Markers of inflammation and weight change in middle-aged adults: results from the prospective MONICA/KORA S3/F3 study.
We investigated associations of markers of inflammation such as albumin, fibrinogen, C-reactive protein (CRP), and white blood cell count (WBCC) with future weight gain and weight loss in middle-aged adults in order to further elucidate the relationship between subclinical inflammation and weight change. Data were derived from the third population-based MONICA (Monitoring of Trends and Determinants in Cardiovascular Diseases) Augsburg survey (S3) conducted as part of the multinational World Health Organization MONICA project in 1994-1995 and a follow-up examination, to which all eligible subjects from S3 were invited in 2004-2005 (F3). In total, 2,792 persons (1,391 men, 1,401 women) aged 25-74 years at baseline were analyzed. Subjects with elevated concentrations of inflammatory markers were more prone to gain weight during follow-up. The odds ratios (OR) for a large mean annual weight gain (i.e., on average 1.02 kg/year) was 1.73 (95% confidence interval (CI) 1.27, 2.35) in fully adjusted analyses for subjects in the highest compared to the lowest quartile of fibrinogen. The respective ORs were 1.45 (95% CI, 1.08, 1.94) and 1.37 (95% CI, 1.03, 1.82) for CRP and WBCC. Stratified analyses revealed that associations were strongest among subjects who quitted smoking during the follow-up period (new quitters). Associations of inflammatory markers with large mean annual weight loss were weaker and became nonsignificant after multivariable adjustment. In conclusion, elevated levels of inflammatory markers are independently associated with weight gain in middle-aged adults, particularly among new quitters. This suggests that inflammation plays a key role in the process of weight gain, especially after smoking cessation.


Transient proarrhythmic state following atrioventricular junctional radiofrequency ablation.
This study was designed to prospectively assess ventricular de- and repolarization by the QRS, QT, and JT intervals, and their dispersion in the 12-lead ECG during right ventricular pacing at 60, 70, and 80 beats/min during the first month after AV junctional RF ablation. Previous reports have found early polymorphic ventricular arrhythmia after RF AV junctional ablation. Our hypothesis was that there is a proarrhythmic state following this procedure, which depends on the paced rate and time after ablation. The analysis of the immediate changes was based on 17 patients (10 men) with a mean age of 64 years (SD 14) (range 38-82 years). A 12-lead ECG was recorded during right ventricular pacing at 60, 70, and 80 beats/min within 24 hours (day 1), between 24 and 48 hours (day 2), and 1 week after ablation (day 7). For analysis of changes beyond 1 week, 13 additional patients with a mean age of 73 years (SD 8) (range 62-90 years) were analyzed on days 1, 7, and 30. All intervals were measured with a digitizing table. The mean QRS duration shortened by 2.4% at 60 beats/min (P <0.01), and the mean QT and JT intervals shortened by 5-7% between days 1 and 7 (P < 0.001). The mean QT was 9% shorter and the mean JT interval was 13% shorter at 80 compared to 60 beats/min on day 1 (P < 0.001). QT dispersion was reduced by 13% when the stimulation rate was increasedfrom 60 to 80 beats/min on day 1 (P < 0.05). There were no significant changes beyond the first week. The study results point to the induction of a proarrhythmic state immediately after AV junctional RF ablation resolving during the first week. Repolarization shortened gradually between 80 and 60 beats/min to an extent that is suggestive of a clinically important antiarrhythmic effect at the higher rate, which was supported also by clinical experience.


Inequalities in esophageal cancer mortality in Brazil: Temporal trends and projections.
The main objective of the study was to analyze the effect of age, period and birth cohort on esophageal cancer mortality in Brazil and its geographic regions, per sex. An ecological study is presented herein, which evaluated the deaths by esophageal cancer and the distribution, per geographic region. Poisson Regression was utilized to calculate the effects of age, period and birth cohort, and projections were made with the statistical software R, using the age-period-cohort model. Projection of data covered the period 2015-2029. Regarding the geographic regions of Brazil, a decrease was verified, throughout time, for the mortality rates of the South and Southeast regions, for men and women. For the North, Northeast and Midwest regions, an increase was evidenced in mortality rates, mainly for men, after the 2000's. Regarding the projections, a progressive increase of mortality rates was verified for the Northeast and North regions. Divergences evidenced for observed and projected esophageal cancer mortality rates revealed inequalities among the geographic regions of Brazil.


The measurement of psychological androgyny: an extended replication.
The Bem Sex-Role Inventory (BSRI), the recently developed measure for psychological androgyny, was administered to 344 middle-Tennessee high school and university students. The BSRS's reliability coefficients and mean scores were very similar to those reported earlier for California junior college and university students, respectively. The present scoring patterns for the BSRI remained unchanged with the introduction of the four "familial context" variables of sex of Ss' siblings, sex of Ss' nearest-in-age sibling, parent whom the Ss considered emotionally warmest, and parent whom the Ss would most prefer to be like. Contrary to Bem's original findings, the present results with the BSRI suggested that Ss' responses to the measure may be affected by the social desirability phenomenon. Moreover, scores on the BSRI did not correlate consistently or highly with those presently obtained with a symbolic sex-role measure and a verbal sex-role scale. This lack of construct validity has been reported previously in at least two other studies. Though apparently reliable, the validity of the BSI remains problematic.


Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy.
Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: (1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. (2) Even with possible access for 'local refrigeration', cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4 °C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.


Task-based functional neuroimaging in infants: a systematic review.
Infancy is characterized by rapid neurological transformations leading to consolidation of lifelong function capabilities. Studying the infant brain is crucial for understanding how these mechanisms develop during this sensitive period. We review the neuroimaging modalities used with infants in stimulus-induced activity paradigms specifically, for the unique opportunity the latter provide for assessment of brain function. Conducted a systematic review of literature published between 1977-2021, via a comprehensive search of four major databases. Standardized appraisal tools and inclusion/exclusion criteria were set according to the PRISMA guidelines. Two-hundred and thirteen papers met the criteria of the review process. The results show clear evidence of overall cumulative growth in the number of infant functional neuroimaging studies, with electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to be the most utilized and fastest growing modalities with behaving infants. However, there is a high level of exclusion rates associated with technical limitations, leading to limited motor control studies (about 6%) in this population. Although the use of functional neuroimaging modalities with infants increases, there are impediments to effective adoption of existing technologies with this population. Developing new imaging modalities and experimental designs to monitor brain activity in awake and behaving infants is vital.


Activated Carbon Produced by Pyrolysis of Waste Wood and Straw for Potential Wastewater Adsorption.
Pyrolysis of straw pellets and wood strips was performed in a fixed bed reactor. The chars, solid products of thermal degradation, were used as potential materials for activated carbon production. Chemical and physical activation processes were used to compare properties of the products. The chemical activation agent KOH was chosen and the physical activation was conducted with steam and carbon dioxide as oxidising gases. The effect of the activation process on the surface area, pore volume, structure and composition of the biochar was examined. The samples with the highest surface area (1349.6 and 1194.4 m2/g for straw and wood activated carbons, respectively) were obtained when the chemical activation with KOH solution was applied. The sample with the highest surface area was used as an adsorbent for model wastewater contamination removal.


[Possibilities to Control Early Stages of Inflammation in and of Thrombus Formation in Cardiovascular Pathology].
Circulating platelet-leukocyte aggregates (PLA) are present in patients with various diseases of the cardiovascular system and are considered as sensitive markers of platelet activation. At the same time characteristics of PLA in the circulating blood continue to be discussed in the context of the search for early markers of inflammation, which would bring us close to ability to limit the development of inflammatory response at the earliest stage. This review is devoted to analysis of studies of LA in the context of assessment of functional activity of platelets and possibilities of cooperation of blood cells during activation of leukocytes at early stage of realization of inflammation process. Platelets are considered as important amplifiers of inflammation. Moreover, the extent and specificity of platelet-leukocyte interactions are determined by the spectrum of receptors on the blood cell surface triggering a variety of intracellular signaling pathways. The facts that the use of known pharmacological agents can result in inhibition of stimulated platelets, blocking the binding of activated platelets with leukocytes are provided. Accumulated knowledge creates the preconditions for simultaneous control of inflammatory and thrombotic processes in various diseases of cardiovascular system.


Predictive value of PRECISE-DAPT score for long-term all-cause mortality in atrial fibrillation patients with non-ST-elevation myocardial infarction.
Atrial fibrillation (AF) may co-exist in patients with non-ST-elevation myocardial infarction (NSTEMI). In patients with NSTEMI, AF should therefore be regarded as an important risk factor irrespective of its presentation. To predict outcomes in AF patients presenting with NSTEMI, early risk stratification can help to identify the patients with a possible poor long-term prognosis. The development of the PRECISE-DAPT score aimed to predict the risk of bleeding in patients who underwent stent implantation and received dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), providing a valuable tool for assessing bleeding risk in this specific patient population. To assess the performance of the PRECISE-DAPT score in predicting long-term prognosis in AF patients with NSTEMI. Five hundred and twenty-six consecutive AF patients presenting with NSTEMI were included in the present study. The PRECISE-DAPT score was calculated in each case and evaluated for the association of increased mortality in the study population, who survived in-hospital but died in the long term. All-cause mortality deaths occurred in 278 (52.6%) patients. Higher PRECISE-DAPT score, shorter duration of P2Y12 inhibitor therapy, decreased left ventricular ejection fraction (LVEF), and a history of diabetes mellitus (DM) were all associated with an increased risk of all-cause mortality in the multivariable logistic regression model. High PRECISE-DAPT score was associated with higher long-term all-cause mortality in AF patients presenting with NSTEMI.


Aesthetic outcomes and complications following post-mastectomy radiation therapy in patients undergoing immediate extended latissimus dorsi flap reconstruction and implant insertion.
Complications of radiotherapy after implant-based reconstruction include capsular contracture development, seroma formation, and reoperation for implant removal or replacement. However, there is a lack of studies regarding aesthetic outcomes and complication rates following radiation therapy among patients undergoing latissimus dorsi (LD) flap-based reconstruction with implant insertion for volume shortage. The present study aimed to evaluate clinical and aesthetic outcomes of post-mastectomy radiation therapy (PMRT) among patients receiving both LD flap reconstruction and implant insertion. This study comprised 66 patients who underwent mastectomy and breast reconstruction between March 2014 and July 2019. Patient demographics and outcomes were compared among patients who did and did not receive PMRT. Aesthetic outcomes were compared using gross photographs. The incidence of complications, including seroma formation, flap necrosis, nipple-areola complex necrosis, hematoma development, and capsular contractures, was compared between groups. No differences in aesthetic outcomes using gross photos during outpatient follow-up were observed between the radiation and control groups. No significant difference in the frequency of complications was observed between groups. The use of implants and LD reconstruction are inevitable in a proportion of patients due to a lack of LD flap volume. For these patients, PMRT could be safe treatment option if the necessary precautions are implemented.


Some cognitive aspects of meditation practice.
This article reviews the role of some cognitive factors in practice of meditation. It is suggested that more attention should be given to such covert aspects of meditation as expectations, attitudes, and imagery, etc. Non-observable subjective experiences during meditation have not been adequately researched.


Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor.
Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight) prevented most of the endotoxin-induced changes and correlated with a significant decrease in plasma TxB2 and 6-keto PGF1 alpha concentrations, compared with concentrations in nontreated horses (ie, pretreated with saline solution). Pretreatment with phenylbutazone (2 mg/kg) attenuated the effects of endotoxin and was associated with a brief, early, significant increase in plasma TxB2 concentrations, but not in plasma 6-keto PGF1 alpha concentrations. Pretreatment with the thromboxane synthetase inhibitor did not appear to clinically benefit the horses involved; however, arachidonic acid metabolism was redirected to prostacyclin production.


Functional Outcomes Following Radical Cystectomy in Women with Bladder Cancer: A Systematic Review.
Gender-specific functional and health-related quality of life (HRQOL) outcomes following radical cystectomy (RC) for bladder cancer (BCa) remain unclear, with many studies excluding women from the study population. To better characterize female-specific functional outcomes following RC and urinary diversion for BCa. We performed a critical review of PubMed/Medline and Embase in August 2015 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Outcomes of interest included urinary function (for orthotopic neobladder), sexual function, bowel function, and quality of life. Excluded were nonbladder malignancies, RCs performed for neurogenic bladder dysfunction, and patients with exposure to radiation therapy prior to surgery. Forty-five publications were selected for inclusion in this analysis. Included reports addressed urinary function (34 studies), sexual function (11 studies), and HRQOL (9 studies). All studies had a high risk of bias and ranged significantly in sample size, inclusion criteria, and follow-up time, precluding meaningful meta-analysis. Daytime incontinence approximated 20%, nighttime incontinence 20%, and hypercontinence 10-20%. Sexual function appeared to be better among those patients undergoing genitalia-sparing RC, but generally poor outcomes were noted among those undergoing routine RC. Only 40% of studies assessed sexual function using standardized instruments. HRQOL differences between diversion types appeared to be minimal, whereas comparisons with the general population revealed significant differences in emotional problems, role functioning, fatigue, and appetite. Functional outcomes among women undergoing RC for BCa are poorly studied with limitations regarding use of validated questionnaires, heterogeneous patient populations, and small sample sizes. Collaborative efforts will be needed to better define functional outcomes among this poorly studied patient population. We reviewed functional outcomes following cystectomy among women with bladder cancer. We found that urinary, sexual, and bowel function and quality of life are poorly studied among women, with function ranging significantly across studies.


On the origin and spread of Dupuytren's disease.
The first author to suggest an origin and spread of Dupuytren's disease was Early who wrote in 1962, "If one postulates the condition as having arisen in one particular racial group (the Nordic for example) then the variable distribution in other parts of the world might be explained on the basis of migration from that group." Dupuytren's disease is currently called a Viking disease on the assumption that the disease was spread to Europe and the British Isles during the Viking Age of the 9th to the 13th centuries. From a literature search, it is proposed that Dupuytren's disease existed in Europe earlier than the Viking Age and originated much earlier in prehistory.


Phase-field study of the effects of the multi-controlling parameters on columnar dendrite during directional solidification in hexagonal materials.
The growth of hexagonal columnar dendrite during directional solidification with respect to the multi-controlling parameters such as anisotropy, cooling rate, temperature gradient and orientation angle were investigated by a quantitative phase-field method, respectively. The simulation results show that the increase of anisotropy, cooling rate and temperature gradient can accelerate the solidification velocity of columnar dendrites. Among them, the cooling rate has the most significant effect on the solidification velocity of columnar dendrite. In contrast, the solidification velocity of columnar dendrite slows down with the increase of the orientation angle. Meanwhile, the primary dendrite spacing decreases with the increase of cooling rates and temperature gradient, and the primary dendrite arms are smooth. The primary dendrite spacing increases with the increase of anisotropy and orientation angle, which provides space for the development of secondary dendrite arms. In addition, the effects of cooling rate and temperature gradient on the solid volume fraction were also studied.


Renorrhaphy using knitted polyglycolic acid mesh.
Surgical techniques for treatment of penetrating trauma to the kidney have ranged from simple drainage to nephrectomy, depending on the severity of the injury. Based upon successful experience in the surgical management of splenic injuries using knitted polyglycolic acid mesh, we report a case in which absorbable mesh was used to repair a laceration of the kidney.


Effect of human plasma proteins on spontaneous contractile activity of rat mesenteric portal vein.
This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, gamma-globulin, alpha-globulin, beta-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the gamma-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or gamma-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to alpha-globulin or alpha- and beta-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of gamma-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by gamma-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on alpha-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension.


Project Head Start. An evaluation of the medical components in California.
Half of 1,135 children medically examined as a part of Project Head Start in California had one or more conditions that warranted referral to a physician or dentist, and only one-fifth of these were under care. In the judgment of the examining physicians, one-third of the referable medical conditions were described as "major." Follow-up procedures were variable and not very successful. Increased local medical society participation in planning the health services for these children is recommended as an especially important step in securing care for the problems that are identified.


Integrated networks and health care provider cooperatives: new models for rural health care delivery and financing.
Minnesota's 1994 health care reform legislation authorized the establishment of community integrated service networks (CISNs) and health care provider cooperatives, which were envisioned as new health care delivery models that could be successfully implemented in rural areas of the state. Four CISNs are licensed, and three organizations are incorporated as health care provider cooperatives. Many of the policy issues Minnesota has faced regarding the development of CISNs and health care provider cooperatives in rural areas are similar to those raised by current Medicare reform proposals.


Hiding Within the Cracks: Case Report of Rare Sutural Bone Found at the Nasion.
Pathology such as skull fractures can be misdiagnosed in the presence of anatomical variations. One variant that has had little description in the literature are the sutural bones associated with the nasal bones. Herein, we describe a case of a rare sutural bone at the nasion, between the bones of the right nasal, frontal, and maxillary frontal process. To our knowledge, this is the first report of such a variant bone in this location, and such it should be considered by clinicians when evaluating patients for pathology in this region.


Determination of free fatty acids and triglycerides by gas chromatography using selective esterification reactions.
A method for selectively determining both free fatty acids (FFA) and triacylglycerides (TAGs) in biological oils was investigated and optimized using gas chromatography after esterification of the target species to their corresponding fatty acid methyl esters (FAMEs). The method used acid catalyzed esterification in methanolic solutions under conditions of varying severity to achieve complete conversion of more reactive FFAs while preserving the concentration of TAGs. Complete conversion of both free acids and glycerides to corresponding FAMEs was found to require more rigorous reaction conditions involving heating to 120°C for up to 2 h. Method validation was provided using gas chromatography-flame ionization detection, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry. The method improves on existing methods because it allows the total esterified lipid to be broken down by FAMEs contributed by FFA compared to FAMEs from both FFA and TAGs. Single and mixed-component solutions of pure fatty acids and triglycerides, as well as a sesame oil sample to simulate a complex biological oil, were used to optimize the methodologies. Key parameters that were investigated included: HCl-to-oil ratio, temperature and reaction time. Pure free fatty acids were found to esterify under reasonably mild conditions (10 min at 50°C with a 2.1:1 HCl to fatty acid ratio) with 97.6 ± 2.3% recovery as FAMEs, while triglycerides were largely unaffected under these reaction conditions. The optimized protocol demonstrated that it is possible to use esterification reactions to selectively determine the free acid content, total lipid content, and hence, glyceride content in biological oils. This protocol also allows gas chromatography analysis of FAMEs as a more ideal analyte than glyceride species in their native state.


Dialyzing women and men: does it matter? An observational study.
Application and consequences of hemodialysis treatment may differ between genders; focusing on these differences may be useful to optimize outcomes. Data from 1 999 648 hemodialysis sessions performed in 10 984 (3316 incident and 7668 prevalent) patients, treated in 55 centers of the European Clinical Database (EuCliD)-Turkey, were analyzed, and various demographic, clinical, biochemical, therapeutic and prognostic parameters were compared. There were 1905 male and 1411 female incident and 4339 male and 3329 female prevalent patients. For females, the mean age in incident (61.8 ± 14.9 years) and prevalent (58.3 ± 15.2 years) patients was higher than for males (60.2 ± 14.8 and 56.5 ± 14.9 years, respectively) (P < 0.001 for both analyses). Also, body mass index was higher, while the hemoglobin level, and the percentage of interdialytic weight gain and arteriovenous fistula were lower. Serum phosphorus was similar in both genders in incident cases, while it was lower in prevalent female patients. Serum parathyroid hormone levels were lower in incident, but higher in prevalent male cases. Erythropoiesis-stimulating agents and vitamin D preparations were more frequently used in female incident and prevalent patients. Hospitalization was more frequent in prevalent females, while it did not differ significantly in the incident cases. Overall, no significant difference was observed in survival rates at 3 years in both incident and prevalent male and female patients. Many parameters differ significantly between female and male dialysis patients. Considering the effects of sex on several parameters may be a valuable approach for achieving better outcomes when formulating treatment strategies in this patient population.


Clinical relevance of serum aquaporin-4 antibody levels in neuromyelitis optica.
Neuromyelitis optica (NMO) is an inflammatory disease that selectively affects the optic nerves and spinal cord. The discovery of NMO-IgG targeting aquaporin-4 (AQP4) in NMO patients suggested that NMO is a distinct entity, with a fundamentally different etiology from that of multiple sclerosis (MS). Although NMO usually leads to grave disability because of the more severe tissue destruction compared with classical MS, there have been several reports describing a benign form of NMO over a long disease term. NMO-IgG/AQP4 antibodies show high specificity but medium sensitivity for NMO, while the clinical relevance of AQP4 antibody titers remains to be determined. We aimed to clarify the clinical relevance of AQP4 antibody levels determined by a bridging enzyme-linked immunosorbent assay in 38 patients with NMO or NMO spectrum disorder. The AQP4 antibody levels were higher in patients with optic neuritis (ON) than in those without ON (p = 0.0164). Among the 12 patients examined in a longitudinal study, four showed an increase in the ELISA values during some relapses, and eight showed no clear correlation between the ELISA values and relapse. Of the four patients who demonstrated a steady rise in the antibody levels over time, two patients had no concomitant relapses, despite elevation of the AQP4 antibody levels. We conclude that high AQP4 antibody levels are associated with the occurrence of ON, but that the antibody levels themselves are not closely correlated with the onset of relapse.


Similar healthy osteoclast and osteoblast activity on nanocrystalline hydroxyapatite and nanoparticles of tri-calcium phosphate compared to natural bone.
While there have been numerous studies to determine osteoblast (bone forming cell) functions on nanocrystalline compared to micron crystalline ceramics, there have been few studies which have examined osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and receptor activator of nuclear factor κB [RANK]). This is despite the fact that osteoclasts are an important part of maintaining healthy bone since they resorb bone during the bone remodeling process. Moreover, while it is now well documented that bone formation is enhanced on nanoceramics compared to micron ceramics, some have pondered whether osteoblast functions (such as osteoprotegerin and RANK ligand [RANKL]) are normal (ie, non-diseased) on such materials compared to natural bone. For these reasons, the objective of the present in vitro study was to determine various functions of osteoclasts and osteoblasts on nanocrystalline and micron crystalline hydroxyapatite as well as tri-calcium phosphate materials and compare such results to cortical and cancellous bone. Results showed for the first time similar osteoclast activity (including tartrate-resistant acid phosphatase, formation of resorption pits, size of resorption pits, and RANK) and osteoblast activity (osteoprotegerin and RANKL) on nanocrystalline hydroxyapatite compared to natural bone, whereas osteoclast and osteoblast functions on micron crystalline versions of these ceramics were much different than natural bone. In this manner, this study provides additional evidence that nanocrystalline calcium phosphates can serve as suitable synthetic analogs to natural bone to improve numerous orthopedic applications. It also provides the first data of healthy osteoclast and osteoblast functions on nanocrystalline calcium phosphates compared to natural bone.


The pharmacology of molluscan neurons.
It is commonly accepted that the basic physiological properties of the neurons as well as the nature of transmitter substances have remained relatively unchanged through evolution, while brain size and neuron number have greatly increased. Among invertebrates the molluscs, due to the large size of their neurons and lesser complexity of the neural networks controlling specific behavior, have proved to be especially useful for studying elementary properties of single neurons, network organization as well as various forms of learning and memory. The study of putative neurotransmitters has indicated that molluscs use the same low molecular-weight substances and peptides or their metabolites and cyclic nucleotides as transmitters and second messengers as the other species of various phyla. At the same time the receptors of neurotransmitters were found to have certain characteristic properties in the molluscs. The large molluscan neurons have permitted the isolation of individual identifiable nerve cells, and the subsequent analysis of quantities of the transmitters and their metabolic enzymes. These studies have demonstrated that single neurons frequently can contain more than one putative neurotransmitter. It can be expected that this model will contribute to an understanding of the role of multiple transmitters within a single neuron assuring the plasticity of the nervous system. The cellular mechanisms of plasticity have been demonstrated first in molluscan nervous systems. It was proved in identified Aplysia neurons that the same transmitter (ACh) can be released from an interneuron onto two or more follower neurons and can excite one and inhibit another or evoke a biphasic response on a third type of cell. The biphasic response of the molluscan neurons to neurotransmitters was the first demonstration of the plastic synaptic changes. The discovery of individual neurons with their groups of follower cells acting as chemical units has provided an insight into the organization of various behavioral acts. Study of the gastropod molluscs has also shown that the giant serotonergic cells can act as peripheral modulator neurons, as well as interneurons, and in this way they can affect their target organs at more than one level. The molluscan studies have provided more information on transmitter receptors as it was shown that molluscan neurons have at least six different 5HT receptors, three Ach receptors which can be separated pharmacologically. This type of study has led to the discovery of numerous new antagonists and poisons.(ABSTRACT TRUNCATED AT 400 WORDS)


[Anticoagulation for secondary prevention: which drug in which situation?].
Thromboembolic events are a major complication of cardiovascular diseases. Secondary prevention of thromboembolic complications can be achieved by anticoagulation with heparin or vitamin-K-antagonists. A new class of direct thrombin inhibitors has been recently introduced into clinical medicine. Clinical studies have demonstrated theses agents to be comparable in efficacy for prophylaxis of venous thromboembolism. However, the results of ongoing trials are awaited in helping to define the place of direct thrombin inhibitors in secondary prevention. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines and glycoprotein IIb/IIIa inhibitors represents an important addition to the physician's armamentarium. Due to the increased risk of major bleeding, for each patient the decision of anticoagulation and antiplatelet therapy must be tightly correlated to the individual benefit-risk ratio.


[Comparison of the suppressing capecitabine and 5-fluorouracil effects on the pronounce of inflammatory cells score in the induction of episcleral fibrosis after trabeculectomy].
Trabeculectomy is a filtering antiglaucoma surgery performed to facilitate the formation of a drainage channel for the aqueous humor from the anterior chamber of the eye to the subconjunctival space making a collector, filtering cushion of the eyeliquid. The cause of unfavourable outcome of trabeculectomy is episcleral fibrosis which leads to the obstruction of the drainage channel Inflammatory reaction is an initial, but, also, the key event in the process of fibrosis and directly proportional to it A successful medicamentous suppression of inflammation could stop fibrosis. Arccordingly, the aim of this study was to comparatively evaluate suppressing effects of capecitabine and 5-fluoroaracil upon inflammation, an initial fibrosis process after trabeculectomy. This study was performed on an experimental animal model, namely 2 4 rabbits (48 eyes), which were exposed to artificial cause of the tissue changes analogous to human subclinical inflammation. During the trabeculectomy, a 5% solution of 5-fluoroaracil was applied to the right eye sclera of a rabbit, while 2% solution of kapecitabine was applied to the left eye sclera, thus making possible to evaluate the effects of different drugs to the same animal. Two weeks after the surgery the subconjunctival - episcleral tissue cuts were analyzed. Semiquantitative histologic test was used to compare the cellular elements of inflammatory (fibroblasts, mononuclears, plasmocytes, eosinophiles), as well as fibrosing (colagen, reticulin fibers) process, and, based on the differences in histopathologic score, suppressive efficacy of 5-fluoroaracil and kapecitabine was evaluated and compared between the groups of the treated tissues. The results were shown as mean values +/- standard deviation. A statistically significantly lower score was revealed in the initial inflammatory cells - mononudears and plasmocytes in the group of the tissues treated with kapecitabine, while there was no differences between the groups in the score of fibroblasts and colagen fibers. The suppression of the initial episcleral fibrosis process obtained by kapecitabine was more significant as compared to the suppression obtained by 5-fluoroaracil, thus providing more favorable outcome of the trabeculectomy.


Psychological consequences of prenatal diagnosis in a case of familial Angelman syndrome.
Angelman Syndrome (AS), characterized by mental retardation, absence of speech, seizures and motor dysfunction, is caused by genetic defects leading to loss of expression of the maternal copy of the chromosome 15q11-13 imprinted region. Most cases are sporadic, being caused by de novo deletion of maternal chromosome 15q11-13 (75%) or by paternal uniparental disomy (3-4%). Familial cases can occur, due to mutations in the UBE3A gene or in the imprinting center. We describe the case of a pregnant woman having two nephews with AS caused by a UBE3A mutation; lack of communication within the family led the woman to be completely unaware of the risk of disease recurrence until 15 weeks of gestation. UBE3A genetic testing revealed she carried the familial mutation 892-893delCT. Prenatal diagnosis was performed on amniotic fluid and demonstrated that the fetus had inherited the mutation. The unexpected diagnosis and the subsequent termination of the pregnancy caused the woman to undergo acute psychological distress showing relevant psychopathological symptoms. Nevertheless, at 2-year follow-up, adverse consequences were minimized, and the couple was planning a new pregnancy. Factors affecting the psychological outcome of abortion and the role of psychological support in reducing the risk of long-term unfavorable consequences are discussed.


The instability of functional connectomes across the first year of life.
The uniqueness and stability of the adolescent and adult functional connectome has been demonstrated to be high (80-95 % identification) using connectome-based identification (ID) or "fingerprinting". However, it is unclear to what extent individuals exhibit similar distinctiveness and stability in infancy, a developmental period of rapid and unparalleled brain development. In this study, we examined connectome-based ID rates within and across the first year of life using a longitudinal infant dataset at 1.5 month and 9 months of age. We also calculated the test-retest reliability of individual connections across the first year of life using the intraclass correlation coefficient (ICC). Overall, we found substantially lower infant ID rates than have been reported in adult and adolescent populations. Within-session ID rates were moderate and significant (ID = 48.94-70.83 %). Between-session ID rates were very low and not significant, with task-to-task connectomes resulting in the highest between-session ID rate (ID = 26.6 %). Similarly, average edge-level test-retest reliability was higher within-session than between-session (mean within-session ICC = 0.17, mean between-session ICC = 0.10). These findings suggest a lack of uniqueness and stability in functional connectomes across the first year of life consistent with the unparalleled changes in brain functional organization during this critical period.


[Mapping stakeholders' preferences in prioritization criteria for horizon scanning in healthcare technologies].
Filtration and prioritization are two basics steps in horizon scanning systems. This article aimed to map stakeholders' preferences in the Brazilian Unified National Health System (SUS) regarding filtration and prioritization criteria. Two filtration criteria (time horizon and innovation) and eight prioritization criteria (relevance to epidemiology, health policies, and clinical practice; potential impact on SUS budget, healthcare providers' costs, and mortality; safety; and legal, ethical, and social aspects) were selected. Multiple correspondence analysis was used to map stakeholders' preferences within and between groups. Two groups were more homogeneous and determinant for selection of prioritization criteria. Stakeholders' professional experience had more influence than institutional affiliations. The approach showed transparent criteria selection and analysis of stakeholders' individual preferences.


Microbes and membrane biology.
General principles of membrane function have been elucidated by the study of lactic acid bacteria. In this review, the operation and function of ion pumps, secondary transport systems and solute ATPases will be discussed. Despite their differences in kinetics and mechanisms between the transport systems, structural similarities can be recognized among these proteins irrespective of whether they originate from prokaryotes, lower or higher eukaryotes.


Comparative Evaluation of Fracture Resistance and Mode of Failure of Zirconia and Titanium Abutments with Different Diameters.
The purpose of the current study was to compare the fracture resistance and mode of failure of zirconia and titanium abutments with different diameters. Fourteen groups of abutments including prefabricated zirconia, copy-milled zirconia and titanium abutments of an implant system (XiVE, Dentsply) were prepared in different diameters. An increasing vertical load was applied to each specimen until failure occurred. Fracture resistance was measured in each group using the universal testing machine. Moreover, the failure modes were studied and categorized as abutment screw fracture, connection area fracture, abutment body fracture, abutment body distortion, screw distortion and connection area distortion. Groups were statistically compared using univariate and post-hoc tests. The level of statistical significance was set at 5%. Fabrication method (p = 0.03) and diameter (p < 0.001) had significant effect on the fracture resistance of abutments. Fracture resistance of abutments with 5.5 mm diameter was higher than other diameters (p < 0.001). The observed modes of failure were dependent on the abutment material as well. All of the prefabricated titanium abutments fractured within the abutment screw. Abutment screw distortion, connection area fracture, and abutment body fracture were the common failure type in other groups. Diameter had a significant effect on fracture resistance of implant abutments, as abutments with greater diameters were more resistant to static loads. Copy-milled abutments showed lower fracture resistance as compared to other experimental groups. Although zirconia abutments have received great popularity among clinicians and even patients selecting them for narrow implants should be with caution.


The Affordable Care Act's implications for a public health workforce agenda: taxonomy, enumeration, and the Standard Occupational Classification system.
The Affordable Care Act brings a renewed emphasis on the importance of public health services and those whose occupations are defined by performing the essential public health functions. The Affordable Care Act Prevention and Public Health Fund is a signal to the field that its work is important and critical to the health of the nation. Recent reports by the Institute of Medicine describe the changing dimensions of public health work in primary care integration and the need for enhanced financing of public health as investment. Gaining knowledge about the public health workforce, that is, how many workers there are and what they are doing, is of growing interest and concern for the field. Although enumeration of the public health workforce has been attempted several times by the federal government beginning as early as 1982, it was not until the year 2000 that a major effort was undertaken to obtain more complete information. Limitations that hampered Enumeration 2000 have persisted however. With implementation of the Affordable Care Act and other new ventures, key federal agencies are developing strategies to pursue a systemic and systematic enumeration and consistent taxonomy process. Included in these efforts is use of the Bureau of Labor Statistics, Standard Occupational Classification system. A clear and accurate understanding of the public health workforce and its characteristics is a major challenge. A well-constructed, systematic enumeration process can add to our understanding of the nature and functions of that workforce. In addition, discussion of enumeration must include the need for a consensus within the field that leads to a consistent taxonomy for the public health occupations. This article will provide a stage-setting brief of historical actions regarding enumeration, and it will examine selected enumeration activities taking place currently. It will discuss positive and negative implications facing public health and the potential for enhancing the existing Standard Occupational Classification system to aid enumeration studies.


Biodegradation of glyceryl trinitrate by Penicillium corylophilum Dierckx.
Penicillium corylophilum Dierckx, isolated from a contaminated water wet, double-base propellant, was able to completely degrade glyceryl trinitrate (GTN) in a buffered medium (pH 7.0) containing glucose and ammonium nitrate. In the presence of 12 mg of initial fungal inoculum, GTN (48.5 to 61.6 mumol) was quantitatively transformed in a stepwise process to glyceryl dinitrate (GDN) and glyceryl mononitrate (GMN) within 48 h followed by a decrease in the GDN content with a concomitant increase in the GMN level. GDN was totally transformed to GMN within 168 h, and the complete degradation of GMN was achieved within 336 h. The presence of glucose and ammonium nitrate in the growth medium was essential for completion of the degradation of GTN and its metabolites. Complete degradation of GTN by a fungal culture has not been previously reported in the literature.


Scenarios for a viral etiology of schizophrenia.
Recent discoveries in the field of virus receptors have revolutionized our concepts of viral pathogenesis. The lysis of cells resulting from virus infection or immune recognition of infected cells is seen as merely one facet of a spectrum of pathogenic mechanisms which may be subtle and complex. This is particularly relevant to the central nervous and immune systems which share cell-surface receptors for various neuropeptides and neurotransmitters. A number of viruses are now known to share receptors for such endogenous ligands; indeed, some viruses (e.g., human immunodeficiency virus and vaccinia) may themselves be structural analogs of these ligands. There is, therefore, considerable scope for interference by viruses in the normal functioning of the brain and neuroendocrine systems. Brief reactive psychoses are occasionally reported as acute sequels to viral infections, but generally these are regarded as unrelated to schizophrenia. An opposite viewpoint is presented in the article: i.e., that the only reason these reactive psychoses do not progress to schizophrenia is that the majority of individuals affected are not predisposed genetically to schizophrenia. Conceivably, therefore, the genetic predisposition to schizophrenia may be attributable to genes which determine idiosyncratic differences in immune responsiveness to common viral pathogens.


Histone deacetylase inhibitors: emerging anticancer therapeutic agents?
Histone deacetylase inhibitors are novel anticancer agents in clinical development that target the family of histone deacetylase (HDAC) enzymes responsible for deacetylating core nucleosomal histones and other proteins. The precise mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known, but there are several proposed mechanistic models, including transcriptional and nontranscriptional processes. Clinical experience with these agents indicates that they are generally well tolerated, and anticancer activity has been observed in early clinical trials in several tumor types including non-small-cell lung cancer. The development of these agents continues, with an emphasis on the discovery of HDAC isoform-selective compounds. Successful future development relies on clearer understanding of the dominant mechanisms involved in the observed antiproliferative effects.


New chain-extended analogues of salacinol and blintol and their glycosidase inhibitory activities. Mapping the active-site requirements of human maltase glucoamylase.
The synthesis of new chain-extended sulfonium and selenonium salts of 1,4-anhydro-4-thio-(or 4-seleno)-d-arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, is described. Nucleophilic attack at the least hindered carbon atom of 4,6-O-benzylidene-2,5-di-O-p-methoxybenzyl-d-mannitol-1,3-cyclic sulfate by 2,3,5-tri-O-p-methoxybenzyl-1,4-anhydro-4-thio-(or 4-seleno)-d-arabinitol gave the sulfonium and selenonium sulfates, respectively. Subsequent deprotection with trifluoroacetic acid yielded the target compounds. In these analogues, an extended polyhydroxylated aliphatic side chain has been incorporated while maintaining the stereochemistry of C-2' and C-3' of salacinol or blintol. These compounds were designed to probe the premise that they would bind with higher affinity to glucosidases than salacinol because the extra hydroxyl groups in the acyclic chain would make favorable polar contacts within the active site. Both target compounds inhibited recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with Ki values in the low micromolar range. Comparison of these values to those of related compounds synthesized in previous studies has provided a better understanding of structure-activity relationships and the optimal stereochemistry at the different stereogenic centers required of an inhibitor of this enzyme. With respect to chain extension, the configurations at C-2' and C-4' are critical for activity, the configuration at C-3', bearing the sulfate moiety, being unimportant. The desired configuration at C-5' is also specified. However, comparison of the activities of the chain-extended analogues with those of salacinol and blintol indicates that there is no particular advantage of the chain-extension relative to salacinol or blintol. These results are similar to those reported earlier for kotalanol, a 7-carbon-extended derivative, versus salacinol against rat intestinal maltase, sucrase, and isomaltase.


Airway Microbiota as a Modulator of Lung Cancer.
Recent research on cancer-associated microbial communities has elucidated the interplay between bacteria, immune cells, and tumor cells; the bacterial pathways involved in the induction of carcinogenesis; and their clinical significance. Although accumulating evidence shows that a dysbiotic condition is associated with lung carcinogenesis, the underlying mechanisms remain unclear. Microorganisms possibly trigger tumor initiation and progression, presumably via the production of bacterial toxins and other pro-inflammatory factors. The purpose of this review is to discuss the basic role of the airway microbiome in carcinogenesis and the underlying molecular mechanisms, with the aim of developing anticancer strategies involving the airway microbiota. In addition, the mechanisms via which the microbiome acts as a modulator of immunotherapies in lung cancer are summarized.


Antibiotic-associated suspected adverse drug reactions among hospitalized patients in Uganda: a prospective cohort study.
We sought to determine the prevalence at admission and incidence during hospitalization of antibiotic-associated suspected adverse drug reactions (aa-ADRs) among Ugandan inpatients; and to characterize these aa-ADRs. We conducted a prospective cohort study of 762 consented adults admitted on medical and gynecological wards of the 1790-bed Mulago National Referral Hospital. Thirty percent were known HIV-seropositive (232/762). Nineteen percent (148/762; 95% CI: 17-22%) of inpatients experienced at least one aa-ADR. At hospital admission, 6% (45/762; 95% CI: 4-8%) of patients had at least one aa-ADR; and 15% (45/300; 11-20%) of those who had received antibiotics in the 4-weeks preadmission. Twenty-four (53%) of these 45 patients had serious aa-ADRs. The incidence of aa-ADRs was 19% (117/629; 95% CI: 16-22%) of patients who received antibiotics [community-acquired: 9% (27/300; 95% CI: 6-13%); hospital-acquired: 16% (94/603; 95% CI: 13-19%)]: 39 (33%) of 117 patients had serious aa-ADRs. Of 269 aa-ADRs, 115 (43%) were community-acquired, 66 (25%) probable/definite, 171 (64%) preventable, 86 (32%) serious, and 24 (9%) rare. Ceftriaxone was the most frequently implicated for serious hospital-acquired aa-ADRs. Cotrimoxazole, isoniazid, rifampicin, ethambutol, and pyrazinamide were the most frequently linked to serious community-acquired aa-ADRs. Fatal jaundice (isoniazid), life-threatening difficulty in breathing with shortness of breath (rifampicin) and disabling itchy skin rash with numbness of lower swollen legs (ethambutol, isoniazid) were observed. Pharmaceutical quality testing of implicated antibiotics could be worthwhile. Periodic on-ward collection and analysis of antibiotic-safety-data standardized by consumption is an efficient method of tracking antibiotics with 1%-risk for serious aa-ADRs.


[Nocturnal long-term monitoring of lung sounds in patients with gastro-oesophageal reflux disease].
Gastro-oesophageal reflux disease (GERD) is one of the most common clinical conditions in the developed countries. Particular interest in pulmonary manifestations of this disease has arisen over the last few years. Although the high coincidence between reflux and chronic cough is unquestioned, the proof of a causal correlation is still lacking. In this paper we present the Marburger Lung-Sound-Monitoring as a new method for the detection of nocturnal respiratory symptoms such as cough, wheezing and throat clearing and their temporal correlation with reflux. This method will in future allow us to precisely record and to evaluate the extent and duration of reflux events and their correlation with respiratory symptoms.


[Contribution of ABVD chemotherapy in refractory Hodgkin's disease. Study of 21 observations (author's transl)].
On a two years period, 21 patients with advanced Hodgkin's disease who failed usual therapeutic proceedings were treated by a sequential combination chemotherapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD, first described by Bonadonna). Initially 16 patients among 21 had a disseminated disease with stage III B (9 obs.) or IV B (7 obs.). Previously all had been submitted, during a four years mean period, to multiple therapeutic trials always involving MOPP plus lymphoid irradiation and/or other combination chemotherapy. In 19 patients among 21, ABVD was decided because of persistent abdominal lymphoid and/or visceral localizations (liver: 6 obs.; lung: 4 9bs; épidural space: 1 obs.). In 12 patients, abdominal localizations were proved after delayed staging laparotomy. Immediate results with ABVD were: CR: 9 obs. (43%); PR: 5 obs. (24%); failure: 7 obs. (33%). With vinblastine interrupted by intermittent ABVD, 4 CR are persisting with a 8 to 23 months' follow up; among 5 patients who relapsed (3 to 24 months), 4 are still alive. After irradiation of résidual lesions, 4 PR among 5 are persisting with a 6 to 12 months' follow up. For the 21 patients, median survival has not been reached at 30 months.


Impact of a state concussion law on pediatric emergency department visits.
Many states have passed concussion laws that mandate that players undergo medical clearance before returning to play. Few data have been collected on the impact of such laws on emergency department (ED) visits. This study measures the impact of Rhode Island concussion legislation on sports-related concussion visits to a pediatric ED. International Classification of Diseases, Ninth Revision, Clinical Modification codes with injury mechanism-associated E-codes were extracted from hospital databases from 2004 to 2011 for both sports-related concussions and sports-related ankle ligamentous injuries (comparison group). Visit rates for sports-related concussions were compared before and after the passage of the state concussion law.Secondary outcome measures included rates of head imaging per ED visit for concussion before and after passage of the law. Times series analysis was used to analyze season-to-season count and rate changes. Overall rate of sports-related concussion visits more than doubled (2.2-fold increase; 95% confidence interval, 1.3-3.6; adjusted P = 0.01) during the fall sports season following the implementation of legislation (2010) relative to the previous year (3.6% vs 1.4%). Rates of sports-related ankle sprain visits tended to increase during the fall sports season but did not achieve statistical significance. Rates of computed tomography scan imaging of the head did not change over time. The data from this study revealed an increase in pediatric ED visits for sports-related concussions, without a corresponding increase in head imaging, suggesting that the passage of a state concussion law has led to increased vigilance in evaluation of sports-related concussions, without an increase in diagnostic computed tomography scans.


Enhanced power within the default mode network in normal subjects with elevated scores on an egocentric scale.
Integrated global power from the primary structures that composed the Default Mode Network (DMN) and from a random collection of other structures were measured by sLORETA (standardized low-resolution electromagnetic tomography) for young university volunteers who had completed an inventory that contained a subscale by which egocentricity has been inferred. Subjects who exhibited higher scores for egocentricity displayed significantly more power within the DMN structures relative to comparison areas. This was not observed for individuals whose egocentricity scores were lowest where the power differences between the DMN and comparison structures were not significant statistically. DMN power was greater in the right hemisphere than the left for men but greater in the left hemisphere than the right for women. The results are consistent with our operating metaphor that elevation of power or activity within the DMN is associated with greater affiliation with the self and its cognitive contents.


Predictive Modeling of Machining Temperatures with Force⁻Temperature Correlation Using Cutting Mechanics and Constitutive Relation.
Elevated temperature in the machining process is detrimental to cutting tools-a result of the effect of thermal softening and material diffusion. Material diffusion also deteriorates the quality of the machined part. Measuring or predicting machining temperatures is important for the optimization of the machining process, but experimental temperature measurement is difficult and inconvenient because of the complex contact phenomena between tools and workpieces, and because of restricted accessibility during the machining process. This paper presents an original analytical model for fast prediction of machining temperatures at two deformation zones in orthogonal cutting, namely the primary shear zone and the tool⁻chip interface. Temperatures were predicted based on a correlation between force and temperature using the mechanics of the cutting process and material constitutive relation. Minimization of the differences between calculated material flow stresses using a mechanics model and a constitutive model yielded an estimate of machining temperatures. Experimental forces, cutting condition parameters, and constitutive model constants were inputs, while machining forces were easily measurable by a piezoelectric dynamometer. Machining temperatures of AISI 1045 steel were predicted under various cutting conditions to demonstrate the predictive capability of each presented model. Close agreements were observed by verifying them against documented values in the literature. The influence of model inputs and computational efficiency were further investigated. The presented model has high computational efficiency that allows real-time prediction and low experimental complexity, considering the easily measurable input variables.


[Regulatory effect of yijing fang on adenine-induced infertility in rat models: a pharmacodynamic study].
To investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency. Sixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups. YJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group. Yifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.


Hemodynamic forces regulate developmental patterning of atrial conduction.
Anomalous action potential conduction through the atrial chambers of the heart can lead to severe cardiac arrhythmia. To date, however, little is known regarding the mechanisms that pattern proper atrial conduction during development. Here we demonstrate that atrial muscle functionally diversifies into at least two heterogeneous subtypes, thin-walled myocardium and rapidly conducting muscle bundles, during a developmental window just following cardiac looping. During this process, atrial muscle bundles become enriched for the fast conduction markers Cx40 and Nav1.5, similar to the precursors of the fast conduction Purkinje fiber network located within the trabeculae of the ventricles. In contrast to the ventricular trabeculae, however, atrial muscle bundles display an increased proliferation rate when compared to the surrounding myocardium. Interestingly, mechanical loading of the embryonic atrial muscle resulted in an induction of Cx40, Nav1.5 and the cell cycle marker Cyclin D1, while decreasing atrial pressure via in vivo ligation of the vitelline blood vessels results in decreased atrial conduction velocity. Taken together, these data establish a novel model for atrial conduction patterning, whereby hemodynamic stretch coordinately induces proliferation and fast conduction marker expression, which in turn promotes the formation of large diameter muscle bundles to serve as preferential routes of conduction.


Microbial airway colonization is associated with noninvasive ventilation failure in exacerbation of chronic obstructive pulmonary disease.
Abnormal airway colonization in patients with chronic obstructive pulmonary disease (COPD) needing invasive mechanical ventilation (IMV) is considered a first step in the acquisition of nosocomial pneumonia. Noninvasive ventilation (NIV) could potentially avoid this, but airway colonization has not been studied in patients who undergo NIV. We hypothesized that patients undergoing NIV would have lower rates of colonization than patients undergoing IMV. The aim of the study was to assess the microbial airway colonization in patients with exacerbated COPD needing NIV and IMV. A 2-yr prospective cohort study. Respiratory intensive and intermediate care unit. Eighty-six patients with exacerbated COPD undergoing NIV on admission (64 successes and 22 failures, according to subsequent intubation), and 51 patients undergoing IMV on admission. Quantitative culture specimens of sputum or tracheal aspirate were collected on admission and at follow-up (day 3) during NIV or IMV, respectively. Clinical assessment, including severity scores, and arterial blood gas measurements were also determined. Compared with the NIV-success group, colonization by potentially pathogenic microorganisms was greater in the NIV-failure group on admission (13 [59%] vs. 14 [22%]; p < .001) and at follow-up while patients still underwent NIV (14 [93%] vs. 7 [14%]; p < .001), and it was even higher than during IMV at follow-up (20 [50%]; p = .027). Colonization by nonfermenting Gram-negative bacilli, mainly Pseudomonas aeruginosa, was significantly associated with NIV failure on admission (OR, 5.6; p = .016) and at follow-up (OR, 23.5; p < .001). Moreover, colonization by these microorganisms at follow-up (OR, 8.8; p = .008) and inadequate antimicrobial treatment (OR 11.3; p = .001) were associated with increased hospital mortality. Airway colonization by nonfermenting Gram-negative bacilli is strongly associated with NIV failure. Because it occurs before intubation, this would be a marker rather than just a consequence of NIV failure necessitating intubation. The efficacy of decreasing airway colonization in preventing NIV failure needs to be assessed.


Effects of fixation and varying target length on the sensitivity of polymerase chain reaction for detection of human T-cell leukemia virus type I proviral DNA in formalin-fixed tissue sections.
In this study, the fixation condition most suitable for maintaining the sensitivity of the polymerase chain reaction (PCR) was investigated by using the alpha-tubulin gene sequence, and the PCR procedure most effective for detecting human T-cell leukemia virus type I (HTLV-I) proviral sequences in fixed, embedded tissues of adult T-cell leukemia patients was explored. First, the sensitivity of the PCR targeting a 286-bp alpha-tubulin sequence was studied in tissue sections fixed in several fixatives for various periods at 25 or 4 degrees C. For histological examination, fixation with 10% buffered formalin at a lower temperature for a shorter period was found to be preferable to retain the sensitivity. And the HTLV-I sequence was detected in only 7 of 18 specimens (38.9%) when the 374-bp sequence of the gag region was targeted, but the rate increased to 77.8% (14 of 18 specimens) when the length of the target sequence was reduced to 120 bp within the same region. Therefore, the one-round PCR targeting a shorter sequence is preferable for application of PCR to archival fixed tissue specimens, the fixation condition of which may not be ideal for DNA preservation.


The origin of binaural interaction in the modulation domain.
The purpose of these experiments was to assess whether the detection of diotic 5 Hz "probe" modulation of a 4000 Hz sinusoidal carrier was influenced by binaural interaction of "masker" modulators presented separately to each ear and applied to the same carrier. A 50 Hz masker modulator was applied to one ear and the masker modulator applied to the other ear had a frequency of 55 or 27.5 Hz. The starting phase of the masker modulators was fixed, and the starting phase of the probe modulator was varied. For both pairs of masker modulators, the threshold for detecting the probe modulation varied slightly but significantly with probe starting phase. Further experiments measuring probe detectability as a function of probe modulation depth did not provide clear evidence to support the idea that the internal representations of the masker modulators interacted binaurally to produce a weak distortion component in the internal representation of the modulation at a 5 Hz frequency. Also, the obtained phase effects were not correctly predicted using a model based on short-term loudness fluctuations.


Quality of life and unmet needs in patients with inflammatory arthropathies: results from the multicentre, observational RAPSODIA study.
The observational RAPSODIA (RA, PsA and spondylitis including AS) study was planned to assess, in patients with RA, AS and PsA, their involvement in medical decisions, quality of life and unmet needs 15 years after the introduction of biologic therapies in Italy. Patients completed a questionnaire during their scheduled rheumatology consultation. They rated their satisfaction with disease knowledge on a 5-point scale (1 = not at all satisfied, 5 = totally satisfied). Self-efficacy, defined as judgement of one's own ability to achieve given levels of performance and exercise control over events, was measured using the pain subscale of the Arthritis Self-Efficacy Scale. Patients' global assessments of pain, fatigue and disease activity were recorded on 100 mm visual analogue scales (0 = best status, 100 = worse status). Disease activity status was assessed using standard tools. Health status was measured using the 36-item Short Form Health Survey and the Italian version of the HAQ. Ninety-eight per cent of patients reported that their health care practitioner used understandable terms to explain their condition. Joint issues and general symptoms (e.g. fatigue and malaise) were common. All measures of disease activity and self-efficacy scores were markedly better in patients receiving biologic vs conventional therapy. Biologic therapy recipients were more productive at work. These results confirm that some patients with rheumatic diseases are not satisfied with the level of information they receive about their treatments. Biologic therapy appears to be an important advance, with patients receiving this form of treatment having improved symptoms and productivity. However, patients still report unmet needs. Thus further research, and perhaps new and more effective therapies, along with better education and multidisciplinary collaboration, are required to improve outcomes.


The cyanobacterial tRNA(Leu) (UAA) intron: evolutionary patterns in a genetic marker.
Cyanobacterial tRNA(Leu) (UAA) intron sequences from natural populations of Nostoc and other cyanobacteria were compared. Variation between the different introns was not randomly distributed but strongly restricted by the secondary and tertiary structure of the intron. Although all Nostoc sequences examined shared high similarity, differences were observed in one stem-loop. This stem-loop could be divided into two classes, both built up from two base pairing heptanucleotide repeats. Size variation was primarily caused by different numbers of repeats, but some strains also contained additional sequences in this stem-loop not following the heptanucleotide repeat motif. Several sequences showing similarity with these additional sequences were identified in the Nostoc punctiforme genome. Furthermore, the regions flanking these sequences contained the same, or similar, heptanucleotide repeats as those flanking the corresponding sequences in the intron. It is proposed that both slipped strand mispairing during replication and homologous recombination among different loci in the genome are important processes causing variation between introns.


Absorption of CO2 in algal mass culture systems: a different characterization approach.
For the characterization of CO(2) absorption in aerated microalgal culture systems, a different approach based on K(L)a(O(2)) determination and transformation was studied. To confirm the validity of this method, the influence of reactions between CO(2) and compounds (OH(-), H(2)O, and NH(3)) present in the culture medium upon the absorption mechanism was evaluated under different physical and chemical culture conditions. Under these conditions, knowledge of the relative magnitudes of the diffusion and reaction kinetics permitted the evaluation of their relative importance. For the determination of the parameters required for the calculation of the CO(2) absorption constant, empirical correlations for K(L) (0) and a were used that had been previously verified with experimental data for O(2) absorption. Since, for the conditions studied, the absorption rate was shown to be independent of the chemical reactions taking place in the liquid phase, the K(L)a for CO(2) could be directly related to the K(L)a for O(2) by a simple factor that took into account the difference in aqueous diffusivity of the two gases. Thus, using methods developed for determining O(2) absorption in gas-liquid contactors, it is possible to adequately characterize CO(2) absorption for laboratory and pilot scale algal production systems.


Enhanced transport of plant-produced rabies single-chain antibody-RVG peptide fusion protein across an in cellulo blood-brain barrier device.
The biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood-brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single-chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv-RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv-RVG fusion. Both ScFv and ScFv-RVG fusion molecules had potent neutralization activity against RABVin cellulo. The ScFv-RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant-produced ScFv-RVGP fusion could translocate across the cells. This study indicates that the plant-produced ScFv-RVGP fusion protein was able to cross the in celluloBBB and neutralize RABV.


Tetraphasic actions of local anesthetics on central nervous system electrical activities in cats.
The effects of seven local anesthetics, mepivacaine, bupivacaine, etidocaine, dibucaine, prilocaine, procaine, and tetracaine, on the central nervous system (CNS) electrical activities were studied in five cats with each agent. Brain electrodes were implanted chronically in the cortex, amygdala, hippocampus, and midbrain reticular formation. The cortical, amygdala, and hippocampus electroencephalograms (EEGs), reticular multiunit activity (R-MUA), and heart rate were recorded. Drugs were administered intravenously with constant rates of equipotent doses until EEG seizures appeared. Effects of lidocaine, 1 mg.kg-1.min-1, were studied for comparison. The rates of infusion were: mepivacaine, 1 mg.kg-1.min-1; procaine, 4 mg.kg-1.min-1; bupivacaine and tetracaine, 0.25 mg.kg-1.min-1; etidocaine, 0.5 mg.kg-1.min-1; dibucaine, 0.15 mg.kg-1.min-1; and prilocaine, 3 mg.kg-1.min-1. The effects of 10-15 times higher rates of infusion were also studied in two cats with each drug. During the slow rates of infusion, a tetraphasic sequence of changes, common to all agents, was observed: the initial stage represented by diffuse EEG slowing and a suppression of the R-MUA; the second stage by low voltage fast wave EEG and an activation of the R-MUA; the third stage by reappearance of slow wave EEG and a suppression of the R-MUA; and the fourth stage by an epileptiform EEG and an activation of the R-MUA. These changes in EEG were not typical in some cats administered procaine, bupivacaine, prilocaine, and dibucaine. During the high rates of infusion, suppressive stages in the R-MUA were less dominant and activations dominated. High rates of infusion of mepivacaine produced sudden epileptic activities in EEG. Tetracaine, procaine, etidocaine, and bupivacaine in the high rates of infusion produced slow waves for a short period, prior to seizure activities in the EEG. Dibucaine or prilocaine in high rates of infusion could not produce seizure activities in the EEG, but slow waves and isoelectrical EEG, which were accompanied with idioventricular rhythm followed by ventricular fibrillation. All local anesthetics have similar tetraphasic CNS actions and whether the expression of CNS intoxication with subconvulsive doses is excitation or suppression may possibly be dependent on the brain drug level and its rate of increase.


Theory for controlling individual self-propelled micro-swimmers by photon nudging I: directed transport.
Photon nudging is a new experimental method which enables the force-free manipulation and localization of individual self-propelled artificial micro-swimmers in fluidic environments. It uses a weak laser to stochastically and adaptively turn on and off the swimmer's propulsion when the swimmer, through rotational diffusion, points towards or away from its target, respectively. This contribution presents a theoretical framework for the statistics of both 2D and 3D controls. The main results are: the on- and off-time distributions for the controlling laser, the arrival time statistics for the swimmer to reach a remote target, and how the experimentally accessible control parameters influence the control, e.g., the optimal acceptance angle for directed transport. The results are general in that they are independent of the propulsion or the actuation mechanisms. They provide a concrete physical picture for how a single artificial micro-swimmer could be navigated under thermal fluctuations-insights that could also be useful for understanding biological micro-swimmers.


Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells.
Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In this study, the underlying mechanism of xylopine cytotoxicity was assessed in human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in different cancer cell lines in monolayer cultures and in a 3D model of cancer multicellular spheroids formed from HCT116 cells. Typical morphology of apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA fragmentation, loss of the mitochondrial transmembrane potential, and increased phosphatidylserine externalization and caspase-3 activation were observed in xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-α), reduced xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by the p53-independent pathway. Treatment with xylopine also caused an increase in the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen peroxide and nitric oxide, but not superoxide anion, and reduced glutathione levels were decreased in xylopine-treated HCT116 cells. Application of the antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. In conclusion, xylopine has potent cytotoxicity to different cancer cell lines and is able to induce oxidative stress and G2/M phase arrest, triggering caspase-mediated apoptosis by the p53-independent pathway in HCT116 cells.


Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis.
Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous "operational tolerance" can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation by a classical statistical microarray analysis and, in the second part, by a nonstatistical analysis.


Biological correlates of mental stress related to anticipated caesarean section.
The relationships between self-reported assessments of acute anxiety and several biochemical and physiological indicators of stress reaction were investigated in pregnant women at term in connection with spinal analgesia for caesarean section. Fear and apprehension were statistically significantly associated only with blood pressure and with an increase in heart rate from the previous day. The subjective estimate of the quality of the preoperative night's sleep was negatively associated with biochemical plasma and cerebrospinal fluid (CSF) measures of sympatho-adrenal activity. The previously reported negative correlation between body height and 5-hydroxyindoleacetic acid (5-HIAA, an indicator of serotonin metabolism) in lumbar CSF was confirmed. The concentration of 5-HIAA in CSF was positively correlated with the levels of other acidic monoamine metabolites and cortisol in CSF. It is concluded that hormone and monoamine metabolite measurements in CSF and plasma have only limited usefulness as quantitative indicators of the intensity of preoperative fear and anxiety.


Adsorption of enzymes on krill chitin modified with carbon disulfide.
Krill chitin modified with carbon disulfide was used as a support of enzymes. The dithiocarbamino groups created after reaction of CS(2) with chitinous NH(2) can participate in binding the enzymes without denaturation and loss in activity. The stability of these bonds depends on pH and decreases gradually at ionic strengths higher than 0.01. Chitin modified with CS(2) can be used as a support for enzymes having high activity at mild conditions of pH and ionic strength.


Staphylococcus aureus manganese transport protein C (MntC) is an extracellular matrix- and plasminogen-binding protein.
Infections caused by Staphylococcus aureus--particularly nosocomial infections--represent a great concern. Usually, the early stage of pathogenesis consists on asymptomatic nasopharynx colonization, which could result in dissemination to other mucosal niches or invasion of sterile sites, such as blood. This pathogenic route depends on scavenging of nutrients as well as binding to and disrupting extracellular matrix (ECM). Manganese transport protein C (MntC), a conserved manganese-binding protein, takes part in this infectious scenario as an ion-scavenging factor and surprisingly as an ECM and coagulation cascade binding protein, as revealed in this work. This study showed a marked ability of MntC to bind to several ECM and coagulation cascade components, including laminin, collagen type IV, cellular and plasma fibronectin, plasminogen and fibrinogen by ELISA. The MntC binding to plasminogen appears to be related to the presence of surface-exposed lysines, since previous incubation with an analogue of lysine residue, ε-aminocaproic acid, or increasing ionic strength affected the interaction between MntC and plasminogen. MntC-bound plasminogen was converted to active plasmin in the presence of urokinase plasminogen activator (uPA). The newly released plasmin, in turn, acted in the cleavage of the α and β chains of fibrinogen. In conclusion, we describe a novel function for MntC that may help staphylococcal mucosal colonization and establishment of invasive disease, through the interaction with ECM and coagulation cascade host proteins. These data suggest that this potential virulence factor could be an adequate candidate to compose an anti-staphylococcal human vaccine formulation.


Dehydration decreases saliva antimicrobial proteins important for mucosal immunity.
The aim of the study was to investigate the effect of exercise-induced dehydration and subsequent overnight fluid restriction on saliva antimicrobial proteins important for host defence (secretory IgA (SIgA), α-amylase, and lysozyme). On two randomized occasions, 13 participants exercised in the heat, either without fluid intake to evoke progressive body mass losses (BML) of 1%, 2%, and 3% with subsequent overnight fluid restriction until 0800 h in the following morning (DEH) or with fluids to offset losses (CON). Participants in the DEH trial rehydrated from 0800 h until 1100 h on day 2. BML, plasma osmolality (Posm), and urine specific gravity (USG) were assessed as hydration indices. Unstimulated saliva samples were assessed for flow rate (SFR), SIgA, α-amylase, and lysozyme concentrations. Posm and USG increased during dehydration and remained elevated after overnight fluid restriction (BML = 3.5% ± 0.3%, Posm = 297 ± 6 mosmol·kg⁻¹, and USG = 1.026 ± 0.002; P < 0.001). Dehydration decreased SFR (67% at 3% BML, 70% at 0800 h; P < 0.01) and increased SIgA concentration, with no effect on SIgA secretion rate. SFR and SIgA responses remained unchanged in the CON trial. Dehydration did not affect α-amylase or lysozyme concentration but decreased secretion rates of α-amylase (44% at 3% BML, 78% at 0800 h; P < 0.01) and lysozyme (46% at 3% BML, 61% at 0800 h; P < 0.01), which were lower than in CON at these time points (P < 0.05). Rehydration returned all saliva variables to baseline. In conclusion, modest dehydration (~3% BML) decreased SFR, α-amylase, and lysozyme secretion rates. Whether the observed magnitude of decrease in saliva AMPs during dehydration compromises host defence remains to be shown.


Chimeric receptor analyses of the interactions of the ectodomains of ErbB-1 with epidermal growth factor and of those of ErbB-4 with neuregulin.
A series of chimeric receptors was generated between the epidermal growth factor (EGF) receptor, ErbB-1, and its homologue, ErbB-4, to investigate the roles of the extracellular domains (I-IV) in the ligand specificities. As compared with ErbB-1 and the chimeras with both domains I and III of ErbB-1, the chimeras with only one of these domains exhibited reduced binding of 125I-labeled EGF. Particularly, the contribution of domain III was appreciably larger than that of domain I of ErbB-1 in 125I-labeled EGF binding. Nevertheless, the chimeras with domain III of ErbB-1 and domain I of ErbB-4 were prevented from binding to 125I-labeled EGF competitively by the ErbB-4 ligand, neuregulin (NRG). On the other hand, NRG did not compete with 125I-labeled EGF for binding to the chimeras with the ErbB-1 domain I and the ErbB-4 domain III. Therefore, NRG binding to ErbB-4 depends much more on domain I than on domain III. With respect to autophosphorylation and subsequent ERK activation, EGF activated the chimeras with either domain I or III of ErbB-1. In contrast, NRG activated the chimeras with the ErbB-4 domain I and the ErbB-1 domain III, but not those with the ErbB-1 domain I and the ErbB-4 domain III. Therefore, the relative contributions between domains I and III of ErbB-4 in the NRG signaling are different from those of ErbB-1 in the EGF signaling.


Frequent clonal relations between metastases and non-index prostate cancer lesions.
Primary prostate cancer lesions are clonally heterogeneous and often arise independently. In contrast, metastases were reported to share a monoclonal background. Because prostate cancer mortality is the consequence of distant metastases, prevention of metastatic outgrowth by primary tumor ablation is the main focus of treatment for localized disease. Focal therapy is targeted ablation of the primary index lesion, but it is unclear whether remaining primary lesions metastasize at a later stage. In this study, we compared copy number aberration profiles of primary prostate cancer lesions with matching pelvic lymph node metastases of 30 patients to establish clonality between a lymph node metastasis and multiple primary lesions within the same patient. Interestingly, in 23.3% of the cases, the regional metastasis was not clonally linked to the index primary lesion. These findings suggest that focal ablation of only the index lesion is potentially an undertreatment of a significant proportion of prostate cancer patients.


Rapid antidepressant effects of Yueju: A new look at the function and mechanism of an old herbal medicine.
Yueju is a traditional herbal medicine which consists of five herbs and formulated to treat depression-related syndromes 800 years ago. Yueju is still widely prescribed to treat conditions which include digestive dysfunction and depression. Recently, Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies. Because conventional antidepressants have a delayed onset in treating depression, the novelty of Yueju's rapid antidepressant effect and its underlying mechanism are of great significance both clinically and scientifically. To review the use of Yueju for treatment of mood-related syndromes, and particularly its use in depression. To evaluate recent evidence of Yueju rapid antidepressant actions, based on new findings at behavioral and molecular levels. To suggest direction for future studies to address further scientific issues. Reports regarding to the history and current use of Yueju are summarized. Recent progress on rapid antidepressant effects of Yueju, the crucial constituent, Gardenia jasminoides J.Ellis (GJ) and other herbs, are reviewed. The medical need for rapid antidepressant actions, as well as breakthrough findings using ketamine and its limitations are introduced. Studies with Yueju using a number of acute, subacute and chronic behavioral paradigms are compared with ketamine. Findings from clinical reports also support the rapid action of Yueju. Studies examine the contribution of the constituent herb GJ, in rapid antidepressant effects. Importantly, research into the mechanism of Yueju or GJ's antidepressant response indicate the importance of up-regulation in the neural circuit responsible for antidepressant activity, and highlight common and specific molecular signaling by Yueju that may explain why this herb formula has unique antidepressant activity. Preclinical and clinical studies demonstrate that Yueju confers rapid antidepressant effects. The common mechanisms shared both for ketamine and Yueju, as well as the novel mechanism specific to Yueju are examined. Yueju and GJ may have great clinic applicability and further more detailed studies are warranted.


A clinical study of sensitivity to sodium nitroprusside during controlled hypotensive anesthesia in young and elderly patients.
Aging has important effects on the cardiovascular system; baroreceptor reflex function decreases and the elderly are more resistant to both beta-receptor agonists and antagonists. The purpose of the present clinical study was to determine the relationship between age and sensitivity to sodium nitroprusside in 16 patients during deliberate hypotensive anesthesia by determining the blood pressure changes in young and elderly patients to incremental increases in dose of sodium nitroprusside. A dose-response curve relating change in mean blood pressure to dose of sodium nitroprusside (microgram X kg-1 X min-1) was constructed for each patient; the slope of this line is a measure of "sensitivity." The change in mean arterial blood pressure per microgram X kg-1 X min-1 nitroprusside dose (i.e., slope), showed a significant correlation with age (r = 0.766, P less than 0.001), demonstrating that sensitivity to sodium nitroprusside increases with advancing years. The maximum change in heart rate produced by nitroprusside showed a reciprocal correlation with age (r = -0.791, P less than 0.001). There was no significant correlation between age and maximum change in plasma norepinephrine or epinephrine concentrations during nitroprusside infusion. The increased sensitivity to nitroprusside might have been due to diminished baroreflex activity, resistance of cardiac adrenergic receptors to catecholamine stimulation, or alteration in sensitivity to the direct vasodilating effects of sodium nitroprusside. Whatever the mechanism, however, this clinical study has shown that lower doses of nitroprusside should be used in elderly patients to achieve the same degree of hypotension achieved in younger patients.


Toward ultrafast magnetic depth profiling using time-resolved x-ray resonant magnetic reflectivity.
During the last two decades, a variety of models have been developed to explain the ultrafast quenching of magnetization following femtosecond optical excitation. These models can be classified into two broad categories, relying either on a local or a non-local transfer of angular momentum. The acquisition of the magnetic depth profiles with femtosecond resolution, using time-resolved x-ray resonant magnetic reflectivity, can distinguish local and non-local effects. Here, we demonstrate the feasibility of this technique in a pump-probe geometry using a custom-built reflectometer at the FLASH2 free-electron laser (FEL). Although FLASH2 is limited to the production of photons with a fundamental wavelength of 4 nm ( ≃ 310 eV ), we were able to probe close to the Fe L 3 edge ( 706.8 eV ) of a magnetic thin film employing the third harmonic of the FEL. Our approach allows us to extract structural and magnetic asymmetry signals revealing two dynamics on different time scales which underpin a non-homogeneous loss of magnetization and a significant dilation of 2 Å of the layer thickness followed by oscillations. Future analysis of the data will pave the way to a full quantitative description of the transient magnetic depth profile combining femtosecond with nanometer resolution, which will provide further insight into the microscopic mechanisms underlying ultrafast demagnetization.


Negative differential conductance and hot phonons in suspended nanotube molecular wires.
Freely suspended metallic single-walled carbon nanotubes (SWNTs) exhibit reduced current carrying ability compared to those lying on substrates, and striking negative differential conductance at low electric fields. Theoretical analysis reveals significant self-heating effects including electron scattering by hot nonequilibrium optical phonons. Electron transport characteristics under strong self-heating are exploited for the first time to probe the thermal conductivity of individual SWNTs (approximately 3600 W m-1 K-1 at T=300 K) up to approximately 700 K, and reveal a 1/T dependence expected for umklapp phonon scattering at high temperatures.