Island biogeography of the Anthropocene.
For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations.


Associations of age, gender and body mass with 1H MR-observed brain metabolites and tissue distributions.
Recent reports have indicated that a measure of adiposity, the body mass index (BMI), is associated with MR-observed brain metabolite concentrations and tissue volume measures. In addition to indicating possible associations between brain metabolism, BMI and cognitive function, the inclusion of BMI as an additional subject selection criterion could potentially improve the detection of metabolic and structural differences between subjects and study groups. In this study, a retrospective analysis of 140 volumetric MRSI datasets was carried out to investigate the value of including BMI in the subject selection relative to age and gender. The findings replicate earlier reports of strong associations of N-acetylaspartate, creatine, choline and gray matter with age and gender, with additional observations of slightly increased spectral linewidth with age and in female relative to male subjects. Associations of metabolite levels, linewidth and gray matter volume with BMI were also observed, although only in some regions. Using voxel-based analyses, it was also observed that the patterns of the relative changes of metabolites with BMI matched those of linewidth with BMI or weight, and that residual magnetic field inhomogeneity and measures of spectral quality were influenced by body weight. It is concluded that, although associations of metabolite levels and tissue distributions with BMI occur, these may be attributable to issues associated with data acquisition and analysis; however, an organic origin for these findings cannot be specifically excluded. There is, however, sufficient evidence to warrant the inclusion of body weight as a subject selection parameter, secondary to age, and as a factor in data analysis for MRS studies of some brain regions.


[Endocrine orbitopathy. Results of therapy in patients with reference to new pathogenetic aspects].
Present available conservative methods of treatment were evaluated in 148 patients with euthyroid endocrine ophthalmopathy. Levothyroxine was used as the basic drug in confirming normal thyroid function after goitre operation or radio-iodine therapy. In addition, prednisone was used, at first in a massive single dose and then alternating daily. Retrobulbar X-radiation was additionally given to 21 patients. Besides, 47 patients also received a lymphokinetic drug (Venalot-Depot) assuming the endocrine eye symptoms are manifestations of "local myxoedema". No single drug was found to be superior to any of the others but a combination can be successful as long as the period between manifestation of the eye symptoms and onset of treatment has not been more than two years.


[The palliative treatment of malignant esophageal stenosis and fistulae with self-expanding metal prostheses].
To evaluate the efficiency of self-expanding metal stents (SES) for the palliative treatment of malignant oesophageal strictures and fistulas. Fifty non-operable patients with malignant oesophageal strictures and/or fistulas were treated with SES placement. All patients had dysphagia, the mean degree for the studied group being 3.36. Ten patients presented associated tumoral fistula. Uncoated SES were placed for simple stenosis cases and coated SES for cancers with associated fistulas. A improvement in dysphagia was obtained in 47 patients (94%). The mean degree of dysphagia after the procedure was 1.12. In nine patients (90%) the fistula closed with resolution of the associated clinical picture. Complication were observed in six patients (12%), the perioperative mortality rate being 2%. During follow-up, twelve patients (25%) had malfunction of the stent, which was successfully treated in eight patients. SES are efficient for the palliative treatment of malignant oesophageal strictures and/or fistulas, but not commonly re-interventions are necessary to maintain a long-term functionality.


The effect of furosemide on luminal sodium, chloride and potassium transport in the early distal tubule of Amphiuma kidney. Effects of potassium adaptation.
Previous experiments in the early distal tubule of the doubly perfused kidney of Amphiuma demonstrated net reabsorption of potassium (K) which is reversed to net K secretion after K adaptation. Furthermore, it is known that this particular segment exhibits extensive chloride (Cl) net reabsorption which depends on the presence of sodium (Na) and which is inhibited by furosemide. In order to test for a possible interrelationship between NaCl and K transport, K activity in lumen and cell, transepithelial electrical potential difference, peritubular cell membrane potentials and volume reabsorption were measured in control animals and after K adaptation, in presence and absence of furosemide. In control animals the direction of net K transport is reversed from reabsorption to secretion upon addition of furosemide or following the removal of Cl from the tubular lumen. Volume reabsorption is inhibited by some 80%. In K adapted animals a similar inhibition of volume reabsorption is observed, however K secretion is not further enhanced. In control as well as in K-adapted animals intracellular K activities are still above electrochemical equilibrium after furosemide. The data suggest that a common transport system for Na, Cl and K is present in the luminal cell membrane which is inhibited by furosemide. K secretion observed in controls after furosemide and in K-adapted animals is driven by the cell to lumen electrochemical gradient for K across the K permeable luminal cell membrane. The shift of the luminal pump-leak system towards K secretion following K adaptation may be explained by an increase of the luminal K conductance and/or by a reduction of the activity of the luminal cotransport system. However, other mechanisms may also contribute to the observed phenomenon of K adaptation and cannot be ruled out at present.


Is there a male menopause?
Inadequate sexual performance is a common complaint of middle aged men. Many studies have shown that testicular function changes with age (mainly falling testosterone and sperm production associated with rising gonadotrophin levels); the effects are most notable after 70 years and are less obvious in subjects who have good health.


[Utilization and effectiveness of the flu vaccination in the prevention of the hospitalization induced by cardiorespiratory decompensation in high-risk patients in Cáceres].
Despite the recommendations to vaccinate annually against the flu to all the elderly and people with various chronic diseases, these recommendations are not comon to fulfill. In this case-control study performed in the service of Internal Medicine of the Hospital of Cáceres we have analyzed the degree of utilization of the flu vaccination in the season 2000/2001 in patients over 65 years of age with high-risk chronic diseases, as well as the effectiveness of this vaccination to avoid the hospitalization induced by cardiorespiratory decompensation, in order to reduce the number of consultations to the primary care physician and in order to reduce the issue of days of hospitalization. PATIENTS OF METHOD: 227 patients over 65 years of age with chronic cardiorespiratory disease, diabetes, chronic renal insufficiency, hepatopathy, previous pneumonia, or other causes of immunosuppression were studied. Of them, 116 were admitted because of cadiac or respiratory decompensation (cases); the control group was made up of 99 patients who went to outpatient consultations, with clinical manifestations similar to the cases and they were not hospitalized during the year of study. All the participants filled a questionnaire that included demographic characteristics and data about the underlying disease; the participants were grouped according to the number of underlying disease (one, two or more), according to if had received correctly the flu vaccination, according to the number of consultations to its Family doctor during the year of the study because of respiratory infections, according to the hospitalizations during the previous year and in the patients that were hospitalized acording to the number of days of the hospitalization. The average age was 71 years and 63% patients had been hospitalized the previous year. The percentage of vaccinated was of 60% and the vaccination was applied most frequently to the patients older than 75 years (p < 0.001), with EPOC (p < 0.005), and with cardiac insufficiency (p < 0.01), as well as to the patients with 2 or more risk factors (p < 0.001). Differences were not observed among the cases and the controls with regard to the age, to the incidence of ICC, to the incidence of DM, nor to the presence of 2 or more risk factors; however, the patients who were hospitalized presented a greater incidence of chronic obstructive pulmonary disease (COPD) (OR: 3.6; IC: 2.01-6.45) and of previous pneumonía (OR: 5.24: CI: 2.4-11-14): The factors most influencing the possibility of hospitalization were: EPOC (OR: 3.67; CI: 1.90-7.13); previous pneumonía (OR: 3.88: CI: 1.69-8.95). The estimate of hospitalizations avoided by the vaccination was of 59 (OR: 0.41; IC: 0.22-0.79). The vaccination did not decrease the number of consultations to the physician nor the days of the hospitalization. The flu vaccination looks underused in patients over 65 years of age with multiple diseases in the hospital environment. The vaccination seems to be effective in order to diminish the number of hospital admissions because of cardiorespiratory decompensation, even in non-epidemic seasons. We should insist on the use of the flu vaccination in these high-risk patients.


Brand name confusion: Subjective and objective measures of orthographic similarity.
Determining brand name similarity is vital in areas of trademark registration and brand confusion. Students rated the orthographic (spelling) similarity of word pairs (Experiments 1, 2, and 4) and brand name pairs (Experiment 5). Similarity ratings were consistently higher when words shared beginnings rather than endings, whereas shared pronunciation of the stressed vowel had small and less consistent effects on ratings. In Experiment 3 a behavioral task confirmed the similarity of shared beginnings in lexical processing. Specifically, in a task requiring participants to decide whether 2 words presented in the clear (a probe and a later target) were the same or different, a masked prime word preceding the target shortened response latencies if it shared its initial 3 letters with the target. The ratings of students for word and brand name pairs were strongly predicted by metrics of orthographic similarity from the visual word identification literature based on the number of shared letters and their relative positions. The results indicate a potential use for orthographic metrics in brand name registration and trademark law. (PsycINFO Database Record


Determination of spatial patterns of DNA damage and repair in intestinal crypts by multi-cell gel electrophoresis.
We have developed a method to quantitate DNA strand breaks as a measure of DNA damage and repair in intact, isolated intestinal crypts. The assay is a modified form of the single-cell gel electrophoresis or 'comet' assay. By maintaining the spatial relationship between the cells we were able to characterise the repair response and the susceptibility to DNA damage of cells as a function of their position in the crypt. All cells were equally repair competent over the first 30 minutes of the repair of UV-C and gamma-radiation induced lesions. DNA damage was equally distributed following gamma-radiation but following incubation with the topoisomerase II inhibitor etoposide, damage was greater in the lower crypt with an unusual component to the comet tall which was tapered, implying an incremental change in susceptibility by cell position. This tapered component of the comet tail resolved rapidly after removal of etoposide. The pattern of damage produced by hydrogen peroxide was dose dependent with lower doses producing more strand breaks in the base of the crypt-an effect lost at higher doses. The assay has the ability to detect differences between cells in their susceptibility to DNA damage and their subsequent repair response which may vary with their proliferative or differentiative status.


Current progress in neonatal surgery.
Neonatal surgery is the most specialized and sophisticated field of pediatric surgery. I herein review esophageal atresia, abdominal wall defects, gastrointestinal perforation, and congenital diaphragmatic hernia (CDH) as representative types of neonatal surgery. The clinical results of esophageal atresia have been considered to reflect the level of medicine of an individual country. Owing to an early diagnosis, improved operative techniques, and better perioperative management, the mortality rate has now become almost 0%. In addition, a minimally invasive thoracotomy is considered to improve long-term quality of life. The overall mortality rate of neonatal surgical disease has markedly decreased and is now less than 10%. However, abdominal wall defects, gastrointestinal perforation, and CDH still show a high mortality rate. A high incidence of chromosomal anomalies results in a poor outcome for abdominal wall defect. A gastrointestinal perforation in an infant complicated with an extremely how birth weight shows a high mortality rate. In CDH, pulmonary hypoplasia as well as pulmonary hypertension often causes an acute respiratory and circulatory deterioration after birth. Neither intensive care for pulmonary hypertension, including ECMO, nor fetal intervention has yet achieved a satisfactory outcome. Permissive hypercapnea and a delayed operation aiming at circulatory stabilization have resulted in a good survival rate. However, CDH survivors may be at risk for long-term morbidities. The method to induce pulmonary development is considered to be mandatory to achieve a good quality of life for severe CDH.


Static magnetic field effects on human subjects related to magnetic resonance imaging systems.
This paper reviews recent studies evaluating human subjects for physiologic or neuro-cognitive function adverse effects resulting from exposure to static magnetic fields of magnetic resonance imaging systems. The results of three studies are summarized. Two studies evaluated exposure to a maximum of 8 Tesla (T). The first series studied 25 normal human subjects' sequential vital signs (heart rate, blood pressure, blood oxygenation, core temperature, ECG, respiratory rate) measured at different magnetic field strengths to a maximum of 8 T. A second series of 25 subjects were studied at 0.05 and 8 T (out and in the bore of the magnet), performing 12 different standardized neuro-psychological tests and auditory-motor reaction times. The subjects' comments were recorded immediately following the study and after a three-month interval. The third study contained 17 subjects, placed near the bore of a 1.5 T magnet, and it used six different cognitive, cognitive-motor, or sensory tests. There were no clinically significant changes in the subjects' physiologic measurements at 8 T. There was a slight increase in the systolic blood pressure with increasing magnetic field strength. There did not appear to be any adverse effect on the cognitive performance of the subjects at 8 T. A few subjects commented at the time of initial exposure on dizziness, metallic taste in the mouth, or discomfort related to the measurement instruments or the head coil. There were no adverse comments at 3 months. The 1.5 T study had two of the four neuro-behavioral domains exhibiting adverse effects (sensory and cognitive-motor). These studies did not demonstrate any clinically relevant adverse effects on neuro-cognitive testing or vital sign changes. One short-term memory, one sensory, and one cognitive-motor test demonstrated adverse effects, but the significance is not clear.


Complementary bonding analysis of the N-Si interaction in pentacoordinated silicon compounds using quantum crystallography.
The N-Si interaction in two pentacoordinated silicon compounds is investigated based on a complementary bonding analysis, which consists of bonding descriptors from real space and orbital space. These are derived from X-ray wavefunction refinements of high-resolution X-ray diffraction data of single crystals and from isolated-molecule theoretical wavefunctions. The two pentacoordinated compounds only differ in one methylene group, so that the amino substituent is more flexible in one of the structures, hence probing the attractive or repulsive character of the N-Si interaction. All studies suggest weak dative interactions, which do, however, greatly influence the character of the Si-F bond: A strong N-Si interaction results in a weakened Si-F bond, which is quantified in this study experimentally and theoretically.


Copper in Wood Preservatives Delayed Wood Decomposition and Shifted Soil Fungal but Not Bacterial Community Composition.
Copper-based fungicides are routinely used for wood and plant protection, which can lead to an enrichment of copper-tolerant microbial communities in soil. To investigate the effect of such wood preservatives on the soil fungal and bacterial community compositions, five different vineyard and fruit-growing soil environments were evaluated using incubation studies over time. Pine sapwood specimens were impregnated with either water or different biocide treatment solutions containing a mixture of copper, triazoles, and quaternary ammonium compounds (CuTriQAC), a mixture of triazoles and quaternary ammonium compounds (TriQAC), or copper alone (Cu). Specimens were incubated in soil from each sample site for 8, 16, 24, and 32 weeks. The effects of preservative treatment on the modulus of elasticity (MOE) of the wood specimens and on the soil fungal as well as bacterial community composition at the soil-wood interface were assessed by quantitative PCR and amplicon sequencing of the fungal internal transcribed spacer (ITS) region and bacterial 16S rRNA gene. Specimens impregnated with CuTriQAC and Cu showed decreased MOE and reduced fungal and bacterial copy numbers over time compared to those impregnated with water and TriQAC. Fungal but not bacterial community composition was significantly affected by wood preservative treatment. The relative abundance of members of the family Trichocomaceae compared to other genera increased in the presence of the Cu and CuTriQAC treatments at three sites, suggesting these to be Cu-tolerant fungi. In conclusion, the copper-containing treatments resulted in marginally increased MOE, lowered microbial gene copy numbers compared to those in the TriQAC and water treatments, and thus enhanced wood protection against soil microbial wood degradation.IMPORTANCE Copper-containing rather than TRIQAC formulations are efficient wood preservatives irrespective of the origin and composition of the soil microbial communities. However, some fungi appear to be naturally insensitive to copper and should be the focus of future wood preservative formulations to facilitate the life span of wooden construction in contact with soil while also minimizing the overall environmental impact.


Helicobacter pylori prevalence in diabetic patients and its relationship with dyspepsia and autonomic neuropathy.
We evaluated the prevalence of Helicobacter pylori (HP) in Type 2 diabetic patients and its relationship with dyspeptic symptoms and complications of diabetes. Seventy-eight Type 2 diabetic patients (54 females, 24 males, mean age: 51.9 +/- 10.6 yr) and 71 non-diabetic control subjects were involved in the study. Patients were questioned for dyspeptic symptoms. Cardiovascular autonomic neuropathy, nephropathy and retinopathy were investigated in diabetic patients. Upper gastrointestinal tract endoscopy was performed for all patients and gastric biopsies were obtained and searched for HP. Helicobacter pylori prevalence was significantly higher in diabetic patients than in control subjects (75.6 vs 46%, p < 0.05). No differences were found between women and men with regard to HP infection status in diabetic patients. There was no relation between HP and diabetic complications, nephropathy and retinopathy. Helicobacter pylori prevalence was significantly higher in diabetic patients with cardiovascular autonomic neuropathy than in diabetic patients without cardiovascular autonomic neuropathy (90.6 vs 44.0%, p < 0.02). Forty-seven subjects with diabetes had symptoms of dyspepsia (60.3%) and the prevalence of HP was higher in these patients (p < 0.002). There is a high prevalence of HP infection in diabetic patients and it is correlated with dyspeptic symptoms. Diabetic subjects complicated with cardiovascular autonomic neuropathy and dyspepsia are at high risk of HP infection and should be carefully investigated and considered for eradication therapy.


HIV-infected parents and their children in the United States.
This study sought to determine the number, characteristics, and living situations of children of HIV-infected adults. Interviews were conducted in 1996 and early 1997 with a nationally representative probability sample of 2864 adults receiving health care for HIV within the contiguous United States. Twenty-eight percent of infected adults in care had children. Women were more likely than men to have children (60% vs 18%) and to live with them (76% vs 34%). Twenty-one percent of parents had been hospitalized during the previous 6 months, and 10% had probably been drug dependent in the previous year. Parents continued to have children after being diagnosed with HIV: 12% of all women conceived and bore their youngest child after diagnosis, and another 10% conceived before but gave birth after diagnosis. Clinical and support services for people affected by the HIV epidemic should have a family focus.


Disruption of transforming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma.
In fibroblasts, transforming growth factor beta (TGF beta) stimulates collagen synthesis and myofibroblast transdifferentiation through the Smad intracellular signal transduction pathway. TGF beta-mediated fibroblast activation is the hallmark of scleroderma and related fibrotic conditions, and disrupting the intracellular TGF beta/Smad signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, we examined the expression of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) in normal skin fibroblasts and its effect on TGF beta-induced cellular responses. The expression and activity of PPAR gamma in normal dermal fibroblasts were examined by Northern and Western blot analyses, immunocytochemistry, flow cytometry, and transient transfections with reporter constructs. The same approaches were used to evaluate the effects of PPAR gamma activation by naturally occurring and synthetic ligands on collagen synthesis and alpha-smooth muscle actin (alpha-SMA) expression. Modulation of Smad-mediated transcriptional responses was examined by transient transfection assays using wild-type and dominant-negative PPAR gamma expression constructs. The PPAR gamma receptor was expressed and fully functional in quiescent normal skin fibroblasts. Whereas ligand activation of cellular PPAR gamma resulted in modest suppression of basal collagen gene expression, it abrogated TGF beta-induced stimulation in a concentration-dependent manner. This response was mimicked by overexpressing PPAR gamma in fibroblasts, and was blocked by a selective antagonist of PPAR gamma signaling or by transfection of fibroblasts with dominant-negative PPAR gamma constructs. Furthermore, PPAR gamma ligands abrogated TGF beta-induced expression of alpha-SMA, a marker of myofibroblasts. Stimulation of Smad-dependent transcriptional responses by TGF beta was suppressed by PPAR gamma despite the absence of a consensus PPAR gamma-response element in the targeted promoters. Ligand-induced activation of fibroblast PPAR gamma had no effect on protein expression of cellular Smad3 or Smad7. By abrogating of TGF beta-induced stimulation of collagen gene expression, myofibroblast transdifferentiation, and Smad-dependent promoter activity in normal fibroblasts, PPAR gamma may play a physiologic role in the regulation of the profibrotic response. Furthermore, our results suggest that PPAR gamma activation by pharmacologic agonists may represent a novel approach to the control of fibrosis in scleroderma.


Memory rehabilitation for the working memory of patients with multiple sclerosis (MS).
The main cognitive impairments in multiple sclerosis (MS) affect the working memory, processing speed, and performances that are in close interaction with one another. Cognitive problems in MS are influenced to a lesser degree by disease recovery medications or treatments,but cognitive rehabilitation is considered one of the promising methods for cure. There is evidence regarding the effectiveness of cognitive rehabilitation for MS patients in various stages of the disease. Since the impairment in working memory is one of the main MS deficits, a particular training that affects this cognitive domain can be of a great value. This study aims to determine the effectiveness of memory rehabilitation on the working memory performance of MS patients. Sixty MS patients with cognitive impairment and similar in terms of demographic characteristics, duration of disease, neurological problems, and mental health were randomly assigned to three groups: namely, experimental, placebo, and control. Patients' cognitive evaluation incorporated baseline assessments immediately post-intervention and 5 weeks post-intervention. The experimental group received a cognitive rehabilitation program in one-hour sessions on a weekly basis for 8 weeks. The placebo group received relaxation techniques on a weekly basis; the control group received no intervention. The results of this study showed that the cognitive rehabilitation program had a positive effect on the working memory performance of patients with MS in the experimental group. These results were achieved in immediate evaluation (post-test) and follow-up 5 weeks after intervention. There was no significant difference in working memory performance between the placebo group and the control group. According to the study, there is evidence for the effectiveness of a memory rehabilitation program for the working memory of patients with MS. Cognitive rehabilitation can improve working memory disorders and have a positive effect on the working memory performance of these patients.


[Teaching, research, and health care: a case study].
The article explores the relations between teaching, research, and health care through an analysis of documents and reports by a group of professors with the Department of Clinical Medicine at the Universidade Federal do Rio de Janeiro's School of Medicine. Findings suggest that the two-hundred year old medical school has a strong tradition in teaching and health care and that although research predated inauguration of the thirty-year-old Clementino Fraga Filho University Hospital, this academic activity has only gradually occupied a larger space within the institution following creation of the hospital, which brought a radical change in clinical research methodology, concomitant with the development of a graduate program and the emergence of clinical epidemiology.


Effects of machined/turned, TiO2-blasted and sandblasted/acid-etched titanium oral implant surfaces on nerve conduction: a study on isolated rat sciatic nerves.
The purpose of this study was to explore the clinical relevance of the effects of machined/turned, TiO(2)-blasted and sandblasted/acid-etched titanium oral implant surfaces on nerve conduction. Isolated rat sciatic nerves were placed between two suction electrodes in a pyrex bath containing a tyrode solution. Evoked compound action potentials (cAPs) of the nerves were recorded before and after contact with the implants. The mandibular incisors of randomly selected animals were extracted and changes in cAP amplitudes were used as controls. The differences in final cAP values of Astra Tech implants and rat natural teeth were insignificant (P < 0.05), whereas the differences between other groups were significant (P < 0.05). Machined/turned-surface implants did not cause any change in cAPs. A slight decrease in cAPs was observed for TiO(2)-blasted and sandblasted/acid-etched implants, and the natural teeth. The reductions of cAPs in latter groups were not 50% after an application time of 300 min. The cAP changes of nerves contacting TiO(2)-blasted and sandblasted/acid-etched oral implants fall within physiologic limits in vitro. Machined/turned, TiO(2)-blasted, and sandblasted/acid-etched titanium implant surfaces do not lead to irreversible neurotoxic effects.


Genetic and environmental variation in lung function drives subsequent variation in aging of fluid intelligence.
Longitudinal studies document an association of pulmonary function with cognitive function in middle-aged and older adults. Previous analyses have identified a genetic contribution to the relationship between pulmonary function with fluid intelligence. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories for pulmonary function and fluid intelligence. Longitudinal data from the Swedish Adoption/Twin Study of Aging were available from 808 twins ranging in age from 50 to 88 years at the first wave. Participants completed up to six assessments covering a 19-year period. Measures at each assessment included spatial and speed factors and pulmonary function. Model-fitting indicated that genetic variance for FEV1 was a leading indicator of variation in age changes for spatial and speed factors. Thus, these data indicate a genetic component to the directional relationship from decreased pulmonary function to decreased function of fluid intelligence.


Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator.
Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)-NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)-NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.


Pay-for-performance and public reporting program participation and administrative challenges among small- and medium-sized physician practices.
A key component of efforts to improve the quality of care in the United States is the use of public reporting and pay-for-performance programs. Little is known, however, about the extent to which small- and medium-sized physician practices are participating in these programs. This study examined the participation of small- and medium-sized physician practices in pay-for-performance and public reporting programs and the characteristics of the participating practices. Using cross-sectional data from a national sample of 1,734 small- and medium-sized physician practices throughout the United States, we found that many practices (61.2%) were participating in at least one program, while far fewer (19.2%) were participating in multiple programs. Among practices participating in multiple programs, relatively few (21.9%) reported high levels of administrative problems due to a lack of standardization on performance measures. The study also suggests that some structural features are associated with participation and may provide leverage points for fostering participation.


Antimicrobial peptides: key components of the innate immune system.
Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.


Sensory characteristics and consumer acceptability of beef stock containing glutathione Maillard reaction products prepared at various conditions.
The sensory characteristics and consumer acceptability of beef soup samples containing 9 types of glutathione Maillard reaction products (GMRPs) were investigated to examine the effects of the GMRPs produced under different reaction conditions on the flavor of the beef soup. The sensory characteristics of the beef stocks were examined using descriptive analysis. In consumer testing, 50 consumers evaluated the overall acceptability and flavor intensities of beef odor, salty taste, beef flavor, and seasoning flavor in the beef soup samples. It was found that the reaction conditions, including sugar type and pH, affected the sensory characteristics of the beef stock containing the GMRPs. The samples containing the GMRPs reacted at pH 7 were characterized with strong beef flavor, chestnut flavor, and cooked rice flavor. However, the GMRP reacted with xylose at pH 7 (XM7) was significantly stronger in beef-related sensory characteristics than the GMRPs reacted with glucose or fructose at pH 7 (GM7 and FM7). The samples containing the GMRPs reacted at pH 3 had strong acid-related attributes whereas the GMRPs reacted at pH 11 exhibited strong sulfur-related attributes and a bitter taste. Overall, the beef soup containing XM7, which was perceived as having a strong beef odor and flavor, was rated the highest consumer acceptability score. This suggests that XM7 has feasibility as a flavor enhancer. To elucidate its effectiveness further, it is required to apply XM7 in various food systems at varying levels and to compare its flavor enhancing effects with other flavor enhancers such as monosodium L-glutamate in future studies. Practical Application: This study characterized sensory attributes of glutathione Maillard reaction products (GMRPs) reacted under various conditions and evaluated their potential as a flavor enhancer by examining consumer acceptability of beef stock containing the GMRPs. This study showed that the GMRP reacted with xylose at pH 7 had strong 71 beef flavor and the highest consumer acceptability score. The results of this study will provide valuable information for understanding sensory aspect of flavors generated by Maillard reaction of GSH and sugars, since most studies on Maillard reaction focused on chemical reactions. Also, the outcome of this study will help flavor and food industries' efforts to develop a new flavor enhancer for use in a variety of processed food products.


Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial.
To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design. Nationwide in the United States. 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment. Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence. The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others. 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease. Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo). ClinicalTrials.gov NCT01351805 and NCT01169259.


Ground-state cooling of mechanical oscillator via quadratic optomechanical coupling with two coupled optical cavities.
We present a scheme for the electromagnetically induced transparency (EIT)-like nonlinear ground-state cooling in a double-cavity optomechanical system in which an optical cavity mode is coupled parametrically to the square of the position of a mechanical oscillator, an additional auxiliary cavity is coupled to the optomechanical cavity. The optimum cooling conditions is derived, based on which the heating process can be well suppressed and the mechanical resonator can be cooled with an optimal effect to near its ground state through EIT-like cooling mechanism even in unresolved sideband regime. It is demonstrated by numerical simulations that not only the average phonon number of steady state is lower than that of single-cavity optomechanical system, but also the cooling rate is greatly faster than that of the linear optomechanical coupling due to the two-phonon cooling process in the quadratic coupling. Also, the ground-state cooling is achievable even with a relatively weak quadratic coupling strengthby tunning the coupling between two cavities to reach the optimum cooling conditions, thus provides an solution for overcoming the limitations of weak quadratic coupling rate in experiments. The proposed approach provides a platform for quantum manipulation of macroscopic mechanical devices beyond the resolved sideband limit and linear coupling regime.


Hydrogelation with a water-insoluble organogelator - surfactant mediated gelation (SMG).
The low-molecular-weight gelator (LMG) 12-hydroxyoctadecanoic acid (12-HOA) is insoluble in water, but can be solubilized in surfactant micelles. We therefore solubilized 12-HOA at 80 °C in an aqueous solution of cetyltrimethylammonium bromide (CTAB) containing spherical micelles. On cooling this system down to room temperature, a hydrogel is obtained. We will refer to this process as "surfactant-mediated gelation" (SMG). The hydrogels were formed at a lower 12-HOA concentration when sodium salicylate (NaSal) was added to the CTAB system, which induced the formation of wormlike micelles. Hydrogels obtained by SMG from spherical and wormlike micelles are referred to as gelled micellar phases (GMs) and gelled wormlike micellar phases (GWLMs), respectively. Optical microscopy and transmission electron microscopy (TEM) showed that 12-HOA forms self-assembled fibrillar networks (SAFiNs) in both GMs and GWLMs. The sol-gel transition temperature, Tsol-gel, of the GWLM samples was higher than that of the GM samples. Dynamic rheological measurements revealed gel properties (G' > G'' at all angular frequencies) for both gels; however, a higher viscoelasticity was observed for the GWLM samples, which in turn, was reflected in the higher Tsol-gel. Small- and wide-angle X-ray scattering (SWAXS) showed that micelles and gel fibers coexist in the GM and GWLM samples. Our study demonstrates the gelation of aqueous micellar solutions with water-insoluble LMGs.


Patient warming excess heat: the effects on orthopedic operating room ventilation performance.
Patient warming has become a standard of care for the prevention of unintentional hypothermia based on benefits established in general surgery. However, these benefits may not fully translate to contamination-sensitive surgery (i.e., implants), because patient warming devices release excess heat that may disrupt the intended ceiling-to-floor ventilation airflows and expose the surgical site to added contamination. Therefore, we studied the effects of 2 popular patient warming technologies, forced air and conductive fabric, versus control conditions on ventilation performance in an orthopedic operating room with a mannequin draped for total knee replacement. Ventilation performance was assessed by releasing neutrally buoyant detergent bubbles ("bubbles") into the nonsterile region under the head-side of the anesthesia drape. We then tracked whether the excess heat from upper body patient warming mobilized the "bubbles" into the surgical site. Formally, a randomized replicated design assessed the effect of device (forced air, conductive fabric, control) and anesthesia drape height (low-drape, high-drape) on the number of bubbles photographed over the surgical site. The direct mass-flow exhaust from forced air warming generated hot air convection currents that mobilized bubbles over the anesthesia drape and into the surgical site, resulting in a significant increase in bubble counts for the factor of patient warming device (P < 0.001). Forced air had an average count of 132.5 versus 0.48 for conductive fabric (P = 0.003) and 0.01 for control conditions (P = 0.008) across both drape heights. Differences in average bubble counts across both drape heights were insignificant between conductive fabric and control conditions (P = 0.87). The factor of drape height had no significant effect (P = 0.94) on bubble counts. Excess heat from forced air warming resulted in the disruption of ventilation airflows over the surgical site, whereas conductive patient warming devices had no noticeable effect on ventilation airflows. These findings warrant future research into the effects of forced air warming excess heat on clinical outcomes during contamination-sensitive surgery.


One Decade Later: What has Gene Expression Profiling Told us About Neuronal Cell Types, Brain Function and Disease?
The many diverse functions executed by the central nervous system (CNS) are mirrored in the diverse shapes, connections, and firing patterns of its individual neuronal cell types. Furthermore, distinct neurological diseases are the result of defects in specific neuronal cell types. However, despite the significance of this cellular diversity underlying brain function and disease, we know relatively little about the genes that contribute to purposeful differences among regions and cell types within the brain. A major challenge in this endeavor is the paucity of markers that define the many regions and cell types thought to exist. Cataloging the neuronal cell types and cell- and region-specific marker genes requires novel avenues that enable researchers to define gene expression profiles of brain regions and individual neurons and to apply this information to understand functional and structural properties in the normal and diseased brain. Functional genomic approaches such as gene expression profiling offers the exclusive opportunity to glimpse the detailed inner workings of distinct neuronal cell types. Recent studies have applied microarray technology in unique and novel ways to understand the molecular mechanisms that underlie such neuronal diversity and their potential role in brain diseases.


DNA mimic proteins: functions, structures, and bioinformatic analysis.
DNA mimic proteins have DNA-like negative surface charge distributions, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. DNA mimic proteins control the activities of a variety of DNA binding proteins and are involved in a wide range of cellular mechanisms such as chromatin assembly, DNA repair, transcription regulation, and gene recombination. However, the sequences and structures of DNA mimic proteins are diverse, making them difficult to predict by bioinformatic search. To date, only a few DNA mimic proteins have been reported. These DNA mimics were not found by searching for functional motifs in their sequences but were revealed only by structural analysis of their charge distribution. This review highlights the biological roles and structures of 16 reported DNA mimic proteins. We also discuss approaches that might be used to discover new DNA mimic proteins.


Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that is broadly chemoresistant, due in part to biophysical properties of tumor stroma, which serves as a barrier to drug delivery for most classical chemotherapeutic drugs. The goal of this work is to evaluate the preclinical efficacy and mechanisms of PTC596, a novel agent with potent anticancer properties in vitro and desirable pharmacologic properties in vivo.Experimental Design: We assessed the pharmacology, mechanism, and preclinical efficacy of PTC596 in combination with standards of care, using multiple preclinical models of PDA. We found that PTC596 has pharmacologic properties that overcome the barrier to drug delivery in PDA, including a long circulating half-life, lack of P-glycoprotein substrate activity, and high systemic tolerability. We also found that PTC596 combined synergistically with standard clinical regimens to improve efficacy in multiple model systems, including the chemoresistant genetically engineered "KPC" model of PDA. Through mechanistic studies, we learned that PTC596 functions as a direct microtubule polymerization inhibitor, yet a prior clinical trial found that it lacks peripheral neurotoxicity, in contrast to other such agents. Strikingly, we found that PTC596 synergized with the standard clinical backbone regimen gemcitabine/nab-paclitaxel, yielding potent, durable regressions in a PDX model. Moreover, similar efficacy was achieved in combination with nab-paclitaxel alone, highlighting a specific synergistic interaction between two different microtubule-targeted agents in the setting of pancreatic ductal adenocarcinoma. These data demonstrate clear rationale for the development of PTC596 in combination with standard-of-care chemotherapy for PDA.


Comparing WTP values of different types of QALY gain elicited from the general public.
The appropriate thresholds for decisions on the cost-effectiveness of medical interventions remain controversial, especially in 'end-of-life' situations. Evidence of the values placed on different types of health gain by the general public is limited. Across nine European countries, 17,657 people were presented with different hypothetical health scenarios each involving a gain of one quality adjusted life year (QALY) and asked about their willingness to pay (WTP) for that gain. The questions included quality of life (QoL) enhancing and life extending health gains, and a scenario where respondents faced imminent, premature death. The mean WTP values for a one-QALY gain composed of QoL improvements were modest (PPP$11,000). When comparing QALY gains obtained in the near future, the valuation of life extension exceeded the valuation of QoL enhancing gains (mean WTP PPP$19,000 for a scenario in which a coma is avoided). The mean WTP values were higher still when respondents faced imminent, premature death (PPP$29,000). Evidence from the largest survey on the value of health gains by the general public indicated a higher value for life extending gains compared with QoL enhancing gains. A further modest premium may be indicated for life extension when facing imminent, premature death.


Use of electrical impedance spectroscopy as a practical method of investigating the formation of aggregates in aqueous solutions of dyes and surfactants.
Molecular aggregation plays a key role in the physicochemical properties of dyes and surfactants. In this work, we show that electrical impedance spectroscopy (EIS) provides a practical method for the investigation of processes such as micellization in surfactants and dye dimerization. The electrical characterization of the structural phase transitions associated with aggregation events in these systems allows an accurate and direct determination of relevant parameters such as the corresponding critical concentrations for micelle formation and dimerization of these types of molecules, without the need of recurring to the use of auxiliary probe or reporter molecules. Because of its competitive advantages with respect to currently used methods (such as conductimetry and spectroscopic techniques), we argue that when implemented along the procedures described in this work, EIS becomes a simple and convenient technique for the characterization of aggregation processes in soft matter.


Implications of Solar Evolution for the Earth's Early Atmosphere.
The roughly 25 percent increase in luminosity over the life of the sun shared by many different solar models is shown to be a very general result, independent of the uncertainties suggested by the solar neutrino experiment. Superficially, this leads to a conflict with the climatic history of the earth, and if basic concepts of stellar evolution are not fundamentally in error, compensating effects must have occurred, as first pointed out by Sagan and Mullen. One possible interpretation supported by recent detailed models of the earth's atmosphere is that the greenhouse effect was substantially more important than at present even as recently as 1 billion to 2 billion years ago.


ESPEN Guidelines on Parenteral Nutrition: adult renal failure.
Among patients with renal failure, those with ARF and critical illness represent by far the largest group undergoing artificial nutrition. ARF, especially in the ICU, seldom occurs as isolated organ failure but rather is a component of a much more complex metabolic environment, in the setting of the multiple organ failure. Nutritional programs for ARF patients must consider not only the metabolic derangements peculiar to renal failure and with the underlying disease process/associated complications, but also the relevant derangements in nutrient balance due to renal replacement therapies, especially when highly efficient renal replacement therapies (RRT) are used, such as continuous veno-venous hemofiltration (CVVH), or prolonged intermittent modalities such as sustained low-efficiency dialysis (SLED). Finally it is to be taken into account that nutrient requirements can change considerably during the course of illness itself (see also guidelines on PN in intensive care). From a metabolic point of view, patients with CKD or on chronic HD who develop a superimposed acute illness should be considered to be similar to patients with ARF. The same principles in respect of PN should therefore be applied.


Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT.
We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall gamma = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress.


Assessment Needs Analysis for Developing Mobile Apps to Encourage Proactive Preventive Medicine Education Among Young Military Personnel.
International travel to underdeveloped areas where both hygienic conditions and sufficient medical care are often in short supply can pose severe health risks. Infectious disease is one of the most common health risks for military forces deployed overseas. Careful personal hygiene and early symptom recognition serve as important steps in averting potential illness. With the ubiquitous deployment threat of chemical and biological warfare agents, the benefit of early detection and action can ultimately be critical for survival. Nowadays game-based learning models, made available on mobile devices in the form of apps, can provide relevant medical knowledge, and they can effectively reach a young military population. The aims of this preliminary research project are twofold: (1) We want to investigate whether young U.S. Army personnel would be open to the use of mobile apps while deployed abroad, and (2) we want to share the research design adopted with the intent of providing a baseline methodology that can be used in future larger studies. We recruited and interviewed Reserve Officers' Training Corps cadets at a university in the United States. Focus groups have been adopted as a research tool for collecting data. Open and close-ended questions were used during the focus group. Four domains were investigated: Cell phone usage, game console perceptions, game genre preferences, and gaming habits and perceptions. The analysis of the focus group data reported that young military personnel often play with videogames and that they prefer first person Action/Combat genre. The data also showed that they do not consider playing videogames to be a leisure activity but a part of their lives. The preliminary results of this study suggest that games on cell phones could be considered as a platform for teaching young military personnel medical-related concepts and health safety procedures.


Dressing Tool Condition Monitoring through Impedance-Based Sensors: Part 2-Neural Networks and K-Nearest Neighbor Classifier Approach.
This paper presents an approach for impedance-based sensor monitoring of dressing tool condition in grinding by using the electromechanical impedance (EMI) technique. This method was introduced in Part 1 of this work and the purpose of this paper (Part 2) is to achieve an optimal selection of the excitation frequency band based on multi-layer neural networks (MLNN) and k-nearest neighbor classifier (k-NN). The proposed approach was validated on the basis of dressing tool condition information obtained from the monitoring of experimental dressing tests with two industrial stationary single-point dressing tools. Moreover, representative damage indices for diverse damage cases, obtained from impedance signatures at different frequency bands, were taken into account for MLNN data processing. The intelligent system was able to select the most damage-sensitive features based on optimal frequency band. The best models showed a general overall error lower than 2%, thus robustly contributing to the efficient automation of grinding and dressing operations. The promising results of this study foster the EMI-based sensor monitoring approach to fault diagnosis in dressing operations and its effective implementation for industrial grinding process automation.


A case of suicidal suffocation simulating homicide.
This case concerns an unusual suicidal plastic bag suffocation. An elderly white man was found dead and partially disrobed in his apartment lying supine on a sofa with a plastic bag closed by a rope over the head and the upper and lower extremities tightly tied with two other ropes, the end of both arranged into slipknots (self-rescue mechanism). Police investigations found no pornography in the apartment, and circumstantial data alleged no psychiatric disorders or suicidal intentions. The autopsy excluded signs of struggle and sexual intercourse as well as any type of injury or physical illness. Chemical analyses on the peripheral blood excluded acute drugs and/or alcohol intoxication. A differential diagnosis of the manner of death was performed, including scenarios of accidental autoerotic asphyxiation, homicide during either sexual activity or ritualistic, elderly suicide. The collected data most strongly supported the hypothesis of a suicidal asphyxiation simulating homicide to devolve a life insurance to the victim's sons because of economic difficulties.


Stereochemistry-dependent hydrogen bonds stabilise stacked conformations in jet-cooled cyclic dipeptides: (LD) vs. (LL) cyclo tyrosine-tyrosine.
Tyrosine-containing cyclic dipeptides based on a diketopiperazine (DKP) ring are studied under jet-cooled conditions using resonance-enhanced multi-photon ionisation (REMPI), conformer-selective IR-UV double resonance vibrational spectroscopy and quantum chemical calculations. The conformational landscape of the dipeptide containing natural L tyrosine (Tyr), namely c-LTyr-LTyr strongly differs from that of its diastereomer c-LTyr-DTyr. A similar family of conformers exists in both systems, with one aromatic ring folded on the dipeptide DKP ring and the other one extended. Weak NHπ and CHπ interactions are observed, which are slightly different in c-LTyr-LTyr and c-LTyr-DTyr. These structures are identical to those of LL and LD cyclo diphenylalanine, which only differ from c-Tyr-Tyr by the absence of hydroxyl on the benzene rings. While this is the only conformation observed for c-LTyr-DTyr, c-LTyr-LTyr exhibits an additional form stabilised by the interaction of the two hydroxyls, in which the two aromatic rings are in a stacked geometry. Stereochemical effects are still visible in the radical cation, for which one structure is observed for c-LTyr-DTyr, while the spectrum of the c-LTyr-LTyr radical cation is explained in terms of two co-existing structures.


Non-immunologic predictors of chronic renal allograft failure: data from the United Network of Organ Sharing.
Experimental evidence and clinical experience suggest that non-immunologic factors are important predictors of long-term renal allograft survival. It has been suggested that chronic allograft failure may in some cases by mediated by non-immunologic factors implicated in the pathobiology of other forms of progressive renal disease. Donor age, sex, and race may influence the "dose" of nephrons delivered in cadaveric renal transplantation. The United Network of Organ Sharing 1994 Public Use Data Tape was used to evaluate these and other risk factors in more than 31,000 recipients of cadaver allografts followed between 1987 and 1992. Female sex and African American race of the donor were important predictors of allograft failure. There was a markedly increased risk of allograft failure at both extremes of donor age. Recipients of large body size had accelerated graft loss. Stratified analyses suggested an interaction between donor and recipient race; nevertheless, all non-immunologic factors examined expressed independent associations with allograft survival. In sum, antigen-independent factors appear to be important determinants of allograft performance. Additional multivariable analyses are required to assess the relative importance of these factors compared with other known immunologic factors, such as HLA antigen mismatch. These findings may have important biomedical and health care policy implications.


Cortical Excitability and Interhemispheric Connectivity in Early Relapsing-Remitting Multiple Sclerosis Studied With TMS-EEG.
Evoked potentials (EPs) are well established in clinical practice for diagnosis and prognosis in multiple sclerosis (MS). However, their value is limited to the assessment of their respective functional systems. Here, we used transcranial magnetic stimulation (TMS) coupled with electroencephalography (TMS-EEG) to investigate cortical excitability and spatiotemporal dynamics of TMS-evoked neural activity in MS patients. Thirteen patients with early relapsing-remitting MS (RRMS) with a median Expanded Disability Status Scale (EDSS) of 1.0 (range 0-2.5) and 16 age- and gender-matched healthy controls received single-pulse TMS of left and right primary motor cortex (L-M1 and R-M1), respectively. Resting motor threshold for L-M1 and R-M1 was increased in MS patients. Latencies and amplitudes of N45, P70, N100, P180, and N280 TMS-evoked EEG potentials (TEPs) were not different between groups, except a significantly increased amplitude of the N280 TEP in the MS group, both for L-M1 and R-M1 stimulation. Interhemispheric signal propagation (ISP), estimated from the area under the curve of TEPs in the non-stimulated vs. stimulated M1, also did not differ between groups. In summary, findings show that ISP and TEPs were preserved in early-stage RRMS, except for an exaggerated N280 amplitude. Our findings indicate that TMS-EEG is feasible in testing excitability and connectivity in cortical neural networks in MS patients, complementary to conventional EPs. However, relevance and pathophysiological correlates of the enhanced N280 will need further study.


Nonmedical Prescription Opioid Use for the Self-treatment of Pain in Young Adults: A National Shame.
: Evans et al. (2017) have pointed out how frequently and pervasively nonmedical prescription opioid use is associated with severe pain in young adults, especially young white males. This is a subset of such nonmedical users at tremendous risk of overdose (indeed 1/3 of the study respondents had an overdose event), especially given their concomitant use of benzodiazepines. Avoiding further contributing to the catastrophic rise in overdoses requires access to comprehensive pain care for these young adults. If they were to require opioid therapy, it would have to be in the context of a highly complex and expert variety of such care. If we fail to make it available, we will fail to address the root cause of overdoses for a sizeable subset of nonmedical prescription opioid users.


Diagnosis of boundary in early gastric cancer.
Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique, which allowsresection of larger superficial tumors in the esophagus, stomach, and colon. Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD, because too much resection can potentially take more time and can induce a higher complication rate, while too little resection can result in a non-curative resection. The boundary diagnosis is often difficult for early gastric cancer, mainly because of the underlying condition of chronic gastritis. Due to recent developments in endoscopy, including magnified endoscopy and narrow band endoscopy, the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.


A 13C labeling strategy reveals a range of aromatic side chain motion in calmodulin.
NMR relaxation experiments often require site-specific isotopic enrichment schemes in order to allow for quantitative interpretation. Here we describe a new labeling scheme for site-specific (13)C-(1)H enrichment of a single ortho position of aromatic amino acid side chains in an otherwise perdeuterated background by employing a combination of [4-(13)C]erythrose and deuterated pyruvate during growth on deuterium oxide. This labeling scheme largely eliminates undesired contributions to (13)C relaxation and greatly simplifies the fitting of relaxation data using the Lipari-Szabo model-free formalism. This approach is illustrated with calcium-saturated vertebrate calmodulin and oxidized flavodoxin from Cyanobacterium anabaena . Analysis of (13)C relaxation in the aromatic groups of calcium-saturated calmodulin indicates a wide range of motion in the subnanosecond time regime.


Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern.
Flow cytometric DNA histograms of colorectal carcinomas from 264 patients were evaluated for the association of tumor site, Dukes' stage, tumor grade, and preoperative carcinoembryonic level with patient survival. The DNA nondiploid carcinomas were significantly more common from the left (descending and sigmoid) colon and the rectum. A poorer prognosis was found for patients with DNA nondiploid cancers than for patients with DNA diploid cancers. This was particularly true for patients with Dukes' stages B2 and C tumors with a small number (one to three) of lymph nodes with metastatic deposits. The DNA nondiploid cancers also had a relatively poorer prognosis in patients with unresectable disease. In a Cox multivariate analysis model, the DNA pattern was an independent prognostic variable for this group of 264 patients with resected colorectal carcinoma.


Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes.
The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.


Balloon Guide Catheter in Endovascular Treatment for Acute Ischemic Stroke: Results from the MR CLEAN Registry.
To compare outcomes after endovascular treatment (EVT) for acute ischemic stroke with and without the use of a balloon guide catheter (BGC) in clinical practice. Data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry were used, in which all patients who underwent EVT for anterior-circulation stroke in The Netherlands between 2014 and 2016 were enrolled. Primary outcome was modified Rankin scale (mRS) score at 90 days. Secondary outcomes included reperfusion grade (extended Thrombolysis In Cerebral Infarction [eTICI] score) and National Institutes of Health Stroke Scale (NIHSS) score 24-48 hours after intervention. The association between the use of a BGC and outcomes was estimated with logistic regression adjusted for age, sex, prestroke mRS score, NIHSS score, collateral grade, and time from onset to EVT. A total of 887 patients were included. Thrombectomy was performed with the use of a BGC in 528 patients (60%) and without in 359 patients (40%). There was no significant association between use of a BGC and a shift on the mRS toward better outcome (adjusted common odds ratio, 1.17; 95% confidence interval [CI], 0.91-1.52). Use of a BGC was associated with higher eTICI score (adjusted common OR, 1.33; 95% CI, 1.04-1.70) and improvement of ≥ 4 points on the NIHSS (adjusted OR, 1.40; 95% CI, 1.04-1.88). In clinical practice, use of a BGC was associated with higher reperfusion grade and early improvement of neurologic deficits, but had no positive effect on long-term functional outcome.


[Peripherally inserted central catheters (PICC) in onco-hematology. PICC line in onco-hematology].
Peripherally inserted central catheters (PICC) have the advantage of limiting the risk of accidents during installation and are easy to remove. Its use in oncology remains debated because of possible infectious complications. We analyzed 52 PICC in patients with hematological tumor from Nice Hospital. An installation failure was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental removal (9.6%). The organic complications such as infection or thrombophlebitis represented 3.8%. The median duration was 26 days [2-291]. The longest duration was associated with PICC for chemotherapy (median: 58 days). Frequent blood samples (above: 2 week) were associated with lower duration (median: 23 days). In conclusion, PICC represent a simple and effective alternative to intra-venous central devices in onco-hematology. However, physicians have to focus on short-course treatment.


Role of genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) on weight loss and cardiovascular risk factors after liraglutide treatment in obese patients with diabetes mellitus type 2.
A polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism (rs1049353) with potential implications in weight loss. We decide to investigate the role of this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide. A population of 86 patients with diabetes mellitus type 2 and obesity, unable to achieve glycemic control (hemoglobine glycate A1c >7%) with metformin alone or associated to sulfonylurea, who require initiation of liraglutide treatment in progressive dose to 1.8 mg/d subcutaneously, was analyzed. Fifty-one patients (59.3%) had the genotype G1359G, and 35 patients (40.7%) had G1359A (28 patients, 32.6%) or A1359A (7 patients, 8.1%) (A allele carriers). In patients with both genotypes, basal glucose, HbA1c, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased. In patients with G1359G genotype, total cholesterol and low-density lipoprotein cholesterol decreased, and in patients with A allele, homeostasis model assessment for insulin resistance decreased, too. There is an association of the A allele with an improvement of insulin resistance secondary to weight loss after liraglutide treatment in obese patients with diabetes mellitus type 2. Noncarriers of A allele showed an improvement in cholesterol levels after weight loss.


A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling.
Preblastoderm Drosophila embryo development is characterized by fast cycles of nuclear divisions. Extracts from these embryos can be used to reconstitute complex chromatin with high efficiency. We now discovered that this chromatin assembly system contains activities that recognize unprotected DNA ends and signal DNA damage through phosphorylation. DNA ends are initially bound by Ku and MRN complexes. Within minutes, the phosphorylation of H2A.V (homologous to γH2A.X) initiates from DNA breaks and spreads over tens of thousands DNA base pairs. The γH2A.V phosphorylation remains tightly associated with the damaged DNA and does not spread to undamaged DNA in the same reaction. This first observation of long-range γH2A.X spreading along damaged chromatin in an in vitro system provides a unique opportunity for mechanistic dissection. Upon further incubation, DNA ends are rendered single-stranded and bound by the RPA complex. Phosphoproteome analyses reveal damage-dependent phosphorylation of numerous DNA-end-associated proteins including Ku70, RPA2, CHRAC16, the exonuclease Rrp1 and the telomer capping complex. Phosphorylation of spindle assembly checkpoint components and of microtubule-associated proteins required for centrosome integrity suggests this cell-free system recapitulates processes involved in the regulated elimination of fatally damaged syncytial nuclei.


Learning procedural skills in family medicine residency: comparison of rural and urban programs.
To determine whether family medicine residents graduating from rural programs assess themselves as more experienced and competent in a range of procedural skills than graduates of urban programs do. Self-administered written survey. Ontario. Residents from 5 Ontario family medicine programs in 2000 and 2001; a total of 535 surveys were available for analysis (response rate of 78%). Mean self-assessed experience and competence scores for 53 procedures at residency entry, end of year 1, and graduation. Upon entry, there was no difference in mean procedural experience (2.89 vs 2.85, P = .54) or mean competence (2.34 vs 2.36, P = .88) scores between rural residents and their urban counterparts. There was a significant increase in procedural experience (P < .001) and competence (P < .001) scores during residency training. At graduation, mean experience (3.98 vs 3.70, P < .001) and competence (3.67 vs 3.39, P = .004) scores were significantly higher for rural residents than for their urban colleagues. A statistically larger proportion of residents graduating from rural programs assessed themselves as competent in 16 procedures. These included skills necessary for treating patients in emergency settings (establish intravenous lines for adults and infants, obtain arterial blood gas measurements, intubate adults and neonates, perform cautery for epistaxis, remove corneal foreign body, aspirate or inject knee and shoulder joints, and apply forearm or walking casts), for diagnostic procedures (endometrial biopsy and bone marrow aspiration), and for management of labour and delivery (vaginal delivery; vacuum extraction; and repair of first-, second-, and third-degree tears). Graduates of rural programs who have had a substantial component of training in communities of fewer than 10,000 people report greater self-assessed experience and competence in procedural skills than graduates of urban programs do. The difference likely reflects the unique aspects of rural training sites, including preceptors' competence in performing procedures.


The Effect of the Molecular Dipole and Quadrupole moments on Ion-Molecule Reaction Rates near 0 K.
We review the results of our recent experimental and theoretical studies of gas-phase ion-molecule reactions involving the He+ ion at low collision energies (Ecoll), in the kB⋅(0 - 40) K range. To avoid heating of the ions by stray electric fields, the reactions are studied within the orbit of a Rydberg electron. We reach collision energies down to ~0 K by employing a merged-beam setup. In the case of a molecule with a dipole moment (e.g., ammonia), we observe a strong enhancement of the measured reaction yield with decreasing Ecoll. This enhancement is attributed to rotational states which experience linear negative Stark shifts in the electric field of the ion. When the molecule has no dipole moment but a negative quadrupole moment (e.g., N2), we observe a suppression of the total reaction yield at the lowest collision energy. Our results are interpreted with the aid of an adiabatic-channel model.


A generalized model for apparently "non-Nernstian" equilibrium responses of ionophore-based ion-selective electrodes. 1. Independent complexation of the ionophore with primary and secondary ions.
A generalized model that describes apparently "non-Nernstian" equilibrium responses of ionophore-based ion-selective electrodes (ISEs) is presented. It is formulated for primary and secondary ions of any charges that enter the membrane phase and independently form complexes with the ionophore, respectively. Equations for the phase boundary potential model were solved numerically to obtain whole response curves as a function of the sample activity of the primary ion, and analytical solutions could be obtained for apparently non-Nernstian response sections in these response curves. Ionophore-based ISEs can give three types of apparently non-Nernstian equilibrium responses, i.e., apparently "super-Nernstian", "inverted-Nernstian", and "sub-Nernstian" responses. The values of the response slopes depend on the charge numbers of the primary and secondary ions and on the stoichiometries of their complexes with the ionophore. The theoretical predictions for super-Nernstian responses agree well with the experimental results obtained with ISEs based on acidic ionophores or metalloporphyrin ionophores. Also, theoretical response curves with inverted-Nernstian slopes were found to be similar in character to the pH responses of Ca2+-selective electrodes based on organophosphate ionophores, which have been known to exhibit a so-called "potential dip". The quantitative understanding of apparently non-Nernstian response slopes presented here provides an insight into ionophore-analyte complexation processes in ISE membranes and should be helpful for the design of new ionophores.


Amplification of resistance genes in Haemophilus influenzae plasmids.
Intramolecular amplification produces tandem repeats of tetracycline and combined tetracycline-chloramphenicol resistance determinants in conjugative plasmids of Haemophilus influenzae. This process depends on host recombination pathways. Physical mapping revealed the tetracycline transposon involved in amplification to be almost identical with Tn10, including two IS10 insertion elements. The chloramphenicol resistance determinant of the combined transposon is 1.9 kilobases (kb) in size and is bound by two 1.3-kb inverted repeats. Insertion in the close vicinity of the inside end of the left-hand IS10 generates a deletion of a 1.6-kb Tn10 region. The amplifiable units were resolved to comprise not only the respective resistance transposons, but also an additional 1.6-kb sequence (designated AS) which was demonstrated to be identically present in the different amplification systems studied. AS separates amplified transposons from each other, thereby maintaining the same orientation. Moreover, AS is present at the left flank of the transposons, but is missing at the right one. It was shown that AS represents a general constituent of the H. influenzae plasmids of the 45-kb class. Evaluation of the results suggests that AS is responsible for the recombinational events involved in the gene amplification process.


Turnover of messenger RNA, apoprotein and haem of cytochrome P-450b + e induced by phenobarbitone in rat liver.
A single injection of phenobarbitone elicits asynchronous behaviour in the pattern of induction of mRNA, apoprotein and haem of cytochrome P-450b + e. The mRNA content reaches a maximum around 16h, the apoprotein content reaches a maximum around 30-36h, and the holoprotein content shows biphasic behaviour, with maxima around 16h and 30-36h. With the use of CoCl2 to block fresh transcription of cytochrome P-450b + e mRNA, the half-life of the preinduced mRNA was found to be 3h. The apoprotein and haem moieties of cytochrome P-450b + e turn over with half-lives of 16h and 8h respectively. The pattern of induction of delta-aminolaevulinate synthase shows biphasic behaviour, with maxima around 16h and 30-36h. The biphasic behaviour of the holoprotein content is thus due to differences in the extent of saturation of the apoprotein with haem, the process being regulated by the activity of the rate-limiting delta-aminolaevulinate synthase and the independent faster turnover rate of haem with respect to the apoprotein. Massive degradation of the haem moiety of preformed cytochrome P-450b + e results in the subsequent degradation of the apoprotein.


NEUROMIMES: ACTION OF A RECIPROCALLY INHIBITORY PAIR.
Two electronic neuron models (neuromimes) connected to a common excitatory input and having both self- and mutual-inhibition were used to simulate the pulse patterns which control wing musculature in certain insects. With variation of stimulus frequency, firing patterns changed in discrete steps. Pattern change was found to be hysteretic: the pattern elicited by a given stimulus frequency depended on whether that frequency was approached from above or below. Pattern selection could be controlled by the injection or deletion of a single pulse in the stimulus pulse-train as well as by smooth frequency change.


[The para-esophageal hernia: a rare hiatal hernia requiring a specific approach].
In three patients, a woman aged 87 years who presented with signs indicating a myocardial infarction, a man aged 31 suffering from postprandial epigastric pain that suddenly worsened, and a woman aged 60 years with longstanding postprandial pain and recent fatigue due to anaemia, a para-oesophageal hernia was diagnosed. Para-oesophageal herniation is an uncommon disorder accounting for approximately 5% of all hernias at the oesophageal hiatus. They are distinguished from the more common sliding hiatal hernia by a relative preservation of the intra-abdominal fixation of the gastro-oesophageal junction. These patients show that the clinical presentation of para-oesophageal rolling hernias is different from that of sliding hernias. Pathological reflux may occur; though symptoms associated with a relative obstruction of the stomach within the hernia sac, such as dysphagia, are more common. Rare non-specific symptoms such as anaemia and loss of weight are also seen. Adequate therapy differs from that of a sliding hernia and should be individualized: surgical correction is indicated in a healthy patient with a symptomatic para-oesophageal hernia, such as in the last patient. However, when the hernia is incidentally diagnosed or when comorbidity is present, such as in the first patient, a wait-and-see policy is recommended. Only in case of a threatening incarceration, such as in the second patient, is an emergency operation indicated.


Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight.
To describe the history, clinical findings, and possible etiologies of ophthalmic findings discovered in 7 astronauts after long-duration space flight, and document vision changes in approximately 300 additional astronauts. Retrospective, observational examination of ophthalmic findings in 7 astronauts and analysis of postflight questionnaires regarding in-flight vision changes in approximately 300 additional astronauts. Seven astronauts with ophthalmic anomalies upon return from long-duration space missions to the International Space Station and 300 additional astronauts who completed postflight questionnaires regarding in-flight vision changes. Before and after long-duration space flight, all 7 subjects underwent complete eye examinations, including cycloplegic and/or manifest refraction and fundus photography. Six underwent postmission optical coherence tomography (OCT) and magnetic resonance imaging (MRI); 4 had lumbar punctures (LP). Approximately 300 astronauts were queried regarding visual changes during space missions. Refractive change, fundus photograph examination, retina OCT, orbital MRI, LP opening pressures, and examination of visual acuity data. After 6 months of space flight, 7 astronauts had ophthalmic findings, consisting of disc edema in 5, globe flattening in 5, choroidal folds in 5, cotton wool spots (CWS) in 3, nerve fiber layer thickening by OCT in 6, and decreased near vision in 6 astronauts. Five of 7 with near vision complaints had a hyperopic shift ≥+0.50 diopters (D) between pre/postmission spherical equivalent refraction in 1 or both eyes (range, +0.50 to +1.75 D). These 5 showed globe flattening on MRI. Lumbar punctures performed in the 4 with disc edema documented opening pressures of 22, 21, 28, and 28.5 cm H(2)O performed 60, 19, 12, and 57 days postmission, respectively. The 300 postflight questionnaires documented that approximately 29% and 60% of astronauts on short and long-duration missions, respectively, experienced a degradation in distant and near visual acuity. Some of these vision changes remain unresolved years after flight. We hypothesize that the optic nerve and ocular changes we describe may result from cephalad fluid shifts brought about by prolonged microgravity exposure. The findings we report may represent parts of a spectrum of ocular and cerebral responses to extended microgravity exposure. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Decoding Immune Heterogeneity of Melanoma and identifying immune-prognostic hub genes.
Melanoma is an aggressive skin cancer that has gained attention worldwide. Growing evidence has highlighted that the tumor microenvironment (TME) is an important feature of carcinogenesis and contributes to therapeutic efficacy in melanoma. However, additional advances in melanoma immuno-oncology are necessary to achieve a comprehensive knowledge of the immune infiltrate population and to identify accurate and readily measurable biomarkers. In this study, we analyzed gene expression of 468 melanoma cases from the TCGA database, which led to the identification of three melanoma clusters (representedby low, median and high infiltration) that display unique immune features. We found that the microenvironment clusters had substantial prognostic efficacy. The median cluster was characterized by an inability to draw immune cells, highlighting possible immune escape mechanisms, and lower CXCL9 and CXCL10 expression, which was correlated to poor prognosis. Deep molecular characterization of immune cells, cytolytic-activity and tumor-inflammatory status revealed diversity of the local immune infiltration landscape in the melanoma clusters. Differentially expressed genes related to TME were extracted from each infiltration cluster. Functional annotations revealed that these genes were mainly related to immune system activation and the processes of immunoreaction. The top ten hub genes in immune infiltration-related protein-protein interaction (PPI) networks were selected for further prognostic investigation. Further validation showed that five of ten hub genes were good prognostic biomarkers for melanoma in two independent groups from the Gene Expression Omnibus database. In brief, these data highlight that systemic characterization of melanoma could uncover tumor infiltrate characteristics, which can help select the most adequate treatment and identify consistent and important indicators of the local immune tumor microenvironment in melanoma patients.


Photosynthetic energy storage of Photosystems I and II in the spectral range of photosynthetically active radiation in intact sugar maple leaves.
The relative activity of Photosystems (PS) I and II in the spectral range between 400 and 720 nm was studied by measuring photosynthetic energy storage (ES) of an intact sugar maple leaf using photoacoustic spectroscopy. ES, determined with a modulated (80 Hz) monochromatic light beam in the presence of saturating intensity of background non-modulated white light, indicated the total energy stored by both photosystems (EST). Using background far-red light, ES of PS I (ESPS I) was quantified. ESPS II was derived from EST-ESPS I. EST dependence on intensity and wavelength of modulated light was studied at 470, 560, 640 and 680 nm. EST was maximum in red light and minimum in blue light. It decreased with an increase in modulated light intensity. The ratio ESPS II/ESPS I, measured at 640 nm, remained nearly constant with an increase in modulated light intensity. The relative quantum yield of EST spectrum showed two peaks around 610 and 660 nm, and declined sharply after 680 nm, revealing a clear red drop. ESPS I spectrum presented peaks around 610 and 670 nm, and a minimum between 440 and 470 nm. ESPS I was observed beyond 700 nm up to 720 nm, indicating the energy stored by cyclic electron transport. ESPS II spectrum showed broad peaks, around 460, 490, 600 and 660 nm, and a shoulder between 530 and 560 nm. ESPS II was always higher than ESPS I between 400 and 690 nm and reached zero around 700 nm.


Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles--initial clinical experience.
To evaluate the clinical and biologic safety of ultrasmall superparamagnetic iron oxide particles (AMI-227) as a contrast agent for magnetic resonance (MR) lymphography and to assess their efficacy for the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancer. Thirty adults suspected of having lymph node metastases underwent MR imaging before and 22-26 hours after intravenous infusion of AMI-227 (1.7 mg Fe/kg). Sixty histopathologically proved lymph nodes were analyzed on MR images, and 29 of these nodes were also analyzed quantitatively. AMI-227 was well tolerated with no major side effects. It allowed the detection of 10 additional nodes relative to those detected at MR imaging without AMI-227. None of the 27 metastatic nodes showed a decrease in signal intensity (SI) on AMI-227-enhanced images; nine of 27 metastatic nodes showed an increase in SI on T1-weighted images, probably resulting from altered capillary permeability in the tumor. A visually perceptible reduction in SI, indicating active AMI-227 uptake, was observed on postcontrast T2- and T2*-weighted images in 16 of 21 benign nodes. The SI ratio of benign nodes was lower than that of metastatic nodes on T2- and T2*-weighted images. The sensitivity of AMI-227-enhanced MR lymphography was 100%, and the specificity was 80%. AMI-227 is safe and may facilitate the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancers.


TAXINOMISIS: A cloud - based platform for risk profiling and patient specific management of the carotid artery disease.
Carotid Artery Disease is a complex multi-disciplinary medical condition causing strokes and several other disfunctions to individuals. Within this work, a cloud - based platform is proposed for clinicians and medical doctors that provides a comprehensive risk assessment tool for carotid artery disease. It includes three modeling levels: baseline data-driven risk assessment, blood flow simulations and plaque progression modeling. The proposed models, which have been validated through a wide set of studies within the TAXINOMISIS project, are delivered to the end users through an easy-to-use cloud platform. The architecture and the deployment of this platform includes interfaces for handling the electronic patient record, the 3D arterial reconstruction, blood flow simulations and risk assessment reporting. TAXINOMISIS, compared with both similar software approaches and with the current clinical workflow, assists clinicians to treat patients more effectively and more accurately by providing innovative and validated tools.Clinical Relevance - Asymptomatic carotid artery disease is a prevalent condition that affects a significant portion of the population, leading to an increased risk of stroke and other cardiovascular events. Early detection and appropriate treatment of this condition can significantly reduce the risk of adverse outcomes and improve patient outcomes. The development of a software tool to assist clinicians in the assessment and management of asymptomatic patients with carotid artery disease is therefore of great clinical relevance. By providing a comprehensive and reliable assessment of the disease and its risk factors, this tool will enable clinicians to make informed decisions regarding patient management and treatment. The impact of this tool on patient outcomes and the reduction of healthcare costs will be of great importance to both patients and the healthcare system.


Differentiation of mesenchymal cells derived from human amniotic membranes into hepatocyte-like cells in vitro.
Mesenchymal stem cells are believed to be involved in the formation of mesenchymal tissues, including bone, cartilage, muscle, tendon and adipose tissue. Interestingly, it has previously been reported that mesenchymal stem cells could also differentiate into endoderm-derived cells, such as hepatocytes. The amniotic membrane contains mesenchymal cells and is a readily available human tissue. Therefore, we investigated the potential of mesenchymal cells derived from human amniotic membrane (MC-HAM) to differentiate into hepatocytes. We analyzed the expression of hepatocyte-specific genes in MC-HAM before and after induction of differentiation into hepatocytes. We observed the expression of mRNAs encoding albumin, a-fetoprotein, cytokeratin 18 and alpha1-antitrypsin, but not those encoding glucose-6-phosphatase or ornithine transcarbamylase, prior to the induction of differentiation. However, immunocytochemistry revealed that albumin and alpha-fetoprotein were abundantly produced only after the induction of differentiation into hepatocytes. In addition, we observed the storage of glycogen, a characteristic feature of hepatocytes, using periodic acid-Schiff staining of MC-HAM induced to differentiate into hepatocytes. Overall, MC-HAM appear to be able to differentiate into cells possessing some characteristics of hepatocytes. Although further studies should be carried out to determine whether such in vitro-differentiated cells can function in vivo as hepatocytes. These cells may be useful in various applications that require human hepatocytes.