Aggressiveness of Cephalosporium maydis causing late wilt of maize in Spain.
Late wilt of maize, caused by the vascular and soilborne pathogen Cephalosporium maydis, was identified in the Iberian Peninsula in 2008. During the last years the incidence and economical impact of the disease has importantly increased both in Portugal and Spain. Varieties of maize displaying tolerance to the pathogen are available, but the effectiveness can be dependent on the virulence of the fungus (i.e. ability to cause disease on a specific genotype). On the other hand, strains of crop pathogens from different geographic origins can differ with regard to the degree of disease caused on a specific genotype (i.e. aggressiveness). Our working hypothesis was that isolates of C. maydis from different maize growing areas may differ in aggressiveness towards maize plants. Seven fungal strains were isolated in 2009 from diseased plants collected in the most important maize growing regions of Spain and used to inoculate two susceptible maize varieties grown in shadehouse from March to July 2010. The experimental unit consisted of two 4-day-old seedlings planted in an 8-liter pot filled with sand/silt previously infested with 200 g of wheat grains colonized by the fungi. Non colonized wheat grains were used for the control treatments. Six replications (pots) were established for each variety/isolate combination according to a complete randomized 2 x 8 factorial design. The percentage of necrotic and dry aboveground tissues was recorded 14 weeks after inoculation and thereafter weekly until physiological senescence of the control plants. At the end of the experiment, weights of roots and aboveground parts of the plants were recorded. Initial occurrence of symptoms in the plants was significantly dependent on the isolate of C. maydis and on the maize variety. However, final severity of aboveground symptoms (leaf necroses and drying up) was only dependent on the fungal isolate. All the isolates significantly reduced the root weight of both varieties of maize. The highest root weight reductions were also associated to a significant low weight of above-ground parts. Considering all the symptoms analysed and their progression in the maize plants, our results reveal that a diversity of aggressiveness exists among isolates of C. maydis. The need for a characterization of maize genotypes by their reaction against highly aggressive isolates of the fungus in the Iberian Peninsula is suggested. This study is a first step towards a recommendation of crop varieties that are tolerant to C. maydis in different areas of the Iberian Peninsula. Future research aims at studying the relationship between aggressiveness levels, molecular characteristics and geographical origin whithin C. maydis.


A rapid and simple in vitro method for evaluating human colorectal epithelial proliferation.
Assessment of colonic epithelial proliferation is a biomarker of risk for large-bowel neoplasia. Until now, in vitro labeling of S-phase crypt cells was usually performed by incorporation of tritiated thymidine. Its major disadvantage is the lengthy period of autoradiography before results can be evaluated. The thymidine analogue bromodeoxyuridine, which is detectable by immunohistochemical examination, allows evaluation of epithelial proliferation within 3 days. Pinch rectal biopsy specimens, from the unprepared bowel, are incubated under 1 atm additional pressure in a medium containing bromodeoxyuridine. The tissue is then fixed in 70% ethanol and embedded in paraffin, and the slides are prepared. The labeled nuclei are revealed using indirect immunoperoxidase staining and are easily counted by light microscopy. Assessment of proliferation is rapidly available for determining cancer risk and response in ongoing experimental and human dietary intervention studies.


[The diagnosis and therapy of acute upper limbs deep venous thrombosis].
To conclude the experience of diagnosis and therapy, the effect analysis and the prognosis factors of acute upper limbs deep venous thrombosis (ULDVT). We retrospectively analyzed the etiological factor, clinical manifestation, diagnosis, therapy and prognosis of 28 patients treated for acute ULDVT admitted in our hospital between 1988 and 2009. The patients were divided into two groups according to the time of admission and management in hospital. Group I, from 1988 to 1998, and group II, from 1999 to 2009. There were 28 patients diagnosed as acute ULDVT, which was 8.1% of lower limbs deep venous thrombosis in synchronization. There were 14 men and 14 women, and the mean age was 46.1 years. 17 patients developed in left upper limbs, and 11 patients developed in right upper limbs. There were 9 patients in group I and 19 in group II. A significant difference was observed between two groups in their risk factors, primary and secondary cause. 8 patients (28.6%) were relevant to venepuncture catheterization, and 13 patients (46.4%) have tumors. There is clear difference between the two groups in the way of primary disease and risk Factors, which means that the probability of ULDVT caused by malignant tumors or other factors in group II is apparently higher than group I, and the prognosis of group II is worse compared with group I. All the patients in the group were made a definite diagnosis by ultrasound, after that our policy were thrombolysis and anticoagulation followed by Warfarin oral administration for 6 months. All the conditions of the patients were well improved, and the symptoms were relieved obviously and discharged. The mean follow-up duration was 2.2 years. 2 recurred, 1 was pulmonary infarction, and 6 was died. The incidence of ULDVT is much lower than LLDVT. The motivations are blood hypercoagulable state, such as tumor, vein catheterization etc. The final diagnosis is mostly based on clinical manifestation combined with ultrasound. Thrombolysis, anticoagulation in time have an obvious therapy effect. After that the anticoagulation therapy through oral administration can prevent recurrence.


Learning to balance efficiency and innovation for optimal adaptive expertise.
It is critical for health professionals to continue to learn and this must be supported by health professions education (HPE). Adaptive expert clinicians are not only expert in their work but have the additional capacity to learn and improve in their practices. The authors review a selective aspect of learning to become an adaptive expert: the capacity to optimally balance routine approaches that maximize efficiency with innovative ones where energy and resources are used to customize actions for novel or difficult situations. Optimal transfer of learning, and hence the design of instruction, differs depending on whether the goal is efficient or innovative practice. However, the task is necessarily further complicated when the aspiration is an adaptive expert practitioner who can fluidly balance innovation with efficiency as the situation requires. Using HPE examples at both the individual and organizational level, the authors explore the instructional implications of learning to shift from efficient to innovative expert functioning, and back. They argue that the efficiency-innovation tension is likely to endure deep into the future and therefore warrants important consideration in HPE.


Bound state properties of the ground states in the DT+ and T(2)+ ions.
Recently developed multibox approach [A.M. Frolov, Phys. Rev. E 64, 036704 (2001)] is used to construct highly accurate, bound state wave functions for the ground states in the heavy adiabatic ions DT+ and T(2)+. The computed variational energies and bound state properties have significantly higher accuracy than results known from earlier computations. Nevertheless, the computed and predicted nucleus-nucleus cusp and nucleus-nucleus delta function differ significantly even for the highly accurate wave functions used in this study.


Environmental monitoring of water resources around a municipal landfill of the Rio Grande do Sul state, Brazil.
In Brazil, landfills are commonly used as a method for the final disposal of waste that is compliant with the legislation. This technique, however, presents a risk to surface water and groundwater resources, owing to the leakage of metals, anions, and organic compounds. The geochemical monitoring of water resources is therefore extremely important, since the leachate can compromise the quality and use of surface water and groundwater close to landfills. In this paper, the results of analyses of metals, anions, ammonia, and physicochemical parameters were used to identify possible contamination of surface water and groundwater in a landfill area. A statistical multivariate approach was used. The values found for alkali metals, nitrate, and chloride indicate contamination in the regional groundwater and, moreover, surface waters also show variation when compared to the other background points, mainly for ammonia. Thus, the results of this study evidence the landfill leachate influence on the quality of groundwater and surface water in the study area.


The conformation of the tRNAPhe anticodon loop monitored by fluorescence.
The intrinsic fluorescence of the Wye base was used to study the conformational change of the anticodon loop of yeast tRNAPhe brought about by the addition of magnesium. The fluorescence emission and excitation spectra show dramatic changes as magnesium is added to the solution. The rotational relaxation time changes from 6 nsec without added magnesium to 33 nsec with 10 mM magnesium at an ionic strength of 0.1 M. Stern-Volmer quenching by iodide or iodoethanol shows greater access of the base to the quencher with no added magnesium. A plausible interpretation of this data is that the base stack of the anticodon loop is altered by tilting or twisting the Wye base with respect to the adjacent bases and the base becomes parallel to its neighbors upon the addition of magnesium.


Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders.
The goal of the present study was to determine whether exposure to adversity in childhood contributes to a differential threshold at which stressful life events provoke depressive reactions in adolescence. In addition, to address empirical and conceptual questions about stress effects, the moderating effect of anxiety disorder history was also explored. This examination was conducted in a sample of 816 children of depressed and nondepressed mothers, who were followed from birth to age 15. Information on adversities experienced in childhood was collected both from mothers during the first five years of their youth's life and from the youths themselves at age 15, and included information on the mother's relationship with her partner, maternal psychopathology, as well as youth-reported abuse. Results indicated that youths with both greater exposure to adversity in childhood and a history of an anxiety disorder displayed increased depressive severity following low levels of episodic stress compared to youths with only one or neither of these risk factors. The results are speculated to reflect the possibility that early anxiety disorders associated with exposure to adversity in childhood may be a marker of dysregulated stress responses, and may help to account for the comorbidity of depression and anxiety in some individuals.


Reinekea blandensis sp. nov., a marine, genome-sequenced gammaproteobacterium.
A novel heterotrophic, moderately halophilic, strictly aerobic, motile bacterium was isolated from a seawater sample collected at the Blanes Bay Microbial Observatory in the north-western Mediterranean Sea. Analysis of its 16S rRNA gene sequence, retrieved from the whole-genome sequence, showed that this bacterium was most closely related to the single-species genera Reinekea and Saccharospirillum (95 and 94 % sequence similarity, respectively) within the class Gammaproteobacteria. The data from phenotypic, genotypic, chemotaxonomic and phylogenetic analyses supported the creation of a novel species of the genus Reinekea to accommodate this bacterium, for which the name Reinekea blandensis sp. nov. is proposed. The type strain is MED297(T) (=CECT 7120(T) =CCUG 52066(T)).


Transoesophageal left ventricular pacing in heart failure patients with permanent right ventricular pacing.
Previous studies of biventricular (BV) pacing for treatment of heart failure (HF) patients with left bundle branch block (LBBB) evaluated responders to BV pacing with acute transvenous left ventricular (LV) pacing and arterial pulse pressure (PP). The aim of this study was to assess transoesophageal LV pacing in evaluation of the haemodynamic response with a view to upgrading responders from permanent right ventricular (RV) pacing to BV pacing. Ten HF patients (age 62+/-8 years; one female, nine males) in NYHA III, LV ejection fraction 24+/-9% and permanent RV pacing by means of an implanted pacemaker or ICD were tested using transoesophageal LV pacing and PP. Permanently RV-paced HF patients were analysed with transoesophageal atrial sensed LV pacing in VAT mode with a different AV delay (n = 6) and with transoesophageal LV pacing in V00 mode during atrial fibrillation (n = 4). In five responders, PP was higher during transoesophageal LV pacing than PP during RV pacing (74+/-42 versus 57+/-31 mmHg, P = 0.015). Responders were upgraded by means of an LV lead via the coronary sinus in the posterior (n = 1) or posterolateral (n = 4) walls and after attaining a high LV pacing threshold with an epicardial LV lead on the anterior (n = 1) or anterolateral (n = 1) walls. NYHA class improved from 3 to 2+/-0.3 (P = 0.003) during 204+/-120 days follow-up and cardiac output increased from 4.4+/-1.5 to 5.6+/-1.7 l/min (P = 0.027) when comparing BV pacing and optimal AV delay with RV pacing. In five nonresponders, PP was not higher during transoesophageal LV pacing than during RV pacing. Transoesophageal LV pacing may be a useful technique to detect responders to BV pacing in permanently RV-paced HF patients.


Metallic micro-ring device for highly efficient large cargo delivery in mammalian cells using infrared light pulses.
Uniform transfection of biomolecules into live cells with high delivery efficiency and cell viability is an immensely important area of biological research and has many biomedical applications. In the present study, we report highly efficient, uniform parallel intracellular delivery of small to very large biomolecules into diverse cell types using a titanium micro-ring (TMR) device activated by infrared (IR) light pulse. A TMR array device (2 cm × 2 cm) consists of a 10 μm outer diameter and 3 μm inner diameter for each micro-ring, and 10 μm interspacing between two micro-rings. Upon IR (1050 nm) pulse laser irradiation on the TMR device, photothermal cavitation bubbles are generated, disrupting the cell plasma membrane, and biomolecules are gently delivered into the cells by a simple diffusion process. This TMR device successfully delivered diverse types of small to very large biomolecules such as propidium iodide (PI; 668.4 Da) dye, dextran (3 kDa), small interfering RNA (13.3 kDa), enhanced green fluorescent protein expression plasmid DNA (6.2 kb), and β-galactosidase enzyme (465 kDa) into human cervical (SiHa), mouse fibroblast (L929), and mouse neural crest-derived (N2a) cancer cells. For smaller molecules (PI dye), delivery efficiency and cell viability were achieved at ∼96% and ∼97%, respectively, with a laser fluence of 21 mJ cm-2 for 250 pulses. In contrast, ∼85% transfection efficiency and ∼90% cell viability were achieved for plasmid DNA with 45 mJ cm-2 laser fluence for 250 pulses in SiHa cells. Moreover, the intracellular delivery of β-galactosidase enzyme was confirmed with confocal microscopy and flow cytometry analysis resulting in ∼83% co-staining of β-galactosidase enzyme and calcein AM. Based on these efficient deliveries of diverse types of biomolecules in different cell types, the device has the potential for cellular diagnostic and therapeutic applications.


Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging(1,2,3).
Age is the main risk factor for sporadic Alzheimer's disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging.


Ultradian and asymmetric rhythms of hemispheric processing speed.
Daily changes in cognitive performance have been documented, both in time of day/effect paradigm studies and in time-isolation studies. However, in both types of studies, phenomena such as the "post-lunch dip" have been found that were difficult to explain in terms of theoretical backgrounds. These phenomena may suggest ultradian rhythms in cognitive performance. A number of studies have also shown ultradian and asymmetric rhythms in activity indices of the brain hemispheres. The aim of this study was to test three hypotheses: the first two assumed that there is a significant ultradian frequency in a component of the endogenous rhythm of processing speed, and the third assumed that the ultradian endogenous rhythms of the processing speed (encoding and recognition) of stimuli addressed to the left brain hemisphere differ in period length from those addressed to right hemisphere. During a 24 h constant-routine experiment, the memory performance of 30 participants was measured eight times (every 2.5-3 h), starting at 06:30 h. Parallel sets of words and pictures were shown to subjects in a random order in either the left or the right visual field on a computer screen. The participants pressed one of two buttons in response to the picture or word, or when answering a question concerning the meaning of a presented stimulus. Cosinor analysis was applied to individual time series data. Two significant ultradian components were found in a majority of the time series. Dominant periods were analyzed using three factor ANOVA. The results showed an asymmetry between both hemispheres in the frequency of ultradian rhythms in encoding speed.


Iterative Methylations Resulting in the Biosynthesis of the t-Butyl Group Catalyzed by a B12-Dependent Radical SAM Enzyme in Cystobactamid Biosynthesis.
B12-dependent radical SAM enzymes that can perform methylations on sp3 carbon centers are important for functional diversity and regulation of biological activity in several nonribosomal peptides. Detailed studies on these enzymes are hindered by the complexity of the substrates and low levels of expression of active enzymes. CysS can catalyze iterative methylations of a methoxybenzene moiety during the biosynthesis of the cystobactamids. Here, we describe the overexpression, purification, substrate identification, and mechanism of this enzyme.


[Shimizu Kôichi (1873-1935): author of "A new textbook of general nursing and psychiatric nursing"].
Shimizu was employed as a male attendant at the Tôkyô Prefectural Mental Hospital at the age of 17. In wartime he worked as a member of a contingent of the Japan Red Cross Society. In 1897 he finished the one-year course of nursing at the Central Red Cross Hospital. He must have been the first Japanese psychiatric nurse who was trained as a nurse. Shimizu, as the male head-nurse of the Tôkyô prefectural mental hospital, assisted Superintendent Dr. Kure Shûzô in reforming the hospital to the non-restraint system. In 1908 he published "A New Textbook of General Nursing and Psychiatric Nursing", which allotted many pages to psychiatric nursing. In prewar Japan almost all textbooks of nursing paid little or no attention to psychiatric nursing. Shimizu's textbook ran into the tenth edition. He died as the present male head-nurse at the age of 61. One might say that Shimizu was to Superintendent Dr. Kure as was Jean-Baptiste Pussin to Philippe Pinel.


Chiral shift reagent for amino acids based on resonance-assisted hydrogen bonding.
[structure: see text] A chiral aldehyde that forms resonance-assisted hydrogen bonded imines with amino acids has been developed. This hydrogen bond not only increases the equilibrium constant for imine formation but also provides a highly downfield-shifted NMR singlet for evaluating enantiomeric excess and absolute stereochemistry of amino acids.


Baseline Lower Urinary Tract Symptoms and Sexual Dysfunction in Men with Newly Diagnosed Localized Prostate Cancer.
We evaluated baseline lower urinary tract symptoms (LUTS) and sexual dysfunction in patients with newly diagnosed localized prostate cancer. Data were obtained from a cohort registry of patients with localized prostate cancer scheduled for radical prostatectomy. Before surgery, patients completed a 3-day voiding diary; International Prostate Symptom Score (IPSS), International Index of Erectile Function-5 (IIEF-5), and Expanded Prostate Cancer Index Composite (EPIC) questionnaires; and a urodynamic study. Data were analyzed according to benign prostatic hyperplasia treatment status and age group. In total, 380 patients (median age, 67 years) were enrolled in this study. On the IPSS, 10.8% of patients had severe symptoms. On the IIEF-5, 8.7% of patients did not have erectile dysfunction and 52.9% had moderate-to-severe erectile dysfunction. On the EPIC, 3% of patients indicated that they did not have urinary control and only 13% responded that their erectile function was good or very good. The mean IPSS and IIEF-5 scores showed significant differences among age groups. Thus, patients with localized prostate cancer show various LUTS and sexual dysfunction at baseline, and these symptoms worsened with increased age.


Toolbox for Research, or how to facilitate a central data management in small-scale research projects.
In most research projects budget, staff and IT infrastructures are limiting resources. Especially for small-scale registries and cohort studies professional IT support and commercial electronic data capture systems are too expensive. Consequently, these projects use simple local approaches (e.g. Excel) for data capture instead of a central data management including web-based data capture and proper research databases. This leads to manual processes to merge, analyze and, if possible, pseudonymize research data of different study sites. To support multi-site data capture, storage and analyses in small-scall research projects, corresponding requirements were analyzed within the MOSAIC project. Based on the identified requirements, the Toolbox for Research was developed as a flexible software solution for various research scenarios. Additionally, the Toolbox facilitates data integration of research data as well as metadata by performing necessary procedures automatically. Also, Toolbox modules allow the integration of device data. Moreover, separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures the compliance to data protection regulations. This pseudonymized data can then be exported in SPSS format in order to enable scientists to prepare reports and analyses. The Toolbox for Research was successfully piloted in the German Burn Registry in 2016 facilitating the documentation of 4350 burn cases at 54 study sites. The Toolbox for Research can be downloaded free of charge from the project website and automatically installed due to the use of Docker technology.


Physical activity motivation and benefits in people with multiple sclerosis.
Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic degenerative neurological disease that the individual lives with for a majority of the lifespan. Physical activity is one means that has been shown to aid is the control of multiple sclerosis symptoms. Increasing patient understanding of the benefits of using physical activity as a means to control multiple sclerosis symptoms may result in long-term physical activity adherence. Physical activity interventions that develop feelings of competence and independent choice in the patient may be more successful for long-term participation.


Can interventions to promote animal production ameliorate undernutrition?
The potential of animal-source foods (ASF) to alleviate micronutrient deficiencies is well recognized. How the intake of ASF can be effectively increased is not known, but promoting animal production (AP) is one possible method. We reviewed the impact of interventions promoting AP on nutritional status and on 6 nutrition-related outcomes: production, household income and expenditure, caregiver income, caregiver time and workload, zoonosis, and dietary intake. Information about the effects on each of the possible outcomes is needed to be able to weigh trade-offs in the potential benefits and costs of promoting AP. The majority of the 14 identified studies found a positive effect of the promotion of AP on production. All studies evaluating the impact on household income or expenditure reported a positive effect on these outcomes. Evidence regarding impact on caregiver income and on caregiver time and workload is too limited to draw any conclusions. We found no studies that examined the impact of the promotion of AP on zoonosis. The studies generally reported a positive impact on dietary intake. Only 4 studies evaluated the impact on nutritional status and found a positive effect. It is unclear whether the improvements in dietary intake and nutritional status were a direct effect of increased production or an indirect effect of increased income. Future studies on the AP-nutrition link would benefit from stronger methodological designs. Available evidence is insufficient to answer whether the promotion of AP is an effective means to alleviate undernutrition.


Dynamics of chains and dendrimers with heterogeneous semiflexibility.
Based on our recent model for the dynamics of semiflexlible treelike networks [M. Dolgushev and A. Blumen, J. Chem. Phys. 131, 044905 (2009)], we study the dynamical properties of chain polymers and of dendrimers whose junctions display different stiffness degrees (SD). In these polymers the functionality f of the inner junctions is constant, being f=2 for the linear chains and f=3 for the dendrimers. This allows us to focus on the effects caused by the heterogeneities due to different SD. For this we study alternating, diblock, as well as random arrangements of the SD. Each of these cases shows a particular, macroscopically observable behavior, which allows to distinguish between the different microscopic SD arrangements.


The cost of care for patients with HIV from the provider economic perspective.
Health care costs for HIV infection are often reported from the economic perspective of third party payors and little data exist to show how total costs are distributed across specific health service categories. We used a retrospective cohort design to measure total medical costs for 1 year in a randomly selected sample of 280 patients treated for HIV infection at an urban health care facility. Inpatient and outpatient costs were measured from the economic perspective of the health care provider. Hospital costs included ward, ancillary, and procedure costs. Ambulatory included medications, primary and specialty care, case management, ancillary, and behavioral comorbidity treatment costs. The mean total was $20,114 per patient, of which $6,322 was for inpatient and $13,842 was for ambulatory services. Specific ambulatory costs were: medications, $9,257; primary, specialty and ancillary services, $3,470; and behavioral comorbidity treatment, $1,111. The mean annual outpatient ancillary cost was $841. Over 30% of the total service cost was for building and administrative overhead and approximately 25% of both hospital and clinic costs were for ancillary services. Independent predictors of high cost were CD4 counts, Medicaid eligibility, and behavorial comorbidities. Our outpatient costs were higher, with less variation than previously reported. Increasingly, there has been a shift of HIV care from hospital to ambulatory settings. We postulate that reimbursement rates have not captured the recent flourishing of ambulatory care. If reimbursement is not commensurate with outpatient advances, providers may be paradoxically underreimbursed for improving care.


MRI findings of an ovarian dermoid cyst with malignant transformation.
The ovarian dermoid cyst is the most common ovarian tumor. However, malignant transformation developing from a dermoid cyst is very rare. Because of this rarity, few reports exist of preoperative diagnosis of this tumor by MRI. We report MRI findings from a 69-year-old patient with a malignant transformation (squamous cell carcinoma with sarcomatoid features) in a right ovarian dermoid cyst.


Effect of traditional Chinese medicine on oligoasthenospermatism: a narrative review.
To summarize the treatment of oligoasthenospermatism (OAS) with Traditional Chinese Medicine (TCM). The literature describing OAS treatment with TCM in the past 4 years was searched. Three studies were reviewed, evaluated, and summarized. The etiology and pathogenesis, pattern differentiation, medicine administration, and combination of TCM with Western Medicine were all examined. TCM had an advantage in treating OAS and had fewer adverse events than conventional treatments. Although TCM has an advantage in treating OAS and fewer adverse events, the efficacy of TCM and modern medicine on OAS is unsatisfactory.


Peritonitis in peritoneal dialysis.
Peritonitis, an infectious complication of peritoneal dialysis, continues to account for much of the morbidity associated with this techniques. The clinical presentation and laboratory data used in diagnosis the peritonitis, as well as its differential diagnosis will be reviewed in this article. The distribution of pathogens is an important outcome determinant, Gram-negative infections being associated with greater rates of catheter loss and higher death rates. Among the five routes of peritoneal contamination, intraluminal and periluminal contamination account for most of the infections. Due to the two prevention methods implemented in the care of the PD population, the incidence of peritonitis has decreased over the last two decades. The recommendations for empiric treatment of peritonitis have changed over the years, as more was learnt about antibiotic resistance and drug toxicity. Future research to address enteric peritonitis, as well as biocompatible dialysis solution or biocompatible catheter materials is needed to further reduce the incidence of PD peritonitis.


Delay in death reporting affects timely monitoring and modeling of the COVID-19 pandemic.
This study describes the COVID-19 death reporting delay in the city of São Luís, Maranhão State, Brazil, and shows its impact on timely monitoring and modeling of the COVID-19 pandemic, while seeking to ascertain how nowcasting can improve death reporting delay. We analyzed COVID-19 death data reported daily in the Epidemiological Bulletin of the State Health Secretariat of Maranhão and calculated the reporting delay from March 23 to August 29, 2020. A semi-mechanistic Bayesian hierarchical model was fitted to illustrate the impact of death reporting delay and test the effectiveness of a Bayesian Nowcasting in improving data quality. Only 17.8% of deaths were reported without delay or the day after, while 40.5% were reported more than 30 days late. Following an initial underestimation due to reporting delay, 644 deaths were reported from June 7 to August 29, although only 116 deaths occurred during this period. Using the Bayesian nowcasting technique partially improved the quality of mortality data during the peak of the pandemic, providing estimates that better matched the observed scenario in the city, becoming unusable nearly two months after the peak. As delay in death reporting can directly interfere with assertive and timely decision-making regarding the COVID-19 pandemic, the Brazilian epidemiological surveillance system must be urgently revised and notifying the date of death must be mandatory. Nowcasting has proven somewhat effective in improving the quality of mortality data, but only at the peak of the pandemic.


A case of treating cathinone dependence and comorbid depression using bupropion.
Cathinone is a potent CNS stimulant found in khat leaves. Cathinone and synthetic cathinone-derivatives have become popular recreational drugs in recent years, commonly marketed as "legal highs." In addition to acute physical and psychiatric adverse effects, dependence on these substances is a concern. The following case reports describes a young man with cathinone dependence and depression that was treated using bupropion. Bupropion is a cathinone-derivative with a dual dopamine-norepinephrine reuptake inhibiting mechanism, which is approved for the treatment of depression and smoking cessation. Clinical awareness to the addictive potential of cathinone and cathinone-derivatives is important. Research regarding the potential effectiveness of bupropion in these cases is needed.


Factors Associated with Physical Activity in a Diverse Older Population.
Physical activity is important for healthy aging, but few older adults achieve the goal of 150 min per week of moderate activity. The purpose of this study was to employ a robust statistical approach in the analysis of the factors related to physical activity in a diverse sample of older adults. A secondary analysis of factors associated with calculated MET-h/week was conducted in a sample of 601 African Americans, Afro-Caribbeans, European Americans, and Hispanic Americans age 59 to 96 living independently in the community. Age, education, social network, pain, and depression were the five variables that accounted for a statistically significant proportion of unique variance in the model. The strongest correlation to total MET-h/week was with depression. Directionality of the relationship between these variables and physical activity is complex: while pain and depression can reduce physical activity, activity may also help to reduce pain and depression. Additionally, of note is that many of these factors may be modified, calling for the design and testing of individual, group, and community level interventions to increase physical activity in the older population.


Photoanalogues of the initiation substrates of the RNA polymerase II, 5-azido-2-nitrobenzoyl derivatives of the ATP gamma-amidophosphate: the possible photoinduced degradation of the functional group to an N-arylhydroxylamine.
Photoanlogues of the initiation substrates of the RNA polymerase II, N3ArNH(CH2)(n)NHpppA where N3Ar is 5-azido-2-nitrobenzoyl group (n = 2 or 4) were synthesized, allowing the preparation of photoreactive oligonucleotides in situ by RNA polymerase II for application as photolabels. Photolysis of p-nitro-substituted aromatic azide in aqueous medium was investigated. Using the azoxy-coupling reaction it was possible to determine whether a nitrene or p-nitrophenyl hydroxylamine azoxy compound is the trappable intermediate that is generated at ambient temperature in aqueous solution.


The mechanism of tissue-restricted antigen gene expression by AIRE.
The autoimmune regulator is a critical transcription factor for generating central tolerance in the thymus. Recent studies have revealed how the autoimmune regulator targets many otherwise tissue-restricted Ag genes to enable negative selection of autoreactive T cells.


Advances in diagnostic bronchoscopy.
Diagnostic bronchoscopy has undergone two major paradigm shifts in the last 40 years. First, the advent of flexible bronchoscopy gave chest physicians improved access to the tracheobronchial tree with a rapid learning curve and greater patient comfort compared with rigid bronchoscopy. The second paradigm shift has evolved over the last 5 years with the proliferation of new technologies that have significantly enhanced the diagnostic capabilities of flexible bronchoscopy compared with traditional methods. At the forefront of these new technologies is endobronchial ultrasound. In its various forms, endobronchial ultrasound has improved diagnostic yield for pulmonary masses, nodules, intrathoracic adenopathy, and disease extent, thereby reducing the need for more invasive surgical interventions. Various navigational bronchoscopy systems have become available to increase flexible bronchoscope access to small peripheral pulmonary lesions. Furthermore, various modalities of airway assessment, including optical microscopic imaging technologies, may play significant roles in the diagnosis of a variety of pulmonary diseases in the future. Finally, the combination of new diagnostic bronchoscopy technologies and novel approaches in molecular analysis and biomarker assessment hold promise for enhanced diagnosis and personalized management of many pulmonary disorders. In this review, we provide a contemporary review of diagnostic bronchoscopy developments over the past decade.


Ultrastructural morphometric analysis of endomyocardial biopsies. Idiopathic dilated cardiomyopathy, anthracycline cardiotoxicity, and normal myocardium.
Anthracycline cardiotoxicity has been regarded as a model of idiopathic dilated cardiomyopathy, and similar histopathologic changes have been described in both. Our purpose was to quantify these changes, using computer-assisted ultrastructural morphometry, and compare them with normal myocardium. Right ventricular endomyocardial biopsies were taken from 10 patients with anthracycline cardiotoxicity (AC), 10 patients with idiopathic dilated cardiomyopathy (CM), and 10 disease-free transplant donor heart controls (C). Mean myocyte width (corrected for sarcomere length) was significantly greater in CM (29.3 microns +/- 7.2) than in AC (19.2 +/- 3.2) or C (20.3 +/- 3.4). Mean nuclear area was significantly greater in CM (88.7 microns 2 +/- 27.1) than in AC (54.2 +/- 15.3) or C (45.0 +/- 9.2). Nuclear form factor (corrected for sarcomere length) was significantly lower (indicating a more irregular outline) in CM (0.28 +/- 0.09) than in AC (0.46 +/- 0.06) or C (0.36 +/- 0.04). Mean mitochondrial area was significantly smaller in CM (0.30 microns 2 +/- 0.05) than in C (0.35 +/- 0.05), but differences between AC (0.35 +/- 0.09) and the other groups were not significant. These results suggest that anthracycline cardiotoxicity is not, quantitatively, a faithful model of idiopathic dilated cardiomyopathy.


Use of Light Protection Equipment at Night Reduces Time Until Discharge From the Neonatal Intensive Care Unit: A Randomized Interventional Study.
Newborn infants' circadian systems are not completely developed and rely on external temporal cues for synchronizing their biological rhythms to the environment. In neonatal intensive care units (NICUs), lighting is usually continuous or irregular and infants are exposed to artificial light at night, which can have negative health consequences. Therefore, the aim of this study was to evaluate the impact of the use of individual light protection equipment at night on the development and growth of preterm neonates. Infants born at less than 37 gestational weeks who no longer needed constant intensive care were admitted into a newborn nursery and randomized to either use eye masks at night (intervention, n = 21) or not (control, n = 20). Infants who used eye protection at night were discharged earlier than those in the control group (8 [5] vs 12 [3.75] days; p < 0.05). A greater variation within the day in heart rate was observed in the intervention group, with lower values of beats per minute at 1400 and 2000 h. There was no significant difference in weight gain between groups. In view of our results and of previous findings present in the literature, we suggest that combining a darkened environment at night with individual light protection devices creates better conditions for the development of preterm infants in the NICU. In addition, eye masks are an affordable and simple-to-use tool that can reduce hospitalization costs by decreasing the number of days spent in the NICU.


Premilking teat disinfection: is it worthwhile in pasture-grazed dairy herds?
A controlled trial was conducted in 5 pasture-grazed commercial dairy herds in Australia in 2012 to determine whether premilking teat disinfection and drying of teats reduces clinical mastitis incidence during early lactation by at least 50%. A 50% reduction was estimated to be the minimum required to justify additional costs of labor, disinfectants, and other resources if premilking teat disinfection was implemented in a 500-cow herd averaging 8 clinical cases per 100 cow-months. A secondary aim was to determine whether this premilking teat disinfection routine reduces incidence of new udder infections. Treatment was applied in each herd for approximately 60 d (range of 59.5 to 61 d), commencing in each herd soon after the start of the herd's main or only calving period. Within each herd, cows were allocated to either the treatment (premilking disinfection) or the control (no premilking disinfection) group based on their herd identity number. During the trial period, any cow having a new case of clinical mastitis or an individual cow cell count greater than 250,000 cells/mL of milk (when preceded by individual cow cell counts of 250,000 cells/mL of milk or below) was deemed to have had a new infection. Overall, neither clinical mastitis incidence nor new infection rate differed significantly between treatment and control groups. Over the whole study period, 98 of the 1,029 cows in the premilking disinfection group and 97 of the 1,025 cows in the control group had clinical mastitis. Total cow-days at risk of clinical mastitis were similar in each group. However, clinical incidence rates were markedly lower in treatment cows in one herd (herd 3; incidence rate ratio=0.34) and there was some evidence that new infection incidence rates were lower in treated cows in this herd (incidence rate ratio=0.42). Rainfall during the study period was below long-term district average in all 5 study herds. Cows' teats were less dirty than in previous, wetter years for the 4 herds where no significant clinical mastitis response was detected but some teat soiling was observed in herd 3 during the study period. Routine application of premilking teat disinfection in pasture-grazed herds is unlikely to produce a worthwhile (economic) reduction in the number of clinical mastitis cases when teats are relatively clean and dry and the clinical mastitis incidence is low. However, premilking disinfection might be worthwhile during periods when teats are heavily soiled and the incidence of clinical mastitis due to environmental pathogens is high.


Starvation in the rat. I. Effect of age and obesity on organ weights, RNA, DNA, and protein.
Previous studies have shown that obese man adapts to prolonged starvation with a conservation of body protein. In an attempt to delineate the biochemical and hormonal changes responsible for this adaptation, the effect of starvation was studied in rats with differing abilities to survive a fast and conserve protein. Sixteen-week-old rats made obese by fat feeding survived starvation for 25-30 dys, whereas 16-wk-old controls survived 11-12 days and the 8-wk-old controls for 6-7 days. Starvation decreased hepatic weight, RNA, and protein early in the fast in all three groups. In heart, the extensor digitorum longus muscle and some other organs decreases in RNA, protein, and weight occurred more slowly and were smaller in magnitude in the 16-wk-old control and obese rats. A pronounced loss of cardiac protein and RNA occurred in the 8-wk-old group. We conclude that 16-wk-old control and obese rats are better able to survive and conserve organ protein and RNA during prolonged starvation than younger rats. To what extent this reflects differences in the age and to what extent differences in adiposity remains to be determined.


[Contemporary views on the pathological mechanism of asthma].
Asthma is a chronic inflammatory disease of the airways. Genetic and environmental factors contribute to the development of asthma. Both inflammation and remodelling are essential mechanisms in the development of subepithelial fibrosis and smooth muscle hypertrophy leading to progressing decrease of FEV1. Inflammatory changes in asthma are characterised by cellular infiltration of airway epithelium, bronchial wall and smooth muscle layer. The most important cells participating in asthma include T lymphocytes, mast cells, airway epithelial cells, eosinophils, antigen-presenting cells, neutrophils, fibroblasts, myofibroblasts and macrophages. They produce many cytokines responsible for the development of allergen-specific clones of Th2 lymphocytes, for production of IgE by B-cells, for increased expression of adhesion molecules, for migration of cells, their activation and release of inflammatory mediators. The mediators coming mainly from mast cells and eosinophils that include leukotrienes, prostaglandins, histamine, alkaline proteins and enzymes are responsible for airway obturation that results from bronchospasm, bronchial mucosal oedema and excessive amount of abnormal mucous secretion. An important role in the obturation is played by smooth muscle hypertrophy and deposition of proteins under the basal membranes of respiratory epithelium.


Factors Affecting Transcranial Motor-Evoked Potential Measurements Using Single-Train Stimulation with an Increased Number of Pulses during Adolescent Scoliosis Surgery: A Prospective Observational Study.
Measurement of transcranial motor-evoked potentials (TcMEPs) during scoliosis surgery helps detect postoperative new neurological defects. However, TcMEP interpretation is difficult owing to the influence of intraoperative physiological, pharmacological, and time-related factors as well as stimulation conditions. In this study, we aimed to investigate the effect of the abovementioned factors on TcMEP amplitude using single-train stimulation with an increased number of pulses (STS-INP) during adolescent scoliosis surgery; moreover, we evaluated the complications of TcMEP measurement. We included 50 patients and 706 TcMEP measurements. A total of 1412 TcMEP waveforms were analyzed, each on the bilateral abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles. We estimated the mean difference (95% confidence interval (CI)) and predicted mean difference (95% CI) evaluated using the interquartile range of each factor, based on a mixed-effect model with random intercepts for TcMEP amplitude. The predicted mean differences in TcMEP amplitude were clinically small compared with the actual TcMEP amplitude, suggesting that each factor had a limited effect on TcMEP amplitude. No intraoperative bite injuries or seizures were observed. Using STS-INP during adolescent scoliosis surgery may enable accurate measurement of TcMEP amplitude with neither complications nor the influence of various intraoperative factors.


Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak.
Clusters of severe respiratory disease in the United States were reported to the CDC beginning in August 2014. Enterovirus D68 (EV-D68) was identified from 83% (30/36) of initial severe cases. Investigations in August and September found severe EV-D68 cases to be widespread across the United States. We report seven EV-D68 genomes from the outbreak.


[Specific count of cerebrospinal fluid cells in the counting chamber using supravital staining].
The authors adapted to the cerebrospinal fluid (CSF) the staining technic developed by Anguiano and Ancira to perform differential leucocyte counts in the counting chamber. The formula they used is the following: methyl alcohol 1 ml, distilled water 2 ml. To this mixture are added: 6 drops of Leishman stain filtered in Whatman paper number 42; toluidine blue 0.25% aqueous solution (filtered in the same manner), 1 drop; acetate buffer 0.1 M, pH 5.4, 1 drop. The technic varies according to the intensity of pleocytosis. If the CSF is turbid or contains more than 100 cells per c.m. 1 drop is dripped in the bottom of a 10X75 test tube and then 2 drops of the staining fluid are added; the mixture is then shaken; after one or two minutes 1 drop is placed in the Fuchs-Rosenthal counting chamber. If the number of total cells is less than 100 per c.m. different CSF volumes are centrifuged at the rate of 2000 r.p.m., during 6 minutes; the supernatant fluid is poured off and the sedimented cells are suspended in 2 drops of the staining fluid. The morphology of the cells as they appear after they are stained by the supravital staining technic (SVST) is described and illustrated in photomicrographies.(ABSTRACT TRUNCATED AT 250 WORDS)


Distribution of lifestyle and emerging risk factors by 10-year risk for coronary heart disease.
The Framingham risk score has been used for coronary heart disease (CHD) risk assessment. Recently, additional risk factors not included in the Framingham algorithm have received much attention and may help improve risk assessment. We examined the distributions of lifestyle and emerging risk factors by 10-year risk of CHD. We calculated 10-year CHD risk (<10%, 10-20%, and >20%) for 8355 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002 using the Framingham risk score as modified by the National Cholesterol Education Program Adult Treatment Panel III guidelines. We examined the prevalence of lifestyle risk factors [body mass index (BMI) and waist circumference] and various emerging risk factors [C-reactive protein (CRP), white blood cell count, fibrinogen, homocysteine, glycosylated hemoglobin, and albuminuria] as well as prevalence of high CHD risk by levels of these risk factors. All examined CHD risk factors were significantly associated with increasing 10-year CHD risk among men and women. Odds of being in the highest CHD risk group were greater at higher levels of examined risk factors. Means for most risk factors were slightly higher for women than the means for men. Sizeable proportions of participants with lower 10-year CHD risk had high levels of lifestyle and emerging risk factors: 60.8% were overweight, 33.8% had high CRP concentrations, 24.1% had serum fibrinogen >400 mg/dl and 6% had an albumin/creatinine ratio >/=30. Lifestyle and emerging risk factors, in addition to those included in the Framingham risk score, may be important in CHD risk assessment.


N-ras gene point mutations in Brazilian acute myelogenous leukemia patients correlate with a poor prognosis.
The frequency of ras gene mutations varies from 11 to 27% in AML populations from the United States and Europe but it seems that there is no study regarding the frequency of mutated N-ras gene in patients with AML in South America. In order to study the frequency of N-ras gene mutations (exons 1 and 2) in Brazilian patients with AML and to evaluate the possible correlation between the presence of the mutation and clinical features, 40 patients were analyzed. N-ras mutations were identified in DNA samples from eight of 40 AML patients (20%). No significant correlation was found between N-ras mutation and age, sex, race, response to therapy, FAB subtype or occupational exposure. However, the overall survival and AML-free survival were significantly shorter in patients with N-ras mutations than in those without these abnormalities.


Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E.
Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid differentiation factor 88 (MyD88) play an essential role in the innate immune responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is associated with a significant reduction of aortic plaque areas in atherosclerosis-prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia, implying an important role for the innate immune system in atherogenesis. Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques. Endothelial-leukocyte adhesion in response to minimally modified low-density lipoprotein was reduced in aortic endothelial cells derived from MyD88-deficient mice. Taken together, our results suggest an important role for TLR4 and MyD88 signaling in atherosclerosis in a hypercholesterolemic mouse model, providing a pathophysiologic link between innate immunity, inflammation, and atherogenesis.


Effect of vanadate on amino acid transport in rat jejunum.
Vanadate has been reported to inhibit (Na+ + K+)-ATPase of many cells and in some systems to stimulate adenylate cyclase. Since intestinal transport is influenced by these enzymes, we studied the effects of varying concentrations of orthovanadate (VO-4) on alanine transport in the in vitro rat jejunum. At the higher concentrations tested (10(-3) and 10(-2) M) vanadate had a ouabainlike action on alanine transport. It decreased the mucosal-to-serosal flux and the influx of alanine into the intestinal epithelium and it caused a reduction of (Na+ + K+)-ATPase activity of basolateral membranes. The relatively lower vanadate concentration of 10(-4) M increased the influx and the efflux of alanine across the mucosal border of the jejunum. The increase was associated with elevation of cyclic AMP in the intestinal mucosa. The studies suggest the presence of a dual action of vanadate on amino acid transport, a stimulatory effect at low concentration, due to increased adenylate cyclase activity, and an inhibitory effect at higher concentrations, due to a decreased activity of (Na+ + K+)-ATPase.


[Cataloging the diversity of the human body: 19th-century French nosology concerning unlawful behavior (1800-1855)].
This work aims to contribute to the study of the factors which influenced the process of the classification of the diversity of human behaviour. As a result this study will look at the changes in operation at the beginning of the nineteenth century regarding the classification of one type of deviant behaviour: homicide. The creation by French psychiatrists of the diagnostic category "monomanie homicide instintive" meant that certain types of homicide were no longer considered a crime and began to be regarded as forms of madness. The emergence and gradual disappearance of this morbid species of psychiatric classifications in the first half of the XIXth century illustrates how the assignation of aberrant behaviour to one kind or other of deviance depends on the way in which various factors are related: changes in scientific theories, permutations in the professional objectives of those who make the classifications, and the degree of social consensus which is achieved for the new meaning that the deviatory behaviour acquires on changing its position among the various forms of deviation.


Analysis of Gastric Body Microbiota by Pyrosequencing: Possible Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.
Gastric microbiota along with Helicobacter pylori (HP) plays a key role in gastric disease. The aim of our study is to investigate the difference of human gastric microbiota between antrum and body according to disease (control vs. gastric cancer) and HP status. Each antrum and body biopsy was collected from 12 subjects at Seoul National University Bundang Hospital. Gastric microbiota was analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Twelve subjects consisted of HP-negative control (n = 2), HP-negative cancer (n = 2), HP-positive control (n = 3), and HP-positive cancer (n = 5). The analysis was focused on non-HP urease-producing bacteria (UB) and non-HP nitrosating or nitroreducing bacteria (NB) between antrum and body. Gastric body samples showed higher diversity compared to gastric antrum mucosa samples but there was no significant difference. The mean of operational taxonomic units was higher in HP(-) cancer than HP(+) cancer (antrum, 273.5 vs. 228.2, P = 0.439; body, 585.5 vs. 183.2, P = 0.053). The number of non-HP UB and non-HP NB was higher in HP(-) cancer groups than the others. These differences were more pronounced in the body (P = 0.051 and P = 0.081, respectively). Analysis of overlap of non-HP UB and non-HP NB revealed the higher composition of Streptococcus pseudopneumoniae, S. parasanguinis, and S. oralis in HP(-) cancer groups than the others, only in the body (P = 0.030) but not in the antrum (P = 0.123). Higher diversity and higher composition of S. pseudopneumoniae, S. parasanguinis, and S. oralis in HP(-) cancer group than the other groups in the body suggest that analysis of microbiota from body mucosa could be beneficial to identify a role of non-HP bacteria in the gastric carcinogenesis.


Activation of N2 on Manganese Nitride-Supported Ni3 and Fe3 Clusters and Relevance to Ammonia Formation.
Dual-site models were constructed to represent manganese nitride (Mn4N)-supported Ni3 and Fe3 clusters for NH3 synthesis. Density functional theory calculations produced an energy barrier of approximately 0.55 eV for N-N bond activation at the interfacial nitrogen vacancy sites (Nv); also, the hydrogenation and removal of interfacial N is promoted by earth-abundant Ni and Fe metals. Steady-state microkinetic modeling revealed that the turnover frequencies of NH3 production follow an order of Fe3@Mn4N ≈ Ni3@Mn4N > Mn4N > Fe ≫ Ni. Moreover, we present clear evidence that, before NH3 formation, NH migrates from Nv onto the metallic sites. Using N binding energy (BEN) and the transition-state energy of N2 activation (ETS) as descriptors, we concluded that the beneficial effects owing to interfacial Nv sites are the most pronounced when BEN is either too strong or too weak while ETS is high; otherwise, excessive Nv sites may hinder catalyst performance.


Review of primary tumors of the diaphragm.
A case report of a man with a huge, left-sided diaphragmatic rhabdomyosarcoma is presented. The mass was attached to the lung, pericardium, left phrenic nerve, sternum, and chest wall. Enbloc resection of the tumor was done with primary repair of the diaphragmatic defect. Only three reported cases of primary diaphragmatic rhabdomyosarcoma were found in the literature.


Blood biochemical and oxidant/antioxidant alterations following stanozolol treatment along with resistance training in rats.
This study was designed to determine the effects of anabolic steroid stanozolol (ST) in conjunction with 8 weeks of resistance training on some blood biochemical and oxidant/antioxidant profile in rats. Twenty-four male rats were divided into four groups of six each: group 1: sedentary + placebo (physiological saline), group 2: training + placebo, group 3: training + ST (2 mg kg-1 b.w.) and group 4: training + ST (5 mg kg-1 b.w.). Erythrocytic activity of glutathione peroxidase was increased significantly in group 4 as compared to control group. Plasma activities of alanine aminotransferase in groups 3 and 4 and also aspartate aminotransferase in group 4 showed significant increase relative to groups 1 and 2. Moreover, alkaline phosphatase and creatine kinase activities increased significantly in groups 3 and 4 in comparison with control group. Elevated values of uric acid were significant in group 4, but not in groups 2 and 3, as compared to control group. Values of other measured parameters did not have significant alterations among experimental groups. Present findings indicate that stanozolol treatment in combination with resistance training induces some side effects especially on liver and muscle as evidenced by alterations in plasma markers of tissue damage.


Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis.
T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP3Δ2, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichia coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17 : Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT.


[A pilot study of cytokine profile in cerebrospinal fluid of children with acute lymphocytic leukemia and neurotoxic side effects of chemotherapy].
In some cases standard chemotherapy of acute lymphocytic leukemia (ALL) leads to neurotoxicity; its mechanisms, methods of prognosis, and prevention are being actively studied. The aim of this study was to assess the cytokine profile in cerebrospinal fluid (CSF) of children with ALL and neurotoxic side effects of chemotherapy. This prospective study included 24 children with ALL aged from 3 to 17 years. Patients were further subdivided into ALL patients with (main group) and without neurological complications (comparison group). The level of cytokines in CSF was measured by Xmap technology (Luminex) using Invitrogen test systems (eBioscience) and the Luminex 200 system. The comparative analysis of the cytokine profile in the group of children with chemotherapy-induced neurotoxic complications revealed elevated levels of chemokine CXCL12 (SDF-1α) and stem cell factor (SCF). Increased level of these cytokines in CSF was characterized by a relatively risk for development of toxic peripheral neuropathy.


A Cross-Cultural Analysis of the Infant Behavior Questionnaire Very Short Form: An Item Response Theory Analysis of Infant Temperament in New Zealand.
The Infant Behavior Questionnaire-Revised Very Short Form (IBQ-R VSF; Putnam, Helbig, Gartstein, Rothbart, & Leerkes, 2014 ) is a newly published measure of infant temperament with a 3-factor structure. Recently Peterson et al. ( 2017 ) suggested that a 5-factor structure (Positive Affectivity/Surgency, Negative Emotionality, Orienting Capacity, Affiliation/Regulation, and Fear) was more parsimonious and showed promising reliability and predictive validity in a large, diverse sample. However, little is known about the 5-factor model's precision across the temperament dimensions range and whether it discriminates equally well across ethnicities. A total of 5,567 mothers responded to the IBQ-R VSF in relation to their infants (N = 5,639) between 23 and 52 weeks old. Using item response theory, we conducted a series of 2 parameter logistic item response models and found that 5 IBQ-R VSF temperament dimensions showed a good distribution of estimates across each latent trait range and these estimates centered close to the population mean. The IBQ-R VSF was also similarly precise across 4 ethnic groups (European, Māori, Pacific peoples, and Asians), suggesting that it can be used as comparable measure for infant temperament in a diversity of ethnic groups.


An Archaeal Chitinase With a Secondary Capacity for Catalyzing Cellulose and Its Biotechnological Applications in Shell and Straw Degradation.
Numerous thermostable enzymes have been reported from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1, which made it an attractive resource for gene cloning. This research reported a glycosyl hydrolase (Tk-ChiA) form T. Kodakarensis with dual hydrolytic activity due to the presence of three binding domains with affinity toward chitin and cellulose. The Tk-ChiA gene was cloned and expressed on Pichia pastoris GS115. The molecular weight of the purified Tk-ChiA is about 130.0 kDa. By using chitosan, CMC-Na and other polysaccharides as substrates, we confirmed that Tk-ChiA with dual hydrolysis activity preferably hydrolyzes both chitosan and CMC-Na. Purified Tk-ChiA showed maximal activity for hydrolyzing CMC-Na at temperature 65°C and pH 7.0. It showed thermal stability on incubation for 4 h at temperatures ranging from 70 to 80°C and remained more than 40% of its maximum activity after pre-incubation at 100°C for 4 h. Particularly, Tk-ChiA is capable of degrading shrimp shell and rice straw through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR) analysis. The main factors affecting shell and straw degradation were determined to be reaction time and temperature; and both factors were optimized by central composite design (CCD) of response surface methodology (RSM) to enhance the efficiency of degradation. Our findings suggest that Tk-ChiA with dual thermostable hydrolytic activities maybe a promising hydrolase for shell and straw waste treatment, conversion, and utilization.


Purification and properties of citrate lyase ligase from Streptococcus diacetilactis.
Citrate lyase ligase (acetate: SH--[acyl-carrier protein] enzyme ligase (AMP) from Streptococcus diacetilactis was purified 920-fold with a yield of 6.3%. The molecular weight of the enzyme was estimated to be 41000; the ligase consisted of one polypeptide chain. The acetylation of 1 mol of deacetyl-citrate lyase to enzymatically active citrate lyase required 6 mol ATP. The formation of AMP and pyrophosphate in the acetylation reaction was demonstrated. Citrate lyase ligase was specific for the lyase from S. diacetilacitis and did not acetylate lyases from Rhodopseudomonas gelatinosa and Enterobacter aerogenes. The substract acetate and ATP could be replaced by propionate and dATP, repectively. The reaction rates for ATP, acetate and deacetyl-citrate lyase followed Michaelis-Menten kinetics (Km values: 26 micron for ATP, 25 mM for acetate and 38 nM for deacetyl-citrate lyase).


Immunolocalization of proton-ATPase in the gills of the elasmobranch, Squalus acanthias.
Proton-ATPase was localized to mitochondria-rich cells in the interlamellar region of the gills of the elasmobranch, Squalus acanthias. Localization was accomplished using a polyclonal antibody specific for the 70 kDa subunit of the (V-type) proton-ATPase as confirmed by Western blot analysis. In addition, significant levels of N-ethymaleimide sensitive ATPase activity (0.116 +/- 0.026 mumol Pi.mg-1 protein.h-1) were also measured in crude gill membrane preparations. These data provide, for the first time, direct evidence of the localization of elements possibly involved in branchial acid-base (or ionic) regulation in elasmobranchs.


Altered Differential Control of Sympathetic Outflow Following Sedentary Conditions: Role of Subregional Neuroplasticity in the RVLM.
Despite the classically held belief of an "all-or-none" activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA) can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10-12 weeks on running wheels) or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM) into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals.


Synthesis of a monofunctional platinum compound and its activity alone and in combination with phytochemicals in ovarian tumor models.
Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. In this study, a new monofunctional planaramineplatinum(II) complex, namely tris(8-hydroxyquinoline)monochloroplatinum(II) chloride (coded as LH3), was synthesised and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistant A2780 (A2780(ZD0473R)) cancer cell lines, alone and in combination with the phytochemicals curcumin, genistein and resveratrol. Cellular levels of glutathione in A2780 and A2780(cisR) cell lines before and after treatment with LH3 and its combinations with genistein and curcumin were also determined. Interaction of the compounds with salmon sperm DNA, pBR322 plasmid DNA and damage to DNA in A2780 and A2780(cisR) cells due to interaction with LH3-alone and in combination with phytochemicals were also investigated. LH3 was found to be much more active than cisplatin against the resistant tumor models and greatest synergism in activity was observed when combinations of LH3 with genistein and curcumin were administered as a bolus. For combinations of LH3 with the phytochemicals, platinum accumulation and the level of Pt-DNA binding were found to be greater in the resistant A2780(cisR) cell line than in the parental A2780 cell line. Greater activity of LH3 than cisplatin against the resistant ovarian cell lines indicates that it may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy.


Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index.
Endothelial dysfunction plays a key role in atherogenesis. We prospectively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease (PAD). The study was specially aimed at assessing whether brachial artery flow-mediated dilation (FMD) added to the predictive value of ankle-brachial pressure index (ABPI). Of 131 patients monitored for a mean of 23+/-10 months, 18 had a coronary event, 12 a cerebrovascular event, and 9 a peripheral event. The median FMD was lower in patients with an event than in those without (5.8% versus 7.6%, P<0.05), whereas vasodilation to nitroglycerin was similar in the two groups. The cardiovascular event rate was higher in patients with FMD below the median versus those with FMD above the median (P<0.001 by log-rank test). In a Cox proportion hazard model, independent predictors of events were FMD below the median (P<0.01), ABPI below the median (P<0.01), and previous stroke (P<0.02). Similar results were obtained when peripheral events were excluded from the analysis. Below-median ABPI and FMD combined was more accurate in predicting risk (relative risk [RR] 13.0; 95% CI, 3.0 to 56.2; P<0.01) than ABPI (RR, 6.4; 95% CI, 1.4 to 29.1; P<0.02) and FMD (RR, 4.8; 95% CI, 1.1 to 23.3; P<0.05) alone. A low brachial artery FMD is an independent predictor of cardiovascular risk in patients with PAD and adds to the prognostic value of ABPI, which is currently the most powerful prognostic indicator in PAD.


A Single Electrochemical Probe Used for Analysis of Multiple Nucleic Acid Sequences.
Electrochemical hybridization sensors have been explored extensively for analysis of specific nucleic acids. However, commercialization of the platform is hindered by the need for attachment of separate oligonucleotide probes complementary to a RNA or DNA target to an electrode's surface. Here we demonstrate that a single probe can be used to analyze several nucleic acid targets with high selectivity and low cost. The universal electrochemical four-way junction (4J)-forming (UE4J) sensor consists of a universal DNA stem-loop (USL) probe attached to the electrode's surface and two adaptor strands (m and f) which hybridize to the USL probe and the analyte to form a 4J associate. The m adaptor strand was conjugated with a methylene blue redox marker for signal ON sensing and monitored using square wave voltammetry. We demonstrated that a single sensor can be used for detection of several different DNA/RNA sequences and can be regenerated in 30 seconds by a simple water rinse. The UE4J sensor enables a high selectivity by recognition of a single base substitution, even at room temperature. The UE4J sensor opens a venue for a re-useable universal platform that can be adopted at low cost for the analysis of DNA or RNA targets.


Stationary oscillation of an impulsive delayed system and its application to chaotic neural networks.
This paper investigates the stationary oscillation for an impulsive delayed system which represents a class of nonlinear hybrid systems. First, a new concept of S-stability is introduced for nonlinear impulsive delayed systems. Based on this new concept and fixed point theorem, the relationship between S-stability and stationary oscillation (i.e., existence, uniqueness and global stability of periodic solutions) for the nonlinear impulsive delayed system is explored. It is shown that the nonlinear impulsive delayed system has a stationary oscillation if the system is S-stable. Second, an easily verifiable sufficient condition is then obtained for stationary oscillations of nonautonomous neural networks with both time delays and impulses by using the new criterion. Finally, an illustrative example is given to demonstrate the effectiveness of the proposed method.


Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients.
Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-β (Aβ) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of Aβ and LOAD patients' macrophage transcriptome and metabolome are deregulated. We previously showed omega-3 fatty acid (ω-3)-mediated repair of unfolded protein response and here we show much broader transcriptomic effects. ω-3 treatment in vitro and ω-3 supplementation by the drink Smartfish (SMF) in vivo increased the transcripts of the genes and pathways of immunity, glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD+ ) synthesis, and reversed the defects in Aβ phagocytosis. In both peripheral blood mononuclear cells (PBMC) and macrophages, ω-3 increased ATP-linked oxygen consumption rate (OCR) and ω-3 with carnitine was superior to ω-3. ω-3 treatment in vitro and supplementation by the ω-3 drink SMF in vivo rescued macrophage phagocytosis when glycolysis or glycosylation were blocked. ω-3 provide flexible energy for immune clearance of the brain throughout the diurnal cycle, even in hypo- or hyper-glycemia. In certain LOAD patients, ω-3 may delay progression to dementia.


Combination therapy with paricalcitol and enalapril ameliorates cardiac oxidative injury in uremic rats.
This study investigated the protective effect of the angiotensin-converting enzyme inhibitor, enalapril, and the vitamin D analog, paricalcitol, alone or in combination, on cardiac oxidative stress in uremic rats. Rats were made uremic by 5/6 nephrectomy and treated for 4 months as follows: (1) uremic + vehicle (n = 11); (2) uremic + enalapril (30 mg/l in drinking water, n = 13); (3) uremic + paricalcitol (200 ng 3x week, n = 6); (4) uremic + enalapril + paricalcitol (n = 14), and (5) controls (n = 6). Cardiac NADPH oxidase activity increased by 300% in uremic rats compared to normal controls. Treatment with enalapril, paricalcitol or the combination of the two protected uremic rats from cardiac oxidative stress by inhibiting enzyme activity. Cardiac malondialdehyde (MDA) levels were significantly increased in uremic rats compared to normal controls. Only the combination therapy inhibited the increase in MDA levels in uremic rats. Cardiac glutathione was significantly reduced in uremic rats compared to normal controls. Enalapril, paricalcitol or the two in combination all protected against this reduction in glutathione. Cardiac copper/zinc superoxide dismutase (CuZn-SOD) activity decreased whereas manganese (Mn-SOD) activity increased in uremic rats compared to controls. Both mono and combination therapies ameliorated the alterations in cardiac SOD activity seen in uremic rats. Enalapril, paricalcitol and their combined therapy afford protection against cardiac oxidative stress in uremia.


First report of Mycoplasma hyopneumoniae seroprevalence in farmed wild boars in China.
Porcine enzootic pneumonia caused by Mycoplasma hyopneumoniae affects the global pig industry with significant economic losses. It is yet to know whether wild boars in China were infected with M. hyopneumoniae. The present study was conducted to examine the seroprevalence and to evaluate risk factors of M. hyopneumoniae infection in farmed wild boars in China. A total of 882 serum samples were collected from farmed wild boars in Jilin City, Siping City and Baishan City in Jilin Province, northeastern China from April 2015 to February 2016, and were examined by the double sandwich enzyme-linked immunosorbent assay (ELISA). Seventy-eight out of 882 (8.8%) serum samples were M. hyopneumoniae-seropositive. Among region groups, wild boars from Jilin city (11.7%, 33/281) had the highest seropositivity, followed by Siping city (11%, 29/263) and Baishan city (4.7%, 16/338), and the difference was statistically significant (P = 0.0031). The M. hyopneumoniae seroprevalence in the female wild boars (9.0%, 75/831) was higher than that in the male wild boars (5.9%, 3/51) (P = 0.4429). The results of this investigation showed that farmed wild boars were susceptible to M. hyopneumoniae. Logistic regression analysis showed that there is a significant correlation between the geographical area and M. hyopneumoniae infection, which may be related to the regional environment. This is the first report of M. hyopneumoniae seroprevalence in farmed wild boars in China, which provided baseline information for further studies and control of M. hyopneumoniae infection in wild boars in China.


Pretransplant biopsy in expanded criteria donors: do we really need it?
Renal transplantation is the best treatment for end-stage renal disease, including when using expanded criteria donors (ECD) kidneys. However, these suboptimal kidneys should be evaluated rigorously to meet their usefulness. Opinions differ about the best way to evaluate them. We retrospectively reviewed kidneys from ECD harvested by a single academic institution between January 2008 and September 2013. Needle biopsies were performed at the time of the harvest when considered relevant by the transplant team. Two pathologists where responsible for their analysis; the Remuzzi classification has been used in all cases. We evaluated 560 ECD kidneys. Biopsies were made in 197 (35.2%) organs, 20 of which were considered not usable and 36 good only for double transplantation. Sixty-three kidneys (11.3%) were discarded by the transplant team based on the biopsy result and clinical criteria. Donors who underwent a biopsy were older (P < .001) and had a worse glomerular filtration rate (GFR; P = .001). Comparing donors approved and rejected by the biopsy, the rejected donors were heavier (P = .003) and had a lower GFR (P = .002). Cold ischemia time was longer for the biopsy group (P < .001). Regarding graft function, the biopsy overall score correlated with the transplant outcome in the short and long term. Separately, glomeruli and interstitium scores were correlated with recipient's GFR in the earlier periods (3 months; P = .025 and .037), and the arteries and tubules correlated with GFR in the longer term (at 3 years P = .004 and .010). The decision on the usability of ECD grafts is complex. At our center, we chose a mixed approach based on donor risk. Low-risk ECD do not require biopsy. In more complex situations, especially older donors or those with a lower GFR, prompted a pretransplant biopsy. The biopsy results proved to be useful as they relate to subsequent transplant outcomes, thereby allowing us to exclude grafts whose function would most probably be less than optimal.


Gangliosides: Structures, Biosynthesis, Analysis, and Roles in Cancer.
Gangliosides are acidic glycosphingolipids containing one or more sialic acid residues. They are essential compounds at the outer leaflet of the plasma membrane, where they interact with phospholipids, cholesterol, and transmembrane proteins, forming lipid rafts. They are involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly governed by the glycan moiety, and changes in the structures of gangliosides occur under pathological conditions, particularly in neuro-ectoderm-derived cancers. With the progress in mass spectrometry analysis of gangliosides, their role in cancer progression can be now investigated in more detail. In this review we summarize the current knowledge on the biosynthesis of gangliosides and their role in cancers, together with the recent development of cancer immunotherapy targeting gangliosides.


Translocation of cdk2 to the nucleus during G1-phase in PDGF-stimulated human fibroblasts.
We studied the subcellular distribution of cdk2 in synchronized, PDGF-stimulated human fibroblasts (FH109). After contact inhibition and serum depletion, more than 95% of FH109 cells were arrested in G0/G1-phase. PDGF-AB led to a 16-fold increase in proliferation compared with untreated cells. Cell cycle progression was studied by flow cytometric analysis, [3H]thymidine incorporation, and phosphorylation of the retinoblastoma gene product, pRB. Using Western blot analysis after subcellular fractionation, we revealed that after PDGF stimulation the phosphorylated (Thr 160), i.e., activated, form of cdk2 (33 kDa) first appeared in the nucleus at late G1-phase and persisted throughout until to the end of S-phase. Since cdk2 was not synthesized de novo, and the amount of inactive cdk2 (35 kDa) remained constant in the nucleus, we suggested a translocation from the cytosol to the nucleus in late G1. Using immunofluorescence techniques, we detected a diffuse staining in quiescent cells. Starting at late G1-phase, cdk2 immunoreactivity was concentrated to the nucleus while immunoreactivity in the cytosol disappeared. We therefore draw the conclusion that cdk2 is translocated from the cytosol into the nucleus in late G1-phase. Since protein levels and activity of cdk7, which is the catalytic subunit of cdk-activating kinase (CAK) phosphorylating cdk2, remained constant throughout the cell cycle, CAK activity might therefore be regulated by the availability of its substrate cdk2.


Prognostic value of inflammation-based indexes for intrahepatic cholangiocarcinoma following curative resection.
It is widely acknowledged that inflammatory indices may serve as effective prognosis indicators for various malignancies. In the present study, the prognostic value of systemic inflammatory biomarkers for patients undergoing curative resection for intrahepatic cholangiocellular carcinoma (ICC) was investigated. Clinical data of ICC patients who underwent curative resection between September 2008 and July 2017 were collected. Inflammatory indictors were analyzed using the Area Under the Receiver Operating Characteristic Curve. Indictors that were significantly associated with the overall survival (OS) were used to establish a systemic inflammation-based score system and tested via nomogram using R software. The neutrophil To lymphocyte ratio (NLR) and lymphocyte to macrophages ratio (LMR) were significantly associated with the OS and disease-free survival of the patients. High NLR and low LMR were associated with worse clinicopathological and survival outcomes. The univariate and multivariate analyses indicated that tumor T stage, incisal margin, NLR and LMR were associated with the OS of the patients. The systemic inflammation-based scoring system based on LMR and NLR demonstrated a stronger discriminatory capacity and may serve as a useful prognostic parameter for patients undergoing curative resection for ICC. Low LMR and high NLR were observed to be associated with poor prognosis and worse clinical outcomes for patients with ICC undergoing curative surgery. A combined inflammation-based scoring system based on LMR and NLR may effectively predict the outcomes and serve as a novel prognostic predictor for these patients.


[Radical and palliative radiotherapy of tumors of the lung].
Radiotherapy can be used in patients with lung carcinoma as a radical treatment or as a palliative, depending on the clinical stage of malignancy, the histological type involved, and the patient's general status. The Author lists tumors that are amenable to radical radiotherapy (after or without surgery, as long as they meet certain requisites of the TNM classification system: thus microcytoma and bronchial stump recurrency after lobectomy or pneumonectomy), and tumors in which radiotherapy, while admittedly of mere symptomatic value, can yield satisfactory short-term results such as reduction of the tumor mass, resolution of atelectasis, or alleviation of a mediastinal syndrome. The paper concludes with a brief description of contraindications to the radiotherapy of pulmonary malignancy, side effects observed in the course of irradiation, and post-irradiation damages, the latter with special regard to sclerosis.


[Solid phase microextraction (SPME) of sample preparation during of a complex biological matrix in biotransformation studies].
Within the scope of the investigation of drug metabolism in keratinocytes solid phase microextraction (SPME) was investigated as a suitable method for sample preparation. The application of SPME is based on the fact, that a amount of analyte is absorbed by the polymer fiber at equilibrium, and the fiber is localized on a tip of a GC-syringe. The stable nitroxyl radical TEMPO (2,2,6,6-tetramthylpiperidine-1-oxyl) and its apolar metabolite 2,2,6,6-tetramethylpiperidine were analyzed by SPME and subsequent GC using thymol as internal standard. By means of the headspace-technique and an apolar fiber the recovery rate of TEMPO and the metabolite was nearly 100% and the precision was high. However, the results of the direct SPME were unsatisfactory. In comparison with conventional liquid/liquid extraction and solid phase extraction SPE the SPME proved the best results with regard to recovery rate and precision. Furthermore, the main advantages of SPME are the renunciation of organic solvents, the saving of time, the possibility to reuse the fiber about 100-150 times and the option for a complete automatisation of the extraction procedure.


Role of WNT16 in the regulation of periosteal bone formation in female mice.
In this study, we evaluated the role of WNT16 in regulating bone size, an important determinant of bone strength. Mice with targeted disruption of the Wnt16 gene exhibited a 24% reduction in tibia cross-sectional area at 12 weeks of age compared with that of littermate wild-type (WT) mice. Histomorphometric studies revealed that the periosteal bone formation rate and mineral apposition rate were reduced (P < .05) by 55% and 32%, respectively, in Wnt16 knockout (KO) vs WT mice at 12 weeks of age. In contrast, the periosteal tartrate resistant acid phosphatase-labeled surface was increased by 20% in the KO mice. Because mechanical strain is an important physiological regulator of periosteal bone formation (BF), we determined whether mechanical loading-induced periosteal BF is compromised in Wnt16 KO mice. Application of 4800-μe strain to the right tibia using a 4-point bending loading method for 2 weeks (2-Hz frequency, 36 cycles per day, 6 days/wk) produced a significant increase in cross-sectional area (11% above that of the unloaded left tibia, P < .05, n = 6) in the WT but not in the KO mice (-0.2% change). Histomorphometric analyses revealed increases in the periosteal bone formation rate and mineral apposition rate in the loaded bones of WT but not KO mice. Wnt16 KO mice showed significant (20%-70%) reductions in the expression levels of markers of canonical (β-catenin and Axin2) but not noncanonical (Nfatc1 and Tnnt2) WNT signaling in the periosteum at 5 weeks of age. Our findings suggest that WNT16 acting via canonical WNT signaling regulates mechanical strain-induced periosteal BF and bone size.


Study of Nitrogen Removal Performance When Treating Low Carbon Sewage Using External Solid Carbon Sources in SBBR Systems.
Based on low carbon wastewater as the research object and using corncob as an external solid carbon source, the performance of corncob organic matter was assessed for its release potential, quantity of release, and safety of use. The effects of varying quantities of the solid carbon source on simultaneous nitrification and denitrification were investigated in a sequencing biofilm batch reactor (SBBR). Results show that the regularity of corncob as solid carbon source material was linear, with released concentrations of heavy metals being below the Chinese national standard limit values for heavy metals according to the surface water environment quality standards (I and II) (GB3838-2002). When temperatures were within 28~31°C, the dissolved oxygen level was 4.0 ± 0.2 mg/L and the pH conditions were within 7.5~8.0. The optimal quantity for corncob dosing was 5 g per 1.5 L of low carbon wastewater. Following treatment, the average effluent concentrations of NH4+-N and TN were 2.85 mg/L and 4.51 mg/L, respectively. The effluent concentration of NH4+-N, TN had reached the A level national standard of sewage treatment plant pollutant discharge standard (GB18918-2002).


Identifying indicators of important diagnostic features of delirium.
To use an expert consensus process to identify indicators of delirium features to help enhance bedside recognition of delirium. Modified Delphi consensus process to assign existing cognitive and delirium assessment items to delirium features in the Confusion Assessment Method (CAM) diagnostic algorithm. Meetings of expert panel. Panel of seven interdisciplinary clinical experts. Panelists' assignments of each assessment item to indicate CAM features. From an initial pool of 119 assessment items, the panel assigned 66 items to at least one CAM feature, and many items were assigned to more than one feature. Experts achieved a high level of consensus, with a postmeeting kappa for agreement of 0.98. The study staff compiled the assignment results to create a comprehensive list of CAM feature indicators, consisting of 107 patient interview questions, cognitive tasks, and interviewer observations, with some items assigned to multiple features. A subpanel shortened this list to 28 indicators of important delirium features. A systematic, well-described qualitative methodology was used to create a list of indicators for delirium based on the features of the CAM diagnostic algorithm. This indicator list may be useful as a clinical tool for enhancing delirium recognition at the bedside and for aiding in the development of a brief delirium screening instrument.


Positivity bias in past and future episodic thinking: Relationship with anxiety, depression, and retrieval-induced forgetting.
Positivity biases in autobiographical memory and episodic future thinking are considered important in mental wellbeing and are reduced in anxiety and depression. The inhibitory processes underlying retrieval-induced forgetting (RIF) have been proposed to contribute to these biases. This investigation found reduced positivity in past and future thinking to be associated with reduced memory specificity alongside greater levels of anxiety, depression, and rumination. Most notably, however, RIF was found to significantly predict memory valence. This indicates that RIF may be important in maintaining such biases, facilitating the forgetting of negative memories when a positive item is actively retrieved.


Chest pain without obstructive coronary artery disease: a case series.
Ischaemic heart disease is a leading cause of mortality in women. Even in those without obstructive coronary artery disease (CAD), women with angina continue to have increased mortality. There are gender differences in prevalence of different pathophysiologies, including functional disorders such as microvascular and vasospastic angina. We describe four cases of angina in women with no obstructive CAD, in whom coronary function testing was performed. These four patients were diagnosed with disorders of coronary vasomotion, including vasospastic angina and different endotypes of microvascular angina. This case series highlights the different mechanisms of ischaemia in the absence of obstructive CAD. Patients with angina and no obstructive CAD classified by computed tomography coronary angiography may have myocardial ischaemia due to microvascular angina, vasospastic angina, or both. Conventional investigations risk under-diagnosing, and as a consequence under-treating, patients with these conditions. Coronary function testing, in the form of diagnostic guidewire-based tests and adjunctive acetylcholine provocation, has proven to be critical in the accurate diagnoses and appropriate management of these patients.