Measuring anisotropic friction on WTe2 using atomic force microscopy in the force-distance and friction modes.
Layered materials which can be easily cleaved have proved to be excellent samples for the study of atomic scale friction. The layered transition metal dichalcogenides have been particularly popular. These materials exhibit a number of interesting properties ranging from superconductivity to low frictional coefficients. In this paper we have investigated the tribology of the dichalcogenide-WTe2. The coefficient of friction is less than 0.040 along the Te rows and increases to over 0.045 across the rows. The frictional forces almost doubled at normal loads of 5000 nN when scanning in the [010] direction in comparison to the [100] direction. The frictional responses of the AFM probe have been monitored in the frictional force and force-versus-distance (f-d) mode. A comparison between the outcomes using the two different modes demonstrates the factors which need to be considered for accurate measurements.


[Low density lipoproteins in patients with cholelithiasis and cholesterosis of the gallbladder].
To study heterogenic forms of LDLP and LP(a) in blood serum of patients with cholelithiasis (CL) and gallbladder cholesterosis (GBC). Native gradient (3-12%) electrophoresis in polyacrylamide gel, rocket immunoelectrophoresis with antibodies to apo(a) were made in 20 patients with CL and 20 with GBC, 13 controls without gastrointestinal disease. Correlation of retardation factor (Rf) of LDLP and LP(a) with blood lipids, cholesterol (C) and triglycerides (TG) levels, body mass index (BMI) and age was studied. CL and GBC risk factors were analysed basing on a retrospective assessment in random representative samples of patients (100 CL and 100 GBC patients). There was a shift of the main peak in LDLP spectrum in the direction of smaller particles in GBC (Rf = 0.171 +/- 0.003) which was significant in comparison with CL group (Rf = 0.146 +/- 0.004, p < 0.001) and control (Rf = 0.114 +/- 0.013, p < 0.05). The analysis of LDLP Rf distribution in patients with different C levels has shown that LDLP small particles can occur in a normal C level: 75% in GBC and 50% in CL groups. Prevalence of small dense LDLP was recorded in both groups (87.5% cases) in hypercholesterolemia. Compared to control, LP(a) concentration was significantly elevated both in GBC (23.7 +/- 4.9 mg/dl) and CL (15.7 +/- 4.4 mg/dl) patients (control--7.5 +/- 1.4 mg/dl, p < 0.01), p > 0.5 in comparison between the groups. The correlation analysis found no correlations between LP9(a), other lipids, BMI and age in both study groups while Rf of LDLP correlated with C and TG levels (r = 0.596 and r = 0.226, respectively, p < 0.05), age and BMI (r = 0. 533 and r = 0.363, respectively, p < 0.05) in CL and did not correlate in GBC. A C level in CL changes with age and BMI while in GBC high LDLP C level was caused by other factors. No correlation of LP(a), LDLP Rf with age, body mass and blood lipids indicates that the above factors are independent in development of GBC.


[Systems analysis of polyparametrical syndromes in students under study-induced stress].
In addition to routine physical examinations, the polyparametrical method was used to examine 250 students to assess their health. For this, the methods of pattern discrimination and classification were employed to analyze multiparameter data. Clinical and polymetric findings correlated well. The polymetric method revealed 4 main classes of the students' functional and autonomic status. Autonomic changes can be systemic and local. The visualized data of objective functional parameters controlled by the autonomic system made it possible to give a syndromal assessment of functional states and to reveal the intermediate stage between health and disease.


A Case of an Anomalous Tract Involving the Cecum After Open Right Inguinal Hernia Repair.
Inguinal hernia repair is a commonly performed surgical procedure and generally is well tolerated with minimal complications. We present the case of a 70-year-old male with an anomalous tract involving the subcutaneous tissue and cecum after an open right inguinal hernia repair via plug and patch approach. A partial cecectomy with appendectomy with excision of the tract was performed. While most complications are relatively minor and fistulas are quite rare, mesh migration is a possibility that should be considered during preoperative planning for recurrent hernia surgery.


Association of depression with evolution of heart failure in patients with type 2 diabetes mellitus.
Depression is a prevalent, independent predictor of mortality in patients with heart failure (HF). Depression is also common in type 2 diabetes mellitus (T2DM), which is itself an important risk factor for HF. However, association of depression with incident HF in T2DM is undefined. The aim of the present study was to evaluate the predictive value of depression in predicting incident HF in a community-based cohort of asymptomatic patients with T2DM. We prospectively recruited 274 asymptomatic T2DM patients ≥ 65 years (age 71 ± 4 year, 56% men) with preserved EF and no ischemic heart disease from a community-based population. The Patient Health Questionnaire 9 (PHQ-9) was used to detect depression, and LV dysfunction was sought with a comprehensive echocardiogram, including LV hypertrophy (LVH) and subclinical diastolic function (E/e'). Over a median follow-up of 1.5 years (range 0.5-3), 20 patients were lost to follow-up and 254 individuals were followed for outcomes. At baseline, depression was present in 9.5%, LVH was identified in 26% and reduced E/e' in 11%. Over a median follow-up of 1.5 years, 37 of 245 patients developed new-onset HF and 3 died, giving an event rate of 107/1000 person-years. In a competing-risks regression analysis, depression (adjusted HR 2.54, 95% CI 1.18-5.46; p = 0.017) was associated with incident HF and had incremental predictive power to clinical, biochemical and echocardiographic variables. Depression is prevalent in asymptomatic elderly patients with T2DM, and depression independently and incrementally predicts incident HF.


Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial.
The Nutritional Prevention of Cancer Trial was a double-blind, randomized, placebo-controlled clinical trial designed to test whether selenium as selenized yeast (200 microg daily) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease. Results from September 15, 1983, through December 31, 1993, showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin. This report summarizes the entire blinded treatment period, which ended on January 31, 1996. The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups, defined by baseline characteristics, was evaluated. Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma (hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 0.94 to 1.26), selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma (HR = 1.25, 95% CI = 1.03 to 1.51) and of total nonmelanoma skin cancer (HR = 1.17, 95% CI = 1.02 to 1.34). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer.


Silica-filled elastomer/methacrylate systems as soft liners.
Denture soft lining materials are compliant cushions used at the oral tissue-denture interface. They are generally required to have sufficient compliance to redistribute mastication load, as well as an adequate modulus for long-term dimensional stability and control over the water uptake. This study investigated the effect of using silane treated fumed silica as a filler on the properties of experimental soft lining materials based on blends of isoprene-styrene (SIS) block co-polymer and mixtures of methyl methacrylate (MMA) and 1,6-hexandiol dimethacrylate (HDMA). The overall elastomer/monomer ratios were maintained, whereas the monomers ranged from 10 to 60% HDMA. The silica filler level was maintained at 10 wt% with respect to SIS. The properties investigated were the dynamic mechanical parameters of storage modulus (E') and tan delta as a function of temperature and the quasi-static mechanical parameters of ultimate tensile strength (UTS) and elongation to break (Eb) as well as absorption properties that were carried out in water and saline. In both unfilled and filled systems there was an increase in E' and a decrease in tan delta with an increase in HDMA. Silica addition tended to increase E' and substantially reduce tan delta in materials with less than 20% HDMA. UTS decreased with filler and HDMA content, however, Eb was greater for filled systems. Generally, in the long term, the water uptake decreased with increasing HDMA content and E'. The silanated silica further reduced the water uptake, indicating a cross-linking effect, thus increasing the restraining force on droplet growth. The uptake in saline was significantly reduced indicating an osmotically controlled uptake process.


How Does Temporal Blurring Alter Movement Timing?
Subjective uncertainty arises because the estimation of the timing of an event into the future is error prone. This impact of stimulus-bound uncertainty on movement preparation has often been investigated using reaction time tasks where a warning stimulus (WS) predicts the occurrence of a "go" signal. The timing of the "go" signal can be chosen from a particular probability distribution with a given variance or uncertainty. It has been repeatedly shown that reaction times covary with the shape of the used "go" signal distribution. This is interpreted as evidence for temporal preparation. Moreover, the variance of the response time should always increase with the duration of the delay between the WS and the "go" signal. This increasing variance has been interpreted as a consequence of the temporal "blurring" of future events (scalar expectancy). The present paper tested the validity of the temporal "blurring" hypothesis in humans with a simple oculomotor reaction time task where subjective and stimulus-bound uncertainties were increased. Subjective uncertainty about the timing of a "go" signal was increased by lengthening the delay between the WS and the "go" signal. Objective uncertainty was altered by increasing the variance of "go" signal timing. Contrary to temporal blurring hypotheses, the study has shown that increasing the delay between events did not significantly increase movement timing variability. These results suggest that temporal blurring could not be a property of movement timing in an implicit timing context.


Biventricular diastolic dysfunction in patients with autosomal-dominant polycystic kidney disease.
Left ventricular diastolic dysfunction has been shown in patients with autosomal-dominant polycystic kidney disease (ADPKD). However, there is no study evaluating right ventricular functions in these patients. In the present study, diastolic functions of both ventricles in normotensive and hypertensive ADPKD patients with well-preserved renal function were investigated. Fifteen hypertensive and 16 normotensive patients with ADPKD with well-preserved renal function, 16 patients with essential hypertension, and 24 healthy subjects were included in the study. Conventional left and right ventricular echocardiographic measurements were performed in all subjects. Left and right ventricular functions were investigated both by myocardial performance index (MPI) [calculated by dividing the sum of isovolumic contraction time and isovolumic relaxation time (IVRT) by ejection time] and by tissue Doppler imaging (TDI). Left ventricular deceleration time and IVRT were significantly prolonged in hypertensive patients with ADPKD compared with patients with essential hypertension and even in normotensive patients with ADPKD compared with healthy subjects. Left and right MPIs were significantly higher in patients with ADPKD compared with healthy subjects, showing systolic and diastolic dysfunction. Moreover, by using TDI, the peak early diastolic mitral annular velocity (Em) to peak late diastolic mitral annular velocity (Am) ratio and the peak early diastolic tricuspid annular velocity (Et) to peak late diastolic tricuspid annular velocity (At) ratio were decreased in patients with ADPKD, suggesting biventricular diastolic dysfunction. Both hypertensive and normotensive patients with ADPKD show significant biventricular diastolic dysfunction, suggesting cardiac involvement very early in the course of ADPKD.


Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities.
Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Subsequent structural optimization and counterscreening of other TLRs produced the first small molecule 17e (CU-CPT17e) capable of simultaneously activating TLRs 3, 8, and 9. Biochemical studies demonstrated that 17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells. Furthermore, 17e inhibited the proliferation of HeLa cancer cells by triggering apoptosis and arresting the cell cycle at the S phase. These results showcase potential therapeutic applications of 17e in both vaccine adjuvants and anticancer therapies based on multi-TLR activation.


Evidence of phenotypic relationships among behavioral characteristics of individual pigs and performance.
The objective of this research was to estimate phenotypic relationships among backtest scores (BTS), resident-intruder test scores (RIS), growth rate, LM area, and backfat in pigs. Little is known about the relationships among measures of behavioral characteristics of individual pigs and economically important traits. However, it may be expected that a pig's behavior affects its performance and that of its pen mates. The backtest was used in this experiment because it was previously shown to be a measure of individual stress-coping behavior and was related to lean gain. The resident-intruder test was used because it is a measure of a pig's tendency for aggressive behavior toward an unfamiliar pig. Each test was performed twice on pigs (n = 150) from 20 litters, and complete performance data was available on 140 pigs. Between 7 and 14 d of age, the backtest was performed by placing each pig in a supine position and gently restraining it for 60 s. The number of escape attempts (bouts of struggling) and total time spent struggling were recorded. The BTS was the summation of escape attempts during both tests. Resident intruder tests were assessed when pigs were between 30 and 50 d of age. A solid divider was placed in the resident pig's pen. The resident was placed alone on 1 side of the divider, away from its penmates. An intruder pig of the same sex and smaller size was then placed into the pen. When an attack was initiated by the resident, the pigs were immediately separated, the test was terminated, and a score of 1 was recorded. If no attack occurred by 5 min, the test was terminated and was given a score of zero. The cumulative score from both tests was the RIS. Dam effects influenced BTS (P < 0.01) and RIS (P < 0.03). Preweaning ADG of pigs with a BTS of 8 was 120 g greater than that of pigs with a BTS of 2. However, ADG from 20 to 76 d of age was 131 g greater in pigs with BTS = 2 than in pigs with BTS = 8. Lean gain of pigs with RIS = 2 was 25 g/d greater than in those with RIS = 0 or 1. This resulted in pigs with RIS = 2 having 1.6 kg more acceptable, standardized, fat-free lean. Conflicting results were found when relating the BTS to performance. However, with the RIS, greater aggression toward other pigs was associated with better performance. It was concluded that an unfavorable phenotypic relationship existed between RIS and lean growth.


Light scattering evidence of selective protein fouling on biocompatible block copolymer micelles.
Selective protein fouling on block copolymer micelles with well-known potential for tumour-targeting drug delivery was evidenced by using dynamic light scattering measurements. The stability and interaction of block copolymer micelles with model proteins (BSA, IgG, lysozyme and CytC) is reported for systems featuring a hydrophobic (poly[2-(diisopropylamino)-ethyl methacrylate]) (PDPA) core and hydrophilic coronas comprising poly(ethylene oxide)/poly(glycerol monomethacrylate) (PEO-b-PG2MA) or poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC). The results revealed that protein size and hydrophilic chain density play important roles in the observed interactions. The PEO(113)-b-PG2MA(30)-b-PDPA(50) nanoparticles are stable and protein adsorption is prevented at all investigated protein environments. The successful protein-repellent characteristic of these nanoparticles is attributed to a high hydrophilic surface chain density (>0.1 chains per nm(2)) and to the length of the hydrophilic chains. On the other hand, although PMPC also has protein-repellent characteristics, the low surface chain density of the hydrophilic shell is supposed to enable interactions with small proteins. The PMPC(40)-b-PDPA(70) micelles are stable in BSA and IgG environments due to weak repulsion forces between PMPC and the proteins, to the hydration layer, and particularly to a size-effect where the large BSA (R(H) = 4.2 nm) and IgG (R(H) = 7.0 nm) do not easily diffuse within the PMPC shell. Conversely, a clear interaction was observed with the 2.1 nm radius lysozyme. The lysozyme protein can diffuse within the PMPC micellar shell towards the PDPA hydrophobic core in a process favored by its smaller size and the low hydrophilic PMPC surface chain density (∼0.049 chains per nm(2)) as compared to PEO-b-PG2MA (∼0.110 chains per nm(2)). The same behavior was not evidenced with the 2.3 nm radius positively charged CytC, probably due to its higher surface hydrophilicity and the consequent chemical incompatibility with PDPA.


The timing of defecation within the sleep-wake cycle of humans during temporal isolation.
Data were collected from 14 human subjects who lived singly in an isolation unit without temporal cues. The subjects used buttons to signal the times when they woke up, took a meal, defecated, and retired. Under these conditions, the "free-running" circadian rhythms (e.g., the sleep-wake cycles and the rhythm of body temperature) remained internally synchronized in 7 subjects (mean circadian period = 24.47 hr); in the remaining 7 subjects the sleep-wake cycle lengthened beyond 28 hr, desynchronizing from the rhythm of body temperature (internal desynchronization; mean sleep-wake cycle = 33.45 hr). In all subjects, the interval from wake-up to defecation increased with the duration of wake time (alpha); on average, the interval varied proportionally with alpha. Furthermore, the interval from the last main meal (dinner) to defecation the following day was proportional to the sleep-wake cycle--either that which included dinner but preceded the defecation, or that which followed the dinner but included the defecation. It is concluded that a lengthening of the sleep-wake cycle (and of the wake time) results in a slowing down of the processes of digestion and evacuation of the bowels, in parallel with an apparent reduction of total energy expenditure.


In vitro effect of novel β-lactam compounds on xanthine oxidase enzyme activity.
Carbazole substituted imines (2a-l) were prepared from N-methyl-3-amino carbazole with different aldehydes. The imines compounds undergo (2+2) cycloaddition reactions with in situ ketenes to produce β-lactam compounds (3a-l). The β-lactam compounds were tested as inhibitors of the xanthine oxidase (XO) purified from bovine milk. The results show that these compounds exhibit inhibitory effects on XO at low concentrations with IC(50) values ranging from 21.65 to 58.04 µM. The most effective compound for XO was 4-(4-chlorophenyl)-1-(9-ethyl-9H-carbazol-3-yl)-3-phenylazetidin-2-one with IC(50) of 21.65 μM. The lactams investigated here showed effective XO inhibitory effects, in the same range as the clinically used allopurinol.


Differential roles of CD14 and toll-like receptors 4 and 2 in murine Acinetobacter pneumonia.
Acinetobacter baumannii is an opportunistic bacterial pathogen that is increasingly associated with gram-negative nosocomial pneumonia, but the molecular mechanisms that play a role in innate defenses during A. baumannii infection have not been elucidated. To gain first insight into the role of CD14 and Toll-like receptors 4 and 2 in host response to A. baumannii pneumonia. Respective gene-deficient mice were intranasally infected with A. baumannii, and bacterial outgrowth, lung inflammation, and pulmonary cytokine/chemokine responses were determined. To study the importance of LPS in the inflammatory response, mice were also challenged with A. baumannii LPS. Bacterial counts were increased in CD14 and Toll-like receptor 4 gene-deficient mice, and only these animals developed bacteremia. The pulmonary cytokine/chemokine response was impaired in Toll-like receptor 4 knockout mice and the onset of lung inflammation was delayed. In contrast, Toll-like receptor 2-deficient animals displayed an earlier cell influx into lungs combined with increased macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 concentrations, which was associated with accelerated elimination of bacteria from the pulmonary compartment. Neither CD14 nor Toll-like receptor 4 gene-deficient mice responded to intranasal administration of LPS, whereas Toll-like receptor 2 knockout mice were indistinguishable from wild-type animals. Our results suggest that CD14 and Toll-like receptor 4 play a key role in innate sensing of A. baumannii via the LPS moiety, resulting in effective elimination of the bacteria from the lung, whereas Toll-like receptor 2 signaling seems to counteract the robustness of innate responses during acute A. baumannii pneumonia.


Phospholipase C activation induced by noradrenaline in rat hippocampal slices is potentiated by GABA-receptor stimulation.
We have studied the effect of gamma-aminobutyric acid (GABA) and other GABA-receptor agonists (3-aminopropanesulphonic acid and muscimol) on the noradrenaline-induced stimulation of polyphosphoinositide metabolism in rat hippocampal slices. Formation of water-soluble inositol phosphates, and polyphosphoinositide metabolism were studied in hippocampal slices prelabelled with [3H]myoinositol. Noradrenaline induced formation of inositol mono-, bis- and trisphosphate during 10 min incubation in the presence of lithium; activation of phospholipase C by noradrenaline was also reflected by the hydrolysis of polyphosphoinositides and by the increased metabolism of phosphatidylinositol. GABA-receptor agonists were unable to activate per se phospholipase C; however, when added together with a low concentration of noradrenaline, they greatly potentiated the noradrenaline-stimulated polyphosphoinositide metabolism. We conclude that GABA-receptor agonists potentiate the effect of noradrenaline on polyphosphoinositide turnover and we discuss the role of this neurotransmitter interaction in the physiology of the hippocampus.


Psychoanalysis in conjunction with medication: a clinical research opportunity.
The increasingly common practice of introducing medication into the analytic relationship is of practical and theoretical concern to analysts. Pharmacological agents and their somatic effects, it is argued, may be seen as a research equivalent to brain lesions, long favored tools in correlating brain with mind function, while psychoanalytic process data may be seen as a fine-tuned instrument for studying the subjective and emotional processes that reflect the underlying brain effect. A method of naturalistic study of psychoanalytic process both with and without a psychopharmacological agent is described and illustrated in two patients. The potential of this method for providing data useful in understanding the mechanism of action of psychoactive medications and of individual variations in response is explored. Both patients, treated with stimulant for ADHD, showed striking differences in self- and object representation, defense, affect, and cognition that correlated with analytic periods on and off the medication. The implications of these observations for understanding both the action of the medication and the fundamental functional disruptions in the condition are explored as well.


Omnidirectional reflection from finite periodic and Fibonacci quasi-periodic multilayers of alternating isotropic and birefringent thin films.
Omnidirectional reflection from periodic and Fibonacci quasi-periodic multilayers that are embedded in an isotropic medium is further analyzed. Besides the isotropic structures, birefringent structures are considered that comprise uniaxial layers in the principal-axis system, alternating with isotropic layers so that the refractive index of isotropic layers is equal to the principal extraordinary refractive index of the uniaxial layers. The transfer-matrix method is applied, and the same formalism is used forboth the isotropic and the uniaxial media in the principal-axis system. Simple and original relations are obtained for the invariant of the one-dimensional Fibonacci sequences at oblique incidence. Numerical examples are given comparatively for the isotropic and the birefringent structures in the case of periodic and Fibonacci quasi-periodic sequences at different values of the refractive indices.


[Morphobiochemical assay of the red blood system in members of the prime crews of the International Space Station].
According to the experiment Hematology protocol, blood samples from the Russian members of ISS prime crews 1 to 5 were gathered on L-30 and R+0, 7, 15 to study metabolic parameters (ATP, reduced glutathione, LHG and glucose-6-phosphate dehydrogenase activities). Lipid spectrum of membrane erythrocytes was determined in frozen erythrocyte mass; iron turnover and erythropoietin were investigated in frozen serum. Ratios of different erythrocyte forms were established in 32 microl of fixated whole blood using scanning electron microscopy. On R+0, the morpho-biochemical parameters of red blood appear to still carry the imprints of space effects and, to an extent, certain difference in the setting of blood sampling from the Mir crew on landing in the space "shuttle" vehicle. Low level of iron and significantly increased erythropoietin on R+0 are the testimony of intensive hemoglobin production and an adequate bone morrow response to the increased oxygen demand. Shifts in erythron are of no clinical implications but indicative of the red blood adaptation to the factors of space fight.


Extracorporeal shockwave therapy for shoulder lameness in dogs.
The purpose of this article was to describe the outcome of dogs with instability, calcifying, and inflammatory conditions of the shoulder treated with extracorporeal shockwave therapy (ESWT). Medical records for 15 dogs with lameness attributable to the shoulder that failed previous conservative management were retrospectively reviewed. ESWT was delivered to those dogs q 3-4 wk for a total of three treatments. Short-term, in-hospital subjective lameness evaluation revealed resolution of lameness in three of nine dogs and improved lameness in six of nine dogs available for evaluation 3-4 wk following the final treatment. Long-term lameness score via telephone interview was either improved or normal in 7 of 11 dogs (64%). ESWT may result in improved function based on subjective patient evaluation and did not have any negative side effects in dogs with lameness attributable to instability, calcifying, and inflammatory conditions of the shoulder.


Birdsong.
Have your ever felt as happy as a lark, feathered your nest or taken someone under your wing? As we watch birds, we cannot help but be struck by their uncannily familiar behaviors - singing, nest building, caring for their young - to name just a few. Songbirds - the oscine suborder of perching birds that constitute roughly half (∼4,000) of all known avian species - are noted for the songs that males and sometimes both sexes in this group sing to court mates and defend territory from rivals. Birdsongs contain several to many acoustically distinct syllables, typically organized into a stereotyped phrase, and span the same audio bandwidth that we exploit for speech and music, making them easy for us to hear and appreciate. Consequently, eavesdropping humans long ago detected the most striking parallel between songbirds and humans: juvenile songbirds learn to sing in a manner similar to a child learning to speak.


Lower Extremity Kinematic Profile of Gait of Patients After Ankle Fracture: A Case-Control Study.
The present study examined the differences in the lower extremity gait kinematic profile of patients recovering from ankle fracture compared with healthy controls. In addition, we inquired whether the profile would differ among fracture severity groups. A total of 48 patients participated in the present prospective, case-control study. The gait of 24 patients recovering from an ankle fracture injury and 24 healthy matched controls was examined using an inertial measurement unit sensor system. The following gait parameters were evaluated: knee range of motion (ROM) during the swing phase, maximum knee flexion angle during stance, thigh and calf ROM, and stride duration. Statistically significant differences were found between the ankle fracture group and the control group for all parameters. The patients with ankle fracture had a lower knee ROM during swing phase compared with the control group (mean ± standard deviation 43.0° ± 15.5° compared with 66.7° ± 5.1°, respectively; p < .001). The maximum knee flexion angle during stance was lower in the patients with ankle fracture than in the control group (mean ± standard deviation 10.5° ± 6.1° compared with 21.2° ± 4.5°, respectively; p < .001). Patients with ankle fracture also had lower gait cycle thigh and calf ROM angles (p < .001) and a longer stride duration (p < .001) compared with the control group. No statistically significant differences were found among the severity groups. These results suggest that the gait kinematic characteristics vary between healthy people and patients recovering from an ankle fracture injury during the short-term period after injury.


Morphometric studies on the juxta-insular and tele-insular acinar cells of the pancreas in normal and streptozotocin-induced diabetic rats.
In the present study on the exocrine pancreas, stereological techniques were applied at the level of electron microscopy to confirm morphological differences between juxta-insular and tele-insular acinar cells of normal rats and to evaluate the effect of B cell secretion on these differences in streptozotocin-diabetic rats. As no similar data have been previously published, we conducted a systematic sampling analysis with special reference to the acinar cell volume, the granule content and the nuclear size. In the normal rats, the juxta-insular acinar cell had an average volume of 918 microns3 and contained 420 zymogen granules which occupied 10.2% of the cell. In tele-insular acini, the average cell volume was estimated at 755 microns3 and the cell contained 231 zymogen granules which amounted to 6.8% of the cell. The juxta-insular acinar cell was 18% larger in size and contained 45% more zymogen granules, but no difference was observed in the size of zymogen granules. In addition, the numerical density of cell nuclei was slightly larger in the tele-insular acini in spite of the similarity in the volume density and diameter of the nuclei in the cells of the two areas. In the streptozotocin-induced diabetic rats, no differences were observed in the cell volume and the zymogen granule content between the juxta- and tele-insular acini. These data suggest that the morphological inhomogeneity in the pancreatic acini is caused by the influence of B cell secretion on the activity of the juxta-insular acini.


Effects of 8-epi-prostaglandin F2 alpha and U46,619 on pulmonary hemodynamics in piglets.
Non-cyclooxygenase-derived prostaglandin F2- (PGF2)-like compounds can be formed by membrane lipid peroxidation. We sought to characterize one member of this class of compounds, 8-epi-PGF2 alpha, for its biological properties on the pulmonary vasculature in young piglets. We first compared 8-epi-PGF2 alpha to a thromboxane (Tx) mimetic, U46,619, to determine relative pulmonary vasoconstrictive effects. We next determined if the vasoconstriction induced by both agonists would be reversed by 50 ppm of inhaled nitric oxide (NO). We also determined the degree of inhibition of U46,619 and of 8-epi-PGF2 alpha by a Tx receptor antagonist, SQ 30,741. Anesthetized, ventilated piglets (18 +/- 2 days, 3.7 +/- 0.5 kg) were infused with randomly selected doses of U46,619 and of 8-epi-PGF2 alpha to describe dose-response curves plotting pulmonary vascular resistance (PVRi) against dose. When a maximal dose was achieved, inhaled NO (50 ppm) was administered. Results for the calculated PVRi (mm Hg/l/ min/kg) are as follows (mean +/- SD): for U46,619, baseline value: 43 +/- 10, peak dose: 165 +/- 46, and peak dose with NO: 73 +/- 33; for 8-epi-PGF2 alpha, baseline value: 38 +/- 9, peak dose: 138 +/- 30, and peak dose with NO: 72 +/- 25, and for both drugs, PVRi at peak dose was greater than at baseline (p < 0.001). PVRi at peak dose plus NO also remained elevated above baseline (p < 0.05; repeated measures ANOVA). The Tx receptor antagonist SQ 30,741 (1-10 mg/kg) inhibited U46,619-induced pulmonary vasoconstriction completely; however, the 1 mg/kg dose provided only 90% inhibition against 8-epi-PGF2 alpha. We conclude that 8-epi-PGF2 alpha can contribute to pulmonary vasoconstriction in young piglets in a dose-dependent reversible manner and that it acts primarily via pulmonary vascular Tx receptors.


PGE2 Promotes the Migration of Mesenchymal Stem Cells through the Activation of FAK and ERK1/2 Pathway.
A critical step of MSCs therapy is dependent on its ability to migrate into the sites of injury, so various approaches have been introduced to boost the migratory ability of MSCs. PGE2 is the major prostaglandin generated by COX enzymes and has been implicated in inflammatory response. Evidence indicates that PGE2 can facilitate MSCs migration. Further exploration of the underlying molecular mechanism participating in the promigratory ability of PGE2 may provide a novel strategy to improve MSC transplantation efficacy. In this study, our findings suggested that EP2 prostanoid receptor promotes MSCs migration through activation of FAK and ERK1/2 pathways. Furthermore, MSCs migration induced by PGE2 was blunted by FAK or ERK1/2 inhibitors. EP2-mediated MSCs migration depends on the activation of FAK and ERK1/2. However, the current study did not investigate the migration of MSCs over a blood vessel endothelial barrier. In conclusion, our findings reveal EP2-mediated FAK and ERK1/2 activation was essential for MSCs migration induced by PGE2, indicating that activation of EP2 receptor and FAK/ERK pathways may be a promising strategy to accelerate homing efficiency of MSCs, which in turn enhances therapeutic potential of MSCs transplantation.


Otolaryngology manpower in the year 2010.
The number of otolaryngologists practicing in the future is particularly pertinent in light of the changes taking place in American medicine today. A mathematical model is presented which projects the growth of otolaryngology manpower in the year 2010, taking into consideration the age distribution of practicing otolaryngologists, death rates, and the current production of residents. This model suggests that there will be a 21% increase in the number of otolaryngologists from 1990 to 2010. The main reason for the increase is the uneven distribution of otolaryngologists by age at the present time, with 49% of otolaryngologists being less than 45 years of age. There is concern that the American medical community is populated with too many specialists and that more emphasis should be placed on training generalists. The manpower issue should be studied in more detail, and future societal needs should be determined so that a rational policy on the growth of otolaryngology can be developed.


Enhanced Nrf2 up-regulation by extracellular basic pH in a human skin equivalent system.
Extracellular basic pH regulates cellular processes in wounds, and consequently influenced wound healing. Oxidative defence system modulation in the skin helps heal wounds, inhibits skin ageing and improves the skin condition. Moreover, the role of keratinocyte growth factor (KGF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in antioxidant systems has been reported in various skin models. However, the effects of extracellular basic pH on wound- or skin ageing-related skin damage have not been examined. Thus, we investigated the antioxidant systems affected by extracellular basic pH in a 3D human skin equivalent system (3HSE). Extracellular basic pH decreased KGF expression and enhanced the oxidative defence system, and thus activated Nrf2 in the 3HSE. Additionally, extracellular basic pH and KGF treatment up-regulated Nrf2 activation and its regulation of the oxidative defence system in the 3HSE. This indicates that Nrf2 up-regulation is enhanced by reactive oxygen species production, rather than KGF, and by extracellular basic pH of the skin. The inhibition of skin damage through pH imbalance and KGF regulation suggests that the development of pH-regulating or pH-maintaining materials may provide effective therapeutic strategies for maintaining a healthy skin.


The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model.
Sepsis is a systemic inflammatory response to infection and is one of the leading causes of morbidity and mortality. The second hit after trauma causes increased inflammatory response and multiple organ failure (MOF). The infection which develops after burn injury is a suitable model for a two-hit trauma study. Sepsis causes the release of biochemical mediators, such as Free Oxygen Radicals (FORs), which may lead to lipid peroxidation, which may play a key role in multiple organ failure. In this study, we aimed to investigate the effects of phosphodiesterase (PDE) inhibitors (sildenafil, milrinone, pentoxifylline) and N-acetylcysteine (NAS) on oxidative stress and organ damage in two-hit models. In this experimental study, peritonitis was created by cecal ligation and puncture (CLP) method in 40 rats, 72 hours after creating a 30% scalding injury. Rats were divided into five groups of eight rats each as follows: Group I: No treatment; Group II: 10/mg/kg/day dosage of intraperitoneal (i.p) sildenafil treatment was applied for 72 hours after CLP; Group III: 1/mg/kg/day dosage of i.p milrinone treatment was applied for 72 hours after CLP; Group IV: 150/mg/kg/day dosage of i.p NAS treatment was applied for 72 hours after CLP; Group V: 50/mg/kg/day dosage of i.p pentoxifylline treatment was applied for 72 hours after CLP. All rats were sacrificed on the seventh day of this study. Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), catalase, Tumor Necrotic Factor-alpha (TNF-α) levels, and tissue (lung, kidney) and serum samples were taken for histopathological study. When compared to the control group, the tissue damage score was found to be lower in all treatment groups. Sildenafil, milrinone and NAS groups had higher kidney GPx levels compared to the control group. Milrinone and pentoxifylline were higher in the lung tissue compared to the SOD control group. TNFα levels were lower in pentoxifylline and milrinone groups compared to the control group. This experimental study has shown that PDE inhibitors and NAS have a decreasing effect on oxidative stress and distant organ damage in the two-hit model. Further clinical and experimental studies are needed on this subject.


Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.
The emergence of chemoresistant disease during chemotherapy with 5-Fluorouracil-based (5-FU-based) regimens is an important factor in the mortality of metastatic CRC (mCRC). The causes of 5-FU resistance are multi-factorial, and besides DNA mismatch repair deficiency (MMR-D), there are no widely accepted criteria for determining which CRC patients are not likely to be responsive to 5-FU-based therapy. Thus, there is a need to systematically understand the mechanistic basis for 5-FU treatment failure and an urgent need to develop new approaches for circumventing the major causes of 5-FU resistance. In this manuscript, we review mechanisms of 5-FU resistance with an emphasis on: (1) altered anabolic metabolism limiting the formation of the primary active metabolite Fluorodeoxyuridylate (5-Fluoro-2'-deoxyuridine-5'-O-monophosphate; FdUMP); (2) elevated expression or activity of the primary enzymatic target thymidylate synthase (TS); and (3) dysregulated programmed cell death as important causes of 5-FU resistance. Importantly, these causes of 5-FU resistance can potentially be overcome through the use of next-generation fluoropyrimidine (FP) polymers (e.g., CF10) that display reduced dependence on anabolic metabolism and more potent TS inhibitory activity.


Responding to the impact of COVID-19 on the mental health and well-being of health workers in LMICs.
The COVID-19 pandemic has worsened mental health among health workers around the world. With a projected global shortage of 10.2 million health workers by 2030, further exacerbated by COVID-19, taking action to support health worker mental health needs to be an integral component of investments to overcome this gap and build resiliency of systems for the future. Health workers are functioning in highly stressful environments at great personal risk to provide services that improve quality of life and save lives. To reduce burnout and early exits from the workforce, health workers must be protected and equipped to work in supportive environments, manage stress, and access mental health services when needed. This article explores the impact of COVID-19 on health worker mental health and proposes actions for health systems and workplaces to support health workers which draw on available evidence and examples of USAID-supported partner activities.


Inhibition of flucloxacillin tubular renal secretion by piperacillin.
To explore the extent, time course, site(s), mechanism and possible clinical relevance of the pharmacokinetic (PK) interaction between piperacillin and flucloxacillin. A single-dose, randomized, six-way crossover study in 10 healthy volunteers where all subjects received all of the following as 5-min intravenous infusions: (i) 1.5 g piperacillin, (ii) 0.5 g flucloxacillin, (iii) 1.5 g piperacillin + 0.5 g flucloxacillin, (iv) 3 g piperacillin, (v) 1 g flucloxacillin, and (vi) 3 g piperacillin + 1 g flucloxacillin. Drug concentrations in plasma and urine were determined by high-performance liquid chromatography. WinNonlin was used for PK modelling and statistics. Piperacillin significantly decreased the renal clearance of flucloxacillin from 5.44 to 2.29 l h(-1) (medians, P < 0.01) and the nonrenal clearance of flucloxacillin from 2.67 to 1.80 l h(-1) (P < 0.01). The renal clearance of flucloxacillin was reduced to 45% (point estimate, 90% confidence interval 40 to 50%) and the nonrenal clearance to 66% (59, 73). The extent of interaction was larger at the higher doses. Competitive inhibition of tubular secretion by piperacillin was identified as the most likely mechanism for the decreased renal clearance of flucloxacillin. Piperacillin had a 15-times higher affinity for the renal transporter than flucloxacillin based on the molar ratio. Piperacillin PK was only slightly affected by flucloxacillin. Piperacillin inhibits renal and nonrenal elimination of flucloxacillin. This interaction seems clinically significant, as total clearance was reduced by a factor of 1.5 for the lower and 2.1 for the higher doses. PK interactions, especially with piperacillin, are likely to occur also with other beta-lactam combinations and might be useful to improve the effectiveness of antibacterial treatment.


Developmental down-regulation of receptor-mediated endocytosis of an insect lipoprotein.
Fat body cells of insects exhibit a high-affinity lipoprotein binding site at their cell surfaces. In the present study, the lipoprotein binding site was identified as an endocytotic receptor involved in receptor-mediated uptake of its lipoprotein ligand, high density lipophorin. After an initial period of high endocytotic uptake of high density lipophorin in the adult stage, this process strongly diminished. In the same period, a dramatic increase in cell surface-associated lipoproteins was observed. When animals were starved, however, internalization of lipoproteins was maintained. The pathway followed by the internalized lipoproteins appears to be different from the endosomal/lysosomal pathway, as the vast majority of apolipoproteins seemed to escape from lysosomal hydrolysis. In addition, no substantial intracellular accumulation of apolipoproteins was observed, suggesting that internalized lipoproteins were resecreted. It is unlikely that internalization is required for transport of the two major lipid components of insect lipoproteins, diacylglycerol and cholesterol, as inhibition of endocytosis neither affected the exchange of these lipids between lipoproteins and fat body cells nor influenced the loading of diacylglycerol onto lipoproteins in response to adipokinetic hormone. We postulate that the endosomal environment may facilitate transport of components which, unlike diacylglycerol and cholesterol, cannot be transported by simple aqueous diffusion.


Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF-κB pathway.
Elevated plasma low‑density lipoprotein (LDL) is associated with systemic inflammation, and is an important factor in the pathogenesis of chronic kidney disease. The aim of the present study was to investigate the effects of endoplasmic reticulum (ER) stress preconditioning on LDL‑induced inflammatory responses, in human mesangial cells (HMCs). HMCs were exposed to LDL (200 nm), with or without pretreatment with tunicamycin, an ER stress inducer, and tested for changes to gene expression levels. Small interfering RNA technology was used to knockdown the expression of inositol‑requiring enzyme‑1α (IRE1α) and X‑box‑binding protein‑1 (XBP‑1), in order to determine their effects on LDL‑treated HMCs. LDL treatment resulted in a significant, and time‑dependent, increase in the relative mRNA expression levels of proinflammatory cytokines and CD40, which was coupled with enhanced phosphorylation of IRE1α, IκB kinase (IKK), and nuclear factor (NF)‑κB p65 and p65 nuclear translocation. The LDL‑induced inflammatory responses were significantly reduced in the IRE1α‑depleted HMCs. Furthermore, pretreatment with tunicamycin significantly attenuated the induction of proinflammatory cytokines and CD40, by LDL. Whereas, silencing XBP1 expression significantly restored the production of proinflammatory cytokines, in the LDL‑treated HMCs with ER stress preconditioning. The phosphorylation levels of IRE1α, IKK, and NF‑κB p65 were markedly increased in the XBP1‑depleted HMCs. Conversely, overexpression of XBP1 blocked LDL‑induced inflammation in the HMCs. The results of the present study demonstrate that ER stress preconditioning antagonizes LDL‑induced inflammatory responses in HMCs, which may be mediated through upregulation of XBP1, and subsequent inactivation of the IRE1α/IKK/NF‑κB pathway.


Thioredoxin-1 and posttranslational modifications.
Thioredoxin-1 is a 12 kDa protein that consists of a redox regulatory domain containing the active cysteine residues 32 and 35. These cysteines are conserved from bacteria to human. Unlike thioredoxins from lower species, mammalian thioredoxin-1 contains three additional nonactive cysteine residues at positions 62, 69, and 73 (for human thioredoxin-1). Key biological functions of thioredoxin-1 are antioxidative, anti-apoptotic, and pro-proliferative properties. Thioredoxin-1 is regulated by the ability of the thioredoxin reductase to reduce oxidized thioredoxin-1 at cysteines 32 and 35. However, posttranslational modifications of thioredoxin-1, including glutathionylation, thiol-oxidation, and S-nitros(yl)ation, at the nonactive cysteines importantly contribute to the regulation and functions of thioredoxin-1. This review focuses on the posttranslational modifications of the active and nonactive cysteines and their contribution for functional regulation of thioredoxin-1.


X-X through-cage bonding in Cu, Ni, and Cr complexes with M3X2 cores (X=S, As).
Density functional calculations on trinuclear complexes bridged by two sulfur atoms, [(tmeda)(3)Cu(3)(mu-S)(2)](3+), [(tmeda)(3)Ni(3)(mu-S)(2)](2+), and [(tmeda)(3)Ni(3)(mu-S(2))](4+), as well as on the formation of [(tmeda)(3)Cu(3)(mu-S)(2)](3+) from a dinuclear [(tmeda)(2)Cu(2)(mu-S(2))](2+) complex and a mononuclear [(tmeda)Cu(eta(2)-S(2))](+) fragment, are reported. A qualitative orbital analysis of the M(3)X(2) framework bonding is presented for the case in which each metal atom M has a square planar coordination sphere completed by one bidentate or two monodentate ligands (that is, [(L(2)M)(3)X(2)] compounds). It is concluded that a framework electron count (FEC) of 12 corresponds to systems with six M-X bonds but no X-X bond through the cage, while an FEC of 10 favors the formation of an X-X bond. Framework electron counting rules are also presented for related M(3)X(2) cores in [(L(5)M)(3)X(2)] complexes, based on a qualitative molecular orbital (MO) analysis supported by DFT calculations on [(OC)(15)Cr(3)(mu-As(2))].


Microvascular alterations in thrombin-induced experimental disseminated intravascular coagulation in the dog.
Disseminated intravascular coagulation is often characterized by organ failure and bleeding. By use of light microscopy, previous studies have shown extensive fibrin deposition in vessels. However, quantification of fibrin deposition using ultrastructural methods has not been reported. In this study dogs were infused with thrombin, and disseminated intravascular coagulation developed. Using a blinded morphometric analysis method, we observed deposition of fibrin in nearly half of the microvascular vessels. Such deposition probably accounts at least for part of the organ dysfunction. Almost half the vessels also had altered endothelial structure including thinning of the endothelial membrane, formation of extremely thin spots, fenestrations, and even a few ruptured areas. These findings at least in part explain the extravasation of blood in disseminated intravascular coagulation.


Disturbed sleep is associated with reduced verbal episodic memory and entorhinal cortex volume in younger middle-aged women with risk-reducing early ovarian removal.
Women with early ovarian removal (<48 years) have an elevated risk for both late-life Alzheimer's disease (AD) and insomnia, a modifiable risk factor. In early midlife, they also show reduced verbal episodic memory and hippocampal volume. Whether these reductions correlate with a sleep phenotype consistent with insomnia risk remains unexplored. We recruited thirty-one younger middleaged women with risk-reducing early bilateral salpingo-oophorectomy (BSO), fifteen of whom were taking estradiol-based hormone replacement therapy (BSO+ERT) and sixteen who were not (BSO). Fourteen age-matched premenopausal (AMC) and seventeen spontaneously peri-postmenopausal (SM) women who were ~10y older and not taking ERT were also enrolled. Overnight polysomnography recordings were collected at participants' home across multiple nights (M=2.38 SEM=0.19), along with subjective sleep quality and hot flash ratings. In addition to group comparisons on sleep measures, associations with verbal episodic memory and medial temporal lobe volume were assessed. Increased sleep latency and decreased sleep efficiency were observed on polysomnography recordings of those not taking ERT, consistent with insomnia symptoms. This phenotype was also observed in the older women in SM, implicating ovarian hormone loss. Further, sleep latency was associated with more forgetting on the paragraph recall task, previously shown to be altered in women with early BSO. Both increased sleep latency and reduced sleep efficiency were associated with smaller anterolateral entorhinal cortex volume. Together, these findings confirm an association between ovarian hormone loss and insomnia symptoms, and importantly, identify an younger onset age in women with early ovarian removal, which may contribute to poorer cognitive and brain outcomes in these women.


ZNF280B promotes the growth of gastric cancer in vitro and in vivo.
Zinc finger protein 280B (ZNF280B) mediates pro-survival and pro-growth functions in prostate cancer. However, in gastric cancer, its clinical significance remains poorly characterized. In the present study, the expression levels of ZNF280B in 60 patients with gastric cancer were examined using immunohistochemistry. The association between ZNF280B expression and clinicopathological features was assessed. Positive ZNF280B staining was demonstrated for 38 (63.3%) samples out of 60 gastric cancer cases in immunohistochemical analysis. ZNF280B expression was significantly associated with tumor size (P=0.017) and TNM stage (P=0.001). Furthermore, the proliferation index in the positive ZNF280B expression group was significantly higher (38.8±6.2) compared with that of the negative ZNF280B expression group (16.9±8.9; P<0.01). These results suggest that ZNF280B expression may be associated with the proliferation of gastric cancer cells. The role of ZNF280B in the growth of gastric cancer cells (MGC-803) was also investigated in vitro and in vivo by enhancing the expression of ZNF280B. A colony formation assay indicated that the number of colonies in the MGC-803 cells with enhanced ZNF280B (146±5.8) was significantly higher than that of the MGC-803 control group (97±5.1) and the negative control group (101±6.5; P<0.05). An MTT assay demonstrated that ZNF280B significantly promoted the proliferation of MGC-803 cells at days 3 and 4 (P<0.05). It was observed that the overexpression of ZNF280B may promote the growth of gastric cancer in vivo in xenograft studies. These findings indicate that ZNF280B may be a novel therapeutic target for gastric cancer.


Association between ABO blood groups and mortality in upper gastrointestinal bleeding.
Gastrointestinal bleeding is an important part of gastrointestinal emergencies. This study aimed to examine the association between ABO blood groups and mortality in patients who were admitted to the emergency department and diagnosed with upper gastrointestinal bleeding. The patients with upper gastrointestinal bleeding in the emergency department of a tertiary hospital in Turkey and the data of healthy blood donors were studied. The data of these patients were analyzed, and it was determined that the primary outcome was in-hospital mortality. The study was completed with 274 patients and 274 control group. The mean age of these patients was 65.1±18.2 years, and 64.2% of patients were males. It was found that the in-hospital mortality rate of patients with O blood group (16.2%) was statistically significantly higher than non-O blood group (7.5%) (p:0.032). The study concluded that the mortality rate of gastrointestinal bleeding patients with O blood group was higher compared to patients with other blood groups. Physicians can use ABO blood groups to predict mortality risk in gastrointestinal bleeding.


Experience, Knowledge, and Concerns About Long-Term Services and Supports: Implications for Financing Reform.
Using the 2014 Survey of Long-Term Care Awareness and Planning, this article examines Americans' experiences, knowledge, and concerns about long-term services and supports (LTSS) and actions they are willing to take if they become disabled. The survey included 15,298 non-institutionalized respondents aged 40 to 70 years drawn from a nationally representative sample. Although many reported some experience with LTSS, knowledge of how LTSS worked was low. Respondents reported widespread concerns about becoming disabled. They preferred informal care over paid care, with a strong desire to remain in their homes. These results can be used to design reform initiatives and to motivate political support.


A new species of Manoa Fittkau (Diptera: Chironomidae), with DNA barcodes from Xianju National Park, Oriental China.
The genus Manoa and the tribe Pseudochironomini are recorded from the Oriental region for the first time. Manoa xianjuensis Qi & Lin sp. n. from Xianju National Park, Zhejiang, China is described and illustrated as adult male and female, the latter associated with the male by standard DNA barcodes. A neighbor joining tree based on available Pseudochironomini DNA barcodes and keys to the adults in Manoa are given.


[Photodynamic therapy of superficial bladder cancer. An alternative to radical cystectomy?].
If transurethral resection and intravesical treatment with BCG or chemotherapeutic agents are unsuccessful in recurrent flat multifocal superficial bladder cancer, cystectomy is considered to be indicated. A whole-bladder photodynamic therapy (PDT) was carried out in 23 patients in this worst-case situation, in 19 of whom minimum follow-up of 3 months has been possible. In 5 patients with carcinoma in situ and in 14 patients with flat papillary tumors covering nearly the whole bladder, Photofrin or Photosan-3 was applied intravesically. Irradiation of the bladder followed about 48 h, later with a light dose of 15 J/cm2 or 30 J/cm2 at a wave length of 630 nm. In 12 patients complete remission was achieved; 7 patients showed no evidence of disease over a follow-up period of 3-31 months (median 16.3 months). One patient was lost to follow-up. In 7 patients recurrent disease or residual tumor was observed following PDT, but these were easily managed by transurethral resection or Nd:YAG laser coagulation. In 4 patients PDT failed and cystectomy was carried out. Systemic progression was not observed. PDT has to be regarded as an alternative to cystectomy in the treatment of refractory superficial bladder cancer.


Metabolism of the cytochrome P450 mechanism-based inhibitor N-benzyl-1-aminobenzotriazole to products that covalently bind with protein in guinea pig liver and lung microsomes: comparative study with 1-aminobenzotriazole.
The metabolism and covalent binding of radioactivity to microsomal protein of the cytochrome P450 (P450) mechanism-based inhibitors 1-amino-[14C]-2,3-benzotriazole ([14C]ABT) and two radiolabeled forms of N-benzyl-1-aminobenzotriazole (BBT), N-benzyl-1-amino-[14C]-2,3-benzotriazole ([14C]-2,3-BBT) and [14C]-N-7-benzyl-1-aminobenzotriazole ([14C]-7-BBT), were examined in hepatic or pulmonary microsomes from untreated and phenobarbital (PB)- or beta-naphthoflavone (betaNF)-induced guinea pigs. [14C]-2,3-BBT and [14C]-7-BBT were converted to multiple metabolites including ABT, benzotriazole, benzaldehyde, 2- or 3-hydroxy-BBT, and 4-hydroxy-BBT by hepatic microsomes, while [14C]ABT, whose primary metabolite was benzotriazole, underwent little biotransformation. Neither ABT nor BBT was extensively metabolized by pulmonary microsomes. Hepatic microsomes from betaNF (vs PB)-treated guinea pigs metabolized [14C]ABT, [14C]-2,3-BBT, and [14C]-7-BBT more extensively. The degree of NADPH-dependent covalent binding of [14C]-2,3-BBT- or [14C]-7-BBT-derived radioactivity (1.0 nmol/mg of protein) was higher than that of [14C]ABT (0.3-0.8 nmol/mg of protein) in hepatic microsomes, especially those from PB-induced animals. Covalent binding per nmol of P450 in pulmonary microsomes was 3-4-fold higher with [14C]-2,3-BBT (2.9 nmol/nmol of P450) than with [14C]-7-BBT (1.0 nmol/nmol of P450), whereas in hepatic microsomes from PB- or betaNF-treated animals the ratio of binding with the two forms of BBT was approximately 1:1. [14C]-2,3-BBT- and [14C]-7-BBT-derived radioactivity was covalently bound to proteins that migrated in the molecular weight region corresponding to P450 on SDS-PAGE following incubation with NADPH. These data indicate that BBT is metabolized to at least two reactive compounds capable of covalent modification of protein and/or a single reactive product is formed which contains both the benzo ring (of benzotriazole) and the benzyl carbon atom (of the N-benzyl group); that P450 apoprotein modification may be an important mechanism of inactivation of pulmonary and hepatic P450 by BBT; and that hepatic microsomes from betaNF-induced guinea pigs generate more metabolites that do not act as mechanism-based P450 inhibitors from BBT than do those from PB-induced animals.


Long-term psychological evaluation of intersex children.
Treatment of psychological problems of 59 children with a physical intersex condition is described. The group consisted of 18 female pseudohermaphrodites with congenital adrenal hyperplasia (CAH), 20 male pseudohermaphrodites and 2 true hermaphrodites born with ambiguous external genitalia assigned the female sex (ambiguous girls), 14 male pseudohermaphrodites born with completely female external genitalia and assigned the female sex (completely female group), and 5 male pseudohermaphrodites born with ambiguous external genitalia and assigned the male sex. Despite the sex assignment, genital organ correction soon after birth, psychological counseling of parents and intensive psychotherapy of the children, general psychopathology developed equally in all 4 groups (39% of total group). Although 87% of the girls with a physical intersex condition developed in line with the assigned sex, 13% developed a gender identity disorder though only 1 girl (2%) failed to accept the assigned sex. Gender identity disorder and deviant gender role were in evidence only in girls with CAH and girls of the ambiguous group. Biological and social factors seem responsible for the development of gender identity disorder, such as pre- and postnatal hormonal influences on the brain enabling deviant gender role behavior to develop, and an inability on the part of parents to accept the sex assignment. A reconsideration of the sex assignment in male pseudohermaphrodites and true hermaphrodites born with ambiguous external genitalia is discussed.


A new nuclear component of the Wnt signalling pathway.
The Wnt signalling pathway is pivotal in normal and malignant development. A key effector is Armadillo (Arm)/beta-catenin, which functions with TCF to transcribe Wnt target-genes. Here, we report the discovery of pygopus (pygo), whose mutant phenotypes specifically mimic loss-of-Wingless (Wg) signalling. pygo is required for dTCF-mediated transcription, but not for Wg-induced stabilization of Arm. Pygo is a nuclear protein that is found in a complex with Arm in vivo. Humans possess two Pygo proteins, both of which are required for TCF-mediated transcription in colorectal cancer cells. The presence of a PHD domain implicates Pygo proteins in a chromatin-related function, and we propose that they mediate chromatin access to TCF or Arm/beta-catenin.


[Percutaneous treatment of chronic total occlusions: state of the art and future perspectives].
Coronary chronic total occlusions (CTO) are a frequent finding in patients undergoing coronary angiography. However, a low percentage of patients is still referred for percutaneous coronary intervention. The main reasons lie in the skepticism concerning the real benefit and high technical complexity of these interventions. In recent years, thanks to the growing operators' experience and the introduction of new techniques and materials, the procedural success has increased with relatively low complication rates. There is growing evidence in recent literature that percutaneous recanalization improves symptoms and quality of life, increases ejection fraction and prolongs survival. Appropriate patient selection alone may involve a real clinical benefit in case of percutaneous CTO treatment. The key to procedural success is to use the right method and the knowledge of dedicated techniques and devices: CTO recanalization should be performed by experienced operators, and non-CTO interventionalists should approach these procedures only after specific training.


Surgical experience with cardiac echinococcosis.
Cardiac echinococcosis is a rare affliction of the heart encountered in areas where the tapeworm Echinococcus is endemic. During the 15 years to September 2005, 19 consecutive patients (11 female; mean age, 25.6 +/- 12.8 years) with cardiac echinococcosis were operated on at Damascus University. Diagnosis was mainly established by 2D-echocardiography. Twelve patients also had extracardiac hydatidosis. All patients were operated on using cardiopulmonary bypass and cardioplegia. Intact cysts were generally enucleated, ruptured cysts were exteriorized, and interventricular septal cysts were managed by controlled puncture and aspiration. There was no operative mortality. All patients were placed on mebendazole postoperatively for periods appropriate to the extent of their hydatidosis. There were 4 known late deaths due to systemic extension of the disease. Cardiac echinococcus is a serious disease that should be managed surgically without delay. Enucleation of intact cysts under cardiopulmonary bypass and cardiac arrest is our preferred method of excision. Anthelmintic medical treatment is a valuable and necessary adjunct to surgical management.


'Absent' pulmonary valve with intact ventricular septum mimicking tricuspid valve atresia: Prenatal diagnosis and postnatal course.
Absent pulmonary valve syndrome is a rare congenital heart disease characterized by absent or rudimentary pulmonary valve leaflets and hypoplastic pulmonary annulus. The most common variant, associated with tetralogy of Fallot, implies dilatation of pulmonary branches and usually absent ductus arteriosus. Rarely, absent pulmonary valve occurs with intact ventricular septum: pulmonary branches are normally sized or mildly dilated and ductus arteriosus is usually patent. The rarest type is associated with intact ventricular septum and tricuspid atresia. A close connection has been raised between pulmonary regurgitation and development of tricuspid valve. We describe a case of prenatal diagnosed absent pulmonary valve with intact ventricular septum and patent ductus arteriosus in which severe pulmonary regurgitation caused reversible functional atresia of tricuspid valve. Postnatally, satisfactory biventricular circulation was obtained with inotropic support for a few days while ductus arteriosus closed spontaneously. At a 3-year follow up the child is asymptomatic without therapy.


Abnormal thalamic functional connectivity correlates with cardiorespiratory fitness and physical activity in progressive multiple sclerosis.
Altered thalamic volumes and resting state (RS) functional connectivity (FC) might be associated with physical activity (PA) and cardiorespiratory fitness (CRF) in people with progressive multiple sclerosis (PMS). To assess thalamic structural and functional alterations and investigate their correlations with PA/CRF levels in people with PMS. Seven-day accelerometry and cardiopulmonary exercise testing were used to assess PA/CRF levels in 91 persons with PMS. They underwent 3.0 T structural and RS fMRI acquisition with 37 age/sex-matched healthy controls (HC). Between-group comparisons of MRI measures and their correlations with PA/CRF variables were assessed. PMS people had lower volumes compared to HC (all p < 0.001). At corrected threshold, PMS showed decreased intra- and inter-thalamic RS FC, and increased RS FC between the thalamus and the hippocampus, bilaterally. At uncorrected threshold, decreased thalamic RS FC with caudate nucleus, cerebellum and anterior cingulate cortex (ACC), as well as increased thalamic RS FC with occipital regions, were also detected. Lower CRF, measured as peak oxygen consumption (VO2peak), correlated with lower white matter volume (r = 0.31, p = 0.03). Moreover, lower levels of light PA correlated with increased thalamic RS FC with the right hippocampus (r = - 0.3, p = 0.05). People with PMS showed widespread brain atrophy, as well as pronounced intra-thalamic and thalamo-hippocampal RS FC abnormalities. White matter atrophy correlated with CRF, while increased thalamo-hippocampal RS FC was associated to worse PA levels. Thalamic RS FC might be used to monitor physical impairment and efficacy of rehabilitative and disease-modifying treatments in future studies.


Pediatric screen time.
Ease of access to technology by the pediatric individual has brought with it new challenges for parents and guardians as they grapple to understand and formulate healthy boundaries between their child and the media. This transition into a media-forward generation has triggered a new wave of research discussing the relationship between early media exposure and the developing pediatric mind; media and the parent-child relationship; and recommendations for healthy boundaries from the American Academy of Pediatrics (AAP) as well as the American Academy of Child and Adolescent Psychiatry (AACAP) and American Psychological Association (APA). This systematic review was written for the purposes of equipping physicians and nurse practitioners to be the bridge between research and their patients. Parents and guardians often do not have access to the same evidence-based resources as health care providers, and to be able to implement the latest recommendations in their home, they must first be introduced to them. The search engines used were PubMed and CINAHL. Review of literature reveals the effect of socioeconomic status, parental education, and ethnicity on pediatric screen time habits. There are also clear positive and negative effects on the developing pediatric mind and undeniable influences on the parent-child relationship. To enhance patient outcomes, the AAP, the AACAP, and the APA have presented recommendations for healthy media use. Early introduction of healthy media boundaries to the pediatric client will ultimately allow for the development of a physically, mentally, and socially healthier, more media-aware generation.


Europe's Shifting Response to HIV/AIDS: From Human Rights to Risk Management.
Despite a history of championing HIV/AIDS as a human rights issue, and a rhetorical commitment to health as a human right, European states and institutions have shifted from a rights-based response to a risk management approach to HIV/AIDS since the economic recession of 2008. An interdisciplinary perspective is applied to analyze health policy changes at the national, regional, and global levels by drawing on data from key informant interviews, and institutional and civil society documents. It is demonstrated that, in the context of austerity measures, member states such as the UK and Greece reduced commitments to rights associated with HIV/AIDS; at the regional level, the EU failed to develop rights-based approaches to address the vulnerabilities and health care needs of key populations affected by HIV/AIDS, particularly migrants and sex workers; and at the global level, the EU backtracked on commitments to global health and is prioritizing the intellectual property rights of pharmaceutical companies over the human rights of people living with HIV/AIDS. The focus within and from the EU is on containment, efficiency, and cost reduction. The rights of those most affected are no longer prioritized.


Sun Safe Workplaces: Effect of an Occupational Skin Cancer Prevention Program on Employee Sun Safety Practices.
Occupational skin cancer prevention is a priority because outdoor workers are exposed to high levels of ultraviolet radiation, the primary risk factor for skin cancer. A 2-year follow-up assessment of the impact of Sun Safe Workplaces (SSW), a workplace sun safety program that promoted policy adoption and education, on employee sun safety behavior was conducted. Sixty-three of 98 local government organizations from the original study participated. Outdoor workers (n = 1724) completed surveys on personal sun protection practices. Employees' sun protection improved statistically significantly in the intervention group receiving the SSW program. SSW's effect was mediated by the number of workplace actions to implement elements of the policy, including sun protection messages and equipment and employee reports of sun safety training. Policy promotion is a feasible approach to occupational skin cancer prevention.


Regional distribution of mu, delta and kappa opioid receptors in human brains from controls and parkinsonian subjects.
The binding properties of mu and delta opioid receptors were investigated in several areas of human brain by using [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr as respective selective ligands, while the totality of opioid receptors was measured by using [3H]etorphine as a non-selective agonist. Receptor densities were highest in cerebral cortex, amygdala and striatum, and lowest in the substantia nigra (pars compacta). In the different brain areas of patients with Parkinson's disease, the density and the proportion of the various opioid receptors were not significantly different from control subjects.


O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation.
The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation.


In memoriam Andre S. Dreiding.
In his talk at the 49th Burgenstock Conference on Stereochemistry, the author paid tribute to Andre S. Dreiding, the founder of this event.


Association of total cholesterol and HDL-C levels and outcome in coronary heart disease patients with heart failure.
The aim of the study was to evaluate associations of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels with prognosis in coronary heart disease (CHD) patients with heart failure (HF).Patients who were angiographical-diagnosis of CHD and echocardiographical-diagnosis of left ventricular ejection fraction (LVEF) < 45% were enrolled. Baseline characteristics were collected and association of TC and HDL-C levels with rehospitalization for HF and all-cause mortality was assessed.A total of 118 patients were recruited. Mean age was 58.6 ± 10.9 years and male accounted for 65%. Mean LVEF was 39.5 ± 4.0%. Twenty-eight patients were rehospitalized for HF and 6 patients were dead. In patients with poor prognosis, lower body mass index (BMI), TC, HDL-C and albumin while higher high sensitivity C-reactive protein (Hs-CRP) was observed. TC was positively correlated with BMI and albumin, and HDL-C was inversely correlated with Hs-CRP. The associations of TC level and rehospitalization for HF and all-cause mortality were attenuated but consistently significant through model 1 to 4, with odds ratio (OR) of 0.97 (95% confidence interval [CI]: 0.92-0.99). Associations of HDL-C level and rehospitalization for HF and all-cause mortality were also consistently significant through model 1 to 4, with OR of 0.95 (95% CI: 0.90-0.98). Strength of association was attenuated prominently in model 3 after adjusted for Hs-CRP, and no change was observed after further adjusted for BMI and albumin.Higher baseline TC and HDL-C levels are associated with better outcome in CHD patients with HF.


[Mid- to long-term outcome of artery bypass in chronic ischemia of lower extremities].
To report the mid- to long-term outcome of artery bypass in chronic ischemia of lower extremities. The clinical data of 212 patients treated with bypass operation from January 2002 to April 2007 were retrospectively reviewed. Femoropopliteal artery bypass to above-knee popliteal (FP-ak) was carried out in 111 cases, femoropopliteal artery bypass to below-knee popliteal (FP-bk) in 59 cases, aortoiliac bypass in 25 cases and femorofemoral bypass in 17 cases. One hundred and eighty-six patients (87.7%) were followed up for 6 to 68 months (median, 18 months). One-year primary patency rate of FP-ak and FP-bk was 69.7% and 53.5%, respectively. After graft revision, 1-year secondary patency rate of FP-ak and FP-bk were 81.6% and 60.5%, respectively. The 3-year patency with FP-ak (56.3%) was significantly higher than that in FP-bk (23.8%) (P < 0.05). Fifty-two cases were reoperated on during the follow-up period. Crural or femoral amputation could not avoid in 23 cases (limb salvage rate 89.2%). Ten cases died in 1 to 30 days after the operation, 20 cases died later during followup, and most of them died of cardio-cerebrovascular diseases. Artificial vessel infection occurred in 6 cases. The selection of surgical treatment for chronic ischemia of lower extremities should based on the ischemic state of the limb. The mid- to long-term patency rate of FP-ak is higher than that of FP-bk.


A New Septum in the Female Breast.
Understanding the female breast fascial system is of paramount importance in breast surgery. Little was written about breast ligaments. Most articles refer to Cooper's work without further anatomical studies. Lately, a horizontal septum has been described conveying nerves and vessels to the nipple areola complex. During the surgical dissection of the lower part of the breast, in supero-medial technique for breast reduction operations, a fascial septum between the lower two quadrants was detected. This fibrous septum was studied through anatomic dissection of breast tissues during routine breast reshaping procedures that was done on 30 female patients. Magnetic resonance imaging (MRI) was performed preoperatively in all cases and correlated with the intraoperative findings. In the other five cases, outside the clinical study, the imaging was done during routine investigation for breast swellings. A vertical septum was identified in the lower part of the breast, lying at the breast meridian between the two lower quadrants. It is a tough bi-laminated structure that extends from the middle of the infra-mammary crease caudally to nipple-areola complex cranially and from the pectoral fascia posteriorly to the overlying skin anteriorly. This was proved by MRI findings. This study describes a new inferior vertical septum which separates the lower half of the breast into two definite anatomical compartments: medial and lateral.


Individuation among bedouin versus urban arab adolescents: ethnic and gender differences.
Three scales assessing individuation (Objective Measure of Ego-Identity Status [OMEIS], Separation-Individuation Test of Adolescence [SITA], and Multigenerational Interconnectedness Scale [MIS]) were administered to 40 female and 38 male Bedouin Arab adolescents and to 39 female and 38 male urban Arab adolescents in Grade 12. It was hypothesized that Bedouin Arab adolescents and female adolescents would manifest less individuation than urban Arab adolescents and male adolescents, respectively. Results from the OMEIS revealed that the identity foreclosed mean of the Bedouin adolescents was higher than that of the urban adolescents. As for the SITA, significant differences were found between Bedouin and urban Arabs in terms of dependency denial, separation anxiety, teacher enmeshment, peer enmeshment, and rejection expectancy. Significant gender differences were found in regard to dependency denial, and a borderline difference was found for separation anxiety. Significant effects of ethnicity and gender were found on the financial interconnectedness subscale of the MIS. The results support the present hypotheses concerning ethnicity differences and indicate that urbanization seems to narrow the differences in individuation between male and female adolescents.


What Is the Contribution of Ia-Afference for Regulating Motor Output Variability during Standing?
Motor variability is an inherent feature of all human movements, and describes the system's stability and rigidity during the performance of functional motor tasks such as balancing. In order to ensure successful task execution, the nervous system is thought to be able to flexibly select the appropriate level of variability. However, it remains unknown which neurophysiological pathways are utilized for the control of motor output variability. In responding to natural variability (in this example sway), it is plausible that the neuro-physiological response to muscular elongation contributes to restoring a balanced upright posture. In this study, the postural sway of 18 healthy subjects was observed while their visual and mechano-sensory system was perturbed. Simultaneously, the contribution of Ia-afferent information for controlling the motor task was assessed by means of H-reflex. There was no association between postural sway and Ia-afference in the eyes open condition, however up to 4% of the effects of eye closure on the magnitude of sway can be compensated by increased reliance on Ia-afference. Increasing the biomechanical demands by adding up to 40% bodyweight around the trunk induced a specific sway response, such that the magnitude of sway remained unchanged but its dynamic structure became more regular and stable (by up to 18%). Such regular sway patterns have been associated with enhanced cognitive involvement in controlling motor tasks. It therefore appears that the nervous system applies different control strategies in response to the perturbations: The loss of visual information is compensated by increased reliance on other receptors; while the specific regular sway pattern associated with additional weight-bearing was independent of Ia-afferent information, suggesting the fundamental involvement of supraspinal centers for the control of motor output variability.


B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses.
The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.


Application of morphometrics as a predictor for survival in female patients with breast cancer spinal metastasis: a retrospective cohort study.
The current standard of care for prediction of survival of cancer staging is based on TNM staging. However, for patients with spinal metastasis, who all have identical stage IV disease, identifying accurate prognostic markers of survival would allow better treatment stratification between more aggressive treatment strategies or palliation. Analytical morphometrics enables physicians to quantify patient frailty by measuring lean muscle mass. Morphometrics also predicts survival in patients with lung cancer metastases to the spine. Our study evaluates whether morphometrics is predictive of survival in patients with breast cancer spinal metastasis. This is an observational retrospective cohort study. This study includes female patients with breast cancer spinal metastases and patients who have undergone stereotactic body radiation therapy. Overall survival was the primary outcome measure. Morphometric measurements of the psoas muscle were taken using computed tomography scans of the lumbar spine. We then stratified patients into tertiles based on the psoas muscle area. We identified 118 patients, with a median survival of 104 days (95% confidence interval [CI]=73-157 days). Overall survival was not associated with age, chemotherapy, or number of levels radiated. Patients in the lowest tertile of psoas size had significantly shorter survival compared with the highest tertile (68 days versus 148 days, hazard ratio 1.76 [95% CI=1.08-2.89], p=.024). The shorter survival was also true for the lowest tertile versus the middle tertile (68 days versus 167 days, hazard ratio 1.95 [95% CI=1.19-3.19], p=.007). Kaplan-Meier survival curves were used to visually illustrate the differences in survival between different tertiles. Morphometric analysis of the psoas muscle size in patients with breast cancer metastases to the spine was effective in identifying patients at risk of shorter survival. Further research is needed to validate these results, as well as to see if these methodologies can be applied to other cancer histologies.


Functional organization of autonomic neural pathways.
There is now abundant functional and anatomical evidence that autonomic motor pathways represent a highly organized output of the central nervous system. Simplistic notions of antagonistic all-or-none activation of sympathetic or parasympathetic pathways are clearly wrong. Sympathetic or parasympathetic pathways to specific target tissues generally can be activated tonically or phasically, depending on current physiological requirements. For example, at rest, many sympathetic pathways are tonically active, such as those limiting blood flow to the skin, inhibiting gastrointestinal tract motility and secretion, or allowing continence in the urinary bladder. Phasic parasympathetic activity can be seen in lacrimation, salivation or urination. Activity in autonomic motor pathways can be modulated by diverse sensory inputs, including the visual, auditory and vestibular systems, in addition to various functional populations of visceral afferents. Identifying the central pathways responsible for coordinated autonomic activity has made considerable progress, but much more needs to be done.


Surface instability of sheared soft tissues.
When a block made of an elastomer is subjected to a large shear, its surface remains flat. When a block of biological soft tissue is subjected to a large shear, it is likely that its surface in the plane of shear will buckle (appearance of wrinkles). One factor that distinguishes soft tissues from rubberlike solids is the presence--sometimes visible to the naked eye--of oriented collagen fiber bundles, which are stiffer than the elastin matrix into which they are embedded but are nonetheless flexible and extensible. Here we show that the simplest model of isotropic nonlinear elasticity, namely, the incompressible neo-Hookean model, suffers surface instability in shear only at tremendous amounts of shear, i.e., above 3.09, which corresponds to a 72 deg angle of shear. Next we incorporate a family of parallel fibers in the model and show that the resulting solid can be either reinforced or strongly weakened with respect to surface instability, depending on the angle between the fibers and the direction of shear and depending on the ratio Emu between the stiffness of the fibers and that of the matrix. For this ratio we use values compatible with experimental data on soft tissues. Broadly speaking, we find that the surface becomes rapidly unstable when the shear takes place "against" the fibers and that as E/mu increases, so does the sector of angles where early instability is expected to occur.


Capture--recapture and anchored prevalence estimation of injecting drug users in England: national and regional estimates.
Capture-recapture (C-RC) using four data sources, one of which accounted for 81% of captured injectors, and multiple indicator methods (MIM) were used to obtain national, regional and local estimates of the prevalence of injecting drug use among opiate and/or crack cocaine users in England. Persons aged 15 to 64 years, in contact with health and/or criminal justice services during 2005/2006, and known to be using opiates and/or crack cocaine and injecting drugs were included in the C-RC analysis. The MIM analysis included indicators relating to drug treatment, drug-related deaths, population density and drug offences.There were an estimated 130,000 opiate and/or crack cocaine users who injected drugs in 2005/06 (95% confidence interval 125,800 to 137,000), corresponding to 3.9 per thousand of the population aged 15 to 64 years (95% confidence interval 3.8-4.1). Regional variation in the prevalence of injecting was evident, ranging from 6.1 per thousand of the population aged 15 to 64 years in Yorkshire and the Humber (95% confidence interval 5.6 to 6.6) to 2.3 per thousand in the East of England (95% confidence interval 1.8 to 2.9). Application of gender and age-group distributions for treated injecting drug users (IDUs) to the prevalence estimates suggested that there were 97,200 male injectors (95% confidence interval 94,000 to 102,500) and 63,600 female injectors aged 25 to 34 years (95% confidence interval 61,500 to 67,000).The prevalence estimates provide a basis from which numbers of current IDUs infected with hepatitis C virus (HCV) can be approximated.


Effect of cantilever geometry on the optical lever sensitivities and thermal noise method of the atomic force microscope.
Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.


Multireference calculations on the ground and lowest excited states and dissociation energy of LuF.
High level multireference calculations were performed for LuF for a total of 132 states, including four dissociation channels Lu(2D) + F(2P), Lu(2P) + F(2P), and two Lu(4F) + F(2P). The 6s, 5d, and 6p orbitals of lutetium, along with the valence 2p and 3p orbitals of fluorine, were included in the active space, allowing for the accurate description of static and dynamic correlation. The Lu(4F) + F(2P) channel has intersystem spin crossings with the Lu(2P) + F(2P) and Lu(2D) + F(2P) channels, which are discussed herein. To obtain spectroscopic constants, bond lengths, and excited states, multi-reference configuration interaction (MRCI) was used at a quadruple-ζ basis set level, correlating also the 4f electrons and corresponding orbitals. Core spin-orbit (C-MRCI) calculations were performed, revealing that 13Π0- is the first excited state closely followed by 13Π0+. In addition, the dissociation energy of LuF was determined at different levels of theory, with a range of basis sets. A balance between core correlation and a relativistic treatment of electrons is fundamental to obtain an accurate description of the dissociation energy. The best prediction was obtained with a combination of coupled-cluster single, double, and perturbative triple excitations /Douglas-Kroll-Hess third order Hamiltonian methods at a complete basis set level with a zero-point energy correction, which yields a dissociation value of 170.4 kcal mol-1. Dissociation energies using density functional theory were calculated using a range of functionals and basis sets; M06-L and B3LYP provided the closest predictions to the best ab initio calculations.


Drug disposition and effects in the fetus.
Surveys of drug use in pregnancy demonstrate that a significant proportion of human fetuses are exposed to prescription and non-prescription drugs antenatally or during labor, although recently a decrease in licit drug consumption during pregnancy may have occurred. However, legitimate medical reasons for drug therapy of the mother or fetus remain and there is an increasing problem with illicit drugs. Several approaches are used to examine placental transfer of and fetal exposure to drugs, including studies on pregnant women, the use of chronically catheterized pregnant animals (particularly sheep), acute studies on small animals (e.g. guinea pig and rabbit) and the use of the perfused placenta. Fetal drug exposure is affected by large number of maternal, placental and fetal factors. For long term maternal drug administration, drug binding in maternal and fetal plasma, and fetal drug elimination seem particularly important. Thus, the rate of non-placental clearance of morphine, methadone, acetamionophen, metoclopramide, ritodrine and diphenhydramine in the fetal lamb is comparable to that in the ewe, although the routes of fetal elimination are not fully elucidated. The fetal liver may be of lesser importance in overall drug elimination than in the adult, but conjugated drug metabolites in the fetus may persist because of limited placental transfer. Hence, we have observed that the glucuronide conjugate of ritodrine accumulates in amniotic fluid after intravenous ritodrine administration. Accumulation of intact drugs in amniotic fluid also occurs via fetal renal excretion and perhaps via the fetal membranes. Also, a number of basic amine drugs are also concentrated in fetal tracheal fluid, probably as a consequence of pulmonary uptake, which also takes place in the adult. However, this could result in high fetal lung levels of agents, such as beta 2-adrenergic agonists, that have potent effects on pulmonary function and maturation. When digoxin, metoclopramide and diphenhydramine are injected into amniotic fluid, they are preferentially distributed to the fetus and, for the latter 2 drugs, uptake by the chorioallantoic membranes appears to be important. Thus, there is the possibility of recycling of drugs from amniotic fluid to the fetal circulation and their persistence in the fetus. Many of the therapeutic agents given to pregnant women in late pregnancy have effects on fetal CNS, cardiovascular or metabolic functions. Alterations in fetal behaviour are elicited by prescription sedatives and anesthetics and illicit drugs, and also by the antihistamine, diphenhydramine, present in various nonprescription medications.


Effect of geometrical orientation on the charge-transfer energetics of supramolecular (tetraphenyl)-porphyrin∕C60 dyads.
The charge transfer (CT) excited state energies of donor-acceptor (D∕A) pairs determine the achievable open-circuit voltage of D∕A-based organic solar cell devices. Changes in the relative orientation of donor-acceptor pairs at the interface influence the frontier orbital energy levels, which impacts the dissociation of bound excitons at the D∕A-interface. We examine the effect of relative orientation on CT excited state energies of porphyrin-fullerene dyads. The donors studied are base- and Zn-tetraphenyl porphyrin coupled to C60 as the acceptor molecule in an end-on configuration. We compare the energetics of a few low-lying CT states for the end-on geometry to our previously calculated CT energetics of a co-facial orientation. The calculated CT excitation energies are larger for the end-on orientation in comparison to the co-facial structure by about 0.7 eV, which primarily occurs due to a decrease in exciton binding energy in going from the co-facial to the end-on orientation. Furthermore, changes in relative donor-acceptor orientation have a larger impact on the CT energies than changes in donor-acceptor distance.