Secretory meningioma: clinicopathologic features of eight cases.
The clinical and morphological features of eight patients with meningothelial meningiomas with numerous pseudopsammoma bodies (secretory meningiomas) are presented. The six female and two male patients ranged in age from 43 to 68 years. Tumours were located at the petroclival region in two, the lateral parasellar region in two, the petrous apex in one and the sphenoid ridge in three patients. On magnetic resonance imaging, they were iso or hypointense on T1-weighted images, and hyper or isointense on T 2-weighted images. Peritumoral brain edema was absent in five cases, and was mild to moderate in three cases. Serum carcinoembryonic antigen (CEA) levels were measured preoperatively in three patients, with one having an elevated serum CEA level which re turned to normal following tumour resection. Immunohistochemical analysis on the resected tumour tissues, pseudopsammoma bodies and surrounding tumour cells were shown to be CEA-positive. Ultrastructurally, pseudopsammoma bodies were composed of granular and filamentous materials located predominantly in the intracellular lumina, which were lined by microvilli. While these morphological features of focal epithelial and secretory differentiation of tumour cells call attention to the broad spectrum of differentiation properties of meningiomas, the biological behavior of the eight tumours reported herein corresponded to those of meningiomas in general.


Altering cortical input unmasks synaptic phenotypes in the YAC128 cortico-striatal co-culture model of Huntington disease.
Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG expansion in the huntingtin (HTT) gene, leading to selective and progressive neuronal death predominantly in the striatum. Mutant HTT expression causes dysfunctional cortico-striatal (CS) transmission, loss of CS synapses, and striatal medium spiny neuron (MSN) dendritic spine instability prior to neuronal death. Co-culturing cortical and striatal neurons in vitro promotes the formation of functional CS synapses and is a widely used approach to elucidate pathogenic mechanisms of HD and to validate potential synapto-protective therapies. A number of relevant in vivo synaptic phenotypes from the YAC128 HD mouse model, which expresses full-length transgenic human mutant HTT, are recapitulated in CS co-culture by 21 days in vitro (DIV). However, striatal spine loss, which occurs in HD patients and in vivo animal models, has been observed in YAC128 CS co-culture in some studies but not in others, leading to difficulties in reproducing and interpreting results. Here, we investigated whether differences in the relative proportion of cortical and striatal neurons alter YAC128 synaptic phenotypes in this model. YAC128 MSNs in 1:1 CS co-culture exhibited impaired dendritic length and complexity compared to wild-type, whereas reducing cortical input using a 1:3 CS ratio revealed a dramatic loss of YAC128 MSN dendritic spines. Chimeric experiments determined that this spine instability was primarily cell autonomous, depending largely on mutant HTT expression in striatal neurons. Moreover, we found that spontaneous electrophysiological MSN activity correlated closely with overall dendritic length, with no differences observed between genotypes in 1:3 co-cultures despite significant YAC128 spine loss. Finally, limiting cortical input with a 1:3 CS ratio impaired the basal survival of YAC128 neurons at DIV21, and this was partially selective for dopamine- and cAMP-regulated phosphoprotein 32-positive MSNs. Our findings reconcile previous discordant reports of spine loss in this model, and improve the utility and reliability of the CS co-culture for the development of novel therapeutic strategies for HD.


Application of Intra-articular Corticosteroid Injection in Juvenile Idiopathic Arthritis.
Juvenile idiopathic arthritis (JIA) is one of the common rheumatic diseases in pediatrics. Persistent synovitis and joint pain cause reduced range of motion, deformity and gait interruption, which are important reasons for children's disability and a decline in their quality of life. Rheumatology experts have explored good treatment strategies, among which intra-articular corticosteroid injections (IACIs) targeting joints can greatly reduce these systemic adverse reactions while still obtaining local anti-inflammatory effects. Local inhibition of synovitis by the use of steroid hormones in a joint cavity can avoid or reduce adverse reactions of systemic therapy, prevent or treat leg length variance and joint contracture, solve Baker's cyst, improve tenosynovitis, promote physical therapy and rehabilitation, make gait change smoothly, relieve pain, and restore joint function. Given the importance of IACIs in treating JIA, this paper reviewed the case selection, drug injection, dose selection, current anesthesia and injection techniques, the efficacy, recurrence, and influencing factors of IACIs, the management of physiotherapy intervention post-injection, the application of ultrasound guidance and the safety and complications of IACIs in children with JIA. This study aims to guide the use of IACIs for the best approach throughout the review.


A Randomised Trial Examining Cardiovascular Morbidity and All-Cause Mortality 24 years Following General Health Checks: the Ebeltoft Health Promotion Project (EHPP).
Global prevalence of risk factors for cardiovascular disease (CVD) and all-cause mortality is increasing. Treatments are available but can only be implemented if individuals at risk are identified. General health checks have been suggested to facilitate this process. To examine the long-term effect of population-based general health checks on CVD and all-cause mortality. The Ebeltoft Health Promotion Project (EHPP) is a parallel randomised controlled trial in a Danish primary care setting. The EHPP enrolled individuals registered in the Civil Registration System as (1) inhabitants of Ebeltoft municipality, (2) registered with a general practitioner (GP) participating in the study and (3) aged 30-49 on 1 January 1991. A total of 3464 individuals were randomised as invitees (n=2000) or non-invitees (n=1464). Of the invitees, 493 declined. As an external control group, we included 1 511 498 Danes living outside the municipality of Ebeltoft. Invitees were offered a general health check and, if test-results were abnormal, recommended a 15-45 min consultation with their GP. Non-invitees in Ebeltoft received a questionnaire at baseline and were offered a general health check at year 5. The external control group, that is, the remaining Danish population, received routine care only. HRs for CVD and all-cause mortality. Every individual randomised was analysed. When comparing invitees to non-invitees within the municipality of Ebeltoft, we found no significant effect of general health checks on CVD (HR=1.11 (0.88; 1.41)) or all-cause mortality (HR=0.93 (0.75; 1.16)). When comparing invitees to the remaining Danish population, we found similar results for CVD (adjusted HR=0.99 (0.86; 1.13)) and all-cause mortality (adjusted HR=0.96 (0.85; 1.09)). We found no effect of general health checks offered to the general population on CVD or all-cause mortality. NCT00145782; 2015-57-0002; 62908, 187.


Characterizing exons 11 and 1 promoters of the mu opioid receptor (Oprm) gene in transgenic mice.
The complexity of the mouse mu opioid receptor (Oprm) gene was demonstrated by the identification of multiple alternatively spliced variants and promoters. Our previous studies have identified a novel promoter, exon 11 (E11) promoter, in the mouse Oprm gene. The E11 promoter is located approximately 10 kb upstream of the exon 1 (E1) promoter. The E11 promoter controls the expression of nine splice variants in the mouse Oprm gene. Distinguished from the TATA-less E1 promoter, the E11 promoter resembles a typical TATA-containing eukaryote class II promoter. The aim of this study is to further characterize the E11 and E1 promoters in vivo using a transgenic mouse model. We constructed a approximately 20 kb transgenic construct in which a 3.7 kb E11 promoter region and an 8.9 kb E1 promoter region controlled expression of tau/LacZ and tau/GFP reporters, respectively. The construct was used to establish a transgenic mouse line. The expression of the reporter mRNAs, determined by a RT-PCR approach, in the transgenic mice during embryonic development displayed a temporal pattern similar to that of the endogenous promoters. X-gal staining for tau/LacZ reporter and GFP imaging for tau/GFP reporter showed that the transgenic E11 and E1 promoters were widely expressed in various regions of the central nervous system (CNS). The distribution of tau/GFP reporter in the CNS was similar to that of MOR-1-like immunoreactivity using an exon 4-specific antibody. However, differential expression of both promoters was observed in some CNS regions such as the hippocampus and substantia nigra, suggesting that the E11 and E1 promoters were regulated differently in these regions. We have generated a transgenic mouse line to study the E11 and E1 promoters in vivo using tau/LacZ and tau/GFP reporters. The reasonable relevance of the transgenic model was demonstrated by the temporal and spatial expression of the transgenes as compared to those of the endogenous transcripts. We believe that these transgenic mice will provide a useful model for further characterizing the E11 and E1 promoter in vivo under different physiological and pathological circumstances such as chronic opioid treatment and chronic pain models.


Photoelectrochemistry of n-type antimony sulfoiodide nanowires.
In the presented work the photoelectrochemical properties of SbSI along with the electronic structure (i.e. conduction and valence band edge potentials as well as conductivity type) of sonochemically obtained nanowires are discussed for the first time. The spectroscopic investigations indicate interesting optical properties, including surface isotope effect and excitonic emission. The photoelectrochemical investigation of SbSI revealed the occurrence of the photoelectrochemical photocurrent switching effect. It may be defined as a change in photocurrent direction (generated at the illuminated semiconducting electrode immersed in electrolyte) due to an appropriate polarization of the electrode versus the reference electrode. It is often observed for semiconductors as a result of the reduction of molecular oxygen dissolved in the electrolyte. However, in the case of SbSI, the photocurrent switching was recorded regardless of the presence of molecular oxygen in the electrolyte, probably due to the reduction of triiodide species formed at anodic polarization of the SbSI electrode, in an iodide-containing electrolyte. The switching potential (i.e. the potential where anodic-to-cathodic photocurrent transition occurs) equals to ca. 0.4 V versus standard hydrogen electrode, which is close to the formal potential of the I(-)/I3(-) redox couple. Therefore, this semiconducting material is of potential interest for the construction of new photovoltaic systems, novel optoelectronic switches and logic devices.


Nicotine-induced conditioned place preference in rats: sex differences and the role of mGluR5 receptors.
To elucidate sex differences in nicotine addiction and the underlying mechanisms of the conditioning aspects of nicotine, nicotine-induced conditioned place preference (CPP) was evaluated in male and female Sprague Dawley rats using a three-chambered CPP apparatus and a biased design. In a series of experiments, the dose-response curve was obtained, pairings between the drug and initially non-preferred versus preferred compartments were compared, and the involvement of mGluR5 receptors in nicotine-induced CPP was evaluated. Modulation of nicotine-induced CPP with mGluR5 inhibition was obtained by MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride). Our results show that nicotine induces CPP dose-dependently in male rats but not in female rats. The comparison of the biased protocol, pairing nicotine with the initially preferred and non-preferred chambers, indicated that nicotine-induced CPP in male rats under both conditions, but the effect was stronger when nicotine was paired with the initially non-preferred side. The selective mGluR5 antagonist MPEP inhibited nicotine-induced CPP in male rats. In conclusion, the results of the current study in rats demonstrate that the conditioning effect of nicotine is more important in males than in females. Furthermore, in line with reported findings, our results suggest that mGluR5 antagonism may be therapeutically useful in smoking cessation during the maintenance of smoking behavior when conditioning plays an important role, notwithstanding the fact that this effect is observed only in male rats, not in females.


Facile Synthesis of Black Phosphorus Nanosheet@NaReF4 Nanocomposites for Potential Bioimaging.
Black phosphorus nanomaterials (BPN) have been well developed in tumor therapy. However, lack of diagnostic function limits the development of BPN in biomedicine. Lanthanide-doped nanoparticles are considered as versatile materials for fluorescence or magnetic resonance imaging. Integration of BPN with lanthanide-doped nanoparticles was rarely reported owing to the complex synthesis processes and poor modification effect. Herein, we report a simple and general method for synthesizing BPN@NaReF4 (Re: Gd or Y, Yb, Er) nanocomposite. TEM and XRD characterization confirm efficient combination of BPN and NaGdF4 or NaYF4:Yb,Er (18.2 mol %) after one-step mixing. The FTIR and XPS spectra were used to prove the generation of PO43--Gd and P-Gd coordination bonds and clarify ligand exchange mechanism. The anchored nanoparticles on BPN were stable and become hydrophilic. The prepared BPN@NaGdF4 exhibit the signals of photoacoustic and magnetic resonance imaging. The obtained BPN@NaYF4:Yb,Er (18.2 mol %) have the potential in fluorescence bioimaging. We believe that this work will expand the applications of BPN in diagnosis and therapy together.


The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.


Cognitive problems in patients on androgen deprivation therapy: a qualitative pilot study.
Androgen deprivation therapy (ADT; also known as hormone therapy) is a well-established treatment for prostate cancer patients with rising prostate-specific antigen levels after localized treatment, and for those with metastatic disease. The neurological impact of ADT has been likened to that of aging and is therefore theorized to impair cognitive functioning in prostate cancer patients. We briefly summarize the research that has examined cognitive functioning of ADT patients primarily through neuropsychological assessment. A qualitative pilot study is presented with the aim of describing ADT patients' experiences of cognitive changes since starting ADT. Semistructured telephone interviews were undertaken with 11 community-dwelling prostate cancer patients undergoing ADT following definitive localized treatment. Participants were recruited via online prostate cancer support forums. Content analyses were conducted to establish relevant themes, which in this case were the cognitive domains of impairment. Eight of the 11 participants reported impairments in the domains of concentration, information processing, verbal fluency, visual information processing/visuospatial function, memory, and executive dysfunction. Neurobehavioral problems, including neurofatigue and apathy were also reported. The interviews illustrate the potential negative effects of ADT on cognitive and neurobehavioral functions, and their impact on patients' work and in their daily lives. We describe how the field of cognitive rehabilitation offers promising tools to assist ADT patients with cognitive problems.


Induction of apoptosis in rat lung epithelial cells by multiwalled carbon nanotubes.
Carbon nanotubes (CNTs), the most promising material with unique characteristics, find its application in different fields ranging from composite materials to medicine and from electronics to energy storage. However, little is known about the mechanism behind the interaction of these particles with cells and their toxicity. So, here we investigated the adverse effects of multiwalled CNTs (MWCNTs) in rat lung epithelial (LE) cells. The results showed that the incubation of LE cells with 0.5-10 microg/mL of MWCNTs caused a dose- and time-dependent increase in the formation of free radicals, the accumulation of peroxidative products, the loss of cell viability, and antioxidant depletion. The significant amount of incorporation of dUTPs in the nucleus after 24 h confirms the induction of apoptosis. It was also observed that there is an increase in the activity of both caspases-3 and caspase-8 in cells, with increases in time and the concentration of MWCNTs. No significant incorporation of dUTPs was observed in cells, incubated with z-VAD-fmk, which confirmed the role of caspases in DNA fragmentation. The present study reveals that MWCNTs induced oxidative stress and stimulated apoptosis signaling pathway through caspase activation in rat LE cell lines.


Assessing the temperature of thermally generated inhalation aerosols.
Condensation aerosols are produced when a drug is vaporized and then cools in the inhalation air. Because energy is applied to vaporize the drug, there is a potential concern that the air temperature might not be well tolerated. A literature review indicates that the proper metric for this is the wet-bulb temperature (T(wb)) of the inhaled air. T(wb) measures the total energy of the air, including moisture content, and reflects the potential impact on safety and tolerability. The Staccato® system (Alexza Pharmaceuticals, Mountain View, CA) uses thermal vaporization for aerosol generation and was used in a series of studies to characterize the peak transient value (peak T(wb)) of the air coming out of the device. These studies evaluated peak T(wb) over a range of air flow rates (15-45 L/min), ambient conditions [15-30°C and 15 to 90% relative humidity (RH)] and vaporization temperatures. Under nominal conditions (30 L/min air flow, 25°C and 50% RH), peak T(wb) was 28.8 ± 0.6°C (mean ± standard deviation). Over the range of operating conditions tested, mean values for peak T(wb) ranged from 26.2 to 33.3°C with similarly low variances. When operated under a combination of extreme conditions, peak T(wb) was measured to be 39.9 ± 0.1°C (mean ± standard deviation). Technical standards indicate that the upper limit on inhaled T(wb) for safety and tolerability is 50°C, and inhalation at that temperature can be sustained for 1 h. Peak values of T(wb) from the Staccato system are well below that threshold, approximately 30°C at nominal conditions and approximately 40°C at a combination of extreme conditions. Moreover, the peak lasts for only a few seconds, well under the time limit of 1 h. These results suggest that aerosols generated with the Staccato system will be safe and well tolerated.


Impact of degradable macromer content in a poly(ethylene glycol) hydrogel on neural cell metabolic activity, redox state, proliferation, and differentiation.
Hydrogels that degrade at different rates were prepared by copolymerizing slowly degrading macromer poly(ethylene glycol) (PEG) dimethacrylate with a faster degrading macromer poly(lactic acid)-b-PEG-b-poly(lactic acid) dimethacrylate. A clinically relevant population of neural cells composed of differentiated neurons and multipotent precursor cells was cultured within hydrogels. Within 2 h after encapsulation, metabolic activity was higher in hydrogels prepared with increasing levels of degradable content. This improvement was accompanied by a reduction in intracellular redox state and an increase in the fraction of glutathione in the reduced state, both of which persisted throughout 7 days of culture and which may be the result of radical scavenging by lactic acid. Importantly, an increase in cellular proliferation was observed in gels prepared with increasing degradable macromer content after 7 days of growth without a shift in the cellular composition of the culture toward the glial cell phenotype. The findings of this study provide additional insight into the growth of neural cells in PEG-based hydrogels. Results suggest that lactic acid released during gel degradation may impact the function of encapsulated cells, a finding of general interest to biomaterials scientists who focus on the development of degradable polymers for cell culture and drug delivery devices.


Regulation of lipid production by light-emitting diodes in human sebocytes.
Light-emitting diodes (LED) have been used to treat acne vulgaris. However, the efficacy of LED on sebaceous lipid production in vitro has not been examined. This study investigated the efficacy of 415 nm blue light and 630 nm red light on lipid production in human sebocytes. When applied to human primary sebocytes, 415 nm blue light suppressed cell proliferation. Based on a lipogenesis study using Oil Red O, Nile red staining, and thin-layered chromatography, 630 nm red light strongly downregulated lipid production in sebocytes. These results suggest that 415 nm blue light and 630 nm red light influence lipid production in human sebocytes and have beneficial effects on acne by suppressing sebum production.


Notch signaling in T-cell acute lymphoblastic leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is a form of pediatric leukemia that is thought to be caused by approximately 12 distinct chromosomal translocations that lead to aberrant expression of as many different cellular genes. Development of novel, rational therapies against such a diverse set of mechanistic targets has thus been a formidable challenge. Recent studies, however, have identified a large fraction of T-ALL cases carrying mutations in one of these genes, Notch1, suggesting for the first time that many cases may share a common pathogenic etiology, and perhaps may allow the development of targeted therapies that benefit the majority of patients with this disease.


Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects.
Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject for a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the end of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5 %, 17 %), intermediate-dose (6 %, 25 %) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.


Subacromial space injection: pain reliever, diagnostic tool.
Some of the most common presentations in a primary care office relate to shoulder pain; disorders of the rotator cuff and potential look-alikes such as referred neck pain or acromioclavicular (AC) joint arthritis are chief among the causes. The differential diagnosis can be difficult, particularly among older patients. And, of course, patients want relief of pain. Subacromial space injection using anesthetic with or without corticosteroid can assist in both phases of management.


Improvement in fatty acid utilization in relation to a change in left ventricular hypertrophy in spontaneously hypertensive rats.
Although fatty acid metabolism is reportedly impaired in myocardial hypertrophy, it is unclear whether the antihypertensive drugs are associated with improved fatty acid metabolism. In order to evaluate the effects of antihypertensive drugs on fatty acid metabolism and myocardial perfusion, the simultaneous uptake of iodine-125(125I)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and thallium-201 (Tl) were measured in 3 groups of rats: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR chronically treated with captopril (SHR-C), and (3) SHR chronically treated with hydralazine (SHR-H). Captopril and hydralazine were administered to their respective groups for 3 weeks from 12 weeks of age. The hearts were removed 10 min after simultaneous intravenous injections of BMIPP and Tl and the 125I and 201Tl counts were measured to calculate the uptake ratio. The systolic blood pressure (SBP) in SHR-N was 222+/-10 mm Hg, whereas the SHR-C and SHR-H groups showed significant SBP reduction (156+/-11, and 158+/-10 mm Hg, respectively) (p<0.01 each). The heart/bodyweight ratio was significantly lower in SHR-C (2.48+/-0.09) than in SHR-N (2.74+/-0.11) (p<0.05). However, there was no significant difference in the heart/bodyweight ratio between SHR-N and SHR-H (2.65+/-0.09). The ratio of BMIPP uptake to Tl uptake (BMIPP/Tl) was significantly higher in SHR-C (0.71+/-0.13) than in SHR-N (0.50+/-0.09) (p<0.05). However, BMIPP/Tl in SHR-H (0.53+/-0.09) was similar to that in SHR-N. These results suggest that captopril improves fatty acid metabolism in the hypertrophied ventricle in SHR. The metabolic alterations may improve with left ventricular hypertrophy regression but are not effected by the reduction of blood pressure only.


Dynamics of plateau bursting depending on the location of its equilibrium.
We present a mathematical analysis of the dynamics that underlies plateau bursting in models of endocrine cells under variation of the location of the (unstable) equilibrium around which these bursting patterns are organised. We focus primarily on the less well-studied case of pseudo-plateau bursting, but also consider the square-wave case. The behaviour of such models is explained using the theory for systems with multiple time scales and it is well known that the underlying so-called fast subsystem organises their dynamics. However, such results are valid only in a sufficiently small neighbourhood of the singular limit that defines the fast subsystem. Hence, the slow variable (intracellular calcium concentration) must be very slow, which is actually not the case for pseudo-plateau bursting. Furthermore, the theoretical predictions are also only valid for parameter values such that the equilibrium is close to a homoclinic bifurcation occuring in the fast subsystem. In the present study, we use numerical explorations to discuss what happens outside this theoretically known neighbourhood of parameter space. In particular, we consider what happens as the equilibrium moves outside a small neighbourhood of the homoclinic bifurcation that occurs in the fast subsystem, and relatively fast speeds are allowed for the slow variable which is controlled by a relatively large value of a parameter ε. The results obtained complement our earlier work [Tsaneva-Atanasova et al. (2010) J Theor Biol264, 1133-1146], which focussed on how the bursting patterns vary with the rate of change ε of the slow variable: we fix ε and move the equilibrium over the full range of the bursting regime. Our findings show that the transitions between different bursting patterns are rather similar for square-wave and pseudo-plateau bursting, provided that the value of ε for the pseudo-plateau-bursting model is chosen so that it is much larger than for the square-wave bursting model. Furthermore, the two families of tonic spiking and plateau bursting, which are generally viewed as two separately generated families, are actually connected into a single family in the two-parameter plane through branches of unstable periodic orbits.


18F-FDG-PET/CT of peritoneal tumors: a pictorial essay.
Cancer imaging on the peritoneum is quite difficult on PET/CT because of the particular anatomical features of this membrane. The abdominal cavity can be the seat of very different primary or secondary tumoral lesions, with heterogeneous aggressiveness and variable fluorine-18 fluorodeoxyglucose uptake and patterns. We aimed to depict a spectrum of appearances with abnormal fluorine-18 fluorodeoxyglucose uptakes localized on the peritoneum in frequent conditions such as peritoneal carcinomatosis and in rarer disease such as desmoplastic round cell tumor.


Degree of applicability and consequences of inappropriate use of units of light.
Since light is defined quantitatively as radiant energy evaluated according to the CIE photopic luminosity curve, ordinary t units are inappropriate whenever the organism's spectral sensitivity differs markedly from the CIE curve. Examples of differing spectral sensitivities include those of animals, of color defective individuals, and curves for all individuals under low light levels or with large fields. Calculations are presented of the amount of error involved when units of light are used for these inappropriate conditions; alternative solutions to the problem are discussed.


The Consortium on the Genetics of Schizophrenia: neurocognitive endophenotypes.
The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, adequate between-site reliability, impairments in patients not due to medications, impairments observed regardless of illness state), heritability, findings of higher rates in relatives of probands than in the general population, and cosegregation within families. The COGS required that, in addition, the measures be "neurocognitive" and thus linked to neurobiology and that they be feasible in multisite studies. The COGS neurocognitive assessment includes measures of attention, verbal memory, working memory, and a computerized neurocognitive battery that also includes facial processing tasks. Here we describe data demonstrating that these neurobehavioral measures meet criteria for endophenotypic candidacy. We conclude that quantitative neurocognitive endophenotypes need further evidence for efficacy in identifying genetic effects but have the potential of providing unprecedented insight into gene-environment interaction related to dimensions of brain and behavior in health and disease.


An update on the role of thioredoxin-interacting protein in diabetic kidney disease: A mini review.
Thioredoxin-interacting protein (TXNIP) was first isolated from Vitamin D3-exposed HL60 cells. TXNIP is the main redox-regulating factor in various organs and tissues. We begin with an overview of the TXNIP gene and protein information, followed by a summary of studies that have shown its expression in human kidneys. Then, we highlight our current understanding of the effect of TXNIP on diabetic kidney disease (DKD) to improve our understanding of the biological roles and signal transduction of TXNIP in DKD. Based on the recent review, the modulation of TXNIP may be considered as a new target in the management of DKD.


Influence of RpoN on isocitrate lyase activity in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in patients with cystic fibrosis (CF). The metabolic pathways utilized by P. aeruginosa during these infections, which can persist for decades, are poorly understood. Several lines of evidence suggest that the glyoxylate pathway, which utilizes acetate or fatty acids to replenish intermediates of the tricarboxylic acid cycle, is an important metabolic pathway for P. aeruginosa adapted to the CF lung. Isocitrate lyase (ICL) is one of two major enzymes of the glyoxylate pathway. In a previous study, we determined that P. aeruginosa is dependent upon aceA, which encodes ICL, to cause disease on alfalfa seedlings and in rat lungs. Expression of aceA in PAO1, a P. aeruginosa isolate associated with acute infection, is regulated by carbon sources that utilize the glyoxyate pathway. In contrast, expression of aceA in FRD1, a CF isolate, is constitutively upregulated. Moreover, this deregulation of aceA occurs in other P. aeruginosa isolates associated with chronic infection, suggesting that high ICL activity facilitates adaptation of P. aeruginosa to the CF lung. Complementation of FRD1 with a PAO1 clone bank identified that rpoN negatively regulates aceA. However, the deregulation of aceA in FRD1 was not due to a knockout mutation of rpoN. Regulation of the glyoxylate pathway by RpoN is likely to be indirect, and represents a unique regulatory role for this sigma factor in bacterial metabolism.


Neuroprotective role of fibronectin in neuron-glial extrasynaptic transmission.
Most hypotheses concerning the mechanisms underlying Parkinson's disease are based on altered synaptic transmission of the nigrostriatal system. However, extrasynaptic transmission was recently found to affect dopamine neurotransmitter delivery by anisotropic diffusion in the extracellular matrix, which is modulated by various extracellular matrix components such as fibronectin. The present study reviewed the neuroprotective effect of fibronectin in extrasynaptic transmission. Fibronectin can regulate neuroactive substance diffusion and receptor activation, and exert anti- neuroinflammatory, adhesive and neuroprotective roles. Fibronectin can bind to integrin and growth factor receptors to transactivate intracellular signaling events such as the phosphatidylinositol 3-kinase/protein kinase B pathway to regulate or amplify growth factor-like neuroprotective actions. Fibronectin is assembled into a fibrillar network around cells to facilitate cell migration, molecule and ion diffusion, and even drug delivery and treatment. In addition, the present study analyzed the neuroprotective mechanism of fibronectin in the pathogenesis of Parkinson's disease, involving integrin and growth factor receptor interactions, and discussed the possible therapeutic and diagnostic significance of fibronectin in Parkinson's disease.


Chronic pulmonary thromboembolism pathologically showing homogeneous cellular alveolitis.
A 60-year-old man was admitted to our hospital complaining of general malaise. Examination of arterial blood gases on room air revealed hypoxia. Pulmonary function test showed restrictive abnormality. Chest high-resolution CT showed diffuse mosaic attenuation without evident pulmonary artery abnormality on contrast chest CT. Based on these findings, interstitial pneumonia or chronic pulmonary thromboembolism was suspected. The findings of bronchoalveolar lavage revealed 4.4×10(5) cells/mL, including 89.6% macrophages, 9.4% lymphocytes, and 1.0% neutrophils. TBLB showed marked alveolitis. Moreover video-assisted thoracoscopic surgical biopsy was performed. Biopsies of the lung specimen showed focal infarct with surrounding mild mononuclear cell infiltrates (homogenous cellular alveolitis). (99m)Tc pulmonary perfusion and (81m)Kr ventilation scintigraphy showed V/Q mismatch. Furthermore, pulmonary angiography also revealed inadequate artery flow corresponding to the mismatch area of scintigraphy. Collagen vascular diseases and abnormality of coagulation factors were not detected. Multiple perfusion defects persisted for more than 6 months. Thus, finally the patient was diagnosed with chronic pulmonary thromboembolism, pathologically showing homogenous cellular alveolitis.


Docking of protein molecular surfaces with evolutionary trace analysis.
We have developed a new method to predict protein- protein complexes based on the shape complementarity of the molecular surfaces, along with sequence conservation obtained by evolutionary trace (ET) analysis. The docking is achieved by optimization of an object function that evaluates the degree of shape complementarity weighted by the conservation of the interacting residues. The optimization is carried out using a genetic algorithm in combination with Monte Carlo sampling. We applied this method to CAPRI targets and evaluated the performance systematically. Consequently, our method could achieve native-like predictions in several cases. In addition, we have analyzed the feasibility of the ET method for docking simulations, and found that the conservation information was useful only in a limited category of proteins (signal related proteins and enzymes).


Quantum effects in energy and charge transfer in an artificial photosynthetic complex.
We investigate the quantum dynamics of energy and charge transfer in a wheel-shaped artificial photosynthetic antenna-reaction center complex. This complex consists of six light-harvesting chromophores and an electron-acceptor fullerene. To describe quantum effects on a femtosecond time scale, we derive the set of exact non-Markovian equations for the Heisenberg operators of this photosynthetic complex in contact with a Gaussian heat bath. With these equations we can analyze the regime of strong system-bath interactions, where reorganization energies are of the order of the intersite exciton couplings. We show that the energy of the initially excited antenna chromophores is efficiently funneled to the porphyrin-fullerene reaction center, where a charge-separated state is set up in a few picoseconds, with a quantum yield of the order of 95%. In the single-exciton regime, with one antenna chromophore being initially excited, we observe quantum beatings of energy between two resonant antenna chromophores with a decoherence time of ∼100 fs. We also analyze the double-exciton regime, when two porphyrin molecules involved in the reaction center are initially excited. In this regime we obtain pronounced quantum oscillations of the charge on the fullerene molecule with a decoherence time of about 20 fs (at liquid nitrogen temperatures). These results show a way to directly detect quantum effects in artificial photosynthetic systems.


Impact of signals and experience on trust and trusting behavior.
Trust is an essential factor that drives virtual interaction and transactions on the Internet. Researchers have investigated the trust development process, and identified several important factors that form the basis for trust. This research combines the signal perspective and trust theory to examine the impact of market signals and past experience on trust formation and trusting behavior. Three market signals, including brand image, Web-site investment, and privacy policies, are identified and empirically tested to determine their impact on consumer trust. Based on 322 active Web users, the quantitative results suggest that brand image, Web-site investment, privacy policies, and past experience all positively impact trust formation. Furthermore, trust shows a positive effect on Web-site stickiness. Both theoretical and practical implications of the results are also offered.


Normal values for distortion product otoacoustic emissions in children: a study using primary levels previously demonstrated to be optimum for identification of hearing loss.
No published data exist for normal values of distortion product otoacoustic emissions (DPOAE) in children at primary levels f1 = 65 dB and f2 = 55 dB SPL. These primary levels have been previously demonstrated to be optimal for identification of hearing impaired ears in adults. A total of 102 normal children underwent audiological assessment, including exclusion of middle ear disease, pure tone audiometry and DPOAE DP-grams (primaries L1/L2 = 65/55 dB SPL, f1:f2 = 1.22). There was a statistically significant decrease in DPOAE amplitude with increasing age. DPOAE amplitude was also dependent on the frequency of f2. However, there was wide inter- and intra-individual variation in DPOAE amplitude at different frequencies of f2. There was also a large overlap between the range of values of DPOAE amplitude between the adjacent age groups. Detailed assessment of DPOAE in children is feasible in the clinical setting. These normal values should prove invaluable in future studies; however, the large range of normal values means that cross-sectional studies may not be able to detect small variations in cochlear function.


Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial.
Patients with chronic hepatitis C and low serum and hepatic iron stores may have an improved response to interferon (IFN). We tested whether iron reduction before and during IFN therapy would lead to an improved sustained biochemical and virological response compared with IFN alone. Eighty-two previously untreated patients with chronic hepatitis C were randomized to either: group A IFN-alpha2b 3 MU 3 times per week for 6 months, or group B iron reduction before and during IFN-alpha2b 3 MU 3 times per week for 6 months. Group B patients had lower mean serum alanine transaminase (ALT) levels than group A patients during treatment and follow-up. Group B patients had significantly lower mean hepatitis C virus (HCV)-RNA levels at treatment weeks 4 and 12 (P <.05). Serum HCV RNA was undetectable at the end of treatment in 15 group B patients compared with 7 group A patients (P =.03); 7 group B patients and 3 group A patients had persistently undetectable serum HCV RNA 24 weeks after the end of therapy (P =.20). Paired pre- and posttreatment liver biopsies in 18 group B patients demonstrated significant improvements in 2 of the 3 inflammation scores of the Knodell histological activity index (P <. 05). No changes occurred in the paired biopsies from 15 group A patients. We conclude that iron reduction via therapeutic phlebotomy improves the end-of-treatment virological and histological response to short-term IFN therapy. Additional studies are needed to determine if iron reduction in combination with higher doses or longer duration of IFN may be of benefit.


[Large-bowel necrosis following open-heart surgery].
In the last 2 years 9 patients have been operated on in our surgical department because of colon necrosis which developed after open heart surgery. The symptoms--abdominal distension, circumscript peritonitis in the right lower part of the abdomen--developed 2-4 days after the heart operation. Laparotomies were carried out within 2 days from the onset of symptoms in all but one patient. In 7 patients the necrosis of the right colon, while in 2 other patients extreme dilatation of the colon was found. In 6 patients right hemicolectomy was carried out. One operation was finished without anastomosis with double stomas. In the 2 patients with no necrosis catheter-cecostomy was performed. All patients but one after hemicolectomy with reconstruction died after several reoperations because of suture leak. The other 3 patients were cured. We examined and analysed the pre-, intra- and postoperative circumstances of the heart operations, which lead to the severe complications. We think the cause of the problems was the liberal use of wide spectrum antibiotics with caused severe dysbacteriosis and Clostridium difficile toxicosis in the colon. This condition could lead to a pseudomembraneous colitis which resulted in the colon necrosis.


Memory control by the B cell antigen receptor.
The generation of memory B cells (MBCs) that have undergone immunoglobulin class switching from IgM, which dominates primary antibody responses, to other immunoglobulin isoforms is a hallmark of immune memory. Hence, humoral immunological memory is characterized by the presence of serum immunoglobulins of IgG subtypes known as the γ-globulin fraction of blood plasma proteins. These antibodies reflect the antigen experience of B lymphocytes and their repeated triggering. In fact, efficient protection against a previously encountered pathogen is critically linked to the production of pathogen-specific IgG molecules even in those cases where the primary immune response required cellular immunity, for example, T cell-mediated clearance of intracellular pathogens such as viruses. Besides IgG, also IgA and IgE can provide humoral immunity depending on the microbe's nature and infection route. The molecular mechanisms underlying the preponderance of switched immunoglobulin isotypes during memory antibody responses are a matter of active and controversial debate. Here, we summarize the phenotypic characteristics of distinct MBC subpopulations and discuss the decisive roles of different B cell antigen receptor isotypes for the functional traits of class-switched B cell populations.


[Usefulness and cogency of gene probes in paternity questions (Personal experiences: 1989/90].
In cases of disputed parentage usually more than 20 polymorphic systems (red and white cell antigens, serum markers and enzyme markers) have to be analyzed using a battery of different techniques. A more recent method involving analysis of restriction fragment length polymorphism in highly polymorphic genes allows assignment of offspring to their parents. To test the latter method, 28 paternity cases were studied in parallel using conventional systems and detection of RFLPs of probes MS 1, MS 31, MS 43, and g 3, developed by Jeffreys et al. Furthermore, the cogency of exclusion of parentage, the average power of exclusion and the probability of parentage is calculated using published mutation rates and gene frequencies of the four probes. In conclusion, use of the four gene probes has both theoretically and practically turned out to be a powerful method for parentage testing.


Alexia without agraphia in multiple sclerosis: case report with magnetic resonance imaging localization.
The syndrome of alexia without agraphia occurs rarely in multiple sclerosis (MS). We report a patient with right homonymous hemianopsia and alexia without agraphia as his initial manifestations of relapsing-remitting MS. Magnetic resonance imaging (MRI) demonstrated a hyperintense lesion in the left occipital subcortical white matter (WM) and an enhancing lesion in the splenium of the corpus callosum. The clinical presentation and MRI findings were consistent with disconnection of the functional right occipital visual cortex from structures responsible for language comprehension in the left hemisphere. The diagnosis of MS was confirmed by subsequent development of additional periventricular WM lesions.


Reconstruction of the tongue with reinnervated rectus abdominis musculoperitoneal flaps after hemiglossectomy.
Reconstruction of the tongue after glossectomy is a primary objective in the process of improving the life quality of patients suffering from tongue cancer. We developed a new method of surgical reconstruction of the tongue after hemiglossectomy, with reinnervated rectus abdominis musculoperitoneal flaps. The rectus abdominis musculoperitoneal flap consisted of the rectus muscle, posterior rectus sheath, peritoneum, the 10th, 11th and 12th intercostal nerves, and the deep inferior epigastric artery and veins. Five patients underwent immediate reconstruction of the tongue with rectus abdominis musculoperitoneal flaps after hemiglossectomy. The intercostal nerves were anastomosed to the descending branch of the hypoglossal nerve. All transplanted flaps survived. The peritoneum was replaced by squamous epithelium eight weeks after surgery. During the follow-up period, the contour and function of the reconstructed tongues was satisfactory. Our experience indicates that reconstruction of the tongue with rectus abdominis musculoperitoneal flaps after hemiglossectomy is a suitable, cosmetically acceptable method.


Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells.
IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen-activated protein kinase (MAPK) family. Inhibition of JNK prevents IL-1beta-mediated beta cell destruction. In mouse embryo fibroblasts and 3DO T cells, overexpression of the gene encoding growth arrest and DNA-damage-inducible 45beta (Gadd45b) downregulates pro-apoptotic JNK signalling. The aim of this study was to investigate if Gadd45b prevents IL-1beta-induced beta cell MAPK signalling and apoptosis. Rat insulinoma INS-1E cells and mouse beta-TC3 cells stably expressing Gadd45b were generated. The effects of Gadd45b expression on signalling by JNK, ERK and p38 were assessed by Western blotting and kinase assays. Apoptosis rate was measured by terminal deoxynucleotidyl-mediated dUTP-biotin nick end-labelling (TUNEL) and an ELISA designed to detect apoptotic nucleosomes. Expression of endogenous Gadd45b mRNA was measured by RT-PCR. In INS-1E and beta-TC3 cells, expression of Gadd45b inhibited IL-1beta-induced activation of JNK and ERK, but augmented IL-1beta-mediated p38 activity. IL-1beta-induced nitric oxide production and decreases in insulin content and secretion were reduced by GADD45beta. IL-1beta-induced apoptosis was reduced by GADD45beta by up to 77%. Although IL-1beta stimulated the time-dependent induction of endogenous Gadd45b in INS-1E cells and rat islets, expression levels were lower in these cells than in IL-1beta-exposed NIH-3T3 and 3DO T cells. Inadequate induction of Gadd45b, which encodes a novel beta cell JNK and ERK inhibitor, may in part explain the pro-apoptotic response of beta cells to IL-1beta.


Nanoscale multiple gaseous layers on a hydrophobic surface.
The nanoscale gas state at the interfaces of liquids (water, acid, and salt solutions) and highly oriented pyrolytic graphite (HOPG) was investigated via tapping-mode atomic force microscopy (AFM). For the first time, we report that the interfacial gases could form bilayers and trilayers, i.e., on the top of a flat gas layer, there are one or two more gas layers. The formation of these gas layers could be induced by a local supersaturation of gases, which can be achieved by (1) temperature difference between the liquids and the HOPG substrates or (2) exchange ethanol with water. Furthermore, we found that the gas layers were less stable than spherical bubbles. They could transform to bubbles with time or under the perturbation of the AFM tip.


Serum Levels of Angiopoietin-Like Protein 2 and Obestatin in Iranian Women with Polycystic Ovary Syndrome and Normal Body Mass Index.
Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproduction age and a major cause of anovulatory infertility. Insulin resistance plays an important role in the development and durability of this disorder. ANGPTL2 is known as an inflammatory mediator derived from adipose tissue that links obesity to systemic insulin resistance, and obestatin has been identified as a hormone associated with insulin resistance that suppresses food reabsorption, inhibits gastric emptying and decreases weight gain. The aim of this study was to evaluate serum levels of ANGPTL2 and obestatin in PCOS women with normal body mass index (BMI). In this case-control study, 26 PCOS women based on the Rotterdam 2003 diagnostic criteria as the case group and 26 women with normal menstrual cycles as the control group were enrolled. Serum levels of ANGPTL2, obestatin, insulin and other hormone factors related with PCOS were measured by ELISA method and biochemical parameters were measured by an autoanalyzer. Data were analyzed by independent samples-T test, Chi Square, Correlation and a single sample Kolmogrov⁻Smirnov test using SPSS software, version 16. There were no significant variations in the amount of ANGPTL2, obestatin, cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein, cholesterol, creatinine and dehydroepiandrosterone-sulfate between the two groups. There were significant increases in serum levels of fasting blood sugar (p = 0.01), insulin (p = 0.04), homeostasis model assessments of insulin resistance (p = 0.04), testosterone (p = 0.02), luteinizing hormone (p = 0.004), luteinizing hormone/follicle stimulating hormone (p = 0.006) and prolactin (p = 0.04) in case group compared to the control group. A significant positive correlation was observed between ANGPTL2 and insulin (p = 0.02), HOMA-IR (p = 0.01) and, on the other hand, a significant negative correlation was observed between obestatin and insulin (p = 0.01), HOMA-IR (p = 0.008) in PCOS group. In this study, no significant variations were observed in serum levels of ANGPTL2 and obestatin in PCOS women with normal BMI.


Irreversible inhibition of serine proteases by peptide derivatives of (alpha-aminoalkyl)phosphonate diphenyl esters.
Peptidyl derivatives of diphenyl (alpha-aminoalkyl)phosphonates have been synthesized and are effective and specific inhibitors of serine proteases at low concentrations. Z-PheP(OPh)2 irreversibly reacts with chymotrypsin (kobsd/[I] = 1200 M-1 s-1) and does not react with two elastases. The best inhibitor for most chymotrypsin-like enzymes including bovine chymotrypsin, cathepsin G, and rat mast cell protease II is the tripeptide Suc-Val-Pro-PheP(OPh)2 which corresponds to the sequence of an excellent p-nitroanilide substrate for several chymases. The valine derivative Z-ValP(OPh)2 is specific for elastases and reacts with human leukocyte elastase (HLE, 280 M-1 s-1) but not with chymotrypsin. The tripeptide Boc-Val-Pro-ValP(OPh)2, which has a sequence found in a good trifluoromethyl ketone inhibitor of HLE, is the best inhibitor for HLE (kobsd/[I] = 27,000 M-1 s-1) and porcine pancreatic elastase (PPE, kobsd/[I] = 11,000 M-1 s-1). The rates of inactivation of chymotrypsin by MeO-Suc-Ala-Ala-Pro-PheP(OPh)2 and PPE and HLE by MeO-Suc-Ala-Ala-Pro-ValP(OPh)2 were decreased 2-5-fold in the presence of the corresponding substrate, which demonstrates active site involvement. Only one of two diastereomers of Suc-Val-Pro-PheP(OPh)2 reacts with chymotrypsin (146,000 M-1 s-1), and the enzyme-inhibitor complex had one broad signal at 25.98 ppm in the 31P NMR spectrum corresponding to the Ser-195 phosphonate ester. Phosphonylated serine proteases are extremely stable since the half-time for reactivation was greater than 48 h for the inhibited elastases and 7.5-26 h for chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)


Indicators of satisfaction in clickers-aided EFL class.
How to identify whether students are satisfied with clickers-aided EFL class might be largely a mystery for most researchers since satisfaction is deeply hidden in human psychology which is subtle and intangible. This study, by using bivariate correlation analysis and structural equation modeling, survey scales claimed both valid and internally consistent, and data collected from randomly selected 227 participants, explored the indicators of satisfaction in clickers-aided EFL class, together with gender differences in the indicators. It was concluded that satisfaction was positively correlated with interaction, self-efficacy and self-regulation in clickers-aided EFL class without statistically significant gender differences. Furthermore, interaction, self-efficacy and self-regulation were mutually and significantly correlated. Although indicators of satisfaction might not be limited to these three factors, the findings should be helpful to future researchers who desire to determine whether users are satisfied with the polling technology. Then teachers could decide what teaching style and contents should be adopted. In order to satisfy users of clickers, future lecturing might be designed to promote peer interaction, self-efficacy and self-regulation.


Reliability of a MEMS Actuator Improved by Spring Corner Designs and Reshaped Driving Waveforms.
In this paper, we report spring corner designs and driving waveforms to improve the reliability for a MEMS (Micro-Electro-Mechanical System) actuator. In order to prevent the stiction problems, no stopper or damping absorber is adopted. Therefore, an actuator could travel long distance by electromagnetic force without any object in moving path to absorb excess momentum. Due to long displacement and large mass, springs of MEMS actuators tend to crack from weak points with high stress concentration and this situation degrades reliability performance. Stress distribution over different spring designs were simulated and a serpentine spring with circular and wide corner design was chosen due to its low stress concentration. This design has smaller stress concentration versus displacement. Furthermore, the resonant frequencies are removed from the driving waveform based on the analysis of discrete Fourier transfer function. The reshaped waveform not only shortens actuator switching time, but also ensures that the spring is in a small displacement region without overshooting so that the maximum stress is kept below 200 MPa. The experimental results show that the MEMS device designed by theses principles can survive 500 g (gravity acceleration) shock test and pass 150 million switching cycles without failure.


Modulation of Disordered Bile Acid Homeostasis and Hepatic Tight Junctions Using Salidroside against Hepatocyte Apoptosis in Furan-Induced Mice.
Furan, a processing-induced food contaminant, has attracted great attention due to its hepatotoxicity. To further investigate the underlying mechanism of salidroside (SAL) alleviating furan-induced liver damage, we divided Balb/c mice into the control group, the furan (8 mg/kg/day) group, and three groups of three different doses of SAL (10/20/40 mg/kg/day) in the current research. The shifted serum profile was observed through untargeted metabonomics, to which the bile acid metabolism was related, and the alleviating effect of SAL against furan-induced apoptosis was caused by the metabolism. Target bile acid quantification for the liver and serum showed that SAL positively regulated the homeostasis of bile acids disturbed by furan. Meanwhile, SAL significantly upregulated the synthesis genes of bile acids (Cyp7a1, Cyp7b1, Cyp8b1, and Cyp27a1) and the uptake transport genes (Ntcp and Oatps) and downregulated the efflux transport genes (Bsep, Ost-α, Ost-β, Mrp2, and Mrp4). Transmission electron microscopy of the bile canaliculi and tight junctions and the levels of tight junction marker proteins (ZO-1, occludin, and claudin-1) confirmed that the disruption of the hepatic tight junction was inhibited by SAL. The connection between the apoptosis- and tight junction-related proteins was observed through the construction of a protein-protein interaction network. SAL suppressed the furan-induced hepatocyte apoptosis evidenced by the detection of TUNEL and Bax, Bcl-2, and caspase-3 levels. Taken together, SAL alleviated furan-induced hepatocyte apoptosis via altering the disordered homeostasis of bile acids and hepatic tight junctions.


Response of Bitot's spots to a single oral 100,000- or 200,000-IU dose of vitamin A.
A randomized, controlled clinical trial was conducted in Indonesia to study the response of Bitot's spots to a 100,000-IU dose of vitamin A, which is known to be associated with fewer acute side effects than the currently recommended 200,000-IU dose. A total of 114 children (ages 13 to 59 months) with Bitot's spots were given an ocular examination; serum retinol concentration was measured, and the relative dose response test carried out. After administering one 100,000- or 200,000-IU oral dose of vitamin A, ocular examinations were repeated weekly for seven weeks and then biweekly for 20 more weeks, or until lesions were healed on two consecutive examinations. Either dose of vitamin A was similarly effective in healing Bitot's spots. The most important factor in predicting responsiveness to treatment was baseline serum retinol concentration: children with lower pretreatment concentrations were more likely to have responsive lesions. No child had a relapse within the first three months after treatment. However, by six months, children who had received the higher dose were 82% less likely to have a relapse compared with children who had received the lower dose. Although either a 100,000- or 200,000-IU dose of vitamin A is similarly effective in healing Bitot's spots, a 200,000-IU dose provides longer protection. This benefit justifies the higher rates of transient mild side effects associated with the 200,000-IU dose. The current 200,000-IU dose of vitamin A recommended by the World Health Organization for prophylactic dosing should not be reduced.


Developmental biology of the leech Helobdella.
Glossiphoniid leeches of the genus Helobdella provide experimentally tractable models for studies in evolutionary developmental biology (Evo-Devo). Here, after a brief rationale, we will summarize our current understanding of Helobdella development and highlight the near term prospects for future investigations, with respect to the issues of: D quadrant specification; the transition from spiral to bilaterally symmetric cleavage; segmentation, and the connections between segmental and non-segmental tissues; modifications of BMP signaling in dorsoventral patterning and the O-P equivalence group; germ line specification and genome rearrangements. The goal of this contribution is to serve as a summary of, and guide to, published work.


Content of reticulocyte hemoglobin is a reliable tool for determining iron deficiency in dialysis patients.
The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.


[Comparative study of two microbiological assay methods of serum isoniazid].
Two microbiological assay techniques for estimation of biologically active isoniazid concentrations in human serum were compared : the vertical diffusion method and a large plate method similar to that commonly used for the antibiotics. Four hundred seventy four tests were carried out on the serum from 133 patients. Parallel titrations were determined by two biologists on the same serum samples, with the same standard solutions, by the two methods performed rapidly after the collection of specimens and after they have been stored in the frozen state during one week and were compared. It was found that the variability obtained in these conditions was 26 per cent for the vertical diffusion method and 14 per cent for the large plate method. The correlation coefficients were 0,87 and 0,95 respectively. Also it will be noted that the large plate method is faster, of lower cost and require smaller volumes of serum. However, it also failed to detect levels lower than 0,5 and upper than 2 micrograms/ml, the standard curve is not stable and must be run with each assay and it is also subject to interference by other antibiotics.


Promoter methylation status of multiple genes in brain metastases of solid tumors.
The aberrant methylation of the CpG island promoter regions acquired by tumor cells is one mechanism for loss of gene function. The high methylation rate for RB1 and death-associated protein-kinase gene (DAP-kinase) (60 and 90%, respectively) previously found in brain metastases suggests this mechanism could be non-randomly associated to tumor progression and metastasis. Thus, in addition to these two genes, we determined the methylation status of the genes p16INK4a, glutathione S-transferase P1 (GSTP1), O6-methylguanine DNA methyltransferase (MGMT), thrombospondin-1 (THBS1), p14ARF, TP53, p73, and tissue inhibitor of metalloproteinase 3 (TIMP-3), in 18 brain metastases of solid tumors, with methylation specific PCR. The metastases were derived from malignant melanoma (three cases), lung carcinoma (six cases), breast carcinoma (three cases), ovarian carcinoma (two cases) and one each from colon, kidney, bladder and undifferentiated carcinoma. We detected methylation levels in the tumor samples of 83% in p16INK4a, 72% in DAP-kinase, 56% in THBS1, 50% in RB1, 39% in MGMT, 33% in GSTP1 and p14ARF each, 22% in p73 and TIMP-3 each, and 11% in TP53. The methylation index (number of genes methylated/number of genes tested) varied between 0.1 and 0.6, with an average of 0.42, indicating that a high grade of gene methylation accumulates parallel to the tumor metastasis process. Our data suggest an important role for gene methylation in the development of brain metastases, primarily involving epigenetic silencing of DAP-kinase, THBS1 and the cell-cycle regulators RB1/p16INK4a.


Combination therapies for deep venous thrombosis.
Nearly 1 million patients are treated for deep venous thrombosis annually in the United States, typically with anticoagulant therapy alone. While anticoagulation reduces risk for pulmonary embolism, up to two-thirds of patients experience some degree of postthrombotic syndrome. This review details the recent introduction of a variety of novel mechanical thrombectomy devices that, in combination with local delivery of thrombolytic agents, offers a new approach for rapid and effective removal of venous thrombus, while minimizing attendant risks of bleeding complications.


Microcapillary clonogenic assays for human marrow hematopoietic progenitor cells.
The capillary clonogenic cell assay was developed and adapted to culture myeloid and erythroid colonies from human bone marrow cells. The plating efficiencies for femoral bone marrow granulocyte-macrophage progenitors (CFU-gm), erythroid colony-forming units (CFU-e) and erythroid burst-forming units (BFU-e) were 0.143%, 0.229% and 0.141%, respectively. Standard bone marrow progenitor Petri dish assays require a total culture volume of 1 ml per dish, and as such are not suitable for the small numbers of cells often obtained from human bone marrow samples. The microcapillary assay as developed and standardized in our laboratory has the unique advantage of being able to utilize small numbers of cells. This technique is suitable for evaluating the myelotoxicity of investigational new anti-cancer and anti-HIV agents and for further investigation of the mechanisms underlying chemotherapy-induced bone marrow toxicity.


Polymer inclusion membranes (PIMs) in chemical analysis - A review.
This review highlights the increasing interest in polymer inclusion membranes (PIMs) in analytical chemistry as they are adapted to new and novel applications. PIMs are polymer-based liquid membranes and were first introduced 50 years ago as the sensing membranes in ion-selective electrodes and optodes. More recently however, PIMs have been used for other applications in analytical chemistry such as for sample separation, sample pre-concentration, electro-driven extraction, and passive sampling, and have also been incorporated into on-line and automated analysis systems. The present review provides a general overview of the analytical chemistry applications of PIMs reported in the literature to date and illustrates their versatility for solving challenging chemical analysis problems.


Effects of elastic stockings on peripheral and central nervous system.
Prospective study to investigate the effects of elastic stockings (GCS) 23-32 mmHg at ankle on Hoffmann reflex (H-reflex) from soleus muscle under rest and after a walking program. Fourteen subjects wore two types of GCS, at different times. Electrophysiological examinations were carried out at rest without and with GCS, immediately after walking with GCS and 20 minutes later after removing GCS. Peripheral nerve conduction remained unchanged after using the GCS. Conversely, walking with GCS led to changes in a spinal cord pathway expressed as a decrease of H-threshold and an increase of H-size as a function of stimulus intensity, which lasted for at least 20 minutes. GCS has no effect on the peripheral nervous system. The GCS intolerance and the discomfort sometimes reported by patients do not derive from a dysfunction of the lower limb peripheral nervous system. A positive action on spinal reflex excitability is detected after walking while wearing GCS. We suggest that nervous descending activity due to voluntary contractions, and afferent cutaneous discharge, enhanced by movement under compression, converge on inhibitory interneurons, thus impinging on presynaptic pathways. All this can lead to an enhancement of the monosynaptic responses. Higher limb oxygenation detected during walking with GCS, found by other Authors, could increase the sensitivity of the muscle spindle afferents and/or motor neuron excitability resulting in an increase in H-reflex excitability, with potential positive effects on neuromuscular activities improving proprioception and postural control of the lower limbs.


Vulnerability reawakened: Increased substance use among aging traumatized veterans during COVID-19 pandemic.
This study prospectively assesses the implication of (a) exposure to distant trauma of war captivity, (b) stressful life events across the life span, and (c) posttraumatic stress disorder (PTSD) trajectories and current PTSD, on substance use during the COVID-19 pandemic. One hundred and twenty Israeli ex-prisoners of war (ex-POWs) and 65 matched veterans of the 1973 Yom Kippur War filled out self-report questionnaires in 4 waves of assessment (T1-18, T2-30, T3-35, and T4-42 years after the war). A fifth wave of assessment (T5) was conducted in the midst of the COVID-19 pandemic, 47 years after the war. Whereas in the earlier assessments (T1-T4) war captivity was not related to substance use, during the COVID-19 pandemic (T5) ex-POWs reported higher increase of use of alcohol, tranquilizers, cannabis, and sleep medications than comparable veterans. War-induced PTSD trajectories that were prospectively measured between T1-T4, and concurrent PTSD during the pandemic (T5) were related to increase in substance use during the pandemic (T5). The findings demonstrate the long-term effects of both earlier experience of severe traumatic stress in young adulthood and the resultant PTSD trajectories, as reflected in increased substance use among the elderly, in the face of subsequent calamity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assessing bottlenecks in Emergency Department flow of patients with abdominal pain.
Abdominal pain has a wide range of possible causes, which may lead to difficulties in diagnosing and lengthy Emergency Department (ED) stays. In this study, bottlenecks in ED processes of patients with abdominal pain were identified. Time-points of patients who presented to a Dutch ED with abdominal pain were observed and documented. The institutional review board approved the study. In total, 3015 min of patient time were observed in 54 patients. Median length of stay (LOS) was 218 min for admitted patients, and 168 min for discharged patients. For 65 patients (27.4%), LOS exceeded 4 h. Delays were found during the diagnostic process, when multiple physicians were needed in order to make a decision, and during departure. Our study concerning individual patients' time-points provides important insight into delays in the patient journey of patients with abdominal pain. Flow improvement can be achieved by focusing on these bottlenecks, for example by minimizing diagnostic delays and by simultaneous specialists' consultations for patients who need more than one physician. The optimization of ED flow for patients with abdominal pain depends on coordinated efforts between ED staff, medical specialists, radiology and laboratory staff, staff from inpatient units, and hospital supporting services.


[Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].
The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.


Metal-colloid partitioning in artificial interstitial waters of marine sediments: influences of salinity, pH, and colloidal organic carbon concentration.
For decades, heavy metals have been deposited into marine sediments as a result of anthropogenic activities. Depending on their bioavailability, these metals may represent a risk to benthic organisms. Dissolved interstitial water metal concentrations have been shown to be better predictors of bioavailability than sediment metal concentrations. In order to improve our understanding of metals bioavailability in sediments, it is essential to fully comprehend metal speciation. Colloidal organic carbon is ubiquitous in marine interstitial water and readily forms complexes with numerous dissolved metals, greatly reducing their bioavailability. Methods were applied to isolate dissolved and colloidal cadmium, copper, nickel, lead, and zinc from interstitial waters using centrifugation and stirred cell ultrafiltration. Influences of salinity, pH, and colloidal carbon concentration on partitioning behavior were investigated. In the pH study, colloidal-dissolved partitioning of each metal (Kp) was observed to increase as pH rose. Conversely, in the salinity experiment, metal Kps declined as salinity increased. For the metal-organic colloid study, linear isotherms were calculated for each of the metals, resulting in log Kcocs ranging from 5.90 for zinc to 7.50 for copper. Kp values calculated from metal-spiked field sediments were in good agreement with those measured in the salinity study. These results provide insight into the behavior of metals associated with colloidal organic carbon in marine sediments under the conditions occurring in estuarine systems.


Effect of walking velocity on forelimb kinematics and kinetics.
A database of biomechanical variables obtained from normal horses walking at a range of velocities is needed for comparison with the variables obtained from lame horses in which velocity cannot be predetermined. The objective was to investigate velocity-dependent changes in selected kinematic variables, ground reaction forces (GRF) and net joint energies in the forelimb and to develop statistical equations to calculate expected values of these variables for horses walking at different velocities. Five sound horses walked at a range of velocities (0.82 to 1.91 m/s) over a force plate. Kinematic data were recorded simultaneously for 51 trials. Kinematic, GRF and energetic variables were determined using standard methods. Correlation and simple regression analyses between velocity and measured variables were performed. An increase in walking velocity was correlated with an increase in stride length and decreases in stride and stance duration. Vertical, braking and propulsive impulses decreased as a consequence of the large reduction in stance duration, even though peak vertical, braking and propulsive GRFs increased. There was no significant increase in energy generation at any of the forelimb joints, indicating that muscle activity was not the source of the increase in GRFs. Changes in the longitudinal GRFs appeared to be influenced by velocity-dependent increases in head and neck oscillations. The equations obtained in this study can be used to calculate the expected normal variables from a range of walking velocities and to detect deviations from normal values in lame horses.


Elucidation of lignin structure by quantitative 2D NMR.
Quick quantitative HSQC (QQ-HSQC) was applied to quantitative evaluation of different inter-unit linkages in an array of milled softwood and hardwood and technical lignins by using the guaiacyl C2 and syringyl C2-C6 signals as internal standards. The results were found to be highly reproducible and comparable with earlier literature reports. The advantage of QQ-HSQC NMR analysis of lignin is contemporary detection and quantification of lignin inter-unit linkages with a direct, non-destructive method requiring short acquisition times.


Phycodnaviruses: a peek at genetic diversity.
The family Phycodnaviridae encompasses a diverse collection of large icosahedral, dsDNA viruses infecting algae. These viruses have genomes ranging from 160 to 560kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV). The genomes of members in three genera in the Phycodnaviridae have recently been sequenced and the purpose of this manuscript is to summarize these data. The viruses have diverse genome structures, some with large regions of non-coding sequence and others with regions of single-stranded DNA. Typically, phycodnaviruses have the coding capacity for hundreds of genes. The genome analyses have revealed in excess of 1000 unique genes, with only 14 homologous genes held in common among the three genera of the phycodnavirses sequenced to date. Thus, the gene diversity far exceeds the number of so-called "core" genes. Little is known about the replication of these viruses, but the consequences of these infections of the phytoplankton have global affects, including altered geochemical cycling and weather patterns.


A micromethod for clotting tests and coagulation factor assays.
A simple microtechnique for carrying out partial thromboplastin time with kaolin tests with 2 microliter or less of test plasma is described. For single stage factor assays, less than 1 microliter of test solution may be used. Reagents and test plasma are loaded in sequence into a 10 microliter, long needle syringe and introduced into a micro test-tube immobilized in a water bath. The end-point is taken as a positive clearing of kaolin turbidity from the mixture while stirring. Correlation with normal techniques has been excellent.


Biomechanics of head injury.
The enormous incidence of closed head injury has resulted in employing the field of biomechanics as a means of predicting the site of a lesion, discovering, and understanding the forces acting during cranial impact. This paper indicates that the possibilities associated with trauma-induced lesions include: the establishment of large pressure gradients associated with damage resulting from absolute motion of the brain and its displacement relative to the skull; flexion-extension of the upper cervical cord; skull deformation and/or rotational acceleration. Analytical representations, inanimate and cadaver models and, experimental paradigms are presented and their behavioral implications discussed.


Freestanding films of crosslinked gold nanoparticles prepared via layer-by-layer spin-coating.
A new, extremely efficient method for the fabrication of films comprised of gold nanoparticles (GNPs) crosslinked by organic dithiols is presented in this paper. The method is based on layer-by-layer spin-coating of both components, GNPs and crosslinker, and enables the deposition of films several tens of nanometers in thickness within a few minutes. X-ray diffraction and conductance measurements reveal the proper adjustment concentration of the crosslinker solution of the critical is in order to prevent the destabilization and coalescence of particles. UV/vis spectroscopy, atomic force microscopy, and conductivity measurements indicate that films prepared via layer-by-layer spin-coating are of comparable quality to coatings prepared via laborious layer-by-layer self-assembly using immersion baths. Because spin-coated films are not bound chemically to the substrate, they can be lifted-off by alkaline underetching and transferred onto 3d-electrodes to produce electrically addressable, freely suspended films. Comparative measurements of the sheet resistances indicate that the transfer process does not compromise the film quality.


Panic response to lactate administration in alcoholic and nonalcoholic patients with panic disorder.
The authors administered lactate to 12 abstinent alcoholics with panic disorder, 10 nonalcoholic patients with panic disorder, and eight control subjects. They found that the alcoholic patients had fewer panic attacks in response to lactate infusion than the nonalcoholic patients. This finding was not attributable to differences in baseline anxiety or the change in plasma chemical values brought about by sodium lactate administration. The authors suggest that there may be subgroups of patients with panic disorder who need further characterization to meaningfully elucidate the pathophysiology of the disorder.


[Etiology of community-acquired pneumonia in children hospitalized in the period of 2009-2012].
The aim of this study was to analyze etiology of childhood pneumonia in the region of Warsaw and to assess the efficacy and usefulness of standard diagnostic procedures used in search of etiology. 663 patients (323 girls and 340 boys) hospitalized due to pneumonia in the period of 2009-2012 were enrolled. Diagnostic procedures to determine the etiology were performed in 400/663 (60.3%) children. Type of diagnostic procedures depended on medical history, disease's course and patient's condition and included 336 blood cultures, 257 measurements of antibody titers against Chlamydophila pneumoniae and Mycoplasma pneumoniae, 12 measurements of antibody titers against Bordetella pertussis, 14 pleural fluid cultures (deriving from 9 patients). Using the BiNet network 51 specimens (45 blood specimens, 4 pleural fluid, 2 bacterial strains) were send to the KOROUN in order to perform molecular diagnostic in search of encapsulated bacteria. Etiology of pneumonia was found in 9.7% (64/663) of all patients with diagnosed CAP, what accounted for 16% (64/400) of children in which the diagnostics was taken. The most frequent agent was atypical bacteria which was found in 14.75% (59/400) patients (in 26 patients - Chlamydophila pneumoniae, 11 - Mycoplasma pneumoniae, 22 - mixed infection). Bacterial etiology was confirmed in 1.25% (5/400) of patients (Streptococcus pneumoniae-3 patients, Streptococcus pyogenes i Bordetella pertussis - 1 patient each other). Efficacy of a single blood culture was very low - 0.6% (2/336). Pleural fluid culture was positive only in 1 of 9 drained patients (S. pyogenes). Thanks to the use of BiNet network (KOROUN) etiology of severe pneumonia in 3 patients has been determined. 2 of those patients suffered from invasive pneumococcal disease, which was not diagnosed with standard microbiological procedures (blood cultures). The methods currently used in the diagnosis of pneumonia is inadequate. It was possible to determine the etiology of only 10% of children hospitalized. The most common cause of pneumonia that seen were atypical infection (8.9%). The effectiveness of single blood culture in determining the etiology of pneumonia was very low and amounted to 0.6%. It is necessary to expand the diagnosis of childhood pneumonia upon the basis of molecular techniques and methods of serotyping.


Preparation of cholesteric (hydroxypropyl)cellulose/polymer networks and ion-mediated control of their optical properties.
(Hydroxypropyl)cellulose (HPC)/vinyl polymer networks were synthesized in film form from liquid-crystalline solutions of HPC in a mixed solvent of methacrylate monomer/methanol/water (2:1:2 in weight) containing cross-linking agents, via photopolymerization of the methacrylate monomer. Di(ethylene glycol) monomethyl ether methacrylate (DEGMEM) or 2-hydroxypropyl methacrylate (HPMA) was used as the polymerizing monomer, and tetra(ethylene glycol) diacrylate and glutaraldehyde were the cross-linkers for the monomers and HPC, respectively. The polymer composite films, HPC/PDEGMEM and HPC/PHPMA, prepared at ca. 60-70 wt % concentrations of HPC in the starting solutions, were iridescently colored due to the selective light reflection, originating from the cholesteric helical arrangement carried over successively into the network system. When the cholesteric films were immersed and swollen in water containing an inorganic neutral salt, their coloration and optical turbidity varied according to a strength of 'chaotropicity' of the impregnant ions. This ionic effect may be interpreted as essentially identical with that found formerly in the coexistent salt-sort dependence of the cholesteric pitch and lower critical solution temperature for HPC aqueous solutions. It is also demonstrated that visual appearance of the swollen networks can be changed by application of an electric potential of practical magnitude between both edges of the samples of rectangular shape.


Pancreatic tissue pH in experimental acidosis and alkalosis.
The pH was studied in pancreatic tissue and arterial blood in 22 dogs. Respiratory acidosis was induced by CO2 inhalations in 5 dogs, respiratory alkalosis by hyperventilation in 5 dogs, metabolic acidosis by intravenous(i.v.) infusion of 0.1 N HCl in 5 dogs, metabolic alkalosis by i.v. infusion of 4.2% Na bicarbonate in 5 dogs. The differences between the shifts of blood pH and tissue pH were not significant statistically. Infusion of Ringer's solution failed to affect the pH in blood and pancreatic tissue in two control animals. It is concluded, that with an adequate tissue blood flow the pancreatic tissue pH is uninformative unless the blood pH is known.


A summary of the new phenomenon of normocalcemic hyperparathyroidism and appropriate management.
The phenomenon of normocalcemic hyperparathyroidism (NCHPT) remains largely unknown and not well understood. Recently, with more investigators reporting on the subject, NCHPT has been proposed to be a precursor of the classic hypercalcemic primary hyperparathyroidism (HPT). This manuscript will discuss the most recent findings regarding the diagnosis, natural history, treatment and follow-up of NCHPT. Approximately 1-4% of patients undergoing parathyroidectomy for HPT are normocalcemic before surgery. To date, observation appears to be a well tolerated approach, as long as these patients remain normocalcemic. When patients with NCHPT are followed for an average of 4 years, 22% will progress to hypercalcemia. In some instances, NCHPT may be treated with parathyroidectomy, but the indications and long-term outcome for this approach are unknown. This condition is now being diagnosed more frequently. Patients with vitamin D deficiency, mild renal dysfunction, and urinary calcium leak are often mislabeled as having NCHPT and these conditions should always be excluded and medically treated. There is some evidence that parathyroidectomy may be beneficial when NCHPT patients are properly selected. The authors suggest caution when approaching these patients surgically because multiglandular disease and operative failure may be more common in these rare patients.


CT fluoroscopy--guided interventional procedures: techniques and radiation dose to radiologists.
To determine the radiation dose to radiologists who perform computed tomographic (CT) fluoroscopic interventional procedures by using a quick-check method and a low-milliampere technique. Two hundred twenty CT fluoroscopy--guided interventional procedures were performed in 189 patients. Procedures included 57 spinal injections, 17 spinal biopsies, 24 chest biopsies, 20 abdominal aspirations, 44 abdominal biopsies, and 58 abdominal drainages. Procedure details were prospectively recorded and included site, depth, target diameter, milliampere value, kilovolt peak, fluoroscopic time, and CT technique (continuous CT fluoroscopy, quick-check method, or a combination of these techniques). An individual collar and finger radiation detector were worn by each radiologist during each procedure to determine the dose per procedure. The quick-check technique was performed in 191 (87%) of 220 procedures. Four procedures were performed with continuous CT fluoroscopy, and a combination technique was used for 25 (11%) procedures. The overall mean CT fluoroscopic time was 17.9 seconds (range, 1.2--101.5 seconds). The mean milliampere value was 13.2 mA (range, 10--50 mA). The overall mean radiologist radiation dose per procedure was 2.5 mrem (0.025 mSv) (whole body). Individual procedure doses ranged from 0.66 to 4.75 mrem (0.007--0.048 mSv). The finger radiation dose was negligible. By using a low-milliampere technique and the quick-check method, CT fluoroscopic time and radiation exposure can be minimized.


Effect of disulfiram on N-nitroso-N-methylbenzylamine metabolism. Biochemical aspects.
The present biochemical experiments show that disulfiram inhibits N-nitroso-N-methylbenzylamine metabolism in the rat. More N-nitroso-N-methylbenzylamine may therefore reach extrahepatic tissues. The pathological lesions observed in the lungs in the present system can be explained by the finding that alkylation of lung DNA is increased and repair processes are impaired by enhanced cell proliferation in this organ.


A monoclonal antibody to the type 1 insulin-like growth factor and insulin receptors stimulates deoxyribonucleic acid synthesis in human and murine fibroblasts.
Insulin-like growth factor I (IGF-I) and insulin are polypeptide hormones that stimulate their cellular responses by binding to specific cell membrane receptors. These receptors, while chemically distinct, have similar structural and functional characteristics. This manuscript describes the production and characterization of a monoclonal antibody that binds to both type I IGF and insulin receptors. This antibody did not inhibit hormone binding to either receptor type, but stimulated DNA synthesis in both human and murine fibroblasts. Ten BALB/c-BYJ mice were immunized with human placental membrane fragments, and their splenic lymphocytes were fused with SP2 AG0 mouse myeloma cells. Of approximately 3000 hybridoma clones thus obtained, 1 viable clone, designated V3,8 D7, was found to produce an antibody directed against the type I IGF receptor. Solubilized radiolabeled placental membranes immunoprecipitated with affinity-purified antibody and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions revealed bands with relative molecular masses corresponding to the nonreduced intact receptor (approximately 350 x 10(3], the alpha-subunit (130-140 x 10(3], and the beta-subunit (90 x 10(3] of the type I IGF receptor. Clonal supernatant and affinity-purified antibody precipitated solubilized receptors affinity labeled with [125I]IGF-I. Antibody V3,8 D7 also precipitated solubilized placental membranes affinity labeled with [125I]insulin. However, solubilized receptors affinity purified by the monoclonal antibody bound IGF-I much better than insulin, suggesting that this antibody has a higher affinity for the type I IGF receptor than for the insulin receptor. Affinity-purified antibody did not inhibit the binding of IGF-I or insulin to receptors on human placental membranes, suggesting that it is directed against a site on the type I IGF and insulin receptor not involved in hormone binding. However, affinity-purified monoclonal antibody stimulated DNA synthesis in human GM 498 and murine BALB/c-3T3 clone A 31 fibroblasts, as determined by [3H]thymidine incorporation. The combination of IGF-I and affinity-purified antibody did not increase thymidine incorporation above levels observed with either substrate alone, suggesting that these factors may be operating through a common mechanism. These results suggest that antibody V3,8 D7 can stimulate receptor responses by binding to a site on the type I IGF and/or insulin receptors that is not involved in hormone binding. These data support the concept that hormone receptors themselves possess the biological information required for stimulating specific cellular responses.


Post lumbar puncture headache: diagnosis and management.
Lumbar puncture is a frequently performed procedure in medical emergencies and anaesthesia. Headache after lumbar puncture is a common occurrence (32%) and carries a considerable morbidity, with symptoms lasting for several days, at times severe enough to immobilize the patient. If untreated, it can result in serious complications such as subdural haematoma and seizures, which could be fatal. Certain factors contribute to the development of headache after lumbar puncture. If these factors are taken into consideration, the incidence of headache could be markedly reduced. It is therefore important that the doctors are aware of the methods available for reducing the incidence of headaches after lumbar puncture. On the other hand, there are several misconceptions that are thought to decrease the incidence of headaches with no scientific basis. This article reviews the scientific literature and highlights the practical issues involved in the diagnosis and management of headaches after lumbar puncture, including the epidural blood patch treatment.


Removal of ventricular shunts.
Although most patients with an implanted ventriculoperitoneal shunt device will require cerebrospinal fluid diversion over the course of their lifetime, there appears to be a small number of patients that are shunt independent and may benefit from shunt removal. We retrospectively analyzed 661 patients with hydrocephalus treated over a 10-year period at a single institution. In 10 patients, a systematic shunt weaning protocol was attempted before removal of the cerebrospinal fluid shunt. Ten patients underwent an attempt at shunt removal. Seven of these patients were successfully weaned and 3 were not. The indications to attempt shunt removal for the 7 patients that were successfully weaned were recurrent complications and infections requiring multiple shunt externalizations and revisions in 4 patients, asymptomatic shunt disconnection in 2 patients, and symptomatic overdrainage in 1 patient. None of the patients that were successfully weaned had a history of shunt failure resulting in ventriculomegaly. Two of the 3 patients who failed shunt weaning attempts had a history of shunt failure that resulted in ventriculomegaly. A small number of patients with shunted hydrocephalus may benefit from removal of their shunt.