptable to a variety of culture media, and require light for optimal development. Further experimentation showed that the propagation protocols described here can be applied broadly within the genus.


Observed smoking in cars: a method and differences by socioeconomic area.
To establish a reproducible method to estimate he point prevalence of smoking and second-hand smoke (SHS) exposure in cars, and to compare this prevalence between two areas of contrasting socioeconomic status. A method involving two teams of observers was developed and evaluated. It involved observing 16,055 cars in Wellington, New Zealand. Two of the observation sites represented a high and a low area of deprivation (based on a neighbourhood deprivation index) and three were in the central city. A 4.1% point prevalence of smoking in cars was observed (95% confidence interval (CI) 3.8% to 4.4%). There was a higher prevalence of smoking in cars in the high deprivation area relative to the other sites, and particularly compared to the low deprivation area (rate ratio relative to the latter 3.2, 95% CI 2.6 to 4.0). Of cars with smoking, 23.7% had other occupants being exposed to SHS. Cars with smoking and other occupants were significantly more likely to have a window open (especially if the smoker was not the driver). The observation method developed was practical, and inter-observer agreement was high (kappa value for the "smoking seen in car" category 0.95). Observational studies can be an effective way of investigating smoking in cars. The data from this survey suggest that smoking in cars occurs at a higher rate in relatively deprived populations and hence may contribute to health inequalities. Fortunately, there are a number of policy options for reducing SHS exposure in cars including mass media campaigns and laws for smoke-free cars.


The use of PowerPoint shareware for making Jeopardy!--type games in the teaching of psychology.
We describe the use of readily available templates to create a Jeopardy!--type game using PowerPoint slides suitable for psychology courses. The templates can accommodate information from any psychology class and can easily be used to incorporate languages other than English. A major limitation of the templates is that they are only available as shareware on internet sites and the links to such sites can be unreliable. To avoid this problem we present our own template. Differences between the shareware and our own program are noted, as are ways to use the game to stimulate interest in psychology.


Inhibition of osteoblast apoptosis by thrombin.
The multifunctional serine protease thrombin has been shown to be a specific agonist for a variety of functional responses of cells including osteoblasts. The current study was conducted to determine if thrombin was capable of inhibiting apoptosis in osteoblasts, and if so, to examine the mechanism by which this occurred. Thrombin (20-100 nM) significantly inhibited apoptosis in serum-starved cultures of the human osteoblast-like Saos-2 cell line and cultures of primary osteoblasts isolated from mouse calvariae, as well as dexamethasone-treated primary mouse osteoblasts. Inhibition of serum deprivation-induced apoptosis was shown to require thrombin's specific proteolytic activity. Primary mouse osteoblasts were found to express two functional thrombin receptors, PAR-1 and PAR-4. Thrombin inhibited serum deprivation-induced apoptosis in osteoblasts isolated from PAR-1 null mice to the same degree as in osteoblasts isolated from wild-type mice. Treatment of serum-deprived osteoblasts, isolated from either PAR-1 null or wild-type mice, with a PAR-4-activating peptide failed to significantly inhibit apoptosis compared to the relevant control. Medium conditioned by thrombin-treated osteoblasts, in which thrombin had been inactivated, was able to inhibit serum deprivation-induced osteoblast apoptosis almost as well as thrombin itself. Blocking protein synthesis, by cycloheximide pretreatment of the conditioning cells, prevented this action. The ability of known osteoblast survival factors, such as transforming growth factor beta1, fibroblast growth factor-2, insulin-like growth factor-II, and interleukin-6, to inhibit serum deprivation-induced osteoblast apoptosis was also tested. None of these factors was able to inhibit serum deprivation-induced osteoblast apoptosis to the same extent as thrombin. The results presented here demonstrate that thrombin treatment of osteoblasts inhibits apoptosis induced either by dexamethasone or by serum deprivation. Furthermore, it does so independently of the known thrombin receptors by bringing about the synthesis and/or secretion of an unknown survival factor or factors, which then act in an autocrine fashion to inhibit apoptosis.


Reliability of a Qualitative Video Analysis for Running.
Study Design Reliability study. Background Video analysis of running gait is frequently performed in orthopaedic and sports medicine practices to assess biomechanical factors that may contribute to injury. However, the reliability of a whole-body assessment has not been determined. Objective To determine the intrarater and interrater reliability of the qualitative assessment of specific running kinematics from a 2-dimensional video. Methods Running-gait analysis was performed on videos recorded from 15 individuals (8 male, 7 female) running at a self-selected pace (3.17 ± 0.40 m/s, 8:28 ± 1:04 min/mi) using a high-speed camera (120 frames per second). These videos were independently rated on 2 occasions by 3 experienced physical therapists using a standardized qualitative assessment. Fifteen sagittal and frontal plane kinematic variables were rated on a 3- or 5-point categorical scale at specific events of the gait cycle, including initial contact (n = 3) and midstance (n = 9), or across the full gait cycle (n = 3). The video frame number corresponding to each gait event was also recorded. Intrarater and interrater reliability values were calculated for gait-event detection (intraclass correlation coefficient [ICC] and standard error of measurement [SEM]) and the individual kinematic variables (weighted kappa [κw]). Results Gait-event detection was highly reproducible within raters (ICC = 0.94-1.00; SEM, 0.3-1.0 frames) and between raters (ICC = 0.77-1.00; SEM, 0.4-1.9 frames). Eleven of the 15 kinematic variables demonstrated substantial (κw = 0.60-0.799) or excellent (κw>0.80) intrarater agreement, with the exception of foot-to-center-of-mass position (κw = 0.59), forefoot position (κw = 0.58), ankle dorsiflexion at midstance (κw = 0.49), and center-of-mass vertical excursion (κw = 0.36). Interrater agreement for the kinematic measures varied more widely (κw = 0.00-0.85), with 5 variables showing substantial or excellent reliability. Conclusion The qualitative assessment of specific kinematic measures during running can be reliably performed with the use of a high-speed video camera. Detection of specific gait events was highly reproducible, as were common kinematic variables such as rearfoot position, foot-strike pattern, tibial inclination angle, knee flexion angle, and forward trunk lean. Other variables should be used with caution. J Orthop Sports Phys Ther 2016;46(7):556-561. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6280.


Inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulatory effect of human chorionic gonadotropin (HCG) and equine chorionic gonadotropin (ECG).
We examined the inhibitory effect of thyroid blocking antibody (TBAb) on the thyroid stimulating activity of human chorionic gonadotropin (HCG) and equine CG (ECG). Five TBAb positive sera obtained from patients who had been hypothyroid but were currently on T4 treatment. The TSH binding inhibitory immunoglobulin (TBII) activities of the sera were 60-160 IU/L. Inhibition of TSH binding to the TSH receptor (TSHR) [TSH binding inhibition (TBI) activity] of HCG or ECG, and inhibition of TBAb on HCG or ECG-stimulated cAMP production were examined. Both HCG and ECG preparations showed weak TBI activity in the presence of small amounts of protein [bovine serum albumin (BSA)] but were negative in the presence of large amounts of protein [normal human serum (NHS) or BSA]. Four thousand IU/mL of HCG and ECG preparation caused cAMP production similar to 100 microU/mL of bovine (b) TSH. The inhibitory effect of TBAb on cAMP production by this amount of HCG or ECG was then examined. The inhibitory effect of TBAb on cAMP production by HCG and ECG was similar to bTSH, and TBAb positive sera with more than 40 IU/L TBII activity completely blocked cAMP production by HCG, ECG and bTSH. This suggests that common alpha -subunit of both HCG and TSH are involved in the inhibitory effect of TBAb. Previous reports demonstrated that the thyroid stimulating activity of thyroid stimulating antibody (TSAb) was blocked by deglycosylated HCG (competitive antagonist of TSH binding to TSHR). The fact and our present study suggest that TSH, HCG ECG, TSAb and TBAb have a similar binding site (alpha-subunit-mimicking binding site) on the TSH receptor.


Procedural fairness for radiotherapy priority setting in a low resource context.
Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve their populations. This mismatch between demand and supply creates the need for priority setting. There is no widely accepted system to guide patient prioritization for radiotherapy in a low resource context. In the absence of consensus on allocation principles, fair procedures for priority setting should be established. Research is needed to understand what elements of procedural fairness are important to decision makers in diverse settings, assess the feasibility of implementing fair procedures for priority setting in low resource contexts, and improve these processes. This study presents the views of decision makers engaged in everyday radiotherapy priority setting at a cancer center in Rwanda. Semi-structured interviews with 22 oncology physicians, nurses, program leaders, and advisors were conducted. Participants evaluated actual radiotherapy priority setting procedures at the program (meso) and patient (micro) levels, reporting facilitators, barriers, and recommendations. We discuss our findings in relation to the leading Accountability for Reasonableness (AFR) framework. Participants emphasized procedural elements that facilitate adherence to normative principles, such as objective criteria that maximize lives saved. They ascribed fairness to AFR's substantive requirement of relevance more than transparency, appeals, and enforcement. They identified several challenges unresolved by AFR, such as conflicting relevant rationales and unintended consequences of publicity and appeals. Implementing fair procedure itself is resource intensive, a paradox that calls for innovative, context-appropriate solutions. Finally, socioeconomic and structural barriers to care that undermine procedural fairness must be addressed.


A review of RSPCA research into wildlife rehabilitation.
Wildlife rehabilitation is defined as 'the treatment and temporary care of injured, diseased, and displaced indigenous animals, and the subsequent release of healthy animals to appropriate habitats in the wild' (Miller 2012). Vets are frequently presented with wildlife casualties and although there are a number of texts available to help vets with the treatment of wild animals, such as the BSAVA Manual of Wildlife Casualties (Mullineaux and others 2003) and papers produced by experienced wildlife vets (eg, Bexton and Couper 2010, Couper and Bexton 2012), there still remains questions regarding which individual animals can, or should, be treated, which animals will survive treatment and which animals will survive after they have been released back to the wild. The RSPCA believes that the welfare of wildlife casualties can be improved by investigating which injuries or illnesses are most likely to result in a successful release for each species, and by collecting data on postrelease survivorship. As a result, there have been a number of papers published based on the work of the RSPCA's four wildlife centres: East Winch in Norfolk, Mallydams Wood in East Sussex, Stapeley Grange in Cheshire and West Hatch in Somerset. This paper summarises this research, to guide those in the profession with an interest in this subject to papers that may prove useful to them.


Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators.
Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism. Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.


Enhanced logic performance with semiconducting bilayer graphene channels.
Realization of logic circuits in graphene with an energy gap (EG) remains one of the main challenges for graphene electronics. We found that large transport EGs (>100 meV) can be fulfilled in dual-gated bilayer graphene underneath a simple alumina passivation top gate stack, which directly contacts the graphene channels without an inserted buffer layer. With the presence of EGs, the electrical properties of the graphene transistors are significantly enhanced, as manifested by enhanced on/off current ratio, subthreshold slope, and current saturation. For the first time, complementary-like semiconducting logic graphene inverters are demonstrated that show a large improvement over their metallic counterparts. This result may open the way for logic applications of gap-engineered graphene.


Varus inclination of the tibial plateau in Thai adults: a concise radiographic evaluation.
To identify the normal inclination of the tibial plateau in Thai adults. Anteroposterior knee-to-ankle radiographs of 13 healthy Thai male (26 knees) and 11 healthy Thai female (21 knees) subjects aged 20-40 years were obtained with the x-ray beam angled 10 degrees caudally.A special splint was used for rotational control of the examined limbs. Medial proximal tibial angles (MPTA) were measured. The tibial plateau inclination (TPI) was calculated (90 degrees minus MPTA) and analyzed. The mean age of the male subjects was 27.9 +/- 2.5 years and that of the female subjects was 30.5 +/- 5.4 years (p = 0.173). There was no significant difference in TPI between the male (3.2 +/- 1.7 degrees, range 0-6 degrees) and female (2.5 +/- 2.3 degrees, range 0-7 degrees) (p = 0.207) subjects. For each gender, there was no significant difference of TPI between the right and the left knees (p = 0.656 and p = 0.386 for men and women, respectively). No correlations of TPI with age, weight, height or BMI were observed in the present study. Through a concise radiographic evaluation, the commonly reported 3 degrees of TPI can be applied in Thai subjects. In clinical use, this finding can assist the surgeons to restore the tibial plateau geometry for fracture treatments and correct the deformity during reconstructive knee surgery.


Gastric Ulcer Secondary to Left Gastric Artery Thrombosis.
Peptic ulcer disease (PUD) is a well-known and commonly encountered gastrointestinal (GI) pathology. Helicobacter pylori and nonsteroidal anti-inflammatory drug (NSAID) use are the cause of the majority of PUD cases, although other rare etiologies may be encountered. PUD is confirmed by endoscopic visualization of gastric ulcers, with radiographic imaging being less impactful in diagnosis. In this paper, we present a middle-aged patient who presented with PUD caused by thrombotic occlusion of the left gastric artery (LGA), with her diagnosis being made with computed tomography (CT) imaging prior to endoscopy. This case emphasizes the importance of radiographic imaging in the undifferentiated patient, as well as the unique role radiologists play in both discovering diagnoses and their etiologies.


Decrease in dietary K intake stimulates the generation of superoxide anions in the kidney and inhibits K secretory channels in the CCD.
We previously demonstrated that K depletion inhibited ROMK-like small-conductance K channels (SK) in the cortical collecting duct (CCD) and that the effect was mediated by superoxide anions that stimulated Src family protein tyrosine kinase (PTK) and mitogen-activated protein kinase (MAPK) (51). However, because animals on a K-deficient diet had a severe hypokalemia, superoxide-dependent signaling may not regulate ROMK channels under physiological conditions with a normal plasma K concentration. In the present study, we used the patch-clamp technique and Western blot to examine the effect of a moderate K restriction on ROMK-like SK channels and the role of PTK and MAPK in regulating apical K channels in the CCD of animals on a low-K diet (LK; 0.1% K). Rats and mice fed a LK diet for 7 days had a normal plasma K concentration. However, a LK intake increased the expression of angiotensin II type 1 receptor in the kidney. Moreover, patch-clamp experiments demonstrated that LK intake decreased the probability finding SK channels and channel activity defined by NP(o) (a product of channel number and open probability) in the CCD of both rat and mouse kidneys. Also, LK intake significantly stimulated the production of superoxide anions in the renal cortex and outer medulla in both rats and mice and increased superoxide level in the rat CCD. Moreover, LK intake augments the phosphorylation of p38 and ERK MAPK, the expression of c-Src and tyrosine phosphorylation of ROMK channels. However, treatment of animals with tempol abolished the effect of LK intake on MAPK and c-Src and increased ROMK channel activity in comparing with those of nontreated rats on a LK diet. Inhibiting p38 and ERK with SB202190 and PD98059 significantly stimulated SK in the CCD in rats on a LK diet. In addition, inhibition of PTK with herbimycin A activated SK channels in the CCD from rats on a LK diet. We conclude that LK intake stimulates the generation of superoxide anion and related products and that MAPK and Src family PTK play a physiological role in inhibiting apical K channels in the principal cells in response to LK intake.


When will faculty retire?: Factors influencing retirement decisions of nurse educators.
This cross-sectional study surveyed a random sample of 129 nurse educators teaching in 61 U.S. schools of nursing. After the educators indicated their desire to participate, the survey instrument was e-mailed to them for completion; a 37.6% response rate was obtained. Demographically, the typical respondent was a healthy, 52-year-old, Caucasian female with a PhD in nursing. Outcomes reflected that respondents' mean anticipated age of retirement was 64.4; however, the optimal age of retirement desired by respondents was younger (62.4). The most influential factor affecting the timing of retirement was financial status. Workplace issues, personal and family health, and attitudes about retirement were other factors that affected participants' retirement decisions. The study findings indicate that nurse educators, as a group, do not plan to work beyond age 65.


Early initiation of beta blockade in heart failure: issues and evidence.
Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.


L-based numerical linked cluster expansion for square lattice models.
We introduce a numerical linked cluster expansion for square-lattice models whose building block is an L-shape cluster. For the spin-1/2 models studied in this work, we find that this expansion exhibits a similar or better convergence of the bare sums than that of the (larger) square-shaped clusters and can be used with resummation techniques (like the site- and bond-based expansions) to obtain results at even lower temperatures. We compare the performance of weak- and strong-embedding versions of this expansion in various spin-1/2 models and show that the strong-embedding version is preferable because of its convergence properties and lower computational cost. Finally, we show that the expansion based on the L-shape cluster can be naturally used to study properties of lattice models that smoothly connect the square and triangular lattice geometries.


Changes in cytokeratin expression in gingiva during inflammation.
Cytokeratins represent specific markers of certain pathways of epithelial differentiation. The purpose of this study was to describe the alterations of cytokeratin pattern and topographical distribution of individual cytokeratins in inflamed gingiva. Five healthy and 15 inflammatory samples of human gingiva were studied. From each biopsy, cryostat sections allowed histological staining, immunofluorescence microscopy using a battery of monoclonal antibodies to cytokeratins, and gel electrophoresis. The results show marked differences in cytokeratin expression by healthy epithelia as compared with inflamed gingiva: in suprabasal cell layers there were reductions or disappearance of cytokeratins 1, 2 and 10, 11--specific for terminal differentiation--and increased expression of cytokeratins 4 and 13, as well as--in basal and parabasal cell layers--expression of cytokeratin 19. These alterations might represent an adaptation of involved epithelia to the alterations brought about by the inflammatory process.


Blood leakage and melphalan leakage from the perfusion circuit during regional hyperthermic perfusion for malignant melanoma.
In regional hyperthermic perfusion with melphalan for patients with malignant melanoma of the leg, plasma leakage between the perfusion circuit and the systemic circulation was 4-7 ml X min-1. The melphalan concentration in the perfusate was biphasic, with half-lives of 8-12 mins for the initial phase and 19-28 mins for the second phase, after the first dose. After a second dose, the corresponding values were 11-13 and 26-34 mins. The highest concentration in general circulation was 0.38 micrograms X ml-1.


Prognostic Implications of Combined Imaging and Histologic Criteria in Squamous Cell Carcinoma with Mandibular Invasion.
Prognosis prediction of squamous cell carcinoma (SCC) with mandibular invasion is controversial, and a more sophisticated staging system to aid prognosis could be developed with imaging characteristics of bone invasion. Imaging-feature analysis provides practical, stratified results for survival prognosis in oral SCC (OSCC) of the mandible, and imaging advances enable more detailed tumor visualization. We retrospectively evaluated significant bone-invasion features associated with poor outcomes in mandibular OSCC to assess the predictive value of staging criteria that combined imaging features and histologic grade (combined imaging-histology (IH) grade) in 65 patients (39 men, 26 women) with mandibular SCC diagnosed from 2006 to 2016. Clinicopathologic features, including T-stage and histologic grade, and prognosis were retrieved. Tumors were classified into three types by extent of mandibular invasion on pretreatment imaging studies. Moreover, we assessed the involvement of the mandibular canal. We examined the correlation of factors associated with locoregional recurrence and overall mortality. The Harrell Concordance Index (C-index) determined prognostic performance of predictors. Nineteen (29%) patients showed locoregional recurrence and 13 (20%) died. For locoregional recurrence and mortality rates, imaging-detected mandibular canal (MC) involvement is a stronger prognostic factor for recurrence (C-index = 0.61 > 0.58) and survival (C-index = 0.58 > 0.63) than histopathologically confirmed perineural invasion, as was the IH grade, especially IH Grade 3, which was significantly associated with worse locoregional recurrence (p < 0.02). Imaging-based staging showed higher prognostic performance than T-staging (C-index = 0.57 (recurrence), 0.60 (death)), when combined with histologic grading (C-index = 0.69 for both) or used alone (C-index = 0.63 (locoregional recurrence), 0.69 (death)). Overall survival was significantly stratified by Imaging type and IH grade. Therefore, analysis of imaging features provided more specific, practical results for survival prognosis in mandibular OSCC. Imaging advances can potentially provide detailed gross views of tumor masses to facilitate development of prognostic criteria for OSCC.


Assessment of Psychopathology, Quality of Life, and Parental Attitudes in Adolescents with Type 1 Diabetes Mellitus.
The aim of the present study was to identify psychopathology, parental attitudes, perceptions of quality of life, and relationships between these factors in adolescents with type 1 diabetes mellitus (DM). Fifty adolescents (12-18 years old) with type 1 diabetes mellitus and 50 healthy adolescents and their parents were recruited for the study. Clinical interviews with the diabetic adolescents were performed using "Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)." Both groups completed the "Depression Scale for Children," "State-Trait Anxiety Inventory," and "Health Related Quality of Life Scale for Children," while their parents completed the "Parental Attitude Research Instrument," "The Coping Strategy Indicator," and "Health Related Quality of Life Scale for Children-Parent Form." The psychological disorder ratio in diabetic adolescents was 68%. No significant difference was found regarding perceptions of quality of life between the diabetic group and control group. However, diabetic adolescents with psychological disorder had reduced perception of quality of life than those without psychological disorder. Among parental attitudes, an authoritarian attitude was found to be more common in the diabetic group. It was found that among coping strategies, parents in the diabetic group use avoidance more commonly. In the present study, a high rate of psychopathology was detected among adolescents with type 1 DM. In addition, no clear impairment in quality of life was reported in patients with type 1 DM; however, there was worsening in the perception of quality of life in the presence of psychiatric disorders accompanying diabetes. It was found that parents of diabetic children use inappropriate coping strategies and negative parental attitudes more often than those of healthy controls.


Factors affecting nurses' decisions to administer PRN analgesic medication to children after surgery: an analog investigation.
Investigated postoperative PRN analgesic medication decisions regarding children in 113 hospital nurses, using analog stimuli. Nurses with greater narcotics knowledge and comfort indicated they would provide significantly more medication. Nurses provided more analgesics to children showing higher pain, and on the first than on the third postoperative day. Seriousness of child's condition also affected medication decisions. On the first day, nurses gave less medication to the child with than without permanent sequelae, whereas on the third postoperative day nurses provided more analgesics to the child with than without sequelae. These findings were consistent across high and low pain conditions. Nurses' ratings of children's pain were also affected by seriousness and time since surgery. Findings are discussed with reference to problems of undermanagement of children's pain.


The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population.
The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0.05). If patients did not have hypoproteinaemia or had hypertension, the SNP in rs1045642 was associated with CR (CC vs. TT: albumin ≥35, P = 0.042; hypertension, P = 0.045; C vs. T: albumin ≥35, P = 0.033; hypertension, P = 0.040). Additionally, the platelet inhibition of the CT+TT genotype in rs1128503 was larger than that of the CC genotype (P = 0.021). Multivariate logistic regression analysis showed that male, higher albumin and hsCRP decreased the risk of CR, and the stent size maybe positively correlated with CR. The SNP in rs1045642 was related to all-cause mortality (P = 0.024). We did not find any relationship between the methylation levels of the ABCB1 promoter and CR. In conclusions, our study indicated that ABCB1 polymorphisms might be useful in further evaluating the pathogenesis of CR.


[Anemia and thrombocytopenia in malaria. I. Mechanisms].
Pathomechanism of thrombocytopenia and anaemia which frequently occur in patients with malaria is of a complex origin. Anaemia occurs due to sequestrating, destruction and hemolysis of damaged, parasite infected erythrocytes, as well as of the impaired and ineffective erythropoiesis in the marrow. Thrombocytopenia in these patients may also result from both increased destruction of blood platelets and decreased thrombocytopoiesis. Similar natures of the processes cause that anaemia and thrombocytopenia frequently co-exist in patients with malaria.


A National Review of Insurance Coverage of Noncancerous Breast Reconstruction.
Breast reconstruction is commonly performed for a multitude of noncancerous indications, such as correction of congenital deformities, acquired tissue disease, burns, and trauma. However, breast reconstruction for noncancerous indications is often considered cosmetic or not explicitly mentioned in insurance policies. The goal of this study was to assess variability in insurance coverage of breast reconstruction for noncancerous indications. The authors conducted a cross-sectional analysis of 102 US insurance companies, including Medicare and Medicaid, for coverage of breast reconstruction for noncancerous indications (Poland syndrome, fibrocystic breast disease, burns and trauma). Insurance companies were selected based on their state enrollment data and market share. A Web-based search and individual telephone interviews were conducted to identify the policy. Medical necessity criteria were abstracted from publicly available policies. Half of the insurers (49%, n = 50) had no policy for Poland syndrome, 46% (n = 47) had no policy for burns and trauma, and 82% (n = 84) had no policy for fibrocystic breast disease. Fifty-two percent (n = 22) of policies providing coverage for Poland syndrome, 24% (n = 13) of policies providing coverage for burns and trauma, and 58% (n = 7) of policies providing coverage for fibrocystic breast disease had specific, stringent criteria for medical necessity. Thirty-six percent (n = 15) of policies covering Poland syndrome, 47% (n = 26) of policies covering burns and trauma, and 33% (n = 4) of policies covering fibrocystic breast disease include coverage of the contralateral breast. There is a paucity of publicly available information on insurance coverage of breast reconstruction for noncancerous indications and a lack of consensus between top US insurance companies on what constitutes medical necessity for surgical correction.


[Morphometric assessment of lesions in the dopaminergic nigrostriatal system in Parkinson disease].
The qualitative changes in substantia nigra were analysed in the material of 25 cases of Parkinson's disease. A morphometric quantitative study of depletion of pigmented dopaminergic cells of substantia nigra was performed in six long-term cases of the disease. In addition, the number of melanin nodules was assessed as a marker of cell disintegration. The results obtained were compared with the morphometric evaluation of neuronal depletion in the mesocorticolimbic system (ventral tegmental area-VTA). The qualitative study indicated that melanin depletion in dopaminergic cells of substantia nigra in Parkinson's disease is diffuse and it is located mainly in the lateral alfa layer. Neuronal depletion with concomitant numerous extracellular neuromelanin nodules and granules was observed. A slight astrocytic gliosis free of macrophages accompanied cellular changes. The qualitative changes in substantia nigra are similar to those observed in VTA. The morphometric evaluation revealed that depletion of dopaminergic neurons in substantia nigra in Parkinson's disease is 73%, on average, while in VTA it remains under 5%. Hence, depletion in substantia nigra is much more intense. The analysis of the relationship between the number of neurons in substantia nigra and the age of subjects in the control group indicated that the number of neurons decreased proportionally to the age. In the group under study no significant relationship between neurons depletion and duration of disease or patients age was found. In the studied group of patients with Parkinson's disease, the number of melanin nodules in substantia nigra was significantly higher than in controls.


Rab11a is required for apical protein localisation in the intestine.
The small GTPase Rab11 plays an important role in the recycling of proteins to the plasma membrane as well as in polarised transport in epithelial cells and neurons. We generated conditional knockout mice deficient in Rab11a. Rab11a-deficient mice are embryonic lethal, and brain-specific Rab11a knockout mice show no overt abnormalities in brain architecture. In contrast, intestine-specific Rab11a knockout mice begin dying approximately 1 week after birth. Apical proteins in the intestines of knockout mice accumulate in the cytoplasm and mislocalise to the basolateral plasma membrane, whereas the localisation of basolateral proteins is unaffected. Shorter microvilli and microvillus inclusion bodies are also observed in the knockout mice. Elevation of a serum starvation marker was also observed, likely caused by the mislocalisation of apical proteins and reduced nutrient uptake. In addition, Rab8a is mislocalised in Rab11a knockout mice. Conversely, Rab11a is mislocalised in Rab8a knockout mice and in a microvillus atrophy patient, which has a mutation in the myosin Vb gene. Our data show an essential role for Rab11a in the localisation of apical proteins in the intestine and demonstrate functional relationships between Rab11a, Rab8a and myosin Vb in vivo.


Computer analyses of auditory evoked cortical potentials in schizophrenic subjects.
Averaged cortical evoked potentials from single clicks were recorded from 51 patients and controls. The patient group consisted of 40 subjects with a diagnosis of 'nuclear' schizophrenia, and 11 subjects with diagnoses including mania, anxiety neurosis and personality disorder. Changes in auditory evoked cortical responses (AECR's) were most marked in clinically stable, dysphoric, chronic schizophrenics. These subjects showed reproducible, low amplitude, 'untidy' responses in which the amplitude of the primary peak was lower than the amplitude of later peaks. Chronic schizophrenics who were rated as being depressed, showed a more 'normal' AECR. AECR changes during the memorising of nonsense syllables demonstrated a functional separation between early and later peaks of the AECR. It was postulated that the AECR changes in schizophrenia and during memorising result from pathological patterns of cortical desynchronisation produced by altered mid-brain activity different from that of anxious arousal, and that the clinical 'steady-state' of chronic schizophrenia is reflected in the 'steady-state' desynchronisation changes in the AECR.


Optimizing calf muscle pump function.
Background The tip toe manoeuvre has been promoted as the gold standard plethysmography test for measuring calf muscle pump function. The aim was to compare the tip toe manoeuvre, dorsiflexion manoeuvre and a body weight transfer manoeuvre using the ejection fraction of air-plethysmography and evaluate which has the best pumping effect. Methods Sixty-six archived tracings on 22 legs were retrieved from an air-plethysmography workshop and analysed. Pumping performance was measured using the calf volume reduction after each manoeuvre. Results Expressed as median [inter-quartile range], body weight transfer manoeuvres resulted in a significantly greater ejection fraction (%) than tip toe manoeuvres at 59.7 [53.5-63.9] versus 42.6 [30.5-52.6], P < 0.0005 (Wilcoxon). There was no significant difference in the ejection fraction between the tip toe manoeuvre versus dorsiflexion manoeuvre, P = 0.615. The repeatability (confidence interval: 95%) of 66 ejection fraction tests was excellent: tip toe manoeuvre (±1.2), dorsiflexion manoeuvre (±1.3) and body weight transfer manoeuvre (±1.6). Conclusion The body weight transfer manoeuvre appears to be a better method of measuring the full potential of the calf muscle pump with a 40.1% relative increase in the ejection fraction compared to a tip toe manoeuvre. Exercises which involve body weight transfers from one leg to the other may be more important in optimizing calf muscle pump function than ankle movement exercises.


Phase-locked patterns and amplitude death in a ring of delay-coupled limit cycle oscillators.
We study the existence and stability of phase-locked patterns and amplitude death states in a closed chain of delay coupled identical limit cycle oscillators that are near a supercritical Hopf bifurcation. The coupling is limited to nearest neighbors and is linear. We analyze a model set of discrete dynamical equations using the method of plane waves. The resultant dispersion relation, which is valid for any arbitrary number of oscillators, displays important differences from similar relations obtained from continuum models. We discuss the general characteristics of the equilibrium states including their dependencies on various system parameters. We next carry out a detailed linear stability investigation of these states in order to delineate their actual existence regions and to determine their parametric dependence on time delay. Time delay is found to expand the range of possible phase-locked patterns and to contribute favorably toward their stability. The amplitude death state is studied in the parameter space of time delay and coupling strength. It is shown that death island regions can exist for any number of oscillators N in the presence of finite time delay. A particularly interesting result is that the size of an island is independent of N when N is even but is a decreasing function of N when N is odd.


Fagraldehyde, a secoiridoid isolated from Fagraea fragrans.
A secoiridoid aglycone with an atypical skeleton, named fagraldehyde (1), together with several known secoiridoids (gentiopicroside (2), sweroside (3), and swertiamarin (4)) were isolated from the bark and leaves of Fagraea fragrans collected in Cambodia. The conformations of 1 were evaluated on the basis of molecular modeling and NOESY correlations. A hypothetical biogenesis of fagraldehyde was proposed to explain the unusual skeleton. Compound 1 was weakly active in vitro against Plasmodium falciparum.


Seed size plasticity in response to embryonic lethality conferred by ectopic CYCD activation is dependent on plant architecture.
The size of seeds is the result of cell proliferation and growth in the three seed compartments: the embryo, endosperm and integuments. Targeting expression of the D-type cyclin CYCD7;1 to the central cell and early endosperm (FWA:CYCD7;1) triggered nuclear divisions and partial ovule abortion, reducing seed number in each silique and leading to increased seed size. A similar effect on seed size was observed with other segregating embryo lethal mutations, suggesting caution is needed in interpreting apparent seed size phenotypes. Here, we show that the positive effect of FWA:CYCD7;1 on Arabidopsis seed size is modulated by the architecture of the mother plant. Larger seeds were produced in FWA:CYCD7;1 lines with unmodified inflorescences, and also upon removal of side branches and axillary stems. This phenotype was absent from inflorescences with increased axillary floral stems produced by pruning of the main stem. Given this apparent confounding influence of resource allocation on transgenes effect, we conclude that plant architecture is a further important factor to consider in appraising seed phenotypes.


Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction.
Platinum combination chemotherapy will regularly produce a 70% complete response rate in testicular cancer. Many patients failing to achieve complete remission can still be rendered disease-free with surgical resection of residual localized disease. Twenty-one patients underwent resection for residual pulmonary lesions and 41 underwent lymphadenectomy for persistent retroperitoneal disease. There were no characteristic radiographic findings for fibrous tissue versus mature teratoma versus carcinoma. Although elevated HCG or AFP levels indicated the presence of carcinoma, negative HCG and AFP did not rule out such a diagnosis as 12 of 22 resected carcinoma patients were seronegative. Of 35 patients, 31 (89%) with fibrous tissue or mature teratomas and all four patients with immature teratomas have been continuously free of disease with a minimal postoperative follow-up time of six months. However, only two of 22 patients with resected carcinomas have been continuously disease-free. Post-operative chemotherapy for mature teratoma or fibrous tissue is probably not necessary. However, we feel that further aggressive chemotherapy is needed in the resected carcinoma patient with at least two courses of platinum combination chemotherapy. Surgical resection of residual disease following chemotherapy-induced cytoreduction with platinum combination chemotherapy may be therapeutic in some cases and helps to define the optimal subsequent treatment strategy.


Non-exercise VO2max estimation for physically active college students.
This study sought to develop a maximal oxygen consumption (VO2max) regression model derived strictly from self-reported non-exercise (N-EX) predictor variables. The VO2max (mean +/- SD; 44.05 +/- 6.6 ml.kg-1.min-1) of 100 physically active college students (50 females, 50 males), aged 18 to 29 yr, was measured using a treadmill protocol and open circuit calorimetry. Questionnaire-based predictor variables used in the N-EX regression model included (a) the subject's perceived functional ability (PFA) to walk, jog, or run given distances, (b) habitual physical activity (PA-R) data, (c) body mass index (BMI), and (d) gender. BMI (kg.m-2) was computed from self-reported body weight in pounds and self-reported body height in feet and inches. The questionnaire-based N-EX regression model (R = 0.85, SEE = 3.44 ml.kg-1.min-1) developed in this study exceeded the accuracy of previously developed N-EX regression models and is comparable to many exercise-based regression models in the literature. Cross-validation using PRESS (predicted residual sum of squares) statistics demonstrated minimal shrinkage (R = 0.84, SEE = 3.60 ml.kg-1.min-1) of the present regression model. The PFA data were useful in explaining observed VO2max variance (squared partial r2 = 0.155, P < 0.0001) and enhanced the ability of the N-EX regression model to accurately predict criterion VO2max. These results suggest that a questionnaire-based N-EX regression model provides a valid and convenient method for predicting VO2max in physically active college students.


Resection of Cervical Juxtacortical Chondroma and Circumferential Spinal Stabilization for Kyphotic Deformity.
Chondromas are rare, benign tumors composed of cartilaginous tissue that mainly affect the metaphases of long tubular bones. Juxtacortical (periosteal) chondromas arise from the surface of periosteum and rarely affect the cervical spine. We present a patient with a spinal juxtacortical chondroma causing spinal cord compression and a cervical deformity treated with surgical resection and circumferential spinal fixation and stabilization. A 55-year-old female with past medical history of Crohn's disease with years of neck pain, balance issues, and left upper extremity radicular symptoms. Cervical spine x-rays show kyphosis with an apex at C5, degenerative changes of the endplates and facet joints, and grade 2 anterolisthesis C4 on C5 with no abnormal motion with flexion/extension. MRI showed a left sided C5-6 extramedullary mass measuring 11 x 11 x 15 mm causing spinal cord compression and neural foraminal narrowing. Her pain is worsening and refractory to physical therapy, gabapentin and methocarbamol. A C4-5 & C5-6 anterior cervical discectomy and fusion, C4-5 & C5-6 laminectomy for tumor resection, and C4-5 & C5-6 posterior fusion with instrumentation was performed. The tumor was completely removed in piecemeal fashion. Microscopic findings showed bland well differentiated cartilaginous neoplasm consistent with juxtacortical chondroma. Postoperative X-rays show partial reduction of C4-5 anterolisthesis and partial reversal of cervical kyphosis. The patient's radicular pain resolved and neck pain improved postoperatively but she still has some left sided neck pain and hand dysesthesias that are controlled with oral medication one year following surgery. Cervical chondromas are rare, benign cartilaginous tumors that may present with spinal cord or nerve root compression. They are more complex when they present in patients with co-existing spinal deformities. Maximal safe resection followed by spinal re-alignment and fixation without adjuvant chemotherapy or radiation is recommended in most cases. Close follow-up is recommended to monitor for recurrence.


Expression of epidermal growth factor receptor in the preimplantation uterus and blastocyst of the western spotted skunk.
The western spotted skunk is unique in that its blastocysts undergo a 180-220-day period of arrested development before implantation. We investigated the potential role of epidermal growth factor (EGF)-related growth factors in regulating uterine and embryonic development in this species by studying the status of EGF receptor (EGF-R) in these tissues during delayed implantation and resumption of embryonic development. The cell-specific distribution of EGF binding sites and the expression of EGF-R mRNA were assayed by autoradiography and Northern blot analysis, respectively. The size of EGF-R was determined by affinity cross-linking studies, and its bioactivity was examined by determining EGF-dependent subcellular protein tyrosine kinase (PTK) activity. EGF binding sites were localized in the uterine luminal and glandular epithelium, endometrial stroma, myometrium, and blood vessels during both stages of pregnancy. As examined by Northern blot hybridization, a cRNA probe specific to mouse EGF-R hybridized to poly(A)+ RNA of skunk uteri. Transcripts similar to those of mouse uterine EGF-R were identified. [125I]-EGF was cross-linked to a 170-kDa protein both in the uterus and in blastocysts collected during the delayed implantation and periimplantation periods. However, EGF-induced PTK activity was significantly elevated above background levels during the period of renewed embryonic development, but not during arrested embryonic development. The results suggest that EGF-related growth factors may play an important role in regulating embryonic development in this species and that a change in the number and/or functional status of the EGF-R may be a prerequisite for blastocyst activation and implantation in the spotted skunk.


[Current concepts on diagnosis and treatment of carcinoid].
Carcinoid tumours are relatively rare neuroendocrine neoplasms that often present as diagnostic dilemmas due to obscure or non-specific symptomatology. They can originate from any location in the body and on the basis of their localisation are traditionally described as originating from the foregut, midgut, and hindgut. Carcinoids occur most frequently in the gastrointestinal system, where they are most common in the small intestine, appendix, and rectum, and in the bronchi. Although, the majority are nonfunctional, some carcinoids can cause so called classical or atypical carcinoid syndrome and sometimes also paraneoplastic syndromes. Carcinoid tumours often present with metastatic disease. Recent years have brought new developments in the field of their diagnostic and treatment options. Despite the fact that many advances have been made in both the basic science and clinical areas, the optimal treatment of carcinoid tumours is still a matter of debate. In this article, the pathogenesis, clinical aspects, classification, diagnosis and treatment of carcinoids are reviewed including the latest advances in each area.


Sound localization in unilateral deafness with the Baha or TransEar device.
To evaluate the sound localization capabilities of patients with unilateral, profound sensorineural hearing loss who had been treated with either a bone-anchored hearing device (Baha BP100) or a TransEar 380-HF bone-conduction hearing device. Nonrandomized, prospective study. SETTING Tertiary referral private practice. Patients with unilateral, profound sensorineural hearing loss treated with a BP100 (n = 10) or a TransEar (n = 10) device. Patients wore the hearing device for at least 1 month and had normal hearing in the contralateral ear. Ten patients with normal, bilateral hearing were used for control. Sound localization of a 3-second recorded sound with and without a TransEar or Baha device was assessed using an array of 7 speakers at head level separated by approximately 45 degrees. The recorded sounds were that of a barking dog or a police siren. Randomized trials of 4 presentations per speaker were given for each hearing condition. Sound localization was assessed by the accuracy in response and the generalized laterality of response. The mean accuracy of speaker localization was 24% and 26% for the aided condition using the BP100 and TransEar devices, respectively. The mean accuracy of laterality judgment was 59% and 69% for the aided condition using the BP100 and TransEar devices, respectively. These results were only slightly better than chance. There was no statistical difference in localization accuracy or laterality judgment between the BP100 and TransEar groups. Neither the BP100 nor the TransEar device improved sound localization accuracy or laterality judgment ability in patients with unilateral, profound sensorineural hearing loss compared with performance in the unaided condition.


Marginal zone lymphomas: second most common lymphomas in older patients.
Choosing an optimal treatment in older patients with indolent lymphomas is a challenge for hematooncologists. They must concomitantly treat some potentially curable entities, manage other symptomatic incurable diseases and protect their patients from life-threatening toxicities. Specific recommendations for older patients with different subtypes of marginal zone lymphomas are thus required in terms of treatment and supportive care. All the data in the literature agree that the therapeutic approach of older patients with malignant hemopathies should include the appraisal of their life expectancy and of the prognostic factors of their tumor, the evaluation of their physiological and cognitive functions and their socioeconomic environment, and their expectancy in terms of quality of life. Major progresses have, therefore, been achieved in the management of lymphoma patients of 80 years and older. With an optimal 'geriatric assessment', most of the recommended treatments are also appropriate in older marginal zone lymphoma patients. Extranodal MALT lymphoma: eradication of the pathogen is a major part of the first-line therapy. Prognosis is excellent in early stages. In advanced stages, observation and anti-CD20 antibodies with or without cytostatic drugs are recommended. Nodal MZL: Usually confined to lymph nodes, bone marrow and peripheral blood, they should be managed as follicular lymphomas. Splenic MZL: in this unique entity involving the spleen, the bone marrow and the peripheral blood. Hepatitis infection should be eradicated before considering treatment. Only symptomatic patients require to be treated by splenectomy and/or anti-CD20 antibodies.


Techniques for the detection of leukocytospermia in human semen.
During the cytological evaluation of 1200 spermiocytograms, we used prestained microscope slides (Testsimplets) in 200 cases as a screening method. In 50 cases, a check was made to determine whether leukocytospermia could be detected with aid of Cytur-Test. The findings were compared with smears that were routinely stained by the Papanicolaou technique and subsequently differentiated. The cytological examination of human sperm with the aid of Testsimplets provides a technically simple and rapid procedure that has sufficient informative value to permit the diagnosis or exclusion of the leukocytospermia and the sperm morphology. Leukocytospermia could also be detected by the use of Cytur-Test. The presence of larger numbers of spermatogenic cells does not lead to a blue coloration of the Cytur-Test areas. In cases of leukocytospermia there is a clear blue coloration. These two rapid techniques are useful for the diagnosis of leukocytospermia.


Hemostatic and rheological variables and risk of cardiovascular disease.
Increasing blood levels of hemostatic variables may increase the risk of thrombosis, while increasing levels of rheological variables which reduce blood flow may increase the risk of ischemic events. Systematic reviews of prospective cohort studies of hemostatic and rheological variables suggest that increasing blood levels of fibrinogen, von Willebrand factor, tissue plasminogen activator antigen, fibrin D-dimer, hematocrit, viscosity, and erythrocyte sedimentation rate may be predictors of risk of coronary heart disease (CHD), but their causal relevance is unknown. At present, data for the associations of other hemostatic variables with CHD, and for the associations of hemostatic variables with stroke, venous thromboembolism, and mortality, is relatively sparse and inconclusive. More detailed syntheses of existing prospective data (such as the Fibrinogen Studies Collaboration), observational studies of CHD and the genetic determinants of these plasma components, as well as large-scale randomized trials should help to determine whether or not these associations are (1) useful in prediction of cardiovascular risk and/or (2) of causal significance.


Diagnostic value of endoscopic ultrasonography in periampullary duodenal tumours.
The objective of this study was to investigate the diagnostic value of endoscopic ultrasonography (EUS) for tumours around the duodenal ampullary. A retrospective analysis was performed on cases diagnosed and treated in our hospital from October 2016 to August 2021 due to the lesions around the duodenal ampulla. All patients received EUS, abdominal enhanced computed tomography (CT) and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography (MRI-MRCP). Pathological diagnosis was used to verify the accuracy of the imaging findings. The detection rates of periampullary tumours by EUS, abdominal enhanced CT and MRI-MRCP were determined and compared. A total of 86 patients were included in this study. According to the pathological diagnosis, the detection rate of EUS was 87% (36/41) for periampullary tumour lesions with a tumour diameter <1 cm, which was significantly higher than that of MRI-MRCP (59%, 24/41) (P = 0.003) and CT (44%, 18/41) (P < 0.001). For periampullary tumour lesions with a tumour diameter ≥1 cm, the detection rate of MRI-MRCP was 93% (42/45), which was significantly higher than that of EUS (78%, 35/45) (P = 0.036) and CT (76%, 34/45) (P = 0.02). EUS can accurately detect tumour lesions around the ampullary part of the duodenum with minimal gas interference. For periampullary tumour lesions <1 cm, EUS has better diagnostic accuracy than abdominal-enhanced CT and MRI-MRCP. In addition, a biopsy of the lesion can be performed at the same time during the EUS examination. Therefore, EUS has an important clinical significance and value in the diagnosis of duodenal periampullary tumours.


Research methodology: endocrinologic measurements in exercise science and sports medicine.
To provide background information on methodologic factors that influence and add variance to endocrine outcome measurements. Our intent is to aid and improve the quality of exercise science and sports medicine research endeavors of investigators inexperienced in endocrinology. Numerous methodologic factors influence human endocrine (hormonal) measurements and, consequently, can dramatically compromise the accuracy and validity of exercise and sports medicine research. These factors can be categorized into those that are biologic and those that are procedural-analytic in nature. Researchers should design their studies to monitor, control, and adjust for the biologic and procedural-analytic factors discussed within this paper. By doing so, they will find less variance in their hormonal outcomes and thereby will increase the validity of their physiologic data. These actions can assist the researcher in the interpretation and understanding of endocrine data and, in turn, make their research more scientifically sound.


What's New in Grade II and Grade III Gliomas?
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH-mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients. We further summarize the results of recent pivotal trials addressing treatment of grade II and grade III gliomas and highlight promising IDH-mutant-specific therapies on the horizon.


m6aViewer: software for the detection, analysis, and visualization of N6-methyladenosine peaks from m6A-seq/ME-RIP sequencing data.
Recent methods for transcriptome-wide N6-methyladenosine (m6A) profiling have facilitated investigations into the RNA methylome and established m6A as a dynamic modification that has critical regulatory roles in gene expression and may play a role in human disease. However, bioinformatics resources available for the analysis of m6A sequencing data are still limited. Here, we describe m6aViewer-a cross-platform application for analysis and visualization of m6A peaks from sequencing data. m6aViewer implements a novel m6A peak-calling algorithm that identifies high-confidence methylated residues with more precision than previously described approaches. The application enables data analysis through a graphical user interface, and thus, in contrast to other currently available tools, does not require the user to be skilled in computer programming. m6aViewer and test data can be downloaded here: http://dna2.leeds.ac.uk/m6a.


Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion.
Metastasis is the major cause of death in ovarian cancer patients. Given that the molecular mechanism underlying metastasis formation is critical for improving therapeutic development and clinical treatment, it must be fully understood. Recent studies have revealed that lipid kinase type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the metastasis of breast cancer and colon cancer by regulating cell migration and invasion. However, its role in the progression of ovarian cancer is unclear. Here we showed that PIPKIγ expression is upregulated in multiple epithelial ovarian cancer cell lines. Silencing of PIPKIγ impaired PI3K/AKT signaling and inhibited the aggressive behaviors of epithelial ovarian cancer cells, including proliferation, migration and invasion. Moreover, we found that PIPKIγ was required for the activation of signal transducer and activator of transcription 3 (STAT3) in epithelial ovarian cancer cells, indicating that STAT3 may also be engaged in the PIPKIγ-dependent aggressiveness of epithelial ovarian cancer cells. Our results, for the first time, identified PIPKIγ as a novel regulator in epithelial ovarian cancer cells that promotes cell proliferation, migration and invasion by activating multiple signaling pathways. Therefore, we propose that PIPKIγ could potentially be a therapeutic target for the early detection and treatment of epithelial ovarian cancer. Further studies employing in vivo models are necessary to test this possibility.


Prognostic markers in AIDS-related cryptococcal meningitis.
Despite the advent and expanding access to antiretroviral therapy, HIV-associated cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with this infection in resource-limited settings. We prospectively studied the clinical, biochemical and mycological parameters of 30 HIV patients diagnosed with cryptococcal meningitis at our centre over a period of 6 months with a view to identify prognostic factors predictive of poor outcome. Our study documented a mortality rate of 36.7%. Age, sex and previous diagnosis of HIV had no bearing on the survival outcome of patients. The study identified several poor prognostic factors including low GCS score, papilledema, elevated CSF opening pressure (>250 mm of H2O) and lack of regular HIV care in those with a prior diagnosis of HIV. CSF pleocytosis was significantly higher in the mortality group. There have been relatively few attempts to focus on poor prognostic markers associated with AIDS related Cryptococcal meningitis in Asian patients. Our study highlights how simple bedside clinical tools like ophthalmoscopy and CSF manometry can help in risk stratification in this group of patients.


Probiotics and antimicrobial protein and peptide levels in preterm infants.
To characterise the secreted and inducible antimicrobial protein and peptide (APP) levels in a prospective cohort of preterm infants (<30 weeks gestational age) with or without Bifidobacterium breve M16V supplementation during the first month of life. We analysed serial biosamples of infants who did (n = 13) or did not receive (n = 62) B. breve (3 × 109 cfu/day). Peripheral blood was obtained on days 1, 14 and 28, and infant stool prior to commencement of probiotic supplementation and on day 21. Levels of APP (bactericidal/permeability inducing protein (BPI), beta defensins 1 and 2, lactoferrin, human cathelicidin, secretory phospholipase A2) in plasma and stool were determined. Further, we characterised induced APP levels in whole blood cultured with live S. epidermidis or with agonists of Toll-like receptors 2/6 and 4. Stool, plasma and stimulated blood APP levels changed significantly during the first month of life. Supplementation with B. breve did not affect basal or stimulated APP levels except for a transient increase in inducible BPI. Supplementation with B. breve does not appear to act via modulation of systemic or enteric APP expression in preterm infants although small effects cannot be excluded. Further work with other probiotic preparations is warranted.


Comparison of the in Vitro Uptake and Toxicity of Collagen- and Synthetic Polymer-Coated Gold Nanoparticles.
We studied the physico-chemical properties (size, shape, zeta-potential), cellular internalization and toxicity of gold nanoparticles (NPs) stabilized with the most abundant mammalian protein, collagen. The properties of these gold NPs were compared to the same sized gold NPs coated with synthetic poly(isobutylene-alt-maleic anhydride) (PMA). Intracellular uptake and cytotoxicity were assessed in two cell lines (cervical carcinoma and lung adenocarcinoma cells) by employing inductively-coupled plasma-mass spectrometry (ICP-MS) analysis and a cell viability assay based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. We found that the collagen-coated gold NPs exhibit lower cytotoxicity, but higher uptake levels than PMA-coated gold NPs. These results demonstrate that the surface coating of Au NPs plays a decisive role in their biocompatibility.