Generalized EM-type reconstruction algorithms for emission tomography.
We provide a general form for many reconstruction estimators of emission tomography. These estimators include Shepp and Vardi's maximum likelihood (ML) estimator, the quadratic weighted least squares (WLS) estimator, Anderson's WLS estimator, and Liu and Wang's multi-objective estimator, and others. We derive a generic update rule by constructing a surrogate function. This work is inspired by the ML-EM (EM, expectation maximization), where the latter naturally arises as a special case. A regularization with a specific form can also be incorporated by De Pierro's trick. We provide a general and quite different convergence proof compared with the proofs of the ML-EM and De Pierro. Theoretical analysis shows that the proposed algorithm monotonically decreases the cost function and automatically meets nonnegativity constraints. We have introduced a mechanism to provide monotonic, self-constraining, and convergent algorithms, from which some interesting existing and new algorithms can be derived. Simulation results illustrate the behavior of these algorithms in term of image quality and resolution-noise tradeoff.


Palmitate-induced insulin resistance is attenuated by Pioglitazone and EGCG through reducing the gluconeogenic key enzymes expression in HepG2 cells.
Palmitate causes insulin resistance (IR) in insulin target tissue. Pioglitazone (an anti-hyperglycemic agent) and epigallocatechin gallate (EGCG, a dietary supplement) can be used for the treatment of type 2 diabetes. However, their molecular effects on gluconeogenesis remain unclear. Hence, we aimed to investigate the simultaneous effect of these anti-hyperglycemic agents on gluconeogenesis through in vitro experiments. HepG2 cells were treated with 0.5 mM palmitate, 10 μM pioglitazone, and 40 μM epigallocatechin gallate (EGCG). Gene expression assay was used to investigate the underlying mechanism. Glucose production assay was applied in culture medium to evaluate the activity of gluconeogenesis pathway. Palmitate induced IR could significantly increase G6Pase and PEPCK gene expressions by 58 and 30%, respectively, compared to the control. EGCG reduced the expression of PEPCK and G6Pase by 53 and 67%, respectively. Pioglitazone reduced the mRNA level of PEPCK and G6Pase by 58 and 62% respectively. Combined treatment of insulin-resistant cells with EGCG and pioglitazone significantly decreased the mRNA level of PEPCK and G6Pase by 73 and 80%, respectively. Treatment with palmitate increased glucose production by 50% in HepG2 cells. When the insulin resistant HepG2 cells were treated alone with EGCG and pioglitazone, the glucose production reduced by 50 and 55%, respectively. The combined treatment with EGCG and pioglitazone resulted in 69% reduction in glucose production compared to the palmitate treated HepG2 cells. These data suggest the additive inhibitory effect of co-treatment with pioglitazone and EGCG on the gluconeogenesis pathway in palmitate-induced insulin resistance HepG2 cells.


Associations between workplace violence and suicidal ideation among Chinese medical staff: a propensity score matching analysis.
Physical and mental health problems had been identified as the negative outcomes of workplace violence (WPV) against medical staff. Considering the proven associations between physical and mental health and suicidal ideation, it is reasonable to assume that WPV may associate with suicidal ideation. However, few studies were conducted to explore the relationship between WPV and their suicidal ideation against medical staff. Based on a cross-sectional design, 3, 426 medical staff working in general hospitals were interviewed in Shandong Province, China. Socio-demographic characteristics, work-related factors, psychological variables, WPV, and suicidal ideation were evaluated. Propensity score matching (PSM) was performed to explore the association between WPV and suicidal ideation. The prevalence of suicidal ideation among medical staff was 9.1% (312/3426), and 52.2% (1788/3426) of medical staff reported the WPV experience. Before PSM, we found that the association between WPV and suicidal ideation was statistically significant (aOR = 1.606, p < 0.01). After PSM, there was a statistically significant correlation between WPV and suicidal ideation (aOR = 1.525, p < 0.01). This study supported the correlations between WPV against medical staff and their suicidal ideation. The results of PSM further implied that WPV might cause suicidal ideation among medical staff. Psychological health, especially for suicidal ideation, should be paid attention for medical staff with WPV experiences.


The effects of physical activity interventions on glycated haemoglobin A1c in non-diabetic populations: a protocol for a systematic review and meta-analysis.
Epidemiological evidence suggests that physical activity has a positive effect on reducing glycated haemoglobin A1c (HbA1c) levels not only in diabetics, but also in healthy subjects. Moreover, a positive association of HbA1c levels with cardiovascular disease and mortality in non-diabetic populations has recently been reported. This is a protocol for a systematic review and meta-analysis aiming to estimate the effects of physical activity on glycaemic control measured by HbA1c levels in non-diabetic populations; and to determine which type of physical activity has a greater influence on glycaemic control. The search will be conducted using MEDLINE, EMBASE, the Cochrane Library and Web of Science databases from inception to mid-2017. Randomised controlled trials, non-randomised experimental studies and controlled pre-post studies written in English, Portuguese, French or Spanish will be included. The Cochrane Collaboration's tool and The Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. Standardised pre-post intervention mean differences of HbA1c will be calculated as the primary outcome. Subgroup analyses will be performed based on the characteristics of physical activity intervention and population included in the studies. This systematic review will synthesise evidence on the association of physical activity and HbA1c in non-diabetic populations. This study is important from the clinical and public health point because it will estimate the effect of physical activity on the glycemic control, and it will also examine which is the type of physical activity that should be recommended for preventing type 2 diabetes and its complications. The results will be disseminated by publication in a peer-reviewed journal. Ethical approval will not be required because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy. PROSPERO CRD42016050991.


Women's perceptions of body mass index.
Women may not have an accurate perception of their own body weight and vary in understanding about healthy weight. The study's aim was to assess women's accuracy of their own body mass index (BMI), understanding of the healthiest body weight and opinion of the most attractive body figure. We surveyed 385 women (age, 19-77 years) attending our obstetrics and gynaecology clinics with an anonymous survey demonstrating a selection of Body Image Scale graphics to represent their current body, the healthiest body and the most attractive body. There was a significant positive correlation between Body Image Scale graphic selected and BMI (r = 0.80; P < 0.0001). The selected Body Image Scale graphic was accurate or within 1 graphic higher or lower than BMI in 88% of participants. The mean BMI of women accurately selecting the appropriate graphic (BMI, 29 ± 8 kg m-2 ) was significantly lower than that of women selecting the graphic lower than their BMI (BMI, 37 ± 7 kg m-2 ) but was significantly higher than those selecting a graphic higher than their BMI (BMI, 25 ± 4 kg m-2 ). For healthiest figure, 58% women selected a graphic representing overweight BMI and 2% women selected a graphic with Class 1 obesity. For most attractive figure, 48% women selected a graphic representing normal BMI, 49% women selected a graphic representing overweight BMI and 1% of women selected a graphic with Class 1 obesity. It is important to provide counselling about ideal weight, healthy lifestyle choices and consequences of obesity.


Flexible nine-channel photodetector probe facilitated intraspinal multisite transcutaneous photobiomodulation therapy dosimetry in cadaver dogs.
Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains speculative due to the lack of evidence for whether photobiomodulatory irradiances can be transcutaneously delivered to the spinal cord under a clinically acceptable PBMT surface irradiation protocol. We developed a flexible nine-channel photodetection probe for deployment within the spinal canal of a cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT irradiance at nine sites over an eight-cm spinal canal length. The probe was built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80 mm×2.10 mm×1.15 mm (length×width×height). Each photodiode was individually calibrated to deliver 1 V per 7.58 μW/cm2 continuous irradiance at 850 nm. The outputs of eight photodiodes were logged concurrently using a data acquisition module interfacing eight channels of differential analog signals, while the output of the ninth photodiode was measured by a precision multimeter. This flexible probe rendered simultaneous intraspinal (nine-site) measurements of transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a surface continuous irradiance of 3.14 W/cm2 applied off-contact between L1 and L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48 μW/cm2 without the skin and 5.68 μW/cm2 with the skin.


Characterization of developmental defects in the forebrain resulting from hyperactivated mTOR signaling by integrative analysis of transcriptomic and proteomic data.
Hyperactivated mTOR signaling in the developing brain has been implicated in multiple forms of pathology including tuberous sclerosis complex (TSC). To date, various phenotypic defects such as cortical lamination irregularity, subependymal nodule formation, dysmorphic astrocyte differentiation and dendritic malformation have been described for patients and animal models. However, downstream networks affected in the developing brain by hyperactivated mTOR signaling have yet to be characterized. Here, we present an integrated analysis of transcriptomes and proteomes generated from wild-type and Tsc1/Emx1-Cre forebrains. This led to comprehensive lists of genes and proteins whose expression levels were altered by hyperactivated mTOR signaling. Further incorporation of TSC patient data followed by functional enrichment and network analyses pointed to changes in molecular components and cellular processes associated with neuronal differentiation and morphogenesis as the key downstream events underlying developmental and morphological defects in TSC. Our results provide novel and fundamental molecular bases for understanding hyperactivated mTOR signaling-induced brain defects which can in turn facilitate identification of potential diagnostic markers and therapeutic targets for mTOR signaling-related neurological disorders.


Drug addiction and diabetes: South Asian action.
Both diabetes and drug addiction are common phenomena across the world. Drug abuse impacts glycaemic control in multiple ways. It becomes imperative, therefore, to share guidance on drug deaddiction in persons with diabetes. The South Asian subcontinent is home to specific forms and patterns of drug abuse. Detailed study is needed to ensure good clinical practice regarding the same. This communication provides a simple and pragmatic framework to address this issue, while calling for concerted action on drug deaddiction in South Asia.


Relationship of cardiorespiratory fitness with screen time and physical activity in adolescents.
To determine the correlation of cardiorespiratory fitness with screen time and physical activity in healthy adolescents. The analytical cross-sectional study was conducted at the Foundation University, Islamabad, Pakistan, from February to July 2019, and comprised healthy adolescents aged 11-17 years of both genders who were enrolled from various schools of Rawalpindi and Islamabad. Cardiorespiratory fitness was evaluated through YMCA 3 min Step test, physical activity levels were evaluated using physical activity questionnaire for adolescents, and screen time was evaluated using Healthy Lifestyle in Europe by Nutrition in Adolescence screen time questionnaire. Data was analysed using SPSS 21. Of the 250 adolescents, 128(51.2%) were males and 122(48.8%) were females. The overall mean age was 14.24±2.177 years (range: 11-17 years). There was no significant correlation between cardiorespiratory fitness and physical activity (p=0.15), and between cardiorespiratory fitness and screen time (p=0.58). There was found to be no significant correlation between cardiorespiratory fitness and physical activity, and between cardiorespiratory fitness and screen time in healthy adolescents.


A novel immunohistochemical staining method allows ultrarapid detection of lymph node micrometastases while conserving antibody.
We developed a novel ultrarapid immunohistochemical staining method in which an AC electric field is used to facilitate detection of tumor cells. Frozen sections of non-small cell lung cancer in lymph nodes were fixed in acetone for 2 min, after which they were incubated for 2 min with an anti-pancytokeratin antibody cocktail and then with EnVision(TM) complex under an alternating current (AC) electric field. The sections were then incubated with a chromogen (3,3'diaminobenzidine) for 3 min and counterstained with hematoxylin. This method enabled detection of tumor cells in frozen sections in less than 15 min. In addition, we were able to reduce the amount of antibody used by more than 90% when the sections were incubated under the AC electric field for a longer period. This method could be a useful tool for frozen section diagnosis and research. Furthermore, with this method the cost of immunohistochemical staining can be reduced.


Inter-comparison of personal monitors for nanoparticles exposure at workplaces and in the environment.
Personal monitors based on unipolar diffusion charging (miniDiSC/DiSCmini, NanoTracer, Partector) can be used to assess the individual exposure to nanoparticles in different environments. The charge acquired by the aerosol particles is nearly proportional to the particle diameter and, by coincidence, also nearly proportional to the alveolar lung-deposited surface area (LDSA), the metric reported by all three instruments. In addition, the miniDiSC/DiSCmini and the NanoTracer report particle number concentration and mean particle size. In view of their use for personal exposure studies, the comparability of these personal monitors was assessed in two measurement campaigns. Altogether 29 different polydisperse test aerosols were generated during the two campaigns, covering a large range of particle sizes, morphologies and concentrations. The data provided by the personal monitors were compared with those obtained from reference instruments: a scanning mobility particle sizer (SMPS) for LDSA and mean particle size and a ultrafine particle counter (UCPC) for number concentration. The results indicated that the LDSA concentrations and the mean particle sizes provided by all investigated instruments in this study were in the order of ±30% of the reference value obtained from the SMPS when the particle sizes of the test aerosols generated were within 20-400nm and the instruments were properly calibrated. Particle size, morphology and concentration did not have a major effect within the aforementioned limits. The comparability of the number concentrations was found to be slightly worse and in the range of ±50% of the reference value obtained from the UCPC. In addition, a minor effect of the particle morphology on the number concentration measurements was observed. The presence of particles >400nm can drastically bias the measurement results of all instruments and all metrics determined.


Allergy to coitus.
Acute systemic hypersensitivity reactions to semen are rare but may be life-threatening. Chronic or recurrent local reactions are more common and may be misdiagnosed as infective or nonspecific vaginitis. The antigen(s) involved in these reactions reside in a glycoprotein fraction of seminal plasma. Allergic vulvovaginitis may also occur in sensitized women when they are exposed to exogenous allergens such as drugs, food and infective agents during sexual activity. Skin testing and other relevant investigations are indicated when these disorders are suspected. Condom usage will prevent symptoms of coital allergy. Desensitization has had variable success in acute systemic hypersensitivity. Precoital antihistamines may modify local reactions.


Evaluation of texture features in spatial and frequency domain for automatic discrimination of histologic tissue.
To investigate the applicability of different texture features in automatic discrimination of microscopic views from benign common nevi and malignant melanoma lesions. In tissue counter analysis (TCA) the images are dissected into square elements used for feature calculation. The first class of features is based on the histogram, the co-occurrence matrix and the texture moments. The second class is derived from spectral properties of the wavelet Daubechie 4 and the Fourier transform. Square elements from images of a training set are classified by Classification and Regression Trees analysis. Features from the histogram and the co-occurrence matrix enable correct classification of 94.7% of nevi elements and 92.6% of melanoma elements in the training set. Classification results are applied to individual test set cases. Discriminant analysis based on the percentage of "malignant elements" showed correct classification of all nevi cases and 95% of melanoma cases. Features derived from the wavelet and Fourier spectrum showed correct results for 88.8% and 79.3% of nevi and 85.6% and 81.5% of melanoma elements, respectively. TCA is a potential diagnostic tool in automatic analysis of melanocytic skin tumors. Histogram and co-occurrence matrix features are superior to the wavelet and the Fourier features.


Lower extremity soft tissue conditions.
Lower extremity soft tissue injuries and overuse conditions are frequently encountered among athletes. Muscles are frequently strained or contused, arteries and nerves can become entrapped, and tendons and bursae can become inflamed. Familiarity with the anatomy of the involved area is essential for making the correct diagnosis. The majority of these conditions can be accurately diagnosed based on a thorough history and physical examination alone, without the need for expensive imaging or invasive tests. Most of these conditions can be successfully managed conservatively, avoiding surgical intervention.


Exploiting Natural Cross-reactivity between Human Immunodeficiency Virus (HIV)-1 p17 Protein and Anti-gp41 2F5 Antibody to Induce HIV-1 Neutralizing Responses In Vivo.
Anti-p17 antibodies are able to neutralize human immunodeficiency virus (HIV) entry in a mouse model. In this study, we identified a region of sequence similarity between the epitopes of anti-p17 neutralizing antibodies and anti-gp41 neutralizing 2F5 antibody and verified cross-reactivity between p17 and 2F5 in vitro. The p17 sequence was modified to increase sequence identity between the p17 and 2F5 epitopes, which resulted in enhanced cross-reactivity in vitro. Immunogenicity of wild-type and modified p17 was characterized in a rabbit model. Both wild-type and mutated p17 induced anti-gp41 responses in rabbits; sera from these animals reacted with gp41 from different HIV clades. Moreover, introduction of the 2F5 sequence in p17 resulted in induction of antibodies with partially neutralizing activity. Based upon these data, we suggest that the natural cross-reactivity between HIV-1 p17 protein and 2F5 antibody can be exploited to induce antibodies with neutralizing activity in an animal model.


A novel strategy for selection and validation of reference genes in dynamic multidimensional experimental design in yeast.
Understanding the dynamic mechanism behind the transcriptional organization of genes in response to varying environmental conditions requires time-dependent data. The dynamic transcriptional response obtained by real-time RT-qPCR experiments could only be correctly interpreted if suitable reference genes are used in the analysis. The lack of available studies on the identification of candidate reference genes in dynamic gene expression studies necessitates the identification and the verification of a suitable gene set for the analysis of transient gene expression response. In this study, a candidate reference gene set for RT-qPCR analysis of dynamic transcriptional changes in Saccharomyces cerevisiae was determined using 31 different publicly available time series transcriptome datasets. Ten of the twelve candidates (TPI1, FBA1, CCW12, CDC19, ADH1, PGK1, GCN4, PDC1, RPS26A and ARF1) we identified were not previously reported as potential reference genes. Our method also identified the commonly used reference genes ACT1 and TDH3. The most stable reference genes from this pool were determined as TPI1, FBA1, CDC19 and ACT1 in response to a perturbation in the amount of available glucose and as FBA1, TDH3, CCW12 and ACT1 in response to a perturbation in the amount of available ammonium. The use of these newly proposed gene sets outperformed the use of common reference genes in the determination of dynamic transcriptional response of the target genes, HAP4 and MEP2, in response to relaxation from glucose and ammonium limitations, respectively. A candidate reference gene set to be used in dynamic real-time RT-qPCR expression profiling in yeast was proposed for the first time in the present study. Suitable pools of stable reference genes to be used under different experimental conditions could be selected from this candidate set in order to successfully determine the expression profiles for the genes of interest.


Saphenous--peritoneal shunt in refractory ascites: a neglected technique.
Management of intractable ascites has always been a challenge. Peritoneovenous shunt (PVS) plays a major role in the surgery of intractable ascites in patients with liver cirrhosis. Positive pressure gradient between the ascitic fluid and venous pressure leading to one-way drainage of ascitic fluid into venous circulation is the mainstay. Over decades, various modifications of shunting technique have been done. Here we report our experience with this procedure which is safe, easy and effective. Here the long saphenous vein is used as a drainage system. One-way ascites flow is ensured by a natural valve in the saphenous orifice.


[Central pontine myelinolysis with a hyperintense lesion in diffusion weighted MRI: overview by means of a case report].
Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with demyelination of other areas of the central nervous system (CNS). The etiology and pathogenesis of this disorder are still not fully understood. However, almost all cases of CPM are related to severe diseases or chronic alcoholism and occur in the setting of rapidly corrected serum hyponatremia and hypotonicity respectively. Depending on the involvement of other CNS structures, the clinical picture can vary considerably. Magnetic resonance imaging is the most sensitive investigation for the antemortem diagnosis of CPM, although the radiological findings lag behind and do not necessarily correlate with the clinical picture. Quite obviously diffusion-weighted imaging can be useful in the rapid diagnosis of CPM. This short review summarizes the current knowledge on the pathogenesis, clinical presentation, radiological findings, prognosis and therapeutic approaches of CPM. Characteristical clinical features and MR-findings including hyperintensity on diffusion-weighted images are illustrated by a typical case.


Epidemiologic and clinical survey of Behcet's disease in Korea: the first multicenter study.
The prevalence of Behcet's disease is the highest in the East Asian and the Mediterranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.


A study on microzooplankton community from the coastal waters of eastern Arabian Sea: emphasis on the dominance of heterotrophic dinoflagellates.
We studied the community composition of microzooplankton (MZP) from the surface waters off Candolim, Goa. The MZP communities were examined for the year 2013, covering different seasons and four stations (Near-shore: G3 & G4, offshore: G5 & G6). A total of 30 species belonging to 24 genera were recorded, which include loricate ciliates (LC: 14 species of 13 genera), aloricate ciliates (ALC: 5 species of 3 genera), heterotrophic dinoflagellates (HDS: 11 species of 8 genera), and copepod nauplii. The MZP abundance in the coastal waters varied spatially irrespective of different seasons, with higher abundance in the offshore stations (G5 & G6, 38-127 cells L-1) and lower abundance in the near-shore stations (G3 & G4, 20-97 cells L-1). The MZP community composition showed the dominance of HDS (16-85%) in the near-shore stations during most of the seasons and inferiority during NEM (16-18%). Moreover, all the coastal waters (near and offshore) were dominated by HDS (58-85%) during spring inter-monsoon. The dominant species of HDS were Dinophysis apicata, Dinophysis caudata, Prorocentrum micans, Protoperidinium breve, Protoperidinium latistriatum, and Protoperidinium granii. The statistical analysis (Canonical correspondence analysis and Spearman's rank correlation) depicts that the MZP abundance and community composition were mainly controlled by salinity (r = 0.4-0.7). Whereas the dominance of HDS in the coastal waters could be the reason for its mixotrophic nature and diverse feeding mechanism. Thus, a strong positive correlation between the HDS and LC (r = 0.73-0.92) showed the feeding ability of HDS in their relative community.


Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial.
The high morbidity and mortality caused by smoking highlights the importance of investigating new strategies for smoking cessation or reduction. Galantamine is an acetylcholinesterase inhibitor that increases the effect of acetylcholine (ACh). The nicotinic ACh receptor is activated via positive allosteric modulation (APL). We investigated whether galantamine reduces smoking by performing a 24-week randomized, placebo-controlled, multicentric clinical trial in recently detoxified alcohol-dependent patients. We included all study subjects irrespective of an intention or motivation to abstain from nicotine. Specific treatment for cessation or reduction of smoking was not provided. Smoking behavior was assessed by means of patients' diaries. The nicotine metabolite cotinine was measured to verify the number of smoked cigarettes as documented in the patient's diary. 114 randomized smokers received galantamine (n = 56) or placebo (n = 58) for 12 weeks. Follow-up examinations were terminated after an additional 12 weeks without treatment. Smoking behavior did not differ between both groups at baseline. After treatment, the intention-to-treat analysis revealed significant differences with a 20% lower cumulative number of smoked cigarettes and a 15% lower number of smoking days in the galantamine group compared to placebo. The average number of smoked cigarettes per smoking day as well as the cotinine values decreased about 10%. Cotinine values showed a positive correlation with the number of documented cigarettes, validating the patients' diaries. Our tentative data indicate that galantamine reduces smoking behavior even without any additional specific intervention. We suggest introducing the term "substitution therapy" into the treatment of smoking. This result could open up a new treatment approach for groups of patients which usually have a low motivation for change.


[A case of adult-onset type II citrullinemia in an elderly patient].
A 72-year-old man presented with consciousness disturbance. The results of brain magnetic resonance imaging and cerebrospinal fluid examination were normal, but triphasic waves were noted on electroencephalography. His plasma ammonia level was elevated due to which encephalopathy secondary to hyperammonemia was suspected. However, his liver function was normal, and no evidence of cirrhosis or portal-systemic shunt was noted. The patient's medical history revealed that he had a tendency to excessively consume pulse products since childhood, and an amino acid analysis showed elevation of citrulline and arginine levels. Thus, we diagnosed the patient with an extremely rare case of adult-onset type II citrullinemia, which was triggered by cessation of the intake of pulse foods (soybeans and peanuts) due to dental problems.


Intravenous human immunoglobulin for the treatment of severe longitudinal extensive transverse myelitis associated with systemic lupus erythematous.
A 39-year-old female with systemic lupus erythematous (SLE) presented with fever, headaches and rash and was treated with empiric antibiotics for a presumable meningitis. However, cerebrospinal fluid turned out to be sterile and fever persisted with onset of hyporeflexive paraparesis with sensory loss below D10. Magnetic resonance imaging (MRI) demonstrated intradural-extramedullary hematoma (related to traumatic lumbar puncture), which was successfully drained. Subsequent surgical scar infection occurred and was treated accordingly. Due to persistent deficits and urinary retention development, she repeated MRI, which showed holocord abnormal T2 hyperintensity. After excluding other causes, SLE-associated longitudinal extensive transverse myelitis was diagnosed and treated with high-dose steroids and intravenous human immunoglobulin (IVIG), with reduction in intensity and extension of abnormal T2 signal within only one week. Monthly IVIG was kept for 6 months with progressive ability to walk and MRI findings resolution in 3 months. Four months after IVIG suspension no recurrence occurred.


TCTP/HRF pathway and angiogenesis: a feasible intercourse in chronic lymphocytic leukemia.
This prospective study was planned to determine the intercourse between translationally controlled tumor protein (TCTP)/histamine releasing factor (HRF)/histamine pathway and angiogenesis in chronic lymphocytic leukemia (CLL). A total of 153 CLL patients were included. Serum histamine levels were higher in CLL patients. A positive correlation was found between microvessel density (MVD)-mast cell (MC) count; MVD-TCTP/HRF and MC count-TCTP/HRF. Microvessel density, MC and ZAP 70 were significantly higher in TCTP/HRF-positive group. Time to first treatment was shorter in patients with increased MVD and TCTP/HRF. Further data is essential to ascertain the role of TCTP/HRF pathway in tumor angiogenesis and CLL prognosis.


Nephrogenic fibrosing dermopathy in a renal transplant recipient with tubulointerstitial nephritis and uveitis.
We report a patient with nephrogenic fibrosing dermopathy. He had chronic renal failure with arthritis, uveitis and histologically severe tubulointerstitial nephritis for which he received a renal transplant from a family relative. After an episode of acute renal failure with the transplant he developed painful, erythematous, firm papules and plaques with geographic borders on the legs, anterior thorax and elbow. A skin biopsy revealed increased fibroblast and collagen fiber content of the dermis and subcutaneous septae. Mucin deposition, sparse smooth-muscle-actin-positive cells and an increased number of CD34-positive cells in the deep dermis were found. After several weeks of hemodialysis, the lesions changed from an inflammatory to a purely sclerotic phase. The fibrocyte, a recently described circulating cell type, that is deposited in scar tissue may be involved in the pathogenesis of this novel pseudosclerodermatous skin disorder.


What Case Managers Should Know About Their Roles and Functions: A National Study From the Commission for Case Manager Certification: Part 1.
The purpose of this national role and function study was to identify the essential activities and necessary knowledge areas for effective case manager practice from the perspective of those currently functioning in various care settings and across diverse professional disciplines. The national study covered all case management practices and/or work settings across the full continuum of health care. This cross-sectional descriptive study used the practice analysis method and online survey research design. It employed a purposive sample of case managers, in which 52,370 individuals received an invitation to participate. Data collection completed over a 4-week period, resulting in 7,668 useable survey responses (nearly a 15% response rate). The study identified the common activities and knowledge areas necessary for competent and effective performance of case managers, as is highlighted in this article, which is the first of a 2-part series on the role and function study. The results informed the needed update of the test specifications for the Certified Case Manager (CCM) certification examination, as will be delineated in Part 2 of the article series, to ensure that it continues to be substantiated in current practice. Of special note are the emergence of specific activity and knowledge domains in the area of case management ethical, legal, and practice standards, and an increase in the number of employers requiring certified case managers to fill vacant positions and compensating them financially for such qualifications. This study helps keep the CCM credentialing examination evidence-based and maintain its validity for evaluating competency of case managers. Specifically, the study identified essential activities and knowledge domains that define competent case management practice. Findings can be used for developing programs and curricula for the training and development of case managers. The study instrument also can be used for further research of case management practice.


Reduced glyoxalase 1 activity in carotid artery plaques of nondiabetic patients with increased hemoglobin A1c level.
Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level. HbA1c level was determined in venous blood of patients with carotid artery disease. Protein level of GLO1 was measured in endarterectomy-derived carotid artery plaques by Western blotting. Activity was measured by spectrophotometric assay in the plaques as well as in the erythrocytes; GLO1 activity in erythrocytes was compared with that in a cohort of healthy individuals (n = 15; 33% men; average age, 60 years). There were 36 patients with carotid artery disease (69% men; average age, 69 years) included in this study and divided into two equal groups: group I, HbA1c < 5.7% (<39 mmol/mol); and group II, 5.7% ≤ HbA1c < 6.5% (39 mmol/mol ≤ HbA1c < 48 mmol/mol). GLO1 activity in carotid plaques was reduced by 29% in group II compared with group I (P = .048), whereas protein expression was unchanged (P = .25). Analysis of GLO1 activity in erythrocytes revealed no difference between the groups (P = .36) or in comparison to healthy controls (P = .15). Examination of clinical parameters showed an increased amount of patients with concomitant peripheral arterial disease in group II (44% vs 10%; P = .020). Reduction of GLO1 activity in atherosclerotic lesions of nondiabetic patients with increased HbA1c is associated with a functional involvement of this protective enzyme in atherogenesis. Systemic GLO1 activity seems to be independent of both HbA1c and localized atherosclerosis as it was unchanged between group I and group II as well as compared with healthy controls, respectively.


The initial stages of radiation damage in ionic liquids and ionic liquid-based extraction systems.
Radical intermediates generated in radiolysis and photoionization of ionic liquids (ILs) composed of ammonium, phosphonium, pyrrolidinium, and imidazolium cations and bis(triflyl)amide, dicyanamide, and bis(oxalato)borate anions have been studied using magnetic resonance spectroscopy. Large yields of terminal and penultimate C-centered radicals are observed in the aliphatic chains of the phosphonium, ammonium, and pyrrolidinium cations, but not for imidazolium cation. This pattern is indicative of efficient deprotonation of a hole trapped on the parent cation (the radical dication) that competes with rapid electron transfer from a nearby anion. This charge transfer leads to the formation of stable N- or O-centered radicals; the dissociation of parent anions is a minor pathway. Addition of 10-40 wt % of trialkyl phosphate (a common extraction agent) has relatively little effect on the fragmentation of the ILs. The yield of the alkyl radical fragment generated by dissociative electron attachment to the trialkyl phosphate is <4% of the yield of the radical fragments derived from the IL solvent. The import of these observations for radiation stability of the prospective nuclear cycle extraction systems based upon the ILs is discussed.


Rapid autophagic regression of the milk gland during involution is critical for maximizing tsetse viviparous reproductive output.
Tsetse flies are important vectors of human and animal trypanosomiasis. Ability to reduce tsetse populations is an effective means of disease control. Lactation is an essential component of tsetse's viviparous reproductive physiology and requires a dramatic increase in the expression and synthesis of milk proteins by the milk gland organ in order to nurture larval growth. In between each gonotrophic cycle, tsetse ceases milk production and milk gland tubules undergo a nearly two-fold reduction in width (involution). In this study, we examined the role autophagy plays during tsetse fly milk gland involution and reproductive output. Autophagy genes show elevated expression in tissues associated with lactation, immediately before or within two hours post-parturition, and decline at 24-48h post-parturition. This expression pattern is inversely correlated with that of the milk gland proteins (lactation-specific protein coding genes) and the autophagy inhibitor fk506-bp1. Increased expression of Drosophila inhibitor of apoptosis 1, diap1, was also observed in the milk gland during involution, when it likely prevents apoptosis of milk gland cells. RNAi-mediated knockdown of autophagy related gene 8a (atg8a) prevented rapid milk gland autophagy during involution, prolonging gestation, and reducing fecundity in the subsequent gonotrophic cycle. The resultant inhibition of autophagy reduced the recovery of stored lipids during the dry (non-lactating) periods by 15-20%. Ecdysone application, similar to levels that occur immediately before birth, induced autophagy, and increased milk gland involution even before abortion. This suggests that the ecdysteroid peak immediately preceding parturition likely triggers milk gland autophagy. Population modeling reveals that a delay in involution would yield a negative population growth rate. This study indicates that milk gland autophagy during involution is critical to restore nutrient reserves and allow efficient transition between pregnancy cycles. Targeting post-birth phases of reproduction could be utilized as a novel mechanism to suppress tsetse populations and reduce trypanosomiasis.


Association of Heritable Cognitive Ability and Psychopathology With White Matter Properties in Children and Adolescents.
Many mental disorders emerge during adolescence, which may reflect a cost of the potential for brain plasticity offered during this period. Brain dysconnectivity has been proposed as a common factor across diagnostic categories. To investigate the hypothesis that brain dysconnectivity is a transdiagnostic phenotype in adolescence with increased susceptibility and symptoms of psychiatric disease. We investigated clinical symptoms as well as cognitive function in 6487 individuals aged 8 to 21 years from November 1, 2009, to November 30, 2011, in the Philadelphia Neurodevelopmental Cohort and analyzed diffusion magnetic resonance imaging brain scans for 748 of the participants. Independent component analysis was used to derive dimensional psychopathology scores, and genome-wide complex trait analysis was used to estimate its heritability. Multimodal fusion simultaneously modeled contributions of the diffusion magnetic resonance imaging metrics fractional anisotropy, mean diffusivity, radial diffusivity, L1 (the principal diffusion tensor imaging eigen value), mode of anisotropy, as well as dominant and secondary fiber orientations, and structural connectivity density, and their association with general psychopathology and cognition. Machine learning with 10-fold cross-validation and permutation testing in 729 individuals (aged 8 to 22 years; mean [SD] age, 15.1 [3.3] years; 343 females [46%]) revealed significant association with general psychopathology levels (r = 0.24, P < .001) and cognition (r = 0.39, P < .001). A brain white matter pattern reflecting frontotemporal connectivity and crossing fibers in the uncinate fasciculus was the most associated feature for both traits. Univariate analysis across a range of clinical domains and cognitive test scores confirmed its transdiagnostic importance. Both the general psychopathology (16%; SE, 0.095; P = .05) and cognitive (18%; SE, 0.09; P = .01) factor were heritable and showed a negative genetic correlation. Dimensional and heritable general cognitive and psychopathology factors are associated with specific patterns of white matter properties, suggesting that dysconnectivity is a transdiagnostic brain-based phenotype in individuals with increased susceptibility and symptoms of psychiatric disorders.


Tissue characterization using simultaneous estimation of backscatter coefficient and elastic shear modulus.
Tissue characterization using quantitative ultrasound (QUS) parameters has received significant attention in recent years due to its potential to improve the detection and diagnosis of diseased states. However, the vast majority of studies in QUS tissue typing have used parameters derived from either longitudinal or shear waves in isolation, thereby discarding potentially useful complementary information these parameters may carry. In this study, the simultaneous estimation of backscatter coefficients (derived from longitudinal waves) and shear modulus (derived from shear waves) was implemented on data from a clinical scanner. Both parameters were estimated from five ex vivo porcine kidney samples and used to calculate the anisotropy ratio in the parameters when analyzing the middle and pole regions of the kidneys. For all samples, the estimated parameters were higher in the pole regions than in the middle region, with anisotropy ratios of 1.42±0.11 and 3.07±0.70 for the shear modulus and the backscatter coefficient, respectively. Therefore, these results demonstrate that QUS parameters derived from both longitudinal and shear waves can be estimated simultaneously and may be used in conjunction to track changes in tissue structure and composition.


Transmission of Staphylococcus aureus from Humans to Green Monkeys in The Gambia as Revealed by Whole-Genome Sequencing.
Staphylococcus aureus is an important pathogen of humans and animals. We genome sequenced 90 S. aureus isolates from The Gambia: 46 isolates from invasive disease in humans, 13 human carriage isolates, and 31 monkey carriage isolates. We inferred multiple anthroponotic transmissions of S. aureus from humans to green monkeys (Chlorocebus sabaeus) in The Gambia over different time scales. We report a novel monkey-associated clade of S. aureus that emerged from a human-to-monkey switch estimated to have occurred 2,700 years ago. Adaptation of this lineage to the monkey host is accompanied by the loss of phage-carrying genes that are known to play an important role in human colonization. We also report recent anthroponotic transmission of the well-characterized human lineages sequence type 6 (ST6) and ST15 to monkeys, probably because of steadily increasing encroachment of humans into the monkeys' habitat. Although we have found no evidence of transmission of S. aureus from monkeys to humans, as the two species come into ever-closer contact, there might be an increased risk of additional interspecies exchanges of potential pathogens. The population structures of Staphylococcus aureus in humans and monkeys in sub-Saharan Africa have been previously described using multilocus sequence typing (MLST). However, these data lack the power to accurately infer details regarding the origin and maintenance of new adaptive lineages. Here, we describe the use of whole-genome sequencing to detect transmission of S. aureus between humans and nonhuman primates and to document the genetic changes accompanying host adaptation. We note that human-to-monkey switches tend to be more common than the reverse and that a novel monkey-associated clade is likely to have emerged from such a switch approximately 2,700 years ago. Moreover, analysis of the accessory genome provides important clues as to the genetic changes underpinning host adaptation and, in particular, shows that human-to-monkey switches tend to be associated with the loss of genes known to confer adaptation to the human host.


Nosocomial Klebsiella pneumoniae infection: clinical and hygienic measures in a neonatal intensive care unit.
An outbreak in a neonatal intensive care nursery of severe infections caused by Klebsiella pneumoniae type K-17 has been studied. Over a 9-month period 20 epidemiologically linked cases of severe septicemia, meningitis and pneumonia were diagnosed. The specific epidemic strain could be identified. After introduction of a policy of hygienic measures the nosocomial infection could be eradicated although colonization still occurred. Thorough handwashing before and after the nursing care of each infant, individual gowning and disposable gloves in the care of infants below 1 500 g were important. The changing bacterial ecology of a neonatal unit should be followed closely by weekly routine throat cultures as well as by cultures of incubators and ventilation equipment. The present investigation has shown the importance of this procedure, which is mandatory for appropriate choice of antimicrobial agents when treating infections in critically ill or very low birth weight infants in the neonatal intensive care unit. Prophylactic antimicrobial treatment is not indicated. Control of K. pneumoniae nosocomial infections can only be achieved by maintaining a high standard of hygiene in the neonatal care.


Simple differentiation of avirulent and virulent strains of avian paramyxovirus serotype-1 (Newcastle disease virus) by PCR and restriction endonuclease analysis in Japan.
To differentiate the avirulent from virulent strains of avian paramyxovirus serotype-1 (APMV-1, Newcastle disease virus), PCR and restriction endonuclease analysis (REA) was employed. Primer sequences were used to amplify a 766-base pair fragment that included the fusion protein cleavage site. REA of PCR products generated by Hin1 I and Apa I enabled the differentiation of avirulent field and vaccine strains from more virulent field strains of APMV-1 in Japan.


Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology.
Liver resection (LR) and living-donor liver transplantation (LDLT) are considered the two potentially curative treatments for hepatocellular carcinoma (HCC). The aim of this study was to investigate whether there is a difference in the oncologic outcomes between LR and LDLT according to tumor biology. Patients (137 LDLTs and 199 LRs) were stratified into four groups by tumor biology according to the number of risk factors for recurrence (preoperative alpha-fetoprotein >200 ng/mL, Edmonson grade 3 or 4, tumor size >3 cm, and presence of microvascular invasion). In the favorable tumor biology patients (groups I and II), there was a significantly worse recurrence-free survival rate in those patients who underwent LR compared to those who underwent LDLT (group I, P = .002; group II, P = .001). The overall survival rates in the LR and LDLT groups were not different (group I, P = .798; group II, P = .981). In the poor tumor biology patients (groups III and IV), there was no significant difference between the two groups in terms of recurrence-free survival rate (group III, P = .342; group IV, P = .616). The LDLT group showed a significantly lower overall survival rate (group III, P = .001; group IV, P = .025). Primary LDLT should not be recommended in early stage HCC patients with poor tumor biology because of lower survival rates and a high chance of HCC recurrence.


Sentinel lymph node mapping with indocyanine green in vaginal cancer.
Sentinel lymph node (SLN) mapping is being adapted to gynecologic cancer. Higher SLN mapping rates were reported with indocyanine green (ICG) compared to other dyes. The aim of this film is to share our experience of SLN mapping with ICG in vaginal cancer. A 40 year-old woman was diagnosed with squamous cell vaginal cancer. About 1.5 cm-sized tumor was located on the posterior vaginal fornix. Preoperatively she was assumed to be stage I vaginal cancer. Beginning of surgery, we performed SLN mapping by ICG injection into 3- and 9-o'clock positions of the vaginal tumor. Concentrated in 1.25 mg/mL, 1 mL of ICG solution was injected into deep stroma and another 1 mL submucosally in both sides. Bilateral SLN identification and lymphadenectomy were done. Afterward, laparoscopic Type C1 Querleu-Morrow radical hysterectomy with vaginectomy was done. A fluorescence endoscope produced by KARL STORZ (Tuttlingen, Germany) was used for ICG detection. To our knowledge, this is the first film report performing SLN mapping with ICG in vaginal cancer. The mapping was successful and we were able to recognize SLN of vaginal cancer. SLNs were located in the bilateral obturator fossa. According to the pathologic diagnosis, the mass size was 15 mm and invasion depth was 1 mm. Subvaginal tissue involvement and pelvic wall extension were absent. Resection margin of the vagina was free from carcinoma. No lymph node metastasis was reported including the bilateral SLNs. For vaginal cancer, SLN mapping can be applied by injecting ICG into the bilateral sides of the vaginal tumor.


IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age.
Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (-1082G/A), rs1800871 (-819C/T), rs1800872 (-592C/A) were available for 99 children and of IL10 rs1800890 (-3575T/A) for 98 children. IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients.


[The effects of anti-inflammatory on activation of nuclear factor-kappaB and expression of cell adhesion molecules in patients with ulcerative colitis].
The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-kappaB and mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-kappaB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1 (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-kappaB activation and reduction of adhesion molecules expression.


Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: urinary organic acid profiles and expanded spectrum of mutations.
Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase (HMCS2) deficiency results in episodes of hypoglycemia and increases in fatty acid metabolites. Metabolite abnormalities described to date in HMCS2 deficiency are nonspecific and overlap with other inborn errors of metabolism, making the biochemical diagnosis of HMCS2 deficiency difficult. Urinary organic acid profiles from periods of metabolic decompensation were studied in detail in HMCS2-deficient patients from four families. An additional six unrelated patients were identified from clinical presentation and/or qualitative identification of abnormal organic acids. The diagnosis was confirmed by sequencing and deletion/duplication analysis of the HMGCS2 gene. Seven related novel organic acids were identified in urine profiles. Five of them (3,5-dihydroxyhexanoic 1,5 lactone; trans-5-hydroxyhex-2-enoate; 4-hydroxy-6-methyl-2-pyrone; 5-hydroxy-3-ketohexanoate; 3,5-dihydroxyhexanoate) were identified by comparison with synthesized or commercial authentic compounds. We provisionally identified trans-3-hydroxyhex-4-enoate and 3-hydroxy-5-ketohexanoate by their mass spectral characteristics. These metabolites were found in samples taken during periods of decompensation and normalized when patients recovered. When cutoffs of adipic >200 and 4-hydroxy-6-methyl-2-pyrone >20 μmol/mmol creatinine were applied, all eight samples taken from five HMCS2-deficient patients during episodes of decompensation were flagged with a positive predictive value of 80% (95% confidence interval 35-100%). Some ketotic patients had increased 4-hydroxy-6-methyl-2-pyrone. Molecular studies identified a total of 12 novel mutations, including a large deletion of HMGCS2 exon 1 in two families, highlighting the need to perform quantitative gene analyses. There are now 26 known HMGCS2 mutations, which are reviewed in the text. 4-Hydroxy-6-methyl-2-pyrone and related metabolites are markers for HMCS2 deficiency. Detection of these metabolites will streamline the biochemical diagnosis of this disorder.


A comparison of quantum and quasiclassical statistical models for reactions of electronically excited atoms with molecular hydrogen.
A detailed comparison of statistical models based on the quasiclassical trajectory (SQCT) and quantum mechanical (SQM) methods is presented in this work for the C((1)D)+H(2), S((1)D)+H(2), O((1)D)+H(2) and N((2)D)+H(2) insertion reactions. Reaction probabilities, integral (ICS) and differential (DCS) cross sections at different levels of product's state resolution are shown and discussed for these reactions. The agreement is in most cases excellent and indicates that the effect of tunneling through the centrifugal barrier is negligible. However, if there exists a dynamical barrier, as in the case of the N((2)D)+H(2) reaction, some of the SQM results can be slightly different than those calculated with the SQCT model. The rationale of the observed similarities and discrepancies can be traced back to the specific topologies of the potential energy surfaces for each of the reactions examined. The SQCT model is sensitive enough to show the relatively small inaccuracies resulting from the decoupling inherent to the centrifugal sudden approximation when used in the SQM calculations. In addition, the effect of ignoring the parity conservation is also examined. This effect is in general minor except in particular cases such as the DCS from initial rotational state j=0, which requires, in order to reproduce the sharp forward and backward peaks, the explicit conservation of parity.


Detecting HIV among persons accompanying patients to an infectious diseases clinic.
Infectious diseases (ID) clinics are locations where members of at risk social networks, including sex partners of HIV-infected patients, make contact with a medical care setting when they accompany HIV-positive patients to appointments. We implemented a free point-of-care rapid HIV testing program for anyone accompanying a patient to the University of North Carolina ID clinic. Acceptability of the program among the general clinic population was assessed via an anonymous survey 1 year after program implementation. Basic frequencies of those who underwent and received results of rapid HIV testing, the proportion of positive rapid tests and confirmatory HIV tests performed, and the level of University of North Carolina ID clinic patient satisfaction with the HIV testing program were calculated. Between October 2007 and June 2013, 450 (99.6%) of 452 individuals tested in the program received their results on the same day as testing. Twenty-two individuals (4.9%) tested HIV positive, of which 16 (72.7%) were newly positive, including 3 never previously tested. Excluding previously diagnosed individuals, HIV prevalence was 3.6% (16/446). Among those testing positive by rapid testing, 19 (86.4%) had confirmatory testing and immediately entered into HIV care at the clinic. The high positivity and confirmatory HIV rates in our program confirm that the provision of rapid HIV testing in an ID clinic capitalizes on missed opportunities among an at-risk population and allows immediate linkage to care.


Vocal Hygiene in Collegiate Singers-Does Formal Training Relate to Practices?
Vocal hygiene is vitally important for protecting vocal quality and promoting vocal longevity. It includes adequate hydration, avoidance of environmental irritants, and refraining from phonotraumatic behaviors such as screaming, excessive talking, and throat clearing. Formal singing training in addition to enhancing singing techniques, is also assumed to promote good vocal hygiene. Consequently, we investigated whether collegiate singers with formal training are more likely to practice good vocal hygiene habits than untrained collegiate singers. We completed a prospective cohort study, where collegiate singers at Stanford University were voluntarily enrolled in an annual vocal health clinic. Full laryngeal exams were performed and demographic information, formal vocal training status, and information on vocal hygiene habits were obtained through questionnaires. The results were then analyzed by grouping singers as "untrained" if less than 1 year of formal training, and "trained" if greater than a year. A total of 82 singers were included for analysis, with 49 (59.8%) having greater than one year of formal training. Trained singers were more likely to employ a primary musical singing style of classical or operatic singing compared to untrained singers who were more likely to utilize "R&B" (P < 0.001). No significant differences were found between groups for hydration practices (P = 0.20), caffeine consumption (P = 0.73), warm up practices (P = 0.08), and phonotraumatic behaviors. Alcohol consumption, smoking tobacco, marijuana, e-cigarette usage was similar between groups. Overall, 11% of our sample reported intermittent less than daily marijuana use, with one singer reporting daily consumption. None of the singers in this sample used e-cigarettes. These rates are noticeably lower than the agematched United States population. Perceptions of cigarettes, marijuana, electronic cigarettes, alcohol, and caffeine were also the same between groups, with the vast majority of singers perceiving these agents as harmful to the voice (64%-100% depending on the agent). No laryngeal pathology was identified during laryngeal examination of any singers. Vocal hygiene habits are similar between trained and untrained collegiate singers. This likely relates to a desire for vocal longevity irrespective of prior training. This may dispel the long-held assumption that formal training was necessary to develop good vocal habits. We do however, present a very homogenous, highly educated sample of collegiate singers from Stanford University, having significantly less at-risk behavior than their aged-matched counterparts in the general US population. A lack of laryngeal pathology despite extensive vocal demands may also be reflective of good vocal hygiene habits.


MDM2 non-genotoxic inhibitors as innovative therapeutic approaches for the treatment of pediatric malignancies.
Since the discovery of p53 as "guardian of the genome", a large number of efforts have been put in place in order to find molecular strategies aiming to restore p53 wild-type functions, particularly in the light of the fact that its pathway results ineffective in most tumors even though they have non-mutated p53. In this context, pediatric cancers, that are mostly p53 wild-type at the time of diagnosis, represent an ideal target for such therapeutic approach. Within the several mechanisms and proteins ruling p53 activity, the murine double minute 2 (MDM2) is its crucial negative regulator, frequently found overexpressed in p53-wild-type tumors. The development of new technologies such as nuclear magnetic resonance structure analyses, computational structure-based design studies, and library peptides screening have recently led to the discovery and characterization of a large number of compounds belonging to different chemical families that are able to target the interaction p53-MDM2, rescuing the p53 wild-type pathway with an overall pro-apoptotic and anticancer activity. Within the preclinical assessment of these molecules, the cis-imidazoline analogue Nutlin-3 has definitely attracted great interest for its in vitro and in vivo antitumor activity in several pediatric cancer models, either as single agent on in combination with standard chemotherapy. In this light, the aim of this review is to summarize the main preclinical evidences of the potential of MDM2 inhibitors for the treatment of childhood cancers and the key suggestions coming from their assessment in the treatment of adult cancers as proof of concept for future pediatric clinical studies.


A response of Panc-1 cells to cis-platinum, assessed with a cDNA array.
The problem posed by the lack of response of cells in most solid cancers to current chemotherapy generally remains intractable. The use of cDNA arrays represents one global approach to identifying reasons for this failure. A messenger RNA response of pancreatic cancer (Panc-1) cells after culture for 24 hours with 12 microM cis-platinum was analyzed with a commercial cDNA array. Major drug-induced events included inhibition of messenger RNAs associated with cell proliferation and up-regulation of generally countervailing DNA repair, cellular stress, heat shock protein, glutathione stress-related and multiple drug resistance enzyme messenger RNAs, accompanied by a limited programmed cell death response. Induction of widespread normal stress-induced countervailing mRNAs by comparatively non-selective agents such as cis-platinum strongly biases against a successful therapeutic outcome. This paradoxical result of a therapeutic intent provides a further compelling argument for the use of specifically-targeted therapy such as growth factor receptor, tyrosine kinase and other discretely focused agents, probably employed in combinations based on expression of their targets in an individual patient's cancer, as identified by cDNA or proteonomic arrays.


Cold agglutinin disease: A case report with atypical clinical findings.
A female in her 60s presented to the allergy and immunology clinic for further investigation of ongoing dermatitis. She presented with chronic acrocyanosis, mainly in her left lower extremity, extending distally from her mid thigh with concurrent ulcerations in her foot resulting in immobility secondary to pain. She experienced these symptoms for years without a definitive diagnosis. The lack of diagnosis was due, in part, to her atypical symptoms and laboratory findings that required a high level of clinical suspicion to diagnose. Extensive autoimmune workup was largely unrevealing with the exception of a cold agglutinin titer of 1:250 and a positive anticomplement C3b direct antiglobulin test. A diagnosis of cold agglutinin disease was made and treatment with rituximab monotherapy was initiated.


Paramedian Submandibular Approach for Removal of Foreign Bodies in the Pterygoid Muscle in Two Dogs.
The purpose of this report is to document a unique location of an oropharyngeal foreign body, diagnosed via contrast computed tomography (CT), as well as a novel surgical approach to the pterygoid muscle region. Oropharyngeal foreign objects are an uncommon but potentially serious disease that can lead to chronic abscessation and pain. Two dogs were presented with chronic complaints, including pain and inability to fully open the mouth for a 1 yr and 5 mo duration, respectively. There was no history or evidence of skin sinus or submandibular/cervical swelling on physical examination of either dog. Both dogs had normal oropharyngeal anatomy with the exception of an asymmetric contrast-enhancing lesion within the pterygoid muscle on CT imaging. As there were no gross abnormalities visible during surgery, the use of contrast CT was vital in order to isolate the focus of infection. A paramedian submandibular approach was used to explore this region, and in both cases, foreign material was successfully removed with subsequent resolution of clinical signs. The dogs were immediately free of clinical signs and showed no recurrence for at least 8 and 17 mo after the exploration, respectively. A novel surgical approach is described to remove oropharyngeal foreign objects and necrotic debris within the pterygoid muscle.


Atezolizumab-induced subacute cerebellar ataxia in a patient with extensive-stage small cell lung cancer.
Recently, immune checkpoint inhibitors (ICIs) have become the standard treatment option for patients with lung cancer, including small cell lung cancer (SCLC). ICI-induced neurological immune-related adverse events are rare and exhibit diverse clinical manifestations, often leading to missed or delayed diagnosis. Herein, we report the case of a patient with extensive-stage SCLC who received atezolizumab with etoposide/platinum and gradually developed neurological symptoms after three cycles of chemoimmunotherapy. Subsequently, the patient received a diagnosis of subacute immune-related cerebellar ataxia and was treated successfully with pulse steroid therapy. The patient exhibited almost complete remission of neurological symptoms and had progression-free survival for >24 months.


[Malignant pleural mesothelioma: diagnosis, therapy and prognosis].
Clinical and radiological signs in 44 patients with a malignant mesothelioma of the pleura are described. 18 patients underwent radical pleuropneumonectomy with total resection of the ipsilateral diaphragma. In addition to mediastinal nodes were resected in eight cases, in three patients parts of the thoracic wall had to be removed, and in six patients partial resection of the pericardium was performed. In 15 patients (34%) palliative tumor resection was performed and in ten other persons an exploratory thoracotomy and palliative tumor resection. One patient is alive 13 years after radical pleuropneumonectomy. The mean survival time of the patients who died is after radical pleuropneumonectomy 20 months (0.2 to 54 months), after radical pleuropneumonectomy with pericardial resection 8.5 months (3 to 16 months), after palliative resection 9.7 months (0.5 to 29 months) and after exploratory thoracotomy 6.5 months (0.5 to 19 months). Three patients died within a month (6.9%), one after a radical pleuropneumonectomy, one after a palliative resection and one after an exploratory thoracotomy. The first patient died in the late sixties due to a postoperative aspiration, the other two due to tumor progression. We conclude that the radical pleuropneumonectomy can contribute to a better prognosis of the malignant pleural mesothelioma.


Actively controlled asymmetric edge states for directional wireless power transfer.
Wireless power transfer (WPT) has triggered immense research interest in a range of practical applications, including mobile phones, logistic robots, medical-implanted devices and electric vehicles. With the development of WPT devices, efficient long-range and robust WPT is highly desirable but also challenging. In addition, it is also very important to actively control the transmission direction of long-range WPT. Recently, the rise of topological photonics provides a powerful tool for near-field robust control of WPT. Considering the technical requirements of robustness, long-range and directionality, in this work we design and fabricate a one-dimensional quasiperiodic Harper chain and realize the robust directional WPT using asymmetric topological edge states. Specially, by further introducing a power source into the system, we selectively light up two Chinese characters, which are composed of LED lamps at both ends of the chain, to intuitively show the long-range directional WPT. Moreover, by adding variable capacitance diodes into the topological quasiperiodic chain, we present an experimental demonstration of the actively controlled directional WPT based on electrically controllable coil resonators. With the increase in voltage, we measure the transmission at two ends of the chain and observe the change of transmission direction. The realization of an actively tuned topological edge states in the topological quasiperiodic chain will open up a new avenue in the dynamical control of robust long-range WPT.


Stereotactic pallidotomy for Parkinson's disease: a long-term follow-up of unilateral pallidotomy.
Eleven patients suffering from Parkinson's disease were followed for up to 4 years after unilateral pallidotomy. We observed persistent contralateral improvement and unexpected ipsilateral improvement of motor symptoms. In addition, there was a protracted relief of contralateral dyskinesias and maintenance of relatively stable levodopa dosage.


[Effects of dobutamine on the respiration, blood pressure, and several blood components in dogs (author's transl)].
In anesthetized Beagle dogs, intravenous bolus administration of dobutamine (DOB) caused an increase of systolic pressure and a decrease of diastolic pressure--increase of pulse pressure. These effects of DOB were not so pronounced as the marked depressor effect of isoproterenol (Iso) and pressor effects of epinephrine (Epi), norepinephrine(NE) and dopamine (DA). The degree of the positive chronotropic effect of DOB was the same as that of DA. Incidences of ventricular extrasystole observed at the maximal dosages of catecholamines, intravenous administration of 300 microgram/kg of DOB, 3 of Iso, 10 of Epi, 10 of NE, and 300 of DA, were 1/4, 1/4, 4/4, 4/4, and 2/4, respectively. With no evidence of ventricular extrasystoles, an increase of pulse pressure was also observed in conscious dogs given an intravenous infusion of DOB (10 or 30 microgram/kg/min for 20 min). Iso infusion resulted in an increase of serum free fatty acid, and a decrease of serum Na and K. Although DA infusion increased blood glucose and serum free fatty acid, DOB infusion produced no significant concentration change of blood components. These experimental results indicate that effects of DOB on the blood pressure, heart rate, and several blood components are weaker than other catecholamines.


Boosted protease inhibitor monotherapy as a maintenance strategy: an observational study.
We aimed to determine the effectiveness of boosted protease inhibitor monotherapy (BPIMT) initiated as a maintenance strategy in routine care and identify predictive factors of failure. Observational study in the FHDH-ANRS CO4 cohort. Five hundred and twenty-nine virologically suppressed individuals switched to BPIMT in the period 2006-2010, 75% had at least 12 and 49% at least 24 months of follow-up. Virological failure (two consecutive HIV-RNA > 50 copies/ml or one HIV-RNA > 50 copies/ml followed by BPIMT discontinuation) and treatment failure (virological failure, antiretroviral reintensification or death) were analysed separately. At baseline, 11% were protease inhibitor-naive, median duration on combined antiretroviral therapy was 84 months and median duration of suppressed viremia was 38 months. Nine percent had a history of virological failure, while on a protease inhibitor-containing regimen, and rates of virological failure were higher among those individuals [adjusted hazard ratio, 1.6; 95% confidence interval (CI), 0.9-2.9]. Compared to individuals with less than 1 year of sustained virological suppression before the switch to BPIMT, those with longer duration were less likely to experience virological failure [hazard ratio, 0.7; (95% CI, 0.4-1.2) and 0.6 (95%CI, 0.4-0.9)] for a duration of 12-23 months and 24 months or more, respectively. Rates of failure were similar for BPIMT with lopinavir-ritonavir (RTV) or darunavir-RTV, but increased for BPIMT with atazanavir-RTV. Same risk factors were associated with treatment failure. The safety and efficacy of a maintenance strategy with BPIMT in a routine care setting matched the results of randomized clinical trials. A longer duration since last virological rebound before switching to BPIMT was associated with a decreased risk of subsequent failure.


Clinical significance of macroscopic T-wave alternans after sodium channel blocker administration in patients with Brugada syndrome.
Macroscopic T-wave alternans (TWA) is sometimes observed after sodium channel blocker administration in patients with Brugada syndrome (BS), but little is known about the association between occurrence of TWA and clinical characteristics in BS patients. We investigated the association between spontaneous ventricular fibrillation (VF) occurrence and TWA after pilsicainide, a sodium channel blocker administration in BS patients. We administered pilsicainide at a dose of 1 mg/kg to 77 BS patients (76 males and one female; mean age, 48.4 years) and examined the association between TWA after pilsicainide administration and clinical characteristics, including age, spontaneous VF, syncope, family history of sudden death, spontaneous coved ST elevation, late potentials (LP), induction of VF by programmed electrical stimulation, and SCN5A mutation. None of the patients had TWA before pilsicainide administration, but TWA became apparent in 17 (22.1%) of the patients after pilsicainide administration. Patients with TWA had a significantly higher incidence of spontaneous VF (52.9% vs 8.3%, P < 0.001) and syncope (58.8% vs 26.7%, P < 0.05) than did patients without TWA. Then, we focused on the association between spontaneous VF and clinical characteristics. Patients with spontaneous VF had a significantly higher incidence of TWA (64.3% vs 12.7%, P < 0.001) and LP positive (92.9% vs 56.5%, P < 0.01) than did patients without spontaneous VF. In multivariate analysis, TWA (P = 0.001) and LP (P = 0.047) appeared as the independent predictor for spontaneous VF. TWA after pilsicainide administration is associated with a high risk of clinical VF in patients with BS.


Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite.
Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.


Myxedema coma: A case report of pediatric emergency care.
Myxedema coma (MC) is extremely rare but lethal in pediatric patients with hypothyroidism leading to altered mental status and hypothermia. But there is no clinical guideline for such cases. A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. Her lab results were: free thyroxin (T4) 4.18 pmol/L and thyroid-stimulating hormone (TSH) > 150 μIU/mL with extremely elevated anti-thyroid peroxidase (TPO-Ab) and anti-thyroglobulin. Pneumonia, mild pleural, and pericardial effusion were seen on computed tomographic (CT) scan. MC, autoimmune hypothyroidism, pneumonia and sepsis were diagnosed. Gastric levothyroxine, intravenous dexamethasone and antibiotics were administered. Her consciousness was restored and temperature returned to normal 2 days after starting levothyroxine. She was discharged two weeks later. MC is rare but may be the initial presentation in pediatric patients with prolonged untreated hypothyroidism. Autoimmune thyroiditis could cause hypothyroidism in children. MC should be suspected in pediatric patients with altered mental status, hypothermia and cardiovascular instability. Treatment with 100 mg/m of gastric levothyroxine is an option for pediatric patients with MC.


Preperitoneal inguinal hernia repair during pelvic surgery.
We report our experience with posterior preperitoneal prosthetic herniorrhaphy for inguinal hernia in patients undergoing concomitant pelvic surgery for both benign and malignant urological pathologies. 116 patients with either unilateral or bilateral inguinal hernia underwent posterior preperitoneal prosthetic herniorrhaphy during a pelvic operation for various urological pathologies. The technique described by Mahorner and Goss was used for unilateral hernia, while the modified Stoppa technique was used for bilateral hernia. All patients had a complication-free peri- and post-operative course, except for one patient who developed a spontaneously resolving small peri-prosthetic hematoma. In the follow-up of all patients (mean 35.7 months, range 4-72) we did not observe any hernia recurrence. Posterior preperitoneal prosthetic inguinal herniorrhaphy during pelvic surgery for urological pathologies is a relatively simple and safe procedure to perform and a recurrence rate of zero, or very close to zero, is to be expected.


Effect of Surface Finishing State on Fatigue Strength of Cast Aluminium and Steel Alloys.
The endurance limit of structural mechanical components is affected by the residual stress state, which depends strongly on the manufacturing process. In general, compressive residual stresses tend to result in an increased fatigue strength. Post-manufacturing processes such as shot peening or vibratory finishing may achieve such a compressive residual stress state. But within complex components, manufacturing-process-based imperfections severely limit the fatigue strength. Thus, the interactions of imperfections, residual stress state and material strength are key aspects in fatigue design. In this work, cast steel and aluminium alloys are investigated, each of them in vibratory finished and polished surface condition. A layer-based fatigue assessment concept is extended towards stable effective mean stress state considering the elastic-plastic material behaviour. Murakami's concept was applied to incorporate the effect of hardness change and residual stress state. Residual stress relaxation is determined by elastic-plastic simulations invoking a combined hardening model. If the effective stress ratio within the local layer-based fatigue strength is evaluated as critical distance value, a sound calculation of fatigue strength can be achieved. Summing up, the layer-based fatigue strength design is extended and features an enhanced understanding of the effective stabilized mean stress state during cyclic loading.


Dietary High Zinc Oxide Modulates the Microbiome of Ileum and Colon in Weaned Piglets.
Dietary zinc oxide (ZnO) at pharmacological level has been widely used to prevent and treat diarrhea in weaning piglets. Despite its importance for promoting animal health and performance, the influence of microbiome profiles in intestinal tracts by ZnO needs to be comprehensively investigated. In this study, we conducted a comparative microbial community analysis in the ileum and colon of piglets fed by either control diet, high ZnO (3,000 mg/kg) supplement or antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) supplement. Our results showed that both high dietary ZnO and in-feed antibiotics supplementations significantly increased 5 phyla of Spirochaetes, Tenericutes, Euryarchaeota, Verrucomicrobia, TM7, and reduced 1 phyla of Chlamydiae in ileal digesta. The relative abundance of opportunistic pathogens Campylobacterales were decreased while Enterobacteriales were increased in ZnO or antibiotics-supplemented group when compared to the control. In the colon, the phyla Euryarchaeota, the genus Methanobrevibacter, and the species Methanobrevibacter smithii were drastically increased by high dietary ZnO supplementation when compared with other groups. The microbial functional prediction analysis showed that high dietary ZnO and in-feed antibiotics had a higher abundance of transporter pathway enrichment in the ileum when compared with the control. While in the colon high dietary ZnO had a higher abundant enrichment of methane metabolism involving energy supply when compared with other groups. Both high dietary ZnO and antibiotics increased the microbiota diversity of ileal digesta while they decreased the microbiota diversity of the colonic digesta. Collectively, these results suggested that dietary ZnO and in-feed antibiotics supplementations presented similar effect on ileal microbiota, and mainly affected the non-predominant microbiota.


Source monitoring.
A framework for understanding source monitoring and relevant empirical evidence is described, and several related phenomena are discussed: old-new recognition, indirect tests, eyewitness testimony, misattributed familiarity, cryptomnesia, and incorporation of fiction into fact. Disruptions in source monitoring (e.g., from confabulation, amnesia, and aging) and the brain regions that are involved are also considered, and source monitoring within a general memory architecture is discussed. It is argued that source monitoring is based on qualities of experience resulting from combinations of perceptual and reflective processes, usually requires relatively differentiated phenomenal experience, and involves attributions varying in deliberateness. These judgments evaluate information according to flexible criteria and are subject to error and disruption. Furthermore, diencephalic and temporal regions may play different roles in source monitoring than do frontal regions of the brain.


Prospective Pilot Study of the Mastering Each New Direction Psychosocial Family Systems Program for Pediatric Chronic Illness.
Psychosocial interventions for pediatric chronic illness (CI) have been shown to support health management. Interventions that include a family systems approach offer potentially stronger and more sustainable improvements. This study explores the biopsychosocial benefits of a novel family systems psychosocial intervention (MEND: Mastering Each New Direction). Forty-five families participated in a 21-session intensive outpatient family systems-based program for pediatric CI. Within this single arm design, families were measured on five domains of Health-Related Quality of Life (HRQL) self-report measures; Stress, Cognitive Functioning, Mental Health, Child HRQL, Family Functioning. Both survey and biological measures (stress: catecholamine) were used in the study. Results from multivariate general linear models showed positive pre-, post-, and 3-month posteffects in all five domains. The program effects ranged from small to moderate (η2 = .07-.64). The largest program effects were seen in the domains of cognitive functioning (η2 = .64) and stress (η2 = .27). Also, between disease groups, differences are noted and future implications for research and clinical practice are discussed. Conclusions suggest that the MEND program may be useful in helping families manage pediatric chronic illnesses. Study results also add to the growing body of literature suggesting that psychosocial interventions for pediatric chronic illness benefit from a family systems level of intervention.


Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma.
Ureteroscopic biopsy is the gold standard for the histopathologic diagnosis of urothelial carcinoma of the upper urinary tract. To assess the accuracy of endoscopically obtained biopsy samples in diagnosing, grading, and staging urothelial carcinoma and correlate diagnostic findings to biopsy sample size. We retrospectively reviewed endoscopic biopsies of the ureter, renal pelvis, and ureteropelvic junction from 2008 to 2011. Biopsy diagnoses that were discordant with follow-up pathology and/or ureteroscopic impression were re-reviewed and samples were immunohistochemically analyzed. Endoscopic biopsies (n = 118) yielded a sensitivity of 85.4% for the ureter (n = 79), 77.8% for the renal pelvis (n = 37), and 100% for the ureteropelvic junction (n = 2). A specificity of 100% for all locations and a diagnostic accuracy of 98.3% were identified. The median sample size was 0.3 cm for true positives, 0.3 cm for true negatives, and 0.2 cm for false negatives with no statistical significance. We found that 87.1% of tumors diagnosed on biopsy had concordant grade and 60.0% had concordant pT stage with follow-up surgical resections (n = 43) and biopsies (n = 24). Biopsy samples with concordant tumor grades (mean = 0.6 cm) compared with follow-up resection were larger than biopsy samples with discordant grades (mean = 0.3 cm) (P = .04). Though highly specific, endoscopic biopsy does provide a significant false-negative rate owing to both sampling and diagnostic errors when assessing the upper urinary tract for urothelial carcinoma. Tumor grading is accurate, particularly with larger tissue samples, but tumor staging is unreliable.


The Notched Stick, an ancient vibrot example.
An intriguing simple toy, commonly known as the Notched Stick, is discussed as an example of a "vibrot", a device designed and built to yield conversion of mechanical vibrations into a rotational motion. The toy, that can be briefly described as a propeller fixed on a stick by means of a nail and free to rotate around it, is investigated from both an experimental and a numerical point of view, under various conditions and settings, to investigate the basic working principles of the device. The conversion efficiency from vibration to rotational motion turns out to be very small, or even not detectable at all, whenever the propeller is tightly connected to the stick nail and perfectly axisymmetrical with respect to the nail axis; the small effects possibly observed can be ascribed to friction forces. In contrast, the device succeeds in converting vibrations into rotations when the propeller center of mass is not aligned with the nail axis, a condition occurring when either the nail-propeller coupling is not tight or the propeller is not completely axisymmetrical relative to the nail axis. The propeller rotation may be induced by a process of parametric resonance for purely vertical oscillations of the nail, by ordinary resonance if the nail only oscillates horizontally or, finally, by a combination of both processes when nail oscillations take place in an intermediate direction. Parametric resonance explains the onset of rotations also when the weight of the propeller is negligible. In contrast with what is commonly claimed in the literature, the possible elliptical motion of the nail, due to a composition of two harmonic motions of the same frequency imposed along orthogonal directions, seems unnecessary to determine the propeller rotation.


Exogenous attention to fear: Differential behavioral and neural responses to snakes and spiders.
Research has consistently shown that threat stimuli automatically attract attention in order to activate the defensive response systems. Recent findings have provided evidence that snakes tuned the visual system of evolving primates for their astute detection, particularly under challenging perceptual conditions. The goal of the present study was to measure behavioral and electrophysiological indices of exogenous attention to snakes, compared with spiders - matched for rated fear levels but for which sources of natural selection are less well grounded, and to innocuous animals (birds), which were presented as distracters, while participants were engaged in a letter discrimination task. Duration of stimuli, consisting in a letter string and a concurrent distracter, was either presented for 180 or 360ms to explore if the stimulus duration was a modulating effect of snakes in capturing attention. Results showed a specific early (P1) exogenous attention-related brain potential with maximal amplitude to snakes in both durations, which was followed by an enhanced late attention-related potential (LPP) showing enhanced amplitudes to spiders, particularly under the longer exposure durations. These results suggest that exogenous attention to different classes of threat stimuli follows a gradual process, with the most evolutionary-driven stimulus, i.e., snakes, being more efficient at attracting early exogenous attention, thus more dependent on bottom-up processes.


Rumen degradation and availability of various amounts of liquid methionine hydroxy analog in lactating dairy cows.
Ruminal escape of various amounts of methionine hydroxy analog [D,L-2-hydroxy-4-(methylthio)-butanoic acid (HMB)] was measured in an experiment designed as a 4 x 4 Latin square using four lactating dairy cows with cannula in the rumen and duodenum. The cows were fed a diet composed of corn silage, alfalfa haylage, rolled barley grain, canola meal, and blood meal, three times per day. The cows were fed the liquid analog each day for 1 wk before the experiment was started. On the day of the experiment, each cow received an intraruminal bolus dose of 0, 25, or 50 g of the liquid analog (Alimet feed supplement, 88% HMB) or 51.2 g of a dry calcium salt of the analog (86% HMB; MHA) mixed with 0.5 kg of ground barley grain. A liquid phase marker (Co-EDTA) was administered as a bolus dose into the rumen at the time of administration of the methionine hydroxy analogs. Rumen and duodenal contents, and blood serum were collected at 0, 1, 3, 6, 9, 12, and 24 h relative to the time of dosing. Rumen and duodenal samples were analyzed for Co and HMB, and serum was analyzed for free methionine. Fractional rate constants for the passage of the liquid marker (k(p)) and the decline of HMB concentration in the rumen (k(rHMB)) were determined by nonlinear regression. Liquid passage from the rumen was similar among the four analog treatments (0.136 +/- 0.012/h; mean +/- SEM). Ruminal escape of HMB as a percentage of the dose (100% x k(p)/k(rHMB)) did not differ between cows receiving 25, 50, and 51.2 g of the methionine analogs (42.5, 41.0, and 34.9 +/- 9.0%, respectively) and averaged 39.5%. Duodenal appearance of HMB as a percentage also did not differ between cows receiving 25, 50, and 51.2 g of the methionine analogs (16.2, 26.8, and 22.7%, respectively) and averaged 22%. Omasal absorption of HMB was variable ranging from 12.3 to 26.3% and averaged 17.6%. Serum methionine concentration peaked at 3 and 6 h after dosing and increased in proportion to the amount of the analog administered. It was concluded that 39.5% of the methionine hydroxy analog escaped rumen degradation, the percentage of the dose that escaped the rumen was not affected by the amount or form of the methionine analog fed, and the analog that escaped ruminal degradation was likely absorbed and metabolized to methionine.


[Hyperbaric oxygen treatment of poisoning].
Experiments have suggested reduction of neurological sequelae from carbon monoxide (CO) poisoning by treatment with hyper-baric oxygen (HBO). Randomised clinical trials have, however, been ambiguous. The discrepancy may be explained by timing of HBO relative to exposure. For other asphyxiants data are too sparse for a qualified judgement. Until more evidence is available, we suggest that HBO is used exclusively for moderate and severe CO poisoning within a time window of 12 hours.


Cobalt-Catalyzed C-H Activation/Annulation of Benzamides with Fluorine-Containing Alkynes: A Route to 3- and 4-Fluoroalkylated Isoquinolinones.
The C-H activation/annulation reaction of various benzamides with fluoroalkylated alkynes in the presence of a Co(acac)2·2H2O catalyst proceeded very smoothly to give the corresponding 3- and 4-fluoroalkylated isoquinolinones in excellent yields with approximately 70% regioselectivities. These regioisomers could be successfully separated and obtained in pure form. Major or minor regioisomers were determined as 4- or 3-fluoroalkylated isoquinolinones, respectively, based on X-ray crystallographic analyses.