Neuron-like differentiation of PC12 cells treated with media conditioned by either sciatic nerves, optic nerves, or Schwann cells.
In previous works we reported the finding of neurotrophic activity in a serum-free Dulbecco's modified Eagle's medium conditioned by rat sciatic nerves, previously maintained in culture for 11 days. This medium produces rapid neuron-like differentiation of cultured PC12 cells, as revealed by an increase in the size of the cell body and by the extension of short and/or long neurites by most of the cells. Neuregulin present in the conditioned medium was demonstrated to play a key role in the observed differentiation. In the present work, taking into consideration those latter results, the neurotrophic activity of conditioned media prepared with sciatic and optic nerves cultured during days 1-4 and 9-12 were studied. Evaluation of the trophic activities of those media revealed an opposite timing in the activities of sciatic and optic nerves conditioned media. The activity of the sciatic nerve was not observed in the 1-4-day period, increasing then up to the 9-12-day period. On the contrary, the optic nerve conditioned medium was active in the 1-4-day period, decreasing down to the 9-12-day period. These results led us to explore the contribution of the different cellular constituents of those nerves to their neurotrophic properties. As a first step in that direction we also investigated the neurotrophic activity of media conditioned during 12 days by cultured Schwann cells isolated from rat sciatic nerves. The Schwann cell conditioned media did produce a rapid differentiation of the PC12 cells similar to that caused by the sciatic nerve conditioned medium, though of a lower magnitude. Variations in the trophic activities of the conditioned media used in the present work is discussed taking into consideration the production of trophic and inhibitory factors by the peripheral and central glial cells. The role played by the optic nerve glia and myelin is being investigated at present.


Increased levels of bovine serum albumin antibodies in patients with type 1 diabetes and celiac disease-related antibodies.
To detect the presence of antibodies against bovine serum albumin in a cohort of Spanish patients with type 1 insulin-dependent diabetes. Antibodies were measured using an in-house enzyme-linked immunosorbent assay test in 80 patients with type 1 diabetes, subdivided according to the presence or absence in their serum of celiac disease-related antibodies. For comparison, 30 patients with celiac disease (nondiabetic), 13 patients with autoimmune thyroiditis, and 45 healthy volunteers were used. Thirty-one percent of patients with diabetes yielded a positive result, with a mean value of 26.1 +/- 21.8 arbitrary units (AU). If the group was split into those with celiac disease-related antibodies and those lacking them, the percentages were 53% and 25%, respectively, with a mean value of 39.6 +/- 28.4 AU and 22.4 +/- 18.3 AU (P = 0.003), respectively. Seventy-three percent of celiac patients showed bovine serum albumin antibodies with a mean level of 38.8 +/- 27.7 AU, comparable to that of patients with diabetes with celiac antibodies, but higher than the group lacking them (P = 0.001). Although 46% of patients with autoimmune thyroiditis had positive results, the level detected (22.1 +/- 8.7 AU) was significantly lower than that recorded in patients with type 1 diabetes who had celiac disease antibodies (P = 0.04) and celiac patients (P = 0.04). Healthy volunteers showed no antibodies against bovine serum albumin. These data suggest that bovine serum albumin antibodies appears in patients with a compromised epithelial permeability, and they reflect a general defect in the process of immunologic tolerance associated with a predisposition to autoimmunity, rather than immunity specific to beta cells.


Treatment of cutaneous T cell lymphoma: current status and future directions.
The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis fungoides and Sezary syndrome, has been in a state of continual change over recent decades, as new therapies are constantly emerging in the search for more effective treatments for the disease. However, prognosis and survival of patients with CTCL remains dependent upon overall clinical stage (stage IA-IVB) at presentation, as well as response to therapy. Past therapies have been limited by toxicity or the lack of consistently durable responses, and few treatments have been shown to actually alter survival, especially in the late stages of disease. Even aggressive chemotherapy has not been shown to improve overall survival compared to conservative sequential therapy in advanced disease, and adds the risk of immunosuppressive complications. Over the last decade, extracorporeal photopheresis has been the only single treatment that has been shown to improve survival in patients with Sezary syndrome, although its true efficacy and place in combination therapy remain unclear. Much of the focus of current research has been on combinations of skin-directed therapies and biological response modifiers, which improve response rates. The results of various trials over the years have also brought into favor the use of post-remission maintenance therapy with topical corticosteroids, topical mechlorethamine (nitrogen mustard), interferon-alpha, or phototherapy to prevent disease relapse. Recent novel developments in CTCL therapy include oral bexarotene, a retinoid X receptor-selective retinoid that has activity in all stages of CTCL, and the topical gel formulation of bexarotene, which plays a role in treating localized lesions. US Food and Drug Administration (FDA)-approved, oral systemic bexarotene has the advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day, and avoids immunosuppression and risk of central line and catheter-related infectious complications that are associated with other systemic therapies. Monitoring of triglycerides and use of concomitant lipid-lowering agents and thyroid replacement is required in most patients. Also recently FDA-approved, denileukin diftitox is the first of a novel class of fusion toxin proteins and is selective for interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in CTCL. Denileukin diftitox is associated with capillary leak syndrome in 20 to 30% of patients, which may be ameliorated by hydration and corticosteroids. Higher response rates are possible by combining bexarotene with "statin" drugs and active CTCL therapies. Studies are being conducted on combining bexarotene and denileukin diftitox with other modalities. Biological response modifier therapies that are in current or future investigational trials include topical tazarotene, pegylated interferon, interleukin-2, and interleukin-12. At the forefront of systemic chemotherapy development, pegylated liposomal doxorubicin, gemcitabine, and pentostatin appear to have the greatest potential for success in CTCL therapy. Bone marrow transplantation, which is currently limited by the risk of graft-versus-host disease, offers the greatest potential for disease cure. Further developments for CTCL may include more selective immunomodulatory agents, vaccines, and monoclonal antibodies.


Strain-specific postnatal changes in the activity and tissue levels of protein kinase C.
The specific activity of protein kinase C from adult mouse lung and spleen was higher than in the corresponding tissues from neonatal mice. BALB/cBy mice had higher lung and spleen protein kinase C activities at both ages than did A/J mice, and the extent of this strain difference increased with age. These activity differences reflected the tissue levels of the 80 kD form of protein kinase C, as determined by quantitative immunoblotting. These genetic and ontogenetic differences provide an interesting model with which to study the regulation of protein kinase C gene expression.


Participant satisfaction with a community-based medication synchronization program.
To assess participant satisfaction with a community pharmacy-based medication synchronization program. A single location of a grocery store pharmacy chain in the Kansas City metropolitan area. A medication synchronization program, Time My Meds (TMM), was implemented in 1 of 20 community pharmacies within the grocery store chain. Current pharmacy patients taking three or more chronic medications were recruited to enroll in the medication synchronization program. After at least 3 months of enrollment in TMM, participants were invited to complete a paper survey to assess satisfaction with the program. Data were collected on overall participant satisfaction with the TMM program. A 10-statement survey gathered demographic information and assessed participant satisfaction using a 5-point Likert scale (1, strongly disagree, to 5, strongly agree). Data collected from 48 surveys were analyzed. No statistical differences in participant satisfaction were found when considering age, education, income, number of medications at pick-up, or number of monthly trips to the pharmacy prior to program enrollment. Median scores for individual survey items were all 5 out of 5 (strongly agree) using a 5-point Likert scale. Participants were highly satisfied with the medication synchronization program. These results, if expanded to a wider population, might provide valuable information for continued justification and implementation of this type of service in community pharmacies.


Ongoing compound field potentials from octopus brain are labile and vertebrate-like.
Ongoing electrical activity was recorded from the brain of the virtually intact, semirestrained, unanesthetized octopus by semimicroelectrodes thrust through the cartilage into the optic, vertical or basal lobe. With flexible lead-in wires such electrodes were carried by and moved with the head without causing movement artifacts. Controls suggest that the activity reported comes from the brain; it is reversibly flattened by doses of urethane that do not embarrass respiration. Muscle potentials are only troublesome on occasion. Seen through a wideband filter, neuronal spikes are usually small or below noise level under these conditions; slow waves (1-70 Hz) dominate, with a maximum less than 25 Hz, usually less than 10 Hz and no consistent sharp peaks. The fall in power above ca. 25 Hz is usually slower than in the typical vertebrate EEG but the average power spectrum is much more like those of vertebrate brains than of cerebral ganglia of other invertebrates (insect, crustacean, gastropod). Variance among sample epochs is large, e.g. short spells may have relatively much more low frequency (less than 25 Hz) or more 'hashy' high frequency (greater than 50 Hz) energy; there may be runs of spikes. Fluctuation in the composition of ongoing activity is graphically shown by writing out in parallel the outputs of several narrow band (one octave) filters; this shows irregular low frequency waxing and waning of the amplitude in each band. The envelopes were computed and their peak power is around 1 Hz or lower; the waxing and waning in the several bands is sometimes strongly correlated, especially when the envelope amplitude is large and slow. Optic lobe activity tends usually to be faster, with more small spikey hash than in the vertical lobe. The described electrical activity of the brain is strikingly episodic; it is recorded during seconds or minutes separated by long intervals of nearly electrical silence (10-40 dB lower power; the difference larger at frequencies greater than 20 Hz). Active and quiet periods are usually not correlated with differences in visible behavior. Under my conditions the animal is usually not moving except for quiet ventilation and occasional local writhing of an arm. Potentials evoked by single flashes of light (0.2-1/sec) are conspicuous in the optic but not in the vertical lobe. They form a sequence of large, slow waves; the first peak may be at about 40 msec, others up to at least 400 msec.(ABSTRACT TRUNCATED AT 400 WORDS)


Cervical Carcinomas With Neuroendocrine Differentiation: A Report of 28 Cases With Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin With Coexisting Squamous and Adenocarcinomas.
Cervical neuroendocrine carcinomas are rare, aggressive tumors and their immunohistochemical features and clonal relationship to coexisting tumors are incompletely described. Twenty-eight cases were identified (17 small cell, 9 large cell, and 2 mixed), 10 of which had an invasive squamous or adenocarcinoma component. Staining for synaptophysin, chromogranin A, TTF1, c-kit, CD44, and p16 was performed. Analyses for loss of heterozygosity (LOH) at 5 polymorphic microsatellite markers (D3S1300, D9S171, D11S914, D13S319, and TP53) and X-chromosome inactivation were performed. Of 17 cases with available blocks, 13 (76%) were synaptophysin+, 8 (47%) were chromogranin A+, 8 (47%) were TTF1+, 7 (41%) were c-kit+, and 6 (35%) were CD44+. Strong patchy or strong diffuse p16 staining was seen in all cases. LOH and X-chromosome inactivation analysis were performed for 17 cases, 8 of which had a coexisting squamous or adenocarcinoma component. Five of the 8 (63%) cases with 2 components showed allelic loss in both components. All 5 of these cases demonstrated identical LOH between the neuroendocrine and squamous or adenocarcinoma components. Nonrandom X-chromosome inactivation was seen in the neuroendocrine and other components in 4 of the 8 cases. In all 4 cases the pattern of inactivation was identical between the 2 components. Cervical neuroendocrine carcinomas have features similar to other extrapulmonary neuroendocrine carcinomas, including expression of TTF1, c-kit, and CD44. Consistent staining for p16 is also seen. Concordant genetic alterations support common clonal origin for neuroendocrine carcinomas with a coexisting squamous or adenocarcinoma component.


Prosthetic heart valve selection in women of childbearing age with acquired heart disease: a case report.
The problem of prosthetic heart valve selection in fertile women with acquired heart defects remains crucial in modern cardiology. Mechanical heart valves require lifelong indirect anticoagulant therapy, which has significant fetal toxicity and is unacceptable for women planning pregnancy. Bioprosthetic heart valves are the best choice for fertile women; however, their durability is limited, and reoperations are required. We describe the clinical case of a 21-year-old Russian woman with infectious endocarditis who underwent heart valve replacement with an epoxy-treated mitral valve prosthesis. Epoxy-treated bioprosthetic heart valves can be used without long-term anticoagulant therapy because of their optimal hemodynamic functional parameters. Moreover, their high thromboresistance and resistance to infection improve patients' quality of life in their late postoperative period. We recommend these valves both in older persons and in young patients including women who are planning pregnancy.


Unification of medicines and excipients: The roles of natural excipients for promoting drug delivery.
Drug delivery systems (DDSs) formed by natural active compounds be instrumental in developing new green excipients and novel DDS from natural active compounds (NACs). 'Unification of medicines and excipients'(UME), the special inherent nature of the natural active compounds, provides the inspiration and conduction to achieve this goal. This review summarizes the typical types of NACs from herbal medicine, such as saponins, flavonoids, polysaccharides, etc. that act as excipients and their main application in DDS. The comparison of the drug delivery systems formed by NACs and common materials and the primary formation mechanisms of these NACs are also introduced to provide a deepened understanding of their performance in DDS. Many natural bioactive compounds, such as saponins, polysaccharides, etc. have been used in DDS. Diversity of structure and pharmacological effects of NACs turn out the unique advantages in improving the performance of DDSs like targeting ability, adhesion, encapsulation efficiency(EE), etc. and enhancing the bioavailability of loaded drugs.


Novel GdTaO4 phase for efficient photocatalytic degradation of organic dye under visible light irradiation: An X-ray spectroscopic investigation.
The novel GdTaO4 phase exhibits good photocatalytic activity under visible light irradiation and holds great promise for the removal of organic dyes from industrial wastes. The GdTaO4 samples were synthesized using the hydrothermal and calcination process with different weight ratios of gadolinium nitrate hydrate (G) and tantalum pentachloride (T), and their structural studies confirmed the formation of the GdTaO4 (GT) phase. Among the samples, GT-4 (with a weight ratio of 4:1) exhibited the highest photocatalytic activity for the degradation of Methyl Orange (MO) dye under visible light irradiation. To enhance the photocatalytic performance, H2O2 was used as a green additive, and the photocatalytic abilities were examined by varying dye types and concentrations. X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) revealed the local atomic and electronic structures around Ta and Gd and highlighted the contribution of Gd3+ to the GT system, which is a crucial factor in supporting the enhanced photocatalytic performance. Moreover, in-situ XAS at Gd M5-edge and O K-edge were examined under illumination/dark conditions to explore the electronic structures of photo-excited electron transition in the photocatalytic process. The analytical results provided strong evidence correlating the electronic structure and photocatalytic property of the GT. This study demonstrates that GdTaO4 exhibits good photocatalytic activity under visible light irradiation, making it a promising new Ta-based photocatalyst for the effective removal of organic dyes from industrial wastes.


Distribution of adrenomedullin and proadrenomedullin N-terminal 20 peptide immunoreactivity in the pituitary gland of the frog Rana perezi.
Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two multifunctional peptides processed from a common precursor which have been described in numerous mammalian organs, including the pituitary gland. Previous studies have found AM immunoreactivity in neurohypophysis nerve fibers of amphibian pituitary. In the present study, immunocytochemical and Western blot analysis in the pituitary gland of the amphibian Rana perezi demonstrated in the adenohypophysis both AM and PAMP. AM-like immunoreactivity was found in a moderate number of endocrine cells of the pars distalis. In the neurohypophysis, AM was observed not only in nerve fibers of pars nervosa and axonal projections innervating the pars intermedia, but also in the outer zone of the median eminence. PAMP staining was observed in numerous endocrine cells scattered all over the pars distalis and in some cells of the pars tuberalis, but not in the neurohypophysis. In order to compare the quantity of AM and PAMP immunoreactivity between pars distalis of female and male specimens, an image analysis study was done. Significant differences for AM immunoreactivity (p<0.001) between sexes was found, the males showing higher immunostained area percentage. Differences of PAMP immunoreactivity were not significant (p=0.599). Western blot analysis detected bands presumably corresponding to precursor and/or intermediate species in the propeptide processing.


Study of embryotoxicity of Perovskia abrotanoides, an adulterant in folk-medicine, during organogenesis in mice.
Perovskia abrotanoides is a medicinal herb which traditionally has been used as a topical application to treat leishmaniasis in Iran. Due to similarities of the flowers of Perovskia abrotanoides and Echium species, it is added as an adulterant to Echium preparations in Iran. Echium flowers have been used in Iranian traditional medicine as an "anti-stress", tranquilizer, and energizer drink, fighting common cold and bronchitis particularly during pregnancy. In this study, the in vivo embryotoxicity of 0.125 and 0.25 g/kg of ethanolic and aqueous extracts of Perovskia abrotanoides during organogenesis in mice has been investigated. Maternal body weights were recorded and pregnant females were observed daily throughout gestation. After cesarean section, fetuses were weighed, lengthed and examined for gross external malformations. Others were fixed then stained with Alcian blue and Alizarin red to view any skeletal malformations. Our results indicated that this herb causes minimal maternal toxicity, while resorption, stillborn, fetal malformations including polydactyly, spina bifida, aglossia, tarsal extensor, gastroschisis, and numerous skeletal abnormalities were detected particularly in the ethanolic extract groups. Specific skeletal abnormalities based on type of extract were also observed. Since Perovskia abrotanoides is widely used in traditional medicine intentionally or inadvertently, it is advisable its use during pregnancy should be avoided and strict regulations are imposed to prevent its addition to commercial preparations of other herbal products.


Role of preoperative cycloplegic refraction in LASIK treatment of hyperopia.
Previous studies have suggested that, to improve refractive predictability in hyperopic LASIK treatments, preoperative cycloplegic or manifest refraction, or a combination of both, could be used in the laser nomogram. We set out to investigate (1) the prevalence of a high difference between manifest and cycloplegic spherical equivalent in hyperopic eyes preoperatively, and (2) the related predictability of postoperative keratometry. Retrospective cross-sectional data analysis of consecutive treated 186 eyes from 186 consecutive hyperopic patients (mean age 42 [±12] years) were analyzed. Excimer ablation for all eyes was performed using a mechanical microkeratome (SBK, Moria, France) and an Allegretto excimer laser platform. Two groups were defined according to the difference between manifest and cycloplegic spherical equivalent which was defined as ≥1.00 diopter (D); the data was analyzed according to refractive outcome in terms of refractive predictability, efficacy, and safety. In 24 eyes (13 %), a preoperative difference of ≥1.00D between manifest spherical equivalent and cycloplegic spherical equivalent (= MCD) occurred. With increasing preoperative MCD, the postoperative achieved spherical equivalent showed hyperopic regression after 3 months. There was no statistically significant effect of age (accommodation) or optical zone size on the achieved spherical equivalent. A difference of ≥1.00D occurs in about 13 % of hyperopia cases. We suggest that hyperopic correction should be based on the manifest spherical equivalent in eyes with preoperative MCD <1.00D. If the preoperative MCD is ≥1.00D, treatment may produce manifest undercorrection, and therefore we advise that the patient should be warrned about lower predictability, and suggest basing conclusions on the arithmetic mean calculated from the preoperative manifest and cycloplegic spheres.


The comparative potency of cholesterol crystallization-effector proteins in supersaturated model bile systems: association with vesicle transformation.
Various proteins which affect cholesterol crystallization are known to be present in bile, although the relative potency of their action is yet to be established. In this study, we evaluated the comparative potency of nucleating-effector proteins using a recently developed method for quantitative assessment of vesicle transformation in supersaturated model bile systems, to partially characterize mechanisms of their action. Concanavalin A-bound glycoproteins isolated from human gall-bladder bile shortened cholesterol crystallization time by 40% and increased cholesterol growth rate and final crystal mass by 161 and 19%, respectively, when compared to the control. In addition, immunoglobulins isolated from human gall-bladder bile increased cholesterol growth rate by 9%, but showed no significant effect on cholesterol crystallization time and final crystal mass. In contrast, human serum apolipoproteins A-I and B reduced cholesterol growth rate by 26 and 31% and reduced final crystal mass by 12 and 21%, but did not affect cholesterol crystallization time. Gel permeation chromatography revealed that proteins were distributed to both vesicles and bile salt micelles, but that no marked redistribution of lipids was caused by addition of these proteins. Furthermore, no significant difference in crystal structure was observed by video-enhanced contrast microscopy. These results indicate that nucleating-effector substances tested in this study may modulate vesicular cholesterol-holding capacity, thus affecting cholesterol crystallization. Such modulation is based upon the protein-vesicle association which defines the physico-chemical metastability of vesicular cholesterol.


Imaging spectrum, associations and outcomes in acute invasive fungal rhino-ocular-cerebral sinusitis in patients with COVID-19 pneumonia.
Coronavirus Disease 2019 (COVID-19) has been speculated to enhance mucormycosis infection due to its immune-altering pathophysiology. Early identification of high-morbidity conditions is crucial for optimal treatment and improved outcomes. A retrospective study was conducted on 63 patients with clinical and microbiological evidence of rhino-ocular-cerebral mucormycosis, who had a history of COVID-19 infection. The clinical, demographic, and imaging data were retrieved and analyzed. Descriptive statistics (mean [SD] and frequency [%]) were used to describe important characteristics across audit cycles. Out of 63 patients, 54 (85.71%) patients had associated comorbidities, with diabetes mellitus being common comorbidity and all patients had received injectable and/or oral corticosteroids. Imaging showed nasal and paranasal sinus, perisinus, maxillary alveolar arch, and hard palate involvement in 62 (98.41%), 33 (52.38%), 5 (7.94%) and 5 (7.94%) patients, respectively. Orbital involvement was seen in 24 (38.10%) patients. Skull base involvement was seen in 11 (17.46%) patients, and intracranial extension of disease was present in 11 (17.46%) patients. A total of 16 patients were on mechanical ventilation, of whom 3 succumbed. The mean (standard deviation [SD]) intensive care unit (ICU) stay was 13.2 days (6.8) for 5 patients who succumbed and 6.4 days (4.6) for 30 patients who survived (P value = 0.008). Cross-sectional imaging not only provides the extent of disease spread but also plays a vital role in providing a surgical roadmap to treating surgeons and in predicting prognosis in patients with invasive fungal infections.


"Candy wrapper" effect after drug-eluting stent implantation: déjà vu or stumbling over the same stone again?
Encouraging results have been obtained with drug-eluting stents (DESs) to prevent restenosis following PCI. However, DESs are not immune from restenosis and we describe a case of "candy wrapper" effect, commonly observed with intracoronary brachytherapy (IBT). In this article, we review the common drawbacks of DES and IBT and their prevention.


Comparison of the anterior and posterior mitral isthmus ablation lines in patients with perimitral annulus flutter or persistent atrial fibrillation.
Catheter ablation of left atrial linear lesions is an effective treatment option for perimitral flutter and is often used as a substrate modification approach for persistent atrial fibrillation. The two most popular mitral isthmus lines are those of the anterior or the posterior mitral isthmus. A comparison of these two mitral isthmus ablation approaches is still pending. Patients undergoing catheter ablation either at the anterior or the posterior mitral isthmus were included. Procedural success, conduction block, procedure durations, complications, and the necessity of a coronary sinus ablation were analyzed. We investigated 80 consecutive patients, 40 (50%) with an anterior and 40 (50%) with a posterior mitral isthmus line. Twenty (25.0%) patients had perimitral annulus flutter; the remainder of the patients had persistent atrial fibrillation. Bidirectional conduction block was achieved in the same proportion in the anterior group (36; 90.0%) as it was in the posterior group (30; 75.0%) (statistically insignificant). Duration of procedure (18 ± 12 vs. 34 ± 24 min, p = 0.001), radiofrequency application (11 ± 7 vs. 18 ± 11 min, p = 0.004), and fluoroscopy (2 ± 2 vs. 8 ± 8 min, p < 0.001) values were all significantly lower in the anterior group. Only patients in the posterior line group had to be ablated via the coronary sinus 24 (60.0 %). Ablation at the anterior mitral isthmus shows the same success rate as the posterior mitral isthmus does. Catheter ablation at the anterior mitral isthmus is associated with significantly shorter procedure durations without the need of a coronary sinus ablation.


One-component quantum mechanics and dynamical leakage-free paths.
We derive an exact one-component equation of motion for the probability amplitude of a target time-dependent state, and use the equation to reformulate quantum dynamics and control for both closed and open systems. Using the one-component equation, we show that an unexpected time-dependent leakage-free path can be induced and we capture a necessary quantity in determining the effect of decoherence suppression. Our control protocol based on the nonperturbative leakage elimination operator provides a unified perspective connecting some subtle, popular, and important concepts of quantum control, such as dynamical decoupling, quantum Zeno effect, and adiabatic passage. The resultant one-component equation will promise significant advantages in both quantum dynamics and control.


Renal hemodynamic responses to hypoxemia during development: relationships to circulating vasoactive substances.
Chronically catheterized fetal lambs (n = 11, gestational age 111-139 days) and neonatal lambs (n = 20, postnatal age 4-30 days) were studied to explore during development the relationship of renal hemodynamic responses during hypoxemia to plasma epinephrine concentration (E), plasma norepinephrine concentration (NE), plasma arginine vasopressin concentration (AVP), and plasma renin activity (PRA). A low oxygen gas mixture (11.1 +/- 0.1% O2) was administered for 30 min to the pregnant ewe or neonatal lamb to induce hypoxemia with maintenance of normal arterial pCO2 and pH. Arterial blood pressure was recorded continuously and renal blood flow (RBF) was determined by the radiolabeled microsphere technique. Moderate hypoxemia (pO2 16 +/- 2 torr and 33 +/- 6 torr in fetus and neonate, respectively) induced increases in E, NE (measured by radioenzymatic assay), and AVP (measured by radioimmunoassay) in both fetus and neonate. PRA (measured by radioimmunoassay) also increased in response to hypoxemia in neonatal lambs. The change in mean arterial pressure with hypoxemia (delta MAP) was significant in fetuses (delta MAP 8 +/- 14%, p less than 0.05) but not in lambs (delta MAP 1 +/- 10%, p greater than 0.5). Similarly, the change in renal blood flow with hypoxemia (delta RBF) was significant (delta RBF -51 +/- 24%, p less than 0.001) in fetuses but not in neonatal lambs (delta RBF -9 +/- 38%, p greater than 0.1). These results reflected a change in renal vascular resistance with hypoxemia (delta RVR) that was significant in fetal lambs (delta RVR 169 +/- 168%, p less than 0.01) but not in neonatal lambs (delta RVR 51 +/- 180%, p greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)


Constitutive modeling of contact angle hysteresis.
We introduce a phase field model of wetting of surfaces by sessile drops. The theory uses a two-dimensional non-conserved phase field variable to parametrize the Gibbs free energy of the three-dimensional system. Contact line tension and contact angle hysteresis arise from the gradient term in the free energy and the kinetic coefficient respectively. A significant advantage of this approach is in the constitutive specification of hysteresis. The advancing and receding angles of a surface, the liquid-vapor interfacial energy and three-phase line tension are the only required constitutive inputs to the model. We first simulate hysteresis on a smooth chemically homogeneous surface using this theory. Next we show that it is possible to study heterogeneous surfaces whose component surfaces are themselves hysteretic. We use this theory to examine the wetting of a surface containing a circular heterogeneous island. The contact angle for this case is found to be determined solely by the material properties at the contact line in accord with recent experimental data.


A Novel Radiomics Model Integrating Luminal and Mesenteric Features to Predict Mucosal Activity and Surgery Risk in Crohn's Disease Patients: A Multicenter Study.
To investigate the feasibility of integrating radiomics and morphological features based on computed tomography enterography (CTE) for developing a noninvasive grading model for mucosal activity and surgery risk of Crohn's disease (CD) patients. A total of 167 patients from three centers were enrolled. Radiomics and image morphological features were extracted to quantify segmental and global simple endoscopic score for Crohn's disease (SES-CD). An image-fusion-based support vector machine (SVM) classifier was used for grading SES-CD and identifying moderate-to-severe SES-CD. The performance of the predictive model was assessed using the area under the receiver operating characteristic curve (AUC). A multiparametric model was developed to predict surgical progression in CD patients by combining sum-image scores and clinical data. The AUC values of the multicategorical segmental SES-CD fusion radiomic model based on a combination of luminal and mesenteric radiomics were 0.828 and 0.709 in training and validation cohorts. The image fusion model integrating the fusion radiomics and morphological features could accurately distinguish bowel segments with moderate-to-severe SES-CD in both the training cohort (AUC = 0.847, 95% confidence interval (CI): 0.784-0.902) and the validation cohort (AUC = 0.896, 95% CI: 0.812-0.960). A predictive nomogram for interval surgery was developed based on multivariable cox analysis. This study demonstrated the feasibility of integrating lumen and mesentery radiomic features to develop a promising noninvasive grading model for mucosal activity of CD. In combination with clinical data, the fusion-image score may yield an accurate prognostic model for time to surgery.


The changing face of Crohn's disease: a population-based study of the natural history of Crohn's disease in Örebro, Sweden 1963-2005.
Changes in medical therapy and surgery might have influenced the natural history of Crohn's disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis. A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963-2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behavior, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis. The proportion of patients with complicated disease behavior five years after diagnosis decreased from 54.4% (95%CI, 43.9-65.6) to 33.3% (27.4-40.0) in patients diagnosed 1963-1975 and 1991-2005, respectively (p = 0.002), whereas the proportion of patients progressing to complicated disease behavior was stable among those with non-stricturing, non-penetrating disease at diagnosis (p = 0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4-76.0) to 34.6% (28.6-41.5) in patients diagnosed 1963-1975 and 1991-2005, respectively (p < 0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p = 0.001). We observed a striking decrease in complicated disease behavior and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.


A microfluidic system for rapid nucleic acid analysis based on real-time convective PCR at point-of-care testing.
A microfluidic system for rapid nucleic acid analysis based on real-time convective PCR is developed. To perform 'sample-in, answer-out' nucleic acid analysis, a microfluidic chip is developed to efficiently extract nucleic acid, and meanwhile convective PCR (CPCR) is applied for rapid nucleic acid amplification. With an integrated microfluidic chip consisting of reagent pre-storage chambers, a lysis & wash chamber, an elution chamber and a waste chamber, nucleic acid extraction based on magnetic beads can be automatically performed for a large size of test sample within a limited time. Based on an easy-to-operate strategy, different pre-stored reagents can be conveniently released for consecutive reaction at different steps. To achieve efficient mixing, a portable companion device is developed to introduce properly controlled 3-D actuation to magnetic beads in nucleic acid extraction. In CPCR amplification, PCR reagent can be spontaneously and repeatedly circulated between hot and cool zones of the reactor for space-domain thermal cycling based on pseudo-isothermal heating. A handheld real-time CPCR device is developed to perform nucleic acid amplification and in-situ detection. To extend the detection throughput, multiple handheld real-time CPCR devices can be grouped together by a common control system. It is demonstrated that influenza A (H1N1) viruses with the reasonable concentration down to 1.0 TCID50/ml can be successfully detected with the microfluidic system.


Preoperative Feeds in Ductal-Dependent Cardiac Disease: A Systematic Review and Meta-analysis.
Our aim for this review is to determine if preoperative feeds in neonates with ductal-dependent congenital heart disease are harmful or beneficial. To summarize current evidence for preoperative feeding in neonates with ductal-dependent congenital heart disease. We used the following databases: Medline, Embase, and Cochrane Central Register of Controlled Trials. We included observational studies in which the following outcomes were addressed: necrotizing enterocolitis (NEC), hospital length of stay (LOS), time to achieve full postoperative enteral feeding, and feeding intolerance. Two reviewers independently screened each study for eligibility and extracted data. Methodologic quality was assessed by using a standardized item bank, and certainty of evidence for each outcome was assessed by using Grading of Recommendations Assessment, Development and Evaluation criteria. Five retrospective cohort studies were eligible for inclusion, for which risk of bias was significant. When comparing neonates who received preoperative feeds with those who did not, there was no significant difference in NEC (pooled odds ratio = 1.09 [95% confidence interval 0.06-21.00; P = .95]; 3 studies, 6807 participants, very low certainty evidence), hospital LOS (mean of 14 days for those not fed versus 9.9 days for those fed preoperatively; P < .01; 1 study, 57 participants, very low certainty evidence), or feeding intolerance (odds ratio = 2.014 [95% confidence interval 0.079-51.703; P = .67]; 1 study, 56 participants, very low certainty evidence). No data were available for the outcome time to achieve full postoperative enteral feeding. All studies were observational and had small sample sizes. There is insufficient evidence to suggest that preoperative enteral feeds in patients with ductal-dependent cardiac lesions adversely influence the rate of NEC, LOS, or feeding intolerance.


Lipid balance remodelling by human positive-strand RNA viruses and the contribution of lysosomes.
A marked reorganization of internal membranes occurs in the cytoplasm of cells infected by single stranded positive-sense RNA viruses. Most cell compartments change their asset to provide lipids for membrane rearrangement into replication organelles, where to concentrate viral proteins and enzymes while hiding from pathogen pattern recognition molecules. Because the endoplasmic reticulum is a central hub for lipid metabolism, when viruses hijack the organelle to form their replication organelles, a cascade of events change the intracellular environment. This results in a marked increase in lipid consumption, both by lipolysis and lipophagy of lipid droplets. In addition, lipids are used to produce energy for viral replication. At the same time, inflammation is started by signalling lipids, where lysosomal processing plays a relevant role. This review is aimed at providing an overview on what takes place after human class IV viruses have released their genome into the host cell and the consequences on lipid metabolism, including lysosomes.


Dietary change without caloric restriction maintains a youthful profile in ageing yeast.
Caloric restriction increases lifespan and improves ageing health, but it is unknown whether these outcomes can be separated or achieved through less severe interventions. Here, we show that an unrestricted galactose diet in early life minimises change during replicative ageing in budding yeast, irrespective of diet later in life. Average mother cell division rate is comparable between glucose and galactose diets, and lifespan is shorter on galactose, but markers of senescence and the progressive dysregulation of gene expression observed on glucose are minimal on galactose, showing that these are not intrinsic aspects of replicative ageing but rather associated processes. Respiration on galactose is critical for minimising hallmarks of ageing, and forced respiration during ageing on glucose by overexpression of the mitochondrial biogenesis factor Hap4 also has the same effect though only in a fraction of cells. This fraction maintains Hap4 activity to advanced age with low senescence and a youthful gene expression profile, whereas other cells in the same population lose Hap4 activity, undergo dramatic dysregulation of gene expression and accumulate fragments of chromosome XII (ChrXIIr), which are tightly associated with senescence. Our findings support the existence of two separable ageing trajectories in yeast. We propose that a complete shift to the healthy ageing mode can be achieved in wild-type cells through dietary change in early life without caloric restriction.


Cortical Auditory Processing of Simple Stimuli Is Altered in Autism: A Meta-analysis of Auditory Evoked Responses.
Auditory perceptual abnormalities are common in persons on the autism spectrum. The neurophysiologic underpinnings of these differences have frequently been studied using auditory event-related potentials (ERPs) and event-related magnetic fields (ERFs). However, no study to date has quantitatively synthesized this literature to determine whether early auditory ERP/ERF latencies or amplitudes in autistic persons differ from those of typically developing control subjects. We searched PubMed and ProQuest for studies comparing 1) latencies/amplitudes of P1/M50, N1b, N1c, M100, P2/M200, and/or N2 ERP/ERF components evoked by pure tones and 2) paired-click sensory gating (P1/N1b amplitude suppression) in autistic individuals and typically developing control subjects. Effects were synthesized using Bayesian 3-level meta-analysis. In response to pure tones, autistic individuals exhibited prolonged P1/M50 latencies (g = 0.341 [95% credible interval = 0.166, 0.546]), prolonged M100 latencies (g = 0.319 [0.093, 0.550]), reduced N1c amplitudes (g = -0.812 [-1.278, -0.187]), and reduced N2 amplitudes (g = -0.374 [-0.633, -0.179]). There were no practically significant group differences in P2/M200 latencies, N2 latencies, P1/M50 amplitudes, N1b amplitudes, M100 amplitudes, or P2/M200 amplitudes. Paired-click sensory gating was also reduced in autistic individuals (g = -0.389 [-0.619, -0.112]), although this effect was primarily driven by smaller responses to the first click stimulus. Relative to typically developing control subjects, autistic individuals demonstrate multiple alterations in early cortical auditory processing of simple stimuli. However, most group differences were modest in size and based on small numbers of heterogeneous studies with variable quality. Future work is necessary to understand whether these neurophysiologic measures can predict clinically meaningful outcomes or serve as stratification biomarkers for the autistic population.


Current approaches to etiology and pathophysiology of specific phobia.
Specific phobia is a common, heterogeneous disorder whose central feature is persistent, unreasonable fear of a circumscribed object or situation. This article reviews current etiological theories and empirical data that seem likely to be important in investigating the pathophysiology of this disorder. These include conditioning, modified conditioning, and nonassociative models of phobia development, physiological response to the phobic stimulus, neuroimaging, primate, and biological challenge studies. Pathophysiological hypotheses suggested by recent research on the neurocircuitry of conditioned fear are also discussed. Though specific phobias have been of less public health and clinical interest than other anxiety disorders, their circumscribed nature and possible relationship to conditioned fear may make them a productive subject for research into basic pathophysiology.


Diagnostic yield of cerebral imaging in patients with acute confusion.
Acute confusion (AC) is a frequent reason for hospital admission in elderly patients. Although in majority of cases the cause is a systemic disorder (e.g., dehydration or septicaemia), patients are frequently subjected to cerebral imaging. This study was undertaken to find clinical predictors of normal cerebral computed tomography (CCT) or magnetic resonance imaging (MRI) scans in AC. Retrospective study of 294 patients admitted with AC of unknown origin, of whom 178 received cerebral imaging. The rate of pathological imaging studies was 14%. The best single predictor of a normal brain scan was the absence of focal signs. Patients without focal abnormalities and either fever or dehydration had a probability of 0.96 of having a normal CCT or MRI. In demented patients without focal signs, the predictive value for a normal brain scan was 0.98, and if either patients with drowsiness were excluded or the existence of fever or dehydration was added as a selection criterion, all patients had normal scans. Patients with AC without focal signs and with either evidence for a medical aetiology of delirium or prediagnosed dementia are at a very low risk of having focal lesions in their CCT or MRI.


Is the mound ofFormica polyctena foerst. in orgin a simulation of a rock.
The red wood antFormica polyctena builds a mound of dead vegetable material which is accumulated into a sort of loose thatch. Some taxonomic relatives ofFormica nest beneath rocks and the two nest types are closely related in a physical sense. Possibly this similarity is more than just coincidental. The hypothesis is suggested that the mound ofFormica polyctena has evolved as a simulation of a rock.


Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers.
In vitro data indicate that biotransformation of the synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor fluvastatin is catalyzed by the cytochrome P450 (CYP) enzyme 2C9. The consequences of CYP2C9 genetic polymorphisms on fluvastatin pharmacokinetics and on its efficacy have not been investigated in humans thus far. Twenty-four healthy heterozygous or homozygous carriers of the CYP2C9 variants Arg144Cys (*2) and Ile359Leu (*3) and 2 individuals with the deficient CYP2D6 genotype *4/*4 took 40 mg racemic fluvastatin daily for 14 days. All subjects had also been genotyped for CYP2C8, CYP2C19, and CYP2D6 polymorphisms. Pharmacokinetics was analyzed after the first fluvastatin administration. Serum lipid concentrations were measured before fluvastatin intake and on day 15. Plasma concentrations of (+)-3R,5S-fluvastatin and of (-)-3S,5R-fluvastatin were quantified by enantiospecific HPLC. Pharmacokinetics of both enantiomers showed statistically significant differences according to the number of CYP2C9*3 alleles (P <.0001, F test). Mean (and SD) values for area under the curve of the active (+)-3R,5S-fluvastatin in carriers of the genotype CYP2C9*1/*1, *1/*3, and *3/*3 were 173 (85) micro g. L(-1). h, 231 (85) micro g. L(-1). h, and 533 (120) micro g. L(-1). h, respectively. The corresponding values for area under the curve of (-)-3S,5R-fluvastatin were 227 (133) micro g. L(-1). h, 360 (103) micro g. L(-1). h, and 1126 (311) micro g. L(-1). h for CYP2C9*1/*1, *1/*3, and *3/*3, respectively. The CYP2C9*2 variant did not have any significant influence on fluvastatin kinetics, nor did the CYP2C8*3 allele, which was tightly linked with CYP2C9*2. Total serum cholesterol and low-density lipoprotein cholesterol concentrations decreased significantly during the 14-day treatment period (P <.001), but no correlation with the CYP2C9 genotype was found. The pharmacokinetics of both enantiomers of fluvastatin depended on the CYP2C9 genotype, with a 3-fold group mean difference in the active enantiomer and even greater differences in the inactive enantiomer, but differences in plasma concentrations were not reflected in cholesterol lowering after 14 days of fluvastatin intake in healthy volunteers.


Asymmetric linkage disequilibrium: Tools for assessing multiallelic LD.
Standard measures of linkage disequilibrium (LD) provide an incomplete description of the correlation between two loci. Recently, Thomson and Single (2014) described a new asymmetric pair of LD measures (ALD) that give a more complete description of LD. The ALD measures are symmetric and equivalent to the correlation coefficient r when both loci are bi-allelic. When the numbers of alleles at the two loci differ, the ALD measures capture this asymmetry and provide additional detail about the LD structure. In disease association studies the ALD measures are useful for identifying additional disease genes in a genetic region, by conditioning on known effects. In evolutionary genetic studies ALD measures provide insight into selection acting on individual amino acids of specific genes, or other loci in high LD (see Thomson and Single (2014) for these examples). Here we describe new software for computing and visualizing ALD. We demonstrate the utility of this software using haplotype frequency data from the National Marrow Donor Program (NMDP). This enhances our understanding of LD patterns in the NMDP data by quantifying the degree to which LD is asymmetric and also quantifies this effect for individual alleles.


Construction and analysis of protein-protein interaction network correlated with ankylosing spondylitis.
Ankylosing spondylitis, a systemic illness is a foundation of progressing joint swelling that for the most part influences the spine. However, it frequently causes aggravation in different joints far from the spine, and in addition organs, for example, the eyes, heart, lungs, and kidneys. It's an immune system ailment that may be activated by specific sorts of bacterial or viral diseases that initiate an invulnerable reaction that don't close off after the contamination is recuperated. The particular reason for ankylosing spondylitis is obscure, yet hereditary qualities assume a huge part in this condition. The rising apparatuses of network medicine offer a stage to investigate an unpredictable illness at framework level. In this study, we meant to recognize the key proteins and the biological regulator pathways including in AS and further investigating the molecular connectivity between these pathways by the topological examination of the Protein-protein communication (PPI) system. The extended network including of 93 nodes and have 199 interactions respectively scanned from STRING database and some separated small networks. 24 proteins with high BC at the threshold of 0.01 and 55 proteins with large degree at the threshold of 1 have been identified. CD4 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for AS and the crosstalk between them. The finding of this research suggests that AS variation is orchestrated by an integrated PPI network centered on CD4 out of 93 nodes. Ankylosing spondylitis, a systemic disease is an establishment of advancing joint swelling that generally impacts the spine. Be that as it may, it as often as possible causes disturbance in various joints a long way from the spine, and what's more organs. It's a resistant framework affliction that might be actuated by particular sorts of bacterial or viral ailments that start an immune response that don't shut off after the pollution is recovered. The specific explanation behind AS is dark, yet innate qualities expect a colossal part in this condition. The rising devices of system solution offer a phase to examine an erratic ailment at structure level. In this study, we intended to perceive the key proteins and the natural controller pathways incorporating into AS. The finding of this research proposes that AS variety is organized by a coordinated PPI system focused on CD4.


"Locked-in State" Following Anterior Circulation Aneurysmal Subarachnoid Hemorrhage.
How to cite this article: Vaithialingam B, Gopal S, Masapu D. "Locked-in State" Following Anterior Circulation Aneurysmal Subarachnoid Hemorrhage. Indian J Crit Care Med 2023;27(8):601-602.


Insulin-like growth factor binding protein-2 (IGFBP-2) in Japanese flounder, Paralichthys olivaceus: molecular cloning, expression patterns and hormonal regulation during metamorphosis.
In this study, we cloned and characterized cDNA sequences of two insulin-like growth factor binding protein-2 (IGFBP-2a and IGFBP-2b) from Japanese flounder, Paralichthys olivaceus. The full-length cDNA of IGFBP-2a is 1,046 bp long and consists an open frame (ORF) of 876 bp, a 5'-untranslated region (UTR) of 125 bp and a 3'-UTR of 45 bp. IGFBP-2b is 1,067 bp, including a 5'-UTR of 53 bp, a 3'-UTR of 198 bp and an ORF of 816 bp. Real-time quantitative PCR results revealed that IGFBP-2a -2b mRNA was expressed in all detected tissues. Interestingly, the levels of IGFBP-2a mRNA in all detected tissues were higher in female than male, but IGFBP-2b was precisely the opposite. At different embryonic stages, the levels of IGFBP-2a mRNA were typically higher than IGFBP-2b. After hatching, IGFBP-2a mRNA was gradually decreased to a relatively lower level. However, the expression of IGFBP-2b mRNA was increased after hatching, including 3, 7, 10, 14, 17, 20 and 23 days post-hatching (dph), and it presents a higher level until 29 (metamorphic climax), 36 (post-climax) and 41 dph (the end of metamorphosis). In levothyroxine sodium salt (T4, the main form of thyroid hormone in animals)-treated and thiourea (TU)-treated larvae, the expressions of IGFBP-2a had not visibly changed, except in T4-treated 17 dph larvae. The expressions of IGFBP-2b mRNA were distinctly increased from 17 to 23 dph, but suddenly dropped to a lower level in and after 29 dph. However, the levels of IGFBP-2b mRNA during metamorphosis were greatly down-regulated after TU treatment. These results provided basic information for further studies on the role of IGF system in flatfish development and metamorphosis.


Metronidazole-induced Encephalopathy.
Metronidazole is commonly used in the treatment of anaerobic infections. While neuropathy is known to be associated with metronidazole, encephalopathy has been rarely reported. We herein present a case of metronidazole-induced encephalopathy presenting as frequent falls and slurred speech. Magnetic resonance imaging of the brain demonstrated T2/FLAIR hyperintensity in the dentate nuclei bilaterally. Soon after the discontinuation of metronidazole, dysarthria and dysmetria resolved. Metronidazole-induced encephalopathy should be considered in patients presenting with new neurologic symptoms after the initiation of metronidazole.


Brief history of the role of nutrition in carcinogenesis.
That diet exerts an influence on the development of tumors in humans and in experimental animals has been recognized for over 60 years. From 1940 to 1960, a number of essential nutrients were shown to significantly alter the carcinogenic activities of specific polycyclic aromatic hydrocarbon and aromatic amine and aminoazo dye carcinogens. Diet has been shown to modify the carcinogenic process at many stages. Since 1970, the number of known interactions between carcinogens and essential nutrients has increased markedly. It is hoped that this volume will provide a comprehensive evaluation increasing our understanding of the multiple effects of the essential nutrients on carcinogenesis.


Effect of cognitive insight on clinical insight from pre-morbid to early psychosis stages.
Poor cognitive insight, including low self-reflectiveness and high self-certainty, contributes to poor clinical insight, which includes awareness of illness, relabelling of specific symptoms, and treatment compliance. However, inconsistent results regarding cognitive insight among individuals at clinical high risk of psychosis (CHR) have been reported. This study investigated the difference in cognitive insight among groups with different severity of positive symptoms and analysed the effect of cognitive insight on clinical insight in each group. All participants, including CHR individuals with 3 or 4 points (L-Pitem, n = 85) and 5 points (H-Pitem, n = 37) on any positive-symptom item of the Scale of Prodromal Syndromes, and patients with first-episode psychosis (FEP, n = 59), were measured cognitive and clinical insight using the Beck Cognitive Insight Scale and the Schedule of Assessment of Insight, respectively. The self-reflectiveness of cognitive insight was highest in the L-Pitem group and lowest in the FEP group. Self-reflectiveness was positively associated with awareness of illness in the L-Pitem and FEP groups; both self-reflectiveness and self-certainty was positively associated with treatment compliance in the L-Pitem group. Improving self-reflectiveness of cognitive insight may conduce to good clinical insight. Self-certainty may have different implication to individuals with mild prodromal symptoms.


Accessibility: global gateway to health literacy.
Health literacy, cited as essential to achieving Healthy People 2010's goals to "increase quality and years of healthy life" and to "eliminate health disparities," is defined by Healthy People as "the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions." Accessibility, by definition, the aforementioned "capacity to obtain," thus is health literacy's primary prerequisite. Accessibility's designation as the global gateway to health literacy is predicated also on life's realities: global aging and climate change, war and terrorism, and life-extending medical and technological advances. People with diverse access needs are health professionals' raison d'être. However, accessibility, consummately cross-cultural and universal, is virtually absent as a topic of health promotion and practice research and scholarly discussion of health literacy and equity. A call to action to place accessibility in its rightful premier position on the profession's agenda is issued.


When, catastrophe happens. Assessment and intervention after sudden traumatic death.
The goals of grief after sudden traumatic death is to acknowledge the loss, identify the changes the loss will have in the co-victim's life, and reinvest in life within the new structure. Although these goals seem simple, there is no definitive timeline for when these tasks will be engaged and completed by each of the family members. The pathway and time frame for each co-victim may differ.


Electrophotocatalytic C-H Functionalization of N-Heteroarenes with Unactivated Alkanes under External Oxidant-Free Conditions.
The Minisci alkylation of N-heteroarenes with unactivated alkanes under external oxidant-free conditions provides an economically attractive route to access alkylated N-heteroarenes but remains underdeveloped. Herein, a new electrophotocatalytic strategy to access alkyl radicals from strong C(sp3 )-H bonds was reported for the following Minisci alkylation reactions in the absence of chemical oxidants. This strategy realized the first example of cerium-catalyzed Minisci alkylation reaction directly from abundant unactivated alkanes with excellent atom economy. It is anticipated that the general design principle would enrich catalytic strategies to explore the functionalizations of strong C(sp3 )-H bonds under external oxidant-free conditions with H2 evolution.


Small Airway Disease in Pediatric Asthma: the Who, What, When, Where, Why, and How to Remediate. A Review and Commentary.
Asthma affects all portions of the airways. Small airways, however, comprise a substantial component of the conducting lung air flow. In asthma, inflammatory processes can affect the whole respiratory tract, from central to peripheral/small airways. The emphasis in adult and pediatric respiratory disease clinics is to focus on large airway obstruction and reversibility. This information, although valuable, underemphasizes a large portion of the conduction airway of asthmatics. Standard descriptions of asthma management focus on a multiple medication approaches. We particularly focused on the management of asthma in the international guidelines for the Global Initiative for Asthma (GINA). Overall, however, minimal attention is placed on the small airway pool in asthma medical management. We took the opportunity to thoroughly review and present specific data from the adult asthma literature which supported the concept that small airway abnormalities may play a role in the pathogenesis and clinical expression of asthma. Based on the conclusions of the adult asthma literature, we here present a thorough review of the literature as it relates to small airway disease in children with asthma. We used, collectively, individual data sources of data to expand the information available from standard diagnostic techniques, especially spirometry, in the evaluation of small airway disease. As the pharmacological approaches to moderate to severe asthma are advancing rapidly into the realm of biologics, we sought to present potential pharmacological options for small airway dysfunction in pediatrics prior to biological modifier intervention.


Workers With Irregular Hours During Seasonal Work Surges: Promoting Healthy Sleep.
A significant proportion of the labor force works irregular hours during harvest, summer, or holiday work surges. Unfortunately such workers are often uninformed about the importance of sleep and fatigue management. Seasonally timed worker training can improve health and safety outcomes during work surges.


Massive upper gastrointestinal bleeding caused by an intercostal arterio-esophageal fistula: A rare case report.
Arterio-esophageal fistula (AEF) is a rare life-threatening cause of upper gastrointestinal bleeding. Realizing the risk factors and clinical presentations of AEF will enable us to provide timely diagnosis, efficient treatment, and better outcome. We present a 43-year-old Taiwanese man who had histories of destructive lung, innominate artery-trachea fistula, and received bilobectomy. He was admitted to our hospital with fresh blood drainage from nasogastric tube. He was diagnosed as right fifth intercostal artery esophageal fistula by computed tomography angiography and transcatheter arterial embolization was performed. The bleeding stopped and the patient was discharged uneventfully. The risk factors of AEF include esophageal foreign body, vascular surgery, thoracic arterial malformations, and concurrent chemoradiotherapy in T4-esophageal cancer. Computed tomography angiography may be the most sensitive diagnostic test. Transcatheter arterial embolization or endovascular stent grafting may be considered as the first-line treatment of AEF in the future.


Proton-dependent transporter gene lndJ confers resistance to landomycin E in Streptomyces globisporus.
Sequence analysis of 2 kb BamHI-SmaI fragment of landomycin E (LaE) gene cluster in S. globisporus 1912 revealed one complete ORF marked as lndJ. Analysis of putative LndJ aminoacid sequence allowed us to suppose that it is proton-dependent antiporter which could be involved in resistance to LaE in the producing strain. Although disruption of lndJ had no significant influence on LaE production and resistance, it's overexpression in wild type and LaE overproducing strains led to qualitative changes in landomycins biosynthesis and increased resistance to LaE. These data support the hypothesis about involvement of lndJ gene in landomycins export.


Glycogen synthase kinase 3 inhibitor attenuates endotoxin-induced liver injury.
Endotoxin (lipopolysaccharide, LPS)-induced acute liver injury was attenuated by endotoxin tolerance (ET), which is characterized by phosphatidylinositol 3-kinase pathway/Akt signaling. Glycogen synthase kinase 3 (GSK-3) acts downstream of phosphatidylinositol 3-kinase pathway/Akt and GSK-3 inhibitor protects against organic injury. This study evaluates the hypothesis that ET attenuated LPS-induced liver injury through inhibiting GSK-3 functional activity and downstream signaling. Sprague-Dawley rats with or without low-dose LPS pretreatment were challenged with or without large dose of LPS and subsequently received studies. Serum tumor necrosis factor-alpha, interleukin-10, alanine aminotransferase, lactate dehydrogenase, and total bilirubin levels were analyzed, morphology of liver tissue was performed, glycogen content, myeloperoxidase content, phagocytosis activity of Kupffer cells, and the expression and inhibitory phosphorylation as well as kinase activity of GSK-3 were examined. Survival after LPS administration was also determined. LPS induced significant increases of serum TNF-α, alanine aminotransferase, lactate dehydrogenase, and total bilirubin (P < 0.05), which were companied by obvious alterations in liver: the injury of liver tissue, the decrease of glycogen, the infiltration of neutrophils, and the enhancement of phagocytosis of Kupffer cells (P < 0.05). LPS pretreatment significantly attenuated these alterations, promoted the inhibitory phosphorylation of GSK-3 and inhibited its kinase activity, and improved the survival rate (P < 0.05). ET attenuated LPS-induced acute liver injury through inhibiting GSK-3 functional activity and its downstream signaling.


Management of Major Vascular Injury During Endoscopic Endonasal Skull Base Surgery.
A major vascular injury is the most feared complication of endoscopic sinus and skull base surgery. Risk factors for vascular injury are discussed, and an algorithm for management of a major vascular injury is presented. A team of surgeons (otolaryngology and neurosurgery) is important for identification and control of a major vascular injury applying basic principles of vascular control. A variety of techniques can be used to control a major injury, including coagulation, a muscle patch, sacrifice of the artery, and angiographic stenting. Immediate and close angiographic follow-up is critical to prevent and manage subsequent complications of vascular injury.


A multinutrient package of iron, vitamin A, and iodine improved the productivity and earnings of women tea pickers in south India.
Tea-picking is a highly skilled activity that is usually performed by women. This study, conducted on the Balanoor Plantations, India, from 1996 to 1998, was successful in empowering 339 women pickers and their families to take iron (60 mg of elemental iron two times a week) and vitamin A (1,600 IU) once a week, and to purchase subsidized iodized salt (30 ppm) from the plantation ration shop. The average hemoglobin level of the pickers rose significantly (p < .001) from 11.0 g/dl at baseline to 11.9 g/dl at the end of the nine months of intervention. The average amount of tea per picker increased significantly (p < .001) from 22.9 to 25.6 kg. There was a significant decrease in the number of "moderate pickers," who picked between 14 and 25 kg per day, and a significant increase in the number of "good pickers," who picked more than 25 kg per day, and the earnings of the majority of the pickers increased. The management of the estate where the intervention occurred benefited from a decrease in the number of pickers needed during the supplement period from 2,857 to 2,763, with no significant change in the yield per hectare in the two years. The yield per hectare on the control estate was not significantly different from that on the intervention estate, and the average amount of tea picked per worker was the same for the two periods (20.8 and 20.7 kg).


Phytoplankton growth control and risk of cyanobacterial blooms in the lower Senegal River delta region.
Eutrophication, and the resulting proliferation of phytoplankton can affect water quality. Although environmental and ecological processes that lead to phytoplankton proliferations in temperate areas have received considerable attention, scientific background regarding this topic in tropical areas, especially West Africa, are scarce. In this study, bioassays in batch cultures were carried out in order to identify factors that may be stimulating or limiting the biomass of phytoplankton at various sites in the lower Senegal River delta region. Complete factorial designs were used to test several factors both alone and combined (nitrogen, phosphorus, sulfate, EDTA and trace elements, stirring). The effects of these factors on the growth of the whole phytoplankton communities were followed by the daily measurement of in vivo fluorescence. At all but two of the sites, enrichment with certain nutrients significantly stimulated phytoplankton biomass growth, with nitrogen and/or phosphorus appearing to be the primary limiting factor(s). Nitrogen was the primary limiting factor in coastal ocean waters and in the Senegal River estuary. In the freshwater ecosystems studied, nitrogen and phosphorus acted as alternating or concomitant limiting factors. We assessed the changes in the phytoplankton composition induced by nutrient enrichments in Lake Guiers, a drinking water reservoir for the population of Dakar. Our findings lead us to define the conditions of a possible proliferation of the potentially toxic cyanobacterium Cylindrospermopsis raciborskii mainly in response to phosphorus inputs.


LSD1: oxidative chemistry for multifaceted functions in chromatin regulation.
Three years after its discovery, lysine-specific demethylase 1 remains at the forefront of chromatin research. Its demethylase activity on Lys4 of histone H3 supports its role in gene repression. By contrast, the biochemical mechanisms underlying lysine-specific demethylase 1 involvement in transcriptional activation are not firmly established. Structural studies highlight a specific binding site for the histone H3 N-terminal tail and a catalytic machinery that is closely related to that of other flavin-dependent amine oxidases. These insights are crucial for the development of demethylation inhibitors. Furthermore, the exploration of putative non-histone substrates and potential signaling roles of hydrogen peroxide produced by the demethylation reaction could lead to new paradigms in chromatin biology.


A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture.
Mitochondria exist in a dynamic cycle of fusion and fission whose balance directly influences the morphology of the 'mitochondrial network', a term that encompasses the branched, reticular structure of fused mitochondria as well as the separate, punctate individual organelles within a eukaryotic cell. Over the past decade, the significance of the mitochondrial network has been increasingly appreciated, motivating the development of various approaches to analyze it. Here, we describe the Mitochondrial Network Analysis (MiNA) toolset, a relatively simple pair of macros making use of existing ImageJ plug-ins, allowing for semi-automated analysis of mitochondrial networks in cultured mammalian cells. MiNA is freely available at https://github.com/ScienceToolkit/MiNA. The tool incorporates optional preprocessing steps to enhance the quality of images before converting the images to binary and producing a morphological skeleton for calculating nine parameters to quantitatively capture the morphology of the mitochondrial network. The efficacy of the macro toolset is demonstrated using a sample set of images from SH-SY5Y, C2C12, and mouse embryo fibroblast (MEF) cell cultures treated under different conditions and exhibiting hyperfused, fused, and fragmented mitochondrial network morphologies.


Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report.
A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS.


A philosophical argument against evidence-based policy.
Evidence-based medicine has two components. The methodological or ontological component consists of randomized controlled trials and their systematic review. This makes use of a difference-making conception of cause. But there is also a policy component that makes a recommendation for uniform intervention, based on the evidence from randomized controlled trials. The policy side of evidence-based medicine is basically a form of rule utilitarianism. But it is then subject to an objection from Smart that rule utilitarianism inevitably collapses. If one assumes (1) you should recommend the intervention that has brought most benefit (the core of evidence-based policy making), (2) individual variation (acknowledged by use of randomization) and (3) no intervention benefits all (contingent but true), then the objection can be brought to bear. A utility maximizer should always ignore the rule in an individual case where greater benefit can be secured through doing so. In the medical case, this would mean that a clinician who knows that a patient would not benefit from the recommended intervention has good reason to ignore the recommendation. This is indeed the feeling of many clinicians who would like to offer other interventions but for an aversion to breaking clinical guidelines.


Sustained beneficial effect of a seventy-two hour intravenous infusion of nitroglycerin in patients with severe chronic congestive heart failure.
To determine whether a 72-hour infusion of nitroglycerin produces hemodynamic improvement in patients with severe congestive heart failure and to assess the contributing role of various possible causes of hemodynamic tolerance to nitroglycerin, 19 patients received an infusion of nitroglycerin 1.5 micrograms/kg/min for 72 hours. In a subgroup of patients (n = 10), there was an increase in stroke work index and a decrease in ventricular filling pressures throughout the infusion and even after it was discontinued. Tolerance to the hemodynamic effects of nitroglycerin was partially reversed 8 hours after the infusion was stopped. Neurohumoral changes occurred but appeared to play only a minor role in the development of nitroglycerin tolerance. However, hematocrit fell 9 +/- 5%, which suggests that an increased intravascular volume contributed to tolerance. In summary: (1) a 72-hour infusion of nitroglycerin improves ventricular function in some patients with severe heart failure; (2) volume shifts from the extravascular to the intravascular compartments may, at least in part, be responsible for nitroglycerin tolerance; and (3) reflex neurohumoral activation may also play a small role in nitrate tolerance.


Developmental changes in the responsiveness to ecdysterone of chromosome region I-18C of Chironomus tentans.
The presence of nascent RNA in chromosome region I-18C was revealed by the method of induced hybrid formation (IEH) and by use of anti-RNA:DNA antibodies. IEH signals were quantitated, and used as a measure of transcriptional activity in the region. The expansion of the I-18C region was also determined and used as an indication of local chromatin decondensation. Chironomus tentans larvae may undergo oligopause or they may develop subitaneously. It was found that the course of basal activity in I-18C differs substantially in these two modes of development. Most interestingly they also differ in activation of I-18C in response to in vitro ecdysterone treatment. Changes in hormonal responsiveness of I-18C parallel changes in the preexisting state of I-18C decondensation. Oligopause stage 5 animals, being most refractory in this respect, exhibit the most condensed I-18C chromosome region.


Medium to long term follow up of a consecutive series of 604 Exeter Trauma Stem Hemiarthroplasties (ETS) for the treatment of displaced intracapsular femoral neck fractures.
The aim of this study was to evaluate the medium to long term follow up results for the Exeter Trauma Stem (ETS) in the treatment of displaced femoral neck fractures. We retrospectively evaluated 604 consecutive cemented ETS hemiarthroplasties performed at our institution between 2007 and 2012. The range of follow up was 2-7 years with a mean follow-up of 4.1 years for the surviving patients. The mean age of the patient population was 84 years (range 46-106) with 81.3% female patients. 382 patients (63.2%) died within the follow up period. Postoperative superficial soft tissue infection occurred in 11 patients and deep prosthetic infection in 5 patients. Dislocation occurred in 11 patients and periprosthetic fracture occurred in 7 patients. 11 patients underwent Girdlestone excision arthroplasty and 6 patients were revised to total hip replacement. This paper represents the largest consecutive series for this implant, with the longest follow up currently available. The results confirm that the prosthesis is an excellent implant for these patients with a low risk of needing revision surgery.


Salinomycin promotes T-cell proliferation by inhibiting the expression and enzymatic activity of immunosuppressive indoleamine-2,3-dioxygenase in human breast cancer cells.
Indoleamine 2,3 dioxygenase (IDO) is upregulated in many tumor types, including breast cancer, and plays a reputable role in promoting tumor immune tolerance. The importance of the immunosuppressive mechanism of IDO by suppressing T-cell function has garnered profound interest in the development of clinical IDO inhibitors. Herein, we established a screening method with cervical HeLa cells to induce IDO expression using interferon-γ (IFN-γ). After screening our chemical library, we found that salinomycin potently inhibited IFN-γ-stimulated kynurenine synthesis with IC50 values of 3.36-4.66 μM in both human cervical and breast cancer cells. Salinomycin lowered the IDO1 and IDO2 expression with no impact on the expression of tryptophan-2,3-dioxygenase. Interestingly, salinomycin potently repressed the IDO1 enzymatic activity by directly targeting the proteins in cells. Molecular docking revealed an alignment that favors nucleophilic attack of salinomycin in the catalytic domain of IDO1. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway by IFN-γ was significantly suppressed by salinomycin, via inhibiting the Jak1, Jak2, and STAT1/3 phosphorylation. Moreover, it inhibited IFN-γ-induced activation of the nuclear factor (NF)-κB pathway by inhibiting IκB degradation and NF-κB phosphorylation without affecting BIN1 expression. Furthermore, salinomycin significantly restored the proliferation of T cells co-cultured with IFN-γ-treated breast cancer cells and potentiated antitumor activity of cisplatin in vivo. These findings suggest that salinomycin suppresses kynurenine synthesis by inhibiting the catalytic activity of IDO1 and its expression by inhibiting the JAK/STAT and NF-κB pathways. Salinomycin warrants further investigation as a novel dual-functional IDO inhibitor for cancer immunotherapy.


Regional cerebral blood flow and anxiety: a correlation study in neurologically normal patients.
Regional CBF (rCBF) was evaluated by the 133Xe inhalation method in 60 neurologically normal patients (30 men and 30 women) and hemispheric and regional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative correlations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with results previously reported by others and could be related to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones to deeper areas of the brain, classically known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects.


Clinical value of FDG PET or PET/CT in urinary bladder cancer: a systemic review and meta-analysis.
The purpose of the current study was to conduct a systemic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of FDG PET or PET/CT in urinary bladder cancer. The authors conducted a systematic MEDLINE search of articles published between January 2000 and December 2010. Two reviewers independently assessed the methodological quality of each study. We conducted a meta-analysis of pooled sensitivity and specificity in detecting primary and metastatic lesions of bladder cancer. Six studies met the inclusion criteria. The pooled sensitivity and specificity of PET/CT for primary lesion detection of bladder cancer were 0.90 (95% CI: 0.70-0.99) and 1.00 (95% CI: 0.74-1.00), respectively. The pooled sensitivity and specificity of FDG PET or PET/CT for staging or restaging (metastatic lesions) of bladder cancer were 0.82 (95% CI: 0.72-0.89) and 0.89 (95% CI: 0.81-0.95), respectively. The diagnostic accuracy of FDG PET or PET/CT is good in metastatic lesions of urinary bladder cancer. Due to the small number of patients and limited number of studies analyzed, the diagnostic capability of FDG PET or PET/CT in detection of primary bladder wall lesions could not be assessed.


Regional and subcellular distribution of [125I]endothelin binding sites in rat brain.
The binding of [125I]endothelin-1 (125I-ET-1) to membranes from whole rat brain, from individual brain regions, and derived from subcellular fractionation of whole rat brain was investigated. 125I-ET-1 binding to whole rat brain membranes was rapid, concentration-dependent, saturable, and characterized as irreversible because it was not displaced by unlabeled endothelin-1 (ET-1) and different concentrations of ligand produced, with time, a similar magnitude of binding. The maximum binding site capacity and second-order forward rate association constant of binding were 1,946 +/- 147 fm/mg protein and 5.53 +/- 1.72 x 10(6) M-1 s-1. Removal of either extramembranal calcium or membrane-bound calcium and calcium binding proteins did not affect the binding of 125I-ET-1 to whole rat brain membranes. The brain stem and cerebellum contained the highest levels of 125I-ET-1 binding sites, whereas the cerebral cortex, striatum, and hippocampus contained binding site levels three- to fourfold less. Subcellular fractionation of whole rat brain and subsequent analyses of the distribution of 125I-ET-1 binding demonstrated a twofold enrichment of binding sites in the synaptosomal fraction compared to the homogenate. The myelin fraction contained a similar density of binding sites compared to the homogenate, while the mitochondrial and microsomal fractions contained considerably less binding sites. The ribosomal fraction did not contain any 125I-ET-1 binding sites. The subcellular distribution of 125I-ET-1 binding sites did not correlate with the distribution of 5'-nucleotidase, cytochrome-C oxidase, phosphodiesterase, and alkaline phosphatase. Depletion of extracellular calcium increased 125I-ET-1 binding in the synaptosomal fraction but not in the myelin and mitochondrial fractions.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and Characterization of Nanoscale Tungsten Particles with Hollow Superstructure Using Spray Drying Combined with Calcination Process.
Nanoscale tungsten (W) powder is used in some special materials. In this study, a hollow superstructure W powder consisting of nanoparticles was synthesized by spray drying combined with two-step calcination from commercial (NH4)6W7O24·6H2O. The high-pressure gas (HPG) was the significant factor in spray drying process, which affect the BET surface area and average particles size of the spray-dried powders. The detailed influences of calcined steps and calcination temperature in the microstructure and average particles size of final W particles were investigated. The size distribution of as-synthesized nanoscale W particles with hollow superstructure was from 40 to 200 nm, and the average size was about 100 nm. The as-synthesized W powder shows good sintering properties. It should be noted that the powder technology in this study can be used to synthesize other powders with high-performance requirements. .


Ocular response analyzer parameters in healthy, keratoconus suspect and manifest keratoconus eyes.
To evaluate and compare corneal biomechanical indices and their specificity among keratoconus (KC), keratoconus suspect (KCS), and normal eyes (NL) before and after controlling potential confounders. A total of 160 eyes in three groups were included prospectively: NL, KC, and KCS groups based on clinical examination and topography. Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured by the ocular response analyzer. CH and CRF were compared between the three groups by analysis of variances test. The three groups consisted of 80 NL, 48 KC, and 32 KCS eyes. The mean CH measured was 10.4 ± 1.25, 7.83 ± 1.28 and 10.17 ± 1.80 mm Hg in NL, KC and KCS eyes, respectively. The mean CRF was 10.23 ± 1.75, 6.5 ± 1.63 and 9.98 ± 2.00 mm Hg in NL, KC and KCS eyes, respectively. Mean CH and CRF were significantly different between the NL and KC (P < 0.05); however after controlling for central corneal thickness and sex; there was no significant difference between NL and KCS (P > 0.05). CH and CRF can be helpful in differentiating KC from NL eyes; however, they are not valuable for detecting KCS that is the main concern for refractive surgery. Future studies focusing on more accurate tests for identifying KCS, using a consistent grading scale for defining KC and KCS are still warranted.


A review of the utility of EEG depth of anaesthesia monitors in the paediatric intensive care environment.
This paper aims to bring together current evidence regarding the use of depth of anaesthesia monitors (DoAM) as objective measures of sedation for paediatric intensive care (PIC) patients. Delivering appropriate dosages of sedative agents, to individual PIC patients, is important to reduce the many risks of over- or under-sedation. Although based on adult anaesthesia, DoAMs could offer increased objectivity to the titration of sedative agents for children in PIC. This article synthesises the current available evidence from studies investigating DoAM use in the PIC environment. Literature regarding DoAM use in PIC was reviewed, from 1996 and August 2011, after EMBASE, PubMed, CINAHL and ProQuest Dissertation & Theses Database were searched using key search terms. Fourteen original research articles addressing sedation assessment using DoAMs in PIC were identified. The main findings were that DoAMs generally have a moderate or poor correlation with sedation scores and their performance varies in varying clinical settings. DoAMs do not make reliable conclusions about depth of sedation of individual PIC children, and can be influenced by children's age. Evidence to support DoAMs in the PIC setting is currently not sufficient to advocate their routine use in clinical practice.


Antitumor efficacy and pharmacokinetic analysis of 4-hydroperoxycyclophosphamide in comparison with cyclophosphamide +/- hepatic enzyme effectors.
4-Hydroperoxycyclophosphamide is an oxazaphosphorine which is readily converted without enzymatic involvement to 4-hydroxycyclophosphamide-a key intermediate in the antitumor activity of this class of drugs. The efficacy of 4-hydroperoxycyclophosphamide as a systemically administered antitumor drug was examined in mice bearing EMT-6 mammary carcinoma and in rats bearing 13762 mammary carcinoma in comparison with other oxazaphosphorines. 4-Hydroperoxycyclophosphamide was a more potent tumor cell killing agent than cyclophosphamide or ifosfamide in animals bearing the EMT-6 tumor. There were no significant differences in the toxicity to bone marrow amongst the three oxazaphosphorines. 4-Hydroperoxycyclophosphamide (90 mg/kg) on days 7, 9 and 11 produced 11.5 days of tumor growth delay compared with 10.4 days and 7.1 days for cyclophosphamide (150 mg/kg) and ifosfamide (150 mg/kg) administered on the same schedule, respectively. 4-Hydroperoxycyclophosphamide was tolerated at 90 mg/kg daily for 5 days and at 75 mg/kg twice daily for 4 days producing tumor growth delays of 14.4 days and 16.6 days, respectively. In rats bearing 13762 tumors, 4-hydroperoxycyclophosphamide (90 mg/kg) on days 8, 10 and 12 produced a tumor growth delay of 14.5 days compared with 8.9 days for cyclophosphamide (100 mg/kg) administered on the same schedule. Treatment of 13762 tumor-bearing rats with phenobarbital, pentobarbital or etanidazole increased the tumor growth delay produced by cyclophosphamide while treatment with cimetidine decreased the tumor growth delay produced by cyclophosphamide but not significantly. Administration of 4-hydroperoxycyclophosphamide (90 mg/kg) produced blood concentrations of 4-hydroxycyclophosphamide three-fold higher than those produced by administration of cyclophosphamide (100 mg/kg) at 15 min after drug injection. Treatment with phenobarbital or pentobarbital increased 4-hydroxycyclophosphamide blood concentration while pretreatment with cimetidine decreased 4-hydroxycyclophosphamide blood concentration from cyclophosphamide. 4-Hydroperoxycyclophosphamide is an effective antitumor agent worthy of further investigation.


The removal of cyanobacteria and their metabolites through anoxic biodegradation in drinking water sludge.
The effects of environmental factors on cyanobacteria damage and microcystin-LR degradation in drinking water sludge were investigated under anoxic conditions. The rates of microcystin-LR release and degradation increased rapidly with the increasing temperature from 15°C to 40°C and the highest degradation rate of 99% was observed at 35°C within 10days. Compared to acidic conditions, microcystin-LR degraded more rapidly in weak alkali environments. In addition, the microbial community structures under different anoxic conditions were studied. The sequencing results showed that four phyla obtained from the DGGE profiles were as follows: Proteobacteria, Acidobacteria, Firmicutes and Cyanobacteria. Proteobacteria containing nine genera were the most common species. Pseudomonas, Methylosinus and Sphingomona all showed stronger activities and had significant increase as microcystin-LR degraded, so they should be responsible for the microcystin-LR degradation. This is the first report of Pseudomonas, Methylosinus and Sphingomonas as the microcystins-degrading microorganisms in anoxic drinking water sludge.


Incorporation of deuterium-labeled cis- and trans-9-octadecenoic acids in humans: plasma, erythrocyte, and platelet phospholipids.
The objective of this study was to follow the uptake and distribution of oleic and elaidic acids into human erythrocytes, platelets, and plasma phospholipids. The use of dual and triple labeling methodology permitted a precise comparison of elaidic and oleic acid utilization. Elaidic acid (EI) was selectively concentrated in all the plasma phospholipids except for lysophosphatidylcholine. Three times more elaidic than oleic acid (OI) accumulated in the 1-acyl position of phosphatidylcholine, as determined by hydrolysis with phospholipase A2. Rapid incorporation and removal of elaidate were observed for all samples. These results support the concept that enzymes responsible for acylation of phospholipids are sensitive to double bond configuration and the physical properties of the fatty acid moieties. Labeled fatty acid levels in red cell and platelet phospholipids were much lower than for plasma phospholipids, indicating a relatively slow rate for the in vivo incorporation of fatty acids into blood cell membrane phospholipids. No isotope effect was found when oleic acid labeled with deuterium on the double bond was used.


Cu(II) complexes with peptides from FomA protein containing -His-Xaa-Yaa-Zaa-His and -His-His-motifs. ROS generation and DNA degradation.
Mono- and dinuclear Cu(II) complexes with Ac-PTVHNEYH-NH2 (L1) and Ac-NHHTLND-NH2 (L2) peptides from FomA protein of Fusobacterium nucleatum were studied by potentiometry, spectroscopic methods (UV-Vis, CD, EPR) and MS technique. The dominant mononuclear complexes for L1 ligand are: CuHL (pH range 5.0-6.0) with 2N {2Nim}, CuH-2L (pH range 8.0-8.5) and CuH-3L species (above pH 9.0) with 4N {Nim, 3N-} coordination modes. The complexes: CuH-1L with 3N {2Nim, N-}, CuH-2L with 3N {Nim, 2N-} and CuH-3L with 4N {Nim, 3N-} binding sites are proposed for the L2 ligand. Probably in the CuH-2L complex for CuL2 system the second His residue in His-His sequence is bound to Cu(II) ion, while the first His residue may stabilize this complex by His-His and/or His-Cu(II) interactions. The dominant dinuclear Cu2L1 complexes in the pH range 6.5-10.5 are: the Cu2H-4L and Cu2H-6L species with 3N{Nim, 2N-}4N{Nim, 3N-} and 4N{Nim, 3N-}4N{Nim, 3N-} binding sites, respectively. In the case of the Cu2L2 complex in the pH range 7.2-10.5, the Cu2H-4L and Cu2H-7L species dominate with 2N{Nim, N-}4N{Nim, 3N-} and (Cu(OH)42-4N{Nim, 3N-}) coordination modes, respectively. The ability to generate reactive oxygen species (ROS) by uncomplexed Cu(II) ions, ligands and their complexes at pH 7.4 in the presence of hydrogen peroxide or ascorbic acid was studied. UV-Vis, luminescence, EPR spin trapping and gel electrophoresis methods were used. Both complexes produce higher level of ROS compared to those of their ligands. ROS produced by Cu(II) complexes are hydroxyl radical and singlet oxygen, which contribute to oxidative DNA cleavage.


Up-regulation of beta-adrenoceptors on circulating mononuclear cells after reduction of central sympathetic outflow by clonidine in normal subjects.
Short term regulation of beta-adrenoceptors in peripheral blood mononuclear cells after sympathetic activation has been previously documented in normal individuals but changes after a central reduction in sympathetic activity are not known. We have studied beta-adrenoceptor number and affinity on peripheral blood mononuclear cells in normal subjects, before and after intravenous clonidine, an alpha 2-adrenoceptor agonist which lowers blood pressure predominantly by reducing central nervous system sympathetic outflow. After clonidine there was a decrease in plasma levels of noradrenaline and adrenaline, and an increase in growth hormone. There was up-regulation of beta-adrenergic receptors on peripheral blood mononuclear cells 30 and 60 min after clonidine which was related to the fall in blood pressure, noradrenaline and adrenaline levels and to the increase in growth hormone levels. The affinity of the receptors was decreased. Return to baseline values was observed after 2 h. Intracellular production of cAMP after isoproterenol stimulation demonstrated that the up-regulation was not functional. Our studies indicate short term up-regulation of beta-adrenoceptors in peripheral blood mononuclear cells after clonidine. These observations after a reduction in sympathetic activity may be of importance if they mirror the pattern of redistribution of adrenoceptors, which are present in a wide range of tissues.


The enigma of insulin resistance and hypertension. Insulin resistance, blood pressure, and the circulation.
The epidemiologic link between obesity and hypertension is more clearly emerging to be one between insulin resistance and hypertension. Relative insulin resistance occurs not only in obese hypertensive patients but also in non-obese lean essential hypertensive patients. Although insulin has complex actions on the circulation, plausible mechanisms by which insulin might raise blood pressure include renal sodium retention and stimulation of the sympathetic nervous system. However, the evidence that insulin can actually raise blood pressure in the long-term is lacking. Since hypertension does not develop in all obese or insulin-resistant subjects, the relationship must be modulated by other genetic or environmental factors. Obesity, diminished physical conditioning, aging, and diabetes are ubiquitous contributors to relative insulin resistance and all are associated with a tendency for blood pressure to rise. Conditions and agents associated with acquired insulin resistance and secondary forms of hypertension include pregnancy, oral contraceptives, acromegaly, and glucocorticoids. Although type 2 non-insulin-dependent diabetes is a state of increased insulin resistance, hypertension is partly sustained by secondary renal mechanisms. Future research should identify the genetic and environmental determinants of insulin resistance in hypertension and utilize these in therapy.